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Sample records for par fsh recombinante

  1. FSH-Receptor Isoforms and FSH-dependent Gene Transcription in Human Monocytes and Osteoclasts

    PubMed Central

    Robinson, Lisa J; Tourkova, Irina; Wang, Yujuan; Sharrow, Allison C; Landau, Michael S; Yaroslavskiy, Beatrice B; Li, Sun; Zaidi, Mone; Blair, Harry C

    2010-01-01

    Cells of the monocyte series respond to follicle stimulating hormone (FSH) by poorly characterized mechanisms. We studied FSH-receptors (FSH-R) and FSH response in nontransformed human monocytes and in osteoclasts differentiated from these cells. Western blot and PCR confirmed FSH-R expression on monocytes or osteoclasts, although at low levels relative to ovarian controls. Monocyte and osteoclast FSH-Rs differed from FSH-R from ovarian cells, reflecting variable splicing in exons 8–10. Monocytes produced no cAMP, the major signal in ovarian cells, in response to FSH. However, monocytes or osteoclasts transcribed TNFα in response to the FSH. No relation of expression of osteoclast FSH-R to the sex of cell donors or to exposure to sex hormones was apparent. Controls for FSH purity and endotoxin contamination were negative. Unamplified cRNA screening in adherent CD14 cells after 2 hours in 25 ng/ml FSH showed increased transcription of RANKL signalling proteins. Transcription of key proteins that stimulate bone turnover, TNFα and TSG-6, increased 2–3 fold after FSH treatment. Smaller but significant changes occurred in transcripts of selected signalling, adhesion, and cytoskeletal proteins. We conclude that monocyte and osteoclast FSH response diverges from that of ovarian cells, reflecting, at least in part, varying FSH-R isoforms. PMID:20171950

  2. FSH isoform pattern in classic galactosemia.

    PubMed

    Gubbels, Cynthia S; Thomas, Chris M G; Wodzig, Will K W H; Olthaar, André J; Jaeken, Jaak; Sweep, Fred C G J; Rubio-Gozalbo, M Estela

    2011-04-01

    Female classic galactosemia patients suffer from primary ovarian insufficiency (POI). The cause for this long-term complication is not fully understood. One of the proposed mechanisms is that hypoglycosylation of complex molecules, a known secondary phenomenon of galactosemia, leads to FSH dysfunction. An earlier study showed less acidic isoforms of FSH in serum samples of two classic galactosemia patients compared to controls, indicating hypoglycosylation. In this study, FSH isoform patterns of five classic galactosemia patients with POI were compared to the pattern obtained in two patients with a primary glycosylation disorder (phosphomannomutase-2-deficient congenital disorders of glycosylation, PMM2-CDG) and POI, and in five postmenopausal women as controls. We used FPLC chromatofocussing with measurement of FSH concentration per fraction, and discovered that there were no significant differences between galactosemia patients, PMM2-CDG patients and postmenopausal controls. Our results do not support that FSH dysfunction due to a less acidic isoform pattern because of hypoglycosylation is a key mechanism of POI in this disease.

  3. FSH (Follicle-Stimulating Hormone) Test

    MedlinePlus

    ... FSH and LH may be ordered when a boy or girl does not appear to be entering puberty at ... hair Growth of the testicles and penis in boys Beginning of menstruation in girls ^ Back to top What does the test result ...

  4. Further evidence for direct pro-resorptive actions of FSH.

    PubMed

    Sun, Li; Zhang, Zhiyuan; Zhu, Ling-Ling; Peng, Yuanzhen; Liu, Xuan; Li, Jianhua; Agrawal, Manasi; Robinson, Lisa J; Iqbal, Jameel; Blair, Harry C; Zaidi, Mone

    2010-03-26

    We confirm that FSH stimulates osteoclast formation, function and survival to enhance bone resorption. It does so via the activation of a pertussis toxin-sensitive G(i)-coupled FSH receptor that we and others have identified on murine and human osteoclast precursors and mature osteoclasts. FSH additionally enhances the production of several osteoclastogenic cytokines, importantly TNFalpha, likely within the bone marrow microenvironment, to augment its pro-resorptive action. FSH levels in humans rise before estrogen falls, and this hormonal change coincides with the most rapid rates of bone loss. On the basis of accumulating evidence, we reaffirm that FSH contributes to the rapid peri-menopausal and early post-menopausal bone loss, which might thus be amenable to FSH blockade.

  5. Ovarian function and FSH receptor characteristics during canine anoestrus.

    PubMed

    McBride, M W; Aughey, E; O'Shaughnessy, P J; Jeffcoate, I A

    2001-01-01

    Ovaries of bitches are relatively inactive during anoestrus despite apparently adequate circulating FSH concentrations. Alternative FSH receptor (FSH-R) transcripts in bitches might hinder the follicular response to gonadotrophins, which may account for anoestrus. The expression of the full length FSH-R and novel isoforms in bitches was examined using in situ hybridization and RT-PCR analysis. Various PCR primers to the FSH-R were used and its expression was assessed in ovarian tissue at different stages of the oestrous cycle. RT-PCR amplification of the extracellular domain (exon 1-10) was generally successful, indicating that cFSH-R expression (> 90%) occurs throughout the oestrous cycle. Two FSH-R isoforms were sequenced, but there were no clear differences in the pattern of expression between anoestrus and other stages of the oestrous cycle, except that isoform expression was less frequent (30% occurrence) in prepubertal bitches. Data from in situ hybridization showed clear expression of the FSH-R in secondary and antral follicles, and corpora lutea. It was concluded that there is no evidence of a change in the expression of the FSH-R specific to anoestrus.

  6. Comparative Assessment of Glycosylation of a Recombinant Human FSH and a Highly Purified FSH Extracted from Human Urine.

    PubMed

    Wang, Hong; Chen, Xi; Zhang, Xiaoxi; Zhang, Wei; Li, Yan; Yin, Hongrui; Shao, Hong; Chen, Gang

    2016-03-04

    Glycosylation is an important PTM and is critical for the manufacture and efficacy of therapeutic glycoproteins. Glycan significantly influences the biological properties of human follicle-stimulating hormone (hFSH). Using a glycoproteomic strategy, this study compared the glycosylation of a putative highly purified FSH (uhFSH) obtained from human urine with that of a recombinant human FSH (rhFSH) obtained from Chinese hamster ovary (CHO) cells. Intact and subunit masses, N-glycans, N-glycosylation sites, and intact N- and O-glycopeptides were analyzed and compared by mass spectrometry. Classic and complementary analytical methods, including SDS-PAGE, isoelectric focusing, and the Steelman-Pohley bioassay were also employed to compare their intact molecular weights, charge variants, and specific activities. Results showed that highly sialylated, branched, and macro-heterogeneity glycans are predominant in the uhFSH compared with those in rhFSH. The O-glycopeptides of both hFSHs, which have not been described previously, were characterized herein. A high degree of heterogeneity was observed in the N-glycopeptides of both hFSHs. The differences in glycosylation provide useful information in elucidating and in further investigation the critical glycan structures of hFSH.

  7. Follicle-stimulating hormone (FSH) unmasks specific high affinity FSH-binding sites in cell-free membrane preparations of porcine granulosa cells

    SciTech Connect

    Ford, K.A.; LaBarbera, A.R.

    1988-11-01

    The purpose of these studies was to determine whether changes in FSH receptors correlated with FSH-induced attenuation of FSH-responsive adenylyl cyclase in immature porcine granulosa cells. Cells were incubated with FSH (1-1000 ng/ml) for up to 24 h, treated with acidified medium (pH 3.5) to remove FSH bound to cells, and incubated with (125I)iodo-porcine FSH to quantify FSH-binding sites. FSH increased binding of FSH in a time-, temperature-, and FSH concentration-dependent manner. FSH (200 ng/ml) increased binding approximately 4-fold within 16 h. Analysis of equilibrium saturation binding data indicated that the increase in binding sites reflected a 2.3-fold increase in receptor number and a 5.4-fold increase in apparent affinity. The increase in binding did not appear to be due to 1) a decrease in receptor turnover, since the basal rate of turnover appeared to be very slow; 2) an increase in receptor synthesis, since agents that inhibit protein synthesis and glycosylation did not block the increase in binding; or 3) an increase in intracellular receptors, since agents that inhibit cytoskeletal components had no effect. Agents that increase intracellular cAMP did not affect FSH binding. The increase in binding appeared to result from unmasking of cryptic FSH-binding sites, since FSH increased binding in cell-free membrane preparations to the same extent as in cells. Unmasking of cryptic sites was hormone specific, and the sites bound FSH specifically. Unmasking of sites was reversible in a time- and temperature-dependent manner after removal of bound FSH. The similarity between the FSH dose-response relationships for unmasking of FSH-binding sites and attenuation of FSH-responsive cAMP production suggests that the two processes are functionally linked.

  8. Immunoreactivity of gonadotrophs (FSH and LH Cells) and gonadotropin subunit gene expression in the male chub mackerel Scomber japonicus pituitary during the reproductive cycle.

    PubMed

    Nyuji, Mitsuo; Selvaraj, Sethu; Kitano, Hajime; Shiraishi, Tetsuro; Yamaguchi, Akihiko; Shimizu, Akio; Matsuyama, Michiya

    2012-09-01

    The gonadotropins (GtHs), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are heterodimers composed of a common α subunit (GPα) and a unique β subunit (FSHβ or LHβ); they are synthesized in and secreted from gonadotrophs (FSH and LH cells) in the pituitary. Little is known about the roles of FSH and LH during spermatogenesis in perciform fishes. In this study, we examined immunoreactive changes in FSH and LH cells, and changes in the gene expression of the three gonadotropin subunits in the pituitary of male chub mackerel Scomber japonicus during testicular development. FSHβ-immunoreactive (ir) and LHβ-ir cell area were measured immuno-histochemically based on the FSH and LH cell-occupying area in the proximal pars distalis. The FSHβ-ir cell area increased significantly during spermiation, while FSHβ mRNA levels, already high at the beginning of spermatogenesis, increased further, peaking during spermiation. In contrast, LHβ-ir cell area and LHβ mRNA levels, which were low at the beginning of spermatogenesis, increased significantly during late spermatogenesis, peaking during spermiation. For both FSH and LH, GtHβ-ir cell area and GtHβ mRNA levels decreased until gonadal resting. GPα mRNA levels showed similar changes to LHβ mRNA levels. These results suggest that in the chub mackerel, FSH may play an important role in the early and late phases of spermatogenesis, and that LH may play a role during late spermatogenesis and spermiation. Moreover, our results demonstrate that changes in GtHβ-ir cell area were accompanied by similar changes in the expression of the FSHβ and LHβ genes, both of which increased during testicular development.

  9. Costs and outcomes associated with IVF using recombinant FSH.

    PubMed

    Ledger, W; Wiebinga, C; Anderson, P; Irwin, D; Holman, A; Lloyd, A

    2009-09-01

    Cost and outcome estimates based on clinical trial data may not reflect usual clinical practice, yet they are often used to inform service provision and budget decisions. To expand understanding of assisted reproduction treatment in clinical practice, an economic evaluation of IVF/intracytoplasmic sperm injection (ICSI) data from a single assisted conception unit (ACU) in England was performed. A total of 1418 IVF/ICSI cycles undertaken there between October 2001 and January 2006 in 1001 women were analysed. The overall live birth rate was 22% (95% CI: 19.7-24.2), with the 30- to 34-year age group achieving the highest rate (28%). The average recombinant FSH (rFSH) dose/cycle prescribed was 1855 IU. Average cost of rFSH/cycle was 646 pound(SD: 219 pound), and average total cost/cycle was 2932 pound (SD: 422 pound). Economic data based on clinical trials informing current UK guidance assumes higher doses of rFSH dose/cycle (1750-2625 IU), higher average cost of drugs/cycle (1179 pound), and higher average total cost/cycle (3266 pound). While the outcomes in this study matched UK averages, total cost/cycle was lower than those cited in UK guidelines. Utilizing the protocols and (lower) rFSH dosages reported in this study may enable other ACU to provide a greater number of IVF/ICSI cycles to patients within given budgets.

  10. Impairing follicle-stimulating hormone (FSH) signaling in vivo: targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance.

    PubMed

    Dierich, A; Sairam, M R; Monaco, L; Fimia, G M; Gansmuller, A; LeMeur, M; Sassone-Corsi, P

    1998-11-10

    Pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone stimulate the gonads by regulating germ cell proliferation and differentiation. FSH receptors (FSH-Rs) are localized to testicular Sertoli cells and ovarian granulosa cells and are coupled to activation of the adenylyl cyclase and other signaling pathways. Activation of FSH-Rs is considered essential for folliculogenesis in the female and spermatogenesis in the male. We have generated mice lacking FSH-R by homologous recombination. FSH-R-deficient males are fertile but display small testes and partial spermatogenic failure. Thus, although FSH signaling is not essential for initiating spermatogenesis, it appears to be required for adequate viability and motility of the sperms. FSH-R-deficient females display thin uteri and small ovaries and are sterile because of a block in folliculogenesis before antral follicle formation. Although the expression of marker genes is only moderately altered in FSH-R -/- mice, drastic sex-specific changes are observed in the levels of various hormones. The anterior lobe of the pituitary gland in females is enlarged and reveals a larger number of FSH- and thyroid-stimulating hormone (TSH)-positive cells. The phenotype of FSH-R -/- mice is reminiscent of human hypergonadotropic ovarian dysgenesis and infertility.

  11. Anti-FSH antibodies associate with poor outcome of ovarian stimulation in IVF.

    PubMed

    Haller, Kadri; Salumets, Andres; Uibo, Raivo

    2008-03-01

    FSH is required for spontaneous folliculogenesis and is widely used in ovarian stimulation in IVF. Previously, increased concentrations of antibodies against FSH (anti-FSH) have been demonstrated in infertile women. This study aimed to: (i) assess the possible association of anti-FSH with an adverse outcome of IVF with regard to clinical parameters characterizing the ovarian reserve; and (ii) compare serum and follicular fluid (FF) anti-FSH concentrations in relation to follicle size and endocrine markers. IVF patients (n = 182) subjected to gonadotrophin-releasing hormone-antagonist protocol were assessed for anti-FSH using enzyme-linked immunosorbent assay. Increased concentrations of serum anti-FSH immunoglobulin (Ig)G and IgA were associated with impaired ovarian stimulation outcome, with cut-off values <1.0 arbitrary units predicting poor ovarian response (FSH IgG and IgA were positively associated with serum anti-FSH concentrations and FSH concentration in FF. Additionally, FF anti-FSH IgG increased with follicle growth (linear regression coefficient = 0.02, P = 0.022). Collectively, these data suggest that serum anti-FSH antibodies are associated with poor ovarian response to FSH stimulation in IVF, with anti-FSH IgA and IgG potentially exerting a local FSH antagonizing effect in maturing follicles.

  12. Biosimilar FSH preparations- are they identical twins or just siblings?

    PubMed

    Orvieto, Raoul; Seifer, David B

    2016-06-14

    As patents expire on innovator products, there is increasing interest in developing biosimilar products globally. Biosimilars are not exact copies and are not considered generic versions of the reference product. They may differ in strength, purity and contain different composition of isoforms and/or various glycosylation profiles, with the consequent alterations in clinical efficacy or safety. Recently 2 new recombinant FSH preparations were introduced to clinical practice following randomized controlled, phase 3 clinical trials. Both, Bemfola and Ovaleap® were referred to the FSH innovator product Gonal-f™ (Follitropin alpha), and were found to yield an equivalent number of oocytes (primary end-point), following a long GnRH agonist suppressive protocol in "ideal" patients, i.e., young, normal responders. However, a closer look at these RCTs reveals a non-significant 4 % difference in clinical and ongoing pregnancy rates, in favor of Gonal f over the biosimilar products, accompanied by half the incidence of OHSS (2.9 vs 5.2 %, respectively). These studies were underpowered with reference to pregnancy rates, Thus, we believe that further comparative studies are needed in additional patient populations, e.g.,older,, poor responders, patients with repeated IVF failures and/or polycystic ovary syndrome, before the universal implementation of biosimilar products for clinical use. Biosimilars are actually a regulatory synonym, facilitating a fast track introduction of a FSH preparation to the COH armamentarium. We therefore recommend against interchanging or substituting innovator and biosimilar agents in clinical practice, and believe that the decision whether to use an innovator or a biosimilar product, should be reserved to the discretion of the treating physician. Furthermore, we believe the time has come that the measurement of the biological activity of FSH in humans should require other methods rather than the Steelman-Pohley assay, such as the determination

  13. FSH stimulates lipid biosynthesis in chicken adipose tissue by upregulating the expression of its receptor FSHR.

    PubMed

    Cui, Huanxian; Zhao, Guiping; Liu, Ranran; Zheng, Maiqing; Chen, Jilan; Wen, Jie

    2012-05-01

    Transcripts and protein for follicle-stimulating hormone receptor (FSHR) were demonstrated in abdominal adipose tissue of female chickens. There was no expression of the Fsh gene, but FSH and FSHR colocalized, suggesting that FSH was receptor bound. Partial correlations indicted that changes in abdominal fat (AF) content were most directly correlated with Fshr mRNA expression, and the latter was directly correlated with tissue FSH content. These relationships were consistent with FSH inducing Fshr mRNA expression and with the finding that FSH influenced the accumulation of AF in chickens, a novel role for the hormone. Chicken preadipocytes responded linearly to doubling concentrations of FSH in Fshr mRNA expression and quantities of FSHR and lipid, without discernable effect on proliferation. Cells exposed to FSH more rapidly acquired adipocyte morphology. Treatment of young chickens with chicken FSH (4 mIU/day, subcutaneous, days 7-13) did not significantly decrease live weight but increased AF weight by 54.61%, AF as a percentage of live weight by 55.45%, and FSHR transcripts in AF by 222.15% (2 h after injection). In cells stimulated by FSH, genes related to lipid metabolism, including Rdh10, Dci, RarB, Lpl, Acsl3, and Dgat2, were expressed differentially, compared with no FSH. Several pathways of retinal and fatty acid metabolism, and peroxisome proliferator-activated receptor (PPAR) signaling changed. In conclusion, FSH stimulates lipid biosynthesis by upregulating Fshr mRNA expression in abdominal adipose tissue of chickens. Several genes involved in fatty acid and retinal metabolism and the PPAR signaling pathway mediate this novel function of FSH.

  14. Fsh controls gene expression in fish both independently of and through steroid mediation.

    PubMed

    Sambroni, Elisabeth; Lareyre, Jean-Jacques; Le Gac, Florence

    2013-01-01

    The mechanisms and the mediators relaying Fsh action on testicular functions are poorly understood. Unlike in mammals, in fish both gonadotropins (Fsh and Lh) are able to efficiently stimulate steroidogenesis, likely through a direct interaction with their cognate receptors present on the Leydig cells. In this context, it is crucial to understand if Fsh effects are mediated through the production of steroids. To address this issue we performed transcriptome studies after in vitro incubations of rainbow trout testis explants in the presence of Fsh alone or in combination with trilostane, an inhibitor of Δ4- steroidogenesis. Trilostane significantly reduced or suppressed the response of many genes to Fsh (like wisp1, testis gapdhs, cldn11, inha, vt1 or dmrt1) showing that, in fish, important aspects of Fsh action follow indirect pathways and require the production of Δ4-steroids. What is more, most of the genes regulated by Fsh through steroid mediation were similarly regulated by Lh (and/or androgens). In contrast, the response to Fsh of other genes was not suppressed in the presence of trilostane. These latter included genes encoding for anti-mullerian hormone, midkine a (pleiotrophin related), angiopoietine-related protein, cyclins E1 and G1, hepatocyte growth factor activator, insulin-like growth factor 1b/3. A majority of those genes were preferentially regulated by Fsh, when compared to Lh, suggesting that specific regulatory effects of Fsh did not depend on steroid production. Finally, antagonistic effects between Fsh and steroids were found, in particular for genes encoding key factors of steroidogenesis (star, hsd3b1, cyp11b2-2) or for genes of the Igf system (igf1b/3). Our study provides the first clear evidence that, in fish, Fsh exerts Δ4-steroid-independent regulatory functions on many genes which are highly relevant for the onset of spermatogenesis.

  15. Transcriptional regulation of the FSH receptor: new perspectives

    PubMed Central

    Hermann, Brian P.; Heckert, Leslie L.

    2013-01-01

    The cell-surface receptor for the gonadotropin follicle-stimulating hormone (FSH) is expressed exclusively on Sertoli cells of the testis and granulosa cells of the ovary. FSH signal transduction through its receptor (Fshr) is critical for the timing and maintenance of normal gametogenesis in the mammalian gonad. In the 13 years since the gene encoding Fshr was first cloned, the mechanisms controlling its transcription have been extensively examined, but a clear understanding of what drives its unique cell-specificity remains elusive. Current knowledge of basal Fshr transcription highlights the role of an E-box in the proximal promoter which is bound by the basic helix-loop-helix transcription factors upstream stimulatory factor 1 (Usf1) and Usf2. Recent studies utilizing knockout mice and chromatin immunoprecipitation validated the importance of Usf to Fshr transcription and demonstrated a sexually dimorphic requirement for the Usf proteins to maintain normal Fshr expression. Studies have also shown that the promoter region itself is insufficient for appropriate Fshr expression in transgenic mice, indicating Fshr transcription depends on regulatory elements that lie outside of the promoter. Identification of such elements has been propelled by recent availability of genome sequence data, which facilitated studies using comparative genomics, DNase I hypersensitivity mapping, and transgenic analysis with large fragments of DNA. This review will focus on the current understanding of transcriptional regulatory processes that control expression of rat Fshr, including recent advances from our laboratory. PMID:17084019

  16. Endocrine control of spermatogenesis: Role of FSH and LH/ testosterone

    PubMed Central

    Ramaswamy, Suresh; Weinbauer, Gerhard F

    2014-01-01

    Evaluation of testicular functions (production of sperm and androgens) is an important aspect of preclinical safety assessment and testicular toxicity is comparatively far more common than ovarian toxicity. This chapter focuses (1) on the histological sequelae of disturbed reproductive endocrinology in rat, dog and nonhuman primates and (2) provides a review of our current understanding of the roles of gonadotropins and androgens. The response of the rodent testis to endocrine disturbances is clearly different from that of dog and primates with different germ cell types and spermatogenic stages being affected initially and also that the end-stage spermatogenic involution is more pronounced in dog and primates compared to rodents. Luteinizing hormone (LH)/testosterone and follicle-stimulating hormone (FSH) are the pivotal endocrine factors controlling testicular functions. The relative importance of either hormone is somewhat different between rodents and primates. Generally, however, both LH/testosterone and FSH are necessary for quantitatively normal spermatogenesis, at least in non-seasonal species. PMID:26413400

  17. Individualization of the FSH starting dose in IVF/ICSI cycles using the antral follicle count

    PubMed Central

    2013-01-01

    Background The FSH starting dose is usually chosen according to women’s age, anamnesis, clinical criteria and markers of ovarian reserve. Currently used markers include antral follicle count (AFC), which is considered to have a very high performance in predicting ovarian response to FSH. The objective of the present study to elaborate a nomogram based on AFC for the calculation of the appropriate FSH starting dose in IVF cycles. Methods This is a retrospective study performed at the Mother-Infant Department of Modena University Hospital. IVF patients (n=505) were subjected to blood sampling and transvaginal ultrasound for measurement of serum day3 FSH, estradiol and AFC. The variables predictive of the number of retrieved oocytes were assessed by backwards stepwise multiple regression. The variables reaching the statistical significance were then used in the calculation for the final predictive model. Results A model based on age, AFC and FSH was able to accurately predict the ovarian sensitivity and accounted for 30% of the variability of ovarian response to FSH. An FSH dosage nomogram was constructed and overall it predicts a starting dose lower than 225 IU in 50.2% and 18.1% of patients younger and older than 35 years, respectively. Conclusions The daily FSH dose may be calculated on the basis of age and two markers of ovarian reserve, namely AFC and FSH, with the last two variables being the most significant predictors. The nomogram seems easily applicable during the daily clinical practice. PMID:23388048

  18. Age-specific reference values for serum FSH and estradiol levels throughout the reproductive period.

    PubMed

    Grisendi, Valentina; Spada, Elena; Argento, Cindy; Plebani, Maddalena; Milani, Silvano; Seracchioli, Renato; Volpe, Annibale; La Marca, Antonio

    2014-06-01

    High serum day 3 FSH levels are associated with poor ovarian reserve and reduced fertility, but the interpretation of FSH values according to age is still not univocal. The purpose of this study was to determine age-dependent reference values in women with regular menstrual cycles and FSH as a guide for specialists. The study was performed at the Department of Mother-Infant of a University-based tertiary care centre. One-hundred ninety-two healthy normal menstruating women were recruited for the study. All patients attended the department on menstrual cycle day 3 for a blood sample for FSH and estradiol determination. A linear relationship between FSH or estradiol serum levels and age was observed. The FSH level increased by 0.11 IU for every year of age (1 IU for every 9 years of age). The values of FSH and estradiol corresponding to the 5th, 25th, 50th, 75th, 95th centiles for any specific age have been calculated. Serum FSH levels need to be interpreted according to age-dependent reference values. Serum FSH levels on 95th centile for any age may represent a warning sign for reduced ovarian reserve.

  19. Can the fall in serum FSH during coasting in IVF/ICSI predict clinical outcomes?

    PubMed

    Datta, Adrija Kumar; Zosmer, Ariel; Tozer, Amanda; Sabatini, Luca; Davis, Colin; Al-Shawaf, Talha

    2012-05-01

    This retrospective cohort study determined whether the total falls in serum FSH and oestradiol concentrations from start to end of coasting in IVF/intracytoplasmic sperm injection could predict clinical outcomes. Ninety-nine cycles, with gonadotrophin-releasing hormone-agonist down-regulation where coasting with serial serum oestradiol and FSH monitoring was adopted due to risk of severe ovarian hyperstimulation syndrome, were consecutively included. The primary clinical outcome was live-birth rate (LBR); other outcomes measured were number of oocytes retrieved and fertilization, implantation and clinical pregnancy rates. LBR for FSH fall>10 IU/l compared with 5-10 and<5 IU/l were 45.4% versus 22.0% and 25.0%, respectively. Mean serum FSH fall was similar with and without live birth (8.4 ± 6.2 versus 7.3 ± 5.0 IU/l) as were mean oestradiol and FSH concentrations on HCG administration, oestradiol fall, percentage fall in FSH/oestradiol and duration of coasting. None of the variables efficiently predicted live birth on regression analysis. The AUC of FSH fall was 0.53 at 11.0 IU/l. Basal FSH, starting and total gonadotrophin dose and duration of coasting were positively correlated with FSH fall. A potentially clinically important association between live birth and FSH fall during coasting was apparent, which requires further evaluation. The purpose of this retrospective cohort study was to determine whether the magnitude of fall in the serum FSH and oestradiol concentrations from start to end of coasting in IVF/intracytoplasmic sperm injection cycles could predict the clinical outcomes. Gonadotrophin-releasing hormone-agonist down-regulated cycles (n=99), where coasting with serial serum oestradiol and FSH monitoring was adopted due to risk of ovarian hyperstimulation, were consecutively included. Live birth was the primary clinical outcome measured; number of oocytes retrieved and fertilization, implantation and clinical pregnancy rates were the other outcomes

  20. Characterization of FSH signalling networks in bovine cumulus cells: a perspective on oocyte competence acquisition.

    PubMed

    Khan, D R; Guillemette, C; Sirard, M A; Richard, F J

    2015-09-01

    Understanding the mechanisms regulating oocyte developmental competence is essential to enhance the clinical efficiency of assisted reproduction. FSH orchestrates the acquisition of oocyte competence, both in vivo and in vitro. Multiple pathways are implicated in FSH signalling; however, their precise coordination remains unresolved. A robust system to investigate FSH signalling is oocyte in vitro maturation (IVM) and we have previously demonstrated better bovine embryo development after FSH addition for the first 6 h during IVM. Using this model, we investigated FSH signalling in cumulus through transcriptomic and pharmacological tools. We demonstrate modulation of cumulus transcriptome by FSH mainly through protein kinase A (PKA) and epidermal growth factor (EGF) pathways. Differentially expressed transcripts were implicated in cumulus expansion, steroidogenesis, cell metabolism and oocyte competence. FSH required rouse-sarcoma oncogene (SRC) for EGF receptor transactivation. PKA and EGF pathway crosstalk was investigated using extracellular signal-regulated kinases (ERK1/2) phosphorylation as the functional end-point. FSH enhanced ERK1/2 activation by the EGF pathway with a simultaneous diminution through PKA. More specifically, FSH increased dual specific phosphatase (DUSP1) transcripts via PKA although DUSP1 protein did not change since EGF was required to prevent degradation. Our findings implicate FSH in PKA and EGF pathway activation, which interact to maintain appropriate levels of ERK1/2 phosphorylation and eventually cumulus expansion, metabolism and steroidogenesis. Moreover, considering the implication of the EGF pathway in GDF9 and BMP15 actions, our findings suggest that FSH may have a role in modulation of the cumulus response to oocyte-secreted factors. This information has implications for improvement of IVM and hence oocyte developmental competence.

  1. [Synthèse of the LH-FSH-RH (author's transl)].

    PubMed

    Loffet, A; Durieux, J P

    1976-01-01

    The Luteinizing hormone-releasing hormone (LH-RH), and the follicle stimulating hormone-releasing hormone (FSH-RH) have been synthesized by a new procedure involving solid phase and conventional solution coupling. The release of LH and FSH by this synthetic product has been measured in both laboratory animals and in men. Results coincide exactly with those in the published literature.

  2. Dose of recombinant FSH and oestradiol concentration on day of HCG affect embryo development kinetics.

    PubMed

    Muñoz, Manuel; Cruz, María; Humaidan, Peter; Garrido, Nicolás; Pérez-Cano, Inmaculada; Meseguer, Marcos

    2012-10-01

    During follicular growth, the follicle is exposed to an almost ever-changing composition of isoforms of FSH and LH, which causes a number of different and divergent biological effects. Through a time-lapse system, embryo kinetics were examined following the use of FSH only (recombinant FSH, rFSH) and gonadotrophins containing LH activity (human menopausal gonadotrophin, HMG, and FSH+HMG) in oocyte donors. No significant differences were seen between the three groups (for rFSH, HMG and rFSH+HMG, t2 was 27.8h, 27.9h and 27.5h respectively). Moreover, although embryos obtained with rFSH showed an increase in the proportions of optimal timings of development, the differences observed were not significant, as shown by the percentages of embryos inside/outside these kinetic variables. In contrast, for gonadotrophin dosage and oestradiol concentration, this study observed differences in embryo development kinetics for some of the variables evaluated, which allowed the description of an optimal range of gonadotrophin dosage and oestradiol concentration. However, these kinetic differences did not translate into important distinctions in the proportion of optimal embryos with a higher implantation potential.

  3. FSH aggravates bone loss in ovariectomised rats with experimental periapical periodontitis

    PubMed Central

    Qian, Hua; Guan, Xiaoyue; Bian, Zhuan

    2016-01-01

    Periapical bone loss is one of the prominent pathological and clinical features of periapical periodontitis. Previous studies have demonstrated that follicle-stimulating hormone (FSH) could directly affect skeletal remodelling by stimulating the formation and the function of osteoclasts in vitro and in vivo. However, the effect of FSH on periapical bone loss remained to be fully elucidated. In the current study, a rat model was established in order to verify the effect of FSH in experimental periapical lesions. It was identified that FSH aggravated the bone loss of periapical lesions. In addition, RANKL-, TRAP-, TNF-α- and IL-1β-positive cells were increased significantly in FSH-treated groups, which indicated that the function of FSH in bone loss may be mediated through the increasing activity of osteoclasts and the increased secretion of inflammatory cytokines. The results of the current study suggested that FSH, independent of oestrogen, may aggravate periapical bone loss by FSH receptors, which may serve an important role in the immune and inflammatory response of the host to root canal and periradicular infection during menopause. PMID:27510616

  4. FSH protects mouse granulosa cells from oxidative damage by repressing mitophagy

    PubMed Central

    Shen, Ming; Jiang, Yi; Guan, Zhiqiang; Cao, Yan; Sun, Shao-chen; Liu, Honglin

    2016-01-01

    Oxidative stress has been implicated in triggering granulosa cell (GC) death during follicular atresia. Recent studies suggested that follicle-stimulating hormone (FSH) has a pivotal role in protecting GCs from oxidative injury, although the exact mechanism remains largely unknown. Here, we report that FSH promotes GC survival by inhibiting oxidative stress-induced mitophagy. The loss of GC viability caused by oxidative stress was significantly reduced after FSH treatment, which was correlated with impaired activation of mitophagy upon oxidative stress. Compared with FSH treatment, blocking mitophagy displayed approximate preventive effect on oxidative stress-induced GC death, but FSH did not further restore viability of cells pretreated with mitophagy inhibitor. Importantly, FSH suppressed the induction of serine/threonine kinase PINK1 during oxidative stress. This inhibited the mitochondrial translocation of the E3 ligase Parkin, which is required for the subsequent clearance of mitochondria, and ultimately cell death via mitophagy. In addition, knocking down PINK1 using RNAi confirmed the role of the FSH-PINK1-Parkin-mitophagy pathway in regulating GC survival under oxidative conditions. These findings introduce a novel physiological function of FSH in protecting GCs against oxidative damage by targeting PINK1-Parkin-mediated mitophagy. PMID:27901103

  5. Development of a flatfish-specific enzyme-linked immunosorbent assay for Fsh using a recombinant chimeric gonadotropin.

    PubMed

    Chauvigné, François; Verdura, Sara; Mazón, María José; Boj, Mónica; Zanuy, Silvia; Gómez, Ana; Cerdà, Joan

    2015-09-15

    In flatfishes with asynchronous and semicystic spermatogenesis, such as the Senegalese sole (Solea senegalensis), the specific roles of the pituitary gonadotropins during germ cell development, particularly of the follicle-stimulating hormone (Fsh), are still largely unknown in part due to the lack of homologous immunoassays for this hormone. In this study, an enzyme-linked immunosorbent assay (ELISA) for Senegalese sole Fsh was developed by generating a rabbit antiserum against a recombinant chimeric single-chain Fsh molecule (rFsh-C) produced by the yeast Pichia pastoris. The rFsh-C N- and C-termini were formed by the mature sole Fsh β subunit (Fshβ) and the chicken glycoprotein hormone common α subunit (CGA), respectively. Depletion of the antiserum to remove anti-CGA antibodies further enriched the sole Fshβ-specific antibodies, which were used to develop the ELISA using the rFsh-C for the standard curve. The sensitivity of the assay was 10 and 50 pg/ml for Fsh measurement in plasma and pituitary, respectively, and the cross-reactivity with a homologous recombinant single-chain luteinizing hormone was 1%. The standard curve for rFsh-C paralleled those of serially diluted plasma and pituitary extracts of other flatfishes, such as the Atlantic halibut, common sole and turbot. In Senegalese sole males, the highest plasma Fsh levels were found during early spermatogenesis but declined during enhanced spermiation, as found in teleosts with cystic spermatogenesis. In pubertal males, however, the circulating Fsh levels were as high as in adult spermiating fish, but interestingly the Fsh receptor in the developing testis containing only spermatogonia was expressed in Leydig cells but not in the primordial Sertoli cells. These results indicate that a recombinant chimeric Fsh can be used to generate specific antibodies against the Fshβ subunit and to develop a highly sensitive ELISA for Fsh measurements in diverse flatfishes.

  6. [Ovulation induction with pure FSH in anovulatory patients resistant to clomifene citrate].

    PubMed

    Kably-Ambe, A; Reyes-Cuervo, H; Barrón-Vallejo, J

    1996-07-01

    The objective was to evaluate the utility of the pure FSH as treatment of women clomiphene-resistant. Seventy two patients clomiphene-resistant were treated with pure FSH. Ovulation induction was started with 75 IU of pure FSH on day 3 of the menstrual cycle, monitoring the follicular growth with transvaginal ultrasonography, additional doses of pure FSH were administered accordingly. Human chorionic gonadotropin (10,000 IU) was administered when the dominant follicle reached a diameter > or = 16 mm. The pregnancy rate per cycle was 18.0%, on the other hand, the cumulate rate of pregnancy was 72.2%. There was not significant difference in the pregnancy rate between patients with primary or secondary infertility. The rate of spontaneous abortions was similar to the general population. As conclusion, it therefore appropriate to offer the treatment with pure FSH to patients clomiphene-resistance. The cases with gonadotropin-resistance, will be candidates to surgical procedures.

  7. Clinical efficacy and cost-effectiveness of HP-human FSH (Fostimon®) versus rFSH (Gonal-F®) in IVF-ICSI cycles: a meta-analysis.

    PubMed

    Gerli, Sandro; Bini, Vittorio; Favilli, Alessandro; Di Renzo, Gian Carlo

    2013-06-01

    Clinical efficacy of human-derived follicle-stimulating hormone (FSH) versus recombinant FSH (rFSH) in IVF-ICSI cycles has long been compared, but no clear evidence of the superiority of a preparation over the other has been found. Human gonadotropins have been often grouped together, but a different glycosylation may be present in each preparation, therefore influencing the specific bioactivity. To exclude confounding factors, a meta-analysis and a cost-effectiveness analysis were designed to compare effectiveness and cost-effectiveness of a specific highly purified human FSH (HP-hFSH) (Fostimon®) versus rFSH (Gonal-F®) in IVF/ICSI cycles. Research methodology filters were applied in MEDLINE, Current Contents and Web of Science from 1980 to February 2012. Eight randomized trials met selection criteria. The meta-analysis showed no significant differences between rFSH and HP-hFSH treatment in live-birth rate (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.63-1.11), clinical pregnancy rate (OR 0.85, 95% CI 0.68-1.07), number of oocytes retrieved, number of mature oocytes and days of stimulation. The cost-effectiveness ratio was € 7174 in the rFSH group and € 2056 in the HP-hFSH group. HP-hFSH is as effective as rFSH in ovarian stimulation for IVF-ICSI cycles, but the human preparation is more cost-effective.

  8. Fasting lowers gastrin-releasing peptide and FSH mRNA in the ovine anterior pituitary gland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogen receptor beta (ER-ß), LH, and FSH are important mediators of reproduction. FSH stimulates follicle recruitment and development. During anorexia, serum concentrations of FSH and LH decrease. Gastrin-releasing peptide (GRP), neuromedin B (NMB), peroxisome proliferator-activated receptor-gamma...

  9. Fasting lowers gastrin-releasing peptide and Fsh mRNA in the ovine anterior pituitary gland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogen receptor beta (ER-ß), LH, and FSH are important mediators of reproduction. FSH stimulates follicle recruitment and development. During anorexia, serum concentrations of FSH and LH decrease. Gastrin-releasing peptide (GRP), neuromedin B (NMB), peroxisome proliferator-activated receptor-gamma...

  10. Synthetic peptides corresponding to human follicle-stimulating hormone (hFSH)-beta-(1-15) and hFSH-beta-(51-65) induce uptake of 45Ca++ by liposomes: evidence for calcium-conducting transmembrane channel formation

    SciTech Connect

    Grasso, P.; Santa-Coloma, T.A.; Reichert, L.E. Jr. )

    1991-06-01

    We have previously described FSH receptor-mediated influx of 45Ca++ in cultured Sertoli cells from immature rats and receptor-enriched proteoliposomes via activation of voltage-sensitive and voltage-independent calcium channels. We have further shown that this effect of FSH does not require cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding protein or activation of adenylate cyclase. In the present study, we have identified regions of human FSH-beta-subunit which appear to be involved in mediating calcium influx. We screened 11 overlapping peptide amides representing the entire primary structure of hFSH-beta-subunit for their effects on 45Ca++ flux in FSH receptor-enriched proteoliposomes. hFSH-beta-(1-15) and hFSH-beta-(51-65) induced uptake of 45Ca++ in a concentration-related manner. This effect of hFSH-beta-(1-15) and hFSH-beta-(51-65) was also observed in liposomes lacking incorporated FSH receptor. Reducing membrane fluidity by incubating liposomes (containing no receptor) with hFSH-beta-(1-15) or hFSH-beta-(51-65) at temperatures lower than the transition temperatures of their constituent phospholipids resulted in no significant (P greater than 0.05) difference in 45Ca++ uptake. The effectiveness of the calcium ionophore A23187, however, was abolished. Ruthenium red, a voltage-independent calcium channel antagonist, was able to completely block uptake of 45Ca++ induced by hFSH-beta-(1-15) and hFSH-beta-(51-65) whereas nifedipine, a calcium channel blocker specific for L-type voltage-sensitive calcium channels, was without effect. These results suggest that in addition to its effect on voltage-sensitive calcium channel activity, interaction of FSH with its receptor may induce formation of transmembrane aqueous channels which also facilitate influx of extracellular calcium.

  11. FSH and bFGF stimulate the production of glutathione in cultured rat Sertoli cells.

    PubMed

    Gualtieri, Ariel F; Mazzone, Graciela L; Rey, Rodolfo A; Schteingart, Helena F

    2009-06-01

    Migration of developing germ cells from the basal to the adluminal compartment of the seminiferous epithelium requires extensive tissue restructuring, resulting in the production of reactive oxygen species. Sertoli cells are involved in this process. Glutathione (GSH), produced by Sertoli cells, has an essential role in cell protection against oxidative stress. Intracellular GSH content is maintained by de novo synthesis, involving glutamate-cysteine ligase catalytic (GCLC) and modulatory (GCLM) subunits, and by recycling from oxidized GSH, catalysed by glutathione reductase (GR). To assess whether follicle-stimulating hormone (FSH) and basic fibroblast growth factor (bFGF) modulate GSH production in Sertoli cells by regulating the expression of GCLC, GCLM and/or GR, we performed in vitro studies using rat Sertoli cells in primary culture. FSH and bFGF stimulation increased Sertoli cell GSH levels after 24 h incubation. The simultaneous addition of FSH and bFGF did not produce any further effect. GCLM expression was upregulated by FSH and bFGF 6 h. At 24 h, only the FSH-mediated effect was still observed. FSH and bFGF also upregulated GR expression. In conclusion, our results show that FSH and bFGF increase GSH levels in Sertoli cells through stimulation of the de novo synthesis and recycling by upregulating GCLM and GR expression respectively. Therefore, protection of germ cells against oxidative stress seems to be regulated by hormones and germ cell-released growth factors capable of influencing the production of Sertoli cell GSH.

  12. Bone loss in ovariectomized rats: dominant role for estrogen but apparently not for FSH.

    PubMed

    Rouach, V; Katzburg, S; Koch, Y; Stern, N; Somjen, D

    2011-01-01

    Estrogen deficiency as the sole factor underlying post-menopausal osteoporosis was challenged, in light of reports that both follicular stimulation hormone (FSH) receptor and FSHβ knockout mice were resistant to bone loss, suggesting a detrimental role for FSH. We assessed whether lowering FSH levels by gonadotropin realizing (GnRH) analog decapeptyl in ovariectomized female rats (OVX) affects bone. Wistar-derived 25 days old OVX female rats were injected for 10 weeks with estradiol-17β (E(2)), with GnRH analog (decapeptyl) or with both. FSH and luteinizing hormone (LH) serum levels were markedly increased in OVX rats, with smaller growth plates with disrupted architecture; heavy infiltration of bone marrow with numerous adipocytes and reduced thickness of cortical bone. In OVX rats treated with E(2), FSH, and LH levels were intermediate, the tibia was similar to that of intact rats, but there was reduced thickness of cortical bone. In decapeptyl treated OVX rats, FSH and LH levels were suppressed, the organization of growth plate and the trabecular bone were disrupted, and there were fewer proliferative and chondroblastic cells and a large adipocytes population in bone marrow, but an increased trabecular bone volume (TBV). In the E(2) + decapeptyl treatment, FSH and LH levels were suppressed, with partially restored growth plate architecture and improved TBV. In conclusion, E(2) deficiency is the dominant factor impairing bone loss in OVX and concomitant changes in FSH/LH levels achieved by decapeptyl have some modulating, though complex role in this setting. The role of high FSH levels in post-menopausal bone loss requires further investigation using combined sub-optimal doses of the different hormones.

  13. An Investigation on a Novel Anti-tumor Fusion Peptide of FSH33-53-IIKK

    PubMed Central

    Yang, Runlin; Liu, Ping; Pan, Donghui; zhang, Pengjun; Bai, Zhicheng; Xu, Yuping; Wang, Lizhen; Yan, Junjie; Yan, Yongjun; Liu, Xingdang; Yang, Min

    2016-01-01

    A novel fusion peptide FSH33-53-IIKK was designed and expected to combine the follicle stimulating hormone receptor (FSHR) targeting and tumor toxicity. In vitro and in vivo study showed the anti-tumor activity of FSH33-53-IIKK was enhanced compared to that of IIKK only. FSH33-53-IIKK could inhibit the growth of tumor via apoptosis and autophagy pathways. In summary, combining the tumor marker-target peptide and anti-tumor peptide together may be an efficient way to search for better anti-tumor candidates. PMID:27313792

  14. LAPS-FSH: a new and effective long-acting follicle-stimulating hormone analogue for the treatment of infertility.

    PubMed

    Jung, Sunyoung; Park, Youngjin; Kim, YoungHoon; Kim, Yu Yon; Choi, Hyun-Ji; Son, Woo-Chan; Kwon, SeChang

    2014-10-01

    Although several long-acting follicle-stimulating hormone (FSH) therapies have been developed to enhance the ovarian response, a disadvantage of FSH therapy is its relatively short half-life, which requires women to receive one to two injections per day for almost 2 weeks. In the present study, we developed a novel FSH analogue by conjugating recombinant human FSH (rhFSH) and the constant region of the human immunoglobulin G4 fragment via non-peptidyl linkers. The efficacy of the FSH analogue was evaluated in vitro by cAMP level assessments, pharmacokinetic studies and a determination of ovarian weight and by comparing these findings with the results from other FSH analogues. In addition, the total number of antral and Graafian follicles was determined after 7 days of treatment with control, 6µgkg(-1) follitropin β, 6, 12 or 42µgkg(-1) corifollitropin α or 3, 6 or 12µgkg(-1) long acting protein/peptide discovery-follicle-stimulating hormone (LAPS-FSH). As a result, the animals treated with 12µgkg(-1) LAPS-FSH produced additional and larger healthy follicles. These data demonstrate that LAPS-FSH promotes growth and inhibits atresia of the ovarian follicle compared with other available drugs, suggesting that our new drug enhances the efficacy and duration of treatment. It is expected that our new FSH analogue will result in a higher chance of pregnancy in patients who are unresponsive to other drugs.

  15. Cellular regulation of basal and FSH-stimulated cyclic AMP production in irradiated rat testes

    SciTech Connect

    Kangasniemi, M.; Kaipia, A.; Toppari, J.; Mali, P.; Huhtaniemi, I.; Parvinen, M. )

    1990-05-01

    Basal and follicle-stimulating hormone (FSH)-stimulated cyclic AMP (cAMP) productions by seminiferous tubular segments from irradiated adult rats were investigated at defined stages of the epithelial cycle when specific spermatogenic cells were low in number. Seven days post-irradiation, depletion of spermatogonia did not influence the basal cAMP production, but FSH response increased in stages II-VIII. Seventeen days post-irradiation when spermatocytes were low in number, there was a small increase in basal cAMP level in stages VII-VIII and FSH-stimulated cAMP production increased in stages VII-XII and XIII-I. At 38 days when pachytene spermatocytes and round spermatids (steps 1-6) were low in number, a decreased basal cAMP production was measured in stages II-VI and IX-XII. FSH-stimulated cAMP output increased in stages VII-XII but decreased in stages II-VI. At 52 days when all spermatids were low in number, basal cAMP levels decreased in all stages of the cycle, whereas FSH response was elevated only in stages VII-XII. All spermatogenic cell types seem to have an effect on cAMP production by the seminiferous tubule in a stage-specific fashion. Germ cells appear to regulate Sertoli cell FSH response in a paracrine way, and a part of cAMP may originate from spermatids stimulated by an unknown FSH-dependent Sertoli cell factor. The FSH-dependent functions may control such phenomena as spermatogonial proliferation, final maturation of spermatids, and onset of meiosis.

  16. FSH Regulates mRNA Translation in Mouse Oocytes and Promotes Developmental Competence.

    PubMed

    Franciosi, Federica; Manandhar, Shila; Conti, Marco

    2016-02-01

    A major challenge in assisted reproductive technology is to develop conditions for in vitro oocyte maturation yielding high-quality eggs. Efforts are underway to assess whether known hormonal and local factors play a role in oocyte developmental competence and to identify the molecular mechanism involved. Here we have tested the hypothesis that FSH improves oocyte developmental competence by regulating the translational program in the oocyte. Accumulation of oocyte proteins (targeting protein for the Xenopus kinesin xklp2 and IL-7) associated with improved oocyte quality is increased when cumulus-oocyte complexes are incubated with FSH. This increase is due to enhanced translation of the corresponding mRNAs, as indicated by microinjection of constructs in which the 3' untranslated region of the Tpx2 or Il7 transcripts is fused to the luciferase reporter. A transient activation of the phosphatidyl-inositol 3-phosphate/AKT cascade in the oocyte preceded the increase in translation. When the epidermal growth factor (EGF) receptor is down-regulated in follicular cells, the FSH-induced rate of maternal mRNA translation and AKT activation were lost, demonstrating that the effects of FSH are indirect and require EGF receptor signaling in the somatic compartment. Using Pten(fl/fl):Zp3cre oocytes in which the AKT is constitutively activated, translation of reporters was increased and was no longer sensitive to FSH stimulation. More importantly, the oocytes lacking the phosphate and tensin homolog gene showed increased developmental competence, even when cultured in the absence of FSH or growth factors. Thus, we demonstrate that FSH intersects with the follicular EGF network to activate the phosphatidyl-inositol 3-phosphate/AKT cascade in the oocyte to control translation and developmental competence. These findings provide a molecular rationale for the use of FSH to improve egg quality.

  17. Cellular regulation of follicle-stimulating hormone (FSH) binding in rat seminiferous tubules

    SciTech Connect

    Kangasniemi, M.; Kaipia, A.; Toppari, J.; Perheentupa, A.; Huhtaniemi, I.; Parvinen, M. )

    1990-07-01

    Stage-specific binding of follicle-stimulating hormone (FSH) was measured in rat seminiferous tubules. The binding in single-point assays was over 3-fold higher (P less than 0.05) in stages XIII to I than in stages VI to VII of the epithelial cycle. No difference was found between the equilibrium association constants (Ka) of FSH binding in stages XIV to IV (10 +/- 1.9 X 10(9) 1/mol) and VII to VIII (9.2 +/- 0.6 X 10(9) 1/mol, mean +/- SEM, n = 5). In another experiment, the testes were dosed locally with 3 Gy of 4 MV x-irradiation to selectively lower the number of spermatogonia. After irradiation, FSH binding in staged seminiferous tubule segments was measured when the desired types of spermatogenic cells were reduced in number. Seven days after irradiation when differentiating spermatogonia and preleptotene spermatocytes were reduced in number, FSH binding was decreased in all stages of the cycle, but the cyclic variation remained. Seventeen days after irradiation when intermediate and type B spermatogonia and spermatocytes up to diplotene of stage XIII showed low numbers, FSH binding was decreased in all stages of the cycle and the stage-dependent variation disappeared. At 38 days when pachytene spermatocytes and early spermatids were reduced in number, similar results were found. But at 52 days postirradiation when all spermatids were low in number, FSH binding was slightly elevated compared with days 17 and 38. There were no significant differences in serum FSH or LH levels between irradiated and non-irradiated animals. These findings suggest that all spermatogenic cell types may stimulate FSH binding in the Sertoli cells.

  18. Corticosterone inhibits normal and FSH-induced testicular recrudescence in the lizard, Mabuya carinata.

    PubMed

    Yajurvedi, H N; Nijagal, B S

    2000-12-01

    Administration (ip) of 1, 10, or 20 microg corticosterone (alternate days for 30 days) to adult male Mabuya carinata did not affect the seasonal recrudescence of spermatogenesis whereas administration of 40 microg corticosterone did result in inhibition of spermatogenesis. Further, administration of FSH (10 IU/lizard/alternate day for 30 days) during the quiescent phase of the testicular cycle stimulated spermatogenetic and steroidogenic activity of the testis as shown by significant increases in the mean number of spermatogonia, spermatocytes, and spermatids and serum levels of testosterone. In addition there were abundant spermatozoa in the lumen of the tubules in FSH-treated lizards. Administration of 10 IU FSH + 40 microg corticosterone (per lizard on alternate days for 30 days) increased the mean number of primary and secondary spermatocytes whereas the mean number of spermatids did not show significant variation compared with that of controls. Further, the mean numbers of spermatocytes and spermatids and serum levels of testosterone were significantly less when compared to those of FSH alone treated lizards. In addition, FSH-induced development of epididymis was also inhibited by corticosterone treatment. The results indicate that corticosterone inhibits FSH-induced testicular recrudescence, possibly by suppressing testosterone secretion in M. carinata.

  19. Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice

    PubMed Central

    Wang, Huizhen; Larson, Melissa; Jablonka-Shariff, Albina; Pearl, Christopher A.; Miller, William L.; Conn, P. Michael; Boime, Irving; Kumar, T. Rajendra

    2014-01-01

    FSH and luteinizing hormone (LH) are secreted constitutively or in pulses, respectively, from pituitary gonadotropes in many vertebrates, and regulate ovarian function. The molecular basis for this evolutionarily conserved gonadotropin-specific secretion pattern is not understood. Here, we show that the carboxyterminal heptapeptide in LH is a gonadotropin-sorting determinant in vivo that directs pulsatile secretion. FSH containing this heptapeptide enters the regulated pathway in gonadotropes of transgenic mice, and is released in response to gonadotropin-releasing hormone, similar to LH. FSH released from the LH secretory pathway rescued ovarian defects in Fshb-null mice as efficiently as constitutively secreted FSH. Interestingly, the rerouted FSH enhanced ovarian follicle survival, caused a dramatic increase in number of ovulations, and prolonged female reproductive lifespan. Furthermore, the rerouted FSH vastly improved the in vivo fertilization competency of eggs, their subsequent development in vitro and when transplanted, the ability to produce offspring. Our study demonstrates the feasibility to fine-tune the target tissue responses by modifying the intracellular trafficking and secretory fate of a pituitary trophic hormone. The approach to interconvert the secretory fate of proteins in vivo has pathophysiological significance, and could explain the etiology of several hormone hyperstimulation and resistance syndromes. PMID:24706813

  20. Isolation and partial characterization of LH, FSH and TSH from canine pituitary gland.

    PubMed

    Chiba, K; Kobayashi, H; Wakabayashi, K

    1997-04-01

    A new preparative procedure without using ion-exchanger is described for the efficient purification of canine LH (cLH), FSH (cFSH) and TSH (cTSH) from the pituitary gland. The hormones were extracted from the pituitary homogenate with an ammonium sulfate solution, and were separated by Concanavalin (Con) A affinity-, hydrophobic interaction-, then immobilized metal ion affinity chromatography. In the immobilized metal ion affinity chromatography, we used copper (Cu2+) as chelated metal ion with ammonium ion gradient and pH gradient in phosphate buffer to attain separation of the hormones. High purity of cLH, cFSH and cTSH was indicated as single bands in SDS-PAGE, with apparent molecular masses of 34, 36 and 37 kDA, respectively. The purified hormones showed two bands corresponding to alpha (20 kDa) and beta subunits (cLH beta: 16 kDa, cFSH beta: 22 kDa, cTSH beta: 16 kDa) under reducing condition in SDS-PAGE. The purified hormones were prepared in good recovery (LH: 53%, FSH: 34%, TSH: 36%) with high biological activity or binding activity to the receptor. Cross-contamination of the purified hormone was less than 0.5%. Examination of the hormone fraction with isoelectric focusing showed that major peaks of isoelectric isoforms were maintained throughout the purification steps of cLH and cFSH, while a few peaks were lost in Con A affinity chromatography in cTSH purification. It was concluded that the present method could prepare highly purified cLH, cFSH and cTSH which retained isoforms of the hormones and biological activity or binding affinity to the receptor.

  1. Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation

    PubMed Central

    Chowdhury, Indrajit; Thomas, Kelwyn; Zeleznik, Anthony

    2016-01-01

    Published results from our laboratory identified prohibitin (PHB), a gene product expressed in granulosa cells (GCs) that progressively increases during follicle maturation. Our current in vitro studies demonstrate that follicle-stimulating hormone (FSH) stimulates Phb expression in rat primary GCs. The FSH-dependent expression of PHB was primarily localized within mitochondria, and positively correlates with the morphological changes in GCs organelles, and synthesis and secretions of estradiol (E2) and progesterone (P4). In order to confirm that PHB plays a regulatory role in rat GC differentiation, endogenous PHB-knockdown studies were carried out in undifferentiated GCs using adenoviral (Ad)-mediated RNA interference methodology. Knockdown of PHB in GCs resulted in the suppression of the key steroidogenic enzymes including steroidogenic acute regulatory protein (StAR), p450 cholesterol side-chain cleavage enzyme (p450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), and aromatase (Cyp19a1); and decreased E2 and P4 synthesis and secretions in the presence of FSH stimulation. Furthermore, these experimental studies also provided direct evidence that PHB within the mitochondrial fraction in GCs is phosphorylated at residues Y249, T258, and Y259 in response to FSH stimulation. The observed levels of phosphorylation of PHB at Y249, T258, and Y259 were significantly low in GCs in the absence of FSH stimulation. In addition, during GC differentiation FSH-induced expression of phospho-PHB (pPHB) requires the activation of MEK1-ERK1/2 signaling pathway. Taken together, these studies provide new evidence supporting FSH-dependent PHB/pPHB upregulation in GCs is required to sustain the differentiated state of GCs. PMID:27044659

  2. Single-chain bifunctional vascular endothelial growth factor (VEGF)-follicle-stimulating hormone (FSH)-C-terminal peptide (CTP) is superior to the combination therapy of recombinant VEGF plus FSH-CTP in stimulating angiogenesis during ovarian folliculogenesis.

    PubMed

    Trousdale, Rhonda K; Pollak, Susan V; Klein, Jeffrey; Lobel, Leslie; Funahashi, Yasuhiro; Feirt, Nikki; Lustbader, Joyce W

    2007-03-01

    Infertility technologies often employ exogenous gonadotropin therapy to increase antral follicle production. In an effort to enhance ovarian response, several long-acting FSH therapies have been developed including an FSH-C-terminal peptide (CTP), where the FSH subunits are linked by the CTP moiety from human chorionic gonadotropin, which is responsible for the increased half-life of human chorionic gonadotropin. We found that administration of FSH-CTP for ovarian hyperstimulation in rats blunted ovarian follicle vascular development. In women, reduced ovarian vasculature has been associated with lower pregnancy rates. We were interested in determining whether vascular endothelial growth factor (VEGF) therapy could enhance ovarian angiogenesis in FSH-CTP-treated rats. Coadministration of systemic FSH-CTP plus recombinant VEGF was compared with treatment with a novel, single-chain bifunctional VEGF-FSH-CTP (VFC) analog. For VFC, the FSH portion targets the protein to the ovary and stimulates follicle growth, whereas VEGF enhances local vascular development. Both in vitro and in vivo studies confirm the dual FSH and VEGF action of the VFC protein. Evaluation of ovarian follicle development demonstrates that administration of combination therapy using VEGF and FSH-CTP failed to increase follicle vasculature above levels seen with FSH-CTP monotherapy. However, treatment with VFC significantly increased follicle vascular development while concurrently increasing the number of large antral follicles produced. In conclusion, we report the production and characterization of a long-acting, bifunctional VEGF-FSH-CTP protein that is superior to combination therapy for enhancing VEGF activity in the ovary and stimulating follicular angiogenesis in rats.

  3. Cloning and sequence analysis of FSH and LH in the giant panda (Ailuropoda melanoleuca).

    PubMed

    Liao, Ming-Juan; Zhu, Mu-Yuan; Zhang, Zhi-He; Zhang, An-Ju; Li, Guang-Han; Sheng, Fu-Jun

    2003-05-15

    The giant panda (Ailuropoda melanoleuca) is an endangered species and indigenous to China. It has been proposed that it has a highly specialized reproductive pattern with low fecundity, but little is known about its basic reproductive biology at the molecular level. In this report the genes encoding gonadotropin subunits alpha, follicle-stimulating hormone (FSH) beta and luteinizing hormone (LH) beta of the giant panda were amplified for the first time by RT-PCR from pituitary total RNA, and were cloned, sequenced and analyzed. The results revealed that the open reading region (ORF) of gonadotropin subunits alpha, FSH beta and LH beta are 363, 390 and 426 bp long, respectively. They displayed a reasonably high degree (74-94, 85-93, 75-91%, for alpha, FSH beta and LH beta subunits, respectively) of identity when deduced amino acids were compared with homologous sequences from partial available mammals including human, cattle, sheep, pig, rat, mouse. Three distinct differences were found at the site of 59 aa of the alpha subunit and 55 aa, 68 aa of FSH beta subunit. Our results provide an insight into understanding the mechanism of reproduction regulation and genetic characteristics of giant panda which will make an actual contribution to its conservation. In addition they lay a foundation for a further study towards producing recombinant panda FSH and LH which can be used in artificial breeding aimed to increase its captive reproductive efficiency.

  4. Androgen and FSH synergistically stimulate lipoprotein degradation and utilization by ovary granulosa cells

    SciTech Connect

    Schreiber, J.R.; Nakamura, K.; Schmit, V.; Weinstein, D.B.

    1984-01-01

    Androgen can directly modulate the induction of steroidogenic enzymes by FSH (follicle stimulating hormone) in ovary granulosa cells. In studies of its mechanism of action, the authors examined the androgen effect on granulosa cell interaction with lipoproteins, the physiologic source of cholesterol. After granulosa cells were cultured for 48 hours with and without androgen and/or FSH, the cells were incubated for 24 hours with /sup 125/I-lipoproteins (human high density lipoprotein (HDL), rat HDL, or human low density lipoprotein (LDL)). The media were then analyzed for lipoprotein protein coat degradation products (mainly /sup 125/I-monoiodotyrosine) and progestin (mainly 20 alpha-dihydroprogesterone (20 alpha-DHP)). In the absence of FSH and androgen, 2 X 10(5) granulosa cells degraded basal levels of all three lipoproteins, but produced no measurable 20 alpha-DHP. The addition of 10(-7) M androstenedione (A), testosterone (T), or 5 alpha-dihydrotestosterone (DHT) had no effect on lipoprotein protein degradation or 20 alpha-DHP production. FSH alone stimulated lipoprotein protein degradation by 50 to 300% while the addition of androgen synergistically augmented the FSH-stimulated 20 alpha-DHP production as well as protein coat degradation of all three lipoproteins. DHT and T were both effective, indicating that androgens themselves, and not estrogen products, were responsible for the effect on lipoprotein protein degradation and 20 alpha-DHP production.

  5. Synthesis and characterization of biologically active recombinant elk and horse FSH.

    PubMed

    Fachal, María Victoria; Furlan, Mike; Clark, Rena; Card, Claire E; Chedrese, P Jorge

    2010-02-01

    The objective of this investigation was to clone and express the elk and horse common alpha-subunit and FSH beta-subunit cDNAs, and to produce recombinant FSH from both species in vitro. The RNAs extracted from elk and horse pituitary glands were reverse-transcribed and amplified by polymerase chain reaction. The cDNAs corresponding to both subunits of elk and horse were cloned into the expression vector pBudCE4.1 and transfected into CRL-9096 cells. Expression of both genes was determined in the transfected cells by Northern and Western blot analysis. Recombinant elk and horse FSH secreted in culture media were characterized by an in vitro bioassay and RIA. When the recombinant products were assessed as activity over mass of FSH measured by RIA, the horse product was 5.6 times more potent than the elk product. The recombinant products injected to immature female Wistar rats stimulated ovarian growth. The results suggest that the products obtained correspond to recombinant versions of the native elk and horse FSH. The availability of these recombinant products may aid in the development of more predictable and efficient techniques of ovarian stimulation in cervids, equids, and other species as well.

  6. Production of biologically active recombinant goose FSH in a single chain form with a CTP linker sequence.

    PubMed

    Li, Hui; Zhu, Huanxi; Qin, Qinming; Lei, Mingming; Shi, Zhendan

    2017-02-01

    FSH is a glycoprotein hormone secreted by the pituitary gland that is essential for gonadal development and reproductive function. In avian reproduction study, especially in avian reproduction hormone study, it is hindered by the lack of biologically active FSH. In order to overcome this shortcoming, we prepared recombinant goose FSH as a single chain molecule and tested its biological activities in the present study. Coding sequences for mature peptides of goose FSH α and β subunits were amplified from goose pituitary cDNA. A chimeric gene containing α and β subunit sequences linked by the hCG carboxyl terminal peptide coding sequence was constructed. The recombinant gene was inserted into the pcDNA3.1-Fc eukaryotic expression vector to form pcDNA-Fc-gFSHβ-CTP-α and then transfected into 293-F cells. A recombinant, single chain goose FSH was expressed and verified by SDS-PAGE and western blot analysis, and was purified using Protein A agarose affinity and gel filtration chromatography. Biological activity analysis results showed that the recombinant, chimeric goose FSH possesses the function of stimulating estradiol secretion and cell proliferation, in cultured chicken granulosa cells. These results indicated that bioactive, recombinant goose FSH has been successfully prepared in vitro. The recombinant goose FSH will have the potential of being used as a research tool for studying avian reproductive activities, and as a standard for developing avian FSH bioassays.

  7. Pubertal Onset in Girls is Strongly Influenced by Genetic Variation Affecting FSH Action

    PubMed Central

    Hagen, Casper P.; Sørensen, Kaspar; Aksglaede, Lise; Mouritsen, Annette; Mieritz, Mikkel G.; Tinggaard, Jeanette; Wohlfart-Veje, Christine; Petersen, Jørgen Holm; Main, Katharina M.; Meyts, Ewa Rajpert-De; Almstrup, Kristian; Juul, Anders

    2014-01-01

    Age at pubertal onset varies substantially in healthy girls. Although genetic factors are responsible for more than half of the phenotypic variation, only a small part has been attributed to specific genetic polymorphisms identified so far. Follicle-stimulating hormone (FSH) stimulates ovarian follicle maturation and estradiol synthesis which is responsible for breast development. We assessed the effect of three polymorphisms influencing FSH action on age at breast deveopment in a population-based cohort of 964 healthy girls. Girls homozygous for FSHR -29AA (reduced FSH receptor expression) entered puberty 7.4 (2.5–12.4) months later than carriers of the common variants FSHR -29GG+GA, p = 0.003. To our knowledge, this is the strongest genetic effect on age at pubertal onset in girls published to date. PMID:25231187

  8. [Low-dose desmopressin (DDAVP) and blood levels of FSH, LH and testosterone in men].

    PubMed

    García-Pascual, I J; Rozán Flores, M A

    1996-03-01

    The effect of desmopressin (DDAVP) administration (2.5 micrograms/12 hours) on serum concentrations of FSH, LH and testosterone was studied in six men. No significant changes were observed in serum concentrations of FSH and LH after 9 days with DDAVP therapy. Nevertheless, serum concentrations of testosterone after 12 hours of DDAVP administration were significantly higher than basal concentrations. Three hours after the administration of DDAVP, serum testosterone concentrations decreased significantly. The conclusion reached was that low doses of desmopressin do not change serum concentrations of FSH and LH, but serum concentration of testosterone is decreased within three hours after the administration, although an increase is observed 12 hours later possibly due to a "rebound effect". Desmopressin would therefore directly act upon human testicle.

  9. Unexpected effect of the vehicle (grain ethanol) of homeopathic FSH on the in vitro survival and development of isolated ovine preantral follicles.

    PubMed

    Lima, Lartiza F; Rocha, Rebeca M P; Duarte, Ana Beatriz G; Brito, Ivina R; Silva, Gerlane M; Rodrigues, Giovanna Q; Nunes-Pinheiro, Diana C S; Sales, Antônia D; Moura, Arlindo A; Wheeler, Matthew B; Rodrigues, Ana Paula R; Campello, Cláudio C; Figueiredo, José Ricardo

    2017-04-01

    The aims of this study were to investigate the effects of medium replacement system (experiment I) and of FSH presentations (homeopathic - FSH 6cH and allopathic FSH - rFSH; experiment II) on the in vitro development, hormone production and gene expression of isolated ovine preantral follicles cultured for 6 days. In experiment I, secondary follicles were cultured in the α-MEM(+) supplemented with FSH 6cH (0.05 fg/ml) or recombinant bovine FSH (100 ng/ml) without/with daily medium addition. The homeopathic FSH treatments with/without medium addition improved (p < .05) follicular development compared to rFSH100 treatment without addition. FSH 6cH with addition showed the highest (p < .05) estradiol production. To verify whether the effects of homeopathic FSH were not due to its vehicle, experiment II was performed. The α-MEM(+) was supplemented or not with alcohol (0.2% grain ethanol, v/v), FSH 6cH or rFSH100 with daily medium addition. Surprisingly, we found that all treatments improved follicular development compared to the α-MEM(+) (p < .05). Moreover, homeopathic FSH was similar to the other treatments including its vehicle. In conclusion, its vehicle (ethanol) causes the effect of homeopathic FSH on in vitro development of isolated ovine preantral follicles.

  10. Fsh and Lh direct conserved and specific pathways during flatfish semicystic spermatogenesis.

    PubMed

    Chauvigné, François; Zapater, Cinta; Crespo, Diego; Planas, Josep V; Cerdà, Joan

    2014-10-01

    The current view of the control of spermatogenesis by Fsh and Lh in non-mammalian vertebrates is largely based on studies carried out in teleosts with cystic and cyclic spermatogenesis. Much less is known concerning the specific actions of gonadotropins during semicystic germ cell development, a type of spermatogenesis in which germ cells are released into the tubular lumen where they transform into spermatozoa. In this study, using homologous gonadotropins and a candidate gene approach, for which the genes' testicular cell-type-specific expression was established, we investigated the regulatory effects of Fsh and Lh on gene expression during spermatogenesis in Senegalese sole (Solea senegalensis), a flatfish with asynchronous and semicystic germ cell development. During early spermatogenesis, Fsh and Lh upregulated steroidogenesis-related genes and nuclear steroid receptors, expressed in both somatic and germ cells, through steroid-dependent pathways, although Lh preferentially stimulated the expression of downstream genes involved in androgen and progestin syntheses. In addition, Lh specifically promoted the expression of spermatid-specific genes encoding spermatozoan flagellar proteins through direct interaction with the Lh receptor in these cells. Interestingly, at this spermatogenic stage, Fsh primarily regulated genes encoding Sertoli cell growth factors with potentially antagonistic effects on germ cell proliferation and differentiation through steroid mediation. During late spermatogenesis, fewer genes were regulated by Fsh or Lh, which was associated with a translational and posttranslational downregulation of the Fsh receptor in different testicular compartments. These results reveal that conserved and specialized gonadotropic pathways regulate semicystic spermatogenesis in flatfish, which may spatially adjust cell germ development to maintain a continuous reservoir of spermatids in the testis.

  11. Superovulation of goats with purified pFSH supplemented with defined amounts of pLH.

    PubMed

    Nowshari, M A; Backers, J F; Holtz, W

    1995-03-01

    The superovulatory response of goats treated with purified pFSH supplemented with 30, 40 or 50% pLH was compared. Sixty-four Boer goat does were synchronized by progestagen-containing ear implant, randomly allotted to 3 groups and, beginning 2 d before implant removal, treated with purified pFSH supplemented with 30, 40 or 50% pLH. Each animal received 16 Armour Units of pFSH administered in 6 descending doses at 12-h intervals. Along with the last 2 injections, the does received 5 mg PGF(2alpha). Embryos were flushed either surgically or after slaughter on Day 5 or 6 after the last day of standing estrus. The percentage of animals responding to treatment was not different among groups treated with pFSH supplemented with 30, 40 or 50% pLH (76, 71 and 63%, respectively). The corresponding data for number of ovulations was 11.3 +/- 1.6, 16.3 +/- 1.8 and 16.4 +/- 2.6, for number of ova and embryos recovered 8.1 +/- 1.9, 12.0 +/- 1.5 and 13.5 +/- 2.9 and for number of transferable embryos 6.6 +/- 1.9, 9.1 +/- 1.5 and 7.1 +/- 2.1 (x +/- SEM). Results confirm the earlier finding of a good response of goats to pFSH preparations with a high FSH:LH ratio, and, although group differences were statistically nonsignificant (P > 0.05), they suggest that supplementation with approximately 40% pLH may be close to the optimum.

  12. NO-mediated regulation of GLUT by T3 and FSH in rat granulosa cells.

    PubMed

    Tian, Ye; Ding, Yu; Liu, Juan; Heng, Dai; Xu, Kaili; Liu, Wenbo; Zhang, Cheng

    2017-03-17

    Thyroid hormones (THs) are important for normal reproductive function. Although 3,5,3'-triiodothyronine (T3) enhances follicle-stimulating hormone (FSH)-induced preantral follicle growth and granulosa cells development in vitro, little is known about the molecular mechanisms regulating ovarian development via glucose. In this study, we investigated whether and how T3 combines with FSH to regulate glucose transporter protein (GLUT) expression and glucose uptake in granulosa cells. Here, we present evidence that T3 and FSH co-treatment significantly increased GLUT-1/GLUT-4 expression, and translocation in cells, as well as glucose uptake. These changes were accompanied by upregulation of NOS3 expression, total NOS and NOS3 activity and NO content in granulosa cells. Furthermore, we found that activation of the mTOR and PI3K/Akt pathway is required for the regulation of GLUT expression, translocation, and glucose uptake by hormones. We also found that L-arginine (L-arg) up-regulated GLUT-1/GLUT-4 expression and translocation, which were related to increased glucose uptake, however, these responses were significantly blocked by L-NAME. In addition, inhibiting NO production attenuated T3 and FSH-induced GLUT expression, translocation, and glucose uptake in granulosa cells. Our data demonstrate that T3 and FSH co-treatment potentiates cellular glucose uptake via GLUT upregulation and translocation, which are mediated through the activation of the mTOR/PI3K/Akt pathway. Meanwhile, NOS3/NO are also involved in this regulatory system. These findings suggest that GLUT is a novel mediator of T3 and FSH-induced follicular development.

  13. Expression profiles of Fsh-regulated ovarian genes during oogenesis in coho salmon.

    PubMed

    Guzmán, José M; Luckenbach, J Adam; Yamamoto, Yoji; Swanson, Penny

    2014-01-01

    The function of follicle-stimulating hormone (Fsh) during oogenesis in fishes is poorly understood. Using coho salmon as a fish model, we recently identified a suite of genes regulated by Fsh in vitro and involved in ovarian processes mostly unexplored in fishes, like cell proliferation, differentiation, survival or extracellular matrix (ECM) remodeling. To better understand the role of these Fsh-regulated genes during oocyte growth in fishes, we characterized their mRNA levels at discrete stages of the ovarian development in coho salmon. While most of the transcripts were expressed at low levels during primary growth (perinucleolus stage), high expression of genes associated with cell proliferation (pim1, pcna, and mcm4) and survival (ddit4l) was found in follicles at this stage. The transition to secondary oocyte growth (cortical alveolus and lipid droplet stage ovarian follicles) was characterized by a marked increase in the expression of genes related to cell survival (clu1, clu2 and ivns1abpa). Expression of genes associated with cell differentiation and growth (wt2l and adh8l), growth factor signaling (inha), steroidogenesis (cyp19a1a) and the ECM (col1a1, col1a2 and dcn) peaked in vitellogenic follicles, showing a strong and positive correlation with transcripts for fshr. Other genes regulated by Fsh and associated with ECM function (ctgf, wapl and fn1) and growth factor signaling (bmp16 and smad5l) peaked in maturing follicles, along with increases in steroidogenesis-related gene transcripts. In conclusion, ovarian genes regulated by Fsh showed marked differences in their expression patterns during oogenesis in coho salmon. Our results suggest that Fsh regulates different ovarian processes at specific stages of development, likely through interaction with other intra- or extra-ovarian factors.

  14. Fsh Stimulates Spermatogonial Proliferation and Differentiation in Zebrafish via Igf3.

    PubMed

    Nóbrega, Rafael Henrique; Morais, Roberto Daltro Vidal de Souza; Crespo, Diego; de Waal, Paul P; de França, Luiz Renato; Schulz, Rüdiger W; Bogerd, Jan

    2015-10-01

    Growth factors modulate germ line stem cell self-renewal and differentiation behavior. We investigate the effects of Igf3, a fish-specific member of the igf family. Fsh increased in a steroid-independent manner the number and mitotic index of single type A undifferentiated spermatogonia and of clones of type A differentiating spermatogonia in adult zebrafish testis. All 4 igf gene family members in zebrafish are expressed in the testis but in tissue culture only igf3 transcript levels increased in response to recombinant zebrafish Fsh. This occurred in a cAMP/protein kinase A-dependent manner, in line with the results of studies on the igf3 gene promoter. Igf3 protein was detected in Sertoli cells. Recombinant zebrafish Igf3 increased the mitotic index of type A undifferentiated and type A differentiating spermatogonia and up-regulated the expression of genes related to spermatogonial differentiation and entry into meiosis, but Igf3 did not modulate testicular androgen release. An Igf receptor inhibitor blocked these effects of Igf3. Importantly, the Igf receptor inhibitor also blocked Fsh-induced spermatogonial proliferation. We conclude that Fsh stimulated Sertoli cell production of Igf3, which promoted via Igf receptor signaling spermatogonial proliferation and differentiation and their entry into meiosis. Because previous work showed that Fsh also released spermatogonia from an inhibitory signal by down-regulating anti-Müllerian hormone and by stimulating androgen production, we can now present a model, in which Fsh orchestrates the activity of stimulatory (Igf3, androgens) and inhibitory (anti-Müllerian hormone) signals to promote spermatogenesis.

  15. Successful use of aromatase inhibitor letrozole in NOA with an elevated FSH level: a case report.

    PubMed

    Zhao, D; Pan, L; Zhang, F; Pan, F; Ma, J; Zhang, X; Liu, Y

    2014-05-01

    Aromatase inhibitors inhibit the conversion of testosterone to oestrogens and could reduce serum oestradiol concentrations. Letrozole is one of aromatase inhibitors frequently used in treatment of men with oligospermia. We present the case of an infertile man with small testes and an elevated FSH level, which was diagnosed as NOA, hypospermatogenesis proven by testicular biopsy. After taking letrozole for 3 months, semen analyses by computer-aided sperm analysis present that this man had normal spermatogenesis. This is the first case report of the activation of spermatogenesis, in man who was NOA with elevated FSH level, resulting from the use of the one of aromatase inhibitors.

  16. Efficacy of a single intramuscular injection of porcine FSH in hyaluronan prior to ovum pick-up in Holstein cattle.

    PubMed

    Vieira, L M; Rodrigues, C A; Netto, A Castro; Guerreiro, B M; Silveira, C R A; Freitas, B G; Bragança, L G M; Marques, K N G; Sá Filho, M F; Bó, G A; Mapletoft, R J; Baruselli, P S

    2016-03-15

    Plasma FSH profiles, in vitro embryo production (IVP) after ovum pickup (OPU), and establishment of pregnancy with IVP embryos were compared in untreated Holstein oocyte donors and those superstimulated with multiple injections or a single intramuscular (IM) injection of porcine FSH (pFSH) in hyaluronan (HA). Plasma FSH profiles were determined in 23 heifers randomly allocated to one of four groups. Controls received no treatment, whereas the F200 group received 200 mg of pFSH in four doses, 12 hours apart. The F200HA and F300HA groups received 200- or 300-mg pFSH in 5 mL or 7.5 mL, respectively of a 0.5% HA solution by a single IM injection. Plasma FSH levels were determined before the first pFSH treatment and every 6 hours over 96 hours. All data were analyzed by orthogonal contrasts. Circulating FSH area under curve (AUC) in pFSH-treated animals was greater than that in the control group (P = 0.02). Although the AUC did not differ among FSH-treated groups (P = 0.56), the total period with elevated plasma FSH was greater in the F200 group than in the HA groups (P < 0.0001). However, the F300HA group had a greater AUC than the F200HA group (P = 0.006), with a similar total period with elevated plasma FSH (P = 0.17). The IVP was performed in 90 nonlactating Holstein cows randomly allocated to one of the four treatment groups as in the first experiment. A greater proportion of medium-sized (6-10 mm) follicles was observed in cows receiving pFSH, regardless of the treatment group (P < 0.0001). Also, numbers of follicles (P = 0.01), cumulus-oocyte complexes (COCs) retrieved (P = 0.01) and matured (P = 0.02), cleavage rates (P = 0.002), and blastocysts produced per OPU session (P = 0.06) were greater in cows receiving pFSH, regardless of the treatment group. Cows in the F200HA group had a greater recovery rate (P = 0.009), number of COCs cultured (P = 0.04), and blastocysts produced per OPU session (P = 0.06) than cows in the F300HA group. Similar pregnancy rates were

  17. Comparing anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH) as predictors of ovarian function.

    PubMed

    Barad, David H; Weghofer, Andrea; Gleicher, Norbert

    2009-04-01

    We compared predictive values of anti-Müllerian hormone (AMH) and baseline FSH with respect to IVF cycle outcomes based on oocyte numbers retrieved and number of clinical pregnancies established. In 76 IVF cycles investigated, AMH was clearly superior in predicting IVF outcomes in comparison with FSH.

  18. High levels of testosterone inhibit ovarian follicle development by repressing the FSH signaling pathway.

    PubMed

    Liu, Tao; Cui, Yu-qian; Zhao, Han; Liu, Hong-bin; Zhao, Shi-dou; Gao, Yuan; Mu, Xiao-li; Gao, Fei; Chen, Zi-jiang

    2015-10-01

    The effect of high concentrations of testosterone on ovarian follicle development was investigated. Primary follicles and granulosa cells were cultured in vitro in media supplemented with a testosterone concentration gradient. The combined effects of testosterone and follicle-stimulating hormone (FSH) on follicular growth and granulosa cell gonadotropin receptor mRNA expression were also investigated. Follicle growth in the presence of high testosterone concentrations was promoted at early stages (days 1-7), but inhibited at later stage (days 7-14) of in vitro culture. Interestingly, testosterone-induced follicle development arrest was rescued by treatment with high concentrations of FSH (400 mIU/mL). In addition, in cultured granulosa cells, high testosterone concentrations induced cell proliferation, and increased the mRNA expression level of FSH receptor (FSHR), and luteinized hormone/choriogonadotropin receptor. It was concluded that high concentrations of testosterone inhibited follicle development, most likely through regulation of the FSH signaling pathway, although independently from FSHR downregulation. These findings are an important step in further understanding the pathogenesis of polycystic ovary syndrome.

  19. FSHbeta gene mutation in a female with delayed puberty and hypogonadism: response to recombinant human FSH.

    PubMed

    Kottler, M L; Richard, N; Chabre, O; Alain, S; Young, J

    2009-01-01

    We report a woman with primary amenorrhoea and infertility associated with an isolated deficiency of pituitary FSH that does not respond to GnRH administration. Serum inhibin B was undetectable and antimullerian hormone (AMH) was within the normal range. Ultra sound examination revealed a small uterus and small ovaries with few small follicles. We identified an homozygous 1-bp (G) deletion at codon 79 in FSHbeta gene suggesting a complete loss of function. The patient underwent studies of ovarian responsiveness to recombinant human FSH according to the following protocol: 150UI/d for five days following by 75 UI/d for 10 days. Estradiol plasma level started to increase from day 5 associated to a sharp increase of inhibine B and a decrease of LH. During the same time, we observed an excessive development of multiple follicles resulting in an arrest of the treatment to avoid hyperstimulation. The present study confirm that follicles up to 5 mm in diameter had developed in the absence of FSH and that FSH is required for the growth of follicles beyond the two-layer granulose stage.

  20. Mutations and polymorphisms in FSH receptor: functional implications in human reproduction.

    PubMed

    Desai, Swapna S; Roy, Binita Sur; Mahale, Smita D

    2013-12-01

    FSH brings about its physiological actions by activating a specific receptor located on target cells. Normal functioning of the FSH receptor (FSHR) is crucial for follicular development and estradiol production in females and for the regulation of Sertoli cell function and spermatogenesis in males. In the last two decades, the number of inactivating and activating mutations, single nucleotide polymorphisms, and spliced variants of FSHR gene has been identified in selected infertile cases. Information on genotype-phenotype correlation and in vitro functional characterization of the mutants has helped in understanding the possible genetic cause for female infertility in affected individuals. The information is also being used to dissect various extracellular and intracellular events involved in hormone-receptor interaction by studying the differences in the properties of the mutant receptor when compared with WT receptor. Studies on polymorphisms in the FSHR gene have shown variability in clinical outcome among women treated with FSH. These observations are being explored to develop molecular markers to predict the optimum dose of FSH required for controlled ovarian hyperstimulation. Pharmacogenetics is an emerging field in this area that aims at designing individual treatment protocols for reproductive abnormalities based on FSHR gene polymorphisms. The present review discusses the current knowledge of various genetic alterations in FSHR and their impact on receptor function in the female reproductive system.

  1. Development of an homologous radioimmunoassay for chicken follicle-stimulating hormone and measurement of plasma FSH during the ovulatory cycle.

    PubMed

    Krishnan, K A; Proudman, J A; Bolt, D J; Bahr, J M

    1993-08-01

    1. A highly specific and sensitive homologous radioimmunoassay was developed for measurement of chicken follicle stimulating hormone (cFSH). 2. Mammalian gonadotropin releasing hormone (GnRH) significantly stimulated secretion of chicken luteinising hormone (cLH) but not cFSH when administered to 22 week non-laying hens. 3. Chicken GnRH-I did not affect circulating cFSH concentrations but significantly stimulated cLH secretion when administered to 3 week cockerels. 4. The plasma concentration of cFSH was low throughout the ovulatory cycle, but a significant decline in cFSH occurred prior to the pre-ovulatory LH surge and a significant increase occurred during the 3 hr prior to oviposition as LH levels decline.

  2. Identification of differential gene expression in in vitro FSH treated pig granulosa cells using suppression subtractive hybridization.

    PubMed

    Bonnet, A; Frappart, P O; Dehais, P; Tosser-Klopp, G; Hatey, F

    2006-07-07

    FSH, which binds to specific receptors on granulosa cells in mammals, plays a key role in folliculogenesis. Its biological activity involves stimulation of intercellular communication and upregulation of steroidogenesis, but the entire spectrum of the genes regulated by FSH has yet to be fully characterized. In order to find new regulated transcripts, however rare, we have used a Suppression Subtractive Hybridization approach (SSH) on pig granulosa cells in primary culture treated or not with FSH. Two SSH libraries were generated and 76 clones were sequenced after selection by differential screening. Sixty four different sequences were identified, including 3 novel sequences. Experiments demonstrated the presence of 25 regulated transcripts.A gene ontology analysis of these 25 genes revealed (1) catalytic; (2) transport; (3) signal transducer; (4) binding; (5) anti-oxidant and (6) structural activities. These findings may deepen our understanding of FSH's effects. Particularly, they suggest that FSH is involved in the modulation of peroxidase activity and remodelling of chromatin.

  3. Phosphoinositide 3-kinase p110δ mediates estrogen- and FSH-stimulated ovarian follicle growth.

    PubMed

    Li, Qian; He, Hui; Zhang, Yin-Li; Li, Xiao-Meng; Guo, Xuejiang; Huo, Ran; Bi, Ye; Li, Jing; Fan, Heng-Yu; Sha, Jiahao

    2013-09-01

    In the mammalian ovary, primordial follicles are generated early in life and remain dormant for prolonged periods. Their growth resumes via primordial follicle activation, and they continue to grow until the preovulatory stage under the regulation of hormones and growth factors, such as estrogen, FSH, and IGF-1. Both FSH and IGF-1 activate the phosphatidylinositol-3 kinase (PI3K)/Akt (acute transforming retrovirus thymoma protein kinase) signaling pathway in granulosa cells (GCs), yet it remains inconclusive whether the PI3K pathway is crucial for follicle growth. In this study, we investigated the p110δ isoform (encoded by the Pik3cd gene) of PI3K catalytic subunit expression in the mouse ovary and its function in fertility. Pik3cd-null females were subfertile, exhibited fewer growing follicles and more atretic antral follicles in the ovary, and responded poorly to exogenous gonadotropins compared with controls. Ovary transplantation showed that Pik3cd-null ovaries responded poorly to FSH stimulation in vitro; this confirmed that the follicle growth defect was intrinsically ovarian. In addition, estradiol (E2)-stimulated follicle growth and GC proliferation in preantral follicles was impaired in Pik3cd-null ovaries. FSH and E2 substantially activated the PI3K/Akt pathway in GCs of control mice but not in those of Pik3cd-null mice. However, primordial follicle activation and oocyte meiotic maturation were not affected by Pik3cd knockout. Taken together, our findings indicate that the p110δ isoform of the PI3K catalytic subunit is a key component of the PI3K pathway for both FSH and E2-stimulated follicle growth in ovarian GCs; however, it is not required for primordial follicle activation and oocyte development.

  4. The effects of insulin and follicle-simulating hormone (FSH) during in vitro development of ovarian goat preantral follicles and the relative mRNA expression for insulin and FSH receptors and cytochrome P450 aromatase in cultured follicles.

    PubMed

    Chaves, Roberta N; Duarte, Ana Beatriz G; Rodrigues, Giovanna Q; Celestino, Juliana J H; Silva, Gerlane M; Lopes, Claudio Afonso P; Almeida, Anderson P; Donato, Mariana A M; Peixoto, C A; Moura, Arlindo A A; Lobo, Carlos H; Locatelli, Yann; Mermillod, Pascalle; Campello, Claudio C; Figueiredo, Jose Ricardo

    2012-09-01

    The actions of different concentrations of insulin alone or in combination with follicle-stimulating hormone (FSH) were evaluated by in vitro follicular development and mRNA expression of cytochrome P450 aromatase (CYP19A1) and as receptors for insulin (INSR) and FSH (FSHR) from isolated, cultured goat preantral follicles. Goat preantral follicles were microdissected and cultured for 18 days in the absence or presence of insulin (5 and 10 ng/ml or 10 μg/ml) alone or in combination with FSH. After 18 days, the addition of the maximum concentration of insulin to the culture medium reduced follicular survival and antrum formation rates significantly compared to the other treatments. However, when FSH was added to the culture medium, no differences between these two parameters were observed. Preantral and antral follicles from the fresh control as well as from all cultured follicles still presented a normal ultrastructural pattern. In medium supplemented with FSH, only insulin at 10 ng/ml presented oocytes with higher rates of meiosis resumption compared to control, as well as oocytes in metaphase II. Treatment with insulin (10 ng/ml) plus FSH resulted in significantly increased levels of INSR and CYP19A1 mRNA compared to that with other treatments. In conclusion, 10 ng/ml insulin associated with FSH was more efficient in promoting resumption of oocyte meiosis, maintaining survival, stimulating follicular development, and increasing expression of the INSR and CYP19A1 genes in goat preantral follicles.

  5. Sphingosine-1-phosphate, regulated by FSH and VEGF, stimulates granulosa cell proliferation.

    PubMed

    Hernández-Coronado, C G; Guzmán, A; Rodríguez, A; Mondragón, J A; Romano, M C; Gutiérrez, C G; Rosales-Torres, A M

    2016-09-15

    Sphingosine-1-phosphate (S1P) is a bioactive polar sphingolipid which stimulates proliferation, growth and survival in various cell types. In the ovary S1P has been shown protect the granulosa cells and oocytes from insults such as oxidative stress and radiotherapy, and S1P concentrations are greater in healthy than atretic large follicles. Hence, we postulate that S1P is fundamental in follicle development and that it is activated in ovarian granulosa cells in response to FSH and VEGF. To test this hypothesis we set out: i) to evaluate the effect of FSH and VEGF on S1P synthesis in cultured bovine granulosa cells and ii) to analyse the effect of S1P on proliferation and survival of bovine granulosa cells in vitro. Seventy five thousand bovine granulosa cells from healthy medium-sized (4-7mm) follicles were cultured in 96-well plates in McCoy's 5a medium containing 10ng/mL of insulin and 1ng/mL of LR-IGF-I at 37°C in a 5% CO2/air atmosphere at 37°C. Granulosa cell production of S1P was tested in response to treatment with FSH (0, 0.1, 1 and 10ng/mL) and VEGF (0, 0.01, 0.1, 1, 10 and 100ng/mL) and measured by HPLC. Granulosa cells produced S1P at 48 and 96h, with the maximum production observed with 1ng/mL of FSH. Likewise, 0.01ng/mL of VEGF stimulated S1P production at 48, but not 96h of culture. Further, the granulosa cell expression of sphingosine kinase-1 (SK1), responsible for S1P synthesis, was demonstrated by Western blot after 48h of culture. FSH increased the expression of phosphorylated SK1 (P<0.05) and the addition of a SK1 inhibitor reduced the constitutive and FSH-stimulated S1P synthesis (P<0.05). Sphingosine-1-phosphate had a biphasic effect on granulosa cell number after culture. At low concentration S1P (0.1μM) increased granulosa cell number after 48h of culture (P<0.05) and the proportion of cells in the G2 and M phase of the cell cycle (P<0.05), whereas higher concentrations decreased cell number (10μM; P<0.05) by an increase (P<0.05) in the

  6. Recombinant human follicle-stimulating hormone (r-hFSH) plus recombinant luteinizing hormone versus r-hFSH alone for ovarian stimulation during assisted reproductive technology: systematic review and meta-analysis

    PubMed Central

    2014-01-01

    Background The potential benefit of adding recombinant human luteinizing hormone (r-hLH) to recombinant human follicle-stimulating hormone (r-hFSH) during ovarian stimulation is a subject of debate, although there is evidence that it may benefit certain subpopulations, e.g. poor responders. Methods A systematic review and a meta-analysis were performed. Three databases (MEDLINE, Embase and CENTRAL) were searched (from 1990 to 2011). Prospective, parallel-, comparative-group randomized controlled trials (RCTs) in women aged 18–45 years undergoing in vitro fertilization, intracytoplasmic sperm injection or both, treated with gonadotrophin-releasing hormone analogues and r-hFSH plus r-hLH or r-hFSH alone were included. The co-primary endpoints were number of oocytes retrieved and clinical pregnancy rate. Analyses were conducted for the overall population and for prospectively identified patient subgroups, including patients with poor ovarian response (POR). Results In total, 40 RCTs (6443 patients) were included in the analysis. Data on the number of oocytes retrieved were reported in 41 studies and imputed in two studies. Therefore, data were available from 43 studies (r-hFSH plus r-hLH, n = 3113; r-hFSH, n = 3228) in the intention-to-treat (ITT) population (all randomly allocated patients, including imputed data). Overall, no significant difference in the number of oocytes retrieved was found between the r-hFSH plus r-hLH and r-hFSH groups (weighted mean difference −0.03; 95% confidence interval [CI] −0.41 to 0.34). However, in poor responders, significantly more oocytes were retrieved with r-hFSH plus r-hLH versus r-hFSH alone (n = 1077; weighted mean difference +0.75 oocytes; 95% CI 0.14–1.36). Significantly higher clinical pregnancy rates were observed with r-hFSH plus r-hLH versus r-hFSH alone in the overall population analysed in this review (risk ratio [RR] 1.09; 95% CI 1.01–1.18) and in poor responders (n = 1179; RR 1.30; 95% CI 1

  7. Characterization of the chicken follicle-stimulating hormone receptor (cFSH-R) complementary deoxyribonucleic acid, and expression of cFSH-R messenger ribonucleic acid in the ovary.

    PubMed

    You, S; Bridgham, J T; Foster, D N; Johnson, A L

    1996-11-01

    Studies were conducted to characterize the chicken (c) FSH receptor (R) cDNA, and to evaluate expression of cFSH-R mRNA in the hen ovary at known stages during follicle development. A total of 2.5 kb of nucleic acid sequence including the complete cFSH-R coding region was isolated by a combination of the reverse-transcription polymerase chain reaction and 5'- and 3'-rapid amplification of cDNA ends techniques. Overall, the nucleic acid sequence homology of the cFSH-R cDNA coding region is 71.8% and 72.2% compared to the rat and bovine FSH-R, respectively, while the deduced amino acid sequence identity for the receptor protein (693 amino acids) is 71.9% and 72.4%, respectively. By comparison, the cFSH-R nucleic acid and amino acid sequences are 60.1% and 49.4% identical to the respective cLH-R sequences. Northern blot analysis detected a single 4.3-kb cFSH-R mRNA transcript, which was selectively expressed in ovarian (granulosa, theca, and stromal) tissues, but not the oviduct, adrenal, liver, muscle, or brain. As the follicle developed from the prehierarchical (6- to 8-mm diameter) to the largest preovulatory (F1 follicle) stage, cFSH-R mRNA levels progressively declined within both the granulosa and theca layers (p < 0.05). Moreover, cFSH-R mRNA levels were lower in whole atretic than in morphologically normal 3- to 5-mm follicles (p = 0.0015). The pattern of cFSH-R mRNA expression within the granulosa layer during follicle development was notably different from that of the recently reported cLH-R, in that cLH-R mRNA levels increase to become readily detectable coincident with dramatically increased steroidogenic capacity during the last few days before ovulation of the follicle. On the other hand, highest levels of cFSH-R mRNA in 6- to 8-mm (prehierarchical) follicles were consistent with a role for the cFSH-R in maintaining the viability of prehierarchical follicles and in initiating granulosa cell differentiation at the time when follicles are selected into the

  8. Superovulation with a single administration of FSH in aluminum hydroxide gel: a novel superovulation method for cattle

    PubMed Central

    KIMURA, Koji

    2016-01-01

    Superovulation (SOV) is a necessary technique to produce large numbers of embryos for embryo transfer. In the conventional methods, follicular stimulating hormone (FSH) is administered to donor cattle twice daily for 3 to 4 days. As this method is labor intensive and stresses cattle, improving this method has been desired. We previously developed a novel and simple SOV method, in which the intramuscular injection of a single dose of FSH in aluminum hydroxide gel (AH-gel) induced the growth of multiple follicles, ovulation and the production of multiple embryos. Here we show that AH-gel can efficiently adsorb FSH and release it effectively in the presence of BSA, a major interstitial protein. When a single intramuscular administration of the FSH and AH-gel mixture was performed to cattle, multiple follicular growth, ovulation and embryo production were induced. However, the treatments caused indurations at the administration sites in the muscle. To reduce the muscle damage, we investigated alternative administration routes and different amounts of aluminum in the gel. By administering the FSH in AH-gel subcutaneously rather than intramuscularly, the amount of aluminum in the gel could be reduced, thus reducing the size of the induration. Moreover, repeated administrations of FSH with AH-gel did not affect the superovulatory response. These results indicate that a single administration of FSH with AH-gel is an effective, novel and practical method for SOV treatment. PMID:27396385

  9. THE MEASURES PAR PROJECT

    NASA Astrophysics Data System (ADS)

    Frouin, R. J.; Franz, B.

    2009-12-01

    The solar energy available for photosynthesis, known as PAR, controls the growth of phytoplankton and, therefore, regulates the composition and evolution of marine ecosystems. Knowing the spatial and temporal distribution of PAR over the oceans is critical to understanding biogeochemical cycles of carbon, nutrients, and oxygen, and to address important climate and global change issues such as the fate of anthropogenic atmospheric carbon dioxide. In view of this, a 12-year time series of PAR at the ocean surface, starting in September 1997, is being produced by the NASA Ocean Biology Processing Group from SeaWiFS, MODIS-Terra, and MODIS-Aqua data. The product covers the global oceans, with a spatial resolution of about 9.3x9.3 km (equal area grid) and a temporal resolution of one day. PAR is computed as the difference between the 400-700 nm solar flux incident on the top of the atmosphere (known) and reflected back to space by the atmosphere and surface (derived from satellite radiance), taking into account atmospheric absorption (modeled). Knowledge of pixel composition is not required, eliminating the need for cloud screening and arbitrary assumptions about sub-pixel cloudiness. Combining data from satellite sensors with different equatorial crossing times accounts for the diurnal variability of clouds and, therefore, increases accuracy on a daily time scale. The processing system, including routine check of accuracy and control of quality, is designed to operate during the entire lifetime of SeaWiFS and MODIS, and to accommodate future sensors with ocean-color capabilities. Maps of daily, weekly, and monthly PAR obtained from individual sensors are presented, as well as merged products. Accuracy is quantified in comparisons with other satellite estimates, the National Centers for Environmental Prediction reanalysis product, and in-situ measurements from fixed buoys and platforms. The good statistical performance makes the satellite PAR product suitable for large

  10. Effects of leptin on FSH cells in the pituitary gland of Podarcis siculus.

    PubMed

    Ferrandino, Ida; Monaco, Antonio; Grimaldi, Maria Consiglio

    2015-03-01

    Leptin is the hormone synthesised by adipocytes, which plays an important role in regulating appetite and metabolism. In mammals, this pleiotropic hormone also plays a key role in controlling gonadotropin secretion by stimulatory hypothalamic and pituitary actions. However, little is known about leptin in lower vertebrates and particularly few studies are available on reptiles. In the present work, we analysed the action of recombinant human leptin on FSH cells in the pituitary gland of Podarcis siculus female lizards exposed to four different concentrations of the hormone. FSH cells showed a dose-dependent reaction. The data are indicative of the role played by leptin in modulating the cellular activity of such cells in the pituitary gland of P. siculus, similar to what was already reported in mammals. A functional receptor is evidently able to respond to leptin in this lizard, but further comparative studies are needed to understand the role of this hormone in ectothermic vertebrates.

  11. Regulation of LH/FSH expression by secretoglobin 3A2 in the mouse pituitary gland.

    PubMed

    Miyano, Yuki; Tahara, Shigeyuki; Sakata, Ichiro; Sakai, Takafumi; Abe, Hiroyuki; Kimura, Shioko; Kurotani, Reiko

    2014-04-01

    Secretoglobin (SCGB) 3A2 was originally identified as a downstream target for the homeodomain transcription factor NKX2-1 in the lung. NKX2-1 plays a role in the genesis and expression of genes in the thyroid, lung and ventral forebrain; Nkx2-1-null mice have no thyroid and pituitary and severely hypoplastic lungs and hypothalamus. To demonstrate whether SCGB3A2 plays any role in pituitary hormone production, NKX2-1 and SCGB3A2 expression in the mouse pituitary gland was examined by immunohistochemical analysis and RT-PCR. NKX2-1 was localized in the posterior pituitary lobe, whereas SCGB3A2 was observed in both anterior and posterior lobes as shown by immunohistochemistry and RT-PCR. Expression of CCAAT-enhancer binding proteins (C/EBPs), which regulate mouse Scgb3a2 transcription, was also examined by RT-PCR. C/EBPβ, γ, δ and ζ were expressed in the adult mouse pituitary gland. SCGB3A2 was expressed in the anterior and posterior lobes from postnatal days 1 and 5, respectively and the areas where SCGB3A2 expression was found coincided with the area where FSH-secreting cells were found. Double-staining for SCGB3A2 and pituitary hormones revealed that SCGB3A2 was mainly localized in gonadotrophs in 49 % of FSH-secreting cells and 47 % of LH-secreting cells. In addition, SCGB3A2 dramatically inhibited LH and FSH mRNA expression in rat pituitary primary cell cultures. These results suggest that SCGB3A2 regulates FSH/LH production in the anterior pituitary lobe and that transcription factors other than NKX2-1 may regulate SCGB3A2 expression.

  12. Omega-3 Fatty Acid Supplementation Lowers Serum FSH in Normal Weight But Not Obese Women

    PubMed Central

    Al-Safi, Zain A.; Liu, Huayu; Carlson, Nichole E.; Chosich, Justin; Harris, Mary; Bradford, Andrew P.; Robledo, Celeste; Eckel, Robert H.

    2016-01-01

    Context: Dietary omega-3 fatty acids delay ovarian aging and promote oocyte quality in mice. Objective: To test whether dietary supplementation with omega-3 polyunsaturated fatty acids (PUFA) modulates reproductive hormones in reproductive-age women. Design: Prospective interventional study. Setting: Academic center. Participants: Fifteen obese and 12 normal-weight (NW) eumenorrheic women, ages 28–34 years. Intervention: Two frequent blood-sampling studies were performed before and after 1 month of omega-3 PUFA supplementation with 4 g of eicosapentaenoic acid and docosahexaenoic acid daily. Main Outcome Measures: Serum LH and FSH (basal and after GnRH stimulation). Results: The ratio of omega-6 to omega-3 PUFA was significantly reduced in plasma and red blood cell components for both groups after treatment (both P < .01). Omega-3 PUFA supplementation resulted in reduction of FSH and FSH response to GnRH by 17% on average (P = .06 and P = .03, respectively) in NW but not obese women. Serum levels of IL-1β and TNF-α were reduced after omega-3 PUFA supplementation (−72% for IL-1β; −56% for TNF-α; both, P < .05) in obese but not in NW women. This reduction, however, was not associated with a hormonal change in obese women. Conclusions: Dietary administration with omega-3 PUFA decreased serum FSH levels in NW but not in obese women with normal ovarian reserve. This effect is intriguing and is directionally consistent with murine data whereby higher dietary omega-3 PUFA extends reproductive lifespan. Our results imply that this nutritional intervention should be tested in women with diminished ovarian reserve in an attempt to delay ovarian aging. PMID:26523525

  13. The effect of Ramadan fasting on LH, FSH, oestrogen, progesterone and leptin in pregnant women.

    PubMed

    Khoshdel, A; Kheiri, S; Hashemi-Dehkordi, E; Nasiri, J; Shabanian-Borujeni, S; Saedi, E

    2014-10-01

    Many pregnant Muslim women fast during Ramadan. Leptin has an important role in the reproductive system and hormones. In this study, FSH, LH, oestrogen, progesterone and leptin were measured in the first, second and fourth week of Ramadan and the second week post-Ramadan, in 30 fasting pregnant women. Data were analysed using repeated measures ANOVA by SPSS. The weight and BMI did not change during the study. A significant change in FSH, oestrogen, progesterone and leptin was observed (p < 0.05). The lowest value of FSH was in the second week of Ramadan. Progesterone increased at the end of Ramadan and the second week after. Oestrogen increased significantly during Ramadan and decreased after Ramadan. A decreasing trend was seen in LH during the Ramadan and 2 weeks after (p < 0.1). Leptin decreased significantly 2 weeks after Ramadan. We found poor weight gain and hypoleptinaemia in pregnant fasted women during the study. Food restriction in pregnant fasted women during Ramadan may induce poor weight gain during pregnancy. These data confirm that Ramadan fasting by pregnant women may have potential risks during pregnancy. We recommend further study to evaluate long-term effects of Ramadan fasting during pregnancy in different countries with different food habits and traditions, to obtain reliable and documented data.

  14. Primary ovarian insufficiency in classic galactosemia: role of FSH dysfunction and timing of the lesion.

    PubMed

    Gubbels, Cynthia S; Land, Jolande A; Evers, Johannes L H; Bierau, Jörgen; Menheere, Paul P C A; Robben, Simon G F; Rubio-Gozalbo, M Estela

    2013-01-01

    FSH inactivity due to secondary hypoglycosylation has been suggested as a potential mechanism for primary ovarian insufficiency in classic galactosemia. To investigate the role of FSH and to gain insight in the timing of the damage, ovarian stimulation tests were performed and data on ovarian imaging collected. Fifteen patients with primary ovarian insufficiency underwent ovarian stimulation with gonadotropins. Only one patient showed a normal increase in estradiol level, all the others had a low or no estradiol response. Anti-Müllerian hormone measurement in all girls and women showed levels below the detection limit of 0.10 μg/l. Ovarian volumes were evaluated by MRI in 14 patients and compared to age matched controls, prepubertal controls and postmenopausal controls. The ovarian volumes of the galactosemic girls were smaller than those of the age matched controls (p = 0.001) and the prepubertal ovaries (p = 0.008), and did not differ significantly from postmenopausal ovarian volumes (p = 0.161). In conclusion we found no evidence that FSH inactivity plays a role in primary ovarian insufficiency in classic galactosemia. Moreover, ovarian imaging results point to an early onset of ovarian failure in this disease.

  15. Serum LH and FSH Responses to Synthetic LH-RH in Normal Infants, Children and Patients With Turner's Syndrome

    ERIC Educational Resources Information Center

    Suwa, Seizo; And Others

    1974-01-01

    Effects of luteinizing hormone-releasing hormone (LH-RH) on LH and follicle-stimulating hormone (FSH) release were studied in 26 normal children and six patients (from 1-to 14-years-old) with Turner's syndrome. (Author)

  16. La pelade par plaques

    PubMed Central

    Spano, Frank; Donovan, Jeff C.

    2015-01-01

    Résumé Objectif Présenter aux médecins de famille des renseignements de base pour faire comprendre l’épidémiologie, la pathogenèse, l’histologie et l’approche clinique au diagnostic de la pelade par plaques. Sources des données Une recension a été effectuée dans PubMed pour trouver des articles pertinents concernant la pathogenèse, le diagnostic et le pronostic de la pelade par plaques. Message principal La pelade par plaques est une forme de perte pileuse auto-immune dont la prévalence durant une vie est d’environ 2 %. Des antécédents personnels ou familiaux de troubles auto-immuns concomitants, comme le vitiligo ou une maladie de la thyroïde, peuvent être observés dans un petit sous-groupe de patients. Le diagnostic peut souvent être posé de manière clinique en se fondant sur la perte de cheveux non cicatricielle et circulaire caractéristique, accompagnée de cheveux en « point d’exclamation » en périphérie chez ceux dont le problème en est aux premiers stades. Le diagnostic des cas plus complexes ou des présentations inhabituelles peut être facilité par une biopsie et un examen histologique. Le pronostic varie largement et de mauvais résultats sont associés à une apparition à un âge précoce, une perte importante, la variante ophiasis, des changements aux ongles, des antécédents familiaux ou des troubles auto-immuns concomitants. Conclusion La pelade par plaques est une forme auto-immune de perte de cheveux périodiquement observée en soins primaires. Les médecins de famille sont bien placés pour identifier la pelade par plaques, déterminer la gravité de la maladie et poser le diagnostic différentiel approprié. De plus, ils sont en mesure de renseigner leurs patients à propos de l’évolution clinique de la maladie ainsi que du pronostic général selon le sous-type de patients.

  17. FSH receptor-specific residues L501 and I505 in extracellular loop 2 are essential for its function.

    PubMed

    Banerjee, Antara A; Dupakuntla, Madhavi; Pathak, Bhakti R; Mahale, Smita D

    2015-06-01

    The extracellular loop 2 (EL2) of FSH receptor (FSHR) plays a pivotal role in various events downstream of FSH stimulation. Because swapping the six FSHR-specific residues in EL2 (chimeric EL2M) with those from LH/choriogonadotropin receptor resulted in impaired internalization of FSH-FSHR complex and low FSH-induced cAMP production, six substitution mutants of EL2 were generated to ascertain the contribution of individual amino acids to the effects shown by chimeric EL2M. Results revealed that L(501)F mainly and I(505)V to a lesser extent contribute to the diminished receptor function in chimeric EL2M. HEK293 cells stably expressing WT and chimeric EL2M FSHR were generated to track the fate of the receptors post FSH induction. The chimeric EL2M FSHR stable clone showed weak internalization and cAMP response similar to transiently transfected cells. Furthermore, reduced FSH-induced ERK phosphorylation was also observed. The interaction of activated chimeric EL2M and L(501)F FSHR with β-arrestins was weak compared with WT FSHR, thus explaining the impaired internalization of chimeric EL2M and corroborating the indispensable role of EL2 in receptor function.

  18. Anti-Müllerian hormone versus antral follicle count for defining the starting dose of FSH.

    PubMed

    Lan, Vuong Thi Ngoc; Linh, Nguyen Khanh; Tuong, Ho Manh; Wong, P C; Howles, Colin M

    2013-10-01

    This pilot study compared the efficacy and safety of two simple dosing algorithms, one based on anti-Müllerian Hormone (AMH) and the other on the antral follicle count (AFC), to determine the starting dose of recombinant FSH (rFSH) for ovarian stimulation in 348 women. Patients were randomized to a predefined AMH- or AFC-based algorithm. The proportion of cycles with the desired response was similar when rFSH dose was determined using AMH or AFC (35.2% versus 28.4%). There was a significant difference between the groups in the proportion of cycles with a hyperresponse (8.6% and 17.4%, but the incidence of ovarian hyperstimulation syndrome was similar (1.1% and 4.6%). There were no significant differences between two groups in outcomes, including implantation (19.3% versus 19.0%), clinical pregnancy (38.0% versus 46.9%), multiple pregnancy (16.5% versus 15.2%) and miscarriage (7.0% versus 8.3%). However, statistically significant differences in ovarian response were evident among the AMH and AFC subgroups: for AMH, Desired and Hypo; for AFC, Hypo and Hyper. This pilot study provides information for developing protocols to further validate the use of either AMH or AFC to guide the starting dose of rFSH in ovarian stimulation. The ideal outcome for couples undergoing IVF treatment is the birth of a healthy baby. One factor that might influence this is retrieving an adequate number of eggs, which are obtained using various treatment protocols. A group of drugs called gonadotrophins have been used for more than 20years to stimulate the ovaries to produce eggs. However, the dose to start treatment has not been clearly defined. A few studies have looked at ways to use the best gonadotrophin dose for each woman, but to be useful in the clinic any approach needs to be simple and easy to use. This study compared the effectiveness and safety of two simple approaches to determining the starting dose of recombinant FSH (rFSH) for ovarian stimulation in women undergoing IVF

  19. La pelade par plaques

    PubMed Central

    Spano, Frank; Donovan, Jeff C.

    2015-01-01

    Résumé Objectif Présenter aux médecins de famille des renseignements de base pour faire comprendre les schémas thérapeutiques et les résultats des traitements pour la pelade par plaques, de même que les aider à identifier les patients pour qui une demande de consultation en dermatologie pourrait s’imposer. Sources des données Une recension a été effectuée dans PubMed pour trouver des articles pertinents concernant le traitement de la pelade par plaques. Message principal La pelade par plaques est une forme auto-immune de perte pileuse qui touche à la fois les enfants et les adultes. Même s’il n’y a pas de mortalité associée à la maladie, la morbidité découlant des effets psychologiques de la perte des cheveux peut être dévastatrice. Lorsque la pelade par plaques et le sous-type de la maladie sont identifiés, un schéma thérapeutique approprié peut être amorcé pour aider à arrêter la chute des cheveux et possiblement faire commencer la repousse. Les traitements de première intention sont la triamcinolone intralésionnelle avec des corticostéroïdes topiques ou du minoxidil ou les 2. Les médecins de famille peuvent prescrire ces traitements en toute sécurité et amorcer ces thérapies. Les cas plus avancés ou réfractaires pourraient avoir besoin de diphénylcyclopropénone topique ou d’anthraline topique. On peut traiter la perte de cils avec des analogues de la prostaglandine. Les personnes ayant subi une perte de cheveux abondante peuvent recourir à des options de camouflage ou à des prothèses capillaires. Il est important de surveiller les troubles psychiatriques en raison des effets psychologiques profonds de la perte de cheveux. Conclusion Les médecins de famille verront de nombreux patients qui perdent leurs cheveux. La reconnaissance de la pelade par plaques et la compréhension du processus pathologique sous-jacent permettent d’amorcer un schéma thérapeutique approprié. Les cas plus graves ou r

  20. Comparison of marmoset and human FSH using synthetic peptides of the β-subunit L2 loop region and anti-peptide antibodies.

    PubMed

    Kutteyil, Susha S; Kulkarni, Bhalchandra J; Mojidra, Rahul; Joseph, Shaini; Pathak, Bhakti R; Mahale, Smita D

    2016-06-01

    Follicle stimulating hormone (FSH) is a glycoprotein hormone required for female and male gametogenesis in vertebrates. Common marmoset (Callithrix jacchus) is a New World primate monkey, used as animal model in biomedical research. Observations like, requirement of extremely high dose of human FSH in marmosets for superovulation compared to other primates and generation of antibodies in marmoset against human FSH after repeated superovulation cycles, point towards the possibility that FSH-FSH receptor (FSHR) interaction in marmosets might be different than in the humans. In this study we attempted to understand some of these structural differences using FSH peptides and anti-peptide antibody approach. Based on sequence alignment, in silico modeling and docking studies, L2 loop of FSH β-subunit (L2β) was found to be different between marmoset and human. Hence, peptides corresponding to region 32-50 of marmoset and human L2β loop were synthesized, purified and characterized. The peptides displayed dissimilarity in terms of molecular mass, predicted isoelectric point, predicted charge and in the ability to inhibit hormone-receptor interaction. Polyclonal antibodies generated against both the peptides were found to exhibit specific binding for the corresponding peptide and parent FSH in ELISA and Western blotting respectively and exhibited negligible reactivity to cross-species peptide and FSH in ELISA. The anti-peptide antibody against marmoset FSH was also able to detect native FSH in marmoset plasma samples and pituitary sections. In summary, the L2β loop of marmoset and human FSH has distinct receptor interaction ability and immunoreactivity indicating possibility of subtle conformational and biochemical differences between the two regions which may affect the FSH-FSHR interaction in these two primates. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  1. FSH up-regulates angiogenic factors in luteal cells of buffaloes.

    PubMed

    Fátima, L A; Evangelista, M C; Silva, R S; Cardoso, A P M; Baruselli, P S; Papa, P C

    2013-11-01

    Follicle-stimulating hormone has been widely used to induce superovulation in buffaloes and cows and usually triggers functional and morphologic alterations in the corpus luteum (CL). Several studies have shown that FSH is involved in regulating vascular development and that adequate angiogenesis is essential for normal luteal development. Angiogenesis is regulated by many growth factors, of which vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) have an established central role. Therefore, we have used a combination of in vitro and in vivo studies to assess the effects of FSH on the expression of VEGF and FGF2 and their receptors in buffalo luteal cells. The in vivo model consisted of 12 buffalo cows, divided into control (n = 6) and superovulated (n = 6) groups, and CL samples were collected on day 6 after ovulation. In this model, we analyzed the gene and protein expression of FGF2 and its receptors and the protein expression of VEGFA systems with the use of real-time PCR, Western blot analysis, and immunohistochemistry. In the in vitro model, granulosa cells were collected from small follicles (diameter, 4-6 mm) of buffaloes and cultured for 4 d in serum-free medium with or without FSH (10 ng/mL). To induce in vitro luteinization, LH (250 ng/mL) and fetal bovine serum (10%) were added to the medium, and granulosa cells were maintained in culture for 4 d more. The progesterone concentration in the medium was measured at days 4, 5, and 8 after the beginning of cell culture. Cells were collected at day 8 and subjected to real-time PCR, Western blot analysis, and immunofluorescence for assessment of the expression of FGF2, VEGF, and their receptors. To address the percentage of steroidogenic and growth factor-expressing cells in the culture, flow cytometry was performed. We observed that in superovulated buffalo CL, the FGF2 system mRNA expression was decreased even as protein expression was increased and that the VEGF protein was

  2. Mixed protocols: Multiple ratios of FSH and LH bioactivity using highly purified, human-derived FSH (BRAVELLE) and highly purified hMG (MENOPUR) are unaltered by mixing together in the same syringe

    PubMed Central

    Scobey, M Joseph; Raike, Elizabeth; Marshall, Dennis C

    2005-01-01

    Background The use of mixed or blended protocols, that utilize both FSH and hMG, for controlled ovarian hyperstimulation is increasing in use. To reduce the number of injections a patient must administer, many physicians instruct their patients to mix their FSH and hMG together to be given as a single injection. Therefore, the goal of this study was to definitively determine if the FSH and LH bioactivities of highly purified, human-derived FSH (Bravelle(R)) and highly purified hMG (Menopur(R)) were altered by reconstituting in 0.9% saline and mixing in the same syringe. Methods Bravelle(R) and Menopur(R) were reconstituted in 0.9% saline and mixed in a Becton Dickinson plastic syringe. The FSH and LH bioactivities of the products were determined after injecting female and male rats, respectively, with Bravelle(R), Menopur(R), or a mixture of Bravelle(R) and Menopur(R). Ratios of FSH:LH activity tested were 150:75 IU (1 vial Bravelle(R): 1 vial Menopur(R)), 300:75 IU (3 vials Bravelle(R): 1 vial Menopur(R)) or 300:225 IU (1 vial Bravelle(R): 3 vials of Menopur(R)). Results There were no statistically significant changes in either FSH or LH bioactivity that occurred after mixing Bravelle(R) with Menopur(R) in the same syringe. The theoretical vs. actual FSH bioactivity for Bravelle(R) and Menopur(R) were 75 vs. 76.58 IU/mL and 75 vs. 76.0 IU/mL, respectively. For the 3 ratios of FSH:LH activity tested, 150:75 IU (1 vial Bravelle(R): 1 vial Menopur(R)), 300:75 IU (3 vials Bravelle(R): 1 vial Menopur(R)) or 300:225 IU (1 vial Bravelle(R): 3 vials of Menopur(R)) tested, the theoretical vs. actual FSH bioactivities were 150 vs. 156.86 IU/mL, 300 vs. 308.69 IU/mL and 300 vs. 306.58 IU/mL, respectively. The theoretical vs. actual LH bioactivity for Menopur(R) in the above mentioned ratios tested were 75 vs. 77.50 IU/mL. For the 3 ratios of FSH:LH activity tested, 150:75 IU (1 vial Bravelle(R): 1 vial Menopur(R)), 300:75 IU (3 vials Bravelle(R): 1 vial Menopur(R)) or 300

  3. Mink aging is associated with a reduction in ovarian hormone release and the response to FSH and ghrelin.

    PubMed

    Sirotkin, Alexander V; Mertin, Dušan; Süvegová, Karina; Lauričik, Jozef; Morovič, Martin; Harrath, Abdel Halim; Kotwica, Jan

    2016-09-15

    The endocrine mechanisms of mink ovarian hormones release and reproductive aging are poorly investigated. The aims of our study were to: (1) identify hormones produced by mink ovaries (the steroids progesterone [P] and estradiol [E], the peptide hormone oxytocin [OT], and the prostaglandin F [PGF] and prostaglandin E [PGE]); (2) examine the effect of FSH and ghrelin on the release of the hormones listed previously; and (3) understand whether these hormones can be involved in the control of mink reproductive aging, i.e., whether aging can be associated with changes (a) in the basal release of P, E, OT, PGF, or PGE and (b) their response to FSH and ghrelin. Fragments of ovaries of young (yearlings) and old (3-5 years of age) minks were cultured with and without FSH and ghrelin (0, 1, 10, or 100 ng/mL), and the release of hormones was analyzed by EIA/RIA. We found that isolated ovaries were able to release P, E, OT, PGF, and PGE, and the levels of P produced in the ovaries of old animals were lower than those produced in the ovaries of young animals, whereas the levels of other hormones did not differ. FSH was able to stimulate P and E and suppress OT and PGF and did not affect PGE release. Aging was associated with the inhibition of the effect of FSH on ovarian P and E, the appearance of the inhibitory action of FSH on OT, and the disappearance of this action on ovarian PGF. PGE was not affected by FSH, irrespective of animal age. Ghrelin was able to promote E (but not P) and suppress OT, PGF, and PGE output. Aging was associated with the appearance of an inhibitory influence of ghrelin on ovarian OT and PGE and with the disappearance of this influence on PGF output. Aging did not affect the action of ghrelin on ovarian P and E. Our observations (1) confirm the production of P and E and show that OT, PGF, and PGE are released from mink ovaries, (2) confirm the involvement of FSH and demonstrate the involvement of ghrelin in the control of mink ovarian hormone

  4. Effects of alcohol on pulsatile luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion in the adult male rat

    SciTech Connect

    Badger, T.M.; Abdallah, M.M.; Hayden, J.B. )

    1989-02-09

    To determine possible hypothalamic actions of alcohol on hormone secretion, the effects of acute intragastric alcohol on plasma LH and FSH pulsations were studied. One jugular and one intragastric cannula were surgically implanted into adult male Sprague Dawley rats. Eight days later, rats were bilaterally castrated at 1400 h and infused intragastrically with either saline or 3 g/kg ethanol between 0700 h 0800 h the next days. Blood samples (300 microliters) were collected every 5 min for 3 h (starting at 0800 h), centrifuged and the plasma was frozen for LH and FSH radioimmunoassay. The blood cells were resuspended in saline and returned to the animal immediately following the next sample collection. While the mean plasma LH or FSH concentration did not vary significantly between the alcohol-treated and saline-treated rats, the mean LH (but not FSH) pulse frequency was lower in ethanol-treated rats (3.3 {plus minus} 0.25 pulses/3 h) than saline-treated controls (7.2 {plus minus} 0.3 pulses/3 h). In addition, mean area under the OH pulses were significantly greater in ethanol-treated than saline controls. These data suggest that: (1) ethanol acts to reduce the frequency of LHRH release for the hypothalamus and increase the area under each LH pulse; and (2) LH and FSH secretion are differentially regulated.

  5. Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis.

    PubMed

    Sicinski, P; Donaher, J L; Geng, Y; Parker, S B; Gardner, H; Park, M Y; Robker, R L; Richards, J S; McGinnis, L K; Biggers, J D; Eppig, J J; Bronson, R T; Elledge, S J; Weinberg, R A

    1996-12-05

    THE D-type cyclins (D1, D2 and D3) are critical governors of the cell-cycle clock apparatus during the G1 phase of the mammalian cell cycle. These three D-type cyclins are expressed in overlapping, apparently redundant fashion in the proliferating tissues. To investigate why mammalian cells need three distinct D-type cyclins, we have generated mice bearing a disrupted cyclin D2 gene by using gene targeting in embryonic stem cells. Cyclin D2-deficient females are sterile owing to the inability of ovarian granulosa cells to proliferate normally in response to follicle-stimulating hormone (FSH), whereas mutant males display hypoplastic testes. In ovarian granulosa cells, cyclin D2 is specifically induced by FSH via a cyclic-AMP-dependent pathway, indicating that expression of the various D-type cyclins is under control of distinct intracellular signalling pathways. The hypoplasia seen in cyclin D2(-/-) ovaries and testes prompted us to examine human cancers deriving from corresponding tissues. We find that some human ovarian and testicular tumours contain high levels of cyclin D2 messenger RNA.

  6. Accelerated growth of bovine preantral follicles in vitro after stimulation with both FSH and BMP-15 is accompanied by ultrastructural changes and increased atresia.

    PubMed

    Passos, M J; Vasconcelos, G L; Silva, A W B; Brito, I R; Saraiva, M V A; Magalhães, D M; Costa, J J N; Donato, M A M; Ribeiro, R P; Cunha, E V; Peixoto, C A; Campello, C C; Figueiredo, J R; van den Hurk, R; Silva, J R V

    2013-06-01

    The objective of the present study was to determine the effects of bone morphogenetic protein (BMP)-15 and FSH on the growth, viability, and expression of mRNA for FSH (FSH-R) and BMP-15 (BMPR-IB and BMPR-II) receptors in cultured bovine secondary follicles. Secondary follicles were microdissected and cultured for 12 days in minimum essential medium-α alone or supplemented with BMP-15, sequential FSH, both BMP-15 and FSH, or BMP-15 from days 0 to 6, and FSH from days 7 to 12. Thereafter, the effect of these treatments on the follicular volume, viability, and antrum formation and the levels of mRNA for BMPR-IB, BMPR-II, and FSH-R were assessed. Compared with day 0, the follicles cultured with FSH or BMP-15, or both, had a significant and progressive increase in volume (P < 0.05). However, the follicles cultured for 12 days with both BMP-15 and FSH had the greatest volume and a greater rate of antrum formation than those in control medium, but results similar to those cultured with FSH (days 0 to 12) or BMP-15 (days 0 to 6) and FSH (days 7 to 12). Together with their accelerating effect on in vitro follicle growth, the combination of FSH and BMP-15 induced ultrastructural changes in the cultured follicles and increased atresia. However, adding either BMP-15 or FSH to the culture medium, not only promoted follicular growth and follicular antrum formation, but also maintained follicular viability during culture. Except for follicles cultured in minimal essential medium-α, the levels of mRNA for BMPR-IB were reduced, and the levels of mRNA for FSH-R were significantly greater in follicles cultured in medium supplemented with BMP-15. In conclusion, all in vitro follicle treatments supported growth of bovine preantral follicles; however, adding both BMP-15 and FSH to the culture medium (minimal essential medium-α) for 12 days provided the greatest stimulation. Furthermore, the viability and ultrastructural integrity of cultured follicles were only maintained when

  7. Effects of FSH extracted from in vitro cultured anterior pituitary cells of male buffalo calves on body and testes weight, serum FSH and total cholesterol and hematological variables in male rabbits.

    PubMed

    Naveed, Muhammad Riaz; Ahmad, Nazir; Ahmad, Ijaz; Akhtar, Nafees; Ali, Shujait; Zubair, Muhammad; Murtaza, Saeed

    2014-11-30

    In this study, anterior pituitary glands were collected from 12 young male buffalo calves after slaughter, cultured with gonadotropin releasing hormone (GnRH) and estrogen stimulus and the extract obtained. Adult male rabbits (n = 15) were divided into three equal groups. Rabbits of Group A served as control; those of Groups B and C were given extract containing 4 and 8 mIU of follicle stimulating hormone (FSH), respectively twice daily for 3 weeks. Body weight of rabbits was recorded before and after treatment; blood samples were collected after treatment and analyzed for hemoglobin (Hb), red blood cell (RBC) count, white blood cell (WBC) count, packed cell volume (PCV), platelet counts, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), while serum samples were analyzed for FSH and total cholesterol. Then, all rabbits were slaughtered, and weight of paired testes was recorded. Results showed that the values for weight gain, RBC count, WBC count, PCV and MCH did not differ among rabbits of three groups. Blood Hb was greater (P < 0.05) in rabbits of Group B than Group C. Testis weight, serum FSH, total cholesterol and blood platelets count were greater in rabbits of Groups B and C, while MCV was less in rabbits of Group C, compared to the control (P < 0.05). In conclusion, in vitro cultured cells of adenohypophysis from male buffalo calves showed FSH activity. This FSH increased testes size, serum FSH, total cholesterol and blood platelets counts and decreased MCV in rabbits. However, it had no effect on weight gain, RBC counts, WBC counts, PCV and MCH.

  8. Development of persistent ovarian follicles during synchronization of estrus influences the superovulatory response to FSH treatment in cattle.

    PubMed

    Wehrman, M E; Fike, K E; Kojima, F N; Bergfeld, E G; Cupp, A S; Mariscal, V; Sanchez, T; Kinder, J E

    1996-02-01

    The synchronization of estrus with synthetic progestins or progesterone (P(4)) results in the development of a large, persistent ovarian follicle. The objectives of the present study were to determine if development of a persistent ovarian follicle during synchronization of estrus suppresses recruitment of additional follicles during FSH treatment. On Day 5 of the estrous cycle (estrus = Day 0), beef cows were treated with 0.5 or 2.0 P(4) releasing intravaginal devices (PRIDs) for 8 d (Experiment 1, n = 20), 5 or 2 d (Experiment 2, n = 44) before initiation of FSH treatment. Prostaglandin F(2alpha) (25 mg) was administered on Days 5 and 6. Superovulation was induced with 24 mg of recombinant bovine FSH (rbFSH, Experiment 1) or 28 mg of FSH-P (Experiment 2) over a 3- or 4-d period, respectively. The PRIDs were removed concurrently with the 5th injection of rbFSH or FSH-P. There was a treatment-by-day interaction (P < 0.001) for the concentration of 17beta-estradiol in cows treated for 8, 5 or 2 d before FSH treatment. In Experiment 1, FSH treatment initiated 8 d after insertion of a 0.5 PRID did not affect the number of CL (6.9 +/- 1.4 vs 6.7 +/- 1.6), ova/embryos (3.7 +/-1.3 vs 3.0 +/- 1.3) and transferable embryos (2.4 +/- 0.9 vs 3.0 +/- 0.9) compared with that of the 2.0 PRIDs. In Experiment 2, FSH treatment initiated 5 d after insertion of a 0.5 PRID decreased the number of CL (4.0 +/- 0.5 vs 8.3 +/- 0.8; P < 0.001), ova/embryos (3.0 +/- 0.6 vs 5.9 +/- 1.2; P < 0.03) and transferable embryos (2.3 +/- 0.6 vs 5.1 +/- 1.0; P < 0.03) compared with that of a 2.0 PRID, respectively. Initiation of FSH treatment 2 d after insertion of a 0.5 PRID compared with a 2.0 PRID had no affect on the number of CL (8.0 +/- 2.1 vs 8.7 +/- 1.2), total ova (4.8 +/- 1.4 vs 6.9 +/- 1.4) and transferable embryos (2.9 +/- 1.2 vs 6.1 +/- 1.7). In conclusion, treatment with low doses of P(4) (0.5 PRID) for 5 d but not for 2 or 8 d before initiation of FSH treatment results in the

  9. Brulures par Diluant

    PubMed Central

    Benbrahim, A.; Jerrah, H.; Diouri, M.; Bahechar, N.; Boukind, E.H.

    2009-01-01

    Summary La flamme de diluant est une cause non rare de brûlure dans le contexte marocain. Nous avons jugé intéressant de faire une étude épidémiologique sur la brûlure par flamme de diluant (BFD) au centre national des brûlés (CNB) du CHU Ibn-Rochd de Casablanca. Ce travail a été réalisé sur une période de 10 mois (septembre 2007/juin 2008). Le but du travail est de montrer les caractéristiques de ce type de brûlures pour les prévenir et ce par l'information sur le diluant, produit causant ces brûlures, et ses différents dangers, la brûlure notamment. Durant cette période, nous avons colligé 17 cas de BFD sur un total de 356 patients admis au CNB pour brûlures aiguës toute étiologie confondue. La moyenne d'age des patients concernés est de 32 ans. Ils sont presque tous de sexe masculin (16 hommes/1 femme) et ont des antécédents de toxicomanie et/ou de délinquance. Tous nos patients sont de bas niveau socio-économique et habitent dans des bidonvilles pour la plupart. La brûlure est souvent secondaire à une agression dans la rue (92% des cas). Concernant les caractéristiques de la brûlure, la surface cutanée brûlée moyenne est de 23%; elle est souvent profonde et siège surtout au niveau des membres supérieurs et du tronc. PMID:21991179

  10. Serum estradiol, progesterone, testosterone, FSH and LH levels in postmenopausal women with Alzheimer's dementia.

    PubMed

    Tsolaki, Magdalini; Grammaticos, Philip; Karanasou, Chrysanthi; Balaris, Vassilios; Kapoukranidou, Dorothea; Kalpidis, Ioannis; Petsanis, Kostas; Dedousi, Eleni

    2005-01-01

    Several studies have suggested that estrogen replacement therapy lowers the risk of Alzheimer's dementia (AD) among postmenopausal women. Other studies have evaluated serum levels of sex hormones and gonadotropins in women with AD. Estrogens (E(1) and E(2)), luteinizing hormone (LH) and follicular stimulating hormone (FSH), dihydroepiandrosterone and sex hormone binding albumin, which normally responds to circulating testosterone, have been investigated by others using the same protocol in postmenopausal women with AD, older than 65 years. Others have studied in elderly women with AD, also using one protocol, fewer sex hormones and/or gonadotropins. We have studied the serum levels of estradiol, progesterone, testosterone, LH and FSH in the same serum sample of postmenopausal women with AD and other dementias and compared them to a group of controls. We are not aware of a similar study in the literature. All patients were diagnosed on clinical grounds and screened by the mini mental score examination (MMSE). Forty eight women had AD (Group A), mean age 72 years and age range 60-84 years, s even had other types of dementia (Group B), mean age 63.5 years and age range 53-74 years and 33 women had no cognitive impairment and were studied as controls (Group C). Group C women had mean age of 65 years and their age ranged between 55-73 years. Estradiol, progesterone and testosterone were measured by radioimmunoassay (RIA), while FSH and LH by radioimmunometric assay (IRMA). Our results showed that estradiol was significantly lower in Group A as compared to Group C (P=0.04). There was no significant difference in the levels of the other four hormones in the three Groups as studied by the Mann-Whitney U and the Pearson's statistical test. Our results were not influenced by differences due to sex, age, ethnic group or education since these factors were either similar or comparable in all Groups studied. All but two of the subjects, with mild alcoholism, smoking, increased

  11. Pretreatment with recombinant bovine somatotropin enhances the superovulatory response to FSH in heifers.

    PubMed

    Gong, J G; Wilmut, I; Bramley, T A; Webb, R

    1996-02-01

    One of the primary limiting factors to superovulation and embryo transfer in cattle has been the large variability in response, both between and within animals. It appears that the primary source of this problem is the variability in the population of gonadotropin-responsive follicles present in ovaries at the time of stimulation. We have shown that treatment of heifers with recombinant bovine somatotropin (rbGH) increases the number of small antral follicles (2 to 5 mm) and, therefore, enhances the subsequent superovulatory response to eCG. To investigate further the potential of using this approach to improve superovulatory regimens in cattle, the effect of rbGH pretreatment on the response to pituitary FSH was studied. The estrous cycles of 16 heifers were synchronized using PGF2alpha. On Day 7 of the synchronized cycle, half of the animals were injected with 320 mg sustained-release formulated rbGH, while the other half received 10 ml saline. Five days later, all heifers were given a decreasing-dose regimen of twice daily injections of oFSH for 4 d, incorporating an injection of PGF2alpha with the fifth FSH treatment, to induce superovulation. All animals were artificially inseminated twice with semen from the same bull during estrus. Ova/embryos were recovered nonsurgically on Days 6 to 8 of the following estrous cycle, and the ovulation rate assessed on Day 9 by laparoscopy. Using the same animals as described above, the experiment was repeated twice, 3 and 6 mo later, with no laparoscopy in the third experiment. The animals were randomized both between experiments and for the day of ova/embryo collection. Pretreatment of heifers with rbGH significantly (P < 0.01) increased the number of ovulations, total number of ova/embryos recovered and the number of transferable embryos. The percentage of transferable embryos was significantly (P < 0.05) increased by rbGH pretreatment. In addition, the incidence (2/16) of follicular cysts with a poor ovulatory response

  12. Toward Fully Synthetic Homogeneous β-Human Follicle-Stimulating Hormone (β-hFSH) with a Biantennary N-linked Dodecasaccharide. Synthesis of β-hFSH with Chitobiose Units at the Natural Linkage Sites

    PubMed Central

    Nagorny, Pavel; Fasching, Bernhard; Li, Xuechen; Chen, Gong; Aussedat, Baptiste; Danishefsky, Samuel J.

    2009-01-01

    A highly convergent synthesis of the sialic acid rich biantennary N-linked glycan found in human glycoprotein hormones, and its use in the synthesis of a fragment derived from the β-domain of human Follicle-Stimulating Hormone (hFSH) are described. The synthesis highlights the use of the Sinaÿ radical glycosidation protocol for the simultaneous installation of both biantennary side-chains of the dodecasaccharide as well as the use of glycal chemistry to construct the tetrasaccharide core in an efficient manner. The synthetic glycan was used to prepare the glycosylated 20–27aa domain of β-subunit of hFSH under a Lansbury aspartylation protocol. The proposed strategy for incorporating the prepared N-linked dodecasaccharide-containing 20–27aa domain into β-hFSH subunit was validated in the context of a model system providing, protected β-hFSH subunit functionalized with chitobiose at positions 7 and 24. PMID:19341309

  13. The effect of cyproterone acetate on serum testosterone, LH, FSH, and prolactin in male sexual offenders.

    PubMed

    Jeffcoate, W J; Matthews, R W; Edwards, C R; Field, L H; Besser, G M

    1980-08-01

    The anti-androgen, cyproterone acetate, was administered in a dose of 100 mg/day to eight adult male sexual offenders for 21-31 days. Serum testosterone fell to subnormal levels within 7 days and remained low for 6-28 days after treatment was stopped. The fall in testosterone was accompanied by a fall in serum luteinizing hormone (LH) and follicle stimulating hormone (FSH), and a rise in serum prolactin. All subjects experienced a decrease in libido and in frequency of masturbation. The probable mechanisms of action of cyproterone acetate are discussed, as is its potential role in the management of sexual offenders. These studies suggest that measurement of serum testosterone could be used as an index of compliance in sexual offenders treated with cyproterone acetate who are released on parole.

  14. Radiotherapy for Rectal Cancer Is Associated With Reduced Serum Testosterone and Increased FSH and LH

    SciTech Connect

    Bruheim, Kjersti Svartberg, Johan; Carlsen, Erik; Dueland, Svein; Haug, Egil; Skovlund, Eva; Tveit, Kjell Magne; Guren, Marianne G.

    2008-03-01

    Purpose: It is known that scattered radiation to the testes during pelvic radiotherapy can affect fertility, but there is little knowledge on its effects on male sex hormones. The aim of this study was to determine whether radiotherapy for rectal cancer affects testosterone production. Methods and Materials: All male patients who had received adjuvant radiotherapy for rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Patients treated with surgery alone were randomly selected from the same registry as control subjects. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sex hormone binding globulin (SHBG) were analyzed, and free testosterone was calculated (N = 290). Information about the radiotherapy treatment was collected from the patient hospital charts. Results: Serum FSH was 3 times higher in the radiotherapy group than in the control group (median, 18.8 vs. 6.3 IU/L, p <0.001), and serum LH was 1.7 times higher (median, 7.5 vs. 4.5 IU/l, p <0.001). In the radiotherapy group, 27% of patients had testosterone levels below the reference range (8-35 nmol/L), compared with 10% of the nonirradiated patients (p <0.001). Irradiated patients had lower serum testosterone (mean, 11.1 vs. 13.4 nmol/L, p <0.001) and lower calculated free testosterone (mean, 214 vs. 235 pmol/L, p <0.05) than control subjects. Total testosterone, calculated free testosterone, and gonadotropins were related to the distance from the bony pelvic structures to the caudal field edge. Conclusions: Increased serum levels of gonadotropins and subnormal serum levels of testosterone indicate that curative radiotherapy for rectal cancer can result in permanent testicular dysfunction.

  15. Shortened estrous cycle length, increased FSH levels, FSH variance, oocyte spindle aberrations, and early declining fertility in aging senescence-accelerated mouse prone-8 (SAMP8) mice: concomitant characteristics of human midlife female reproductive aging.

    PubMed

    Bernstein, Lori R; Mackenzie, Amelia C L; Kraemer, Duane C; Morley, John E; Farr, Susan; Chaffin, Charles L; Merchenthaler, István

    2014-06-01

    Women experience a series of specific transitions in their reproductive function with age. Shortening of the menstrual cycle begins in the mid to late 30s and is regarded as the first sign of reproductive aging. Other early changes include elevation and increased variance of serum FSH levels, increased incidences of oocyte spindle aberrations and aneuploidy, and declining fertility. The goal of this study was to investigate whether the mouse strain senescence-accelerated mouse-prone-8 (SAMP8) is a suitable model for the study of these midlife reproductive aging characteristics. Midlife SAMP8 mice aged 6.5-7.85 months (midlife SAMP8) exhibited shortened estrous cycles compared with SAMP8 mice aged 2-3 months (young SAMP8, P = .0040). Midlife SAMP8 mice had high FSH levels compared with young SAMP8 mice, and mice with a single day of high FSH exhibited statistically elevated FSH throughout the cycle, ranging from 1.8- to 3.6-fold elevation on the days of proestrus, estrus, metestrus, and diestrus (P < .05). Midlife SAMP8 mice displayed more variance in FSH than young SAMP8 mice (P = .01). Midlife SAMP8 ovulated fewer oocytes (P = .0155). SAMP8 oocytes stained with fluorescently labeled antitubulin antibodies and scored in fluorescence microscopy exhibited increased incidence of meiotic spindle aberrations with age, from 2/126 (1.59%) in young SAMP8 to 38/139 (27.3%) in midlife SAMP8 (17.2-fold increase, P < .0001). Finally, SAMP8 exhibited declining fertility from 8.9 pups/litter in young SAMP8 to 3.5 pups/litter in midlife SAMP8 mice (P < .0001). The age at which these changes occur is younger than for most mouse strains, and their simultaneous occurrence within a single strain has not been described previously. We propose that SAMP8 mice are a model of midlife human female reproductive aging.

  16. Concanavalin-A induces granulosa cell death and inhibits FSH-mediated follicular growth and ovarian maturation in female rats.

    PubMed

    Velasquez, Ethel V; Ríos, Mariana; Ortiz, María Elena; Lizama, Carlos; Nuñez, Elizabeth; Abramovich, Dalhia; Orge, Felipe; Oliva, Barbara; Orellana, Renán; Villalon, Manuel; Moreno, Ricardo D; Tesone, Marta; Rokka, Anne; Corthals, Garry; Croxatto, Horacio B; Parborell, Fernanda; Owen, Gareth I

    2013-05-01

    Reproductive success stems from a finely regulated balance between follicular maturation and atresia, in which the role of carbohydrate structure is poorly understood. Here, we describe for the first time a fraction of purified recombinant human FSH that is capable of bringing about the cell death of granulosa cells and preventing follicular maturation in a rat model. Further analysis by mass spectrometry revealed the presence of the lectin Concanavalin-A (Con-A) within this fraction of recombinant FSH. Using both the fractionated FSH and Con-A, the observed cell death was predominantly located to the granulosa cells. Ex vivo culture of rat follicles demonstrated that follicle degeneration occurred and resulted in the release of a denuded and deteriorated oocyte. Moreover, in vivo experiments confirmed an increase in atresia and a corresponding reduction confined to follicle in early antral stage. As a mechanism of action, Con-A reduces ovarian proliferation, Von Willebrand staining, and angiogenesis. Based on the observation that Con-A may induce granulosa cell death followed by follicle death, our results further demonstrate that follicular carbohydrate moiety is changing under the influence of FSH, which may allow a carbohydrate-binding lectin to increase granulosa cell death. The physiological consequences of circulating lectin-like molecules remain to be determined. However, our results suggest a potential exploitation of carbohydrate binding in fertility and ovarian cancer treatment. This work may shed light on a key role of carbohydrates in the still obscure physiological process of follicular selection and atresia.

  17. Modulation of gene expression in small follicle porcine granulosa cells by human follicle stimulating hormone (hFSH)

    SciTech Connect

    Calvo, F.O.; Ryan, R.J.; Woloschak, G.E.

    1986-03-01

    Small follicle (1-3 mm) porcine granulosa cells (SFPGF) were isolated by puncture, aspiration and cultured under standard conditions in DMEM, HEPES, BSA, MIX. At the start of culture, cells were stimulated with 100ng hFSH/ml. At various times afterwards total cellular RNA was prepared using guanidine-hydrochloride solubilization, phenol extraction and precipitation from 3M NaOAc, pH 6.0. RNA was 5'-end labelled with /sup 32/P in a kinase reaction and hybridized to an excess of clone-specific DNA immobilized on nitrocellulose filters using stringent hybridization and wash conditions. After autoradiography the RNA hybridized to the DNA blot filter were quantitated by microdensitometry. Hybridization to parent plasmid was negative. RNA derived from control cultures showed patterns of hybridization similar to those obtained from freshly obtained cells. Results of these experiments demonstrate hFSh induction of RNA specific for transferrin receptor, ..cap alpha..-interferon, H-ras, and K-ras. Increased RNA levels were apparent within 10 min of treatment and had declined by 180 min. Expression of actin, p53 and for RNAs declined by 10 min of hFSH addition but was enhanced by 160 min. Levels of ..beta..-interferon, myc, mos, abl and yb RNAs were not detectable under these conditions. These results demonstrate specific gene modulation in SFPGC cultured with hFSH.

  18. Effects and interactions of tachykinins and dynorphin on FSH and LH secretion in developing and adult rats.

    PubMed

    Ruiz-Pino, F; Garcia-Galiano, D; Manfredi-Lozano, M; Leon, S; Sánchez-Garrido, M A; Roa, J; Pinilla, L; Navarro, V M; Tena-Sempere, M

    2015-02-01

    Kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which coexpress kisspeptins (Kps), neurokinin B (NKB), and dynorphin (Dyn), regulate gonadotropin secretion. The KNDy model proposes that NKB (a stimulator, through NK3R) and Dyn (an inhibitor, through κ-opioid receptor) shape Kp secretion onto GnRH neurons. However, some aspects of this paradigm remain ill defined. Here we aimed to characterize the following: 1) the effects of NKB signaling on FSH secretion and 2) the role of Dyn in gonadotropin secretion after NK3R activation; 3) additionally, we explored the roles of other tachykinin receptors, NK1R and NK2R, on gonadotropin release. Thus, the effects of the NK3R agonist, senktide, on FSH release were explored across postnatal development in male and female rats; gonadotropin responses to agonists of NK1R substance P and NK2R [neurokinin A (NKA)] were also monitored. Moreover, the effects of senktide on gonadotropin secretion were assessed after antagonizing Dyn actions by nor-binaltorphimine didydrochloride. Before puberty, rats of both sexes showed increased FSH secretion to senktide (and Kp-10). Conversely, adult female rats were irresponsive to senktide in terms of FSH, despite proven LH responses, whereas the adult males did not display FSH or LH responses to senktide, even at high doses. In turn, substance P and NKA stimulated gonadotropin secretion in prepubertal rats, whereas in adults modest gonadotropin responses to NKA were detected. By pretreatment with a Dyn antagonist, adult males became responsive to senktide in terms of LH secretion and displayed elevated basal LH and FSH levels; nor-binaltorphimine didydrochloride treatment uncovered FSH responses to senktide in adult females. Furthermore, the expression of Pdyn and Opkr1 (encoding Dyn and κ-opioid receptor, respectively) in the mediobasal hypothalamus was greater in males than in females at prepubertal ages. Overall, our data contribute to refining our understanding on how the elements of the

  19. Effects of cyproterone acetate on FSH and testosterone influenced spermatogenesis, steroidogenesis and epididymis in the Indian wall lizard, Hemidactylus flaviviridis (Ruppell).

    PubMed

    Rai, U; Haider, S

    1995-11-01

    The effects of FSH, testosterone and either cyproterone acetate (CPA) alone or in combination with FSH or testosterone on testis and epididymis in male lizards were studied histologically and histochemically during recrudescent phase to find out whether the onset of spermatogenesis is androgen dependent or FSH dependent. The testes of control lizards consisted of mainly spermatogonia, a few primary spermatocytes and secondary spermatocytes rarely. The interstitial or Leydig cells were atrophied. FSH treatment induced spermatogenic activity substantially as indicated by increase in number of primary and secondary spermatocytes and transformation of secondary spermatocytes into spermatids and into spermatozoa in a few cases. Besides, steroidogenic activity was also remarkably stimulated as evidences by considerable depletion of sudanophilic lipid and an increase in Delta5-3beta-hydroxysteroid dehydrogenase enzyme activity in Leydig cells. However, testosterone treatment resulted in the inhibition of spermatogenesis. A significant inhibition of spermatogenesis was noted in lizards treated either with CPA alone or in combination with FSH. The inhibitory effect of CPA on spermatogenesis was increased when it was given in combination with testosterone. The results indicate that onset of spermatogenic activity is dependent on FSH (or FSH-like protein), but not on the androgen. The ductus epididymidis in control lizards was regressed with low cuboidal epithelium. The lumen of the tubules was totally devoid of secretory material and spermatozoa. FSH treatment induced a marked hypertrophy in epididymidis. The lumen became filled with secretory material mixed with spermatozoa. The hypertrophy in epididymidis was also recorded after the treatment with testosterone, but the degree of induction was not to that extent as noted in FSH treated ones. However, CPA injected either with FSH or with testosterone resulted in the profound atrophy in epididymidis.

  20. Subunit structure of the follitropin (FSH) receptor. Photoaffinity labeling of the membrane-bound receptor follitropin complex in situ

    SciTech Connect

    Smith, R.A.; Branca, A.A.; Reichert, L.E. Jr.

    1985-11-15

    Human follicle-stimulating hormone (hFSH) was acylated with N-hydroxysuccinimidyl-4-azidobenzoate (HSAB) and radioiodinated (55 microCi/micrograms) for use as a photoaffinity probe to investigate the subunit structure of the FSH receptor in calf testis. After incubation with the photoaffinity probe and photolysis with UV light, the cross-linked hormone-receptor complex was solubilized from the membrane and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence and absence of the reducing agent dithiothreitol. Autoradiography of the polyacrylamide gels revealed two major bands, 64 kDa and 84 kDa. These were equivalent in molecular mass to those observed in a previous study in which performed hormone-receptor complexes were solubilized with detergent prior to formation of covalent cross-linkages through the use of homobifunctional cross-linking reagents. Reduction with dithiothreitol resulted in the loss of radioactivity from the 84-kDa band with a concomitant increase in the intensity of the 64-kDa band. Since dithiothreitol increases the dissociation of intact radioiodinated azidobenzoyl-FSH into subunits, it is suggested that the conversion of the 84-kDa band to the 64-kDa band by dithiothreitol is due to the loss of non-cross-linked hFSH subunit from the 84-kDa band and that the two bands observed after photoaffinity labeling arise from covalent bond formation between hFSH and a receptor subunit having a relative molecular weight (Mr) of 48,000. In addition to the predominant photolabeling of the receptor to yield the 64-kDa and 84-kDa bands, several other, less intense bands (54 kDa, 76 kDa, 97 kDa, and 116 kDa) were also consistently observed on autoradiographs.

  1. HP-HMG versus rFSH in treatments combining fresh and frozen IVF cycles: success rates and economic evaluation.

    PubMed

    Wex-Wechowski, Jaro; Abou-Setta, Ahmed M; Kildegaard Nielsen, Sandy; Kennedy, Richard

    2010-08-01

    The economic implications of the choice of gonadotrophin influence decision making but their cost-effectiveness in frozen-embryo transfer cycles has not been adequately studied. An economic evaluation was performed comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) using individual patient data (n=986) from two large randomized controlled trials using a long agonist IVF protocol. The simulation model incorporated live birth data and published UK costs of IVF-related medical resources. After treatment for up-to-three cycles (one fresh and up to two subsequent fresh or frozen cycles conditional on availability of cryopreserved embryos), the cumulative live birth rate was 53.7% (95% CI 49.3-58.1%) for HP-HMG and 44.6% (40.2-49.0%) for rFSH (OR 1.44, 95% CI 1.12-1.85; P<0.005). The mean costs per IVF treatment for HP-HMG and rFSH were pound5393 ( pound5341-5449) and pound6269 ( pound6210-6324), respectively (number needed to treat to fund one additional treatment was seven; P<0.001). With maternal and neonatal costs applied, the median cost per IVF baby delivered with HP-HMG was pound11,157 ( pound11,089-11,129) and pound14,227 ( pound14,183-14,222) with rFSH (P<0.001). The cost saving using HP-HMG remained after varying model parameters in a probabilistic sensitivity analysis.

  2. Use of FSH in two different regimens for ovarian superstimulation prior to ovum pick up and in vitro embryo production in Holstein cows.

    PubMed

    da Silva, Júlio César Barboza; Ferreira, Roberta Machado; Maturana Filho, Milton; Naves, Julianne de Rezende; Santin, Thiago; Pugliesi, Guilherme; Madureira, Ed Hoffmann

    2017-03-01

    We aimed with the present study to evaluate the effects of FSH treatment (200 mg) split in four or six administrations on ovarian follicle stimulation and in vitro oocyte competence for embryo production in dairy cows with synchronized follicular wave emergence. On random days of the estrous cycle (Day 0), non-lactating Holstein cows received a progesterone (P4)-releasing intravaginal device and 2 mg estradiol benzoate IM. On Day 3, they received 0.530 mg sodium cloprostenol (PGF2α) IM. Control cows (n = 35) received no further treatments, whereas FSH-treated cows received 200 mg FSH split in four (FSH4 group; n = 33) or six (FSH6 group; n = 33) administration regimens. Starting on Day 4, cows in FSH4 group received 200 mg FSH split in four equivalent doses of 50 mg 12 h apart. Cows in FSH6 group received the same total FSH dose split in six equivalent doses of 33.3 mg 12 h apart, but treatments started on Day 3. On Day 7 AM (36 h of "coasting" period for FSH-treated groups), the P4 devices were removed and cows were subjected to ovum pick up (OPU). Viable oocytes were in vitro fertilized using sexed-sorted semen. Although FSH treatment did not (P > 0.1) increase the total number of follicles (Control, 53.2 ± 4.5 vs. FSH-treated, 51.4 ± 3.1), the two hormonal stimulation regimens, FSH4 and FSH6, increased the number of medium follicles (6-10 mm; 5.2 ± 0.5 vs. 18.1 ± 1.4; P < 0.0001) and reduced the number of small follicles (2-5.9 mm; 46.3 ± 5.1 vs. 31.0 ± 2.4 P < 0.0001). Also, FSH treatment or regimen did not increase (P > 0.1) the number of viable oocytes (Control, 12.6 ± 1.26 vs. FSH-treated, 12.70 ± 1.03), recovery rate (Control, 36.5% vs. FSH-treated, 36%) and the number of in vitro produced blastocyst (Control, 4.1 ± 0.52 vs. FSH-treated 4.3 ± 0.5). We concluded that FSH stimulation protocol proposed herein is effective to stimulate the growth of small antral follicle population prior to OPU, but it

  3. Par Pond vegetation status 1996

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1996-12-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the newly emergent, shoreline aquatic plant communities of Par Pond began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level. These surveys continued in July, September, and late October, 1995, and into the early spring and late summer of 1996. Communities similar to the pre-drawdown, Par Pond aquatic plant communities continue to become re-established. Emergent beds of maidencane, lotus, waterlily, watershield, and Pontederia are extensive and well developed. Measures of percent cover, width of beds, and estimates of area of coverage with satellite data indicate regrowth within two years of from 40 to 60% of levels prior to the draw down. Cattail occurrence continued to increase during the summer of 1996, especially in the former warm arm of Par Pond, but large beds common to Par Pond prior to the draw down still have not formed. Lotus has invaded and occupies many of the areas formerly dominated by cattail beds. To track the continued development of macrophytes in Par Pond, future surveys through the summer and early fall of 1997, along with the evaluation of satellite data to map the extent of the macrophyte beds of Par Pond, are planned.

  4. Testis and epididymis of the Indian wall lizard (Hemidactylus flaviviridis): effects of flutamide on FSH and testosterone influenced spermatogenesis, Leydig cell, and epididymis.

    PubMed

    Rai, U; Haider, S

    1991-08-01

    To determine the separate spermatogenic actions of FSH and testosterone, adult male lizards Hemidactylus flaviviridis with recrudescent testes were administered the non-steroidal antiandrogen flutamide either alone or in combination with FSH or testosterone, and the histology and histochemistry of the testes and ductus epididymides were studied. Flutamide-treated animals displayed a marked hypertrophy of Leydig cells. A few spermatids were also seen in testis of more than half the animals treated with flutamide. Flutamide also produced a significant increase of primary spermatocytes; no spermatids were observed in controls. A significant inhibition of spermatogenesis was noted in lizards treated either with testosterone alone or in combination with flutamide. Ovine FSH treatment caused a significant stimulation of spermatogenesis, as indicated by the increase of primary and secondary spermatocytes and the transformation of secondary spermatocytes into spermatids or, in a few cases, into spermatozoa. A considerable depletion of sudanophilic lipid and moderate delta 5-3 beta-hydroxysteroid dehydrogenase activity was noted in the Leydig cells of FSH-treated animals indicating enhanced steroidogenesis. Similar results were obtained when lizards were treated with flutamide + FSH. The effects of simultaneous treatment of flutamide with FSH or testosterone on ductus epididymidis revealed that flutamide markedly inhibited the epithelial cell height and lumen diameter with a loss of luminal content when compared to FSH or testosterone-treated lizards.

  5. The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial

    PubMed Central

    2012-01-01

    Background Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. Methods/Design Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of

  6. Extracellular loop 2 in the FSH receptor is crucial for ligand mediated receptor activation.

    PubMed

    Dupakuntla, Madhavi; Pathak, Bhakti; Roy, Binita Sur; Mahale, Smita D

    2012-10-15

    The present study aims to determine the role of the specific residues of the extracellular loops (ELs) of the FSH receptor (FSHR) in hormone binding and receptor activation. By substituting the sequences of each of the ELs of human FSHR with those of the luteinizing hormone/choriogonadotropin receptor (LH/CGR), we generated three mutant constructs where the three ELs were individually replaced. A fourth construct had all the three substituted ELs. The receptor expression and hormone binding ability of the mutants were comparable to that of the wild type. Hormone-induced signaling and internalization were lower in the EL2 substitution mutant (EL2M). In this mutant, the EL2 of FSHR was substituted with the corresponding loop of LH/CGR. Interestingly, homology modeling revealed a change in the orientation of EL2 in the mutant receptor. Thus, disruption of EL2 affected overall receptor function, suggesting the role of FSHR specific residues of the loop in ligand mediated signaling.

  7. Exploration of locomotion in the ParA/ParB system

    NASA Astrophysics Data System (ADS)

    Jindal, Lavisha; Emberly, Eldon

    2015-03-01

    In many bacteria the ParA/ParB system is responsible for actively segregating DNA during replication. ParB precessively moves by hydrolyzing DNA bound ParA-ATP forming a depleted ParA region in its wake. Recent in-vitro experiments have shown that a ParB covered bead can traverse a ParA bound DNA substrate. It has been suggested that the formation of a gradient in ParA leads to diffusion-ratchet like motion of the ParB bead but its origin and potential consequences requires investigation. We have developed a deterministic model for the in-vitro ParA/ParB system and show that any amount of spatial noise in ParA can lead to the spontaneous formation of its gradient. The velocity of the bead is independent of this noise but depends on the scale over which ParA exerts a force on the bead and the scale over which ParB hydrolyzes ParA from the substrate. There is a particular ratio of these scales at which the velocity is a maximum. We also explore the effects of cooperative vs independent rebinding of ParA to the substrate. Our model shows how the driving force for ParB originates and highlights necessary conditions for directed motion in the in-vitro system that may provide insight into the in-vivo behaviour of the ParA/ParB system.

  8. Induction of spermatogenesis by rhFSH for azoospermia due to spermatogenic dysfunction with maturation arrest: five case series.

    PubMed

    Kobori, Yoshitomo; Suzuki, Keisuke; Iwahata, Toshiyuki; Shin, Takeshi; Sato, Ryo; Nishio, Kojiro; Yagi, Hiroshi; Arai, Gaku; Soh, Shigehiro; Okada, Hiroshi

    2015-06-01

    When sperm cannot be retrieved from the testes of patients with azoospermia due to spermatogenic dysfunction (ASD), there is no rational way for the patient to become a biological father. We investigated the possibility of inducing spermatogenesis in such patients by hormonal therapy with recombinant human follicle-stimulating hormone (rhFSH) alone. Twenty-six ASD patients who could not obtain spermatozoa by microdissection testicular sperm extraction (micro-TESE) were confirmed to have arrested spermatogenesis at the late stage of maturation arrest. They were subsequently treated with 75-150 IU two times/week rhFSH alone for 12 months. The primary endpoint was the appearance of sperm in ejaculate, and we followed the patients to determine the outcome of inseminating their partners. After rhFSH treatment, mature spermatozoa were found in the ejaculate in five of 26 (19.2%) patients, all of whom showed histology of non-uniform type maturation arrest. Intracytoplasmic sperm injection of the mature spermatozoa resulted in two ongoing clinical pregnancies (insemination success rate, 40.0%). Recombinant human follicle-stimulating hormone treatment can be used as an advanced assisted reproductive technology to improve spermatogenesis in some azoospermic patients with maturation arrest of spermatogenesis and is a potential treatment option after unsuccessful micro-TESE.

  9. Pituitary gonadotropins FSH and LH are oppositely regulated by the activin/follistatin system in a basal teleost, the eel.

    PubMed

    Aroua, Salima; Maugars, Gersende; Jeng, Shan-Ru; Chang, Ching-Fong; Weltzien, Finn-Arne; Rousseau, Karine; Dufour, Sylvie

    2012-01-01

    European eels are blocked at a prepubertal silver stage due to a deficient production of pituitary gonadotropins. We investigated the potential role of activin/follistatin system in the control of eel gonadotropins. Through the development of qPCR assays for European eel activin β(B) and follistatin, we first analyzed the tissue distribution of the expression of these two genes. Both activin β(B) and follistatin are expressed in the brain, pituitary and gonads. In addition, a striking expression of both transcripts was also found in the retina and in adipose tissue. The effects of recombinant human activins and follistatin on eel gonadotropin gene expression were studied using primary cultures of eel pituitary cells. Activins A and B strongly stimulated FSHβ subunit expression in a time- and dose-dependent manner. In contrast, activin reduced LHβ expression, an inhibitory effect which was highlighted in the presence of testosterone, a known activator of eel LHβ expression. No effect of activin was observed on other pituitary hormones. Follistatin antagonized both the stimulatory and inhibitory effects of activin on FSHβ and LHβ expression, respectively. Activin is the first major stimulator of FSH expression evidenced in the eel. These results in a basal teleost further support the ancient origin and strong conservation of the activin/follistatin system in the control of FSH in vertebrates. In contrast, the opposite regulation of FSH and LH may have emerged in the teleost lineage.

  10. In vitro growth and maturation of isolated caprine preantral follicles: Influence of insulin and FSH concentration, culture dish, coculture, and oocyte size on meiotic resumption.

    PubMed

    Silva, G M; Brito, I R; Sales, A D; Aguiar, F L N; Duarte, A B G; Araújo, V R; Vieira, L A; Magalhães-Padilha, D M; Lima, L F; Alves, B G; Silveira, L B R; Lo Turco, E G; Rodrigues, A P; Campello, C C; Wheeler, M B; Figueiredo, J R

    2017-03-01

    The aims of this study were: (1) to evaluate the effect of different insulin concentrations, alone or in combination with either a fixed FSH concentration or increasing FSH concentrations on the in vitro culture of isolated caprine preantral follicles and (2) to analyze the efficiency of two IVM media and maturation culture systems (with or without coculture with in vivo grown oocytes) on the meiosis resumption. Secondary follicles were cultured for 18 days in a basic medium supplemented with low- or high-insulin concentration alone or with a fixed FSH concentration or with increasing FSH concentrations. Oocytes grown in vivo or in vitro were matured alone or cocultured. The high-insulin concentration associated with fixed FSH treatment had higher meiotic resumption rate (P < 0.05) and was the only treatment capable of producing oocytes in metaphase II. The rates of germinal vesicle, germinal vesicle breakdown, metaphase I, metaphase II (MII), meiotic resumption, and oocyte diameter were similar between the maturation media. In conclusion, a basic medium supplemented with 10-μg/mL insulin and 100-μg/mL FSH throughout the culture period improved meiotic resumption rate and produced MII oocytes from caprine preantral follicles cultured in vitro. The MII rate was similar between in vivo and in vitro grown oocytes ≥110 μm.

  11. Effect of three pFSH doses on superovulation and embryo quality in goats during two breeding seasons in north-eastern mexico.

    PubMed

    Sánchez-Dávila, F; Ledezma-Torres, R A; Padilla-Rivas, G; Del Bosque-González, A S; González Gómez, A; Bernal-Barragán, H

    2014-08-01

    The aim of this research was to evaluate the effectiveness of three pFSH doses (80 mg; 145 mg and 215 mg) on ovarian response and on quantity and quality of transferable embryos of goats during the breeding and the non-breeding seasons. Ovary structures were exposed (laparatomy under general anaesthesia) and numbers of follicles and corpora lutea were registered. Surgical embryo flushing was conducted to count and classify embryos. There were more follicles (3.4 ± 1.1) in does administered 80 mg of pFSH (p < 0.05) than in goats administered 145 mg of pFSH (2.2 ± 1.1) and 215 mg of pFSH (0.9 ± 0.6). Numbers of corpora lutea, blastocysts, and recovered and transferable embryos of goats administered 145 mg pFSH (13.4 ± 3.7, 2.42 ± 1.0, 3.4 ± 1.2 and 3.2 ± 1.1, respectively) and those of goats administered 215 mg pFSH (11.6 ± 2.6, 3.2 ± 0.9, 5.7 ± 1.5, and 5.6 ± 1.5) were greater (p < 0.05) than values obtained from goats administered 80 mg pFSH (4.0 ± 1.5, 0.5 ± 0.3, 1.0 ± 0.5, and 0.8 ± 0.5). Numbers of morula of does administered 80 and 145 mg pFSH (0.4 ± 0.4 and 0.8 ± 0.3) were lower (p < 0.05) than those obtained from animals treated with 215 mg pFSH (2.4 ± 0.9). There was no effect of season upon the analyzed variables. In conclusion, under the prevalent conditions in north-eastern Mexico, administration of 145 or 215 mg pFSH in a decreasing dose schedule over 3.5 days to bred goats provided a satisfactory superovulatory result.

  12. Par Pond Fish, Water, and Sediment Chemistry

    SciTech Connect

    Paller, M.H.; Wike, L.D.

    1996-06-01

    The objectives of this report are to describe the Par Pond fish community and the impact of the drawdown and refill on the community, describe contaminant levels in Par Pond fish, sediments, and water and indicate how contaminant concentrations and distributions were affected by the drawdown and refill, and predict possible effects of future water level fluctuations in Par Pond.

  13. Directed and persistent movement arises from mechanochemistry of the ParA/ParB system

    NASA Astrophysics Data System (ADS)

    Hu, Longhua; Vecchiarelli, Anthony G.; Mizuuchi, Kiyoshi; Neuman, Keir C.; Liu, Jian

    The segregation of DNA prior to cell division is essential for faithful genetic inheritance. In many bacteria, segregation of the low-copy-number plasmids involves an active partition system composed of ParA ATPase and its stimulator protein ParB. Recent experiments suggest that ParA/ParB system motility is driven by a diffusion-ratchet mechanism in which ParB-coated plasmid both creates and follows a ParA gradient on the nucleoid surface. However, the detailed mechanism of ParA/ParB-mediated directed and persistent movement remains unknown. We develop a theoretical model describing ParA/ParB-mediated motility. We show that the ParA/ParB system can work as a Brownian ratchet, which effectively couples the ATPase-dependent cycling of ParA-nucleoid affinity to the motion of the ParB bound cargo. Paradoxically, the resulting processive motion relies on quenching diffusive plasmid motion through a large number of transient ParA/ParB-mediated tethers to the nucleoid surface. Our work sheds light on a new emergent phenomenon in which non-motor proteins work collectively via mechanochemical coupling to propel cargos -- an ingenious solution shaped by evolution to cope with the lack of processive motor proteins in bacteria.

  14. Effects of eCG and FSH on ovarian response, recovery rate and number and quality of oocytes obtained by ovum pick-up in Holstein cows.

    PubMed

    Sendag, Sait; Cetin, Yunus; Alan, Muhammet; Hadeler, Klaus-Gerd; Niemann, Heiner

    2008-06-01

    The goal of the present study was to compare the ovarian response, oocyte yields per animal, and the morphological quality of oocytes collected by ultrasound guided follicular aspiration from Holstein cows treated either with FSH or eCG. Twenty four normal cyclic, German Holstein cows were randomly divided into two groups. Fourteen cows received 3000 IU eCG on day-4 prior to ovum pick-up (OPU) (day 0), 2 days later (day-2), 625 microg cloprostenol was administered. On day-1 GnRH was administered i.m. and 24h later OPU (day 0) was performed. In ten cows a total dose of 500 IU follicle stimulating hormone (Pluset) was administered intramuscularly in a constant dosage for 4 days with intervals of 12h, starting on day-5. Luteolysis was induced by application of 625 microg cloprostenol on day-2. On day-1 (24h after the last FSH treatment) GnRH was administered i.m. and 24h later OPU (day 0) was performed. Ovarian follicles were visualized on the ultrasound monitor, counted and recorded. All visible antral follicles were punctured. Recovered oocytes were graded morphologically based on the cumulus investment. Average follicle number in ovaries was higher in FSH group than eCG group (p<0.05). Oocyte yields per animal did not differ between FSH and eCG groups. The proportion of grade A oocytes was higher in the FSH group in the than eCG group (p<0.05). Likewise, rate of grade C oocytes in FSH group were lower than eCG group (p<0.05). In conclusion, these results suggest that ovarian response, follicle number in ovaries and oocyte quality are affected by the type of gonadotropin and FSH is better alternative than eCG for OPU treatment.

  15. Effects of different batches of /sup 125/iodine on properties of /sup 125/I-hFSH and characteristics of radioligand-receptor assays

    SciTech Connect

    Melson, B.E.; Sluss, P.M.; Reichert, L.E. Jr.

    1987-02-01

    Radioiodination of highly purified human follicle-stimulating hormone (hFSH) (4000 IU/mg) was performed every other week for 23 weeks using 2 mCI carrier free Na/sup 125/I (Amersham Corp., 15 mCi/micrograms I2) in the presence of lactoperoxidase. Incorporation of /sup 125/I into hFSH was determined by the method of R. C. Greenwood, W. M. Hunter, and J. S. Grover (1963) Biochem. J. 89, 114). Hormone binding was studied in vitro under steady-state conditions (16 h, 20 degrees C) using different calf testis membrane preparations having similar receptor characteristics. Each /sup 125/I-hFSH preparation was characterized for maximum bindability, specific activity of bindable radioligand as determined by self-displacement analysis, and by determination of Ka and Rt. Incorporation of /sup 125/I into FSH was relatively constant over the large number of experiments (62.4 +/- 6.4 microCi/micrograms; n = 23). By comparison, however, specific radioactivity of the receptor bindable fraction of /sup 125/I-hFSH was related to the lot of /sup 125/I utilized, and was significantly (P less than or equal to 0.01) lower and more variable (28.7 +/- 10.5 microCi/micrograms). Maximum bindability of /sup 125/I-hFSH was not correlated to specific activity (r = 0.06) but was negatively correlated to hFSH /sup 125/I incorporation (r = -0.47; P less than or equal to 0.05). These observations demonstrate the need to assess the quality of each batch of radioligand before undertaking radioligand-receptor assays and suggest that differences in Na/sup 125/I lots affect specific radioactivity of the radioligand and its receptor binding characteristics.

  16. Follicle-stimulating hormone receptor (FSHR) alternative skipping of exon 2 or 3 affects ovarian response to FSH.

    PubMed

    Karakaya, Cengiz; Guzeloglu-Kayisli, Ozlem; Hobbs, Rebecca J; Gerasimova, Tsilya; Uyar, Asli; Erdem, Mehmet; Oktem, Mesut; Erdem, Ahmet; Gumuslu, Seyhan; Ercan, Deniz; Sakkas, Denny; Comizzoli, Pierre; Seli, Emre; Lalioti, Maria D

    2014-07-01

    Genes critical for fertility are highly conserved in mammals. Interspecies DNA sequence variation, resulting in amino acid substitutions and post-transcriptional modifications, including alternative splicing, are a result of evolution and speciation. The mammalian follicle-stimulating hormone receptor (FSHR) gene encodes distinct species-specific forms by alternative splicing. Skipping of exon 2 of the human FSHR was reported in women of North American origin and correlated with low response to ovarian stimulation with exogenous follicle-stimulating hormone (FSH). To determine whether this variant correlated with low response in women of different genetic backgrounds, we performed a blinded retrospective observational study in a Turkish cohort. Ovarian response was determined as low, intermediate or high according to retrieved oocyte numbers after classifying patients in four age groups (<35, 35-37, 38-40, >40). Cumulus cells collected from 96 women undergoing IVF/ICSI following controlled ovarian hyperstimulation revealed four alternatively spliced FSHR products in seven patients (8%): exon 2 deletion in four patients; exon 3 and exons 2 + 3 deletion in one patient each, and a retention of an intron 1 fragment in one patient. In all others (92%) splicing was intact. Alternative skipping of exons 2, 3 or 2 + 3 were exclusive to low responders and was independent of the use of agonist or antagonist. Interestingly, skipping of exon 3 occurs naturally in the ovaries of domestic cats--a good comparative model for human fertility. We tested the signaling potential of human and cat variants after transfection in HEK293 cells and FSH stimulation. None of the splicing variants initiated cAMP signaling despite high FSH doses, unlike full-length proteins. These data substantiate the occurrence of FSHR exon skipping in a subgroup of low responders and suggest that species-specific regulation of FSHR splicing plays diverse roles in mammalian ovarian function.

  17. suPAR: The Molecular Crystal Ball

    PubMed Central

    Thunø, Maria; Macho, Betina; Eugen-Olsen, Jesper

    2009-01-01

    soluble urokinase Plasminogen Activator Receptor (suPAR) levels reflect inflammation and elevated suPAR levels are found in several infectious diseases and cancer. suPAR exists in three forms; suPARI-III, suPARII-III and suPARI which show different properties due to structural differences. Studies suggest that full-length suPAR is a regulator of uPAR/uPA by acting as uPA-scavenger, whereas the cleaved suPARII-III act as a chemotactic agent promoting the immune response via the SRSRY sequence in the linker-region. This review focus on the various suPAR fragments and their involvement in inflammation and pathogenic processes. We focus on the molecular mechanisms of the suPAR fragments and the link to the inflammatory process, as this could lead to medical applications in infectious and pathological conditions. PMID:19893210

  18. Involvement of ERK1/2 signaling pathway in atrazine action on FSH-stimulated LHR and CYP19A1 expression in rat granulosa cells

    SciTech Connect

    Fa, Svetlana; Pogrmic-Majkic, Kristina; Samardzija, Dragana; Glisic, Branka; Kaisarevic, Sonja; Kovacevic, Radmila; Andric, Nebojsa

    2013-07-01

    Worldwide used herbicide atrazine is linked to reproductive dysfunction in females. In this study, we investigated the effects and the mechanism of atrazine action in the ovary using a primary culture of immature granulosa cells. In granulosa cells, follicle-stimulating hormone (FSH) activates both cyclic adenosine monophosphate (cAMP) and extracellular-regulated kinase 1/2 (ERK1/2) cascades, with cAMP pathway being more important for luteinizing hormone receptor (LHR) and aromatase (CYP19A1) mRNA expression. We report that 48 h after atrazine exposure the FSH-stimulated LHR and CYP19A1 mRNA expression and estradiol synthesis were decreased, with LHR mRNA being more sensitive to atrazine than CYP19A1 mRNA. Inadequate acquisition of LHR in the FSH-stimulated and atrazine-exposed granulosa cells renders human chorionic gonadotropin (hCG) ineffective to stimulate amphiregulin (Areg), epiregulin (Ereg), and progesterone receptor (Pgr) mRNA expression, suggesting anti-ovulatory effect of atrazine. To dissect the signaling cascade involved in atrazine action in granulosa cells, we used U0126, a pharmacological inhibitor of ERK1/2. U0126 prevents atrazine-induced decrease in LHR and CYP19A1 mRNA levels and estradiol production in the FSH-stimulated granulosa cells. ERK1/2 inactivation restores the ability of hCG to induce expression of the ovulatory genes in atrazine-exposed granulosa cells. Cell-based ELISA assay revealed that atrazine does not change the FSH-stimulated ERK1/2 phosphorylation in granulosa cells. The results from this study reveal that atrazine does not affect but requires ERK1/2 phosphorylation to cause decrease in the FSH-induced LHR and CYP19A1 mRNA levels and estradiol production in immature granulosa cells, thus compromising ovulation and female fertility. - Highlights: • Atrazine inhibits estradiol production in FSH-stimulated granulosa cells. • Atrazine inhibits LHR and Cyp19a1 mRNA expression in FSH-stimulated granulosa cells. • Atrazine

  19. Infertility and ovarian follicle reserve depletion are associated with dysregulation of the FSH and LH receptor density in human antral follicles.

    PubMed

    Regan, Sheena L P; Knight, Phil G; Yovich, John L; Stanger, James D; Leung, Yee; Arfuso, Frank; Dharmarajan, Arun; Almahbobi, Ghanim

    2017-02-07

    The low take-home baby rate in older women in Australia (5.8%) undergoing IVF (5.8%) is linked to the depletion of the ovarian reserve of primordial follicles. Oocyte depletion causes an irreversible change to ovarian function. We found that the young patient FSH receptor and LH receptor expression profile on the granulosa cells collected from different size follicles were similar to the expression profile reported in natural cycles in women and sheep. This was reversed in the older patients with poor ovarian reserve. The strong correlation of BMPR1B and FSH receptor density in the young was not present in the older women; whereas, the LH receptor and BMPR1B correlation was weak in the young but was strongly correlated in the older women. The reduced fertilisation and pregnancy rate was associated with a lower LH receptor density and a lack of essential down-regulation of the FSH and LH receptor. The mechanism regulating FSH and LH receptor expression appears to function independently, in vivo, from the dose of FSH gonadotrophin, rather than in response to it. Restoring an optimum receptor density may improve oocyte quality and the pregnancy rate in older women.

  20. Determination of biological activity of gonadotropins hCG and FSH by Förster resonance energy transfer based biosensors

    PubMed Central

    Mazina, Olga; Allikalt, Anni; Tapanainen, Juha S.; Salumets, Andres; Rinken, Ago

    2017-01-01

    Determination of biological activity of gonadotropin hormones is essential in reproductive medicine and pharmaceutical manufacturing of the hormonal preparations. The aim of the study was to adopt a G-protein coupled receptor (GPCR)-mediated signal transduction pathway based assay for quantification of biological activity of gonadotropins. We focussed on studying human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH), as these hormones are widely used in clinical practice. Receptor-specific changes in cellular cyclic adenosine monophosphate (cAMP, second messenger in GPCR signalling) were monitored by a Förster resonance energy transfer (FRET) biosensor protein TEpacVV in living cells upon activation of the relevant gonadotropin receptor. The BacMam gene delivery system was used for biosensor protein expression in target cells. In the developed assay only biologically active hormones initiated GPCR-mediated cellular signalling. High assay sensitivities were achieved for detection of hCG (limit of detection, LOD: 5 pM) and FSH (LOD: 100 pM). Even the small-scale conformational changes caused by thermal inactivation and reducing the biological activity of the hormones were registered. In conclusion, the proposed assay is suitable for quantification of biological activity of gonadotropins and is a good alternative to antibody- and animal-testing-based assays used in pharmaceutical industry and clinical research. PMID:28181555

  1. Transvaginal follicle aspiration in Thai swamp buffalo heifers using different vacuum pressures after FSH pretreatment (Bubalus bubalis).

    PubMed

    Techakumphu, Mongkol; Promdireg, Akachart; Phutikanit, Nawapen; Nachiengmai, Anchalee; Thongjan, Sak

    2004-08-01

    The objective of the experiment was to study oocyte recovery by transvaginal, ultrasound-guided, follicle aspiration, from Thai swamp buffalo using different vacuum pressures. Six adult buffalo heifers, aged 2.5-3.0 yrs were treated with a total dose of 280 mg FSH, given twice a day in a divided doses over a three day period (60/60 mg, 50/50 mg, 30/30 mg) at d7 after progesterone implant. Three vacuum pressures were used; 100 (n=12), 80 (n=12) and 60 mmHg (n=12) and all of the pressures were performed in each animal. The animals were treated repeatedly and collection took place using 2 sets of each pressure every 2 months, giving a total of 36 collections from each animal. The oocyte recovery rates from each pressure were 81.2% (69/85) 79.1% (53/67) and 90.3% (93/103) for 100, 80 and 60 mmHg respectively. The number of oocytes collected per donor were 5.33 +/- 3.27, 4.42 +/- 2.71 and 7.75 +/- 4.31 respectively. The quality of the oocytes did not improved with the lower vacuum pressure. In conclusion, the application of FSH pretreatment improves the yield of oocytes from Thai, swamp buffalo heifers after gonadotropin treatment when using the vacuum pressures between 60-100 mmHg.

  2. USGS field activity 08FSH01 on the west Florida shelf, Gulf of Mexico, in August 2008

    USGS Publications Warehouse

    Robbins, Lisa L.; Knorr, Paul O.; Liu, Xuewu; Byrne, Robert H.; Raabe, Ellen A.

    2009-01-01

    From August 11 to 15, 2008, a cruise led by the U.S. Geological Survey (USGS) collected air and sea surface partial pressure of carbon dioxide (pCO2), pH, dissolved inorganic carbon (DIC), and total alkalinity (TA) data on the west Florida shelf. Approximately 1,600 data points were collected underway over a 650-kilometer (km) trackline using the Multiparameter Inorganic Carbon Analyzer (MICA). The collection of data extended from Crystal River southward to Marco Island, Florida (~400 km), and westward up to 160 km off the Florida coast. Discrete water samples from approximately 40 locations were also taken at specific localities to corroborate underway data measurements. The USGS St. Petersburg Coastal and Marine Science Center (SPCMSC) assigns a unique identifier to each cruise or field activity. For example, 08FSH01 tells us the data were collected in 2008 for the Response of Florida Shelf (FSH) Ecosystems to Climate Change project, and the data were collected during the first field activity for that study in that calendar year.

  3. USGS field activity 09FSH01 on the west Florida shelf, Gulf of Mexico, in February 2009

    USGS Publications Warehouse

    Robbins, Lisa L.; Knorr, Paul O.; Liu, Xuewu; Byrne, Robert H.; Raabe, Ellen A.

    2009-01-01

    From February 24 to 28, 2009, a cruise led by the U.S. Geological Survey (USGS) collected air and sea surface partial pressure of carbon dioxide (pCO2), pH, dissolved inorganic carbon (DIC), and total alkalinity (TA) data on the west Florida shelf. Approximately 1,800 data points were collected underway over a 1,300-kilometer (km) trackline using the Multiparameter Inorganic Carbon Analyzer (MICA). The collection of data extended from Crystal River to Marco Island, Florida (~400 km), and westward up to 160 km off the Florida coast. Discrete water samples were also taken at specific localities to corroborate underway data measurements. The USGS St. Petersburg Coastal and Marine Science Center (SPCMSC) assigns a unique identifier to each cruise or field activity. For example, 09FSH01 tells us that the data were collected in 2009 for the Response of Florida Shelf (FSH) Ecosystems to Climate Change project, and the data were collected during the first field activity for that study in that calendar year.

  4. USGS field activity 09FSH02 on the west Florida shelf, Gulf of Mexico, in August 2009

    USGS Publications Warehouse

    Robbins, Lisa L.; Knorr, Paul O.; Liu, Xuewu; Byrne, Robert H.; Raabe, Ellen A.

    2009-01-01

    From August 17 to 21, 2009, a cruise led by the U.S. Geological Survey (USGS) collected air and sea surface partial pressure of carbon dioxide (pCO2), pH, dissolved inorganic carbon (DIC), and total alkalinity (TA) data on the west Florida shelf. Approximately 2,000 data points were collected underway over a 1,320-kilometer (km) track line using the Multiparameter Inorganic Carbon Analyzer (MICA). The collection of data extended from Crystal River to Marco Island, Florida (~400 km), and westward up to 160 km off the Florida coast. Discrete water samples were also taken at specific localities to corroborate underway data measurements. The USGS St. Petersburg Coastal and Marine Science Center (SPCMSC) assigns a unique identifier to each cruise or field activity. For example, 09FSH02 tells us that the data were collected in 2009 for the Response of Florida Shelf (FSH) Ecosystems to Climate Change project, and the data were collected during the second field activity for that study in that calendar year.

  5. Determination of biological activity of gonadotropins hCG and FSH by Förster resonance energy transfer based biosensors.

    PubMed

    Mazina, Olga; Allikalt, Anni; Tapanainen, Juha S; Salumets, Andres; Rinken, Ago

    2017-02-09

    Determination of biological activity of gonadotropin hormones is essential in reproductive medicine and pharmaceutical manufacturing of the hormonal preparations. The aim of the study was to adopt a G-protein coupled receptor (GPCR)-mediated signal transduction pathway based assay for quantification of biological activity of gonadotropins. We focussed on studying human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH), as these hormones are widely used in clinical practice. Receptor-specific changes in cellular cyclic adenosine monophosphate (cAMP, second messenger in GPCR signalling) were monitored by a Förster resonance energy transfer (FRET) biosensor protein (T)Epac(VV) in living cells upon activation of the relevant gonadotropin receptor. The BacMam gene delivery system was used for biosensor protein expression in target cells. In the developed assay only biologically active hormones initiated GPCR-mediated cellular signalling. High assay sensitivities were achieved for detection of hCG (limit of detection, LOD: 5 pM) and FSH (LOD: 100 pM). Even the small-scale conformational changes caused by thermal inactivation and reducing the biological activity of the hormones were registered. In conclusion, the proposed assay is suitable for quantification of biological activity of gonadotropins and is a good alternative to antibody- and animal-testing-based assays used in pharmaceutical industry and clinical research.

  6. FSH-initiated differentiation of newt spermatogonia to primary spermatocytes in germ-somatic cell reaggregates cultured within a collagen matrix.

    PubMed

    Ito, R; Abé, S I

    1999-03-01

    We previously cultured fragments of newt testes in chemically defined media and showed that mammalian follicle-stimulating hormone (FSH) stimulates proliferation of spermatogonia as well as their differentiation into primary spermatocytes (Ji et al., 1992; Abe and Ji, 1994). Next, we indicated in cultures composed of spermatogonia and somatic cells (mainly Sertoli cells) that FSH stimulates germ cell proliferation via Sertoli cells (Maekawa et al., 1995). However, the spermatogonia did not differentiate into primary spermatocytes, but instead died. In the present study, we embedded large reaggregates of spermatogonia and somatic cells (mainly Sertoli cells) within a collagen matrix and cultured the reaggregates on a filter that floated on chemically defined media containing FSH; in this revised culture system, spermatogonia proliferated and differentiated into primary spermatocytes. The viability and percentage of germ cells differentiating into primary spermatocytes were proportional to the percentage of somatic cells in the culture, indicating that differentiation of spermatogonia into primary spermatocytes is mediated by Sertoli cells.

  7. Effects of ovum pick-up frequency and FSH stimulation: a retrospective study on seven years of beef cattle in vitro embryo production.

    PubMed

    De Roover, R; Feugang, J M N; Bols, P E J; Genicot, G; Hanzen, Ch

    2008-04-01

    The aim of this retrospective study was to compare the number of follicles, cumulus oocyte complexes (COCs) and cultured In Vitro Produced (IVP) embryos obtained from 1396 non-stimulated Ovum Pick-up (OPU) sessions on 81 donor animals in a twice weekly OPU scheme. Results were obtained from 640 sessions following FSH-LH superstimulation, on 112 donors subjected to OPU once every 2 weeks. The stimulation protocol started with the insertion of an ear implant containing 3 mg norgestomet (Crestar, Intervet, Belgium) 8 days before puncture (day -8). The dominant follicle was ablated by ultrasound-guided follicle puncture on day -6. On day -3 and day -2, cows were injected with FSH (Ovagen, ICP) twice daily (8 am to 8 pm), i.e. a total dose of 160 mug FSH and 40 mug LG per donor per stimulation cycle. Animals were punctured 48 h after the last FSH injection (day 0). Progesterone implants were removed the next day. Stimulated donor cows were treated with this protocol at 14-day intervals. Follicles were visualized with a Dynamic Imaging ultrasound scanner, equipped with a 6.5 MHz sectorial probe. Follicles were punctured with 55 cm long, 18 gauge needles at an aspiration pressure corresponding to a flow rate of 15 ml/min. Cumulus oocyte complexes were recovered and processed in a routine IVF set-up. Results demonstrate that, expressed per session, FSH stimulation prior to OPU increases production efficiency with significantly more follicles punctured and oocytes retrieved. However, when overall results during comparable 2-week periods are considered (four non-stimulated sessions vs one stimulated), more follicles are punctured and more oocytes are retrieved using the non-stimulated protocol. No significant differences in the number of cultured embryos could be detected, indicating that FSH/LH stimulation prior to OPU might have a positive effect on in vitro oocyte developmental competence as more embryos are cultured with less, presumably better-quality, oocytes.

  8. Effects of growth differentiation factor-9 and FSH on in vitro development, viability and mRNA expression in bovine preantral follicles.

    PubMed

    Vasconcelos, G L; Saraiva, M V A; Costa, J J N; Passos, M J; Silva, A W B; Rossi, R O D S; Portela, A M L R; Duarte, A B G; Magalhães-Padilha, D M; Campelo, C C; Figueiredo, J R; van den Hurk, R; Silva, J R V

    2013-01-01

    The present study investigated the role of growth differentiation factor (GDF)-9 and FSH, alone or in combination, on the growth, viability and mRNA expression of FSH receptor, proliferating cell nuclear antigen (PCNA) and proteoglycan-related factors (i.e., hyaluronan synthase (HAS) 1, HAS2, versican, perlecan) in bovine secondary follicles before and after in vitro culture. After 12 days culture, sequential FSH (100 ng mL⁻¹) from Days 0 to 6 and 500 ng mL⁻¹ from Days 7 to 12) increased follicular diameter and resulted in increased antrum formation (P<0.05). Alone, 200 ng mL⁻¹ GDF-9 significantly reduced HAS1 mRNA levels, but increased versican and perlecan mRNA levels in whole follicles, which included the oocyte, theca and granulosa cells. Together, FSH and GDF-9 increased HAS2 and versican (VCAN) mRNA levels, but decreased PCNA mRNA expression, compared with levels in follicles cultured in α-minimum essential medium supplemented with 3.0 mg mL⁻¹ bovine serum albumin, 10 µg mL⁻¹ insulin, 5.5 µg mL⁻¹ transferrin, 5 ng mL⁻¹ selenium, 2 mM glutamine, 2mM hypoxanthine and 50 μg mL⁻¹ ascorbic acid (α-MEM⁺). Comparisons of uncultured (0.2 mm) and α-MEM⁺ cultured follicles revealed that HAS1 mRNA expression was higher, whereas VCAN expression was lower, in cultured follicles (P<0.05). Expression of HAS1, VCAN and perlecan (HSPG2) was higher in cultured than in vivo-grown (0.3 mm) follicles. In conclusion, FSH and/or GDF-9 promote follicular growth and antrum formation. Moreover, GDF-9 stimulates expression of versican and perlecan and interacts positively with FSH to increase HAS2 expression.

  9. PIVET rFSH dosing algorithms for individualized controlled ovarian stimulation enables optimized pregnancy productivity rates and avoidance of ovarian hyperstimulation syndrome.

    PubMed

    Yovich, John L; Alsbjerg, Birgit; Conceicao, Jason L; Hinchliffe, Peter M; Keane, Kevin N

    2016-01-01

    The first PIVET algorithm for individualized recombinant follicle stimulating hormone (rFSH) dosing in in vitro fertilization, reported in 2012, was based on age and antral follicle count grading with adjustments for anti-Müllerian hormone level, body mass index, day-2 FSH, and smoking history. In 2007, it was enabled by the introduction of a metered rFSH pen allowing small dosage increments of ~8.3 IU per click. In 2011, a second rFSH pen was introduced allowing more precise dosages of 12.5 IU per click, and both pens with their individual algorithms have been applied continuously at our clinic. The objective of this observational study was to validate the PIVET algorithms pertaining to the two rFSH pens with the aim of collecting ≤15 oocytes and minimizing the risk of ovarian hyperstimulation syndrome. The data set included 2,822 in vitro fertilization stimulations over a 6-year period until April 2014 applying either of the two individualized dosing algorithms and corresponding pens. The main outcome measures were mean oocytes retrieved and resultant embryos designated for transfer or cryopreservation permitted calculation of oocyte and embryo utilization rates. Ensuing pregnancies were tracked until live births, and live birth productivity rates embracing fresh and frozen transfers were calculated. Overall, the results showed that mean oocyte numbers were 10.0 for all women <40 years with 24% requiring rFSH dosages <150 IU. Applying both specific algorithms in our clinic meant that the starting dose was not altered for 79.1% of patients and for 30.1% of those receiving the very lowest rFSH dosages (≤75 IU). Only 0.3% patients were diagnosed with severe ovarian hyperstimulation syndrome, all deemed avoidable due to definable breaches from the protocols. The live birth productivity rates exceeded 50% for women <35 years and was 33.2% for the group aged 35-39 years. Routine use of both algorithms led to only 11.6% of women generating >15 oocytes

  10. PIVET rFSH dosing algorithms for individualized controlled ovarian stimulation enables optimized pregnancy productivity rates and avoidance of ovarian hyperstimulation syndrome

    PubMed Central

    Yovich, John L; Alsbjerg, Birgit; Conceicao, Jason L; Hinchliffe, Peter M; Keane, Kevin N

    2016-01-01

    The first PIVET algorithm for individualized recombinant follicle stimulating hormone (rFSH) dosing in in vitro fertilization, reported in 2012, was based on age and antral follicle count grading with adjustments for anti-Müllerian hormone level, body mass index, day-2 FSH, and smoking history. In 2007, it was enabled by the introduction of a metered rFSH pen allowing small dosage increments of ~8.3 IU per click. In 2011, a second rFSH pen was introduced allowing more precise dosages of 12.5 IU per click, and both pens with their individual algorithms have been applied continuously at our clinic. The objective of this observational study was to validate the PIVET algorithms pertaining to the two rFSH pens with the aim of collecting ≤15 oocytes and minimizing the risk of ovarian hyperstimulation syndrome. The data set included 2,822 in vitro fertilization stimulations over a 6-year period until April 2014 applying either of the two individualized dosing algorithms and corresponding pens. The main outcome measures were mean oocytes retrieved and resultant embryos designated for transfer or cryopreservation permitted calculation of oocyte and embryo utilization rates. Ensuing pregnancies were tracked until live births, and live birth productivity rates embracing fresh and frozen transfers were calculated. Overall, the results showed that mean oocyte numbers were 10.0 for all women <40 years with 24% requiring rFSH dosages <150 IU. Applying both specific algorithms in our clinic meant that the starting dose was not altered for 79.1% of patients and for 30.1% of those receiving the very lowest rFSH dosages (≤75 IU). Only 0.3% patients were diagnosed with severe ovarian hyperstimulation syndrome, all deemed avoidable due to definable breaches from the protocols. The live birth productivity rates exceeded 50% for women <35 years and was 33.2% for the group aged 35–39 years. Routine use of both algorithms led to only 11.6% of women generating >15 oocytes

  11. PAR for the Course: A Congruent Pedagogical Approach for a PAR Methods Class

    ERIC Educational Resources Information Center

    Hammond, Joyce D.; Hicks, Maria; Kalman, Rowenn; Miller, Jason

    2005-01-01

    In the past two years, three graduate students and a senior faculty member have co-taught a participatory action research (PAR) course to undergraduate and graduate students. In this article the co-teachers advocate a set of pedagogical principles and practices in a PAR-oriented classroom that establishes congruency with community PAR projects in…

  12. Stimulation of LH, FSH, and luteal blood flow by GnRH during the luteal phase in mares.

    PubMed

    Castro, T; Oliveira, F A; Siddiqui, M A R; Baldrighi, J M; Wolf, C A; Ginther, O J

    2016-03-01

    A study was performed on the effect of a single dose per mare of 0 (n = 9), 100 (n = 8), or 300 (n = 9) of GnRH on Day 10 (Day 0 = ovulation) on concentrations of LH, FSH, and progesterone (P4) and blood flow to the CL ovary. Hormone concentration and blood flow measurements were performed at hours 0 (hour of treatment), 0.25, 0.5, 1, 2, 3, 4, and 6. Blood flow was assessed by spectral Doppler ultrasonography for resistance to blood flow in an ovarian artery before entry into the CL ovary. The percentage of the CL with color Doppler signals of blood flow was estimated from videotapes of real-time color Doppler imaging by an operator who was unaware of mare identity, hour, or treatment dose. Concentrations of LH and FSH increased (P < 0.05) at hour 0.25 and decreased (P < 0.05) over hours 1 to 6; P4 concentration was not altered by treatment. Blood flow resistance decreased between hours 0 and 1, but the decrease was greater (P < 0.05) for the 100-μg dose than for the 300-μg dose. The percentage of CL with blood flow signals increased (P < 0.05) between hours 0 and 1 with no significant difference between the 100- and 300-μg doses. The results supported the hypothesis that GnRH increases LH concentration, vascular perfusion of the CL ovary, and CL blood flow during the luteal phase; however, P4 concentration was not affected.

  13. Par Pond vegetation status Summer 1995 -- Summary

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1996-01-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the newly emergent, shoreline aquatic plant communities of Par Pond began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level. These surveys continued in July, September, and late October, 1995. Communities similar to the pre-drawdown, Par Pond aquatic plant communities are becoming re-established. Emergent beds of maidencane, lotus, waterlily, and watershield are extensive and well developed. Cattail occurrence continued to increase during the summer, but large beds common to Par Pond prior to the drawdown have not formed. Estimates from SPOT HRV, remote sensing satellite data indicated that as much as 120 hectares of emergent wetlands vegetation may have been present along the Par Pond shoreline by early October, 1995. To track the continued development of macrophytes in Par Pond, future surveys throughout 1996 and 1997, along with the continued evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned.

  14. Cost effectiveness of letrozole and purified urinary FSH in treating women with clomiphene citrate-resistant polycystic ovarian syndrome: a randomized controlled trial.

    PubMed

    Hassan, AbdelGany; Shehata, Nesreen; Wahba, Amr

    2017-04-01

    We aimed to compare the cost effectiveness of letrozole versus purified urinary follicle stimulating hormone (FSH) in treating patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). This was a randomized trial conducted in Cairo University and Beni-Suef University Hospitals, Egypt. A cohort of 140 eligible women was randomized to receive either letrozole 2.5 mg twice daily for five days, or FSH using a graduated regimen starting with a dose of 75 IU. Treatment was repeated for three months if pregnancy did not occur. There were no significant differences between the two treatments in the cumulative clinical pregnancy rate (30% vs. 34%; p = 0.578), cumulative ovulation rate (47% vs. 57%; p = 0.236), miscarriage rate (9% vs. 4%, p > 0.999) or multiple pregnancy rate (0% and 8%, p = 0.491) but the FSH cycles were 4.8 times more expensive. Letrozole and FSH were both effective in treating women with CC-resistant PCOS but letrozole was more cost effective.Study registration number: NCT02304107.

  15. A randomized controlled trial investigating the use of a predictive nomogram for the selection of the FSH starting dose in IVF/ICSI cycles.

    PubMed

    Allegra, Adolfo; Marino, Angelo; Volpes, Aldo; Coffaro, Francesco; Scaglione, Piero; Gullo, Salvatore; La Marca, Antonio

    2017-01-23

    The number of oocytes retrieved is a relevant intermediate outcome in women undergoing IVF/intracytoplasmic sperm injection (ICSI). This trial compared the efficiency of the selection of the FSH starting dose according to a nomogram based on multiple biomarkers (age, day 3 FSH, anti-Müllerian hormone) versus an age-based strategy. The primary outcome measure was the proportion of women with an optimal number of retrieved oocytes defined as 8-14. At their first IVF/ICSI cycle, 191 patients underwent a long gonadotrophin-releasing hormone agonist protocol and were randomized to receive a starting dose of recombinant (human) FSH, based on their age (150 IU if ≤35 years, 225 IU if >35 years) or based on the nomogram. Optimal response was observed in 58/92 patients (63%) in the nomogram group and in 42/99 (42%) in the control group (+21%, 95% CI = 0.07 to 0.35, P = 0.0037). No significant differences were found in the clinical pregnancy rate or the number of embryos cryopreserved per patient. The study showed that the FSH starting dose selected according to ovarian reserve is associated with an increase in the proportion of patients with an optimal response: large trials are recommended to investigate any possible effect on the live-birth rate.

  16. The long-term effects of FSH and triiodothyronine administration during the pubertal period on Connexin 43 expression and spermatogenesis efficiency in adult rats.

    PubMed

    Marchlewska, Katarzyna; Slowikowska-Hilczer, Jolanta; Walczak-Jedrzejowska, Renata; Oszukowska, Elzbieta; Filipiak, Eliza; Kula, Krzysztof

    2015-04-01

    Follicle-stimulating hormone (FSH) and triiodothyronine (T3) are known regulatory factors of spermatogenesis initiation. Hyperstimulation of both hormones evokes regressional changes in connexin 43 expression and the seminiferous epithelium in young rats during testicular maturation. However, separate treatments with T3 reduce Sertoli cell number, which seems to be closely connected with the maturation of connexin 43 gap junctions. FSH elevates Sertoli cell number and function, but this effect may take place regardless of the presence of connexin 43-dependent intercellular communication. The aim of the study was to evaluate the later effects of such treatments. Newborn, male Wistar rats were divided randomly into experimental groups receiving daily subcutaneous injections of either 7.5 IU/animal FSH, or 100 mg/kg b.w. T3, or both substances or the same volume of vehicle (control group) until day 15 of life. The animals were sacrificed on day 50. Morphometric analysis and immunohistochemical reactions were performed using antibodies against Vimentin, Proliferating Cell Nuclear Antigen and Connexin 43 in the testis. Sertoli cell count, efficiency of spermatogenesis, and hormonal pattern were examined. Disturbances in the connexin 43 expression reduced the number of Sertoli cells, the efficiency of spermatogenesis and impaired endocrine function of testes in adult rats treated with FSH and T3 during puberty. Stimulation with FSH alone increased Sertoli cell number, but was associated with a negative effect on cell-to-cell connexin 43-dependent communication, with a consequential reduction of spermatogenesis efficiency. J. Exp. Zool. 323A: 256-265, 2015. © 2015 Wiley Periodicals, Inc.

  17. Control of oestradiol secretion and of cytochrome P450 aromatase messenger ribonucleic acid accumulation by FSH involves different intracellular pathways in oestrogenic bovine granulosa cells in vitro.

    PubMed

    Silva, J M; Hamel, M; Sahmi, M; Price, C A

    2006-12-01

    The objective of this study was to determine the major intracellular signalling pathways used by FSH and insulin to stimulate cytochrome P450 aromatase (Cyp19) mRNA and oestradiol accumulation in oestrogenic bovine granulosa cells in vitro. Bovine granulosa cells from small follicles (2-4 mm diameter) were cultured for 6 days under non-luteinizing conditions in the presence of insulin at 100 ng/ml, or insulin (10 ng/ml) and FSH (1 ng/ml). On day 4 of culture, specific inhibitors of phosphatidylinositol 3-kinase (PI3K; LY-294002), protein kinase C (PKC; GF-109203X), protein kinase A (PKA; H-89) or mitogen-activated protein (MAP) kinase activation (PD-98059) were added. The addition of PI3K and PKC inhibitors, but not of PKA inhibitor, significantly decreased insulin-stimulated Cyp19 mRNA levels and oestradiol accumulation (P < 0.001). The PKA inhibitor significantly decreased FSH-stimulated Cyp19 mRNA abundance and oestradiol secretion, whereas PI3K and PKC inhibitors decreased oestradiol secretion without affecting Cyp19 mRNA accumulation. Inhibition of MAP kinase pathway significantly increased Cyp19 mRNA abundance in insulin- and FSH-stimulated cells. P450scc mRNA levels and progesterone secretion were not affected by any inhibitor in either experiment. Although FSH stimulates Cyp19 expression predominantly through PKA, oestradiol secretion is altered by PI3K and PKC pathways independently of Cyp19 mRNA levels. In addition, we suggest that Cyp19 is under tonic inhibition mediated through a MAP kinase pathway.

  18. Comparative cactus architecture and par interception

    SciTech Connect

    Geller, G.N.; Nobel, P.S. )

    1987-07-01

    Because CO{sup 2} uptake by cacti can be limited by low levels of photosynthetically active radiation (PAR) and because plant form affects PAR interception, various cactus forms were studied using a computer model, field measurements, and laboratory phototropic studies. Model predictions indicated that CO{sub 2} uptake by individual stems at an equinox was greatest when the stem were vertical, but at the summer and the winter solstice CO{sub 2} uptake was greatest for stems titled 30{degree} away from the equator. Stem tilting depended on form and taxonomic group. Not only can the shape of cacti be affected by PAR, but also shape influences PAR interception and hence CO{sub 2} uptake.

  19. Activin Decoy Receptor ActRIIB:Fc Lowers FSH and Therapeutically Restores Oocyte Yield, Prevents Oocyte Chromosome Misalignments and Spindle Aberrations, and Increases Fertility in Midlife Female SAMP8 Mice

    PubMed Central

    Mackenzie, Amelia C. L.; Lee, Se-Jin; Chaffin, Charles L.; Merchenthaler, István

    2016-01-01

    Women of advanced maternal age (AMA) (age ≥ 35) have increased rates of infertility, miscarriages, and trisomic pregnancies. Collectively these conditions are called “egg infertility.” A root cause of egg infertility is increased rates of oocyte aneuploidy with age. AMA women often have elevated endogenous FSH. Female senescence-accelerated mouse-prone-8 (SAMP8) has increased rates of oocyte spindle aberrations, diminished fertility, and rising endogenous FSH with age. We hypothesize that elevated FSH during the oocyte's FSH-responsive growth period is a cause of abnormalities in the meiotic spindle. We report that eggs from SAMP8 mice treated with equine chorionic gonadotropin (eCG) for the period of oocyte growth have increased chromosome and spindle misalignments. Activin is a molecule that raises FSH, and ActRIIB:Fc is an activin decoy receptor that binds and sequesters activin. We report that ActRIIB:Fc treatment of midlife SAMP8 mice for the duration of oocyte growth lowers FSH, prevents egg chromosome and spindle misalignments, and increases litter sizes. AMA patients can also have poor responsiveness to FSH stimulation. We report that although eCG lowers yields of viable oocytes, ActRIIB:Fc increases yields of viable oocytes. ActRIIB:Fc and eCG cotreatment markedly reduces yields of viable oocytes. These data are consistent with the hypothesis that elevated FSH contributes to egg aneuploidy, declining fertility, and poor ovarian response and that ActRIIB:Fc can prevent egg aneuploidy, increase fertility, and improve ovarian response. Future studies will continue to examine whether ActRIIB:Fc works via FSH and/or other pathways and whether ActRIIB:Fc can prevent aneuploidy, increase fertility, and improve stimulation responsiveness in AMA women. PMID:26713784

  20. Regulation of Pcsk6 expression during the preantral to antral follicle transition in mice: opposing roles of FSH and oocytes.

    PubMed

    Diaz, Francisco J; Sugiura, Koji; Eppig, John J

    2008-01-01

    Several secreted products of the TGFbeta superfamily have important roles during follicular development and are produced by both oocytes and somatic cells (granulosa and theca) in the follicle. The proprotein convertases are a family of seven known proteins that process TGFbeta ligands and other secreted products to their mature active form. The present study examined the regulation of steady-state levels of Pcsk6 mRNA, which encodes a convertase protein known to process members of the TGFbeta superfamily, during mouse follicular development. Pcsk6 mRNA and protein were expressed in preantral but not cumulus or mural granulosa cells. Pcsk6 mRNA levels in preantral granulosa cells were not regulated by growing oocytes of preantral follicles, but were elevated by FSH. Furthermore, Pcsk6 mRNA in preantral granulosa cells was potently suppressed by factor(s) secreted by fully grown oocytes from antral follicles, in part through SMAD2/3-mediated pathways. Oocytes acquired the ability to suppress the steady-state levels of Pcsk6 mRNA in granulosa cells during the preantral to antral follicle transition. Suppression of Pcsk6 mRNA by oocytes could reflect a change in the mechanism(s) regulating the activity of members of the TGFbeta superfamily.

  1. Techniques for measuring intercepted and absorbed PAR in corn canopies

    NASA Technical Reports Server (NTRS)

    Gallo, K. P.; Daughtry, C. S. T.

    1984-01-01

    The quantity of radiation potentially available for photosynthesis that is captured by the crop is best described as absorbed photosynthetically active radiation (PAR). Absorbed PAR (APAR) is the difference between descending and ascending fluxes. The four components of APAR were measured above and within two planting densities of corn (Zea mays L.) and several methods of measuring and estimating APAR were examined. A line quantum sensor that spatially averages the photosynthetic photon flux density provided a rapid and portable method of measuring APAR. PAR reflectance from the soil (Typic Argiaquoll) surface decreased from 10% to less than 1% of the incoming PAR as the canopy cover increased. PAR reflectance from the canopy decreased to less than 3% at maximum vegetative cover. Intercepted PAR (1 - transmitted PAR) generally overestimated absorbed PAR by less than 4% throughout most of the growing season. Thus intercepted PAR appears to be a reasonable estimate of absorbed PAR.

  2. Protease-activated receptor (PAR) 1 and PAR4 differentially regulate factor V expression from human platelets.

    PubMed

    Duvernay, Matthew; Young, Summer; Gailani, David; Schoenecker, Jonathan; Hamm, Heidi E; Hamm, Heidi

    2013-04-01

    With the recent interest of protease-activated receptors (PAR) 1 and PAR4 as possible targets for the treatment of thrombotic disorders, we compared the efficacy of protease-activated receptor (PAR)1 and PAR4 in the generation of procoagulant phenotypes on platelet membranes. PAR4-activating peptide (AP)-stimulated platelets promoted thrombin generation in plasma up to 5 minutes earlier than PAR1-AP-stimulated platelets. PAR4-AP-mediated factor V (FV) association with the platelet surface was 1.6-fold greater than for PAR1-AP. Moreover, PAR4 stimulation resulted in a 3-fold greater release of microparticles, compared with PAR1 stimulation. More robust FV secretion and microparticle generation with PAR4-AP was attributable to stronger and more sustained phosphorylation of myosin light chain at serine 19 and threonine 18. Inhibition of Rho-kinase reduced PAR4-AP-mediated FV secretion and microparticle generation to PAR1-AP-mediated levels. Thrombin generation assays measuring prothrombinase complex activity demonstrated 1.5-fold higher peak thrombin levels on PAR4-AP-stimulated platelets, compared with PAR1-AP-stimulated platelets. Rho-kinase inhibition reduced PAR4-AP-mediated peak thrombin generation by 25% but had no significant effect on PAR1-AP-mediated thrombin generation. In conclusion, stimulation of PAR4 on platelets leads to faster and more robust thrombin generation, compared with PAR1 stimulation. The greater procoagulant potential is related to more efficient FV release from intracellular stores and microparticle production driven by stronger and more sustained myosin light chain phosphorylation. These data have implications about the role of PAR4 during hemostasis and are clinically relevant in light of recent efforts to develop PAR antagonists to treat thrombotic disorders.

  3. Gene expression and secretion of LH and FSH in relation to gene expression of GnRH receptors in the brushtail possum (Trichosurus vulpecula) demonstrates highly conserved mechanisms.

    PubMed

    Crawford, J L; Heath, D A; Haydon, L J; Thomson, B P; Eckery, D C

    2009-01-01

    In eutherian mammals, the gonadotrophins (LH and FSH) are synthesized and stored in gonadotroph cells under the regulation of multiple mechanisms including GnRH. Very little is known about the regulation of gonadotrophin secretion and storage in pituitary glands of marsupials. This study revealed, using quantitative PCR and heterologous RIA techniques, that LHB mRNA expression levels remained constant over the oestrous cycle, regardless of the presence of a preovulatory LH surge, which is characteristic of a hormone secreted under regulation. Our sampling regime was unable to detect pulses of LH during the follicular phase, although GNRHR mRNA levels had increased at this time. Pulses of LH were, however, detected in the luteal phase of cycling females, in anoestrus females and in males. There was a positive correlation between gene expression of FSHB and plasma levels of FSH at different stages of the oestrous cycle and no pulses of FSH were detected at any time; all characteristics of a hormone secreted via the constitutive pathway. Using in situ hybridisation and immunohistochemistry methods, we determined that mRNA expression of LHB and FSHB, and protein storage of gonadotrophins exhibited a similar pattern of localisation within the pituitary gland. Additionally, sexual dimorphism of gonadotroph populations was evident. In summary, these findings are similar to that reported in eutherians and considering that marsupial evolution diverged from eutherians over 100 million years ago suggests that the regulation of gonadotrophins is highly conserved indeed.

  4. Serum FSH level below 10 mIU/mL at twelve years old is an index of spontaneous and cyclical menstruation in Turner syndrome.

    PubMed

    Aso, Keiko; Koto, Shinobu; Higuchi, Asako; Ariyasu, Daisuke; Izawa, Masako; Miyamoto Igaki, Junko; Hasegawa, Yukihiro

    2010-01-01

    The gonadal function of patients with Turner syndrome (TS) is variable. Individuals with mosaicism characterized by 45,X/46,XX or 45,X/47,XXX are more likely to experience spontaneous menarche compared with other karyotypes. Prepubertal gonadotropins of TS patients with spontaneous menarche are reportedly normal or significantly lower than those of patients with induced menarche. The present study investigated an index of spontaneous and cyclical menstruation at 10-12 years old in TS. Subjects comprised 50 patients with TS, divided into three groups: Group A (n=7), with spontaneous menarche before 16 years old and regular menstruation for at least 1 year and 6 months; Group B (n=6), with irregular menstruation since menarche leading to secondary amenorrhea despite spontaneous menarche before 16 years old; and Group C (n=37), without spontaneous breast budding before 14 years old or without spontaneous menarche before 16 years old. Karyotype, LH and FSH concentrations at 10 and 12 years old were analyzed retrospectively. Spontaneous and cyclical menstruation was more frequently observed in TS with mosaicism characterized by 45,X/46,XX or 45,X/47,XXX than in TS with other karyotypes, as previously described. Spontaneous and cyclical menstruation in TS was observed when serum FSH level was <10 mIU/mL at 12 years old, suggesting this FSH level as an index of spontaneous and cyclical menstruation in TS.

  5. PAR2 regulates regeneration, transdifferentiation, and death

    PubMed Central

    Piran, Ron; Lee, Seung-Hee; Kuss, Pia; Hao, Ergeng; Newlin, Robbin; Millán, José Luis; Levine, Fred

    2016-01-01

    Understanding the mechanisms by which cells sense and respond to injury is central to developing therapies to enhance tissue regeneration. Previously, we showed that pancreatic injury consisting of acinar cell damage+β-cell ablation led to islet cell transdifferentiation. Here, we report that the molecular mechanism for this requires activating protease-activated receptor-2 (PAR2), a G-protein-coupled receptor. PAR2 modulation was sufficient to induce islet cell transdifferentiation in the absence of β-cells. Its expression was modulated in an islet cell type-specific manner in murine and human type 1 diabetes (T1D). In addition to transdifferentiation, PAR2 regulated β-cell apoptosis in pancreatitis. PAR2's role in regeneration is broad, as mice lacking PAR2 had marked phenotypes in response to injury in the liver and in digit regeneration following amputation. These studies provide a pharmacologically relevant target to induce tissue regeneration in a number of diseases, including T1D. PMID:27809303

  6. ATP-regulated interactions between P1 ParA, ParB and non-specific DNA that are stabilized by the plasmid partition site, parS

    PubMed Central

    Havey, James C.; Vecchiarelli, Anthony G.; Funnell, Barbara E.

    2012-01-01

    Localization of the P1 plasmid requires two proteins, ParA and ParB, which act on the plasmid partition site, parS. ParB is a site-specific DNA-binding protein and ParA is a Walker-type ATPase with non-specific DNA-binding activity. In vivo ParA binds the bacterial nucleoid and forms dynamic patterns that are governed by the ParB–parS partition complex on the plasmid. How these interactions drive plasmid movement and localization is not well understood. Here we have identified a large protein–DNA complex in vitro that requires ParA, ParB and ATP, and have characterized its assembly by sucrose gradient sedimentation and light scattering assays. ATP binding and hydrolysis mediated the assembly and disassembly of this complex, while ADP antagonized complex formation. The complex was not dependent on, but was stabilized by, parS. The properties indicate that ParA and ParB are binding and bridging multiple DNA molecules to create a large meshwork of protein–DNA molecules that involves both specific and non-specific DNA. We propose that this complex represents a dynamic adaptor complex between the plasmid and nucleoid, and further, that this interaction drives the redistribution of partition proteins and the plasmid over the nucleoid during partition. PMID:21965538

  7. A novel mechanism of FSH regulation of DNA synthesis in the granulosa cells of hamster preantral follicles. Involvement of a protein kinase C mediated MAP kinase 3/1 self- activation loop

    PubMed Central

    Yang, Peixin; Roy, Shyamal K.

    2006-01-01

    Summary FSH- or EGF-induced granulosa cell proliferation in intact preantral follicles depends on a novel PKC-mediated MAPK3/1 self-activation loop. The objective was to reveal whether a PKC-mediated self-sustaining MAPK3/1 activation loop was necessary for FSH- or EGF-induced DNA synthesis in the granulosa cells of intact preantral follicles. For this purpose, hamster preantral follicles were cultured with FSH or EGF in the presence of selective kinase inhibitors. FSH or EGF phosphorylated RAF1, MAP2K1 and MAPK3/1. However, relatively higher dose of EGF was necessary to sustain the MAPK3/1 activity, which was essential for CDK4 activation and DNA synthesis. In intact preantral follicles, FSH or EGF stimulated DNA synthesis only in the granulosa cells. Sustained activation of MAPK3/1 beyond 3h was independent of EGFR kinase activity, but dependent on PKC activity, which appeared to form a self-sustaining MAPK3/1 activation loop by activating RAF1, MAP2K1 and PLA2G4. Inhibition of PKC activity as late as 4h after the administration of FSH or EGF arrested DNA synthesis, which corresponded with attenuated phosphorylation of RAF1 and MAPK3/1, thus suggesting an essential role of PKC in MAPK3/1 activation. Collectively, these data present a novel self-sustaining mechanism comprised of MAPK3/1, PLA2G4, PKC and RAF1 for CDK4 activation leading to DNA synthesis in granulosa cells. Either FSH or EGF can activate the loop to activate CDK4 and initiate DNA synthesis; however, consistent with our previous findings, FSH effect seems to be mediated by EGF, which initiates the event by stimulating EGFR kinase. PMID:16525034

  8. The FSHB -211G>T variant attenuates serum FSH levels in the supraphysiological gonadotropin setting of Klinefelter syndrome.

    PubMed

    Busch, Alexander S; Tüttelmann, Frank; Zitzmann, Michael; Kliesch, Sabine; Gromoll, Jörg

    2015-05-01

    Klinefelter syndrome (47, XXY) is the most frequent genetic cause of male infertility and individuals share the endocrine hallmark of hypergonadotropic hypogonadism. Single-nucleotide polymorphisms located within the FSHB/FSHR gene were recently shown to impact serum follicle-stimulating hormone (FSH) levels and other reproductive parameters in men. The objective of this study was to analyse the effect of FSHB-211G>T (c.-280G>T, rs10835638) as well as FSHR c.2039G>A (rs6166) and FSHR c.-29G>A (rs1394205) on endocrine and reproductive parameters in untreated and testosterone-treated Klinefelter patients. Patients were retrospectively selected from the clientele attending a university-based andrology centre. A total of 309 non-mosaic Klinefelter individuals between 18 and 65 years were included and genotyped for the variants by TaqMan assays. The untreated group comprised 248 men, in which the FSHB -211G>T allele was significantly associated with the reduced serum follicle-stimulating hormone levels (-6.5 U/l per T allele, P=1.3 × 10(-3)). Testosterone treatment (n=150) abolished the observed association. When analysing patients before and under testosterone treatment (n=89), gonadotropin levels were similarly suppressed independently of the FSHB genotype. The FSHR polymorphisms did not exhibit any significant influence in any group, neither on the endocrine nor reproductive parameters. In conclusion, a hypergonadotropic setting such as Klinefelter syndrome does not mask the FSHB -211G>T genotype effects on the follicle-stimulating hormone serum levels. The impact was indeed more pronounced compared with normal or infertile men, whereas gonadotropin suppression under testosterone treatment seems to be independent of the genotype. Thus, the FSHB -211G>T genotype is a key determinant in the regulation of gonadotropins in different reproductive-endocrine pathopyhsiologies.

  9. Receptor specificity and functional comparison of recombinant sea bass (Dicentrarchus labrax) gonadotropins (FSH and LH) produced in different host systems.

    PubMed

    Molés, Gregorio; Zanuy, Silvia; Muñoz, Iciar; Crespo, Berta; Martínez, Iago; Mañanós, Evaristo; Gómez, Ana

    2011-06-01

    Different yields, biopotency, and in vivo pharmacokinetics are obtained for recombinant sea bass gonadoltropins depending on the production system and DNA construct, but they show specific activation of their corresponding receptors. Gonadotropins (GTHs) are glycoprotein hormones that play a major role in the regulation of gonadal functions. Recently, we succeeded in isolating the native sea bass Fsh from sea bass pituitaries, but to ensure the availability of bioactive GTHs and no cross-contamination with other related glycoproteins, recombinant sea bass GTHs were produced using two expression systems-insect and mammalian cells-and different constructs that yielded tethered or noncovalently bound dimers. Their production levels, binding specificity to their homologous cognate receptors, and bioactivity were investigated and compared. Both expression systems were successful in the generation of bioactive recombinant GTHs, but insect Sf9 cells yielded higher amounts of recombinant proteins than mammalian Chinese Hamster Ovary (CHO) stable clones. All recombinant GTHs activated their cognate receptors without cross-ligand binding and were able to stimulate sea bass gonadal steroidogenesis in vitro, although with different biopotencies. To assess their use for in vivo applications, their half-life in sea bass plasma was evaluated. Sf9-GTHs had a lower in vivo stability compared with CHO-GTHs due to their rapid clearance from the blood circulation. Cell-dependent glycosylation could be contributing to the final in vivo stability and biopotency of these recombinant glycoproteins. In conclusion, both insect and mammalian expression systems produced bioactive sea bass recombinant gonadotropins, although with particular features useful for different proposes (e.g., antibody production or in vivo studies, respectively).

  10. Humanizing the Protease-Activated Receptor (PAR) Expression Profile in Mouse Platelets by Knocking PAR1 into the Par3 Locus Reveals PAR1 Expression Is Not Tolerated in Mouse Platelets

    PubMed Central

    French, Shauna L.; Paramitha, Antonia C.; Moon, Mitchell J.; Dickins, Ross A.; Hamilton, Justin R.

    2016-01-01

    Anti-platelet drugs are the mainstay of pharmacotherapy for heart attack and stroke prevention, yet improvements are continually sought. Thrombin is the most potent activator of platelets and targeting platelet thrombin receptors (protease-activated receptors; PARs) is an emerging anti-thrombotic approach. Humans express two PARs on their platelets–PAR1 and PAR4. The first PAR1 antagonist was recently approved for clinical use and PAR4 antagonists are in early clinical development. However, pre-clinical studies examining platelet PAR function are challenging because the platelets of non-primates do not accurately reflect the PAR expression profile of human platelets. Mice, for example, express Par3 and Par4. To address this limitation, we aimed to develop a genetically modified mouse that would express the same repertoire of platelet PARs as humans. Here, human PAR1 preceded by a lox-stop-lox was knocked into the mouse Par3 locus, and then expressed in a platelet-specific manner (hPAR1-KI mice). Despite correct targeting and the predicted loss of Par3 expression and function in platelets from hPAR1-KI mice, no PAR1 expression or function was detected. Specifically, PAR1 was not detected on the platelet surface nor internally by flow cytometry nor in whole cell lysates by Western blot, while a PAR1-activating peptide failed to induce platelet activation assessed by either aggregation or surface P-selectin expression. Platelets from hPAR1-KI mice did display significantly diminished responsiveness to thrombin stimulation in both assays, consistent with a Par3-/- phenotype. In contrast to the observations in hPAR1-KI mouse platelets, the PAR1 construct used here was successfully expressed in HEK293T cells. Together, these data suggest ectopic PAR1 expression is not tolerated in mouse platelets and indicate a different approach is required to develop a small animal model for the purpose of any future preclinical testing of PAR antagonists as anti-platelet drugs. PMID

  11. ParA and ParB coordinate chromosome segregation with cell elongation and division during Streptomyces sporulation

    PubMed Central

    Donczew, Magdalena; Mackiewicz, Paweł; Wróbel, Agnieszka; Flärdh, Klas; Zakrzewska-Czerwińska, Jolanta

    2016-01-01

    In unicellular bacteria, the ParA and ParB proteins segregate chromosomes and coordinate this process with cell division and chromosome replication. During sporulation of mycelial Streptomyces, ParA and ParB uniformly distribute multiple chromosomes along the filamentous sporogenic hyphal compartment, which then differentiates into a chain of unigenomic spores. However, chromosome segregation must be coordinated with cell elongation and multiple divisions. Here, we addressed the question of whether ParA and ParB are involved in the synchronization of cell-cycle processes during sporulation in Streptomyces. To answer this question, we used time-lapse microscopy, which allows the monitoring of growth and division of single sporogenic hyphae. We showed that sporogenic hyphae stop extending at the time of ParA accumulation and Z-ring formation. We demonstrated that both ParA and ParB affect the rate of hyphal extension. Additionally, we showed that ParA promotes the formation of massive nucleoprotein complexes by ParB. We also showed that FtsZ ring assembly is affected by the ParB protein and/or unsegregated DNA. Our results indicate the existence of a checkpoint between the extension and septation of sporogenic hyphae that involves the ParA and ParB proteins. PMID:27248800

  12. ParA and ParB coordinate chromosome segregation with cell elongation and division during Streptomyces sporulation.

    PubMed

    Donczew, Magdalena; Mackiewicz, Paweł; Wróbel, Agnieszka; Flärdh, Klas; Zakrzewska-Czerwińska, Jolanta; Jakimowicz, Dagmara

    2016-04-01

    In unicellular bacteria, the ParA and ParB proteins segregate chromosomes and coordinate this process with cell division and chromosome replication. During sporulation of mycelial Streptomyces, ParA and ParB uniformly distribute multiple chromosomes along the filamentous sporogenic hyphal compartment, which then differentiates into a chain of unigenomic spores. However, chromosome segregation must be coordinated with cell elongation and multiple divisions. Here, we addressed the question of whether ParA and ParB are involved in the synchronization of cell-cycle processes during sporulation in Streptomyces To answer this question, we used time-lapse microscopy, which allows the monitoring of growth and division of single sporogenic hyphae. We showed that sporogenic hyphae stop extending at the time of ParA accumulation and Z-ring formation. We demonstrated that both ParA and ParB affect the rate of hyphal extension. Additionally, we showed that ParA promotes the formation of massive nucleoprotein complexes by ParB. We also showed that FtsZ ring assembly is affected by the ParB protein and/or unsegregated DNA. Our results indicate the existence of a checkpoint between the extension and septation of sporogenic hyphae that involves the ParA and ParB proteins.

  13. suPAR and Team Nephrology

    PubMed Central

    2014-01-01

    Primary focal segmental glomerulosclerosis (FSGS) accounts for nearly 10 % of patients who require renal replacement therapy. Elevated circulating levels of soluble urokinase receptor (suPAR) have been identified as a biomarker to discriminate primary FSGS from other glomerulopathies. Subsequent reports have questioned the diagnostic utility of this test. In a study in BMC Medicine, Huang et al. demonstrate that urinary soluble urokinase receptor (suPAR) excretion assists in distinguishing primary FSGS from other glomerular diseases, and that high plasma suPAR concentrations are not directly linked to a decline in glomerular filtration rate (GFR). This observation suggests that further investigation of suPAR is warranted in patients with FSGS. It should be interpreted in light of a recent report that B7-1 is expressed in the podocytes of a subset of patients with FSGS, and that blocking this molecule may represent the first successful targeted intervention for this disease. These advances highlight the rapid pace of scientific progress in the field of nephrology. Nephrologists should work together, share resources, and expedite the design of protocols to evaluate these novel biomarkers in a comprehensive and scientifically valid manner. Please see related article http://www.biomedcentral.com/1741-7015/12/81. PMID:24885021

  14. Binding characteristics of 125I-labelled human FSH to granulosa cells from Booroola ewes which were homozygous, heterozygous or non-carriers of a major gene(s) influencing their ovulation rate.

    PubMed

    McNatty, K P; Lun, S; Heath, D A; Hudson, N L; O'Keeffe, L E; Henderson, K M

    1989-05-01

    At 37 degrees C 125I-labelled human (h) FSH (NIAMDD-hFSH-I-3) bound rapidly to granulosa cells from Booroola and Romney ewes with 50% maximum binding achieved after 3 min and equilibrium being reached within 45 min, irrespective of whether the cells were obtained from the FF, F+ or ++ Booroola genotypes or from Romney ewes. Binding of 125I-labelled FSH followed second order kinetics and there was no effect of follicle diameter (1-2.5 mm vs greater than or equal to 3 mm). Irrespective of breed, genotype or follicle size, the mean (+/- s.e.m.) calculated association rate constant, (ka) was 7.3 (+/- 0.8) x 10(5) litres mol-1 sec-1 (n = 12). Dissociation of receptor bound 125I-labelled hFSH was less than 5% after 30 min and low but variable (i.e. between 0 and 30%) after 2-6 h irrespective of breed, genotype or follicle size. No gene-specific differences were noted in binding specificity between F+ and ++ genotypes: studies were not performed with cells from FF ewes because of insufficient cells. The binding of 125I-labelled hFSH could be displaced with sheep FSH (NIH-FSH-S16; 10% cross-reaction) and FSH-P (2.5% cross-reaction) but other sheep pituitary hormones and hCG showed little or no cross-reaction (less than or equal to 0.1%). The calculated binding capacities (Bmax) and equilibrium dissociation constants (Kd) for 125I-labelled hFSH binding to granulosa cells did not differ between the Booroola genotypes or between Booroola or Romney follicles of different diameter (i.e. 1-2.5 mm; or greater than or equal to 3 mm). The overall mean +/- s.e.m. (n = 24) Bmax and Kd values were 16.7 +/- 0.8 fm/mg protein (i.e. approximately 800 available receptor binding sites/cell) and 1.1 +/- 0.1 nM respectively. Collectively, these findings suggest that the earlier maturation of follicles in FF or F+ ewes compared to ++ ewes is unlikely to be due to gene-specific differences in the FSH binding characteristics of the granulosa cells.

  15. PAR Corneal Topography System (PAR CTS): the clinical application of close-range photogrammetry.

    PubMed

    Belin, M W; Cambier, J L; Nabors, J R; Ratliff, C D

    1995-11-01

    The PAR Corneal Topography System (CTS) is a computer-driven corneal imaging system which uses close-range photogrammetry (rasterphotogrammetry) to measure and produce a topographic map of the corneal surface. The PAR CTS makes direct point-by-point measurements of surface elevation using a stereo-triangulation technique. The CTS uses a grid pattern composed of horizontal and vertical lines spaced about 0.2 mm (200 microns) apart. Each grid intersection comprises a surface feature which can be located in multiple images and used to generate an (x,y,z) coordinate. Unlike placido disc-based videokeratoscopes, the PAR CTS requires neither a smooth reflective surface nor precise spatial alignment for accurate imaging. In addition to surface elevation, the PAR CTS computes axial and tangential curvatures and refractive power. Difference maps are available in all curvatures, refractive power, and in absolute elevation.

  16. Specific activation, signalling and secretion profiles of human platelets following PAR-1 and PAR-4 stimulation.

    PubMed

    Nguyen, Kim Anh; Hamzeh-Cognasse, Hind; Laradi, Sandrine; Pozzetto, Bruno; Garraud, Olivier; Cognasse, Fabrice

    2015-01-01

    Blood platelets play a central haemostatic function; however, they also play a role in inflammation and are capable of secreting various cytokines, chemokines and related products. The purpose of this study was to identify subtle variations in platelet physiology using proteomics. We compared the levels of membrane proteins (n = 3), α and δ granule proteins (n = 18), and signalling proteins (n = 30) from unstimulated platelets with those of protease-activated receptor (PAR)-1- and PAR-4-stimulated platelets (n = 10). The vast majority of these proteins responded similarly to PAR-1 or PAR-4 engagement. However, differences were observed within membrane CD40L expressed, and α granule GRO-α and MDC secreted proteins.

  17. Élaboration de films de molécules organiques par ablation par laser UV

    NASA Astrophysics Data System (ADS)

    Hernandez-Perez, M. A.; Garapon, C.; Champeaux, C.; Coleman, A. W.

    2006-12-01

    Les potentialités des méthodes de dépôt par ablation laser (PLD) pour la préparation de films minces de matériaux organiques sont illustrées par un bref rappel bibliographique et par des résultats expérimentaux concernant des molécules d'intérêt biologique (acides aminés, calix-arènes, protéines). Les films sont préparés par PLD avec un laser KrF sans dégradation de la structure chimique des molécules dans une gamme de fluences de quelques dizaines à quelques centaines de mJ/cm2. Les propriétés structurales et optiques des films sont étudiées en fonction de la fluence du laser et mettent en évidence des arrangements moléculaires particuliers induits par cette méthode de dépôt. Le guidage optique a été obtenu pour des films de toutes ces molécules.

  18. Kallikrein 6 Signals through PAR1 and PAR2 to Promote Neuron Injury and Exacerbate Glutamate Neurotoxicity

    PubMed Central

    Yoon, Hyesook; Radulovic, Maja; Wu, Jianmin; Blaber, Sachiko I.; Blaber, Michael; Fehlings, Michael G.; Scarisbrick, Isobel A.

    2014-01-01

    CNS trauma generates a proteolytic imbalance contributing to secondary injury, including axonopathy and neuron degeneration. Kallikrein 6 (Klk6) is a serine protease implicated in neurodegeneration and here we investigate the role of protease activated receptors 1 (PAR1) and PAR2 in mediating these effects. First we demonstrate Klk6 and the prototypical activator of PAR1, thrombin, as well as PAR1 and PAR2, are each elevated in murine experimental traumatic spinal cord injury (SCI) at acute or subacute time points. Recombinant Klk6 triggered ERK1/2 signaling in cerebellar granule neurons and in the NSC34 spinal cord motoneuron cell line, in a PI3K and MEK-dependent fashion. Importantly, lipopeptide inhibitors of PAR1 or PAR2, and PAR1 genetic deletion, each reduced Klk6-ERK1/2 activation. In addition, Klk6 and thrombin promoted degeneration of cerebellar neurons and exacerbated glutamate neurotoxicity. Moreover, genetic deletion of PAR1 blocked thrombin-mediated cerebellar neurotoxicity and reduced the neurotoxic effects of Klk6. Klk6 also increased glutamate-mediated Bim signaling, PARP cleavage and lactate dehydrogenase (LDH) release in NSC34 motoneurons and these effects were blocked by PAR1 and PAR2 lipopeptide inhibitors. Taken together these data point to a novel Klk6-signaling axis in CNS neurons that is mediated by PAR1 and PAR2 and is positioned to contribute to neurodegeneration. PMID:23647384

  19. A Combined Global and Local Approach to Elucidate Spatial Organization of the Mycobacterial ParB-parS Partition Assembly

    SciTech Connect

    B Chaudhuri; S Gupta; V Urban; M Chance; R DMello; L Smith; K Lyons; J Gee

    2011-12-31

    Combining diverse sets of data at global (size, shape) and local (residue) scales is an emerging trend for elucidating the organization and function of the cellular assemblies. We used such a strategy, combining data from X-ray and neutron scattering with H/D-contrast variation and X-ray footprinting with mass spectrometry, to elucidate the spatial organization of the ParB-parS assembly from Mycobacterium tuberculosis. The ParB-parS participates in plasmid and chromosome segregation and condensation in predivisional bacterial cells. ParB polymerizes around the parS centromere(s) to form a higher-order assembly that serves to recruit cyto-skeletal ParA ATPases and SMC proteins for chromosome segregation. A hybrid model of the ParB-parS was built by combining and correlating computational models with experiment-derived information about size, shape, position of the symmetry axis within the shape, internal topology, DNA-protein interface, exposed surface patches, and prior knowledge. This first view of the ParB-parS leads us to propose how ParB spread on the chromosome to form a larger assembly.

  20. A Combined Global and Local Approach to Elucidate Spatial Organization of the Mycobacterial ParB-parS Partition

    SciTech Connect

    Chaudhuri, Barnali; Gupta, Sayan; Urban, Volker S; Chance, Mark; D'Mello, Rhijuta; Smith, Lauren; Lyons, Kelly; Gee, Jessica

    2010-01-01

    Combining diverse sets of data at global (size, shape) and local (residue) scales is an emerging trend for elucidating the organization and function of the cellular assemblies. We used such a strategy, combining data from X-ray and neutron scattering with H/D-contrast variation and X-ray footprinting with mass spectrometry, to elucidate the spatial organization of the ParB-parS assembly from Mycobacterium tuberculosis. The ParB-parS participates in plasmid and chromosome segregation and condensation in predivisional bacterial cells. ParB polymerizes around the parS centromere(s) to form a higher-order assembly that serves to recruit cyto-skeletal ParA ATPases and SMC proteins for chromosome segregation. A hybrid model of the ParB-parS was built by combining and correlating computational models with experiment-derived information about size, shape, position of the symmetry axis within the shape, internal topology, DNA-protein interface, exposed surface patches, and prior knowledge. This first view of the ParB-parS leads us to propose how ParB spread on the chromosome to form a larger assembly.

  1. Concomitant use of FSH and low-dose recombinant hCG during the late follicular phase versus conventional controlled ovarian stimulation for intracytoplasmic sperm injection cycles.

    PubMed

    Iaconelli, Carla Andrade Rebello; Setti, Amanda Souza; Braga, Daniela Paes Almeida Ferreira; Maldonado, Luiz Guilherme Louzada; Iaconelli, Assumpto; Borges, Edson; Aoki, Tsutomu

    2017-03-22

    The objective of this study was to investigate the effects of low-dose hCG supplementation on ICSI outcomes and controlled ovarian stimulation (COS) cost. Three hundred and thirty patients undergoing ICSI were split into groups according to the COS protocol: (i) control group (n = 178), including patients undergoing conventional COS treatment; and (ii) low-dose hCG group (n = 152), including patients undergoing COS with low-dose hCG supplementation. Lower mean total doses of FSH administered and higher mean oestradiol level and mature oocyte rates were observed in the low-dose hCG group. A significantly higher fertilization rate, high-quality embryo rate and blastocyst formation rate were observed in the low-dose hCG group as compared to the control group. The miscarriage rate was significantly higher in the control group compared to the low-dose hCG group. A significantly lower incidence of OHSS was observed in the low-dose hCG group. There was also a significantly lower gonadotropin cost in the low-dose hCG group as compared to the control group ($1235.0 ± 239.0×$1763.0 ± 405.3, p < 0.001). The concomitant use of low-dose hCG and FSH results in a lower abortion rate and increased number of mature oocytes retrieved, as well as improved oocyte quality, embryo quality and blastocyst formation and reduced FSH requirements.

  2. Predictive value of FSH, testicular volume, and histopathological findings for the sperm retrieval rate of microdissection TESE in nonobstructive azoospermia: a meta-analysis.

    PubMed

    Li, Hao; Chen, Li-Ping; Yang, Jun; Li, Ming-Chao; Chen, Rui-Bao; Lan, Ru-Zhu; Wang, Shao-Gang; Liu, Ji-Hong; Wang, Tao

    2017-03-24

    We performed this meta-analysis to evaluate the predictive value of different parameters in the sperm retrieval rate (SRR) of microdissection testicular sperm extraction (TESE) in patients with nonobstructive azoospermia (NOA). All relevant studies were searched in PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO. We chose three parameters to perform the meta-analysis: follicle-stimulating hormone (FSH), testicular volume, and testicular histopathological findings which included three patterns: hypospermatogenesis (HS), maturation arrest (MA), and Sertoli-cell-only syndrome (SCOS). If there was a threshold effect, only the area under the summary receiver operating characteristic curve (AUSROC) was calculated. Otherwise, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR) were also calculated. Twenty-one articles were included in our study finally. There was a threshold effect among studies investigating FSH and SCOS. The AUSROCs of FSH, testicular volume, HS, MA, and SCOS were 0.6119, 0.6389, 0.6758, 0.5535, and 0.2763, respectively. The DORs of testicular volume, HS, and MA were 1.98, 16.49, and 1.26, respectively. The sensitivities of them were 0.80, 0.30, and 0.27, while the specificities of them were 0.35, 0.98, and 0.76, respectively. The PLRs of them were 1.49, 10.63, and 1.15, respectively. And NLRs were 0.73, 0.72, and 0.95, respectively. All the investigated factors in our study had limited predictive value. However, the histopathological findings were helpful to some extent. Most patients with HS could get sperm by microdissection TESE.

  3. Host response biomarker in sepsis: suPAR detection.

    PubMed

    Giamarellos-Bourboulis, Evangelos J; Georgitsi, Marianna

    2015-01-01

    Recent studies of our group have shown that suPAR may complement APACHE II score for risk assessment in sepsis. suPAR may be measured in serum of patients by an enzyme immunosorbent assay developed by Virogates (suPARnostic™). Production of suPAR from circulating neutrophils and monocytes may be assessed after isolation of neutrophils and monocytes and ex vivo culture. This is followed by measurement of suPAR in culture supernatants.

  4. Changes in plasma melanocyte-stimulating hormone, ACTH, prolactin, GH, LH, FSH, and thyroid-stimulating hormone in response to injection of sulpiride, thyrotropin-releasing hormone, or vehicle in insulin-sensitive and -insensitive mares.

    PubMed

    Valencia, N Arana; Thompson, D L; Mitcham, P B

    2013-05-01

    Six insulin-sensitive and 6 insulin-insensitive mares were used in a replicated 3 by 3 Latin square design to determine the pituitary hormonal responses (compared with vehicle) to sulpiride and thyrotropin-releasing hormone (TRH), 2 compounds commonly used to diagnose pituitary pars intermedia dysfunction (PPID) in horses. Mares were classified as insulin sensitive or insensitive by their previous glucose responses to direct injection of human recombinant insulin. Treatment days were February 25, 2012, and March 10 and 24, 2012. Treatments were sulpiride (racemic mixture, 0.01 mg/kg BW), TRH (0.002 mg/kg BW), and vehicle (saline, 0.01 mL/kg BW) administered intravenously. Blood samples were collected via jugular catheters at -10, 0, 5, 10, 20, 30, 45, 60, 90, and 120 min relative to treatment injection. Plasma ACTH concentrations were variable and were not affected by treatment or insulin sensitivity category. Plasma melanocyte-stimulating hormone (MSH) concentrations responded (P < 0.01) to both sulpiride and TRH injection and were greater (P < 0.05) in insulin-insensitive mares than in sensitive mares. Plasma prolactin concentrations responded (P < 0.01) to both sulpiride and TRH injection, and the response was greater (P < 0.05) for sulpiride; no effect of insulin sensitivity was observed. Plasma thyroid-stimulating hormone (TSH) concentrations responded (P < 0.01) to TRH injection only and were higher (P < 0.05) in insulin-sensitive mares in almost all time periods. Plasma LH and FSH concentrations varied with time (P < 0.05), particularly in the first week of the experiment, but were not affected by treatment or insulin sensitivity category. Plasma GH concentrations were affected (P < 0.05) only by day of treatment. The greater MSH responses to sulpiride and TRH in insulin-insensitive mares were similar to, but not as exaggerated as, those observed by others for PPID horses. In addition, the reduced TSH concentrations in insulin-insensitive mares are

  5. Temporal relationships between minor, preovulatory, or periovulatory FSH surges and the emergence and development of 2-mm follicles of wave 1 in Bos taurus heifers.

    PubMed

    Baldrighi, J M; Siddiqui, M A R; Ginther, O J

    2016-10-01

    The number and day of emergence (first detection) of 2-mm follicles and the number and day when the 2-mm follicles reached 3-, 4-, 5-, and 6-mm during wave 1 were determined every 0.5 d (n = 9 heifers). Emergence of the follicles at each of the indicated diameters was normalized to the beginning and ending nadir and the peak of each of a minor FSH surge, the preovulatory surge, and the periovulatory surge. Relative to the day of ovulation (day 0), the minor FSH surge, preovulatory surge, and periovulatory surge encompassed (nadir to nadir) days -7.0 to -2.5 (peak, day -4.0), days -2.5 to -0.5 (peak, day -1.0), and days -0.5 to 4 (peak, day 0), respectively. Distinct mean nadirs occurred between the minor and preovulatory surges and between the preovulatory and periovulatory surges. A small percentage of 2-mm follicles (12%) and 3-mm follicles (2%) emerged during the minor FSH surge. The 4-mm follicles emerged during the preovulatory surge (24% of follicles) and periovulatory surge (76%). The 5-mm and 6-mm follicles emerged only during the periovulatory surge. The first increase (P < 0.05) in number of 2-, 3-, and 4-mm follicles began at 1.5, 1.0, and 0 d, respectively, before the nadir at the beginning of the preovulatory surge. The first increase (P < 0.05) in number of 5- and 6-mm follicles began at 0.5 and 0 d, respectively, before the intervening nadir between the preovulatory and periovulatory surges. Results demonstrated that each of the 3 surges including the minor surge contributed to the emergence of follicles at various diameters during wave 1. The emergence of 2-mm follicles during the descending portion of the minor surge indicated that smaller follicles (eg, 1 mm) apparently emerged during the major portion of the minor surge. The increasing diameter of the 2 largest follicles was not interrupted during the distinct intervening nadir between the preovulatory and periovulatory FSH surges.

  6. Transcription factor p53 can regulate proliferation, apoptosis and secretory activity of luteinizing porcine ovarian granulosa cell cultured with and without ghrelin and FSH.

    PubMed

    Sirotkin, A V; Benco, A; Tandlmajerova, A; Vasícek, D; Kotwica, J; Darlak, K; Valenzuela, F

    2008-11-01

    The aim of our in vitro experiments was to examine the role of transcription factor p53 in controlling the basic functions of ovarian cells and their response to hormonal treatments. Porcine ovarian granulosa cells, transfected and non-transfected with a gene construct encoding p53, were cultured with ghrelin and FSH (all at concentrations of 0, 1, 10, or 100 ng/ml). Accumulation of p53, of apoptosis-related (MAP3K5) and proliferation-related (cyclin B1) substances was evaluated by immunocytochemistry. The secretion of progesterone (P(4)), oxytocin (OT), prostaglandin F (PGF), and E (PGE) was measured by RIA. Transfection with the p53 gene construct promoted accumulation of this transcription factor within cells. It also stimulated the expression of a marker of apoptosis (MAP3K5). Over-expression of p53 resulted in reduced accumulation of a marker of proliferation (cyclin B1), P(4), and PGF secretion and increased OT and PGE secretion. Ghrelin, when added alone, did not affect p53 or P(4), but reduced MAP3K5 and increased PGF and PGE secretion. Over-expression of p53 reversed the effect of ghrelin on OT, caused it to be inhibitory to P(4) secretion, but did not modify its action on MAP3K5, PGF, or PGE. FSH promoted the accumulation of p53, MAP3K5, and cyclin B1; these effects were unaffected by p53 transfection. These multiple effects of the p53 gene construct on luteinizing granulosa cells, cultured with and without hormones 1) demonstrate the effects of ghrelin and FSH on porcine ovarian cell apoptosis and secretory activity, 2) confirm the involvement of p53 in promoting apoptosis and inhibiting P(4) secretion in these cells, 3) provide the first evidence that p53 suppress proliferation of ovarian cells, 4) provide the first evidence that p53 is involved in the control of ovarian peptide hormone (OT) and prostaglandin (PGF and PGE) secretion, and 5) suggest that p53 can modulate, but probably not mediate, the effects of ghrelin and FSH on the ovary.

  7. Drosophila 14-3-3/PAR-5 is an essential mediator of PAR-1 function in axis formation.

    PubMed

    Benton, Richard; Palacios, Isabel M; St Johnston, Daniel

    2002-11-01

    PAR-1 kinases are required to determine the anterior-posterior (A-P) axis in C. elegans and Drosophila, but little is known about their molecular function. We identified 14-3-3 proteins as Drosophila PAR-1 interactors and show that PAR-1 binds a domain of 14-3-3 distinct from the phosphoserine binding pocket. PAR-1 kinases phosphorylate proteins to generate 14-3-3 binding sites and may therefore directly deliver 14-3-3 to these targets. 14-3-3 mutants display identical phenotypes to par-1 mutants in oocyte determination and the polarization of the A-P axis. Together, these results indicate that PAR-1's function is mediated by the binding of 14-3-3 to its substrates. The C. elegans 14-3-3 protein, PAR-5, is also required for A-P polarization, suggesting that this is a conserved mechanism by which PAR-1 establishes cellular asymmetries.

  8. [Ambroise Paré and Latin].

    PubMed

    Drouin, Emmanuel

    2010-06-01

    We report a study of a medical book written by Antoine Mizaud (Memorabilium utilium, in ac iucundorum aphorismos Arcanorum omnis generis locupletes, perpulchre digestae), which was written in Latin, but has been extensively annotated in French.The book is from the personal collection of one of the physicians of Napoleon III. There is an oral tradition within his family that one of the works in the book had been annotated by Ambroise Paré. We know very little, apart from a few receipts and his signature, about the writing of the master of French surgery. Did he understand the language of Galen? There are many annotated passages in the works of Pare which are in the book. We examine whether these annotations were actually made by Ambroise Paré or whether they were done for him.

  9. [Ambroise Paré in French literature].

    PubMed

    Dumaitre, P

    1995-01-01

    The 16th century by its passionate side has been the favourite one of authors of historical novels in which among the heroes of "cloak and dagger stories" appears sometime Ambroise Paré. Alexandre Dumas (the father) has shown him at the court of Charles IX in La Reine Margot (1845) where he does not however play a great role. On the contrary, Balzac in Le Martyr calviniste (1842) has given him a capital part close to the dying François II, whom he intended to trepanize but had to give up this idea as a consequence of the opposition of the queen-mother Catherine de Médicis. In the present century, Robert Merle in Paris ma bonne ville (Fortune de France, 3, 1980) shows Paré at the time of the Saint Barthélemy.

  10. Les Brulures Chimiques Par Le Laurier Rose

    PubMed Central

    Bakkali, H.; Ababou, M.; Nassim Sabah, T.; Moussaoui, A.; Ennouhi, A.; Fouadi, F.Z.; Siah, S.; Ihrai, H.

    2010-01-01

    Summary Le laurier rose ou Nerium oleander est un arbuste qui pousse naturellement dans les régions méditerranéennes. Au Maroc on le trouve dans les lieux humides. Il est réputé par ses risques de toxicité systémique en cas d'empoisonnement à cause de la présence de deux alcaloïdes, surtout l'oléandrine. La littérature illustre des cas d'utilisation locale des feuilles de cette plante contre la gale, les hémorroïdes et les furoncles. Nous rapportons deux cas de brûlures chimiques par le laurier rose de gravité différente. Cela doit aboutir à une information élargie de la population, ainsi qu'une réglementation stricte de sa commercialisation. PMID:21991211

  11. Expression of 17?-hydroxysteroid dehydrogenase and the effects of LH, FSH and prolactin on oestrone and 17?-oestradiol secretion in the endometrium of pigs during early pregnancy and the oestrous cycle.

    PubMed

    Wojciechowicz, B; Kotwica, G; Zglejc, K; Waszkiewicz, E; Franczak, A

    2016-03-07

    The endometrium of pregnant and cyclic pigs is a source of oestrone (E1) and 17β-oestradiol (E2). However, the roles of LH, FSH and prolactin (PRL) as regulators of endometrial steroidogenesis, and the presence of 17β-hydroxysteroid dehydrogenase (17β-HSD) in the porcine endometrium, remain unknown. Therefore, in the present study we examined 17β-HSD expression and the effects of LH, FSH and PRL on E1 and E2 release in vitro in endometrial explants harvested from gravid pigs on Days 10-11 (embryo migration within the uterus), 12-13 (maternal recognition of pregnancy) and 15-16 (beginning of implantation) and compared them with results obtained in non-gravid pigs. The results show that: (1) endometrial 17β-HSD activity was decreased on Days 15-16 in pregnant and cyclic pigs compared with the preceding days; (2) LH, FSH and PRL increased endometrial E1 secretion on Days 10-11 and 15-16 of pregnancy and on Days 12-13 and 15-16 of the oestrous cycle; and (3) LH, FSH and PRL increased endometrial E2 secretion on Days 15-16 of pregnancy and during the days studied in the oestrous cycle. In conclusion, data suggest that LH, FSH and PRL affect endometrial secretion of estrogens in pigs.

  12. An essential role for insulin and IGF1 receptors in regulating sertoli cell proliferation, testis size, and FSH action in mice.

    PubMed

    Pitetti, Jean-Luc; Calvel, Pierre; Zimmermann, Céline; Conne, Béatrice; Papaioannou, Marilena D; Aubry, Florence; Cederroth, Christopher R; Urner, Françoise; Fumel, Betty; Crausaz, Michel; Docquier, Mylène; Herrera, Pedro Luis; Pralong, François; Germond, Marc; Guillou, Florian; Jégou, Bernard; Nef, Serge

    2013-05-01

    Testis size and sperm production are directly correlated to the total number of adult Sertoli cells (SCs). Although the establishment of an adequate number of SCs is crucial for future male fertility, the identification and characterization of the factors regulating SC survival, proliferation, and maturation remain incomplete. To investigate whether the IGF system is required for germ cell (GC) and SC development and function, we inactivated the insulin receptor (Insr), the IGF1 receptor (Igf1r), or both receptors specifically in the GC lineage or in SCs. Whereas ablation of insulin/IGF signaling appears dispensable for GCs and spermatogenesis, adult testes of mice lacking both Insr and Igf1r in SCs (SC-Insr;Igf1r) displayed a 75% reduction in testis size and daily sperm production as a result of a reduced proliferation rate of immature SCs during the late fetal and early neonatal testicular period. In addition, in vivo analyses revealed that FSH requires the insulin/IGF signaling pathway to mediate its proliferative effects on immature SCs. Collectively, these results emphasize the essential role played by growth factors of the insulin family in regulating the final number of SCs, testis size, and daily sperm output. They also indicate that the insulin/IGF signaling pathway is required for FSH-mediated SC proliferation.

  13. “Platelet-associated regulatory system (PARS)” with particular reference to female reproduction

    PubMed Central

    2014-01-01

    Background Blood platelets play an essential role in hemostasis, thrombosis and coagulation of blood. Beyond these classic functions their involvement in inflammatory, neoplastic and immune processes was also investigated. It is well known, that platelets have an armament of soluble molecules, factors, mediators, chemokines, cytokines and neurotransmitters in their granules, and have multiple adhesion molecules and receptors on their surface. Methods Selected relevant literature and own views and experiences as clinical observations have been used. Results Considering that platelets are indispensable in numerous homeostatic endocrine functions, it is reasonable to suppose that a platelet-associated regulatory system (PARS) may exist; internal or external triggers and/or stimuli may complement and connect regulatory pathways aimed towards target tissues and/or cells. The signal (PAF, or other tissue/cell specific factors) comes from the stimulated (by the e.g., hypophyseal hormones, bacteria, external factors, etc.) organs or cells, and activates platelets. Platelet activation means their aggregation, sludge formation, furthermore the release of the for-mentioned biologically very powerful factors, which can locally amplify and deepen the tissue specific cell reactions. If this process is impaired or inhibited for any reason, the specifically stimulated organ shows hypofunction. When PARS is upregulated, organ hyperfunction may occur that culminate in severe diseases. Conclusion Based on clinical and experimental evidences we propose that platelets modulate the function of hypothalamo-hypophyseal-ovarian system. Specifically, hypothalamic GnRH releases FSH from the anterior pituitary, which induces and stimulates follicular and oocyte maturation and steroid hormone secretion in the ovary. At the same time follicular cells enhance PAF production. Through these pathways activated platelets are accumulated in the follicular vessels surrounding the follicle and due to

  14. Critical Role for PAR1 in Kallikrein 6-Mediated Oligodendrogliopathy

    PubMed Central

    Burda, Joshua E.; Radulovic, Maja; Yoon, Hyesook; Scarisbrick, Isobel A.

    2014-01-01

    Kallikrein 6 (Klk6) is a secreted serine protease preferentially expressed by oligodendroglia in CNS white matter. Elevated levels of Klk6 occur in actively demyelinating multiple sclerosis (MS) lesions and in cases of spinal cord injury (SCI), stroke and glioblastoma. Taken with recent evidence establishing Klk6 as a CNS-endogenous activator of protease-activated receptors (PARs), we hypothesized that Klk6 activates a subset of PARs to regulate oligodendrocyte physiology and potentially pathophysiology. Here, primary oligodendrocyte cultures derived from wild type or PAR1-deficient mice and the murine oligodendrocyte cell line, Oli-neu, were used to demonstrate that Klk6 mediates loss of oligodendrocyte processes and impedes morphological differentiation of oligodendrocyte progenitor cells (OPCs) in a PAR1-dependent fashion. Comparable gliopathy was also elicited by the canonical PAR1 agonist, thrombin, as well as PAR1-activating peptides (PAR1-APs). Klk6 also exacerbated ATP-mediated oligodendrogliopathy in vitro, pointing to a potential role in augmenting excitotoxicity. In addition, Klk6 suppressed the expression of proteolipid protein (PLP) RNA in cultured oligodendrocytes by a mechanism involving PAR1-mediated Erk1/2 signaling. Microinjection of PAR1 agonists, including Klk6 or PAR1-APs, into the dorsal column white matter of PAR+/+ but not PAR−/− mice promoted vacuolating myelopathy and a loss of immunoreactivity for myelin basic protein (MBP) and CC-1+ oligodendrocytes. These results demonstrate a functional role for Klk6-PAR1 signaling in oligodendroglial pathophysiology and suggest that PAR1 or PAR1-agonists may represent new targets to moderate demyelination and to promote myelin regeneration in cases of CNS white matter injury or disease. PMID:23832758

  15. Modelisation par elements finis du muscle strie

    NASA Astrophysics Data System (ADS)

    Leonard, Mathieu

    Ce present projet de recherche a permis. de creer un modele par elements finis du muscle strie humain dans le but d'etudier les mecanismes engendrant les lesions musculaires traumatiques. Ce modele constitue une plate-forme numerique capable de discerner l'influence des proprietes mecaniques des fascias et de la cellule musculaire sur le comportement dynamique du muscle lors d'une contraction excentrique, notamment le module de Young et le module de cisaillement de la couche de tissu conjonctif, l'orientation des fibres de collagene de cette membrane et le coefficient de poisson du muscle. La caracterisation experimentale in vitro de ces parametres pour des vitesses de deformation elevees a partir de muscles stries humains actifs est essentielle pour l'etude de lesions musculaires traumatiques. Le modele numerique developpe est capable de modeliser la contraction musculaire comme une transition de phase de la cellule musculaire par un changement de raideur et de volume a l'aide des lois de comportement de materiau predefinies dans le logiciel LS-DYNA (v971, Livermore Software Technology Corporation, Livermore, CA, USA). Le present projet de recherche introduit donc un phenomene physiologique qui pourrait expliquer des blessures musculaires courantes (crampes, courbatures, claquages, etc.), mais aussi des maladies ou desordres touchant le tissu conjonctif comme les collagenoses et la dystrophie musculaire. La predominance de blessures musculaires lors de contractions excentriques est egalement exposee. Le modele developpe dans ce projet de recherche met ainsi a l'avant-scene le concept de transition de phase ouvrant la porte au developpement de nouvelles technologies pour l'activation musculaire chez les personnes atteintes de paraplegie ou de muscles artificiels compacts pour l'elaboration de protheses ou d'exosquelettes. Mots-cles Muscle strie, lesion musculaire, fascia, contraction excentrique, modele par elements finis, transition de phase

  16. The beta104-109 sequence is essential for the secretion of correctly folded single-chain beta alpha horse LH/CG and for its FSH activity.

    PubMed

    Galet, Colette; Guillou, Florian; Foulon-Gauze, Florence; Combarnous, Yves; Chopineau, Maryse

    2009-10-01

    The dual LH and FSH activity of the equine LH (eLH)/equine chorionic gonadotropin (eCG) in heterologous species makes eLH/CG a good model to study structure/function relationships of gonadotropins. In order to bypass the problem of intracellular association of the heterodimer, a recombinant single-chain beta alpha eLH/CG was used to identify sequences in the beta-subunit involved in the secretion and activities of the hormone. The C-terminal region of the beta-subunit was progressively truncated. All resulting truncated single-chains were secreted in the media as detected by an anti-beta peptide antibody in reducing conditions. However, using a conformation sensitive ELISA we show that the truncated single-chains were differently recognized: deletion of the last 40 amino acids of the beta-subunit (beta109alpha eLH/CG) resulted in a 90% decrease in the recognized correctly folded hormone compared with the full-length beta alpha eLH/CG single-chain and no properly folded hormone was detected in the secretion medium when the last 46 amino acids of the beta-subunit were deleted (beta103alpha eLH/CG). We thus focused on the six amino acids sequence 104-109, which belongs to the seat-belt region. Mutation of the 104-109 sequence in alanines in the full-length beta alpha eLH/CG (beta104-109Ala alpha) led to a 50% decrease in the production of properly folded hormone in COS-7 as well as in alphaT3 pituitary cells. Moreover, the FSH activity of this mutant was decreased by 70% whereas its LH activity remained intact. These data lead us to conclude that the 104-109 region of the beta eLH/CG subunit is essential for the secretion of a fully folded beta alpha eLH/CG and for its FSH activity but not for its LH activity.

  17. A new model for estimating boreal forest fPAR

    NASA Astrophysics Data System (ADS)

    Majasalmi, Titta; Rautiainen, Miina; Stenberg, Pauline

    2014-05-01

    Life on Earth is continuously sustained by the extraterrestrial flux of photosynthetically active radiation (PAR, 400-700 nm) from the sun. This flux is converted to biomass by chloroplasts in green vegetation. Thus, the fraction of absorbed PAR (fPAR) is a key parameter used in carbon balance studies, and is listed as one of the Essential Climate Variables (ECV). Temporal courses of fPAR for boreal forests are difficult to measure, because of the complex 3D structures. Thus, they are most often estimated based on models which quantify the dependency of absorbed radiation on canopy structure. In this study, we adapted a physically-based canopy radiation model into a fPAR model, and compared modeled and measured fPAR in structurally different boreal forest stands. The model is based on the spectral invariants theory, and uses leaf area index (LAI), canopy gap fractions and spectra of foliage and understory as input data. The model differs from previously developed more detailed fPAR models in that the complex 3D structure of coniferous forests is described using an aggregated canopy parameter - photon recollision probability p. The strength of the model is that all model inputs are measurable or available through other simple models. First, the model was validated with measurements of instantaneous fPAR obtained with the TRAC instrument in nine Scots pine, Norway spruce and Silver birch stands in a boreal forest in southern Finland. Good agreement was found between modeled and measured fPAR. Next, we applied the model to predict temporal courses of fPAR using data on incoming radiation from a nearby flux tower and sky irradiance models. Application of the model to simulate diurnal and seasonal values of fPAR indicated that the ratio of direct-to-total incident radiation and leaf area index are the key factors behind the magnitude and variation of stand-level fPAR values.

  18. 2. HI PAR (ACQUISITION RADAR) TOWER AND ENLISTED MEN (EM) ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. HI PAR (ACQUISITION RADAR) TOWER AND ENLISTED MEN (EM) BARRACKS WITH RADAR ATTACHED. - Nike Hercules Missile Battery Summit Site, Battery Control Administration & Barracks Building, Anchorage, Anchorage, AK

  19. A new way of setting rFSH deposit: a case of severe injection error in IVF/ICSI cycle ending with live birth.

    PubMed

    Mayer, Richard Bernhard; Ebner, Thomas; Shebl, Omar; Tews, Gernot

    2012-01-01

    Ciddi enjeksiyon hatası olan bir olgu sunuyoruz: Erkek faktörünün yol açtığı ikincil infertilitesi olan 25 yaşındaki bir kadın IVF/ICSI-ET programımıza alındı. Stimulasyon uzun protokol ile gerçekleştirildi ve over stimulasyonu, rFSH follitropin beta kullanılarak, menstrüel döngünün üçüncü günü başlatıldı. Günlük rFSH dozu şöyleydi: 900 IU-0 IU-0 IU-0 IU. Normal over yanıtı ve folikül büyümesi nedeniyle stimulasyona devam edildi, oosit kalitesinde bozulma ve OHSS semptomları yoktu. Blastokist transferini takiben sezaryenle doğum, kalıcı transvers duruş nedeniyle 37+5’inci gebelik haftasında önlenemez durumdaydı. Çeşitli hastaların uygun tedavisi için, tedavi uygulamasının doğru bir şekilde yapılmasını sağlayan, farklı stimulasyon protokollerine gerek duyulmaktadır. Enjeksiyon hataları durumunda, hormon düzeyleri ve folikül büyümesi süreci göz önüne alınarak, stimulasyon protokolünün sürdürülmesi bazı olgularda başarılabilir görünmektedir.

  20. Secretory pattern of GH, TSH, thyroid hormones, ACTH, cortisol, FSH, and LH in patients with fibromyalgia syndrome following systemic injection of the relevant hypothalamic-releasing hormones.

    PubMed

    Riedel, W; Layka, H; Neeck, G

    1998-01-01

    To study the hormonal perturbations in FMS patients we injected sixteen FMS patients and seventeen controls a cocktail of the hypothalamic releasing hormones: Corticotropin-releasing hormone (CRH), Thyrotropin-releasing hormone (TRH), Growth hormone-releasing hormone (GHRH), and Luteinizing hormone-releasing hormone (LHRH) and observed the hormonal secretion pattern of the pituitary together with the hormones of the peripheral endocrine glands. We found in FMS patients elevated basal values of ACTH and cortisol, lowered basal values of insulin-like growth factor I (IGF-I) and of triiodothyronine (T3), elevated basal values of follicle-stimulating hormone (FSH) and lowered basal values of estrogen. Following injection of the four releasing-hormones, we found in FMS patients an augmented response of ACTH, a blunted response of TSH, while the prolactin response was exaggerated. The effects of LHRH stimulation were investigated in six FMS patients and six controls and disclosed a significantly blunted response of LH in FMS. We explain the deviations of hormonal secretion in FMS patients as being caused by chronic stress, which, after being perceived and processed by the central nervous system (CNS), activates hypothalamic CRH neurons. CRH, on the one hand, activates the pituitary-adrenal axis, but also stimulates at the hypothalamic level somatostatin secretion which, in turn, causes inhibition of GH and TSH at the pituitary level. The suppression of gonadal function may also be attributed to elevated CRH by its ability to inhibit hypothalamic LHRH release, although it could act also directly on the ovary by inhibiting FSH-stimulated estrogen production. We conclude that the observed pattern of hormonal deviations in FMS patients is a CNS adjustment to chronic pain and stress, constitutes a specific entity of FMS, and is primarily evoked by activated CRH neurons.

  1. Overexpression of hyaluronan synthase 2 and gonadotropin receptors in cumulus cells of goats subjected to one-shot eCG/FSH hormonal treatment for ovarian stimulation.

    PubMed

    Santos, Juliana D R; Batista, Ribrio I T P; Magalhães, Livia C; Paula, Alexandre R; Souza, Samara S; Salamone, Daniel F; Bhat, Maajid H; Teixeira, Dárcio I A; Freitas, Vicente J F; Melo, Luciana M

    2016-07-01

    Hormonal ovarian stimulation may affect transcripts in somatic cells of cumulus-oocyte complexes (COCs) and affect the resulting oocyte quality. Here, in parallel with morphological classification and in vitro maturation (IVM) rate analysis, we investigated the expression of hyaluronan synthase 2 (HAS2), gonadotropic receptors (FSHR and LHR) and connexin 43 (GJA1) in cumulus cells (CCs) from goat COCs after multi-dose FSH (MD) or one-shot FSH/eCG (OS) treatments, using bovine COCs as control groups. The MD treatment produced more large follicles, and the resulting COCs had a better morphology and IVM rate than were obtained with OS. The OS treatment produced COCs with increased HAS2, FSHR, LHR and GJA1 expression. This gene expression pattern was also observed in the CCs of COCs that showed poor morphological characteristics. On the other hand, the mRNA levels were more similar between groups after IVM; FSHR and LHR were the main genes that showed decreased expression. Some events that occurred in bovine CCs during IVM, such as cell expansion, increased HAS2 expression and decreased GJA1 expression, were less evident or did not occur in goat COCs. In conclusion, increasing HAS2, FSHR, LHR and GJA1 expression in goat COCs does not confer greater meiotic competence to oocytes. Instead, it may result from poor regulation of gene expression in CCs by lower quality oocytes. Finally, cumulus expansion, together with HAS2 upregulation and GJA1 downregulation, seems to be more important for bovine COCs than for goat COCs. Additional studies are needed to investigate the importance of other HAS isoforms and connexins in goat COCs.

  2. Reproductive Physiology in Young Men Is Cumulatively Affected by FSH-Action Modulating Genetic Variants: FSHR -29G/A and c.2039 A/G, FSHB -211G/T

    PubMed Central

    Grigorova, Marina; Punab, Margus; Punab, Anna Maria; Poolamets, Olev; Vihljajev, Vladimir; Žilaitienė, Birutė; Erenpreiss, Juris; Matulevičius, Valentinas; Laan, Maris

    2014-01-01

    Follicle-Stimulating Hormone Receptor (FSHR) -29G/A polymorphism (rs1394205) was reported to modulate gene expression and reproductive parameters in women, but data in men is limited. We aimed to bring evidence to the effect of FSHR -29G/A variants in men. In Baltic young male cohort (n = 982; Estonians, Latvians, Lithuanians; aged 20.2±2.0 years), the FSHR -29 A-allele was significantly associated with higher serum FSH (linear regression: effect 0.27 IU/L; P = 0.0019, resistant to Bonferroni correction for multiple testing) and showed a non-significant trend for association with higher LH (0.19 IU/L) and total testosterone (0.93 nmol/L), but reduced Inhibin B (−7.84 pg/mL) and total testes volume (effect −1.00 mL). Next, we extended the study and tested the effect of FSHR gene haplotypes determined by the allelic combination of FSHR -29G/A and a well-studied variant c.2039 A/G (Asn680Ser, exon 10). Among the FSHR -29A/2039G haplotype carriers (A-Ser; haplotype-based linear regression), this genetic effect was enhanced for FSH (effect 0.40 IU/L), Inhibin B (−16.57 pg/mL) and total testes volume (−2.34 mL). Finally, we estimated the total contribution of three known FSH-action modulating SNPs (FSHB -211G/T; FSHR -29G/A, c.2039 A/G) to phenotypic variance in reproductive parameters among young men. The major FSH-action modulating SNPs explained together 2.3%, 1.4%, 1.0 and 1.1% of the measured variance in serum FSH, Inhibin B, testosterone and total testes volume, respectively. In contrast to the young male cohort, neither FSHR -29G/A nor FSHR haplotypes appeared to systematically modulate the reproductive physiology of oligozoospermic idiopathic infertile patients (n = 641, Estonians; aged 31.5±6.0 years). In summary, this is the first study showing the significant effect of FSHR -29G/A on male serum FSH level. To account for the genetic effect of known common polymorphisms modulating FSH-action, we suggest haplotype-based analysis of FSHR SNPs

  3. The effect of the intracervical administration of FSH or LH on the levels of hyaluronan, COX2, and COX2 mRNA in the cervix of the nonpregnant ewe.

    PubMed

    Leethongdee, Sukanya; Khalid, Muhammad; Scaramuzzi, Rex J

    2016-12-01

    During the periovulatory period, the cervix relaxes in response to changes in circulating concentrations of reproductive hormones. The present study investigated the role of gonadotrophins in cervical function by examining the expression of cyclooxygenase-2 (COX2) and COX2 mRNA and the concentration of hyaluronan (HA) in the cervix, after intracervical treatment with either FSH or LH. Eighteen ewes were assigned to four groups. They were then treated with commercial intravaginal progestagen sponges and eCG to synchronize their estrous cycles. Intracervical treatments were given 24 hours after removal of the sponges as follows: group 1: FSH, 2 mg; group 2: LH, 2 mg; group 3: vehicle; and group 4: control. Cervices were collected 54 hours after sponge removal and then divided into three regions. The expression of COX2 and COX2 mRNA was determined by immunohistochemistry and in situ hybridization and those of HA by ELISA. The levels of expression of COX2, COX2 mRNA, and HA were compared in six tissue layers (luminal epithelium, subepithelial stroma, circular, longitudinal and transverse muscle, and serosa) and in three cervical regions (vaginal, mid, and uterine). The results showed that both FSH and LH significantly increased the levels the COX2 mRNA and COX2 in the cervix, but the effects of the gonadotrophins were selective. The effects of both FSH and LH were most evident at the vaginal end of the cervix and least at the uterine end of the cervix. Furthermore, their effects were confined to the stroma and smooth muscle layers of the cervix in the case of FSH and to smooth muscle only in the case of LH. Neither FSH nor LH affected the concentration of HA in the cervix although FSH but not LH reduced the concentration of HA in cervical mucus. These findings suggest that the gonadotrophins regulate the expression of COX2 in the cervix and that they may have a role facilitating relaxation of the cervix during estrus in the ewe.

  4. Taare Zameen Par and dyslexic savants

    PubMed Central

    Chakravarty, Ambar

    2009-01-01

    The film Taare Zameen Par (Stars upon the Ground) portrays the tormented life at school and at home of a child with dyslexia and his eventual success after his artistic talents are discovered by his art teacher at the boarding school. The film hints at a curious neurocognitive phenomenon of creativity in the midst of language disability, as exemplified in the lives of people like Leonardo da Vinci and Albert Einstein, both of whom demonstrated extraordinary creativity even though they were probably affected with developmental learning disorders. It has been hypothesized that a developmental delay in the dominant hemisphere most likely ‘disinhibits’ the nondominant parietal lobe, unmasking talents—artistic or otherwise—in some such individuals. It has been suggested that, in remedial training, children with learning disorders be encouraged to develop such hidden talents to full capacity, rather than be subjected to the usual overemphasis on the correction of the disturbed coded symbol operations. PMID:20142854

  5. Transcriptome profiling reveals links between ParS/ParR, MexEF-OprN, and quorum sensing in the regulation of adaptation and virulence in Pseudomonas aeruginosa

    PubMed Central

    2013-01-01

    Background The ParS/ParR two component regulatory system plays critical roles for multidrug resistance in Pseudomonas aeruginosa. It was demonstrated that in the presence of antimicrobials, ParR enhances bacterial survival by distinct mechanisms including activation of the mexXY efflux genes, enhancement of lipopolysaccharide modification through the arn operon, and reduction of the expression of oprD porin. Results In this study, we report on transcriptomic analyses of P. aeruginosa PAO1 wild type and parS and parR mutants growing in a defined minimal medium. Our transcriptomic analysis provides the first estimates of transcript abundance for the 5570 coding genes in P. aeruginosa PAO1. Comparative transcriptomics of P. aeruginosa PAO1 and par mutants identified a total of 464 genes regulated by ParS and ParR. Results also showed that mutations in the parS/parR system abolished expression of the mexEF-oprN operon by down-regulating the regulatory gene mexS. In addition to the known effects on drug resistance genes, transcript abundances of the quorum sensing genes (rhlIR and pqsABCDE-phnAB) were higher in both parS and parR mutants. In accordance with these results, a significant portion of the ParS/ParR regulated genes belonged to the MexEF-OprN and quorum sensing regulons. Deletion of the par genes also led to increased phenazine production and swarming motility, consistent with the up-regulation of the phenazine and rhamnolipid biosynthetic genes, respectively. Conclusion Our results link the ParS/ParR two component signal transduction system to MexEF-OprN and quorum sensing systems in P. aeruginosa. These results expand our understanding of the roles of the ParS/ParR system in the regulation of gene expression in P. aeruginosa, especially in the absence of antimicrobials. PMID:24034668

  6. Stimulatory effect of a specific substance P antagonist (RPR 100893) of the human NK1 receptor on the estradiol-induced LH and FSH surges in the ovariectomized cynomolgus monkey.

    PubMed

    Kerdelhué, B; Gordon, K; Williams, R; Lenoir, V; Fardin, V; Chevalier, P; Garret, C; Duval, P; Kolm, P; Hodgen, G; Jones, H; Jones, G S

    1997-10-01

    Utilizing a human NK1 receptor antagonist (RPR 100893), the present in vivo study was designed to test the hypothesis that endogenous substance P (SP) modulates the action of 17beta-estradiol in inducing luteinizing hormone (LH) and follicle stimulating hormone (FSH) surges in ovariectomized cynomolgus monkey. Plasma concentrations of LH and FSH as well as NK1 receptor antagonist and SP were measured during the development of the negative and positive feedback phases which follow a single administration of estradiol benzoate (50 microg/kg) to long-term ovariectomized monkeys. Daily administration by gastric intubation of 1 mg/kg or 10 mg/kg of the NK1 receptor antagonist (RPR 100893) leads to detectable levels of the antagonist in the blood of treated animals for at least 6 hr after its administration. These levels are in agreement with the experimentally determined IC50 value of the antagonist. The most striking finding of this study is that LH and FSH releases are enhanced during the descending arm of the estradiol benzoate-induced LH and FSH surges, which suggests that endogenous SP normally has an inhibitory role during this time. The enhancement of LH release is approximately 50%, regardless of the amount of the NK1 antagonist used. However, the enhanced FSH release is more important. Furthermore, blockade of the NK1 receptor with the smaller dose of the antagonist leads to a small, but significant, increase in plasma levels of SP, indicating that blockade of SP receptors leads to an increased release of SP. Collectively, these results further substantiate the link which exists between the ovarian steroid 17beta-estradiol and SP systems. Also, for the first time, these results demonstrate an inhibitory involvement of the human NK1 receptor in the 17beta-estradiol-induced pseudo-ovulatory gonadotropin surges in the ovariectomized monkey.

  7. Recombination in the Human Pseudoautosomal Region PAR1

    PubMed Central

    Hinch, Anjali G.; Altemose, Nicolas; Noor, Nudrat; Donnelly, Peter; Myers, Simon R.

    2014-01-01

    The pseudoautosomal region (PAR) is a short region of homology between the mammalian X and Y chromosomes, which has undergone rapid evolution. A crossover in the PAR is essential for the proper disjunction of X and Y chromosomes in male meiosis, and PAR deletion results in male sterility. This leads the human PAR with the obligatory crossover, PAR1, to having an exceptionally high male crossover rate, which is 17-fold higher than the genome-wide average. However, the mechanism by which this obligatory crossover occurs remains unknown, as does the fine-scale positioning of crossovers across this region. Recent research in mice has suggested that crossovers in PAR may be mediated independently of the protein PRDM9, which localises virtually all crossovers in the autosomes. To investigate recombination in this region, we construct the most fine-scale genetic map containing directly observed crossovers to date using African-American pedigrees. We leverage recombination rates inferred from the breakdown of linkage disequilibrium in human populations and investigate the signatures of DNA evolution due to recombination. Further, we identify direct PRDM9 binding sites using ChIP-seq in human cells. Using these independent lines of evidence, we show that, in contrast with mouse, PRDM9 does localise peaks of recombination in the human PAR1. We find that recombination is a far more rapid and intense driver of sequence evolution in PAR1 than it is on the autosomes. We also show that PAR1 hotspot activities differ significantly among human populations. Finally, we find evidence that PAR1 hotspot positions have changed between human and chimpanzee, with no evidence of sharing among the hottest hotspots. We anticipate that the genetic maps built and validated in this work will aid research on this vital and fascinating region of the genome. PMID:25033397

  8. Recombination in the human Pseudoautosomal region PAR1.

    PubMed

    Hinch, Anjali G; Altemose, Nicolas; Noor, Nudrat; Donnelly, Peter; Myers, Simon R

    2014-07-01

    The pseudoautosomal region (PAR) is a short region of homology between the mammalian X and Y chromosomes, which has undergone rapid evolution. A crossover in the PAR is essential for the proper disjunction of X and Y chromosomes in male meiosis, and PAR deletion results in male sterility. This leads the human PAR with the obligatory crossover, PAR1, to having an exceptionally high male crossover rate, which is 17-fold higher than the genome-wide average. However, the mechanism by which this obligatory crossover occurs remains unknown, as does the fine-scale positioning of crossovers across this region. Recent research in mice has suggested that crossovers in PAR may be mediated independently of the protein PRDM9, which localises virtually all crossovers in the autosomes. To investigate recombination in this region, we construct the most fine-scale genetic map containing directly observed crossovers to date using African-American pedigrees. We leverage recombination rates inferred from the breakdown of linkage disequilibrium in human populations and investigate the signatures of DNA evolution due to recombination. Further, we identify direct PRDM9 binding sites using ChIP-seq in human cells. Using these independent lines of evidence, we show that, in contrast with mouse, PRDM9 does localise peaks of recombination in the human PAR1. We find that recombination is a far more rapid and intense driver of sequence evolution in PAR1 than it is on the autosomes. We also show that PAR1 hotspot activities differ significantly among human populations. Finally, we find evidence that PAR1 hotspot positions have changed between human and chimpanzee, with no evidence of sharing among the hottest hotspots. We anticipate that the genetic maps built and validated in this work will aid research on this vital and fascinating region of the genome.

  9. Megestrol acetate NCD oral suspension -- Par Pharmaceutical: megestrol acetate nanocrystal dispersion oral suspension, PAR 100.2, PAR-100.2.

    PubMed

    2007-01-01

    Par Pharmaceutical has developed megestrol acetate (Megace ES) oral suspension for the treatment of anorexia, cachexia and a significant weight loss associated with AIDS. Par Pharmaceutical used Elan Corporation's NanoCrystal Dispersion (NCD) technology to develop an advanced, concentrated formulation of megestrol acetate with improved bioavailability, more rapid onset of action, more convenient dosing and a lower dosing regimen compared with the original marketed formulation of megestrol acetate oral suspension. Patients are administered a teaspoon (5mL) of the new NCD formulation once daily, compared with a daily 20mL dosage cup of the original formulation. The new megestrol acetate NCD formulation represents a line-extension of Par's megestrol acetate oral suspension (800mg/20mL, Megace O/S) that has been marketed for anorexia, cachexia and AIDS-related weight loss since July 2001. Par's megestrol acetate is the generic version of Bristol-Myers Squibb's Megace Oral Suspension. NanoCrystal Dispersion (NCD) is a trademark of Elan Corporation. Par Pharmaceutical will market megestol acetate NCD oral suspension under the Megace brand name. The company licensed the Megace name from Bristol-Myers Squib in August 2003. The US FDA approved megestrol acetate oral suspension (625 mg/mL) in July 2005 for the treatment of anorexia, cachexia or a significant, unexplained weight loss in patients with AIDS. The NDA for the product was accepted for review by the agency in September 2004, following its submission in June of that year.Par Pharmaceutical commenced the first of two phase III clinical trials of megestrol acetate oral suspension (PAR 100.2) in cancer-induced anorexia in the first quarter of 2006. However, this trial was discontinued in September 2006 because of slow patient enrolment. The company intends to discuss future development options in this indication with the FDA.New formulations or dosage forms of megestrol acetate concentrated suspension are also in

  10. Megestrol acetate NCD oral suspension--Par Pharmaceutical: megestrol acetate nanocrystal dispersion oral suspension, PAR 100.2, PAR-100.2.

    PubMed

    2007-01-01

    Par Pharmaceutical has developed megestrol acetate (Megace ES) oral suspension for the treatment of anorexia, cachexia and a significant weight loss associated with AIDS. Par Pharmaceutical used Elan Corporation's NanoCrystal Dispersion (NCD) technology to develop an advanced, concentrated formulation of megestrol acetate with improved bioavailability, more rapid onset of action, more convenient dosing and a lower dosing regimen compared with the original marketed formulation of megestrol acetate oral suspension. Patients are administered a teaspoon (5mL) of the new NCD formulation once daily, compared with a daily 20mL dosage cup of the original formulation. The new megestrol acetate NCD formulation represents a line-extension of Par's megestrol acetate oral suspension (800mg/20mL, Megace O/S) that has been marketed for anorexia, cachexia and AIDS-related weight loss since July 2001. Par's megestrol acetate is the generic version of Bristol-Myers Squibb's Megace Oral Suspension. NanoCrystal Dispersion (NCD) is a trademark of Elan Corporation. Par Pharmaceutical will market megestol acetate NCD oral suspension under the Megace brand name. The company licensed the Megace name from Bristol-Myers Squib in August 2003. The US FDA approved megestrol acetate oral suspension (625 mg/mL) in July 2005 for the treatment of anorexia, cachexia or a significant, unexplained weight loss in patients with AIDS. The NDA for the product was accepted for review by the agency in September 2004, following its submission in June of that year.Par Pharmaceutical commenced the first of two phase III clinical trials of megestrol acetate oral suspension (PAR 100.2) in cancer-induced anorexia in the first quarter of 2006. However, this trial was discontinued in September 2006 because of slow patient enrolment. The company intends to discuss future development options in this indication with the FDA.New formulations or dosage forms of megestrol acetate concentrated suspension are also in

  11. Condensation and localization of the partitioning protein ParB on the bacterial chromosome.

    PubMed

    Broedersz, Chase P; Wang, Xindan; Meir, Yigal; Loparo, Joseph J; Rudner, David Z; Wingreen, Ned S

    2014-06-17

    The ParABS system mediates chromosome segregation and plasmid partitioning in many bacteria. As part of the partitioning mechanism, ParB proteins form a nucleoprotein complex at parS sites. The biophysical basis underlying ParB-DNA complex formation and localization remains elusive. Specifically, it is unclear whether ParB spreads in 1D along DNA or assembles into a 3D protein-DNA complex. We show that a combination of 1D spreading bonds and a single 3D bridging bond between ParB proteins constitutes a minimal model for a condensed ParB-DNA complex. This model implies a scaling behavior for ParB-mediated silencing of parS-flanking genes, which we confirm to be satisfied by experimental data from P1 plasmids. Furthermore, this model is consistent with experiments on the effects of DNA roadblocks on ParB localization. Finally, we show experimentally that a single parS site is necessary and sufficient for ParB-DNA complex formation in vivo. Together with our model, this suggests that ParB binding to parS triggers a conformational switch in ParB that overcomes a nucleation barrier. Conceptually, the combination of spreading and bridging bonds in our model provides a surface tension ensuring the condensation of the ParB-DNA complex, with analogies to liquid-like compartments such as nucleoli in eukaryotes.

  12. Condensation and localization of the partitioning protein ParB on the bacterial chromosome

    PubMed Central

    Broedersz, Chase P.; Wang, Xindan; Meir, Yigal; Loparo, Joseph J.; Rudner, David Z.; Wingreen, Ned S.

    2014-01-01

    The ParABS system mediates chromosome segregation and plasmid partitioning in many bacteria. As part of the partitioning mechanism, ParB proteins form a nucleoprotein complex at parS sites. The biophysical basis underlying ParB–DNA complex formation and localization remains elusive. Specifically, it is unclear whether ParB spreads in 1D along DNA or assembles into a 3D protein–DNA complex. We show that a combination of 1D spreading bonds and a single 3D bridging bond between ParB proteins constitutes a minimal model for a condensed ParB–DNA complex. This model implies a scaling behavior for ParB-mediated silencing of parS-flanking genes, which we confirm to be satisfied by experimental data from P1 plasmids. Furthermore, this model is consistent with experiments on the effects of DNA roadblocks on ParB localization. Finally, we show experimentally that a single parS site is necessary and sufficient for ParB–DNA complex formation in vivo. Together with our model, this suggests that ParB binding to parS triggers a conformational switch in ParB that overcomes a nucleation barrier. Conceptually, the combination of spreading and bridging bonds in our model provides a surface tension ensuring the condensation of the ParB–DNA complex, with analogies to liquid-like compartments such as nucleoli in eukaryotes. PMID:24927534

  13. High live birth rate in the subsequent IVF cycle after first-cycle poor response among women with mean age 35 and normal FSH.

    PubMed

    Moolenaar, Lobke M; Mohiuddin, Seema; Munro Davie, Moira; Merrilees, Margaret A; Broekmans, Frank J M; Mol, Ben Willem J; Johnson, Neil P

    2013-10-01

    Poor ovarian response in IVF cycles is associated with diminished ovarian reserve and poor pregnancy outcome. Little is known about pregnancy outcome after a poor response in women with a normal ovarian reserve. This retrospective study studied women undergoing IVF/intracytoplasmic sperm injection between January 2003 to December 2008 in the FertilityPLUS Clinic in Auckland, New Zealand. All women with a poor response in the first cycle were selected. Primary outcome was live birth after the second cycle. Secondary outcomes were poor response in the second cycle and the predictive values of female age and basal FSH at first cycle and IVF outcome at second cycle. Of the 2487 women starting IVF, 142 women (5.7%) with a poor response in the first cycle were selected, of which 66 (46.5%) women had a repeated poor response in the second cycle. There were 31 live births in the second cycle (21.8%). Female age was the only significant predictor for repeated poor response (AUC 0.69, 95% CI 0.61-0.78) and clinical pregnancy (AUC 0.66, 95% CI 0.57-0.75), but the predictive value was low. Therefore poor response in women with a normal ovarian reserve should not be a reason to discontinue further IVF treatment. Poor ovarian response in IVF cycles is associated with diminished ovarian reserve and poor pregnancy outcome. Little is known about pregnancy outcome after a poor response in women with a normal ovarian reserve. In this retrospective study, we studied women undergoing IVF/intracytoplasmic sperm injection (ICSI) between January 2003 to December 2008 in the FertilityPLUS Clinic in Auckland, New Zealand. All women with a poor response in the first cycle were selected. Primary outcome was live birth after the second cycle. Secondary outcomes were poor response in the second cycle and the predictive value of female age and basal FSH at first cycle and IVF outcome at the second cycle. Of the 2487 women starting wit IVF, a total of 142 women (5.7%) with a poor response in the

  14. Scleral Buckling for Rhegmatogenous Retinal Detachment Associated with Pars Planitis

    PubMed Central

    Ahn, Jae Kyoun

    2016-01-01

    Purpose. To evaluate the surgical outcome of scleral buckling (SB) in rhegmatogenous retinal detachment (RRD) patients associated with pars planitis. Methods. Retrospective review of RRD patients (32 eyes of pars planitis RRD and 180 eyes of primary RRD) who underwent SB. We compared primary and final anatomical success rates and visual outcomes between two groups. Results. Primary and final anatomical success were achieved in 25 (78.1%) and 31 (96.8%) eyes in the pars planitis RRD group and in 167 eyes (92.7%) and 176 eyes (97.7%) in primary RRD group, respectively. Both groups showed significant visual improvement (p < 0.001) and there were no significant differences in final visual acuity. Pars planitis RRD group was associated with higher rate of postoperative proliferative vitreoretinopathy (PVR) development (12.5% versus 2.8%, p = 0.031). Pars planitis and high myopia were significant preoperative risk factors and pseudophakia was borderline risk for primary anatomical failure after adjusting for various clinical factors. Conclusions. Pars planitis associated RRD showed inferior primary anatomical outcome after SB due to postoperative PVR development. However, final anatomical and visual outcomes were favorable. RRD cases associated with pars planitis, high myopia, and pseudophakia might benefit from different surgical approaches, such as combined vitrectomy and SB. PMID:27688907

  15. The Pars Triangularis in Dyslexia and ADHD

    PubMed Central

    Kibby, Michelle Y.; Kroese, Judith M.; Krebbs, Hillery; Hill, Crystal E.; Hynd, George W.

    2009-01-01

    Limited research has been conducted on the structure of the pars triangularis (PT) in dyslexia despite functional neuroimaging research finding it may play a role in phonological processing. Furthermore, research to date has not examined PT size in ADHD even though the right inferior frontal region has been implicated in the disorder. Hence, one of the purposes of this study was to examine the structure of the PT in dyslexia and ADHD. The other purposes included examining the PT in relation to overall expressive language ability and in relation to several specific linguistic functions given language functioning often is affected in both dyslexia and ADHD. Participants included 50 children: 10 with dyslexia, 15 with comorbid dyslexia/ADHD, 15 with ADHD, and 10 controls. Using a 2 (dyslexia or not) X 2 (ADHD or not) MANCOVA, findings revealed PT length and shape were comparable between those with and without dyslexia. However, children with ADHD had smaller right PT lengths than those without ADHD, and right anterior ascending ramus length was related to attention problems in the total sample. In terms of linguistic functioning, presence of an extra sulcus in the left PT was related to poor expressive language ability. In those with adequate expressive language functioning, left PT length was related to phonological awareness, phonological short-term memory and rapid automatic naming (RAN). Right PT length was related to RAN and semantic processing. Further work on PT morphology in relation to ADHD and linguistic functioning is warranted. PMID:19356794

  16. Multi-scale photoacoustic remote sensing (PARS) (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Haji Reza, Parsin; Bell, Kevan; Shi, W.; Zemp, Roger J.

    2016-03-01

    We introduce a novel multi-scale photoacoustic remote sensing (PARS) imaging system. Our system can provide optical resolution details for superficial structures as well as acoustic resolution for deep-tissue imaging down to 5 cm, in a non-contact setting. PARS system does not require any contact with the sample or ultrasound coupling medium. The optical resolution PARS (OR-OARS) system uses optically focused pulsed excitation with optical detection of photoacoustic signatures using a long-coherence interrogation beam co-focused and co-scanned with the excitation spot. In the OR-PARS initial pressures are sampled right at their subsurface origin where acoustic pressures are largest. The Acoustic resolution PARS (AR-PARS) picks up the surface oscillation of the tissue caused by generated photoacoustic signal using a modified version of Michelson interferometry. By taking advantage of 4-meters polarization maintaining single-mode fiber and a green fiber laser we have generated a multi-wavelength source using stimulated Raman scattering. Remote functional imaging using this multi-wavelength excitation source and PARS detection mechanism has been demonstrated. The oxygen saturation estimations are shown for both phantom and in vivo studies. Images of blood vessel structures for an In vivo chicken embryo model is demonstrated. The Phantom studies indicates ~3µm and ~300µm lateral resolution for OR-PARS and AR-PARS respectively. To the best of our knowledge this is the first dual modality non-contact optical and acoustic resolution system used for in vivo imaging.

  17. Predicted PAR1 inhibitors from multiple computational methods

    NASA Astrophysics Data System (ADS)

    Wang, Ying; Liu, Jinfeng; Zhu, Tong; Zhang, Lujia; He, Xiao; Zhang, John Z. H.

    2016-08-01

    Multiple computational approaches are employed in order to find potentially strong binders of PAR1 from the two molecular databases: the Specs database containing more than 200,000 commercially available molecules and the traditional Chinese medicine (TCM) database. By combining the use of popular docking scoring functions together with detailed molecular dynamics simulation and protein-ligand free energy calculations, a total of fourteen molecules are found to be potentially strong binders of PAR1. The atomic details in protein-ligand interactions of these molecules with PAR1 are analyzed to help understand the binding mechanism which should be very useful in design of new drugs.

  18. In vitro seasonal variations of LH, FSH and prolactin secretion of the male rat are dependent on the maternal pineal gland.

    PubMed

    Díaz, E; Vázquez, N; Fernández, C; Jiménez, V; Esquifino, A; Díaz, B

    2012-01-17

    The maternal pineal gland is involved in the seasonal rhythms entrainment. We evaluate the effect of maternal pinealectomy (PIN-X), also melatonin replacement (PIN-X+MEL) during pregnancy on "in vitro" gonadotropins and prolactin seasonal variations. Male offspring from control, PIN-X and PIN-X+MEL mother Wistar rats were studied at 31 and 60 days of age. In vitro LH release from controls was season-dependent during prepubertal and pubertal periods showing reduced values in winter. The mother pineal gland seems to be important in the entrainment of seasonal variations of in vitro pituitary LH release, since altered secretion showing very high values was observed in summer. Melatonin treatment to PIN-X mothers partially restored the LH response. The effect of pinealectomy upon LH secretion disappears at the pubertal phase. A different pattern was observed for FSH release, without seasonal variations at 31 or at 60 days of age in control offspring, but pinealectomy to mothers or melatonin treatment resulted in seasonal variations. Seasonal influence was also observed in the prolactin pituitary release of controls. PIN-X mother offspring showed delayed seasonal variations at 31 and 60 days of age. The effect of maternal melatonin treatment during pregnancy was observed up to 60 days of age.

  19. Data in support of FSH induction of IRS-2 in human granulosa cells: Mapping the transcription factor binding sites in human IRS-2 promoter.

    PubMed

    Kaur, Surleen; Anjali, G; Bhardwaj, Priya; Taneja, Jyoti; Singh, Rita

    2016-03-01

    Insulin receptor substrate-2 (IRS-2) plays critical role in the regulation of various metabolic processes by insulin and IGF-1. The defects in its expression and/or function are linked to diseases like polycystic ovary syndrome (PCOS), insulin resistance and cancer. To predict the transcription factors (TFs) responsible for the regulation of human IRS-2 gene expression, the transcription factor binding sites (TFBS) and the corresponding TFs were investigated by analysis of IRS-2 promoter sequence using MatInspector Genomatix software (Cartharius et al., 2005 [1]). The ibid data is part of author׳s publication (Anjali et al., 2015 [2]) that explains Follicle stimulating hormone (FSH) mediated IRS-2 promoter activation in human granulosa cells and its importance in the pathophysiology of PCOS. Further analysis was carried out for binary interactions of TF regulatory genes in IRS-2 network using Cytoscape software tool and R-code. In this manuscript, we describe the methodology used for the identification of TFBSs in human IRS-2 promoter region and provide details on experimental procedures, analysis method, validation of data and also the raw files. The purpose of this article is to provide the data on all TFBSs in the promoter region of human IRS-2 gene as it has the potential for prediction of the regulation of IRS-2 gene in normal or diseased cells from patients with metabolic disorders and cancer.

  20. The effect of androgens on ovarian follicle maturation: Dihydrotestosterone suppress FSH-stimulated granulosa cell proliferation by upregulating PPARγ-dependent PTEN expression.

    PubMed

    Chen, Mei-Jou; Chou, Chia-Hung; Chen, Shee-Uan; Yang, Wei-Shiung; Yang, Yu-Shih; Ho, Hong-Nerng

    2015-12-17

    Intraovarian hyperandrogenism is one of the determining factors of follicular arrest in women with polycystic ovary syndrome (PCOS). Using androgenized rat models, we investigated the effects of androgens on metabolism, as well as on factors involved in follicular arrest and the reduced number of estrus cycles. The dihydrotestosterone (DHT)-treated rats had fewer estrus cycles, higher numbers of large arrested follicles and an increased in body weight gain compared with the dehydroepiandrostenedione (DHEA)- and placebo-treated rats. In cultured rat granulosa cells, DHT suppressed follicle stimulating hormone (FSH)-induced granulosa cell proliferation and increased the accumulation of cells in the G2/M phase. DHT decreased phosphorylated Akt (p-Akt) and cyclin D1 levels through increasing PTEN. DHT-promoted PTEN expression was regulated by peroxisome proliferator-activated receptor gamma (PPARγ) in granulosa cells. Meanwhile, in the large follicles of the DHT-treated rats, the expressions of PPARγ and PTEN were higher, but the expression of p-Akt and proliferating cell nuclear antigen (PCNA) were lower. Conclusively, DHT and DHEA produced differential effects on metabolism in prepubertal female rats like clinical manifestations of women with PCOS. DHT treatment may affect ovarian follicular maturation by altering granulosa cell proliferation through the regulation of enhancing PPARγ dependent PTEN/p-Akt expression in the granulosa cells.

  1. The effect of androgens on ovarian follicle maturation: Dihydrotestosterone suppress FSH-stimulated granulosa cell proliferation by upregulating PPARγ-dependent PTEN expression.

    PubMed Central

    Chen, Mei-Jou; Chou, Chia-Hung; Chen, Shee-Uan; Yang, Wei-Shiung; Yang, Yu-Shih; Ho, Hong-Nerng

    2015-01-01

    Intraovarian hyperandrogenism is one of the determining factors of follicular arrest in women with polycystic ovary syndrome (PCOS). Using androgenized rat models, we investigated the effects of androgens on metabolism, as well as on factors involved in follicular arrest and the reduced number of estrus cycles. The dihydrotestosterone (DHT)-treated rats had fewer estrus cycles, higher numbers of large arrested follicles and an increased in body weight gain compared with the dehydroepiandrostenedione (DHEA)- and placebo-treated rats. In cultured rat granulosa cells, DHT suppressed follicle stimulating hormone (FSH)-induced granulosa cell proliferation and increased the accumulation of cells in the G2/M phase. DHT decreased phosphorylated Akt (p-Akt) and cyclin D1 levels through increasing PTEN. DHT-promoted PTEN expression was regulated by peroxisome proliferator-activated receptor gamma (PPARγ) in granulosa cells. Meanwhile, in the large follicles of the DHT-treated rats, the expressions of PPARγ and PTEN were higher, but the expression of p-Akt and proliferating cell nuclear antigen (PCNA) were lower. Conclusively, DHT and DHEA produced differential effects on metabolism in prepubertal female rats like clinical manifestations of women with PCOS. DHT treatment may affect ovarian follicular maturation by altering granulosa cell proliferation through the regulation of enhancing PPARγ dependent PTEN/p-Akt expression in the granulosa cells. PMID:26674985

  2. View from northeast to southwest of PAR site sentry station; ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View from northeast to southwest of PAR site sentry station; formerly the bachelor's enlisted men's quarter (BEQ) - Stanley R. Mickelsen Safeguard Complex, Sentry Station, North of Second Avenue & West of Electrical Switch Station No. 2, Nekoma, Cavalier County, ND

  3. PARS: Programs for Analysis and Resizing of Structures, user manual

    NASA Technical Reports Server (NTRS)

    Haftka, R. T.; Prasad, B.; Tsach, U.

    1979-01-01

    PARS processors and their use, flutter analysis, sensitivity analysis for stresses, and resizing are presented. Design variable definition and interface with finite element model, static constraints and their derivatives, flutter derivatives, and optimization are discussed.

  4. View from southwest to northeast of PAR site fresh water ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View from southwest to northeast of PAR site fresh water pump house - Stanley R. Mickelsen Safeguard Complex, Fresh Water Pump House, In Limited Access Area, on Patrol Road next to Open Storage Reservoir No. 736, Nekoma, Cavalier County, ND

  5. Croissance epitaxiale de GaAs sur substrats de Ge par epitaxie par faisceaux chimiques

    NASA Astrophysics Data System (ADS)

    Belanger, Simon

    La situation energetique et les enjeux environnementaux auxquels la societe est confrontee entrainent un interet grandissant pour la production d'electricite a partir de l'energie solaire. Parmi les technologies actuellement disponibles, la filiere du photovoltaique a concentrateur solaire (CPV pour concentrator photovoltaics) possede un rendement superieur et mi potentiel interessant a condition que ses couts de production soient competitifs. La methode d'epitaxie par faisceaux chimiques (CBE pour chemical beam epitaxy) possede plusieurs caracteristiques qui la rendent interessante pour la production a grande echelle de cellules photovoltaiques a jonctions multiples a base de semi-conducteurs III-V. Ce type de cellule possede la meilleure efficacite atteinte a ce jour et est utilise sur les satellites et les systemes photovoltaiques a concentrateur solaire (CPV) les plus efficaces. Une des principales forces de la technique CBE se trouve dans son potentiel d'efficacite d'utilisation des materiaux source qui est superieur a celui de la technique d'epitaxie qui est couramment utilisee pour la production a grande echelle de ces cellules. Ce memoire de maitrise presente les travaux effectues dans le but d'evaluer le potentiel de la technique CBE pour realiser la croissance de couches de GaAs sur des substrats de Ge. Cette croissance constitue la premiere etape de fabrication de nombreux modeles de cellules solaires a haute performance decrites plus haut. La realisation de ce projet a necessite le developpement d'un procede de preparation de surface pour les substrats de germanium, la realisation de nombreuses sceances de croissance epitaxiale et la caracterisation des materiaux obtenus par microscopie optique, microscopie a force atomique (AFM), diffraction des rayons-X a haute resolution (HRXRD), microscopie electronique a transmission (TEM), photoluminescence a basse temperature (LTPL) et spectrometrie de masse des ions secondaires (SIMS). Les experiences ont permis

  6. Molecular Mechanisms of Par-4-Induced Apoptosis in Prostate Cancer

    DTIC Science & Technology

    2007-05-01

    Sambrook J, Fritsch EF, Maniatis T. (1989). Molecular Cloning : A Laboratory Manual (Cold Spring Harbor, New York: Cold Spring Harbor Laboratory...AD_________________ Award Number: W81XWH-05-1-0622 TITLE: Molecular Mechanisms of Par-4-Induced...SUBTITLE 5a. CONTRACT NUMBER Molecular Mechanisms of Par-4-Induced Apoptosis in Prostate Cancer 5b. GRANT NUMBER W81XWH-05-1-0622 5c. PROGRAM

  7. Multiple binding sites for nuclear proteins of the anterior pituitary are located in the 5'-flanking region of the porcine follicle-stimulating hormone (FSH) beta-subunit gene.

    PubMed

    Kato, Y; Tomizawa, K; Kato, T

    1999-12-20

    Gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), are synthesized specifically in the gonadotropes of the anterior pituitary. The aim of this study was to investigate nuclear factors that bind specifically to the porcine FSH beta-subunit gene. We examined nuclear protein binding to 2.75 kilobase pairs (kbp) of DNA adjacent to the porcine FSH beta-subunit gene: about 2.32 kbp of upstream DNA and 0.43 kbp of downstream DNA. The upstream region contains only TATA box, CACCC element, and some imperfect sequences of cAMP-responsive element, activator protein-1 binding site, and activator protein-2 binding site. Gel mobility shift assay using nuclear proteins extracted from the porcine anterior pituitary revealed that the proteins bound to a limited region of DNA, 107 bp long (designated as Fd2), located about -800 bp upstream from the transcription initiation site. Competitive binding assays demonstrated that the protein binding was sequence specific; the addition of excess amounts of several putative regulatory sequences and plasmid (non-homologous) DNA fragments did not reduce the binding. Furthermore, all five subfragments of Fd2 were also bound by the pituitary nuclear proteins, showing that the entire region of Fd2 is involved in this interaction. Southwestern blotting demonstrated that at least seven protein species of 110, 98, 78, 63, 52, 42, and 35 kDa recognize Fd2. Nuclear proteins from several other porcine tissues were also able to bind to the Fd2 fragment but the gel shift patterns were different and the bindings were weak, although only the cerebellum showed a pattern of binding that was similar to that of the anterior pituitary. These data suggest that multiple proteins of the anterior pituitary recognize a specific region of the porcine FSH beta-subunit gene.

  8. Reduction of the amplitude of preovulatory LH and FSH surges and of the amplitude of the in vitro GnRH-induced LH release by substance P. Reversal of the effect by RP 67580.

    PubMed

    Duval, P; Lenoir, V; Garret, C; Kerdelhue, B

    1996-01-01

    The effects of Substance P (SP) and of a specific nonpeptide antagonist of the NK1 receptor (RP 67580) on preovulatory gonadotropin surges and on the in vitro GnRH induced LH surge were investigated in cycling female rats. A subcutaneous injection of SP (0.5 mg/kg body weight) at 12.00 h on the proestrous day significantly decreased the LH preovulatory surge. RP 67580 (1.5 mg/kg) significantly increased this LH surge. However, when SP and its antagonist were administered together, LH preovulatory surge was normal. The FSH preovulatory surge at 18.00 h and also at 19.00 h was significantly inhibited by SP administration. RP 67580 alone had no effect on the FSH preovulatory surge. When SP and RP 67580 were both administered, there was no diminution of FSH plasma levels at 18.00 h and 19.00 h. In vitro perifusions of anterior pituitaries showed that SP inhibits GnRH-induced LH release via a NK1 receptor. Thus, SP inhibits the LH preovulatory surge via NK1 receptors and SP modulation of gonadotropin surges is at least partly exerted at the pituitary.

  9. Conjugated linoleic acids attenuate FSH- and IGF1-stimulated cell proliferation; IGF1, GATA4, and aromatase expression; and estradiol-17β production in buffalo granulosa cells involving PPARγ, PTEN, and PI3K/Akt.

    PubMed

    Sharma, Isha; Singh, Dheer

    2012-09-01

    Conjugated linoleic acid (CLA) has drawn much interest in last two decades in the area ranging from anticancer activity to obesity. A number of research papers have been published recently with regard to CLA's additional biological functions as reproductive benefits. However, not much is known how this mixture of isomeric compounds mediates its beneficial effects particularly on fertility. In this study, we demonstrated the cross talk between downstream signaling of CLA and important hormone regulators of endocrine system, i.e. FSH and IGF1, on buffalo granulosa cell function (proliferation and steroidogenesis). Experiments were performed in primary serum-free buffalo granulosa cell culture, where cells were incubated with CLA in combination with FSH (25 ng/ml) and IGF1 (50  ng/ml). Results showed that 10 μM CLA inhibits FSH- and IGF1-induced granulosa cell proliferation; aromatase, GATA4, and IGF1 mRNA; and estradiol-17β production. Western blot analysis of total cell lysates revealed that CLA intervenes the IGF1 signaling by decreasing p-Akt. In addition, CLA was found to upregulate peroxisome proliferator-activated receptor-gamma (PPARG) and phosphatase and tensin homolog (PTEN) level in granulosa cells. Further study using PPARG- and PTEN-specific inhibitors supports the potential role of CLA in granulosa cell proliferation and steroidogenesis involving PPARG, PTEN, and PI3K/Akt pathway.

  10. Stabilization of Cell Polarity by the C. elegans RING Protein PAR-2

    PubMed Central

    Hao, Yingsong; Boyd, Lynn; Seydoux, Geraldine

    2006-01-01

    Summary Asymmetric localization of PAR proteins is a hallmark of polarized cells, but the mechanisms that create PAR asymmetry are not well understood. In the C. elegans zygote, PAR asymmetry is initiated by a transient actomyosin contraction, which sweeps the PAR-3/PAR-6/PKC-3 complex toward the anterior pole of the egg. The RING finger protein PAR-2 accumulates in a complementary pattern in the posterior cortex. Here we present evidence that PAR-2 participates in a feedback loop to stabilize polarity. PAR-2 is a target of the PKC-3 kinase and is excluded from the anterior cortex by PKC-3-dependent phosphorylation. The RING domain of PAR-2 is required to overcome inhibition by PKC-3 and stabilize PAR-2 on the posterior cortex. Cortical PAR-2 in turn prevents PAR-3/PAR-6/PKC-3 from returning to the posterior, in a PAR-1- and PAR-5-dependent manner. Our findings suggest that reciprocal inhibitory interactions among PAR proteins stabilize polarity by reinforcing an initial asymmetry in PKC-3. PMID:16459299

  11. Pars Planitis: Epidemiology, Clinical Characteristics, Management and Visual Prognosis

    PubMed Central

    Ozdal, Pinar Cakar; Berker, Nilufer; Tugal-Tutkun, Ilknur

    2015-01-01

    Pars planitis is an idiopathic chronic intermediate uveitis which predominantly affects children and adolescents, and accounts for 5-26.7% of pediatric uveitis. Although an autoimmune process with a genetic predisposition has been suggested, its etiology still remains unknown. The most common presenting symptoms are floaters and blurred vision. Diffuse vitreous cells, haze, snowballs and snowbanks are typical findings of pars planitis. Peripheral retinal vasculitis, optic disc edema and anterior segment inflammation are other well-known findings. Although pars planitis is known to be a benign form of uveitis in most cases, it may become a potentially blinding disease due to complications including cataract, cystoid macular edema, vitreous opacities and optic disc edema. Cystoid macular edema is the most common cause of visual morbidity. Band keratopathy, epiretinal membrane formation, vitreous condensation, neovascularizations, vitreous hemorrhage, retinal detachment, cyclitic membranes, glaucoma and amblyopia may develop as a consequence of the chronic course of the disease. Exclusion of infectious and non-infectious causes which may present with intermediate uveitis is of utmost importance before starting treatment. Treatment of pars planitis has been a controversial issue. There is no consensus specifically for treatment of cases with minimal inflammation and relatively good visual acuity. However, current experience shows that pars planitis may cause severe inflammation and needs an aggressive treatment. A stepladder approach including corticosteroids, immunosupressive agents, anti-tumor necrosis factor-alpha and pars plana vitrectomy and/or laser photocoagulation is the most commonly used method for treatment of pars planitis. Adequate control of inflammation and prompt detection of associated complications are crucial in order to improve the overall prognosis of the disease. PMID:27051493

  12. Par Pond vegetation status Summer 1995 -- June survey descriptive summary

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1995-06-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the shoreline aquatic plant communities in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level, indicated that much of the original plant communities and the intermediate shoreline communities present on the exposed sediments have been lost. The extensive old-field and emergent marsh communities that were present on the exposed shoreline during the drawdown have been flooded and much of the pre-drawdown Par Pond aquatic plant communities have not had sufficient time for re-establishment. The shoreline does, however, have extensive beds of maidencane which extend from the shoreline margin to areas as deep as 2 and perhaps 3 meters. Scattered individual plants of lotus and watershield are common and may indicate likely directions of future wetland development in Par Pond. In addition, within isolated coves, which apparently received ground water seepage and/or stream surface flows during the period of the Par Pond draw down, extensive beds of waterlilies and spike rush are common. Invasion of willow and red maple occurred along the lake shoreline as well. Although not absent from this survey, evidence of the extensive redevelopment of the large cattail and eel grass beds was not observed in this first survey of Par Pond. Future surveys during the growing seasons of 1995, 1996, and 1997 along with the evaluation of satellite date to map the areal extent of the macrophyte beds of Par Pond are planned.

  13. Is assessment of anti-Müllerian hormone and/or antral follicle count useful in the prediction of ovarian response in expected normal responders treated with a fixed dose of recombinant FSH and GnRH antagonists? A prospective observational study.

    PubMed

    Ganidou, Maria A; Kolibianakis, Efstratios M; Venetis, Christos A; Gerou, Spiros; Makedos, Georgios A; Klearchou, Nikolaos; Tarlatzis, Basil C

    2014-11-01

    The purpose of this prospective observational study was to evaluate whether the assessment of AMH and AFC is useful in the prediction of ovarian response in expected normal responders treated with a fixed dose of recombinant FSH (rec-FSH) and GnRH antagonists. A base model including age and basal FSH as independent predictors of COCs could explain 15% of the variance observed in the number of COCs retrieved (p = 0.002). The addition of AFC did not increase significantly the predictive ability of the above model, whereas the addition of AMH increased the performance of the base model by 13% (p < 0.001). Logistic regression analysis showed that only when AMH was added to the base model, including age and FSH, its predictive capacity for high ovarian response was statistically significant (F-test: p = 0.001; c-statistic: 0.80, 95% CI: 0.70-0.88), but this was not the case for poor ovarian response. In conclusion, the addition of AMH, but not of AFC, to a model including female age and basal FSH, is useful in the prediction of ovarian response in expected normal responders treated with a fixed dose of recombinant FSH and GnRH antagonists.

  14. Par Pond vegetation status Summer 1995 -- September survey descriptive summary

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1995-09-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the emergent shoreline aquatic plant communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level and continued with this mid-September survey. Communities similar to the pre-drawdown Par Pond aquatic plant communities are becoming re-established; especially, beds of maidencane, lotus, waterlily, and watershield are now extensive and well established. Cattail occurrence continues to increase, but large beds common to Par Pond prior to the drawdown have not formed. Future surveys during the late growing seasons of 1995, and throughout 1996 and 1997, along with the evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned.

  15. Par Pond vegetation status Summer 1995 -- October survey descriptive summary

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1995-11-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the emergent shoreline aquatic plant communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level and continued with this late October survey. Communities similar to the pre-drawdown Par Pond aquatic plant communities are becoming re-established; especially, beds of maiden cane, lotus, waterlily, and watershield are now extensive and well established. Cattail occurrence continues to increase, but large beds common to Par Pond prior to the drawdown have not formed. Future surveys throughout 1996 and 1997, along with the continued evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned.

  16. FSH — EDRN Public Portal

    Cancer.gov

    Follicle stimulating hormone, a heterodimer glycoprotein of a common alpha chain and a unique beta chain which confers biological specificity to thyrotropin, lutropin, follitropin and gonadotropin, stimulates development of follicle and spermatogenesis in the reproductive organs. In conjunction with luteinizing hormone, follicle-stimulating hormone induces egg and sperm production. Defects in FSHB are a cause of isolated follicle-stimulating hormone deficiency. Selective follicle-stimulating hormone deficiency is an uncommon cause of infertility, producing amenorrhea and hypogonadism in women and oligo or azoospermia with normal testosterone levels in normally virilised men. FSHB belongs to the glycoprotein hormones subunit beta family. There are two transcript variants from alternative splicing that each encode the same protein.

  17. Couches Minces de Titanate de Baryum Par Depot Organometallique

    NASA Astrophysics Data System (ADS)

    Ousi Benomar, Wahib

    1993-01-01

    Nous avons demontre la possibilite de realiser des couches minces de titanate de baryum par depot organometallique. Les films sont obtenus apres dissolution d'organometalliques choisis dans un solvant et une cuisson a une temperature determinee par thermogravimetrie. Apres un second traitement thermique a des temperatures plus elevees, les echantillons presentent une structure polycristalline tetragonale; les cristallites sont observes par microscopie electronique a balayage. La mesure de la constante dielectrique a permis de mettre en evidence une transition de phase de la structure tetragonale a la structure cubique a une temperature d'environ 125^circC. Les mesures d'indice ont ete effectuees. On note une augmentation de l'indice de refraction des films avec la temperature indiquant une meilleure densification des films. Nous avons aussi montre qu'il etait possible d'utiliser ce materiau en tant que guide d'onde optique pour pouvoir exploiter ses proprietes electrooptiques dans l'avenir.

  18. Protease-activated receptor-2 (PAR2) in cardiovascular system.

    PubMed

    Bucci, Mariarosaria; Roviezzo, Fiorentina; Cirino, Giuseppe

    2005-10-01

    Vascular system is constituted by a complex and articulate network, e.g. arteries, arterioles, venules and veins, that requires a high degree of coordination between different elemental cell types. Proteinase-activated receptors (PARs) constitute a recent described family of 7-transmembrane G protein-coupled receptors that are activated by proteolysis. In recent years several evidence have been accumulated for an involvement of this receptor in the response to endothelial injury in vitro and in vivo experimental settings suggesting a role for PAR2 in the pathophysiology of cardiovascular system. This review will deal with the role of PAR2 receptor in the cardiovascular system analyzing both in vivo and in vitro published data. In particular this review will deal with the role of this receptor in vascular reactivity, ischemia/reperfusion injury, coronary atherosclerotic lesions and angiogenesis.

  19. Both PHYTOCHROME RAPIDLY REGULATED1 (PAR1) and PAR2 Promote Seedling Photomorphogenesis in Multiple Light Signaling Pathways1[C][W][OPEN

    PubMed Central

    Zhou, Peng; Song, Meifang; Yang, Qinghua; Su, Liang; Hou, Pei; Guo, Lin; Zheng, Xu; Xi, Yulin; Meng, Fanhua; Xiao, Yang; Yang, Li; Yang, Jianping

    2014-01-01

    Arabidopsis (Arabidopsis thaliana) seedlings undergo photomorphogenesis in the light and etiolation in the dark. Light-activated photoreceptors transduce the light signals through a series of photomorphogenesis promoting or repressing factors to modulate many developmental processes in plants, such as photomorphogenesis and shade avoidance. CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) is a conserved RING finger E3 ubiquitin ligase, which mediates degradation of several photomorphogenesis promoting factors, including ELONGATED HYPOCOTYL5 (HY5) and LONG HYPOCOTYL IN FAR-RED1 (HFR1), through a 26S proteasome-dependent pathway. PHYTOCHROME RAPIDLY REGULATED1 (PAR1) was first detected as an early repressed gene in both phytochrome A (phyA)-mediated far-red and phyB-mediated red signaling pathways, and subsequent studies showed that both PAR1 and PAR2 are negative factors of shade avoidance in Arabidopsis. However, the role of PAR1 and PAR2 in seedling deetiolation, and their relationships with other photomorphogenesis promoting and repressing factors are largely unknown. Here, we confirmed that both PAR1 and PAR2 redundantly enhance seedling deetiolation in multiple photoreceptor signaling pathways. Their transcript abundances are repressed by phyA, phyB, and cryptochrome1 under far-red, red, and blue light conditions, respectively. Both PAR1 and PAR2 act downstream of COP1, and COP1 mediates the degradation of PAR1 and PAR2 through the 26S proteasome pathway. Both PAR1 and PAR2 act in a separate pathway from HY5 and HFR1 under different light conditions, except for sharing in the same pathway with HFR1 under far-red light. Together, our results substantiate that PAR1 and PAR2 are positive factors functioning in multiple photoreceptor signaling pathways during seedling deetiolation. PMID:24335334

  20. Traumatisme de la main par injection a haute pression

    PubMed Central

    Mabchoure, K.; Diouri, M.; Bahechar, N.; Chlihi, A.

    2016-01-01

    Summary Les traumatismes de la main par injection à haute pression sont des accidents relativement rares et souvent mal connus par le praticien. Les lésions qui dépendent du produit injecté et du site d’injection sont pourvoyeuses de séquelles esthétiques et fonctionnelles lourdes. Le traitement repose sur la chirurgie, l’antibiothérapie et la rééducation précoce et spécifique. Nous rapportons notre expérience ainsi qu’une revue de la littérature. PMID:27857654

  1. PAR-3 oligomerization may provide an actin-independent mechanism to maintain distinct par protein domains in the early Caenorhabditis elegans embryo.

    PubMed

    Dawes, Adriana T; Munro, Edwin M

    2011-09-21

    Par proteins establish discrete intracellular spatial domains to polarize many different cell types. In the single-cell embryo of the nematode worm Caenorhabditis elegans, the segregation of Par proteins is crucial for proper division and cell fate specification. Actomyosin-based cortical flows drive the initial formation of anterior and posterior Par domains, but cortical actin is not required for the maintenance of these domains. Here we develop a model of interactions between the Par proteins that includes both mutual inhibition and PAR-3 oligomerization. We show that this model gives rise to a bistable switch mechanism, allowing the Par proteins to occupy distinct anterior and posterior domains seen in the early C. elegans embryo, independent of dynamics or asymmetries in the actin cortex. The model predicts a sharp loss of cortical Par protein asymmetries during gradual depletion of the Par protein PAR-6, and we confirm this prediction experimentally. Together, these results suggest both mutual inhibition and PAR-3 oligomerization are sufficient to maintain distinct Par protein domains in the early C. elegans embryo.

  2. Regulation of expression of Sertoli cell glucose transporters 1 and 3 by FSH, IL1 beta, and bFGF at two different time-points in pubertal development.

    PubMed

    Galardo, María Noel; Riera, María Fernanda; Pellizzari, Eliana Herminia; Chemes, Héctor Edgardo; Venara, Marcela Cristina; Cigorraga, Selva Beatriz; Meroni, Silvina Beatriz

    2008-11-01

    Sertoli cells are necessary to provide adequate levels of lactate for germ cell development. Lactate production is hormonally regulated by follicle-stimulating hormone (FSH) and by a large set of intratesticular regulators such as interleukin-1 beta (IL1 beta) and basic fibroblast growth factor (bFGF). Little is known regarding the critical step in the production of this metabolite, viz., the entrance of glucose into the cell as mediated by GLUTs. The aim of the present study was to investigate the expression of the glucose transporters GLUT1 and GLUT3 and its possible regulation by FSH, IL1 beta, and bFGF in Sertoli cells at two different time-points in sexual development. Sertoli cells retaining the ability to undergo mitosis (obtained from 8-day-old rats) and in the process of terminal differentiation (obtained from 20-day-old rats) were examined. Testicular tissue sections and Sertoli cell monolayers obtained from 8- and 20-day-old rats showed positive immunostaining for GLUT1 and GLUT3 proteins. GLUT1 and GLUT3 mRNA levels were detected at the two ages analyzed. Treatment of Sertoli cells obtained from 8- and 20-day-old rats with FSH, IL1 beta, and bFGF for various periods of time (12, 24, and 48 h) increased GLUT1 without changing GLUT3 mRNA levels. Our results thus show that Sertoli cells express GLUT1 and GLUT3 throughout pubertal development, and that, in Sertoli cells, only GLUT1 is regulated by hormones during pubertal development. Hormonal regulation of GLUT1 expression and consequently glucose uptake and lactate production may be a key molecular event in the regulation of spermatogenesis by hormones.

  3. Effects of oestradiol-17 beta, progesterone or bovine follicular fluid on the plasma concentrations of FSH and LH in ovariectomized Booroola ewes which were homozygous carriers or non-carriers of a fecundity gene.

    PubMed

    McNatty, K P; Hudson, N L; Collins, F; Fisher, M; Health, D A; Henderson, K M

    1989-11-01

    The plasma concentrations of FSH and LH were measured in ovariectomized Booroola FF and ++ ewes before and after treatment with subcutaneous implants of oestradiol-17 beta (0, 2 or 8 cm Silastic capsules; 5 ewes/genotype per dose) or progesterone (0, 1 or 3 Silastic envelopes; 5 ewes/genotype per dose) or subcutaneous injections of steroid-free bovine follicular fluid (bFF; 0, 0.5, 1.0, 2.5 or 5 ml; 4 ewes/genotype per dose). During the first 50 h after implantation of oestradiol or progesterone, or the first 24 h after bFF treatment, the FSH and LH concentrations in plasma were not different between the genotypes although there were significant effects of the steriods and bFF with respect to dose (P less than 0.05). At 6 days after steroid implantation, no gene-specific effects were noted for the plasma concentrations of FSH although significant effects of dose of oestradiol (P less than 0.01) but not progesterone were noted. Also at 6 days after steroid implantation, no gene-specific differences in the pulsatile patterns (i.e. peak frequency or amplitude) of plasma LH concentrations were noted although there were significant effects of steriod dose (P less than 0.05) on frequency and/or amplitude. It is concluded that the higher ovulation-rate in FF than ++ Booroola ewes is unlikely to be due to gene-specific differences in the sensitivity of the hypothalamic-pituitary axis to ovarian hormones.

  4. BOREAS RSS-10 TOMS Circumpolar One-Degree PAR Images

    NASA Technical Reports Server (NTRS)

    Dye, Dennis G.; Holben, Brent; Nickeson, Jaime (Editor); Hall, Forrest G. (Editor); Smith, David E. (Technical Monitor)

    2000-01-01

    The Boreal Ecosystem-Atmosphere Study (BOREAS) Remote Sensing Science (RSS)-10 team investigated the magnitude of daily, seasonal, and yearly variations of Photosynthetically Active Radiation (PAR) from ground and satellite observations. This data set contains satellite estimates of surface-incident PAR (400-700 nm, MJ/sq m) at one-degree spatial resolution. The spatial coverage is circumpolar from latitudes of 41 to 66 degrees north. The temporal coverage is from May through September for years 1979 through 1989. Eleven-year statistics are also provided: (1) mean, (2) standard deviation, and (3) coefficient of variation for 1979-89. The PAR estimates were derived from the global gridded ultraviolet reflectivity data product (average of 360, 380 nm) from the Nimbus-7 Total Ozone Mapping Spectrometer (TOMS). Image mask data are provided for identifying the boreal forest zone, and ocean/land and snow/ice-covered areas. The data are available as binary image format data files. The PAR data are available from the Earth Observing System Data and Information System (EOSDIS) Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC). The data files are available on a CD-ROM (see document number 20010000884).

  5. Par Pond vegetation status summer 1995 - July survey descriptive summary

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1995-07-01

    A survey of the emergent shoreline aquatic plant, communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet (61 meters) above mean sea level, and continued with this July survey. Aquatic plant communities, similar to the pre-drawdown Par Pond communities, are becoming reestablished. Beds of maidencane (Panicum hemitomon), lotus (Nelumbo lutea), water lily (Nymphaea odorata), and watershield (Brasenia schreberi) are now extensive and well established. In addition, within isolated coves, extensive beds of water lilies and spike-rush (Eleocharis sp.) are common. Cattail occurrence has increased since refill, but large beds common to Par Pond prior to the drawdown have not formed. Invasion of willow (Salix sp.) and red maple (Acer rubrum) occurred along the lake shoreline during drawdown. The red maples along the present shoreline are beginning to show evidence of stress and mortality from flooding over the past four months. Some of the willows appear to be stressed as well. The loblolly pines (Pinus taeda), which were flooded in all but the shallow shoreline areas, are now dead. Future surveys are planned for the growing seasons of 1995, 1996, and 1997, along with the evaluation of satellite data for mapping the areal extent of the macrophyte beds of Par Pond.

  6. Radiological impact of Par Pond drawdown from liquid effluent pathways

    SciTech Connect

    Carlton, W.H.; Hamby, D.M.

    1991-10-25

    The water level of Par Pond has been lowered over the past several months to reduce the effects in the event of catastrophic dam failure while assessing the condition of the dam and determining if repairs are necessary. In lowering the level of Par Pond, 60 billion liters of water containing low levels of tritium and cesium-137 were discharged to several onsite streams. SRS surface streams flow to the Savannah River. An assessment made to determine the total amount of tritium and Cs-137 discharged and to estimate the consequences to downstream Savannah River users. It is estimated that a total of 160 curies of tritium were displaced from Par Pond to the Savannah River between June 28, 1991 and September 19, 1991. This release could hypothetically result in a maximum individual dose of 3. 2{times}10{sup {minus}4} mrem and a total (80-km and drinking water populations) population dose of 1.4{times}10{sup {minus}2} person-rem. Likewise, a maximum individual dose of 5.0{times}10{sup {minus}2} mrem and a total population dose of 1.7{times}10{sup {minus}1} person- rem are predicted as a result of an estimated 0.21 curies of Cs-137 being discharged from Par Pond to the Savannah River.

  7. Are You Up to PAR? (Program Administrative Review).

    ERIC Educational Resources Information Center

    Southwest Regional Resource Center, Salt Lake City, UT.

    The document focuses on the workings of PAR (Program Administrative Review), a method by which local education agencies (LEAs) and state operated programs (SOPs) in Utah can conduct ongoing self-evaluation and identify areas where additional efforts are needed to improve the quality of programs and services for handicapped children. It is…

  8. Promiscuous stimulation of ParF protein polymerization by heterogeneous centromere binding factors.

    PubMed

    Machón, Cristina; Fothergill, Timothy J G; Barillà, Daniela; Hayes, Finbarr

    2007-11-16

    The segrosome is the nucleoprotein complex that mediates accurate segregation of bacterial plasmids. The segrosome of plasmid TP228 comprises ParF and ParG proteins that assemble on the parH centromere. ParF, which exemplifies one clade of the ubiquitous ParA superfamily of segregation proteins, polymerizes extensively in response to ATP binding. Polymerization is modulated by the ParG centromere binding factor (CBF). The segrosomes of plasmids pTAR, pVT745 and pB171 include ParA homologues of the ParF subgroup, as well as diverse homodimeric CBFs with no primary sequence similarity to ParG, or each other. Centromere binding by these analogues is largely specific. Here, we establish that the ParF homologues of pTAR and pB171 filament modestly with ATP, and that nucleotide hydrolysis is not required for this polymerization, which is more prodigious when the cognate CBF is also present. By contrast, the ParF homologue of plasmid pVT745 did not respond appreciably to ATP alone, but polymerized extensively in the presence of both its cognate CBF and ATP. The co-factors also stimulated nucleotide-independent polymerization of cognate ParF proteins. Moreover, apart from the CBF of pTAR, the disparate ParG analogues promoted polymerization of non-cognate ParF proteins suggesting that filamentation of the ParF proteins is enhanced by a common mechanism. Like ParG, the co-factors may be modular, possessing a centromere-specific interaction domain linked to a flexible region containing determinants that promiscuously stimulate ParF polymerization. The CBFs appear to function as bacterial analogues of formins, microtubule-associated proteins or related ancillary factors that regulate eucaryotic cytoskeletal dynamics.

  9. Re-Signifying Participatory Action Research (PAR) in Higher Education: What Does "P" Stand for in PAR?

    ERIC Educational Resources Information Center

    Santos, Doris

    2016-01-01

    While carrying out a study aimed at understanding the contribution of participatory action research (PAR) to the political realm in contemporary higher education, a problematic situation was found when doing a literature review in the field of action research. This problem concerns the intermittent appearance of the "participatory"…

  10. Targeting a Proteinase-Activated Receptor 4 (PAR4) Carboxyl Terminal Motif to Regulate Platelet Function.

    PubMed

    Ramachandran, Rithwik; Mihara, Koichiro; Thibeault, Pierre; Vanderboor, Christina M; Petri, Björn; Saifeddine, Mahmoud; Bouvier, Michel; Hollenberg, Morley D

    2017-04-01

    Thrombin initiates human platelet aggregation by coordinately activating proteinase-activated receptors (PARs) 1 and 4. However, targeting PAR1 with an orthosteric-tethered ligand binding-site antagonist results in bleeding, possibly owing to the important role of PAR1 activation on cells other than platelets. Because of its more restricted tissue expression profile, we have therefore turned to PAR4 as an antiplatelet target. We have identified an intracellular PAR4 C-terminal motif that regulates calcium signaling and β-arrestin interactions. By disrupting this PAR4 calcium/β-arrestin signaling process with a novel cell-penetrating peptide, we were able to inhibit both thrombin-triggered platelet aggregation in vitro and clot consolidation in vivo. We suggest that targeting PAR4 represents an attractive alternative to blocking PAR1 for antiplatelet therapy in humans.

  11. ParCAT: A Parallel Climate Analysis Toolkit

    NASA Astrophysics Data System (ADS)

    Haugen, B.; Smith, B.; Steed, C.; Ricciuto, D. M.; Thornton, P. E.; Shipman, G.

    2012-12-01

    Climate science has employed increasingly complex models and simulations to analyze the past and predict the future of our climate. The size and dimensionality of climate simulation data has been growing with the complexity of the models. This growth in data is creating a widening gap between the data being produced and the tools necessary to analyze large, high dimensional data sets. With single run data sets increasing into 10's, 100's and even 1000's of gigabytes, parallel computing tools are becoming a necessity in order to analyze and compare climate simulation data. The Parallel Climate Analysis Toolkit (ParCAT) provides basic tools that efficiently use parallel computing techniques to narrow the gap between data set size and analysis tools. ParCAT was created as a collaborative effort between climate scientists and computer scientists in order to provide efficient parallel implementations of the computing tools that are of use to climate scientists. Some of the basic functionalities included in the toolkit are the ability to compute spatio-temporal means and variances, differences between two runs and histograms of the values in a data set. ParCAT is designed to facilitate the "heavy lifting" that is required for large, multidimensional data sets. The toolkit does not focus on performing the final visualizations and presentation of results but rather, reducing large data sets to smaller, more manageable summaries. The output from ParCAT is provided in commonly used file formats (NetCDF, CSV, ASCII) to allow for simple integration with other tools. The toolkit is currently implemented as a command line utility, but will likely also provide a C library for developers interested in tighter software integration. Elements of the toolkit are already being incorporated into projects such as UV-CDAT and CMDX. There is also an effort underway to implement portions of the CCSM Land Model Diagnostics package using ParCAT in conjunction with Python and gnuplot. Par

  12. Is There an "F" in Your PAR? Understanding, Teaching and Doing Action Research

    ERIC Educational Resources Information Center

    Lorenzetti, Liza; Walsh, Christine Ann

    2014-01-01

    Participatory Action Research (PAR) is increasingly recognized within academic research and pedagogy. What are the benefits of including feminism within participatory action research and teaching? In responding to this question, we discuss the similarities and salient differences between PAR and feminist informed PAR (FPAR). There are eight themes…

  13. Intraoperative raster photogrammetry--the PAR Corneal Topography System.

    PubMed

    Belin, M W

    1993-01-01

    The PAR Corneal Topography System (CTS) is a computer-driven corneal imaging system that uses close-range raster photogrammetry to measure and produce a topographic map of the corneal surface. The CTS determines distortion in a projected two-dimensional grid. Unlike Placido-disc-based videokeratoscopes, the PAR CTS produces a true topographic map (elevation map) and requires neither a smooth reflective surface nor precise spatial alignment for accurate imaging. Because the system uses two noncoaxial optical paths, it can be integrated into other optical devices. A modified CTS was integrated into an experimental erbium: YAG photoablative laser. The CTS successfully imaged corneas before, after, and during laser photoablation. Its ability to image nonreflective surfaces and to be integrated into other optical systems may make it suitable for intraoperative refractive monitoring.

  14. Endophthalmitis following 27-Gauge Pars Plana Vitrectomy for Vitreous Floaters

    PubMed Central

    Lin, Zhong; Wu, Rong Han; Moonasar, Nived

    2016-01-01

    Purpose To report a case of Staphylococcus epidermidis endophthalmitis following 27-gauge pars plana vitrectomy for symptomatic vitreous floaters. Methods The clinical course and imaging findings, including fundus optomap, and spectral domain optical coherence tomography of a 24-year-old male patient were documented. Results The patient, with a preoperative best-corrected visual acuity (BCVA) of 1.0, developed endophthalmitis following 27-gauge pars plana vitrectomy for symptomatic vitreous floaters. After a series of treatments, including emergent vitreous tap and silicone oil injection, antibiotic treatment, and silicone oil removal, the patient regained a BCVA of 0.6. Conclusion Although rare, the potential risk of endophthalmitis should be explicitly discussed with patients considering surgical intervention for vitreous floaters. PMID:28101041

  15. Exploration of a new series of PAR1 antagonists.

    PubMed

    Planty, Bruno; Pujol, Chantal; Lamothe, Marie; Maraval, Catherine; Horn, Clemens; Le Grand, Bruno; Perez, Michel

    2010-03-01

    Two series of new PAR1 antagonists have been identified. The first incorporates a cinnamoylpiperidine motif and the second a cinnamoylpyridine pattern. The synthesis, biological activity and structure-activity relationship of these compounds are presented. In each series, one analog showed potent in vivo antithrombotic activity in a rat AV shunt model, with up to 53% inhibition at 1.25mpk iv for compound 30.

  16. Accuracy of the PAR corneal topography system with spatial misalignment.

    PubMed

    Belin, M W; Zloty, P

    1993-01-01

    The PAR Corneal Topography System is a computerized corneal imaging system which uses close-range raster photogrammetry to measure and produce a topographic map of the corneal surface. Raster photogrammetry is a standard method of extracting object information by projecting a known pattern onto an object and recording the distortion when viewed from an oblique angle. Unlike placido disc based videokeratoscopes, the PAR system requires neither a smooth reflective surface nor precise spatial alignment for accurate imaging. We studied both the accuracy of the system with purposeful misalignment (defocusing) of the test object and determined the ability to image freshly deepithelialized, keratectomized, and photoablated corneas. The PAR system was both accurate and reproducible in imaging calibrated spheres within a defined zone in space. Whole cadaver eyes were imaged both before and immediately after removal of the epithelium, lamellar keratectomy, and laser photoablation. The system demonstrated the ability to image irregular, deepithelialized, and keratectomized corneas. The ability to maintain accuracy without precise alignment and the facility to image freshly deepithelialized and keratectomized corneas may make the system suitable for intraoperative refractive monitoring.

  17. The Pars Interarticularis Stress Reaction, Spondylolysis, and Spondylolisthesis Progression

    PubMed Central

    Motley, Gina; Nyland, John; Jacobs, Jake; Caborn, David N. M.

    1998-01-01

    Objective: To review the classification, etiology, clinical and radiologic evaluation, and management of the pars interarticularis stress reaction, spondylolysis, and spondylolisthesis progression. Data Sources: Grateful Med was searched from 1980 to 1998 using the terms “spondylolysis,” “spondylolisthesis,” “female athlete” “spondylogenic,” and “pars interarticularis.” Data Synthesis: The progression from pars interarticularis stress reaction through spondylolysis to spondylolisthesis is common in adolescent athletes, and, because of hormonal influences and cheerleading and gymnastic maneuvers, females are particularly at risk. Proper diagnosis and management include a thorough evaluation, radiographs (possibly with technetium bone scan or single-photon emission computed tomography), activity modification, dietary counseling, a therapeutic exercise program focusing on proper trunk and hip muscle strength and extensibility balances, and education regarding proper back postures, positioning, lifting mechanics, and jump landings. Conclusions/Recommendations: The athletic trainer plays an integral part in managing this injury progression, particularly with identifying at-risk individuals and intervening appropriately. ImagesFigure 4. PMID:16558534

  18. La modélisation par Reverse Monte Carlo (RMC)

    NASA Astrophysics Data System (ADS)

    McGreevy, R. L.

    2003-09-01

    La technique de modélisation par Reverse Monte Carlo (RMC) est une méthode générale de modélisation structurale à partir d'un ensemble de données expérimentales. Cette méthode étant très souple, elle peut s'appliquer à de nombreux types de données. Jusqu'à présent ces applications comprennent : la diffraction des neutrons (y compris la substitution isotopique), la diffraction des rayons X (y compris la diffusion anomale), la diffraction des électrons, la RMN (les techniques d'angle magique et de 2ème moment) et l'EXAFS. Les systèmes étudiés sont également d'une grande variété : liquides, verres, polymères, cristaux et matériaux magnétiques, par exemple. Ce cours présente les bases de la méthode RMC en signalant certaines des idées fausses répandues. L'accent sera mis sur le fait que les modèles structuraux obtenus par RMC ne sont ni'uniques' ni 'exacts' ; cependant ils sont souvent utiles à la compréhension soit de la structure du système, soit des relations entre structure et autres propriétés physiques.

  19. Two cases of malignant glaucoma unresolved by pars plana vitrectomy

    PubMed Central

    Hosoda, Yoshikatsu; Akagi, Tadamichi; Yoshimura, Nagahisa

    2014-01-01

    Malignant glaucoma, which is characterized by a shallow or flat anterior chamber with high intraocular pressure, can usually be resolved by pars plana vitrectomy with anterior hyaloidectomy. We describe two cases in which malignant glaucoma was refractory to conventional treatment and complete vitrectomy. Case one an 88-year-old woman with pseudoexfoliation glaucoma underwent trabeculotomy and subsequently developed malignant glaucoma. Four months after transient recovery by pars plana vitrectomy, the malignant glaucoma recurred. She underwent peripheral iridectomy and local zonulectomy with successful control of her intraocular pressure. In case two, an 85-year-old man had a history of pseudoexfoliation glaucoma. Seven months after phacoemulsification and intraocular lens implantation, he developed malignant glaucoma that was refractory to pars plana vitrectomy. He underwent peripheral iridectomy, goniosynechialysis and trabectome surgery resulting in the successful control of his intraocular pressure. In rare cases of malignant glaucoma refractive to vitrectomy, peripheral iridectomy with or without local zonulectomy is a reasonable and minimally invasive surgical procedure. PMID:24729683

  20. ParB Partition Proteins: Complex Formation and Spreading at Bacterial and Plasmid Centromeres

    PubMed Central

    Funnell, Barbara E.

    2016-01-01

    In bacteria, active partition systems contribute to the faithful segregation of both chromosomes and low-copy-number plasmids. Each system depends on a site-specific DNA binding protein to recognize and assemble a partition complex at a centromere-like site, commonly called parS. Many plasmid, and all chromosomal centromere-binding proteins are dimeric helix-turn-helix DNA binding proteins, which are commonly named ParB. Although the overall sequence conservation among ParBs is not high, the proteins share similar domain and functional organization, and they assemble into similar higher-order complexes. In vivo, ParBs “spread,” that is, DNA binding extends away from the parS site into the surrounding non-specific DNA, a feature that reflects higher-order complex assembly. ParBs bridge and pair DNA at parS and non-specific DNA sites. ParB dimers interact with each other via flexible conformations of an N-terminal region. This review will focus on the properties of the HTH centromere-binding protein, in light of recent experimental evidence and models that are adding to our understanding of how these proteins assemble into large and dynamic partition complexes at and around their specific DNA sites. PMID:27622187

  1. Specific and non-specific interactions of ParB with DNA: implications for chromosome segregation

    PubMed Central

    Taylor, James A.; Pastrana, Cesar L.; Butterer, Annika; Pernstich, Christian; Gwynn, Emma J.; Sobott, Frank; Moreno-Herrero, Fernando; Dillingham, Mark S.

    2015-01-01

    The segregation of many bacterial chromosomes is dependent on the interactions of ParB proteins with centromere-like DNA sequences called parS that are located close to the origin of replication. In this work, we have investigated the binding of Bacillus subtilis ParB to DNA in vitro using a variety of biochemical and biophysical techniques. We observe tight and specific binding of a ParB homodimer to the parS sequence. Binding of ParB to non-specific DNA is more complex and displays apparent positive co-operativity that is associated with the formation of larger, poorly defined, nucleoprotein complexes. Experiments with magnetic tweezers demonstrate that non-specific binding leads to DNA condensation that is reversible by protein unbinding or force. The condensed DNA structure is not well ordered and we infer that it is formed by many looping interactions between neighbouring DNA segments. Consistent with this view, ParB is also able to stabilize writhe in single supercoiled DNA molecules and to bridge segments from two different DNA molecules in trans. The experiments provide no evidence for the promotion of non-specific DNA binding and/or condensation events by the presence of parS sequences. The implications of these observations for chromosome segregation are discussed. PMID:25572315

  2. Dynamic Filament Formation by a Divergent Bacterial Actin-Like ParM Protein

    PubMed Central

    Brzoska, Anthony J.; Jensen, Slade O.; Barton, Deborah A.; Davies, Danielle S.; Overall, Robyn L.; Skurray, Ronald A.; Firth, Neville

    2016-01-01

    Actin-like proteins (Alps) are a diverse family of proteins whose genes are abundant in the chromosomes and mobile genetic elements of many bacteria. The low-copy-number staphylococcal multiresistance plasmid pSK41 encodes ParM, an Alp involved in efficient plasmid partitioning. pSK41 ParM has previously been shown to form filaments in vitro that are structurally dissimilar to those formed by other bacterial Alps. The mechanistic implications of these differences are not known. In order to gain insights into the properties and behavior of the pSK41 ParM Alp in vivo, we reconstituted the parMRC system in the ectopic rod-shaped host, E. coli, which is larger and more genetically amenable than the native host, Staphylococcus aureus. Fluorescence microscopy showed a functional fusion protein, ParM-YFP, formed straight filaments in vivo when expressed in isolation. Strikingly, however, in the presence of ParR and parC, ParM-YFP adopted a dramatically different structure, instead forming axial curved filaments. Time-lapse imaging and selective photobleaching experiments revealed that, in the presence of all components of the parMRC system, ParM-YFP filaments were dynamic in nature. Finally, molecular dissection of the parMRC operon revealed that all components of the system are essential for the generation of dynamic filaments. PMID:27310470

  3. Developmental Control of a parAB Promoter Leads to Formation of Sporulation-Associated ParB Complexes in Streptomyces coelicolor

    PubMed Central

    Jakimowicz, Dagmara; Mouz, Sebastien; Zakrzewska-Czerwińska, Jolanta; Chater, Keith F.

    2006-01-01

    The Streptomyces coelicolor partitioning protein ParB binds to numerous parS sites in the oriC-proximal part of the linear chromosome. ParB binding results in the formation of large complexes, which behave differentially during the complex life cycle (D. Jakimowicz, B. Gust, J. Zakrzewska-Czerwinska, and K. F. Chater, J. Bacteriol. 187:3572-3580, 2005). Here we have analyzed the transcriptional regulation that underpins this developmentally specific behavior. Analysis of promoter mutations showed that the irregularly spaced complexes present in vegetative hyphae are dependent on the constitutive parABp1 promoter, while sporulation-specific induction of the promoter parABp2 is required for the assembly of arrays of ParB complexes in aerial hyphae and thus is necessary for efficient chromosome segregation. Expression from parABp2 depended absolutely on two sporulation regulatory genes, whiA and whiB, and partially on two others, whiH and whiI, all four of which are needed for sporulation septation. Because of this pattern of dependence, we investigated the transcription of these four whi genes in whiA and whiB mutants, revealing significant regulatory interplay between whiA and whiB. A strain in which sporulation septation (but not vegetative septation) was blocked by mutation of a sporulation-specific promoter of ftsZ showed close to wild-type induction of parABp2 and formed fairly regular ParB-enhanced green fluorescent protein foci in aerial hyphae, ruling out strong morphological coupling or checkpoint regulation between septation and DNA partitioning during sporulation. A model for developmental regulation of parABp2 expression is presented. PMID:16484182

  4. Caracterisation et transformation par hydroviscoreduction du brut lourd de Doba/Tchad: Strategie de pompage par pipeline

    NASA Astrophysics Data System (ADS)

    Dehkissia, Soumaine

    Le projet de la these est defini par rapport a la recente exploitation commerciale du brut lourd de Doba, une region du Tchad, pays enclave d'ou le brut ainsi produit doit etre achemine par pipeline. Le but dans ce travail est de caracteriser ce brut et de determiner une strategie thermique de transformation en vue de reduire de la facon la plus economique, la viscosite du brut pour permettre son transport par pipeline. Concernant la partie caracterisation, nous avons utilise entre autres, un rheometre rotatif et des analyseurs (LECO CHN-2000 & LECO S-144DR Elemental Analyzers) pour evaluer respectivement la viscosite et les elements tels que C, H, N, O, S. Sur la base des methodes de transformation disponibles, nous avons determine une strategie simple de transformation thermique par hydroviscoreduction , strategie dans laquelle, la fraction legere du brut comme le naphta (80--180°C), pourrait constituer la source d'hydrogene a utiliser. Le brut de Doba, a une faible teneur en soufre (0.14%) et sa densite specifique de 0.940 a 15.6°C, soit 18.8° API, le classe parmi les bruts lourds. Outre le point initial se situant a 85°C, la distillation du brut a revele que la fraction distillant avant 250°C ne represente que 10% (v/v) et que le craquage thermique du substrat debute a 300°C. Par ailleurs, outre son caractere Newtonien, les densites specifiques de la fraction lourde de l'essence (100--200°C) et de la fraction distillant au-dessus 350°C, etant respectivement de 0.813 (0.813 > 0.800) et de 0.951 (0.930 < 0.951 < 0.975), le brut de Doba est donc de type aromatique. Les viscosites du brut et du brut desasphalte, sont respectivement de 184.4 cSt et 152.4 cSt a 50°C, suggerant que le desasphaltage ne constitue pas une methode efficace pouvant aider au pompage du brut par pipeline, d'ou la necessite de transformation. Les resultats des travaux en autoclave montrent que, si le brut doit etre traite entierement, la viscosite de 25cSt 50°C, recommandee pour le

  5. ParABS Systems of the Four Replicons of Burkholderia cenocepacia: New Chromosome Centromeres Confer Partition Specificity†

    PubMed Central

    Dubarry, Nelly; Pasta, Franck; Lane, David

    2006-01-01

    Most bacterial chromosomes carry an analogue of the parABS systems that govern plasmid partition, but their role in chromosome partition is ambiguous. parABS systems might be particularly important for orderly segregation of multipartite genomes, where their role may thus be easier to evaluate. We have characterized parABS systems in Burkholderia cenocepacia, whose genome comprises three chromosomes and one low-copy-number plasmid. A single parAB locus and a set of ParB-binding (parS) centromere sites are located near the origin of each replicon. ParA and ParB of the longest chromosome are phylogenetically similar to analogues in other multichromosome and monochromosome bacteria but are distinct from those of smaller chromosomes. The latter form subgroups that correspond to the taxa of their hosts, indicating evolution from plasmids. The parS sites on the smaller chromosomes and the plasmid are similar to the “universal” parS of the main chromosome but with a sequence specific to their replicon. In an Escherichia coli plasmid stabilization test, each parAB exhibits partition activity only with the parS of its own replicon. Hence, parABS function is based on the independent partition of individual chromosomes rather than on a single communal system or network of interacting systems. Stabilization by the smaller chromosome and plasmid systems was enhanced by mutation of parS sites and a promoter internal to their parAB operons, suggesting autoregulatory mechanisms. The small chromosome ParBs were found to silence transcription, a property relevant to autoregulation. PMID:16452432

  6. Is PAR a Good Investment? Understanding the Costs and Benefits of Teacher Peer Assistance and Review Programs

    ERIC Educational Resources Information Center

    Papay, John P.; Johnson, Susan Moore

    2012-01-01

    Peer Assistance and Review (PAR) is a local labor-management initiative designed to improve teacher quality. In PAR, expert "consulting teachers" mentor, support, and evaluate novice and underperforming veteran teachers. Evaluations under PAR can lead to dismissals. The authors examine the costs and benefits of PAR, both financial and…

  7. Structures of actin-like ParM filaments show architecture of plasmid-segregating spindles.

    PubMed

    Bharat, Tanmay A M; Murshudov, Garib N; Sachse, Carsten; Löwe, Jan

    2015-07-02

    Active segregation of Escherichia coli low-copy-number plasmid R1 involves formation of a bipolar spindle made of left-handed double-helical actin-like ParM filaments. ParR links the filaments with centromeric parC plasmid DNA, while facilitating the addition of subunits to ParM filaments. Growing ParMRC spindles push sister plasmids to the cell poles. Here, using modern electron cryomicroscopy methods, we investigate the structures and arrangements of ParM filaments in vitro and in cells, revealing at near-atomic resolution how subunits and filaments come together to produce the simplest known mitotic machinery. To understand the mechanism of dynamic instability, we determine structures of ParM filaments in different nucleotide states. The structure of filaments bound to the ATP analogue AMPPNP is determined at 4.3 Å resolution and refined. The ParM filament structure shows strong longitudinal interfaces and weaker lateral interactions. Also using electron cryomicroscopy, we reconstruct ParM doublets forming antiparallel spindles. Finally, with whole-cell electron cryotomography, we show that doublets are abundant in bacterial cells containing low-copy-number plasmids with the ParMRC locus, leading to an asynchronous model of R1 plasmid segregation.

  8. Urokinase type plasminogen activator receptor (uPAR) as a new therapeutic target in cancer

    PubMed Central

    Montuori, Nunzia; Pesapane, Ada; Rossi, Francesca W; Giudice, Valentina; De Paulis, Amato; Selleri, Carmine; Ragno, Pia

    2016-01-01

    The urokinase (uPA)-type plasminogen activator receptor (uPAR) is a GPI-anchored receptor that focuses urokinase (uPA) proteolytic activity on the cell surface. uPAR also regulates cell adhesion, migration and proliferation, protects from apoptosis and contributes to epithelial mesenchymal transition (EMT), independently of uPA enzymatic activity. Indeed, uPAR interacts with beta1, beta2 and beta3 integrins, thus regulating their activities. uPAR cross-talks with receptor tyrosine kinases through integrins and regulates cancer cell dormancy, proliferation and angiogenesis. Moreover, uPAR mediates uPA-dependent cell migration and chemotaxis induced by fMet-Leu-Phe (fMLF), through its association with fMLF-receptors (fMLF-Rs). Further, uPAR is an adhesion receptor because it binds vitronectin (VN), a component of provisional extracellular matrix. High uPAR expression predicts for more aggressive disease in several cancer types for its ability to increase invasion and metastasis. In fact, uPAR has been hypothesized to be the link between tumor cell dormancy and proliferation that usually precedes the onset of metastasis. Thus, inhibiting uPAR could be a feasible approach to affect tumor growth and metastasis. Here, we review the more recent advances in the development of uPAR-targeted anti-cancer therapeutic agents suitable for further optimization or ready for the evaluation in early clinical trials. PMID:27896223

  9. A model for the condensation of the bacterial chromosome by the partitioning protein ParB

    NASA Astrophysics Data System (ADS)

    Broedersz, Chase; Wingreen, Ned

    2013-03-01

    The molecular machinery responsible for faithful segregation of the chromosome in bacteria such as Caulobacter crescentus and Bacillus subtilis includes the ParABS a.k.a. Spo0J/Soj partitioning system. In Caulobacter, prior to division, hundreds of ParB proteins bind to the DNA near the origin of replication, and localize to one pole of the cell. Subsequently, the ParB-DNA complex is translocated to the far pole by the binding and retraction of the ParA spindle-like apparatus. Remarkably, the localization of ParB proteins to specific regions of the chromosome appears to be controlled by only a few centromeric parS binding sites. Although lateral interactions between DNA-bound ParB are likely to be important for their localization, the long-range order of ParB domains on the chromosome appears to be inconsistent with a picture in which protein-protein interactions are limited to neighboring DNA-bound proteins. We developed a coarse-grained Brownian dynamics model that allows for lateral and 3D protein-protein interactions among bound ParB proteins. Our model shows how such interactions can condense and organize the DNA spatially, and can control the localization and the long-range order of the DNA-bound proteins.

  10. PAR-2 expression in the gingival crevicular fluid reflects chronic periodontitis severity.

    PubMed

    Fukushima, Henrique; Alves, Vanessa Tubero Euzebio; Carvalho, Verônica Franco de; Ambrósio, Lucas Macedo Batitucci; Eichler, Rosangela Aparecida Dos Santos; Carvalho, Maria Helena Catelli de; Saraiva, Luciana; Holzhausen, Marinella

    2017-01-26

    Recent studies investigating protease-activated receptor type 2 (PAR-2) suggest an association between the receptor and periodontal inflammation. It is known that gingipain, a bacterial protease secreted by the important periodontopathogen Porphyromonas gingivalis can activate PAR-2. Previous studies by our group found that PAR-2 is overexpressed in the gingival crevicular fluid (GCF) of patients with moderate chronic periodontitis (MP). The present study aimed at evaluating whether PAR-2 expression is associated with chronic periodontitis severity. GCF samples and clinical parameters, including plaque and bleeding on probing indices, probing pocket depth and clinical attachment level, were collected from the control group (n = 19) at baseline, and from MP patients (n = 19) and severe chronic periodontitis (SP) (n = 19) patients before and 6 weeks after periodontal non-surgical treatment. PAR-2 and gingipain messenger RNA (mRNA) in the GCF of 4 periodontal sites per patient were evaluated by Reverse Transcription Polymerase Chain Reaction (RT-qPCR). PAR-2 and gingipain expressions were greater in periodontitis patients than in control group patients. In addition, the SP group presented increased PAR-2 and gingipain mRNA levels, compared with the MP group. Furthermore, periodontal treatment significantly reduced (p <0.05) PAR-2 expression in patients with periodontitis. In conclusion, PAR-2 is associated with chronic periodontitis severity and with gingipain levels in the periodontal pocket, thus suggesting that PAR-2 expression in the GCF reflects the severity of destruction during periodontal infection.

  11. PAR-1 contributes to the innate immune response during viral infection

    PubMed Central

    Antoniak, Silvio; Owens, A. Phillip; Baunacke, Martin; Williams, Julie C.; Lee, Rebecca D.; Weithäuser, Alice; Sheridan, Patricia A.; Malz, Ronny; Luyendyk, James P.; Esserman, Denise A.; Trejo, JoAnn; Kirchhofer, Daniel; Blaxall, Burns C.; Pawlinski, Rafal; Beck, Melinda A.; Rauch, Ursula; Mackman, Nigel

    2013-01-01

    Coagulation is a host defense system that limits the spread of pathogens. Coagulation proteases, such as thrombin, also activate cells by cleaving PARs. In this study, we analyzed the role of PAR-1 in coxsackievirus B3–induced (CVB3-induced) myocarditis and influenza A infection. CVB3-infected Par1–/– mice expressed reduced levels of IFN-β and CXCL10 during the early phase of infection compared with Par1+/+ mice that resulted in higher viral loads and cardiac injury at day 8 after infection. Inhibition of either tissue factor or thrombin in WT mice also significantly increased CVB3 levels in the heart and cardiac injury compared with controls. BM transplantation experiments demonstrated that PAR-1 in nonhematopoietic cells protected mice from CVB3 infection. Transgenic mice overexpressing PAR-1 in cardiomyocytes had reduced CVB3-induced myocarditis. We found that cooperative signaling between PAR-1 and TLR3 in mouse cardiac fibroblasts enhanced activation of p38 and induction of IFN-β and CXCL10 expression. Par1–/– mice also had decreased CXCL10 expression and increased viral levels in the lung after influenza A infection compared with Par1+/+ mice. Our results indicate that the tissue factor/thrombin/PAR-1 pathway enhances IFN-β expression and contributes to the innate immune response during single-stranded RNA viral infection. PMID:23391721

  12. Microscopie en champ proche par réflexion

    NASA Astrophysics Data System (ADS)

    Spajer, M.; Courjon, D.; Sarayeddine, K.; Jalocha, A.; Vigoureux, J.-M.

    1991-01-01

    This communication presents two techniques for high resolution surface analysis. In the first one, the illumination beam is totally reflected under the object surface, which must be transparent. The evanescent wave confined on the surface is frustrated locally by a dielectric probe of nanometric dimension which scans the objetc. A horizontal resolution of 10 nm and a vertical one of 1 nm have been obtained. In the second one, more adapted to metallic objects, the surface is illuminated by the near-field of the stylus, in which the reflected beam is Partially launched. First results dealing with the characterization of the dielectric stylus are presented. Cette communication présente deux techniques permettant l'analyse de surface haute résolution. Dans la première, le faisceau d'éclairage est réfléchi totalement sous la surface de l'objet, nécessairement transparent. L'onde évanescente qui l'accompagne est frustrée localement par une pointe diélectrique de dimension nanométrique balayant la surface. Une résolution de 10 nm horizontalement et de 1nm verticalement a été obtenue. Dans la seconde, qui permet d'étudier un objet opaque, celui-ci est éclairé par le champ proche émis par la pointe, dans laquelle le faisceau réfléchi est partiellement réinjecté. Les premiers résultats concernant la caractérisation de la pointe sont présentés.

  13. [Relationships of rice canopy PAR interception and light use efficiency to grain yield].

    PubMed

    Tang, Liang; Zhu, Xiang-Cheng; Cao, Meng-Ying; Cao, Wei-Xing; Zhu, Yan

    2012-05-01

    Taking two rice cultivars (Liangyoupeijiu and Wuxiangjing 14) with different plant types as test materials, a 2-year field experiment was conducted to study the relationships of rice canopy photosynthetically active radiation (PAR) interception and light use efficiency to grain yield under three planting densities and five nitrogen (N) application rates. From tillering to maturing stage, the average PAR reflectance in all treatments was 3.45%. The ratio of reflected PAR to the total loss of PAR from tillering to heading stage was 10.90%, which was significantly lower than that (22.06%) from heading to maturiting stage. The PAR conversion efficiency from tillering to maturing stage decreased with increasing planting density but increased with increasing nitrogen rate, and the conversion efficiency was significantly higher from tillering to heading than from heading to maturing stage. The PAR use efficiency from tillering to maturing stage increased with the increase of planting density and nitrogen application rate, and the average PAR use efficiency of Liangyoupeijiu (1.83 g x MJ(-1)) was significantly higher than that of Wuxiangjing 14 (1.42 g x MJ(-1)). Due to the longer growth period of Wuxiangjing 14, its incident PAR and intercepted PAR under midium and high planting densities were higher, as compared with Liangyoupeijiu. The grain yield was significantly positively correlated with the canopy PAR interceptance and use efficiency at different growth stages, but less correlated with the PAR conversion efficiency. To increase the canopy PAR use efficiency and conversion efficiency on the basis of maintaining higher PAR interception rate could be an effective way to increase rice yield.

  14. PAR1 is selectively over expressed in high grade breast cancer patients: a cohort study

    PubMed Central

    Hernández, Norma A; Correa, Elma; Avila, Esther P; Vela, Teresa A; Pérez, Víctor M

    2009-01-01

    Background The protease-activated receptor (PAR1) expression is correlated with the degree of invasiveness in cell lines. Nevertheless it has never been directed involved in breast cancer patients progression. The aim of this study was to determine whether PAR1 expression could be used as predictor of metastases and mortality. Methods In a cohort of patients with infiltrating ductal carcinoma studied longitudinally since 1996 and until 2007, PAR1 over-expression was assessed by immunoblotting, immunohistochemistry, and flow citometry. Chi-square and log rank tests were used to determine whether there was a statistical association between PAR1 overexpression and metastases, mortality, and survival. Multivariate analysis was performed including HER1, stage, ER and nodes status to evaluate PAR1 as an independent prognostic factor. Results Follow up was 95 months (range: 2–130 months). We assayed PAR1 in a cohort of patients composed of 136 patients; we found PAR1 expression assayed by immunoblotting was selectively associated with high grade patients (50 cases of the study cohort; P = 0.001). Twenty-nine of 50 (58%) patients overexpressed PAR1, and 23 of these (46%) developed metastases. HER1, stage, ER and PAR1 overexpression were robustly correlated (Cox regression, P = 0.002, P = 0.024 and P = 0.002 respectively). Twenty-one of the 50 patients (42%) expressed both receptors (PAR1 and HER1 P = 0.0004). We also found a statistically significant correlation between PAR1 overexpression and increased mortality (P = 0.0001) and development of metastases (P = 0.0009). Conclusion Our data suggest PAR1 overexpression may be involved in the development of metastases in breast cancer patient and is associated with undifferentiated cellular progression of the tumor. Further studies are needed to understand PAR1 mechanism of action and in a near future assay its potential use as risk factor for metastasis development in high grade breast cancer patients. PMID:19538737

  15. Recalculation of shielding for the addition of a PAR

    SciTech Connect

    Moe, H.J.

    1988-08-01

    The shielding estimates for the Electron and Positron Linacs and the Booster Synchrotron, contained in the 1987 Conceptual Design Report (CDR) of the APS (ANL-87-15), have been reviewed and recalculated, along with newly initiated calculations of the required shielding for the addition of a Positron Accumulator Ring (PAR). Several new assumptions with respect to beam intensity, projected losses in the system, and assumed operational time have been incorporated into the calculations. Details of the previous calculations, which describe the methodology used, may be found in APS Light Source Note LS-90.

  16. BOREAS TE-12 Incoming PAR Through the Forest Canopy Data

    NASA Technical Reports Server (NTRS)

    Hall, Forrest G. (Editor); Papagno, Andrea (Editor); Walter-Shea, Elizabeth A.; Mesarch, Mark A.

    2000-01-01

    The Boreal Ecosystem-Atmospheric Study (BOREAS) TE-12 (Terrestrial Ecology) team collected photosynthetically active radiation (PAR) data sets in support of its efforts to characterize and interpret information on shoot geometry, leaf optical properties, leaf water potential, and leaf gas exchange. The data were collected at the Southern Study Area-Old Black Spruce (SSA-OBS) site from 04-Jul-1996 to 25-Jul-1996. The data are stored in tabular ASCII files. The data files are available on a CD-ROM (see document number 20010000884), or from the Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC).

  17. A systematic computation scheme of PAR-WIG cruising performance

    NASA Astrophysics Data System (ADS)

    Ando, Shigenori

    1993-08-01

    A systematic computation scheme is presented for PAR-WIG cruising performance, on a FORTRAN program. It is suitable for implementation on PCs. Effects of many parameters on the transportation efficiency are explored. Two concepts are presented in three views and artist impressions. One is a smallest single-crewman vehicle for experiment, sports, or pleasure. The other is a large vehicle for civil transportation. Both have twin hulls, which are quite suitable for installing a 'SMALL-TAIL-WIG' or 'WIG-let' to establish longitudinal attitude stability.

  18. David Kasner, MD, and the Road to Pars Plana Vitrectomy

    PubMed Central

    Blodi, Christopher F.

    2016-01-01

    David Kasner, MD (1927–2001), used his extensive dissections of eye bank eyes and experiences in teaching cataract surgery to resident physicians to realize that excision of vitreous when present in the anterior chamber of eyes undergoing cataract surgery was preferable to prior intraoperative procedures. Noting that eyes tolerated his maneuvers, he then performed planned subtotal open-sky vitrectomies; first on a traumatized eye in 1961, then on two eyes of patients with amyloidosis (1966–1967). The success of these operations was noted by others, most particularly Robert Machemer, MD. Kasner’s work directly led to further surgical developments, including closed pars plana vitrectomy. PMID:27660504

  19. Mutations in the gyrB, parC, and parE genes of quinolone-resistant isolates and mutants of Edwardsiella tarda.

    PubMed

    Kim, Myoung Sug; Jun, Lyu Jin; Shin, Soon Bum; Park, Myoung Ae; Jung, Sung Hee; Kim, Kwangil; Moon, Kyung Ho; Jeong, Hyun Do

    2010-12-01

    The full length genes gyrB (2,415 bp), parC (2,277 bp), and parE (1,896 bp) in Edwardsiella tarda were cloned by PCR with degenerate primers based on the sequence of the respective quinolone resistance-determining region (QRDR), followed by elongation of 5' and 3' ends using cassette ligation-mediated PCR (CLMP). Analysis of the cloned genes revealed open reading frames (ORFs) encoding proteins of 804 (GyrB), 758 (ParC), and 631 (ParE) amino acids with conserved gyrase/topoisomerase features and motifs important for enzymatic function. The ORFs were preceded by putative promoters, ribosome binding sites, and inverted repeats with the potential to form cruciform structures for binding of DNA-binding proteins. When comparing the deduced amino acid sequences of E. tarda GyrB, ParC, and ParE with those of the corresponding proteins in other bacteria, they were found to be most closely related to Escherichia coli GyrB (87.6% identity), Klebsiella pneumoniae ParC (78.8% identity) and Salmonella typhimurium ParE (89.5% identity), respectively. The two topoisomerase genes, parC and parE, were found to be contiguous on the E. tarda chromosome. All 18 quinoloneresistant isolates obtained from Korea thus far did not contain subunit alternations apart from a substitution in GyrA (Ser83→Arg). However, an alteration in the QRDR of ParC (Ser84→Ile) following an amino acid substitution in GyrA (Asp87→Gly) was detected in E. tarda mutants selected in vitro at 8 microng/ml ciprofloxacin (CIP). A mutant with a GyrB (Ser464→Leu) and GyrA (Asp87→Gly) substitution did not show a significant increase in the minimum inhibitory concentration (MIC) of CIP. None of the in vitro mutants exhibited mutations in parE. Thus, gyrA and parC should be considered to be the primary and secondary targets, respectively, of quinolones in E. tarda.

  20. Estimating Photosynthetically Available Radiation (PAR) at the Earth's surface from satellite observations

    NASA Technical Reports Server (NTRS)

    Frouin, Robert

    1993-01-01

    Current satellite algorithms to estimate photosynthetically available radiation (PAR) at the earth' s surface are reviewed. PAR is deduced either from an insolation estimate or obtained directly from top-of-atmosphere solar radiances. The characteristics of both approaches are contrasted and typical results are presented. The inaccuracies reported, about 10 percent and 6 percent on daily and monthly time scales, respectively, are useful to model oceanic and terrestrial primary productivity. At those time scales variability due to clouds in the ratio of PAR and insolation is reduced, making it possible to deduce PAR directly from insolation climatologies (satellite or other) that are currently available or being produced. Improvements, however, are needed in conditions of broken cloudiness and over ice/snow. If not addressed properly, calibration/validation issues may prevent quantitative use of the PAR estimates in studies of climatic change. The prospects are good for an accurate, long-term climatology of PAR over the globe.

  1. The Par3 polarity protein is an exocyst receptor essential for mammary cell survival

    PubMed Central

    Ahmed, Syed Mukhtar; Macara, Ian G.

    2017-01-01

    The exocyst is an essential component of the secretory pathway required for delivery of basolateral proteins to the plasma membranes of epithelial cells. Delivery occurs adjacent to tight junctions (TJ), suggesting that it recognizes a receptor at this location. However, no such receptor has been identified. The Par3 polarity protein associates with TJs but has no known function in membrane traffic. We now show that, unexpectedly, Par3 is essential for mammary cell survival. Par3 silencing causes apoptosis, triggered by phosphoinositide trisphosphate depletion and decreased Akt phosphorylation, resulting from failure of the exocyst to deliver basolateral proteins to the cortex. A small region of PAR3 binds directly to Exo70 and is sufficient for exocyst docking, membrane-protein delivery and cell survival. PAR3 lacking this domain can associate with the cortex but cannot support exocyst function. We conclude that Par3 is the long-sought exocyst receptor required for targeted membrane-protein delivery. PMID:28358000

  2. Brulure par Foudre. A Propos d’une Observation

    PubMed Central

    Mradmi, W.; Fassi-Fihri, J.; Mehaji, G.; Ezzoubi, M.; Diouri, M.; Bahechar, N.; Boukind, E.H.

    2005-01-01

    Summary Aussi loin que l’on remonte dans la littérature, on retrouve des récits relatant des accidents consécutifs à la fulguration chez l’homme. La foudre était alors associée à la colère des dieux ou à la notion de châtiment. La fulguration correspond à un transfert d’énergie entre un cumulonimbus de charge négative et un objet de charge positive se trouvant au niveau du sol. Les lésions déterminées sont à la fois thermiques et électrothermiques. Bien que l’arrêt cardiorespiratoire soit une cause bien documentée de décès, la plupart des cas rapportés dans la littérature décrivent un éventail très disparate des séquelles qui surviennent suite à cet accident. Les Auteurs rapportent le cas d’un patient atteint par la foudre en insistant particulièrement sur les complications neurologiques qui sont survenues en cours d’évolution. Se basant sur cette observation et sur une revue de la littérature, les Auteurs soulignent que le pronostic des patients atteints par la foudre est plus favorable que généralement rapporté. PMID:21990993

  3. Fluoroquinolone Resistance Mutations in the parC, parE, and gyrA Genes of Clinical Isolates of Viridans Group Streptococci

    PubMed Central

    González, Irene; Georgiou, Marios; Alcaide, Fernando; Balas, Delia; Liñares, Josefina; de la Campa, Adela G.

    1998-01-01

    The nucleotide sequences of the quinolone resistance-determining regions (QRDRs) of the parC and gyrA genes from seven ciprofloxacin-resistant (Cpr) isolates of viridans group streptococci (two high-level Cpr Streptococcus oralis and five low-level Cpr Streptococcus mitis isolates) were determined and compared with those obtained from susceptible isolates. The nucleotide sequences of the QRDRs of the parE and gyrB genes from the five low-level Cpr S. mitis isolates and from the NCTC 12261 type strain were also analyzed. Four of these low-level Cpr isolates had changes affecting the subunits of DNA topoisomerase IV: three in Ser-79 (to Phe or Ile) of ParC and one in ParE at a position not previously described to be involved in quinolone resistance (Pro-424). One isolate did not show any mutation. The two high-level Cpr S. oralis isolates showed mutations affecting equivalent residue positions of ParC and GyrA, namely, Ser-79 to Phe and Ser-81 to Phe or Tyr, respectively. The parC mutations were able to transform Streptococcus pneumoniae to ciprofloxacin resistance, while the gyrA mutations transformed S. pneumoniae only when mutations in parC were present. These results suggest that DNA topoisomerase IV is a primary target of ciprofloxacin in viridans group streptococci, DNA gyrase being a secondary target. PMID:9797205

  4. The PARA-suite: PAR-CLIP specific sequence read simulation and processing

    PubMed Central

    Kloetgen, Andreas; Borkhardt, Arndt; Hoell, Jessica I.

    2016-01-01

    Background Next-generation sequencing technologies have profoundly impacted biology over recent years. Experimental protocols, such as photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation (PAR-CLIP), which identifies protein–RNA interactions on a genome-wide scale, commonly employ deep sequencing. With PAR-CLIP, the incorporation of photoactivatable nucleosides into nascent transcripts leads to high rates of specific nucleotide conversions during reverse transcription. So far, the specific properties of PAR-CLIP-derived sequencing reads have not been assessed in depth. Methods We here compared PAR-CLIP sequencing reads to regular transcriptome sequencing reads (RNA-Seq) to identify distinctive properties that are relevant for reference-based read alignment of PAR-CLIP datasets. We developed a set of freely available tools for PAR-CLIP data analysis, called the PAR-CLIP analyzer suite (PARA-suite). The PARA-suite includes error model inference, PAR-CLIP read simulation based on PAR-CLIP specific properties, a full read alignment pipeline with a modified Burrows–Wheeler Aligner algorithm and CLIP read clustering for binding site detection. Results We show that differences in the error profiles of PAR-CLIP reads relative to regular transcriptome sequencing reads (RNA-Seq) make a distinct processing advantageous. We examine the alignment accuracy of commonly applied read aligners on 10 simulated PAR-CLIP datasets using different parameter settings and identified the most accurate setup among those read aligners. We demonstrate the performance of the PARA-suite in conjunction with different binding site detection algorithms on several real PAR-CLIP and HITS-CLIP datasets. Our processing pipeline allowed the improvement of both alignment and binding site detection accuracy. Availability The PARA-suite toolkit and the PARA-suite aligner are available at https://github.com/akloetgen/PARA-suite and https

  5. Participation of the urokinase-type plasminogen activator receptor (uPAR) in neutrophil transendothelial migration.

    PubMed

    Pliyev, Boris K; Antonova, Olga A; Menshikov, Mikhail

    2011-05-01

    The mechanisms underlying migration of neutrophils across endothelium are not completely understood. The urokinase-type plasminogen activator receptor (uPAR) plays a key role in neutrophil adhesion and migration. In the present study, we addressed whether uPAR regulates neutrophil transendothelial migration. We first showed that siRNA-mediated knockdown of uPAR in human umbilical vein endothelial cells (HUVECs) did not affect neutrophil migration across HUVEC monolayers indicating that endothelial uPAR does not regulate neutrophil transmigration. In contrast, the transmigration was significantly inhibited by Fab' fragment of anti-uPAR monoclonal antibody and proteolytically inactive urokinase (uPA), whereas inhibition of proteolytical activity of endogenous uPA (with amiloride or plasminogen activator inhibitor-1) did not affect the transmigration. Both the anti-uPAR Fab' fragment and proteolytically inactive uPA did not exert significant effects upon the transmigration conducted in the presence of F(ab')(2) fragment of blocking antibody to integrin Mac-1 indicating that uPAR regulates Mac-1-dependent transmigration. Mac-1-dependent, but not Mac-1-independent, transmigration was significantly reduced in the presence of N-acetyl-d-glucosamine and d-mannose, the saccharides that disrupt uPAR/Mac-1 association, but was unaffected in the presence of control saccharides (d-sorbitol and sucrose). We conclude that physical association of uPAR with Mac-1 mediates the regulatory effect of uPAR over the transmigration. Finally, we provide evidence that the functional cooperation between uPAR and Mac-1 is essential at both adhesion and diapedesis steps of neutrophil migration across endothelium. Thus, uPAR expressed on neutrophil plasma membrane regulates transendothelial migration independently of uPA proteolytical activity and acting as a cofactor for integrin Mac-1.

  6. Cancer-Selective Apoptotic Effects of Extracellular and Intracellular Par-4

    PubMed Central

    Bhattarai, Tripti Shrestha; Rangnekar, Vivek M.

    2010-01-01

    Selectivity toward cancer cells is the most desirable element in cancer therapeutics. Par-4 is a cancer cell-selective pro-apoptotic protein that functions intracellularly in the cytoplasmic and nuclear compartments, as a tumor suppressor. Moreover, recent findings indicate that the Par-4 protein is secreted by cells, and extracellular Par-4 induces cancer cell-specific apoptosis by interaction with the cell-surface receptor GRP78. This review describes the mechanisms underlying the apoptotic effects of both extracellular and intracellular Par-4 acting via its effector domain SAC. PMID:20440265

  7. Tryptase - PAR2 axis in Experimental Autoimmune Prostatitis, a model for Chronic Pelvic Pain Syndrome

    PubMed Central

    Roman, Kenny; Done, Joseph D.; Schaeffer, Anthony J.; Murphy, Stephen F.; Thumbikat, Praveen

    2014-01-01

    Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine experimental autoimmune prostatitis (EAP). Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia lead to ERK1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS. PMID:24726923

  8. A Desired PAR-Achieving Precoder Design for Multiuser MIMO OFDM Based on Concentration of Measure

    NASA Astrophysics Data System (ADS)

    Cha, Hyun-Su; Kim, Dong Ku

    2017-03-01

    For multi-user multiple-input and multiple-output (MIMO) wireless communications in orthogonal frequency di- vision multiplexing systems, we propose a MIMO precoding scheme providing a desired peak-to-average power ratio (PAR) at the minimum cost that is defined as received SNR degradation. By taking advantage of the concentration of measure, we formulate a convex problem with constraint on the desired PAR. Consequently, the proposed scheme almost exactly achieves the desired PAR on average, and asymptotically attains the desired PAR at the 0.001 point of its complementary cumulative distribution function, as the number of subcarriers increases.

  9. TRIM21 is a novel regulator of Par-4 in colon and pancreatic cancer cells

    PubMed Central

    Nguyen, Jeffrey Q.; Irby, Rosalyn B.

    2017-01-01

    ABSTRACT The prostate apoptosis response protein 4 (Par-4) is a tumor-suppressor that has been shown to induce cancer-cell selective apoptosis in a variety of cancers. The regulation of Par-4 expression and activity is a relatively understudied area, and identifying novel regulators of Par-4 may serve as novel therapeutic targets. To identify novel regulators of Par-4, a co-immunoprecipitation was performed in colon cancer cells, and co-precipitated proteins were identified by mass-spectometry. TRIM21 was identified as a novel interacting partner of Par-4, and further shown to interact with Par-4 endogenously and through its PRY-SPRY domain. Additional studies show that TRIM21 downregulates Par-4 levels in response to cisplatin, and that TRIM21 can increase the resistance of colon cancer cells to cisplatin. Furthermore, forced Par-4 expression can sensitize pancreatic cancer cells to cisplatin. Finally, we demonstrate that TRIM21 expression predicts survival in pancreatic cancer patients. Our work highlights a novel mechanism of Par-4 regulation, and identifies a novel prognostic marker and potential therapeutic target for pancreatic cancer. PMID:27830973

  10. Tryptase-PAR2 axis in experimental autoimmune prostatitis, a model for chronic pelvic pain syndrome.

    PubMed

    Roman, Kenny; Done, Joseph D; Schaeffer, Anthony J; Murphy, Stephen F; Thumbikat, Praveen

    2014-07-01

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine EAP. Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia led to extracellular signal-regulated kinase (ERK)1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS.

  11. The polarity protein Par3 regulates APP trafficking and processing through the endocytic adaptor protein Numb.

    PubMed

    Sun, Miao; Asghar, Suwaiba Z; Zhang, Huaye

    2016-09-01

    The processing of amyloid precursor protein (APP) into β-amyloid peptide (Aβ) is a key step in the pathogenesis of Alzheimer's disease (AD), and trafficking dysregulations of APP and its secretases contribute significantly to altered APP processing. Here we show that the cell polarity protein Par3 plays an important role in APP processing and trafficking. We found that the expression of full length Par3 is significantly decreased in AD patients. Overexpression of Par3 promotes non-amyloidogenic APP processing, while depletion of Par3 induces intracellular accumulation of Aβ. We further show that Par3 functions by regulating APP trafficking. Loss of Par3 decreases surface expression of APP by targeting APP to the late endosome/lysosome pathway. Finally, we show that the effects of Par3 are mediated through the endocytic adaptor protein Numb, and Par3 functions by interfering with the interaction between Numb and APP. Together, our studies show a novel role for Par3 in regulating APP processing and trafficking.

  12. Common variants in the human platelet PAR4 thrombin receptor alter platelet function and differ by race

    PubMed Central

    Edelstein, Leonard C.; Simon, Lukas M.; Lindsay, Cory R.; Kong, Xianguo; Teruel-Montoya, Raúl; Tourdot, Benjamin E.; Chen, Edward S.; Ma, Lin; Coughlin, Shaun; Nieman, Marvin; Holinstat, Michael; Shaw, Chad A.

    2014-01-01

    Human platelets express 2 thrombin receptors: protease-activated receptor (PAR)-1 and PAR4. Recently, we reported 3.7-fold increased PAR4-mediated aggregation kinetics in platelets from black subjects compared with white subjects. We now show that platelets from blacks (n = 70) express 14% more PAR4 protein than those from whites (n = 84), but this difference is not associated with platelet PAR4 function. Quantitative trait locus analysis identified 3 common single nucleotide polymorphisms in the PAR4 gene (F2RL3) associated with PAR4-induced platelet aggregation. Among these single nucleotide polymorphisms, rs773902 determines whether residue 120 in transmembrane domain 2 is an alanine (Ala) or threonine (Thr). Compared with the Ala120 variant, Thr120 was more common in black subjects than in white subjects (63% vs 19%), was associated with higher PAR4-induced human platelet aggregation and Ca2+ flux, and generated greater inositol 1,4,5-triphosphate in transfected cells. A second, less frequent F2RL3 variant, Phe296Val, was only observed in blacks and abolished the enhanced PAR4-induced platelet aggregation and 1,4,5-triphosphate generation associated with PAR4-Thr120. PAR4 genotype did not affect vorapaxar inhibition of platelet PAR1 function, but a strong pharmacogenetic effect was observed with the PAR4-specific antagonist YD-3 [1-benzyl-3(ethoxycarbonylphenyl)-indazole]. These findings may have an important pharmacogenetic effect on the development of new PAR antagonists. PMID:25293779

  13. Mapping transmembrane residues of proteinase activated receptor 2 (PAR2) that influence ligand-modulated calcium signaling.

    PubMed

    Suen, J Y; Adams, M N; Lim, J; Madala, P K; Xu, W; Cotterell, A J; He, Y; Yau, M K; Hooper, J D; Fairlie, D P

    2017-03-01

    Proteinase-activated receptor 2 (PAR2) is a G protein-coupled receptor involved in metabolism, inflammation, and cancers. It is activated by proteolysis, which exposes a nascent N-terminal sequence that becomes a tethered agonist. Short synthetic peptides corresponding to this sequence also activate PAR2, while small organic molecules show promising PAR2 antagonism. Developing PAR2 ligands into pharmaceuticals is hindered by a lack of knowledge of how synthetic ligands interact with and differentially modulate PAR2. Guided by PAR2 homology modeling and ligand docking based on bovine rhodopsin, followed by cross-checking with newer PAR2 models based on ORL-1 and PAR1, site-directed mutagenesis of PAR2 was used to investigate the pharmacology of three agonists (two synthetic agonists and trypsin-exposed tethered ligand) and one antagonist for modulation of PAR2 signaling. Effects of 28 PAR2 mutations were examined for PAR2-mediated calcium mobilization and key mutants were selected for measuring ligand binding. Nineteen of twenty-eight PAR2 mutations reduced the potency of at least one ligand by >10-fold. Key residues mapped predominantly to a cluster in the transmembrane (TM) domains of PAR2, differentially influence intracellular Ca(2+) induced by synthetic agonists versus a native agonist, and highlight subtly different TM residues involved in receptor activation. This is the first evidence highlighting the importance of the PAR2 TM regions for receptor activation by synthetic PAR2 agonists and antagonists. The trypsin-cleaved N-terminus that activates PAR2 was unaffected by residues that affected synthetic peptides, challenging the widespread practice of substituting peptides for proteases to characterize PAR2 physiology.

  14. Solar PAR and UVR modify the community composition and photosynthetic activity of sea ice algae.

    PubMed

    Enberg, Sara; Piiparinen, Jonna; Majaneva, Markus; Vähätalo, Anssi V; Autio, Riitta; Rintala, Janne-Markus

    2015-10-01

    The effects of increased photosynthetically active radiation (PAR) and ultraviolet radiation (UVR) on species diversity, biomass and photosynthetic activity were studied in fast ice algal communities. The experimental set-up consisted of nine 1.44 m(2) squares with three treatments: untreated with natural snow cover (UNT), snow-free (PAR + UVR) and snow-free ice covered with a UV screen (PAR). The total algal biomass, dominated by diatoms and dinoflagellates, increased in all treatments during the experiment. However, the smaller biomass growth in the top 10-cm layer of the PAR + UVR treatment compared with the PAR treatment indicated the negative effect of UVR. Scrippsiella complex (mainly Scrippsiella hangoei, Biecheleria baltica and Gymnodinium corollarium) showed UV sensitivity in the top 5-cm layer, whereas Heterocapsa arctica ssp. frigida and green algae showed sensitivity to both PAR and UVR. The photosynthetic activity was highest in the top 5-cm layer of the PAR treatment, where the biomass of the pennate diatom Nitzschia frigida increased, indicating the UV sensitivity of this species. This study shows that UVR is one of the controlling factors of algal communities in Baltic Sea ice, and that increased availability of PAR together with UVR exclusion can cause changes in algal biomass, photosynthetic activity and community composition.

  15. Participatory Action Research (PAR) cum Action Research (AR) in Teacher Professional Development: A Literature Review

    ERIC Educational Resources Information Center

    Morales, Marie Paz E.

    2016-01-01

    This paper reviews Participatory Action Research as an approach to teacher professional development. It maps the origins of Participatory Action Research (PAR) and discusses the benefits and challenges that have been identified by other researchers in utilizing PAR approaches in conducting research. It draws ideas of combining the features of…

  16. Loss of Par3 promotes lung adenocarcinoma metastasis through 14-3-3ζ protein.

    PubMed

    Song, Tong; Tian, Xia; Kai, Fan; Ke, Jiang; Wei, Zhai; Jing-Song, Li; Si-Hua, Wang; Jian-Jun, Wang

    2016-09-27

    Partitioning defective protein 3 (Par3) can activate the Tiam1/Rac pathway to inhibit invasion and metastasis in many cancers; however, the role of Par3 in lung adenocarcinoma remains unknown. Here we show that Par3 is downregulated in lung adenocarcinoma tissues and is associated with higher rates of lymph node metastasis and recurrence. Our functional study demonstrated that knock-down of Par3 promoted lung adenocarcinoma cell growth, cell migration, tumor formation, and metastasis, all of which were effectively inhibited when 14-3-3ζ was silenced. We found that Par3 binded with 14-3-3ζ protein and also showed that Par3 abrogated the binding of 14-3-3ζ to Tiam1, which was responsible for Rac1 activation. Knock-down of 14-3-3ζ inhibited Tiam1/Rac-GTP activation and blocked the invasive behavior of cells lacking Par3. These data suggest that loss of Par3 promotes metastatic behavior in lung adenocarcinoma cells through 14-3-3ζ protein.

  17. 12 CFR 925.19 - Par value and price of stock.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Par value and price of stock. 925.19 Section 925.19 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOME LOAN BANK MEMBERS AND HOUSING ASSOCIATES MEMBERS OF THE BANKS Stock Requirements § 925.19 Par value and price of stock. The capital...

  18. Human bronchial epithelial cells express PAR-2 with different sensitivity to thermolysin.

    PubMed

    Ubl, Joachim J; Grishina, Zoryana V; Sukhomlin, Tatiana K; Welte, Tobias; Sedehizade, Fariba; Reiser, Georg

    2002-06-01

    Protease-activated receptor-2 (PAR-2) plays a role in inflammatory reactions in airway physiology. Proteases cleaving the extracellular NH(2) terminus of receptors activate or inactivate PAR, thus possessing a therapeutic potential. Using RT-PCR and immunocytochemistry, we show PAR-2 in human airway epithelial cell lines human bronchial epithelial (HBE) and A549. Functional expression of PAR-2 was confirmed by Ca(2+) imaging studies using the receptor agonist protease trypsin. The effect was abolished by soybean trypsin inhibitor and mimicked by the specific PAR-2 peptide agonist SLIGKV. Amplitude and duration of PAR-2-elicited Ca(2+) response in HBE and A549 cells depend on concentration and time of agonist superfusion. The response is partially pertussis toxin (PTX) insensitive, abolished by the phospholipase C inhibitor U-73122, and diminished by the inositol 1,4,5-trisphosphate receptor antagonist 2-aminoethoxydiphenyl borate. Cathepsin G altered neither the resting Ca(2+) level nor PAR-2-elicited Ca(2+) response. Thermolysin, a prototypic bacterial metalloprotease, induced a dose-dependent Ca(2+) response in HBE, but not A549, cells. In both cell lines, thermolysin abolished the response to a subsequent trypsin challenge but not to SLIGKV. Thus different epithelial cell types express different PAR-2 with identical responses to physiological stimuli (trypsin, SLIGKV) but different sensitivity to modifying proteases, such as thermolysin.

  19. Slmb antagonises the aPKC/Par-6 complex to control oocyte and epithelial polarity.

    PubMed

    Morais-de-Sá, Eurico; Mukherjee, Avik; Lowe, Nick; St Johnston, Daniel

    2014-08-01

    The Drosophila anterior-posterior axis is specified when the posterior follicle cells signal to polarise the oocyte, leading to the anterior/lateral localisation of the Par-6/aPKC complex and the posterior recruitment of Par-1, which induces a microtubule reorganisation that localises bicoid and oskar mRNAs. Here we show that oocyte polarity requires Slmb, the substrate specificity subunit of the SCF E3 ubiquitin ligase that targets proteins for degradation. The Par-6/aPKC complex is ectopically localised to the posterior of slmb mutant oocytes, and Par-1 and oskar mRNA are mislocalised. Slmb appears to play a related role in epithelial follicle cells, as large slmb mutant clones disrupt epithelial organisation, whereas small clones show an expansion of the apical domain, with increased accumulation of apical polarity factors at the apical cortex. The levels of aPKC and Par-6 are significantly increased in slmb mutants, whereas Baz is slightly reduced. Thus, Slmb may induce the polarisation of the anterior-posterior axis of the oocyte by targeting the Par-6/aPKC complex for degradation at the oocyte posterior. Consistent with this, overexpression of the aPKC antagonist Lgl strongly rescues the polarity defects of slmb mutant germline clones. The role of Slmb in oocyte polarity raises an intriguing parallel with C. elegans axis formation, in which PAR-2 excludes the anterior PAR complex from the posterior cortex to induce polarity, but its function can be substituted by overexpressing Lgl.

  20. Bacterial DNA segregation dynamics mediated by the polymerizing protein ParF

    PubMed Central

    Barillà, Daniela; Rosenberg, Mark F; Nobbmann, Ulf; Hayes, Finbarr

    2005-01-01

    Prokaryotic DNA segregation most commonly involves members of the Walker-type ParA superfamily. Here we show that the ParF partition protein specified by the TP228 plasmid is a ParA ATPase that assembles into extensive filaments in vitro. Polymerization is potentiated by ATP binding and does not require nucleotide hydrolysis. Analysis of mutations in conserved residues of the Walker A motif established a functional coupling between filament dynamics and DNA partitioning. The partner partition protein ParG plays two separable roles in the ParF polymerization process. ParF is unrelated to prokaryotic polymerizing proteins of the actin or tubulin families, but is a homologue of the MinD cell division protein, which also assembles into filaments. The ultrastructures of the ParF and MinD polymers are remarkably similar. This points to an evolutionary parallel between DNA segregation and cytokinesis in prokaryotic cells, and reveals a potential molecular mechanism for plasmid and chromosome segregation mediated by the ubiquitous ParA-type proteins. PMID:15775965

  1. The parA resolvase performs site-specific genomic excision in Arabidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have designed a site-specific excision detection system in Arabidopsis to study the in planta activity of the small serine recombinase ParA. Using a transient expression assay as well as stable transgenic plant lines, we show that the ParA recombinase is catalytically active and capable of perfo...

  2. Questioning Our Questions: Assessing Question Asking Practices to Evaluate a yPAR Program

    ERIC Educational Resources Information Center

    Grace, Sarah; Langhout, Regina Day

    2014-01-01

    The purpose of this research was to examine question asking practices in a youth participatory action research (yPAR) after school program housed at an elementary school. The research question was: In which ways did the adult question asking practices in a yPAR setting challenge and/or reproduce conventional models of power in educational…

  3. Regulation of long-term repopulating hematopoietic stem cells by EPCR/PAR1 signaling

    PubMed Central

    Gur-Cohen, Shiri; Kollet, Orit; Graf, Claudine; Esmon, Charles T.; Ruf, Wolfram; Lapidot, Tsvee

    2016-01-01

    The common developmental origin of endothelial and hematopoietic cells is manifested by coexpression of several cell surface receptors. Adult murine bone marrow (BM) long-term repopulating hematopoietic stem cells (LT-HSCs), endowed with the highest repopulation and self-renewal potential, express endothelial protein C receptor (EPCR), which is used as a marker to isolate them. EPCR/PAR1 signaling in endothelial cells has anticoagulant and anti-inflammatory roles, while thrombin/PAR1 signaling induces coagulation and inflammation. Recent studies define two new PAR1-mediated signaling cascades that regulate EPCR+ LT-HSC BM retention and egress. EPCR/PAR1 signaling facilitates LT-HSC BM repopulation, retention, survival, and chemotherapy resistance by restricting nitric oxide (NO) production, maintaining NOlow LT-HSC BM retention with increased VLA4 expression, affinity, and adhesion. Conversely, acute stress and clinical mobilization upregulate thrombin generation and activate different PAR1 signaling which overcomes BM EPCR+ LT-HSC retention, inducing their recruitment to the bloodstream. Thrombin/PAR1 signaling induces NO generation, TACE-mediated EPCR shedding, and upregulation of CXCR4 and PAR1, leading to CXCL12-mediated stem and progenitor cell mobilization. This review discusses new roles for factors traditionally viewed as coagulation related, which independently act in the BM to regulate PAR1 signaling in bone- and blood-forming progenitor cells, navigating their fate by controlling NO production. PMID:26928241

  4. Loss of Par3 promotes lung adenocarcinoma metastasis through 14-3-3ζ protein

    PubMed Central

    Tong, Song; Xia, Tian; Fan, Kai; Jiang, Ke; Zhai, Wei; Li, Jing-Song; Wang, Si-Hua; Wang, Jian-Jun

    2016-01-01

    Partitioning defective protein 3 (Par3) can activate the Tiam1/Rac pathway to inhibit invasion and metastasis in many cancers; however, the role of Par3 in lung adenocarcinoma remains unknown. Here we show that Par3 is downregulated in lung adenocarcinoma tissues and is associated with higher rates of lymph node metastasis and recurrence. Our functional study demonstrated that knock-down of Par3 promoted lung adenocarcinoma cell growth, cell migration, tumor formation, and metastasis, all of which were effectively inhibited when 14-3-3ζ was silenced. We found that Par3 binded with 14-3-3ζ protein and also showed that Par3 abrogated the binding of 14-3-3ζ to Tiam1, which was responsible for Rac1 activation. Knock-down of 14-3-3ζ inhibited Tiam1/Rac-GTP activation and blocked the invasive behavior of cells lacking Par3. These data suggest that loss of Par3 promotes metastatic behavior in lung adenocarcinoma cells through 14-3-3ζ protein. PMID:27588399

  5. Design and synthesis of peptides from bacterial ParE toxin as inhibitors of topoisomerases.

    PubMed

    Barbosa, Luiz Carlos Bertucci; Garrido, Saulo Santesso; Garcia, Anderson; Delfino, Davi Barbosa; Santos, Laura do Nascimento; Marchetto, Reinaldo

    2012-08-01

    Toxin-antitoxin (TA) proteic systems encode a toxin and an antitoxin that regulate the growth and death of bacterial cells under various stress conditions. The ParE protein is a toxin that inhibits DNA gyrase activity and thereby blocks DNA replication. Based on the Escherichia coli ParE structure, a series of linear peptides were designed and synthesized by solid-phase methodology. The ability of the peptides to inhibit the activity of bacterial topoisomerases was investigated. Four peptides (ParELC3, ParELC8, ParELC10 and ParELC12), showed complete inhibition of DNA gyrase supercoiling activity with an IC(100) between 20 and 40 μmol L(-1). In contrast to wild-type ParE, the peptide analogues were able to inhibit the DNA relaxation of topoisomerase IV, another type IIA bacterial topoisomerase, with lower IC(100) values. Interestingly only ParELC12 displayed inhibition of the relaxation activity of human topoisomerase II. Our findings reveal new inhibitors of bacterial topoisomerases and are a good starting point for the development of a new class of antibacterial agents that targets the DNA topoisomerases.

  6. Lack of changes in serum prolactin, FSH, TSH, and estradiol after melatonin treatment in doses that improve sleep and reduce benzodiazepine consumption in sleep-disturbed, middle-aged, and elderly patients.

    PubMed

    Siegrist, C; Benedetti, C; Orlando, A; Beltrán, J M; Tuchscherr, L; Noseda, C M; Brusco, L I; Cardinali, D P

    2001-01-01

    An open pilot study on the safety and efficacy of melatonin in the treatment of insomniac patients was conducted in 22 subjects (16 females), mean +/- S.D. age 60.1 +/- 9.5 years. All patients received 3 mg of gelatin melatonin capsules per os daily for 6 months, 30 min before expected sleep time. Twenty of 22 patients were on benzodiazepine treatment and they continued this treatment for part of or for the entire melatonin administration period. Serum concentrations of prolactin, follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), or estradiol were measured by radioimmunoassay (RIA) in morning samples at the beginning and after 6 months of melatonin administration, and standard clinical laboratory tests for blood components were performed. Urinary 6-sulphatoxymelatonin (aMT6s) excretion was measured by RIA before treatment. Serum concentrations of prolactin, FSH, TSH, or estradiol did not exhibit changes after 6 months of melatonin administration, nor were any indications of hematologic or blood biochemistry alteration found. Melatonin augmented significantly the quality and duration of sleep, and decreased sleep latency and the number of awakening episodes, as assessed from sleep logs filled by the patients (first 21 days) and from structured interviews performed by incumbent physicians (up to 6 months). Estimates of next-day function (i.e., alertness in the morning and during the day) also improved significantly during melatonin treatment. The observed effect lasted for the entire period examined (up to 6 months), with 22 out of 22 patients showing improved sleep at the end of treatment. The urinary excretion of aMT6s before starting administration of melatonin correlated negatively and significantly with age, but not with the intensity of sleep the disorder or the outcome of treatment. In 13 of 20 patients taking benzodiazepines together with melatonin, benzodiazepine use could be stopped, and in another four patients, benzodiazepine dose

  7. Compression Myelopathy due to Proliferative Changes around C2 Pars Defects without Instability

    PubMed Central

    Kimura, Tetsuya; Tezuka, Fumitake; Abe, Mitsunobu; Yamashita, Kazuta; Takata, Yoichiro; Higashino, Kosaku; Sairyo, Koichi

    2016-01-01

    We report a case with compression myelopathy due to proliferative changes around the C2 pars defects without instability. A 69-year-old man presented with progressive clumsy hands and spastic gait. Plain radiographs showed bilateral spondylolysis (pars defects) at C2 and fusion between C2 and C3 spinous processes. Dynamic views revealed mobility through the pars defects, but there was no apparent instability. Computed tomography showed proliferative changes at the pars defects, which protruded into spinal canal. On magnetic resonance imaging, the spinal cord was compressed and intramedullary high signal change was found. A diagnosis of compression myelopathy due to proliferative changes around the C2 pars defects was made. We performed posterior decompression. Postoperatively, symptoms have been alleviated and images revealed sufficient decompression and no apparent instability. In patients with the cervical spondylolysis, myelopathy caused by instability or slippage have been periodically reported. The present case involving C2 spondylolysis is extremely rare. PMID:27340539

  8. Loss of the Par3 polarity protein promotes breast tumorigenesis and metastasis.

    PubMed

    McCaffrey, Luke Martin; Montalbano, JoAnne; Mihai, Constantina; Macara, Ian G

    2012-11-13

    Loss of epithelial organization is a hallmark of carcinomas, but whether polarity regulates tumor growth and metastasis is poorly understood. To address this issue, we depleted the Par3 polarity gene by RNAi in combination with oncogenic Notch or Ras(61L) expression in the murine mammary gland. Par3 silencing dramatically reduced tumor latency in both models and produced invasive and metastatic tumors that retained epithelial marker expression. Par3 depletion was associated with induction of MMP9, destruction of the extracellular matrix, and invasion, all mediated by atypical PKC-dependant JAK/Stat3 activation. Importantly, Par3 expression is significantly reduced in human breast cancers, which correlates with active aPKC and Stat3. These data identify Par3 as a regulator of signaling pathways relevant to invasive breast cancer.

  9. PAR Interception and Utilization in Different Maize and Soybean Intercropping Patterns

    PubMed Central

    Liu, Xin; Rahman, Tanzeelur; Yang, Feng; Song, Chun; Yong, Taiwen; Liu, Jiang; Zhang, Cuiying; Yang, Wenyu

    2017-01-01

    The crop intercepted photosynthetically active radiation (PAR) and radiation use efficiency (RUE) vary markedly in different intercropping systems. The HHLA (horizontally homogeneous leaf area) and ERCRT (extended row crop radiation transmission) models have been established to calculate the intercepted PAR for intercrops. However, there is still a lack of study on the intercepted PAR and RUE under different intercropping configurations using different models. To evaluate the intercepted PAR and RUE in maize and soybean under different intercropping systems, we tested different strip intercropping configurations (SI1, SI2, and SI3 based on ERCRT model) and a row intercropping configurations (RI based on HHLA model) in comparison to monoculture. Our results showed that the intercepted PAR and RUE of intercropping systems were all higher than those of monoculture. The soybean intercepted PAR in strip intercropping was 1.35 times greater than that in row intercropping. In row intercropping (RI), the lack of soybean intercepted PAR resulted in a significant reduction of soybean dry matter. Therefore, it is not the recommended configuration for soybean. In strip intercropping patterns, with the distance between maize strip increased by 0.2 m, the intercepted PAR of soybean increased by 20%. The SI2 (maize row spacing at 0.4 m and the distance between maize strip at 1.6 m) was the recommended configuration to achieve the highest value of intercepted PAR and RUE among tested strip intercropping configurations. The method of dry matter estimation using intercepted PAR and RUE is useful in simulated experiments. The simulated value was verified in comparison with experimental data, which confirmed the credibility of the simulation model. Moreover, it also provides help in the development of functional-structural plant model (FSPM). PMID:28056056

  10. Facteurs de risque de mortalité par tuberculose pulmonaire

    PubMed Central

    Janah, Hicham; Souhi, Hicham; Kouismi, Hatim; Mark, Karima; Zahraoui, Rachida; Benamor, Jouda; Soualhi, Mona; Bourkadi, Jamal Eddine

    2014-01-01

    La tuberculose est une maladie infectieuse transmissible provoquée par myco-bacterium tuberculosis (bacille de Koch ou BK). Elle représente, selon les estimations del'Organisation Mondiale de la Santé (OMS), l'une des pathologies infectieuses causant le plus de décès au niveau mondial avec plus de 1 million de décès par an. Pour déterminer les facteurs de risque de mortalité au cours de la tuberculose pulmonaire à microscopie positive nous avons mené une étude rétrospective portant sur tous les cas de tuberculose pulmonaire à microscopie positive et qui étaient décédés au cours de leur hospitalisation. Cette étude a colligé 1803 cas de tuberculose sur une période de 2 ans et demi dont 46 sont décédés. La prévalence de décès est de 2,55%. La population se répartit en 32 hommes et 14 femmes. L’âge moyen était de 53ans ± 17 ans. Le tabagisme était retrouvé chez la moitié des cas. Une comorbidité était retrouvée dans 43%, avec 17% de diabète. Le délai de diagnostic avait une médiane de 60 jours avec percentile (30j; 105j). La symptomatologie clinique était dominée par la toux, la dyspnée et les expectorations soit respectivement: 97,8%, 69,6% et 67,4% des cas. Sur le plan radiologique les lésions étaient diffuses et bilatérales dans 76,1% des cas. Tous les patients étaient mis sous SRHZ. 11% avaient présenté une toxicité aux antibacillaires (de type hépatiques dans 3 cas et neurologiques dans 2 cas). Le délai médian de décès était de 8,5 jours (5j; 17j). Les causes de décès retrouvées étaient: Une hépatite fulminante (3 cas), une décompensation acido-cétosique (3 cas), un SDRA (2 cas), des hémoptysies foudroyantes (2 cas), et respectivement un cas secondaire à une décompensation de BPCO, une décompensation cardiaque, une hypoglycémie et un tableau d'anasarque. Cette étude suggère que le terrain, le retard diagnostique et les effets secondaires du traitement sont les principaux facteurs de risque de

  11. PAR-2 receptor-induced effects on human eccrine sweat gland cells.

    PubMed

    L Bovell, Douglas; Kofler, Barbara; Lang, Roland

    2009-01-01

    Serine proteases can induce cell signaling by stimulating G-protein-coupled receptors, called proteinase-activated receptors (PAR's) on a variety of epithelial cells. While PAR-2, one such receptor, activates cell signaling in a secretory cell line derived from human sweat glands, there was no information on their presence and effects on intact sweat glands. PAR-2 presence and activation of eccrine sweat glands isolated from human skin samples was investigated using Western blot analysis, immunohistochemistry, electron microscopy (EM) and Ca(2+) imaging. Anti-human PAR-2 antibody demonstrated the presence of these receptors in eccrine sweat glands. EM showed that PAR-2 activation resulted in degranulation of secretory cells. Ca(2+) imaging using PAR-2 activators demonstrated a two phase increase in [Ca(2+)](i) which was dependent on extracellular Ca(2+) for the second phase, and that the response could be blocked by prior incubation with xestospongin, the IP(3) receptor blocker. The results demonstrated that PAR-2 receptors are present in human sweat gland secretory cells and that these receptors are functionally active and can induce changes associated with secretory events in eccrine glands.

  12. Blocking PAR2 Alleviates Bladder Pain and Hyperactivity via TRPA1 Signal.

    PubMed

    Chen, Daihui; Liu, Nian; Li, Mao; Liang, Simin

    2016-01-01

    Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The goals of this study were to examine 1) the effects of blocking proteinase-activated receptor-2 (PAR2) on the exaggerated bladder activity and pain evoked by cystitis and 2) the underlying mechanisms responsible for the role of PAR2 in regulating cystic sensory activity. The protein expression of PAR2 was amplified in rats with cystitis by inducing it with systemic administration of cyclophosphamide (CYP) as compared with control rats. Blocking PAR2 by intrathecal infusion of PAR2 antagonist FSLLRY-NH2 attenuated bladder hyperactivity and pain. In addition, blocking PAR2 attenuated the transient receptor potential A1 (TRPA1) signal pathway, whereas inhibition of the TRPA1 decreased bladder hyperactivity and pain. The data revealed specific signaling pathways leading to CYP-induced bladder hyperactivity and pain, including the activation of PAR2 and TRPA1. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis.

  13. Evidence for a DNA-relay mechanism in ParABS-mediated chromosome segregation.

    PubMed

    Lim, Hoong Chuin; Surovtsev, Ivan Vladimirovich; Beltran, Bruno Gabriel; Huang, Fang; Bewersdorf, Jörg; Jacobs-Wagner, Christine

    2014-05-23

    The widely conserved ParABS system plays a major role in bacterial chromosome segregation. How the components of this system work together to generate translocation force and directional motion remains uncertain. Here, we combine biochemical approaches, quantitative imaging and mathematical modeling to examine the mechanism by which ParA drives the translocation of the ParB/parS partition complex in Caulobacter crescentus. Our experiments, together with simulations grounded on experimentally-determined biochemical and cellular parameters, suggest a novel 'DNA-relay' mechanism in which the chromosome plays a mechanical function. In this model, DNA-bound ParA-ATP dimers serve as transient tethers that harness the elastic dynamics of the chromosome to relay the partition complex from one DNA region to another across a ParA-ATP dimer gradient. Since ParA-like proteins are implicated in the partitioning of various cytoplasmic cargos, the conservation of their DNA-binding activity suggests that the DNA-relay mechanism may be a general form of intracellular transport in bacteria.DOI: http://dx.doi.org/10.7554/eLife.02758.001.

  14. Targeting uPAR with antagonistic recombinant human antibodies in aggressive breast cancer.

    PubMed

    LeBeau, Aaron M; Duriseti, Sai; Murphy, Stephanie T; Pepin, Francois; Hann, Byron; Gray, Joe W; VanBrocklin, Henry F; Craik, Charles S

    2013-04-01

    Components of the plasminogen activation system, which are overexpressed in aggressive breast cancer subtypes, offer appealing targets for development of new diagnostics and therapeutics. By comparing gene expression data in patient populations and cultured cell lines, we identified elevated levels of the urokinase plasminogen activation receptor (uPAR, PLAUR) in highly aggressive breast cancer subtypes and cell lines. Recombinant human anti-uPAR antagonistic antibodies exhibited potent binding in vitro to the surface of cancer cells expressing uPAR. In vivo these antibodies detected uPAR expression in triple negative breast cancer (TNBC) tumor xenografts using near infrared imaging and (111)In single-photon emission computed tomography. Antibody-based uPAR imaging probes accurately detected small disseminated lesions in a tumor metastasis model, complementing the current clinical imaging standard (18)F-fluorodeoxyglucose at detecting non-glucose-avid metastatic lesions. A monotherapy study using the antagonistic antibodies resulted in a significant decrease in tumor growth in a TNBC xenograft model. In addition, a radioimmunotherapy study, using the anti-uPAR antibodies conjugated to the therapeutic radioisotope (177)Lu, found that they were effective at reducing tumor burden in vivo. Taken together, our results offer a preclinical proof of concept for uPAR targeting as a strategy for breast cancer diagnosis and therapy using this novel human antibody technology.

  15. Blocking PAR2 Alleviates Bladder Pain and Hyperactivity via TRPA1 Signal

    PubMed Central

    Chen, Daihui; Liu, Nian; Li, Mao

    2016-01-01

    Abstract Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The goals of this study were to examine 1) the effects of blocking proteinase-activated receptor-2 (PAR2) on the exaggerated bladder activity and pain evoked by cystitis and 2) the underlying mechanisms responsible for the role of PAR2 in regulating cystic sensory activity. The protein expression of PAR2 was amplified in rats with cystitis by inducing it with systemic administration of cyclophosphamide (CYP) as compared with control rats. Blocking PAR2 by intrathecal infusion of PAR2 antagonist FSLLRY-NH2 attenuated bladder hyperactivity and pain. In addition, blocking PAR2 attenuated the transient receptor potential A1 (TRPA1) signal pathway, whereas inhibition of the TRPA1 decreased bladder hyperactivity and pain. The data revealed specific signaling pathways leading to CYP-induced bladder hyperactivity and pain, including the activation of PAR2 and TRPA1. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis. PMID:28123833

  16. PAR1 activation induces rapid changes in glutamate uptake and astrocyte morphology

    PubMed Central

    Sweeney, Amanda M.; Fleming, Kelsey E.; McCauley, John P.; Rodriguez, Marvin F.; Martin, Elliot T.; Sousa, Alioscka A.; Leapman, Richard D.; Scimemi, Annalisa

    2017-01-01

    The G-protein coupled, protease-activated receptor 1 (PAR1) is a membrane protein expressed in astrocytes. Fine astrocytic processes are in tight contact with neurons and blood vessels and shape excitatory synaptic transmission due to their abundant expression of glutamate transporters. PAR1 is proteolytically-activated by bloodstream serine proteases also involved in the formation of blood clots. PAR1 activation has been suggested to play a key role in pathological states like thrombosis, hemostasis and inflammation. What remains unclear is whether PAR1 activation also regulates glutamate uptake in astrocytes and how this shapes excitatory synaptic transmission among neurons. Here we show that, in the mouse hippocampus, PAR1 activation induces a rapid structural re-organization of the neuropil surrounding glutamatergic synapses, which is associated with faster clearance of synaptically-released glutamate from the extracellular space. This effect can be recapitulated using realistic 3D Monte Carlo reaction-diffusion simulations, based on axial scanning transmission electron microscopy (STEM) tomography reconstructions of excitatory synapses. The faster glutamate clearance induced by PAR1 activation leads to short- and long-term changes in excitatory synaptic transmission. Together, these findings identify PAR1 as an important regulator of glutamatergic signaling in the hippocampus and a possible target molecule to limit brain damage during hemorrhagic stroke. PMID:28256580

  17. Par-4/NF-κB Mediates the Apoptosis of Islet β Cells Induced by Glucolipotoxicity

    PubMed Central

    QiNan, Wu; XiaGuang, Gan; XiaoTian, Lei; WuQuan, Deng; Ling, Zhang; Bing, Chen

    2016-01-01

    Apoptosis of islet β cells is a primary pathogenic feature of type 2 diabetes, and ER stress and mitochondrial dysfunction play important roles in this process. Previous research has shown that prostate apoptosis response-4 (Par-4)/NF-κB induces cancer cell apoptosis through endoplasmic reticulum (ER) stress and mitochondrial dysfunction. However, the mechanism by which Par-4/NF-κB induces islet β cell apoptosis remains unknown. We used a high glucose/palmitate intervention to mimic type 2 diabetes in vitro. We demonstrated that the high glucose/palmitate intervention induced the expression and secretion of Par-4. It also causes increased expression and activation of NF-κB, which induced NIT-1 cell apoptosis and dysfunction. Overexpression of Par-4 potentiates these effects, whereas downregulation of Par-4 attenuates them. Inhibition of NF-κB inhibited the Par-4-induced apoptosis. Furthermore, these effects occurred through the ER stress cell membrane and mitochondrial pathway of apoptosis. Our findings reveal a novel role for Par-4/NF-κB in islet β cell apoptosis and type 2 diabetes. PMID:27340675

  18. CERCLA interim action at the Par Pond unit: A case study

    SciTech Connect

    Hickey, H.M.; Matthews, S.S.; Neal, L.W.; Weiss, W.R.

    1993-11-01

    The Par Pond unit designated under CERCLA consists of sediments within a Savannah River Site (SRS) cooling water reservoir. The sediments are contaminated with radionuclides and nonradioactive constituents from nuclear production reactor operations. The mercury in Par Pond is believed to have originated from the Savannah River. Because of Par Pond Dam safety Issues, the water level of the reservoir was drawn down, exposing more than 1300 acres of contaminated sediments and triggering the need for CERCLA interim remedial action. This paper presents the interim action approach taken with Par Pond as a case study. The approach considered the complexity of the Par Pond ecosystem, the large size of Par Pond, the volume of contaminated sediments, and the institutional controls existing at SRS. The Environmental Protection Agency (EPA) considers units with large volumes of low-concentration wastes, as is the case with Par Pond, to be {open_quotes}special sites.{close_quotes} Accordingly, EPA guidance establishes that the range of alternatives developed focus primarily on containment options and other remedial approaches that mitigate potential risks associated with the {open_quotes}special site.{close_quotes} The remedial alternatives, according to EPA, are not to be prohibitively expensive or difficult to implement. This case study also is representative of the types of issues that will need to be addressed within the Department of Energy (DOE) complex as nuclear facilities are transitioned to inactive status and corrective/remedial actions are warranted.

  19. Protease-activated receptors (PARs)--biology and role in cancer invasion and metastasis.

    PubMed

    Wojtukiewicz, Marek Z; Hempel, Dominika; Sierko, Ewa; Tucker, Stephanie C; Honn, Kenneth V

    2015-12-01

    Although many studies have demonstrated that components of the hemostatic system may be involved in signaling leading to cancer progression, the potential mechanisms by which they contribute to cancer dissemination are not yet precisely understood. Among known coagulant factors, tissue factor (TF) and thrombin play a pivotal role in cancer invasion. They may be generated in the tumor microenvironment independently of blood coagulation and can induce cell signaling through activation of protease-activated receptors (PARs). PARs are transmembrane G-protein-coupled receptors (GPCRs) that are activated by a unique proteolytic mechanism. They play important roles in vascular physiology, neural tube closure, hemostasis, and inflammation. All of these agents (TF, thrombin, PARs-mainly PAR-1 and PAR-2) are thought to promote cancer invasion and metastasis at least in part by facilitating tumor cell migration, angiogenesis, and interactions with host vascular cells, including platelets, fibroblasts, and endothelial cells lining blood vessels. Here, we discuss the role of PARs and their activators in cancer progression, focusing on TF- and thrombin-mediated actions. Therapeutic options tailored specifically to inhibit PAR-induced signaling in cancer patients are presented as well.

  20. Plaies des membres par agression: analyse de 245 dossiers

    PubMed Central

    Boufettal, Monsef; Mahfoud, Mustapha; Ismael, Farid; Kharmaz, Mohamed; Bardouni, Ahmed El; Berrada, Mohamed Saleh; Yaacoubi, Moradh El

    2015-01-01

    Il s'agit d'une étuderétrospective, analytique, monocentrique rentrant dans le cadre d'une étude épidémiologique s’étalant sur une période de trois années (de 2010 à 2012) durant laquelle nous avons revu les dossiers de 245 patients victimes de violence et d'agression. Nous avons exclu les lésions simples traitées en ambulatoire. Par conséquent, nous nous sommes limités aux cas de blessures ayant nécessité une prise en charge spécialisée au bloc opératoire. Les objectifs de notre travail étaient de connaitre la fréquence des agressions au service de traumatologie du CHU de Rabat, classer les différents types de lésions, évaluer leur gravité, mettre la lumière sur les populations les plus touchées et enfin montrer les différentes modalités de prise en charge thérapeutiques. PMID:26918078

  1. Photometric monitoring of the young star Par 1724 in Orion

    NASA Astrophysics Data System (ADS)

    Neuhäuser, R.; Koeltzsch, A.; Raetz, St.; Schmidt, T. O. B.; Mugrauer, M.; Young, N.; Bertoldi, F.; Roell, T.; Eisenbeiss, T.; Hohle, M. M.; Vaňko, M.; Ginski, C.; Rammo, W.; Moualla, M.; Broeg, C.

    2009-05-01

    We report new photometric observations of the ˜ 200 000 year old naked weak-line run-away T Tauri star Par 1724, located north of the Trapezium cluster in Orion. We observed in the broad band filters B, V, R, and I using the 90 cm Dutch telescope on La Silla, the 80 cm Wendelstein telescope, and a 25 cm telescope of the University Observatory Jena in Großschwabhausen near Jena. The photometric data in V and R are consistent with a ˜ 5.7 day rotation period due to spots, as observed before between 1960ies and 2000. Also, for the first time, we present evidence for a long-term 9 or 17.5 year cycle in photometric data (V band) of such a young star, a cycle similar to that to of the Sun and other active stars. Based on observations obtained with telescopes of the University Observatory Jena, which is operated by the Astrophysical Institute of the Friedrich-Schiller-University; a telescope of the University Observatory Munich on Mount Wendelstein, the 0.9m ESO-Dutch telescope on La Silla, Chile, and with the All Sky Automated Survey (ASAS) project (www.astrouw.edu.pl/asas).

  2. [Development of agonists/antagonists for protease-activated receptors (PARs) and the possible therapeutic application to gastrointestinal diseases].

    PubMed

    Sekiguchi, Fumiko

    2005-06-01

    Protease-activated receptors (PARs), a family of G-protein-coupled seven-transmembrane-domain receptors, are activated by proteolytic unmasking of the N-terminal cryptic tethered ligand by certain serine proteases. Among four PAR family members cloned to date, PAR-1, PAR-2, and PAR-4 can also be activated through a non-enzymatic mechanism, which is achieved by direct binding of exogenously applied synthetic peptides based on the tethered ligand sequence, known as PARs-activating peptides, to the body of the receptor. Various peptide mimetics have been synthesized as agonists for PARs with improved potency, selectivity, and stability. Some peptide mimetics and/or nonpeptide compounds have also been developed as antagonists for PAR-1 and PAR-4. PARs are widely distributed in the mammalian body, especially throughout the alimentary systems, and play various roles in physiological/pathophysiological conditions, i.e., modulation of salivary, gastric, or pancreatic glandular exocrine secretion, gastrointestinal smooth muscle motility, gastric mucosal cytoprotection, suppression/facilitation of visceral pain and inflammation, etc. Thus PARs are now considered novel therapeutic targets, and development of selective agonists and/or antagonists for PARs might provide a novel strategy for the treatment of various diseases that are resistant to current therapeutics.

  3. Caractérisation par ellipsométrie spectroscopique de films minces de tellurure de bismuth obtenus par voie électrochimique

    NASA Astrophysics Data System (ADS)

    Zimmer, A.; Stein, N.; Boulanger, C.; Johann, L.

    2004-12-01

    Des films de tellurure de bismuth (Bi2Te3) d’épaisseur proche de 1 mm ont été développés par voie électrochimique. Leurs indices optiques ont été déterminés par ellipsométrie spectroscopique (SE). Le domaine spectral des indices optiques s’étend de 400 nm à 1300 nm. L’ellipsométrie spectroscopique à angle d’incidence variable (VASE) a été utilisée pour corréler les données SE. Cette partie a été complétée par des analyses par microscopie à force atomique (AFM) qui ont permis de déterminer la rugosité des films. A partir de ces résultats et en associant l’absorption fondamentale des films de Bi2Te3 à une transition indirecte, l’énergie de bande interdite a été évaluée à 0,3 eV. Par ailleurs des mesures associant ellipsométrie spectroscopique à temps réel et électrochimie ont pu être réalisées. Ainsi les premiers instants de croissance ont été observés.

  4. Evaluation of orthodontists' perception of treatment need and the peer assessment rating (PAR) index.

    PubMed

    McGorray, S P; Wheeler, T T; Keeling, S D; Yurkiewicz, L; Taylor, M G; King, G J

    1999-08-01

    This paper examines the relationship between orthodontists' subjective assessment of treatment need and objective measurements obtained during standardized intra- and extraoral examinations. Logistic regression modeling was used to develop predictive models of treatment need. Data were obtained from 1155 eighth-grade students by four orthodontists who used standardized examination forms to assess demographics, trauma, skeletal relationships, morphologic malocclusion traits, and mandibular function. At the conclusion of the examination, the orthodontist rated the subjective treatment need as none, elective, recommended, soon, or immediate. For some analyses, the categories were collapsed to represent no need and need. The peer assessment rating (PAR) index (American validated version) was computed from the clinical exam findings and scoring of dental models; PAR scores were used to document malocclusion severity and treatment difficulty. Spearman rank correlation coefficients quantified the relationship between PAR scores and need categories. Logistic regression analysis modeled treatment need using components of the PAR index as well as other variables. The components of these models, as well as sensitivity and specificity, were compared with malocclusion severity/treatment difficulty scores obtained from malocclusion assessments using the PAR index. The five subjective treatment need categories and the PAR index scores were significantly correlated (rho = 0.62, p<0.001). Significant differences were detected between the need and no need groups for all PAR components (p<0.001). PAR index scores and predicted probabilities from logistic regression models performed equally well for classification purposes (no need, need). The data suggest that the PAR index is highly correlated with orthodontists' subjective assessment of treatment need when that assessment is made in the absence of financial considerations and patient desires.

  5. Small caliber arterial endothelial cells calcium signals elicited by PAR2 are preserved from endothelial dysfunction

    PubMed Central

    Hennessey, John C; Stuyvers, Bruno D; McGuire, John J

    2015-01-01

    Endothelial cell (EC)-dependent vasodilation by proteinase-activated receptor 2 (PAR2) is preserved in small caliber arteries in disease states where vasodilation by muscarinic receptors is decreased. In this study, we identified and characterized the PAR2-mediated intracellular calcium (Ca2+)-release mechanisms in EC from small caliber arteries in healthy and diseased states. Mesenteric arterial EC were isolated from PAR2 wild-type (WT) and null mice, after saline (controls) or angiotensin II (AngII) infusion, for imaging intracellular calcium and characterizing the calcium-release system by immunofluorescence. EC Ca2+ signals comprised two forms of Ca2+-release events that had distinct spatial-temporal properties and occurred near either the plasmalemma (peripheral) or center of EC. In healthy EC, PAR2-dependent increases in the densities and firing rates of both forms of Ca2+-release were abolished by inositol 1,4,5- trisphosphate receptor (IP3R) inhibitor, but partially reduced by transient potential vanilloid channels inhibitor ruthenium red (RR). Acetylcholine (ACh)-induced less overall Ca2+-release than PAR2 activation, but enhanced selectively the incidence of central events. PAR2-dependent Ca2+-activity, inhibitors sensitivities, IP3R, small- and intermediate-conductance Ca2+-activated potassium channels expressions were unchanged in EC from AngII WT. However, the same cells exhibited decreases in ACh-induced Ca2+-release, RR sensitivity, and endothelial nitric oxide synthase expression, indicating AngII-induced dysfunction was differentiated by receptor, Ca2+-release, and downstream targets of EC activation. We conclude that PAR2 and muscarinic receptors selectively elicit two elementary Ca2+ signals in single EC. PAR2-selective IP3R-dependent peripheral Ca2+-release mechanisms are identical between healthy and diseased states. Further study of PAR2-selective Ca2+-release for eliciting pathological and/or normal EC functions is warranted. PMID:25729579

  6. KSHV-Mediated Regulation of Par3 and SNAIL Contributes to B-Cell Proliferation

    PubMed Central

    Jha, Hem C.; Sun, Zhiguo; Upadhyay, Santosh K.; El-Naccache, Darine W.; Singh, Rajnish K.; Sahu, Sushil K.; Robertson, Erle S.

    2016-01-01

    Studies have suggested that Epithelial–Mesenchymal Transition (EMT) and transformation is an important step in progression to cancer. Par3 (partitioning-defective protein) is a crucial factor in regulating epithelial cell polarity. However, the mechanism by which the latency associated nuclear antigen (LANA) encoded by Kaposi's Sarcoma associated herpesvirus (KSHV) regulates Par3 and EMTs markers (Epithelial-Mesenchymal Transition) during viral-mediated B-cell oncogenesis has not been fully explored. Moreover, several studies have demonstrated a crucial role for EMT markers during B-cell malignancies. In this study, we demonstrate that Par3 is significantly up-regulated in KSHV-infected primary B-cells. Further, Par3 interacted with LANA in KSHV positive and LANA expressing cells which led to translocation of Par3 from the cell periphery to a predominantly nuclear signal. Par3 knockdown led to reduced cell proliferation and increased apoptotic induction. Levels of SNAIL was elevated, and E-cadherin was reduced in the presence of LANA or Par3. Interestingly, KSHV infection in primary B-cells led to enhancement of SNAIL and down-regulation of E-cadherin in a temporal manner. Importantly, knockdown of SNAIL, a major EMT regulator, in KSHV cells resulted in reduced expression of LANA, Par3, and enhanced E-cadherin. Also, SNAIL bound to the promoter region of p21 and can regulate its activity. Further a SNAIL inhibitor diminished NF-kB signaling through upregulation of Caspase3 in KSHV positive cells in vitro. This was also supported by upregulation of SNAIL and Par3 in BC-3 transplanted NOD-SCID mice which has potential as a therapeutic target for KSHV-associated B-cell lymphomas. PMID:27463802

  7. Prostate apoptosis response 4 (PAR4) expression modulates WNT signaling pathways in MCF7 breast cancer cells: A possible mechanism underlying PAR4-mediated docetaxel chemosensitivity

    PubMed Central

    De Bessa Garcia, Simone Aparecida; Pavanelli, Ana Carolina; Melo, Natália Cruz E; Nagai, Maria Aparecida

    2017-01-01

    Docetaxel is an effective drug for the treatment of metastatic breast cancer. However, the exact mechanisms and/or markers associated with chemosensitivity or resistance to docetaxel remain unclear. We previously showed that the expression of prostate apoptosis response 4 (PAR4) inhibits the growth of MCF7 breast cancer cells and increases their sensitivity to docetaxel. Using cDNA microarray analysis, we evaluated transcriptome changes in MCF7 cells expressing increased levels of PAR4 and control cells before and after docetaxel treatment. Some of the top gene networks generated from the differentially expressed genes were related to the wingless-type MMTV integration 1 (WNT) canonical (WNT/β-catenin) and non-canonical (β-catenin-independent) pathways. The Human WNT signaling pathway RT2 profiler™ PCR array was used to validate the effects of PAR4 on the expression pattern of genes involved in the WNT pathway. CACNAD2A3, GDF5 and IL6 were upregulated and NANOG was downregulated in the MCF7 breast cancer cells expressing increased levels of PAR4 after treatment with docetaxel, likely indicating inactivation of the WNT/β-catenin pathway. Upregulation of FGF7, LEF1 and TWIST1 indicated activation of the WNT/β-catenin pathway. Although preliminary, our findings could be of particular interest for understanding the action of PAR4 in chemosensitivity, particularly to increase the specificity and effectiveness of drug treatment and overcome resistance to chemotherapy. Further studies are needed to better understand the biological roles of PAR4 in the regulation of WNT pathways in breast cancer cells in response to docetaxel and other chemotherapeutic agents. PMID:28259909

  8. Developpement de techniques de diagnostic non intrusif par tomographie optique

    NASA Astrophysics Data System (ADS)

    Dubot, Fabien

    Que ce soit dans les domaines des procedes industriels ou de l'imagerie medicale, on a assiste ces deux dernieres decennies a un developpement croissant des techniques optiques de diagnostic. L'engouement pour ces methodes repose principalement sur le fait qu'elles sont totalement non invasives, qu'elle utilisent des sources de rayonnement non nocives pour l'homme et l'environnement et qu'elles sont relativement peu couteuses et faciles a mettre en oeuvre comparees aux autres techniques d'imagerie. Une de ces techniques est la Tomographie Optique Diffuse (TOD). Cette methode d'imagerie tridimensionnelle consiste a caracteriser les proprietes radiatives d'un Milieu Semi-Transparent (MST) a partir de mesures optiques dans le proche infrarouge obtenues a l'aide d'un ensemble de sources et detecteurs situes sur la frontiere du domaine sonde. Elle repose notamment sur un modele direct de propagation de la lumiere dans le MST, fournissant les predictions, et un algorithme de minimisation d'une fonction de cout integrant les predictions et les mesures, permettant la reconstruction des parametres d'interet. Dans ce travail, le modele direct est l'approximation diffuse de l'equation de transfert radiatif dans le regime frequentiel tandis que les parametres d'interet sont les distributions spatiales des coefficients d'absorption et de diffusion reduit. Cette these est consacree au developpement d'une methode inverse robuste pour la resolution du probleme de TOD dans le domaine frequentiel. Pour repondre a cet objectif, ce travail est structure en trois parties qui constituent les principaux axes de la these. Premierement, une comparaison des algorithmes de Gauss-Newton amorti et de Broyden- Fletcher-Goldfarb-Shanno (BFGS) est proposee dans le cas bidimensionnel. Deux methodes de regularisation sont combinees pour chacun des deux algorithmes, a savoir la reduction de la dimension de l'espace de controle basee sur le maillage et la regularisation par penalisation de Tikhonov

  9. Regulation of the proapoptotic functions of prostate apoptosis response-4 (Par-4) by casein kinase 2 in prostate cancer cells.

    PubMed

    de Thonel, A; Hazoumé, A; Kochin, V; Isoniemi, K; Jego, G; Fourmaux, E; Hammann, A; Mjahed, H; Filhol, O; Micheau, O; Rocchi, P; Mezger, V; Eriksson, J E; Rangnekar, V M; Garrido, C

    2014-01-23

    The proapoptotic protein, prostate apoptosis response-4 (Par-4), acts as a tumor suppressor in prostate cancer cells. The serine/threonine kinase casein kinase 2 (CK2) has a well-reported role in prostate cancer resistance to apoptotic agents or anticancer drugs. However, the mechanistic understanding on how CK2 supports survival is far from complete. In this work, we demonstrate both in rat and humans that (i) Par-4 is a new substrate of the survival kinase CK2 and (ii) phosphorylation by CK2 impairs Par-4 proapoptotic functions. We also unravel different levels of CK2-dependent regulation of Par-4 between species. In rats, the phosphorylation by CK2 at the major site, S124, prevents caspase-mediated Par-4 cleavage (D123) and consequently impairs the proapoptotic function of Par-4. In humans, CK2 strongly impairs the apoptotic properties of Par-4, independently of the caspase-mediated cleavage of Par-4 (D131), by triggering the phosphorylation at residue S231. Furthermore, we show that human Par-4 residue S231 is highly phosphorylated in prostate cancer cells as compared with their normal counterparts. Finally, the sensitivity of prostate cancer cells to apoptosis by CK2 knockdown is significantly reversed by parallel knockdown of Par-4. Thus, Par-4 seems a critical target of CK2 that could be exploited for the development of new anticancer drugs.

  10. An in vitro investigation of the actions of reproductive hormones on the cervix of the ewe in the follicular stage: the effects of 17β-estradiol, oxytocin, FSH, and arachidonic acid on the cervical pathway for the synthesis of prostaglandin E2.

    PubMed

    Falchi, L; Scaramuzzi, R J

    2015-04-01

    During the periovulatory period, the cervix of the ewe relaxes and this mechanism is thought to be mediated by oxytocin and prostaglandin E2 (PGE2) in response to increased concentrations of 17β-estradiol and perhaps FSH. The aim of the study was to determine the in vitro effects of 17β-estradiol, FSH, oxytocin, and arachidonic acid (AA) on the synthesis of PGE2 and on the expression of oxytocin receptor (OTR), cytoplasmic phospholipase A2 (cPLA2), and cyclooxygenase 2 (COX-2) in explants of cervical tissue collected from ewes in the periovulatory phase of the estrous cycle. Cervical minces from ewes in the follicular phase of the estrous cycle were cultured in supplemented Eagle's Minimum Essential Medium for 48 hours with 17β-estradiol, FSH, oxytocin, or AA. After incubation, the tissue was stored at -80 °C and the media at -20 °C. Western immunoblotting was used to determine relative levels of OTR, cPLA2, and COX-2 in cervical tissue, and the media was analyzed by RIA, to determine the concentration of PGE2. The addition of 17β-estradiol increased the concentration of PGE2 in the media (P = 0.001), the levels of COX-2 (P = 0.02) and OTR (P = 0.006) but not those of cPLA2 (P = 0.15). The addition of FSH increased the levels of COX-2 (P = 0.01) but, it had no effect on the concentration of PGE2 (P = 0.08) or on the levels of OTR (P = 0.07) and cPLA2 (P = 0.15). Oxytocin did not increase the levels of COX-2 (P = 0.38) but increased those of OTR (P = 0.001) and cPLA2 (P = 0.01) but not on the concentration of PGE2 in the media. Arachidonic acid increased the levels of cPLA2 (P = 0.01) and those of COX-2 (P = 0.02) but not the concentration of PGE2 in the media. Our findings suggest that the PGE2-mediated mechanisms of cervical relaxation in the ewe during the follicular phase are stimulated by FSH, 17β-estradiol, oxytocin, and AA. They all appear to act by inducing receptors and enzymes along the synthetic pathway for PGE2.

  11. ParFit: A Python-Based Object-Oriented Program for Fitting Molecular Mechanics Parameters to ab Initio Data.

    PubMed

    Zahariev, Federico; De Silva, Nuwan; Gordon, Mark S; Windus, Theresa L; Dick-Perez, Marilu

    2017-03-27

    A newly created object-oriented program for automating the process of fitting molecular-mechanics parameters to ab initio data, termed ParFit, is presented. ParFit uses a hybrid of deterministic and stochastic genetic algorithms. ParFit can simultaneously handle several molecular-mechanics parameters in multiple molecules and can also apply symmetric and antisymmetric constraints on the optimized parameters. The simultaneous handling of several molecules enhances the transferability of the fitted parameters. ParFit is written in Python, uses a rich set of standard and nonstandard Python libraries, and can be run in parallel on multicore computer systems. As an example, a series of phosphine oxides, important for metal extraction chemistry, are parametrized using ParFit. ParFit is in an open source program available for free on GitHub ( https://github.com/fzahari/ParFit ).

  12. Role of protease-activated receptors 2 (PAR2) in ocular infections and inflammation

    PubMed Central

    Tripathi, Trivendra; Alizadeh, Hassan

    2015-01-01

    Protease-activated receptors (PARs) belong to a unique family of G protein-coupled receptors (GPCRs) that are cleaved at an activation site within the N-terminal exodomain by a variety of proteinases, essentially of the serine (Ser) proteinase family. After cleavage, the new N-terminal sequence functions as a tethered ligand, which binds intramolecularly to activate the receptor and initiate signaling. Cell signals induced through the activation of PARs appear to play a significant role in innate and adoptive immune responses of the cornea, which is constantly exposed to proteinases under physiological or pathophysiological conditions. Activation of PARs interferes with all aspects of the corneal physiology such as barrier function, transports, innate and adoptive immune responses, and functions of corneal nerves. It is not known whether the proteinase released from the microorganism can activate PARs and triggers the inflammatory responses. The role of PAR2 expressed by the corneal epithelial cells and activation by serine protease released from microorganism is discussed here. Recent evidences suggest that activation of PAR2, by the serine proteinases, play an important role in innate and inflammatory responses of the corneal infection. PMID:26078987

  13. The RNA-binding protein ATX-2 regulates cytokinesis through PAR-5 and ZEN-4

    PubMed Central

    Gnazzo, Megan M.; Uhlemann, Eva-Maria E.; Villarreal, Alex R.; Shirayama, Masaki; Dominguez, Eddie G.; Skop, Ahna R.

    2016-01-01

    The spindle midzone harbors both microtubules and proteins necessary for furrow formation and the completion of cytokinesis. However, the mechanisms that mediate the temporal and spatial recruitment of cell division factors to the spindle midzone and midbody remain unclear. Here we describe a mechanism governed by the conserved RNA-binding protein ATX-2/Ataxin-2, which targets and maintains ZEN-4 at the spindle midzone. ATX-2 does this by regulating the amount of PAR-5 at mitotic structures, particularly the spindle, centrosomes, and midbody. Preventing ATX-2 function leads to elevated levels of PAR-5, enhanced chromatin and centrosome localization of PAR-5–GFP, and ultimately a reduction of ZEN-4–GFP at the spindle midzone. Codepletion of ATX-2 and PAR-5 rescued the localization of ZEN-4 at the spindle midzone, indicating that ATX-2 mediates the localization of ZEN-4 upstream of PAR-5. We provide the first direct evidence that ATX-2 is necessary for cytokinesis and suggest a model in which ATX-2 facilitates the targeting of ZEN-4 to the spindle midzone by mediating the posttranscriptional regulation of PAR-5. PMID:27559134

  14. Examining relational empowerment for elementary school students in a yPAR program.

    PubMed

    Langhout, Regina Day; Collins, Charles; Ellison, Erin Rose

    2014-06-01

    This paper joins relational empowerment, youth empowerment, and Bridging Multiple Worlds frameworks to examine forms of relational empowerment for children in two intermediary institutions-school and a youth participatory action research after-school program (yPAR ASP). Participants were twelve children, most of whom were Latina/o and from im/migrant families, enrolled in a yPAR ASP for 2 years. A mixed-method approach was utilized; we analyzed children's interviews, self-defined goals, and their social networks to examine their experiences of relational empowerment. We conclude that children experienced each of the five relational empowerment factors-collaborative competence, bridging social divisions, facilitating others' empowerment, mobilizing networks, and passing on a legacy-in the yPAR ASP setting, and some factors in school. These experiences, however, were more pronounced in the yPAR ASP setting. Additionally, social network analyses revealed that a small but meaningful percentage of actors bridged worlds, especially home and family, but by year 2, also school and the yPAR ASP. Finally, most helpers for school-based goals came from school, but a sizable number came from family, friends, and home worlds, and by year 2, also came from the yPAR ASP. Implications range from theoretical to methodological development, including the use of social network analysis as a tool to descriptively examine relational power in context.

  15. Breaking the epithelial polarity barrier in cancer: the strange case of LKB1/PAR-4

    PubMed Central

    Partanen, Johanna I.; Tervonen, Topi A.; Klefström, Juha

    2013-01-01

    The PAR clan of polarity regulating genes was initially discovered in a genetic screen searching for genes involved in asymmetric cell divisions in the Caenorhabditis elegans embryo. Today, investigations in worms, flies and mammals have established PAR proteins as conserved and fundamental regulators of animal cell polarization in a broad range of biological phenomena requiring cellular asymmetries. The human homologue of invertebrate PAR-4, a serine–threonine kinase LKB1/STK11, has caught attention as a gene behind Peutz–Jeghers polyposis syndrome and as a bona fide tumour suppressor gene commonly mutated in sporadic cancer. LKB1 functions as a master regulator of AMP-activated protein kinase (AMPK) and 12 other kinases referred to as the AMPK-related kinases, including four human homologues of PAR-1. The role of LKB1 as part of the energy sensing LKB1-AMPK module has been intensively studied, whereas the polarity function of LKB1, in the context of homoeostasis or cancer, has gained less attention. Here, we focus on the PAR-4 identity of LKB1, discussing the weight of evidence indicating a role for LKB1 in regulation of cell polarity and epithelial integrity across species and highlight recent investigations providing new insight into the old question: does the PAR-4 identity of LKB1 matter in cancer? PMID:24062587

  16. Ocular trauma treated with pars plana vitrectomy: early outcome report

    PubMed Central

    Mansouri, Mohammad Reza; Tabatabaei, Seyed Ali; Soleimani, Mohammad; Kiarudi, Mohammad Yaser; Molaei, Saber; Rouzbahani, Mehdi; Mireshghi, Meysam; Zaeferani, Mohsen; Ghasempour, Mehrbod

    2016-01-01

    AIM To evaluate demographic variables and visual outcomes, among patients with ocular injuries involving the posterior segment, managed with pars plana vitrectomy. METHODS The records of patients were studied retrospectively from March to September 2010, to determine the age, gender, place of occurrence of trauma, visual acuity, anatomical site, nature of injury, wound length, the presence of an afferent pupillary defect, and the timing of vitrectomy. The Ocular Trauma Score was measured. The minimum follow-up from presentation was 6mo. RESULTS Ninety patients (77 males, 13 females), with a mean age of 32.7±15.8y were included over the 6-month period. The majority of cases occurred in the workplace (47 patients), followed by home (14 patients). The mean visual acuity (logMAR) of patients significantly improved from 2.36±0.72 preoperatively to 1.50±1.14 postoperatively. Twenty-three patients had preoperative vision better than 2.0 logMAR, the postoperative visual acuity was significantly better among these patients than patients with worse than 2.0 logMAR (P<0.001). Visual improvement between groups with early vitrectomy (<7d) and delayed vitrectomy (>7d) was not significantly different (P=0.66). Postoperative visual acuity was not significantly different between patients with injury in Zone I and II (P=0.64), but patients with injury in Zone III had significantly poorer visual acuity (P=0.02). Patients with relative afferent pupillary defect had significantly poorer postoperative visual acuity (P=0.02). Preoperative visual acuity, the difference of preoperative and postoperative visual acuity, and postoperative visual acuity were significantly different between groups with different ocular trauma scores (P<0.001). CONCLUSION Trauma is more likely to occur in men under 40y of age and in the workplace. The favorable final visual outcome is associated with the absence of afferent pupillary defect, ocular trauma score and presenting visual acuity as well as the zone

  17. Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells

    NASA Astrophysics Data System (ADS)

    Hansen, Line; Unmack Larsen, Esben Kjær; Nielsen, Erik Holm; Iversen, Frank; Liu, Zhuo; Thomsen, Karen; Pedersen, Michael; Skrydstrup, Troels; Nielsen, Niels Chr.; Ploug, Michael; Kjems, Jørgen

    2013-08-01

    Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient management when combined with MRI and drug delivery.Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific

  18. Heat stress-induced disruption of endothelial barrier function is via PAR1 signaling and suppressed by Xuebijing injection.

    PubMed

    Xu, Qiulin; Liu, Jingxian; Wang, Zhenglian; Guo, Xiaohua; Zhou, Gengbiao; Liu, Yanan; Huang, Qiaobing; Su, Lei

    2015-01-01

    Increased vascular permeability leading to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is central to the pathogenesis of heatstroke. Protease-activated receptor 1 (PAR1), the receptor for thrombin, plays a key role in disruption of endothelial barrier function in response to extracellular stimuli. However, the role of PAR1 in heat stress-induced endothelial hyper-permeability is unknown. In this study, we measured PAR1 protein expression in heat-stressed human umbilical venous endothelial cells (HUVECs), investigated the influences of PAR1 on endothelial permeability, F-actin rearrangement, and moesin phosphorylation by inhibiting PAR1 with its siRNA, neutralizing antibody (anti-PAR1), specific inhibitor(RWJ56110), and Xuebijing injection (XBJ), a traditional Chinese medicine used for sepsis treatment, and evaluated the role of PAR1 in heatstroke-related ALI/ARDS in mice by suppressing PAR1 with RWJ56110, anti-PAR1and XBJ. We found that heat stress induced PAR1 protein expression 2h after heat stress in endothelial cells, caused the release of endothelial matrix metalloprotease 1, an activator of PAR1, after 60 or 120 min of heat stimulation, as well as promoted endothelial hyper-permeability and F-actin rearrangement, which were inhibited by suppressing PAR1 with RWJ56110, anti-PAR1 and siRNA. PAR1 mediated moesin phosphorylation, which caused F-actin rearrangement and disruption of endothelial barrier function. To corroborate findings from in vitro experiments, we found that RWJ56110 and the anti-PAR1 significantly decreased lung edema, pulmonary microvascular permeability, protein exudation, and leukocytes infiltrations in heatstroke mice. Additionally, XBJ was found to suppress PAR1-moesin signal pathway and confer protective effects on maintaining endothelial barrier function both in vitro and in vivo heat-stressed model, similar to those observed above with the inhibition of PAR1. These results suggest that PAR1 is a potential

  19. Post-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells

    PubMed Central

    Brasseur, Kevin; Fabi, François; Adam, Pascal; Parent, Sophie; Lessard, Laurent; Asselin, Eric

    2016-01-01

    We recently reported the caspase3-dependent cleavage of Par-4 resulting in the accumulation of a 25kDa cleaved-Par-4 (cl-Par-4) fragment and we investigated in the present study the mechanisms regulating this fragment using cl-Par-4-expressing stable clones derived from ovarian and endometrial cancer cell lines. Cl-Par-4 protein was weakly express in all stable clones despite constitutive expression. However, upon cisplatin treatment, cl-Par-4 levels increased up to 50-fold relative to baseline conditions. Treatment of stable clones with proteasome and translation inhibitors revealed that cisplatin exposure might in fact protect cl-Par-4 from proteasome-dependent degradation. PI3K and MAPK pathways were also implicated as evidenced by an increase of cl-Par-4 in the presence of PI3K inhibitors and a decrease using MAPK inhibitors. Finally using bioinformatics resources, we found diverse datasets showing similar results to those we observed with the proteasome and cl-Par-4 further supporting our data. These new findings add to the complex mechanisms regulating Par-4 expression and activity, and justify further studies addressing the biological significance of this phenomenon in gynaecological cancer cells. PMID:27175591

  20. Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates DNA damage

    PubMed Central

    Kang, Ho Chul; Lee, Yun-Il; Shin, Joo-Ho; Andrabi, Shaida A.; Chi, Zhikai; Gagné, Jean-Philippe; Lee, Yunjong; Ko, Han Seok; Lee, Byoung Dae; Poirier, Guy G.; Dawson, Valina L.; Dawson, Ted M.

    2011-01-01

    Ubiquitin mediated protein degradation is crucial for regulation of cell signaling and protein quality control. Poly(ADP-ribose) (PAR) is a cell-signaling molecule that mediates changes in protein function through binding at PAR binding sites. Here we characterize the PAR binding protein, Iduna, and show that it is a PAR-dependent ubiquitin E3 ligase. Iduna’s E3 ligase activity requires PAR binding because point mutations at Y156A and R157A eliminate Iduna’s PAR binding and Iduna’s E3 ligase activity. Iduna’s E3 ligase activity also requires an intact really interesting new gene (RING) domain because Iduna possessing point mutations at either H54A or C60A is devoid of ubiquitination activity. Tandem affinity purification reveals that Iduna binds to a number of proteins that are either PARsylated or bind PAR including PAR polymerase-1, 2 (PARP1, 2), nucleolin, DNA ligase III, KU70, KU86, XRCC1, and histones. PAR binding to Iduna activates its E3 ligase function, and PAR binding is required for Iduna ubiquitination of PARP1, XRCC1, DNA ligase III, and KU70. Iduna’s PAR-dependent ubiquitination of PARP1 targets it for proteasomal degradation. Via PAR binding and ubiquitin E3 ligase activity, Iduna protects against cell death induced by the DNA damaging agent N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and rescues cells from G1 arrest and promotes cell survival after γ-irradiation. Moreover, Iduna facilitates DNA repair by reducing apurinic/apyrimidinic (AP) sites after MNNG exposure and facilitates DNA repair following γ-irradiation as assessed by the comet assay. These results define Iduna as a PAR-dependent E3 ligase that regulates cell survival and DNA repair. PMID:21825151

  1. The measurement of LH, FSH, and prolactin.

    PubMed

    Wheeler, Michael J

    2013-01-01

    In the clinical laboratory, the reproductive hormones are probably the second most commonly measured hormones after the thyroid hormones. More than 300 laboratories participate in the UK National External Quality Control Scheme. In addition, investigations into reproduction and fertility in humans and animals remain a major area of research. Illustrative methods are described for the three reproductive hormones (luteinizing hormone, follicle-stimulating hormone, prolactin). Radioimmunoassay, immunoradiometric, and enzyme assays are described to give a wide choice of assay formats. There are many commercial assays available and illustrative ones are described. Possible interferences are discussed and procedures for investigating their presence and removal are given.

  2. Follicle-stimulating hormone (FSH) blood test

    MedlinePlus

    ... 25.8 to 134.8 mIU/ml Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test result.

  3. A method for estimating the diffuse attenuation coefficient (KdPAR)from paired temperature sensors

    USGS Publications Warehouse

    Read, Jordan S.; Rose, Kevin C.; Winslow, Luke A.; Read, Emily K.

    2015-01-01

    A new method for estimating the diffuse attenuation coefficient for photosynthetically active radiation (KdPAR) from paired temperature sensors was derived. We show that during cases where the attenuation of penetrating shortwave solar radiation is the dominant source of temperature changes, time series measurements of water temperatures at multiple depths (z1 and z2) are related to one another by a linear scaling factor (a). KdPAR can then be estimated by the simple equation KdPAR ln(a)/(z2/z1). A suggested workflow is presented that outlines procedures for calculating KdPAR according to this paired temperature sensor (PTS) method. This method is best suited for conditions when radiative temperature gains are large relative to physical noise. These conditions occur frequently on water bodies with low wind and/or high KdPARs but can be used for other types of lakes during time periods of low wind and/or where spatially redundant measurements of temperatures are available. The optimal vertical placement of temperature sensors according to a priori knowledge of KdPAR is also described. This information can be used to inform the design of future sensor deployments using the PTS method or for campaigns where characterizing sub-daily changes in temperatures is important. The PTS method provides a novel method to characterize light attenuation in aquatic ecosystems without expensive radiometric equipment or the user subjectivity inherent in Secchi depth measurements. This method also can enable the estimation of KdPAR at higher frequencies than many manual monitoring programs allow.

  4. Detecting Plant Photoprotective Response to Water Stress Through Variation In PAR Reflectance

    NASA Astrophysics Data System (ADS)

    Zygielbaum, A. I.; Arkebauer, T. J.; Walter-Shea, E.

    2012-12-01

    Published papers over several decades have shown increasing leaf-level optical reflectance with decreasing leaf water content. Our experimental results using maize and sorghum showed this increase consistently, caused by variation in optical absorption, in the visible (photosynthetically active radiation - PAR) and middle infrared (MIR) spectral regions. Relatively smaller response, driven by variation in optical scatter, was observed in near infrared (NIR). The concomitant increasing reflectance in the PAR and MIR regions is perplexing. PAR reflectance is dominated by chlorophyll absorption while MIR reflectance is dominated by water molecule absorption. However, changes in chlorophyll concentration, determined by chemical extraction, were too small to account for the variation in PAR reflectance. PAR and MIR reflectances were also influenced by the strength of incident light. Hence PAR reflectance appears to be modulated not only by pigment concentration, the classical description, but also by the strength of incident light and the severity of water deficit. We previously reported that these findings were consistent with chloroplast avoidance movement, a plant photoprotective response, which limits light absorption by pigments. We report here our continuing investigation of this phenomenon. In addition to reflectance measurements, time-lapse microscope images of leaves under increasing water deficit conditions were obtained. These show a brightening between veins which strongly supports our assertion that changes in PAR reflectance accompanying water deficit are caused primarily by chloroplast avoidance movement. Our results suggest that leaf, and possibly canopy, reflectance can therefore be used to detect and measure plant stress. These results also indicate that chloroplast avoidance movement may cause poor estimates of leaf chlorophyll content using techniques based on fluoresced, reflected or transmitted light.

  5. ParsEval: parallel comparison and analysis of gene structure annotations

    PubMed Central

    2012-01-01

    Background Accurate gene structure annotation is a fundamental but somewhat elusive goal of genome projects, as witnessed by the fact that (model) genomes typically undergo several cycles of re-annotation. In many cases, it is not only different versions of annotations that need to be compared but also different sources of annotation of the same genome, derived from distinct gene prediction workflows. Such comparisons are of interest to annotation providers, prediction software developers, and end-users, who all need to assess what is common and what is different among distinct annotation sources. We developed ParsEval, a software application for pairwise comparison of sets of gene structure annotations. ParsEval calculates several statistics that highlight the similarities and differences between the two sets of annotations provided. These statistics are presented in an aggregate summary report, with additional details provided as individual reports specific to non-overlapping, gene-model-centric genomic loci. Genome browser styled graphics embedded in these reports help visualize the genomic context of the annotations. Output from ParsEval is both easily read and parsed, enabling systematic identification of problematic gene models for subsequent focused analysis. Results ParsEval is capable of analyzing annotations for large eukaryotic genomes on typical desktop or laptop hardware. In comparison to existing methods, ParsEval exhibits a considerable performance improvement, both in terms of runtime and memory consumption. Reports from ParsEval can provide relevant biological insights into the gene structure annotations being compared. Conclusions Implemented in C, ParsEval provides the quickest and most feature-rich solution for genome annotation comparison to date. The source code is freely available (under an ISC license) at http://parseval.sourceforge.net/. PMID:22852583

  6. Exacerbation of Apoptosis of Cortical Neurons Following Traumatic Brain Injury in Par-4 Transgenic Mice

    PubMed Central

    Payette, Daniel J; Xie, Jun; Shirwany, Najeeb; Guo, Qing

    2008-01-01

    Traumatic brain injury (TBI) is a significant clinical problem, yet few effective strategies for treating it have emerged. People that sustain and survive a TBI are left with significant cognitive, behavioral, and communicative disabilities. Apoptotic neuronal death occurs following TBI. Prostate apoptosis response-4 (Par-4) is a death domain-containing protein initially characterized as a critical regulator of apoptosis in prostate cancer cells. We have recently generated and characterized Par-4 transgenic mice in which the expression of the par-4 transgene was limited to cells of neuronal lineage. We now provide evidence that, in cortical neurons from these mice, Par-4 drastically increases apoptotic neuronal death in both in vitro and in vivo models of TBI. In vitro experiments were performed in 7-day-old primary cultures of cortical neurons using a previously published, scratch-induced mechanical trauma model. Neurons that overexpress Par-4 showed not only a significant decrease in overall neuron survival after TBI compared to wild-type cells, but also exhibited a sharper decrease in mitochondrial transmembrane potential, a higher degree of free radical accumulation, and earlier activation of caspase-3 than wild-type cells did. In vivo experiments were performed utilizing a weight drop TBI model. A significantly increased volume of cortical injury and exacerbated activation of caspase-3 were observed in Par-4 transgenic mice when compared to those in wild-type mice. These data suggests that aberrant Par-4 expression exacerbates neuronal cell death following TBI by altering mitochondrial function, enhancing oxidative damage, and execution of apoptosis via caspase activation. PMID:18784822

  7. Evaluation of treatment and posttreatment changes of protraction facemask treatment using the PAR index.

    PubMed

    Ngan, P; Yiu, C

    2000-10-01

    The purpose of this study was to use the Peer Assesment Rating (PAR) index score to evaluate the treatment and posttreatment changes of Class III patients treated by protraction facemask. The sample consisted of 20 Chinese children, 6 to 11 years old, with Class III skeletal malocclusion who had been treated with maxillary expansion and a protraction facemask. The average treatment time was 8.2 months, followed by 1 year of retention with a Class III functional appliance. Study casts were taken pretreatment (T1), posttreatment (T2), 1 year follow-up (T3), and 2 years follow-up (T4). After treatment, PAR scores were calculated for each time period. Differences among the 4 time periods were analyzed with the Wilcoxin matched-pairs test. Significant reductions in PAR scores were found at T2 (56%), T3 (70%), and T4 (63%) compared with T1. Immediately posttreatment (T2), 17 (85%) of 20 patients had improved PAR scores by a reduction of at least 30%. Reductions were caused primarily by correction of the anterior crossbite. One year after treatment (T3), further reductions in PAR score were noted (P <.01) as a result of better alignment of the anterior segment, improvement of the buccal occlusion, and overbite and midline corrections. Two years after treatment (T4), PAR scores were higher than at the previous time period. The increases were due to relapses in overjet (4 of 20 patients), overbite, and centerline corrections. These results indicate that significant reductions in the severity of Class III malocclusion can be achieved with early orthopedic facemask treatment. In most cases, further improvement in the PAR score can be expected 1 and 2 years after treatment. In a few patients, the benefits of early treatment are negated by relapses in overjet, overbite, and centerline corrections during the follow-up period.

  8. Cortical Polarity of the RING Protein PAR-2 Is Maintained by Exchange Rate Kinetics at the Cortical-Cytoplasmic Boundary.

    PubMed

    Arata, Yukinobu; Hiroshima, Michio; Pack, Chan-Gi; Ramanujam, Ravikrishna; Motegi, Fumio; Nakazato, Kenichi; Shindo, Yuki; Wiseman, Paul W; Sawa, Hitoshi; Kobayashi, Tetsuya J; Brandão, Hugo B; Shibata, Tatsuo; Sako, Yasushi

    2016-08-23

    Cell polarity arises through the spatial segregation of polarity regulators. PAR proteins are polarity regulators that localize asymmetrically to two opposing cortical domains. However, it is unclear how the spatially segregated PAR proteins interact to maintain their mutually exclusive partitioning. Here, single-molecule detection analysis in Caenorhabditis elegans embryos reveals that cortical PAR-2 diffuses only short distances, and, as a result, most PAR-2 molecules associate and dissociate from the cortex without crossing into the opposing domain. Our results show that cortical PAR-2 asymmetry is maintained by the local exchange reactions that occur at the cortical-cytoplasmic boundary. Additionally, we demonstrate that local exchange reactions are sufficient to maintain cortical asymmetry in a parameter-free mathematical model. These findings suggest that anterior and posterior PAR proteins primarily interact through the cytoplasmic pool and not via cortical diffusion.

  9. EBV LMP-1 negatively regulates expression and pro-apoptotic activity of Par-4 in nasopharyngeal carcinoma cells.

    PubMed

    Lee, Jeng-Woei; Liu, Po-Fan; Hsu, Lee-Ping; Chen, Peir-Rong; Chang, Chung-Hsing; Shih, Wen-Ling

    2009-07-08

    Latent membrane protein-1 (LMP-1) of the Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC), and in this study we sought to determine whether the pro-apoptotic activity of prostate apoptosis response-4 (Par-4) is modulated by LMP-1 in NPC cells. We found that LMP-1 diminished the pro-apoptotic activity of Par-4 and negatively regulated Par-4 protein by de novo synthesis; moreover, although LMP-1 accelerated a Par-4 activator, PKA, we demonstrated that LMP-1 also activated the PI3K/Akt pathway and increased Bcl-2 expression to suppress the activity of Par-4. Consequently, our results revealed a novel negative action of LMP-1 on the pro-apoptosis protein Par-4 by the coordination of multiple signaling pathways.

  10. Spatiotemporal Variability of Global and Diffuse PAR in the Amazon Region and its Significance for Tropical Forest Photosynthesis

    NASA Astrophysics Data System (ADS)

    Dye, D. G.

    2003-12-01

    This study examines seasonal and inter-annual variation in surface fluxes of global and diffuse photosynthetically active radiation (PAR, 400-700 nm) in the tropical forest of the Amazon region. Spatial and temporal patterns of global and diffuse PAR are determined from reanalysis data from the National Center for Environmental Prediction (NCEP), and from the SeaWIFS Solar Surface Irradiance (SSI) data set. The PAR data and satellite-derived estimates of leaf area index (LAI) are applied to an existing sun-shade model of forest canopy photosynthesis. The seasonality of atmospheric scattering (quantified as the diffuse fraction of global PAR) as a determining factor for the relative influence of variation and trends in incident PAR on tropical forest photosynthesis is quantitatively evaluated. The results provide insight into the role of the surface PAR regime in the dynamics of ecosystem-atmosphere carbon exchange in the Amazon and other tropical forest regions.

  11. Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase

    PubMed Central

    Barber, Kara R.; Sherman, Michael

    2017-01-01

    Disruption of synapses underlies a plethora of neurodevelopmental and neurodegenerative disease. Presynaptic specialization called the active zone plays a critical role in the communication with postsynaptic neuron. While the role of many proteins at the active zones in synaptic communication is relatively well studied, very little is known about how these proteins are transported to the synapses. For example, are there distinct mechanisms for the transport of active zone components or are they all transported in the same transport vesicle? Is active zone protein transport regulated? In this report we show that overexpression of Par-1/MARK kinase, a protein whose misregulation has been implicated in Autism spectrum disorders (ASDs) and neurodegenerative disorders, lead to a specific block in the transport of an active zone protein component- Bruchpilot at Drosophila neuromuscular junctions. Consistent with a block in axonal transport, we find a decrease in number of active zones and reduced neurotransmission in flies overexpressing Par-1 kinase. Interestingly, we find that Par-1 acts independently of Tau-one of the most well studied substrates of Par-1, revealing a presynaptic function for Par-1 that is independent of Tau. Thus, our study strongly suggests that there are distinct mechanisms that transport components of active zones and that they are tightly regulated. PMID:28222093

  12. Role of PAR2 in regulating oxaliplatin-induced neuropathic pain via TRPA1.

    PubMed

    Tian, Liujun; Fan, Tianren; Zhou, Nan; Guo, Hui; Zhang, Weijie

    2015-01-01

    Oxaliplatin (OXL) is a third-generation chemotherapeutic agent commonly used to treat metastatic digestive tumors; however, one of the main limiting complications of OXL is neuropathic pain. In this study, the underlying mechanisms responsible for OXL evoked-neuropathic pain were examined. Using a rat model, the results demonstrated that intraperitoneal (i.p.) injection of OXL significantly increased mechanical pain and cold sensitivity as compared with control animals (P < 0.05 vs. control rats). Blocking proteinase-activated receptor 2 (PAR2) significantly attenuated mechanical pain and cold sensitivity observed in control rats and OXL rats (P < 0.05 vs. vehicle control). The attenuating effect of PAR2 on mechanical pain and cold sensitivity were significantly smaller in OXL-rats than in control rats. The role played by PAR2 downstream signaling pathways [namely, transient receptor potential ankyrin 1 (TRPA1)] in regulating OXL evoked-neuropathic pain was also examined. The data shows that TRPA1 expression was upregulated in the lumbar dorsal root ganglion (DRG) of OXL rats and blocking TRPA1 inhibited mechanical pain and heightened cold sensitivity (P < 0.05 vs. control rats). Blocking PAR2 also significantly decreased TRPA1 expression in the DRG. Findings in this study show that OXL intervention amplifies mechanical hyperalgesia and cold hypersensitivity and PAR2 plays an important role in regulating OXL-induced neuropathic pain via TRPA1 pathways.

  13. Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain.

    PubMed

    Dai, Yi; Wang, Shenglan; Tominaga, Makoto; Yamamoto, Satoshi; Fukuoka, Tetsuo; Higashi, Tomohiro; Kobayashi, Kimiko; Obata, Koichi; Yamanaka, Hiroki; Noguchi, Koichi

    2007-07-01

    Proinflammatory agents trypsin and mast cell tryptase cleave and activate PAR2, which is expressed on sensory nerves to cause neurogenic inflammation. Transient receptor potential A1 (TRPA1) is an excitatory ion channel on primary sensory nerves of pain pathway. Here, we show that a functional interaction of PAR2 and TRPA1 in dorsal root ganglion (DRG) neurons could contribute to the sensation of inflammatory pain. Frequent colocalization of TRPA1 with PAR2 was found in rat DRG neurons. PAR2 activation increased the TRPA1 currents evoked by its agonists in HEK293 cells transfected with TRPA1, as well as DRG neurons. Application of phospholipase C (PLC) inhibitors or phosphatidylinositol-4,5-bisphosphate (PIP(2)) suppressed this potentiation. Decrease of plasma membrane PIP(2) levels through antibody sequestration or PLC-mediated hydrolysis mimicked the potentiating effects of PAR2 activation at the cellular level. Thus, the increased TRPA1 sensitivity may have been due to activation of PLC, which releases the inhibition of TRPA1 from plasma membrane PIP(2). These results identify for the first time to our knowledge a sensitization mechanism of TRPA1 and a novel mechanism through which trypsin or tryptase released in response to tissue inflammation might trigger the sensation of pain by TRPA1 activation.

  14. Nanomechanical recognition of prognostic biomarker suPAR with DVD-ROM optical technology

    NASA Astrophysics Data System (ADS)

    Bache, Michael; Bosco, Filippo G.; Brøgger, Anna L.; Frøhling, Kasper B.; Sonne Alstrøm, Tommy; Hwu, En-Te; Chen, Ching-Hsiu; Eugen-Olsen, Jesper; Hwang, Ing-Shouh; Boisen, Anja

    2013-11-01

    In this work the use of a high-throughput nanomechanical detection system based on a DVD-ROM optical drive and cantilever sensors is presented for the detection of urokinase plasminogen activator receptor inflammatory biomarker (uPAR). Several large scale studies have linked elevated levels of soluble uPAR (suPAR) to infectious diseases, such as HIV, and certain types of cancer. Using hundreds of cantilevers and a DVD-based platform, cantilever deflection response from antibody-antigen recognition is investigated as a function of suPAR concentration. The goal is to provide a cheap and portable detection platform which can carry valuable prognostic information. In order to optimize the cantilever response the antibody immobilization and unspecific binding are initially characterized using quartz crystal microbalance technology. Also, the choice of antibody is explored in order to generate the largest surface stress on the cantilevers, thus increasing the signal. Using optimized experimental conditions the lowest detectable suPAR concentration is currently around 5 nM. The results reveal promising research strategies for the implementation of specific biochemical assays in a portable and high-throughput microsensor-based detection platform.

  15. Nanomechanical recognition of prognostic biomarker suPAR with DVD-ROM optical technology.

    PubMed

    Bache, Michael; Bosco, Filippo G; Brøgger, Anna L; Frøhling, Kasper B; Alstrøm, Tommy Sonne; Hwu, En-Te; Chen, Ching-Hsiu; Eugen-Olsen, Jesper; Hwang, Ing-Shouh; Boisen, Anja

    2013-11-08

    In this work the use of a high-throughput nanomechanical detection system based on a DVD-ROM optical drive and cantilever sensors is presented for the detection of urokinase plasminogen activator receptor inflammatory biomarker (uPAR). Several large scale studies have linked elevated levels of soluble uPAR (suPAR) to infectious diseases, such as HIV, and certain types of cancer. Using hundreds of cantilevers and a DVD-based platform, cantilever deflection response from antibody-antigen recognition is investigated as a function of suPAR concentration. The goal is to provide a cheap and portable detection platform which can carry valuable prognostic information. In order to optimize the cantilever response the antibody immobilization and unspecific binding are initially characterized using quartz crystal microbalance technology. Also, the choice of antibody is explored in order to generate the largest surface stress on the cantilevers, thus increasing the signal. Using optimized experimental conditions the lowest detectable suPAR concentration is currently around 5 nM. The results reveal promising research strategies for the implementation of specific biochemical assays in a portable and high-throughput microsensor-based detection platform.

  16. Lambeaux autofermants pour le traitement des brulures electriques du scalp par haut voltage

    PubMed Central

    Hafidi, J.; El Mazouz, S.; El Mejatti, H.; Fejjal, N.; Gharib, N.E.; Abbassi, A.; Belmahi, A.M.

    2011-01-01

    Summary Les brûlures électriques par haut voltage sont responsables de gros dégâts tissulaires en immédiat et dans les jours suivant l’accident du fait de la chaleur importante dégagée par effet joule et de la thrombose microvasculaire évolutive. Les pertes de substances du scalp secondaires à ces brûlures nécessitent une couverture par lambeaux vu la destruction du périoste et du calvarium en regard. De juin 1997 à juin 2008, 15 patients ont été traités pour des pertes de substance du scalp secondaires à des brûlures électriques par haut voltage de diamètre allant de 8 à 11 cm et siégeant dans la région tonsurale. Ces patients ont été opérés dans la première semaine suivant l’accident. Les pertes de substance du scalp de taille moyenne secondaires à ces brûlures peuvent être couvertes per primam de façon fiable par des lambeaux locaux axialisés et multiples. Nous relatons l’expérience du Service de Chirurgie Plastique du Centre Hospitalier Universitaire Ibn-Sina, Rabat, Maroc, dans la gestion et la prise en charge de ces brûlures. PMID:22262963

  17. Towards an improved LAI collection protocol via simulated field-based PAR sensing

    DOE PAGES

    Yao, Wei; Van Leeuwen, Martin; Romanczyk, Paul; ...

    2016-07-14

    In support of NASA’s next-generation spectrometer—the Hyperspectral Infrared Imager (HyspIRI)—we are working towards assessing sub-pixel vegetation structure from imaging spectroscopy data. Of particular interest is Leaf Area Index (LAI), which is an informative, yet notoriously challenging parameter to efficiently measure in situ. While photosynthetically-active radiation (PAR) sensors have been validated for measuring crop LAI, there is limited literature on the efficacy of PAR-based LAI measurement in the forest environment. This study (i) validates PAR-based LAI measurement in forest environments, and (ii) proposes a suitable collection protocol, which balances efficiency with measurement variation, e.g., due to sun flecks and various-sized canopymore » gaps. A synthetic PAR sensor model was developed in the Digital Imaging and Remote Sensing Image Generation (DIRSIG) model and used to validate LAI measurement based on first-principles and explicitly-known leaf geometry. Simulated collection parameters were adjusted to empirically identify optimal collection protocols. Furthermore, these collection protocols were then validated in the field by correlating PAR-based LAI measurement to the normalized difference vegetation index (NDVI) extracted from the “classic” Airborne Visible Infrared Imaging Spectrometer (AVIRIS-C) data (R2 was 0.61). The results indicate that our proposed collecting protocol is suitable for measuring the LAI of sparse forest (LAI < 3–5 ( m2/m2)).« less

  18. Towards an improved LAI collection protocol via simulated field-based PAR sensing

    SciTech Connect

    Yao, Wei; Van Leeuwen, Martin; Romanczyk, Paul; van Aardt, Jan; Kelbe, David

    2016-07-14

    In support of NASA’s next-generation spectrometer—the Hyperspectral Infrared Imager (HyspIRI)—we are working towards assessing sub-pixel vegetation structure from imaging spectroscopy data. Of particular interest is Leaf Area Index (LAI), which is an informative, yet notoriously challenging parameter to efficiently measure in situ. While photosynthetically-active radiation (PAR) sensors have been validated for measuring crop LAI, there is limited literature on the efficacy of PAR-based LAI measurement in the forest environment. This study (i) validates PAR-based LAI measurement in forest environments, and (ii) proposes a suitable collection protocol, which balances efficiency with measurement variation, e.g., due to sun flecks and various-sized canopy gaps. A synthetic PAR sensor model was developed in the Digital Imaging and Remote Sensing Image Generation (DIRSIG) model and used to validate LAI measurement based on first-principles and explicitly-known leaf geometry. Simulated collection parameters were adjusted to empirically identify optimal collection protocols. Furthermore, these collection protocols were then validated in the field by correlating PAR-based LAI measurement to the normalized difference vegetation index (NDVI) extracted from the “classic” Airborne Visible Infrared Imaging Spectrometer (AVIRIS-C) data (R2 was 0.61). The results indicate that our proposed collecting protocol is suitable for measuring the LAI of sparse forest (LAI < 3–5 ( m2/m2)).

  19. Towards an Improved LAI Collection Protocol via Simulated and Field-Based PAR Sensing

    PubMed Central

    Yao, Wei; Kelbe, David; van Leeuwen, Martin; Romanczyk, Paul; van Aardt, Jan

    2016-01-01

    In support of NASA’s next-generation spectrometer—the Hyperspectral Infrared Imager (HyspIRI)—we are working towards assessing sub-pixel vegetation structure from imaging spectroscopy data. Of particular interest is Leaf Area Index (LAI), which is an informative, yet notoriously challenging parameter to efficiently measure in situ. While photosynthetically-active radiation (PAR) sensors have been validated for measuring crop LAI, there is limited literature on the efficacy of PAR-based LAI measurement in the forest environment. This study (i) validates PAR-based LAI measurement in forest environments, and (ii) proposes a suitable collection protocol, which balances efficiency with measurement variation, e.g., due to sun flecks and various-sized canopy gaps. A synthetic PAR sensor model was developed in the Digital Imaging and Remote Sensing Image Generation (DIRSIG) model and used to validate LAI measurement based on first-principles and explicitly-known leaf geometry. Simulated collection parameters were adjusted to empirically identify optimal collection protocols. These collection protocols were then validated in the field by correlating PAR-based LAI measurement to the normalized difference vegetation index (NDVI) extracted from the “classic” Airborne Visible Infrared Imaging Spectrometer (AVIRIS-C) data (R2 was 0.61). The results indicate that our proposed collecting protocol is suitable for measuring the LAI of sparse forest (LAI < 3–5 (m2/m2)). PMID:27428969

  20. Rassf5 and Ndr kinases regulate neuronal polarity through Par3 phosphorylation in a novel pathway.

    PubMed

    Yang, Rui; Kong, Eryan; Jin, Jing; Hergovich, Alexander; Püschel, Andreas W

    2014-08-15

    The morphology and polarized growth of cells depend on pathways that control the asymmetric distribution of regulatory factors. The evolutionarily conserved Ndr kinases play important roles in cell polarity and morphogenesis in yeast and invertebrates but it is unclear whether they perform a similar function in mammalian cells. Here, we analyze the function of mammalian Ndr1 and Ndr2 (also known as STK38 or STK38L, respectively) in the establishment of polarity in neurons. We show that they act downstream of the tumor suppressor Rassf5 and upstream of the polarity protein Par3 (also known as PARD3). Rassf5 and Ndr1 or Ndr2 are required during the polarization of hippocampal neurons to prevent the formation of supernumerary axons. Mechanistically, the Ndr kinases act by phosphorylating Par3 at Ser383 to inhibit its interaction with dynein, thereby polarizing the distribution of Par3 and reinforcing axon specification. Our results identify a novel Rassf5-Ndr-Par3 signaling cascade that regulates the transport of Par3 during the establishment of neuronal polarity. Their role in neuronal polarity suggests that Ndr kinases perform a conserved function as regulators of cell polarity.

  1. PAR-1 mediated apoptosis of breast cancer cells by V. cholerae hemagglutinin protease.

    PubMed

    Ray, Tanusree; Pal, Amit

    2016-05-01

    Bacterial toxins have emerged as promising agents in cancer treatment strategy. Hemagglutinin (HAP) protease secreted by Vibrio cholerae induced apoptosis in breast cancer cells and regresses tumor growth in mice model. The success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity for normal tissues. Increased expression of Protease Activated Receptor-1 (PAR-1) has been reported in different malignant cells. In this study we report that HAP induced activation and over expression of PAR-1 in breast cancer cells (EAC). Immunoprecipitation studies have shown that HAP specifically binds with PAR-1. HAP mediated activation of PAR-1 caused nuclear translocation of p50-p65 and the phosphorylation of p38 which triggered the activation of NFκB and MAP kinase signaling pathways. These signaling pathways enhanced the cellular ROS level in malignant cells that induced the intrinsic pathway of cell apoptosis. PAR-1 mediated apoptosis by HAP of malignant breast cells without effecting normal healthy cells in the same environment makes it a good therapeutic agent for treatment of cancer.

  2. Participatory action research (PAR) in middle school: opportunities, constraints, and key processes.

    PubMed

    Ozer, Emily J; Ritterman, Miranda L; Wanis, Maggie G

    2010-09-01

    Late childhood and early adolescence represent a critical transition in the developmental and academic trajectory of youth, a time in which there is an upsurge in academic disengagement and psychopathology. PAR projects that can promote youth's sense of meaningful engagement in school and a sense of efficacy and mattering can be particularly powerful given the challenges of this developmental stage. In the present study, we draw on data from our own collaborative implementation of PAR projects in secondary schools to consider two central questions: (1) How do features of middle school settings and the developmental characteristics of the youth promote or inhibit the processes, outcomes, and sustainability of the PAR endeavor? and (2) How can the broad principles and concepts of PAR be effectively translated into specific intervention activities in schools, both within and outside of the classroom? In particular, we discuss a participatory research project conducted with 6th and 7th graders at an urban middle school as a means of highlighting the opportunities, constraints, and lessons learned in our efforts to contribute to the high-quality implementation and evaluation of PAR in diverse urban public schools.

  3. uPAR induces epithelial–mesenchymal transition in hypoxic breast cancer cells

    PubMed Central

    Lester, Robin D.; Jo, Minji; Montel, Valérie; Takimoto, Shinako; Gonias, Steven L.

    2007-01-01

    Hypoxia activates genetic programs that facilitate cell survival; however, in cancer, it may promote invasion and metastasis. In this study, we show that breast cancer cells cultured in 1.0% O2 demonstrate changes consistent with epithelial–mesenchymal transition (EMT). Snail translocates to the nucleus, and E-cadherin is lost from plasma membranes. Vimentin expression, cell migration, Matrigel invasion, and collagen remodeling are increased. Hypoxia-induced EMT is accompanied by increased expression of the urokinase-type plasminogen activator receptor (uPAR) and activation of cell signaling factors downstream of uPAR, including Akt and Rac1. Glycogen synthase kinase-3β is phosphorylated, and Snail expression is increased. Hypoxia-induced EMT is blocked by uPAR gene silencing and mimicked by uPAR overexpression in normoxia. Antagonizing Rac1 or phosphatidylinositol 3-kinase also inhibits development of cellular properties associated with EMT in hypoxia. Breast cancer cells implanted on chick chorioallantoic membranes and treated with CoCl2, to model hypoxia, demonstrate increased dissemination. We conclude that in hypoxia, uPAR activates diverse cell signaling pathways that cooperatively induce EMT and may promote cancer metastasis. PMID:17664334

  4. Towards an Improved LAI Collection Protocol via Simulated and Field-Based PAR Sensing.

    PubMed

    Yao, Wei; Kelbe, David; Leeuwen, Martin van; Romanczyk, Paul; Aardt, Jan van

    2016-07-14

    In support of NASA's next-generation spectrometer-the Hyperspectral Infrared Imager (HyspIRI)-we are working towards assessing sub-pixel vegetation structure from imaging spectroscopy data. Of particular interest is Leaf Area Index (LAI), which is an informative, yet notoriously challenging parameter to efficiently measure in situ. While photosynthetically-active radiation (PAR) sensors have been validated for measuring crop LAI, there is limited literature on the efficacy of PAR-based LAI measurement in the forest environment. This study (i) validates PAR-based LAI measurement in forest environments, and (ii) proposes a suitable collection protocol, which balances efficiency with measurement variation, e.g., due to sun flecks and various-sized canopy gaps. A synthetic PAR sensor model was developed in the Digital Imaging and Remote Sensing Image Generation (DIRSIG) model and used to validate LAI measurement based on first-principles and explicitly-known leaf geometry. Simulated collection parameters were adjusted to empirically identify optimal collection protocols. These collection protocols were then validated in the field by correlating PAR-based LAI measurement to the normalized difference vegetation index (NDVI) extracted from the "classic" Airborne Visible Infrared Imaging Spectrometer (AVIRIS-C) data ( R 2 was 0.61). The results indicate that our proposed collecting protocol is suitable for measuring the LAI of sparse forest (LAI < 3-5 ( m 2 / m 2 )).

  5. Participatory Action Research (PAR) in Middle School: Opportunities, Constraints, and Key Processes

    PubMed Central

    Ritterman, Miranda L.; Wanis, Maggie G.

    2010-01-01

    Late childhood and early adolescence represent a critical transition in the developmental and academic trajectory of youth, a time in which there is an upsurge in academic disengagement and psychopathology. PAR projects that can promote youth’s sense of meaningful engagement in school and a sense of efficacy and mattering can be particularly powerful given the challenges of this developmental stage. In the present study, we draw on data from our own collaborative implementation of PAR projects in secondary schools to consider two central questions: (1) How do features of middle school settings and the developmental characteristics of the youth promote or inhibit the processes, outcomes, and sustainability of the PAR endeavor? and (2) How can the broad principles and concepts of PAR be effectively translated into specific intervention activities in schools, both within and outside of the classroom? In particular, we discuss a participatory research project conducted with 6th and 7th graders at an urban middle school as a means of highlighting the opportunities, constraints, and lessons learned in our efforts to contribute to the high-quality implementation and evaluation of PAR in diverse urban public schools. PMID:20676754

  6. Étude par microscopie acoustique de couches minces de Ag2S déposées par spray

    NASA Astrophysics Data System (ADS)

    Amlouk, M.; Brunet, N.; Cros, B.; Belgacem, S.; Barjon, D.

    1997-09-01

    Silver sulfide Ag2S thin films have been prepared on pyrex glass substrates by the spray pyrolysis technique at 250 °C. We have analyzed by acoustic microscopy and particularly by acoustic signature V(z) these films with various thickness (0.4 2 μm). The acoustic signature, performed at 50, 130 and 570 MHz allow us to reach elastic properties of Ag2S material and specially Young modulus. Its value, of the order of 180 GPa, is consistent with the relative low linkage of Ag^+ in the structure and the character of fast-ion conductor of Ag2S. Besides elastic properties and using MEB and AFM investigations, we have shown that the V(z) signature gives valuable information about the bulk defects in the material. Finally, the experimental results have been discussed related to the dispersion curves of velocity of the first mode of Ag2S/pyrex system. Des couches minces de sulfure d'argent Ag2S sont préparées sur substrat de pyrex, à la température de 250 °C, par la technique de pulvérisation chimique réactive en phase liquide ou “spray". Ces dépôts, d'épaisseur variable (0,4 2 μm), sont analysés par microscopie acoustique et, plus particulièrement, par la méthode de relevé de la signature acoustique V(z). Cette signature, effectuée à différentes fréquences (50, 130, 570 MHz), a permis de caractériser les propriétés élastiques du matériau Ag2S. La valeur du module d'Young, de l'ordre de 180 GPa, est en accord avec la faible cohésion de la liaison Ag-S et le caractère de conducteur ionique rapide de Ag2S. Les observations par MEB et AFM permettent d'expliquer l'allure des courbes V(z) par les défauts de compacité liés à la méthode de préparation. Les résultats expérimentaux sont discutés en liaison avec la courbe de dispersion de vitesses du premier mode du système Ag2S/pyrex.

  7. First record of the coffee berry borer, Hypothenemus hampei (Ferrari) (Coleoptera: Scolytidae), in Pará nut, Bertholletia excelsa (Lecythidaceae).

    PubMed

    Gumier-Costa, Fabiano

    2009-01-01

    We report the occurrence of Hypothenemus hampei (Ferrari) attacking Pará nuts stored in the southeast of Para state. The coffee berry borer successfully colonized and reproduced using Pará nuts as a food source. Based on this observation, the Pará nuts can be used as an alternative food source in rearing the coffee berry borer. Also, attention should be brought to need of proper storage of these nuts to avoid infestation by this pest.

  8. Endothelial progenitor cell-dependent angiogenesis requires localization of the full-length form of uPAR in caveolae.

    PubMed

    Margheri, Francesca; Chillà, Anastasia; Laurenzana, Anna; Serratì, Simona; Mazzanti, Benedetta; Saccardi, Riccardo; Santosuosso, Michela; Danza, Giovanna; Sturli, Niccolò; Rosati, Fabiana; Magnelli, Lucia; Papucci, Laura; Calorini, Lido; Bianchini, Francesca; Del Rosso, Mario; Fibbi, Gabriella

    2011-09-29

    Endothelial urokinase-type plasminogen activator receptor (uPAR) is thought to provide a regulatory mechanism in angiogenesis. Here we studied the proangiogenic role of uPAR in endothelial colony-forming cells (ECFCs), a cell population identified in human umbilical blood that embodies all of the properties of an endothelial progenitor cell matched with a high proliferative rate. By using caveolae-disrupting agents and by caveolin-1 silencing, we have shown that the angiogenic properties of ECFCs depend on caveolae integrity and on the presence of full-length uPAR in such specialized membrane invaginations. Inhibition of uPAR expression by antisense oligonucleotides promoted caveolae disruption, suggesting that uPAR is an inducer of caveolae organization. Vascular endothelial growth factor (VEGF) promoted accumulation of uPAR in ECFC caveolae in its undegraded form. We also demonstrated that VEGF-dependent ERK phosphorylation required integrity of caveolae as well as caveolar uPAR expression. VEGF activity depends on inhibition of ECFC MMP12 production, which results in impairment of MMP12-dependent uPAR truncation. Further, MMP12 overexpression in ECFC inhibited vascularization in vitro and in vivo. Our data suggest that intratumor homing of ECFCs suitably engineered to overexpress MMP12 could have the chance to control uPAR-dependent activities required for tumor angiogenesis and malignant cells spreading.

  9. Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation.

    PubMed

    Chen, Chen-Wen; Chen, Qian-Bo; Ouyang, Qing; Sun, Ji-Hu; Liu, Fang-Ting; Song, Dian-Wen; Yuan, Hong-Bin

    2012-06-25

    Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1 β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.

  10. Participatory action research (PAR): an approach for improving black women's health in rural and remote communities.

    PubMed

    Etowa, Josephine B; Bernard, Wanda Thomas; Oyinsan, Bunmi; Clow, Barbara

    2007-10-01

    Women are among the most disadvantaged members of any community, and they tend to be at greatest risk of illness. Black women are particularly vulnerable and more prone than White women to illnesses associated with social and economic deprivation, including heart disease and diabetes. They utilize preventive health services less often, and when they fall ill, the health of their families and communities typically suffers as well. This article discusses the process of doing innovative participatory action research (PAR) in southwest Nova Scotia Black communities. The effort resulted in the generation of a database, community action, and interdisciplinary analysis of the intersecting inequities that compromise the health and health care of African Canadian women, their families, and their communities. This particular research effort serves as a case study for explicating the key tenets of PAR and the barriers to and contradictions in implementing PAR in a community-academic collaborative research project.

  11. Potential Ecological Effects of Contaminants in the Exposed Par Pond Sediments

    SciTech Connect

    Paller, M.H.; Wike, L.D.

    1996-08-01

    Sediment and small mammal samples were collected from the exposed sediments of Par Pond in early 1995, shortly before the reservoir was refilled after a 4-year drawdown. Sampling was confined to elevations between 58 and 61 meters (190 and 200 feet) above mean sea level, which includes the sediments likely to be exposed if the Par Pond water level is permitted to fluctuate naturally. Both soil and small mammal samples were analyzed for a number of radionuclides and metals. Some of the soil samples were also analyzed for organic contaminants. The objective of the study was to determine if contaminant levels in the Par Pond sediments were high enough to cause deleterious ecological effects.

  12. The Par complex and integrins direct asymmetric cell division in adult intestinal stem cells.

    PubMed

    Goulas, Spyros; Conder, Ryan; Knoblich, Juergen A

    2012-10-05

    The adult Drosophila midgut is maintained by intestinal stem cells (ISCs) that generate both self-renewing and differentiating daughter cells. How this asymmetry is generated is currently unclear. Here, we demonstrate that asymmetric ISC division is established by a unique combination of extracellular and intracellular polarity mechanisms. We show that Integrin-dependent adhesion to the basement membrane induces cell-intrinsic polarity and results in the asymmetric segregation of the Par proteins Par-3, Par-6, and aPKC into the apical daughter cell. Cell-specific knockdown and overexpression experiments suggest that increased activity of aPKC enhances Delta/Notch signaling in one of the two daughter cells to induce terminal differentiation. Perturbing this mechanism or altering the orientation of ISC division results in the formation of intestinal tumors. Our data indicate that mechanisms for intrinsically asymmetric cell division can be adapted to allow for the flexibility in lineage decisions that is required in adult stem cells.

  13. Peptidomics of the pars intercerebralis-corpus cardiacum complex of the migratory locust, Locusta migratoria.

    PubMed

    Clynen, E; Baggerman, G; Veelaert, D; Cerstiaens, A; Van der Horst, D; Harthoorn, L; Derua, R; Waelkens, E; De Loof, A; Schoofs, L

    2001-04-01

    The pars intercerebralis-corpora cardiaca system (PI-CC) of insects is the endocrinological equivalent of the hypothalamus-pituitary system of vertebrates. Peptide profiles of the pars intercerebralis and the corpora cardiaca were characterized using simple sampling protocols in combination with MALDI-TOF and electrospray ionization double quadrupole time of flight (ESI-Qq-TOF) mass spectrometric technologies. The results were compared with earlier results of conventional sequencing methods and immunocytochemical methods. In addition to many known peptides, several m/z signals corresponding to putative novel peptides were observed in the corpora cardiaca and/or pars intercerebralis. Furthermore, for a number of peptides evidence was provided about their localization and MALDI-TOF analysis of the released material from the corpora cardiaca yielded information on the hormonal status of particular brain peptides.

  14. Parádsasvárite, a new member of the malachite-rosasite group from Parádsasvár, Mátra Mountains, Hungary

    NASA Astrophysics Data System (ADS)

    Fehér, Béla; Szakáll, Sándor; Zajzon, Norbert; Mihály, Judith

    2015-08-01

    Parádsasvárite (IMA No. 2012-077) was found in the Nagy-Lápafő area, Parádsasvár, Mátra Mountains, Hungary. It forms pale beige, globular aggregates up to 0.2 mm in diameter on calcite. Associated secondary minerals are smithsonite, hemimorphite, hydrozincite, aurichalcite and rosasite. The mineral was formed as an alteration product of sphalerite and chalcopyrite in a carbonate-rich environment. Parádsasvárite is translucent with a weakly vitreous, dull or silky lustre and white streak. Its Mohs hardness is about 2-3, cleavage and parting were not observed. It is brittle; the fracture is finely fibrous. Average of nine electron-microprobe analyses gave ZnO 58.08, CuO 12.60, PbO 1.27, CO2 (calc.) 19.50, H2O (calc.) 7.94, total 99.39 wt.%, corresponding to the empirical formula (Zn0.62Cu0.36Pb0.01)Σ0.99Zn1.00(CO3)(OH)2. The seven strongest lines in the X-ray powder diffraction pattern are [dhkl in Å (Iobs %, hkl)] 6.054 (67, 200), 5.085 (100, 210), 3.703 (87, 310 and 220), 3.021 (25, 400 and 130), 2.971 (25, -211 and 001), 2.603 (62, -221) and 2.539 (36, 420). According to its X-ray powder diffraction data and chemical formula, parádsasvárite belongs to the malachite-rosasite group and it is isostructural with rosasite. It is monoclinic, space group P21/ a, a = 12.92(1), b = 9.372(7), c = 3.159(4) Å, β = 110.4(1)°, V = 358.5(5) Å3, Z = 4.

  15. Factor Xa stimulates fibroblast procollagen production, proliferation, and calcium signaling via PAR{sub 1} activation

    SciTech Connect

    Blanc-Brude, Olivier P. . E-mail: olivier.blanc-brude@larib.inserm.fr; Archer, Fabienne; Leoni, Patricia; Derian, Claudia; Bolsover, Steven; Laurent, Geoffrey J.; Chambers, Rachel C.

    2005-03-10

    Fibroblast proliferation and procollagen production are central features of tissue repair and fibrosis. In addition to its role in blood clotting, the coagulation cascade proteinase thrombin can contribute to tissue repair by stimulating fibroblasts via proteolytic activation of proteinase-activated receptor-1 (PAR{sub 1}). During hemostasis, the coagulation cascade proteinase factor X is converted into factor Xa. We have previously shown that factor Xa upregulates fibroblast proliferation via production of autocrine PDGF. In this study, we further examined the effects of factor Xa on fibroblast function and aimed to identify its signaling receptor. We showed that factor Xa stimulates procollagen promoter activity and protein production by human and mouse fibroblasts. This effect was independent of PDGF and thrombin production, but dependent on factor Xa proteolytic activity. We also showed that PAR{sub 1}-deficient mouse fibroblasts did not upregulate procollagen production, mobilize cytosolic calcium, or proliferate in response to factor Xa. Desensitization techniques and PAR{sub 1}-specific agonists and inhibitors were used to demonstrate that PAR{sub 1} mediates factor Xa signaling in human fibroblasts. This is the first report that factor Xa stimulates extracellular matrix production. In contrast with endothelial cells and vascular smooth muscle cells, fibroblasts appear to be the only cell type in which the effects of factor Xa are mediated mainly via PAR{sub 1} and not PAR{sub 2}. These findings are critical for our understanding of tissue repair and fibrotic mechanisms, and for the design of novel approaches to inhibit the profibrotic effects of the coagulation cascade without compromising blood hemostasis.

  16. Linking the fPAR, forest albedo and biomass in the northern biomes of Europe

    NASA Astrophysics Data System (ADS)

    Lukeš, Petr; Stenberg, Pauline; Manninen, Terhikki; Rautiainen, Miina; Mõttus, Matti

    2014-05-01

    Land surface albedo and the fraction of photosynthetically active radiation (fPAR) absorbed by plant canopies are two of the essential climate variables controlling the planetary radiative energy budget. Albedo is directly related to the energy exchange between land and the atmosphere as it is the reflectivity of the surface - the higher the albedo, the more incoming solar radiation is reflected and the less absorbed by the surface. The fPAR is related to plant productivity, quantifying the amount of absorbed light available for photosynthesis. It is a key parameter in the modelling of net primary production (NPP) of terrestrial ecosystems. Global climate scenarios are very sensitive to albedo and fPAR estimates, and thus, the effect of changes in canopy structure and density (biomass) on these two variables needs to be quantified reliably. Both parameters are routinely retrieved from current Earth Observation sensors using specialized algorithms. To date, these satellite products have not been linked to extensive forest inventory data sets due to the lack of ground reference data. Data availability for Finland has significantly improved in December 2012, when National Forest Inventory (NFI) data became freely available to the public. The dataset covers the geographical area of Finland (26.1 million hectares) at a spatial resolution of 20 meters including several forest structural variables. In this study, we use the NFI data to study the links between forest albedo, fPAR and forest structure and density during the green vegetation season. More specifically, we investigated the seasonal trends in fPAR and albedo of different spectral regions of northern forests. Empirical relationships between forest albedo, fPAR and total aboveground biomass were established for selected days within the vegetation growing period and across a latitudinal transect of Finland.

  17. Comparing the 7-Day PAR with a Triaxial Accelerometer for Measuring Time in Exercise

    PubMed Central

    Sloane, Richard; Snyder, Denise Clutter; Demark-Wahnefried, Wendy; Lobach, David; Kraus, William E.

    2009-01-01

    Purpose The primary study aim was to evaluate associations of estimated weekly minutes of moderate-to-vigorous intensity exercise from self-reports of the telephone-administered 7-Day Physical Activity Recall (PAR) with data captured by the RT3 triaxial accelerometer. Methods This investigation was undertaken as part of the FRESH START study, a randomized clinical trial that tested an iteratively-tailored diet and exercise mailed print intervention among newly diagnosed breast and prostate cancer survivors. A convenience sample of 139 medically-eligible subjects living within a 60-mile radius of the study center provided both 7-Day PAR and accelerometer data at enrollment. Ultimately n=115 substudy subjects were found eligible for the FRESH START study and randomized to one of two study treatment arms. Follow-up assessments at Year 1 (n=103) and Year 2 (n=99) provided both the 7-Day PAR and accelerometer data. Results There was moderate agreement between the 7-Day PAR and the accelerometer with longitudinal serial correlation coefficients of .54 (baseline), .24 (Year 1) and .53 (Year 2), all P-values < .01, though the accelerometer estimates for weekly time in moderate-to-vigorous physical activity were much higher than those of the 7-Day PAR at all time points. The two methods were poorly correlated in assessing sensitivity to change from baseline to Year 1 (rho=.11, P=.30). Using mixed models repeated measures analysis, both methods exhibited similar non-significant treatment arm X time interaction P-values (7-Day PAR=.22, accelerometer=.23). Conclusions The correlations for three serial time points were in agreement with findings of other studies that compared self-reported time in exercise with physical activity captured by accelerometry. However, these methods capture somewhat different dimensions of physical activity and provide differing estimates of change over time. PMID:19461530

  18. Function inferences from a molecular structural model of bacterial ParE toxin

    PubMed Central

    Barbosa, Luiz Carlos Bertucci; Garrido, Saulo Santesso; Garcia, Anderson; Delfino, Davi Barbosa; Marchetto, Reinaldo

    2010-01-01

    Toxin-antitoxin (TA) systems contribute to plasmid stability by a mechanism that relies on the differential stabilities of the toxin and antitoxin proteins and leads to the killing of daughter bacteria that did not receive a plasmid copy at the cell division. ParE is the toxic component of a TA system that constitutes along with RelE an important class of bacterial toxin called RelE/ParE superfamily. For ParE toxin, no crystallographic structure is available so far and rare in vitro studies demonstrated that the target of toxin activity is E. coli DNA gyrase. Here, a 3D Model for E. coli ParE toxin by molecular homology modeling was built using MODELLER, a program for comparative modeling. The Model was energy minimized by CHARMM and validated using PROCHECK and VERIFY3D programs. Resulting Ramachandran plot analysis it was found that the portion residues failing into the most favored and allowed regions was 96.8%. Structural similarity search employing DALI server showed as the best matches RelE and YoeB families. The Model also showed similarities with other microbial ribonucleases but in a small score. A possible homologous deep cleft active site was identified in the Model using CASTp program. Additional studies to investigate the nuclease activity in members of ParE family as well as to confirm the inhibitory replication activity are needed. The predicted Model allows initial inferences about the unexplored 3D structure of the ParE toxin and may be further used in rational design of molecules for structure­function studies. PMID:20975905

  19. K-Area and Par Pond Sewage Sludge Application Sites groundwater monitoring reports, second quarter 1992

    SciTech Connect

    Not Available

    1992-10-01

    During second quarter 1992, the three wells at the K-Area Sewage Sludge Application Site (KSS wells) and the three wells at the Par Pond Sewage Sludge Application Site (PSS wells) were sampled for analyses required each quarter or annually by South Carolina Department of Health and Environmental Control Construction Permit 13, 173. This report includes the results of those analyses. None of the analyzed constituents exceeded the Primary Drinking Water Standard or the Savannah River Site Flag 2 criteria at either the K-Area Sewage Sludge Application Site or the Par Pond Sewage Sludge Application Site.

  20. Planar Cell Polarity Breaks the Symmetry of PAR Protein Distribution prior to Mitosis in Drosophila Sensory Organ Precursor Cells.

    PubMed

    Besson, Charlotte; Bernard, Fred; Corson, Francis; Rouault, Hervé; Reynaud, Elodie; Keder, Alyona; Mazouni, Khalil; Schweisguth, François

    2015-04-20

    During development, cell-fate diversity can result from the unequal segregation of fate determinants at mitosis. Polarization of the mother cell is essential for asymmetric cell division (ACD). It often involves the formation of a cortical domain containing the PAR complex proteins Par3, Par6, and atypical protein kinase C (aPKC). In the fly notum, sensory organ precursor cells (SOPs) divide asymmetrically within the plane of the epithelium and along the body axis to generate two distinct cells. Fate asymmetry depends on the asymmetric localization of the PAR complex. In the absence of planar cell polarity (PCP), SOPs divide with a random planar orientation but still asymmetrically, showing that PCP is dispensable for PAR asymmetry at mitosis. To study when and how the PAR complex localizes asymmetrically, we have used a quantitative imaging approach to measure the planar polarization of the proteins Bazooka (Baz, fly Par3), Par6, and aPKC in living pupae. By using imaging of functional GFP-tagged proteins with image processing and computational modeling, we find that Baz, Par6, and aPKC become planar polarized prior to mitosis in a manner independent of the AuroraA kinase and that PCP is required for the planar polarization of Baz, Par6, and aPKC during interphase. This indicates that a "mitosis rescue" mechanism establishes asymmetry at mitosis in PCP mutants. This study therefore identifies PCP as the initial symmetry-breaking signal for the planar polarization of PAR proteins in asymmetrically dividing SOPs.

  1. Molecular networks implicated in speech-related disorders: FOXP2 regulates the SRPX2/uPAR complex.

    PubMed

    Roll, Patrice; Vernes, Sonja C; Bruneau, Nadine; Cillario, Jennifer; Ponsole-Lenfant, Magali; Massacrier, Annick; Rudolf, Gabrielle; Khalife, Manal; Hirsch, Edouard; Fisher, Simon E; Szepetowski, Pierre

    2010-12-15

    It is a challenge to identify the molecular networks contributing to the neural basis of human speech. Mutations in transcription factor FOXP2 cause difficulties mastering fluent speech (developmental verbal dyspraxia, DVD), whereas mutations of sushi-repeat protein SRPX2 lead to epilepsy of the rolandic (sylvian) speech areas, with DVD or with bilateral perisylvian polymicrogyria. Pathophysiological mechanisms driven by SRPX2 involve modified interaction with the plasminogen activator receptor (uPAR). Independent chromatin-immunoprecipitation microarray screening has identified the uPAR gene promoter as a potential target site bound by FOXP2. Here, we directly tested for the existence of a transcriptional regulatory network between human FOXP2 and the SRPX2/uPAR complex. In silico searches followed by gel retardation assays identified specific efficient FOXP2-binding sites in each of the promoter regions of SRPX2 and uPAR. In FOXP2-transfected cells, significant decreases were observed in the amounts of both SRPX2 (43.6%) and uPAR (38.6%) native transcripts. Luciferase reporter assays demonstrated that FOXP2 expression yielded a marked inhibition of SRPX2 (80.2%) and uPAR (77.5%) promoter activity. A mutant FOXP2 that causes DVD (p.R553H) failed to bind to SRPX2 and uPAR target sites and showed impaired down-regulation of SRPX2 and uPAR promoter activity. In a patient with polymicrogyria of the left rolandic operculum, a novel FOXP2 mutation (p.M406T) was found in the leucine-zipper (dimerization) domain. p.M406T partially impaired the FOXP2 regulation of SRPX2 promoter activity, whereas that of the uPAR promoter remained unchanged. Together with recently described FOXP2-CNTNAP2 and SRPX2/uPAR links, the FOXP2-SRPX2/uPAR network provides exciting insights into molecular pathways underlying speech-related disorders.

  2. AP-3 regulates PAR1 ubiquitin-independent MVB/lysosomal sorting via an ALIX-mediated pathway

    PubMed Central

    Dores, Michael R.; Paing, May M.; Lin, Huilan; Montagne, William A.; Marchese, Adriano; Trejo, JoAnn

    2012-01-01

    The sorting of signaling receptors within the endocytic system is important for appropriate cellular responses. After activation, receptors are trafficked to early endosomes and either recycled or sorted to lysosomes and degraded. Most receptors trafficked to lysosomes are modified with ubiquitin and recruited into an endosomal subdomain enriched in hepatocyte growth factor–regulated tyrosine kinase substrate (HRS), a ubiquitin-binding component of the endosomal-sorting complex required for transport (ESCRT) machinery, and then sorted into intraluminal vesicles (ILVs) of multivesicular bodies (MVBs)/lysosomes. However, not all receptors use ubiquitin or the canonical ESCRT machinery to sort to MVBs/lysosomes. This is exemplified by protease-activated receptor-1 (PAR1), a G protein–coupled receptor for thrombin, which sorts to lysosomes independent of ubiquitination and HRS. We recently showed that the adaptor protein ALIX binds to PAR1, recruits ESCRT-III, and mediates receptor sorting to ILVs of MVBs. However, the mechanism that initiates PAR1 sorting at the early endosome is not known. We now report that the adaptor protein complex-3 (AP-3) regulates PAR1 ubiquitin-independent sorting to MVBs through an ALIX-dependent pathway. AP-3 binds to a PAR1 cytoplasmic tail–localized tyrosine-based motif and mediates PAR1 lysosomal degradation independent of ubiquitination. Moreover, AP-3 facilitates PAR1 interaction with ALIX, suggesting that AP-3 functions before PAR1 engagement of ALIX and MVB/lysosomal sorting. PMID:22833563

  3. The Rac-GAP Bcr is a novel regulator of the Par complex that controls cell polarity

    PubMed Central

    Narayanan, Anjana S.; Reyes, Steve B.; Um, Kyongmi; McCarty, Joseph H.; Tolias, Kimberley F.

    2013-01-01

    Cell polarization is essential for many biological processes, including directed cell migration, and loss of polarity contributes to pathological conditions such as cancer. The Par complex (Par3, Par6, and PKCζ) controls cell polarity in part by recruiting the Rac-specific guanine nucleotide exchange factor T-lymphoma invasion and metastasis 1 (Tiam1) to specialized cellular sites, where Tiam1 promotes local Rac1 activation and cytoskeletal remodeling. However, the mechanisms that restrict Par-Tiam1 complex activity to the leading edge to maintain cell polarity during migration remain unclear. We identify the Rac-specific GTPase-activating protein (GAP) breakpoint cluster region protein (Bcr) as a novel regulator of the Par-Tiam1 complex. We show that Bcr interacts with members of the Par complex and inhibits both Rac1 and PKCζ signaling. Loss of Bcr results in faster, more random migration and striking polarity defects in astrocytes. These polarity defects are rescued by reducing PKCζ activity or by expressing full-length Bcr, but not an N-terminal deletion mutant or the homologous Rac-GAP, Abr, both of which fail to associate with the Par complex. These results demonstrate that Bcr is an integral member of the Par-Tiam1 complex that controls polarized cell migration by locally restricting both Rac1 and PKCζ function. PMID:24152735

  4. Soluble urokinase receptor (suPAR) predicts microalbuminuria in patients at risk for type 2 diabetes mellitus

    PubMed Central

    Guthoff, Martina; Wagner, Robert; Randrianarisoa, Elko; Hatziagelaki, Erifili; Peter, Andreas; Häring, Hans-Ulrich; Fritsche, Andreas; Heyne, Nils

    2017-01-01

    Early identification of patients at risk of developing diabetic nephropathy is essential. Elevated serum concentrations of soluble urokinase receptor (suPAR) associate with diabetes mellitus and predict onset and loss of renal function in chronic kidney disease. We hypothesize, that suPAR may be an early risk indicator for diabetic nephropathy, preceding microalbuminuria. The relationship of baseline suPAR and incident microalbuminuria was assessed in a prospective long-term cohort of subjects at increased risk for type 2 diabetes (TULIP, n = 258). Association with albuminuria at later stages of disease was studied in a cross-sectional cohort with manifest type 2 diabetes (ICEPHA, n = 266). A higher baseline suPAR was associated with an increased risk of new-onset microalbuminuria in subjects at risk for type 2 diabetes (hazard ratio 5.3 (95% CI 1.1–25.2, p = 0.03) for the highest vs. lowest suPAR quartile). The proportion of subjects with prediabetes at the end of observation was higher in subjects with new-onset microalbuminuria. suPAR consistently correlated with albuminuria in a separate cohort with manifest type 2 diabetes. Elevated baseline suPAR concentrations independently associate with new-onset microalbuminuria in subjects at increased risk of developing type 2 diabetes. suPAR may hence allow for earlier risk stratification than microalbuminuria. PMID:28091558

  5. A Type Ib ParB Protein Involved in Plasmid Partitioning in a Gram-Positive Bacterium▿

    PubMed Central

    Yin, Ping; Li, Tai-Yuan; Xie, Mao-Hua; Jiang, Lina; Zhang, Yi

    2006-01-01

    Our current understanding of segregation of prokaryotic plasmids has been derived mainly from the study of the gram-negative bacterial plasmids. We previously reported a replicon of the cryptic plasmid from a gram-positive bacterium, Leifsonia xyli subsp. cynodontis. The replicon contains a putative plasmid partition cassette including a Walker-type ATPase followed by open reading frame 4 without sequence homologue. Here we reported that the orf4 gene was essential for maintaining the plasmid stability in L. xyli subsp. cynodontis. Furthermore, the purified orf4 protein specifically and cooperatively bound to direct repeat sequences located upstream of the parA gene in vitro, indicating that orf4 is a parB gene and that the direct repeat DNA sequences constitute a partition site, parS. The location of parS and the features of ParA and ParB proteins suggest that this plasmid partition cassette belongs to type Ib, representing the first type Ib cassette identified from a gram-positive bacterial plasmid. PMID:16997970

  6. Urokinase-type plasminogen activator receptor (uPAR) as a promising new imaging target: potential clinical applications

    PubMed Central

    Persson, Morten; Kjaer, Andreas

    2013-01-01

    Urokinase-type plasminogen activator receptor (uPAR) has been shown to be of special importance during cancer invasion and metastasis. However, currently, tissue samples are needed for measurement of uPAR expression limiting the potential as a clinical routine. Therefore, non-invasive methods are needed. In line with this, uPAR has recently been identified as a very promising imaging target candidate. uPAR consists of three domains attached to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor and binds it natural ligand uPA with high affinity to localize plasminogen activation at the cell surface. Due to the importance of uPAR in cancer invasion and metastasis, a number of high-affinity ligands have been identified during the last decades. These ligands have recently been used as starting point for the development of a number of ligands for imaging of uPAR using various imaging modalities such as optical imaging, magnetic resonance imaging, single photon emission computer tomography (SPECT) and positron emission topography (PET). In this review, we will discuss recent advances in the development of uPAR-targeted imaging ligands according to imaging modality. In addition, we will discuss the potential future clinical application for uPAR imaging as a new imaging biomarker. PMID:23701192

  7. Soluble urokinase receptor (suPAR) predicts microalbuminuria in patients at risk for type 2 diabetes mellitus.

    PubMed

    Guthoff, Martina; Wagner, Robert; Randrianarisoa, Elko; Hatziagelaki, Erifili; Peter, Andreas; Häring, Hans-Ulrich; Fritsche, Andreas; Heyne, Nils

    2017-01-16

    Early identification of patients at risk of developing diabetic nephropathy is essential. Elevated serum concentrations of soluble urokinase receptor (suPAR) associate with diabetes mellitus and predict onset and loss of renal function in chronic kidney disease. We hypothesize, that suPAR may be an early risk indicator for diabetic nephropathy, preceding microalbuminuria. The relationship of baseline suPAR and incident microalbuminuria was assessed in a prospective long-term cohort of subjects at increased risk for type 2 diabetes (TULIP, n = 258). Association with albuminuria at later stages of disease was studied in a cross-sectional cohort with manifest type 2 diabetes (ICEPHA, n = 266). A higher baseline suPAR was associated with an increased risk of new-onset microalbuminuria in subjects at risk for type 2 diabetes (hazard ratio 5.3 (95% CI 1.1-25.2, p = 0.03) for the highest vs. lowest suPAR quartile). The proportion of subjects with prediabetes at the end of observation was higher in subjects with new-onset microalbuminuria. suPAR consistently correlated with albuminuria in a separate cohort with manifest type 2 diabetes. Elevated baseline suPAR concentrations independently associate with new-onset microalbuminuria in subjects at increased risk of developing type 2 diabetes. suPAR may hence allow for earlier risk stratification than microalbuminuria.

  8. TGFβ upregulates PAR-1 expression and signalling responses in A549 lung adenocarcinoma cells

    PubMed Central

    Smoktunowicz, Natalia; Platé, Manuela; Stern, Alejandro Ortiz; D'Antongiovanni, Vanessa; Robinson, Eifion; Chudasama, Vijay; Caddick, Stephen; Scotton, Chris J.; Jarai, Gabor; Chambers, Rachel C.

    2016-01-01

    The major high-affinity thrombin receptor, proteinase activated receptor-1 (PAR-1) is expressed at low levels by the normal epithelium but is upregulated in many types of cancer, including lung cancer. The thrombin-PAR-1 signalling axis contributes to the activation of latent TGFβ in response to tissue injury via an αvβ6 integrin-mediated mechanism. TGFβ is a pleiotropic cytokine that acts as a tumour suppressor in normal and dysplastic cells but switches into a tumour promoter in advanced tumours. In this study we demonstrate that TGFβ is a positive regulator of PAR-1 expression in A549 lung adenocarcinoma cells, which in turn increases the sensitivity of these cells to thrombin signalling. We further demonstrate that this effect is Smad3-, ERK1/2- and Sp1-dependent. We also show that TGFβ-mediated PAR-1 upregulation is accompanied by increased expression of integrin αv and β6 subunits. Finally, TGFβ pre-stimulation promotes increased migratory potential of A549 to thrombin. These data have important implications for our understanding of the interplay between coagulation and TGFβ signalling responses in lung cancer. PMID:27566553

  9. UTILITY OF A WIDE SPECTRUM LIGHT METER AS AN UNDERWATER SENSOR OF PHOTOSYNTHETICALLY ACTIVE RADIATION (PAR)

    EPA Science Inventory

    The strong attenuation of infra red wavelengths (>700 nm) in coastal waters is suggestive that some instruments with broad spectral responses might be useful, inexpensive substitutes for PAR sensors in studies of estuarine plant dynamics. Wide spectrum (350-1100 nm) light intensi...

  10. Appropriately Targeting Group Interventions for Academic Success Adopting the Clinical Model and PAR Profiles

    ERIC Educational Resources Information Center

    Johnson, Craig W.; Johnson, Ronald; Steigman, Michael; Odo, Chioma; Vijayan, Suvendra; Tata, Devadatta V.

    2016-01-01

    Prevalence of academic risk (PAR) group profiles provide data enabling empirically based group-specialized prescriptions for targeted academic success interventions to increase student retention, completion, and graduation rates, while improving allocation of institutional resources. Postsecondary student attrition engenders student debt,…

  11. Dengue epidemic in Belém, Pará, Brazil, 1996-97.

    PubMed Central

    Trravassos da Rosa, A. P.; Vasconcelos, P. F.; Travassos Da Rosa, E. S.; Rodrigues, S. G.; Mondet, B.; Cruz, A. C.; Sousa, M. R.; Travassos Da Rosa, J. F.

    2000-01-01

    We describe clinical and epidemiologic findings during the first epidemic of dengue fever in Belém, Pará State, Brazil, in 1996-97. Of 40,237 serum samples, 17,440 (43%) were positive for dengue by virus isolation or serologic testing. No hemorrhagic cases or deaths were reported. Mycobacterium tuberculosis PMID:10827121

  12. An Overview of the Peer Assessment Rating (par) Index for Primary Dental Care Practitioners.

    PubMed

    Green, James Ij

    2016-11-01

    The Peer Assessment Rating (PAR) index is a valid and reliable measure of orthodontic treatment outcome and is the most widely accepted such index. Assessing outcomes with the PAR index requires the examination of pre-treatment and post-treatment orthodontic study models. Beginning with the pre-treatment models, a score is given to each feature that deviates from an ideal occlusion (all anatomical contact points adjacent, good interdigitation between posterior teeth and non-excessive overjet/overbite), the scores are then added together to give a total that represents the severity of the malocclusion. The process is then repeated with the post-treatment models. The difference between the pre-treatment and the post-treatment scores reflects the improvement that has taken place during treatment. A score of zero represents an ideal occlusion and in general the higher the score, the more extensive the malocclusion. It is currently a condition of the NHS orthodontic contract for providers to monitor a proportion of their cases using the PAR index. This paper aims to provide primary dental care practitioners with an overview of the PAR index and should provide a useful guide for those wishing to seek calibration in the use of the index.

  13. Leuconychie transversale induite par la manucurie: y a-t-il un apport de la dermoscopie?

    PubMed Central

    Gallouj, Salim; Mernissi, Fatima Zahra

    2014-01-01

    La leuconychie transversale induite par la manucurie est une leuconychie secondaire au microtraumatisme transmis à la matrice unguéale. Nous rapportant une observation où la dermoscopie avait un intérêt considérable pour l'orientation diagnostic. PMID:25368728

  14. Measurement of the topography of human cadaver lenses using the PAR corneal topography system

    NASA Astrophysics Data System (ADS)

    Fernandez, Viviana; Manns, Fabrice; Zipper, Stanley; Sandadi, Samith; Hamaoui, Marie; Tahi, Hassan; Ho, Arthur; Parel, Jean-Marie A.

    2001-06-01

    To measure the radius of curvature and asphericity of the anterior and posterior surfaces of crystalline lenses of human Eye-Bank eyes using the PAR Corneal Topography System. The measured values will be used in an optical model of the eye for lens refilling procedures.

  15. CALiPER Report 20.3: Robustness of LED PAR38 Lamps

    SciTech Connect

    none,

    2014-12-30

    A small sample of each of the CALiPER Application Summary Report 20 PAR38 lamp types underwent stress testing that included substantial temperature and humidity changes, electrical variation, and vibration. The results do not directly address expected lifetime, but can be compared with one another, as well as with benchmark conventional products, to assess the relative robustness of the product designs.

  16. Cortical PAR polarity proteins promote robust cytokinesis during asymmetric cell division

    PubMed Central

    Jordan, Shawn N.; Davies, Tim; Zhuravlev, Yelena; Dumont, Julien; Shirasu-Hiza, Mimi

    2016-01-01

    Cytokinesis, the physical division of one cell into two, is thought to be fundamentally similar in most animal cell divisions and driven by the constriction of a contractile ring positioned and controlled solely by the mitotic spindle. During asymmetric cell divisions, the core polarity machinery (partitioning defective [PAR] proteins) controls the unequal inheritance of key cell fate determinants. Here, we show that in asymmetrically dividing Caenorhabditis elegans embryos, the cortical PAR proteins (including the small guanosine triphosphatase CDC-42) have an active role in regulating recruitment of a critical component of the contractile ring, filamentous actin (F-actin). We found that the cortical PAR proteins are required for the retention of anillin and septin in the anterior pole, which are cytokinesis proteins that our genetic data suggest act as inhibitors of F-actin at the contractile ring. Collectively, our results suggest that the cortical PAR proteins coordinate the establishment of cell polarity with the physical process of cytokinesis during asymmetric cell division to ensure the fidelity of daughter cell formation. PMID:26728855

  17. Tuberculosis prevalence and risk factors for water buffalo in Pará, Brazil.

    PubMed

    Barbosa, José D; da Silva, Jenevaldo B; Rangel, Charles P; da Fonseca, Adivaldo H; Silva, Natália S; Bomjardim, Henrique A; Freitas, Nayra F Q R

    2014-03-01

    The prevalence of and possible risk factors for tuberculosis were studied in water buffalo from Pará, Brazil. In this study, 3,917 pregnant and nonpregnant female Murrah and Mediterranean buffaloes were studied; 2,089 originated from Marajó Island, and 1,108 were from the mainland. The comparative cervical tuberculin test was used as a diagnostic test for tuberculosis in these animals. The prevalence of positive buffaloes was 3.5 % (100/2,809) on Marajó Island and 7.2 % (80/1,108) on the mainland. The municipalities with the highest tuberculosis prevalence rates in animals were Ipixuna do Pará (10.1 %), Marapanim (9.8 %), Chaves (9.4 %), Paragominas (8.6 %), and Cachoeira do Arari (6.7 %). The tuberculosis prevalence was not significantly different between the Murrah (4.3 %) and Mediterranean (4.8 %) breeds or between pregnant (5 %) and nonpregnant (4.3 %) buffaloes. Tuberculosis was detected in water buffaloes from Pará, Brazil; the mainland buffalo exhibited the highest tuberculosis prevalence. These results indicate that this disease is dangerous to public health and buffalo farming in Pará.

  18. The Utility of Clinicians Ratings of Anxiety Using the Pediatric Anxiety Rating Scale (PARS)

    ERIC Educational Resources Information Center

    Ginsburg, Golda S.; Keeton, Courtney P.; Drazdowski, Tess K.; Riddle, Mark A.

    2011-01-01

    Clinician ratings of anxiety hold the promise of clarifying discrepancies often found between child and parent reports of anxiety. The Pediatric Anxiety Rating Scale (PARS) is a clinician-administered instrument that assesses the frequency, severity, and impairment of common pediatric anxiety disorders and has been used as a primary outcome…

  19. Participation and Participatory Action Research (PAR) in Environmental Education Processes: For What Are People Empowered?

    ERIC Educational Resources Information Center

    Le Grange, Lesley

    2009-01-01

    Participatory action research (PAR) derived from anti-colonial struggles in the third world in the 1960s. Traditionally it has been a method of the margins because of its commitment to linking social justice to research. Because of its counter-hegemonic tendency it has had great appeal among environmental educators advocating a socially critical…

  20. [Capsulotomy through the pars plana in the eye with pseudophakia of the posterior chamber].

    PubMed

    Radian, A B; Mocanu, C

    1996-01-01

    It described one surgical technique for capsulotomy in the case of secondary cataract at an eye with pseudophakic by posterior chamber. The approaching makes with an simple instrument, through pars plana, the tearing of posterior capsule making under control with operator microscope, in area of visual axie, excluding any possibility to harm the lens, its luxation in vitreous or anothers complications.

  1. The interaction between uPAR and vitronectin triggers ligand-independent adhesion signalling by integrins

    PubMed Central

    Ferraris, Gian Maria Sarra; Schulte, Carsten; Buttiglione, Valentina; De Lorenzi, Valentina; Piontini, Andrea; Galluzzi, Massimiliano; Podestà, Alessandro; Madsen, Chris D; Sidenius, Nicolai

    2014-01-01

    The urokinase-type plasminogen activator receptor (uPAR) is a non-integrin vitronectin (VN) cell adhesion receptor linked to the plasma membrane by a glycolipid anchor. Through structure–function analyses of uPAR, VN and integrins, we document that uPAR-mediated cell adhesion to VN triggers a novel type of integrin signalling that is independent of integrin–matrix engagement. The signalling is fully active on VN mutants deficient in integrin binding site and is also efficiently transduced by integrins deficient in ligand binding. Although integrin ligation is dispensable, signalling is crucially dependent upon an active conformation of the integrin and its association with intracellular adaptors such as talin. This non-canonical integrin signalling is not restricted to uPAR as it poses no structural constraints to the receptor mediating cell attachment. In contrast to canonical integrin signalling, where integrins form direct mechanical links between the ECM and the cytoskeleton, the molecular mechanism enabling the crosstalk between non-integrin adhesion receptors and integrins is dependent upon membrane tension. This suggests that for this type of signalling, the membrane represents a critical component of the molecular clutch. PMID:25168639

  2. Crystal Structure of Thrombin Bound to the Uncleaved Extracellular Fragment of PAR1

    SciTech Connect

    Gandhi, Prafull S.; Chen, Zhiwei; Di Cera, Enrico

    2010-05-11

    Abundant structural information exists on how thrombin recognizes ligands at the active site or at exosites separate from the active site region, but remarkably little is known about how thrombin recognizes substrates that bridge both the active site and exosite I. The case of the protease-activated receptor PAR1 is particularly relevant in view of the plethora of biological effects associated with its activation by thrombin. Here, we present the 1.8 {angstrom} resolution structure of thrombin S195A in complex with a 30-residue long uncleaved extracellular fragment of PAR1 that documents for the first time a productive binding mode bridging the active site and exosite I. The structure reveals two unexpected features of the thrombin-PAR1 interaction. The acidic P3 residue of PAR1, Asp{sup 39}, does not hinder binding to the active site and actually makes favorable interactions with Gly{sup 219} of thrombin. The tethered ligand domain shows a considerable degree of disorder even when bound to thrombin. The results fill a significant gap in our understanding of the molecular mechanisms of recognition by thrombin in ways that are relevant to other physiological substrates.

  3. The loss of circadian PAR bZip transcription factors results in epilepsy

    PubMed Central

    Gachon, Frédéric; Fonjallaz, Philippe; Damiola, Francesca; Gos, Pascal; Kodama, Tohru; Zakany, Jozsef; Duboule, Denis; Petit, Brice; Tafti, Mehdi; Schibler, Ueli

    2004-01-01

    DBP (albumin D-site-binding protein), HLF (hepatic leukemia factor), and TEF (thyrotroph embryonic factor) are the three members of the PAR bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor family. All three of these transcriptional regulatory proteins accumulate with robust circadian rhythms in tissues with high amplitudes of clock gene expression, such as the suprachiasmatic nucleus (SCN) and the liver. However, they are expressed at nearly invariable levels in most brain regions, in which clock gene expression only cycles with low amplitude. Here we show that mice deficient for all three PAR bZip proteins are highly susceptible to generalized spontaneous and audiogenic epilepsies that frequently are lethal. Transcriptome profiling revealed pyridoxal kinase (Pdxk) as a target gene of PAR bZip proteins in both liver and brain. Pyridoxal kinase converts vitamin B6 derivatives into pyridoxal phosphate (PLP), the coenzyme of many enzymes involved in amino acid and neurotransmitter metabolism. PAR bZip-deficient mice show decreased brain levels of PLP, serotonin, and dopamine, and such changes have previously been reported to cause epilepsies in other systems. Hence, the expression of some clock-controlled genes, such as Pdxk, may have to remain within narrow limits in the brain. This could explain why the circadian oscillator has evolved to generate only low-amplitude cycles in most brain regions. PMID:15175240

  4. Kis antitoxin couples plasmid R1 replication and parD (kis,kid) maintenance modules.

    PubMed

    López-Villarejo, Juan; Diago-Navarro, Elizabeth; Hernández-Arriaga, Ana María; Díaz-Orejas, Ramón

    2012-03-01

    The coupling between the replication and parD (kis, kid) maintenance modules of R1 has been revisited here by the isolation of a significant collection of conditional replication mutants in the pKN1562 mini-R1 plasmid, and in its derivative, pJLV01, specifically affected in the RNase activity of the Kid toxin. This new analysis aims to identify key factors in this coupling. For this purpose we have quantified and characterized the restriction introduced by parD to isolate conditional replication mutants of this plasmid, a signature of the modular coupling. This restriction depends on the RNase activity of the Kid toxin and it is relieved by either over-expression of the Kis antitoxin or by preventing its degradation by Lon and ClpAP proteases. Based on these data and on the correlation between copy numbers and parD transcriptional levels obtained in the different mutants, it is proposed that a reduction of Kis antitoxin levels in response to inefficient plasmid replication is the key factor for coupling plasmid replication and parD modules.

  5. Participatory Action Research: Reflections on Critical Incidents in a PAR Project.

    ERIC Educational Resources Information Center

    Santelli, Betsy; Singer, George H. S.; DiVenere, Nancy; Ginsberg, Connie; Powers, Laurie E.

    1998-01-01

    This article describes a participatory action research (PAR) project designed to evaluate Parent to Parent programs in five states. The process of developing a shared understanding of the program and of the purpose for evaluating them, along with an on-going willingness of parents and researchers to compromise, led to creative solutions to…

  6. Plant-derived SAC domain of PAR-4 (Prostate Apoptosis Response 4) exhibits growth inhibitory effects in prostate cancer cells

    PubMed Central

    Sarkar, Shayan; Jain, Sumeet; Rai, Vineeta; Sahoo, Dipak K.; Raha, Sumita; Suklabaidya, Sujit; Senapati, Shantibhusan; Rangnekar, Vivek M.; Maiti, Indu B.; Dey, Nrisingha

    2015-01-01

    The gene Par-4 (Prostate Apoptosis Response 4) was originally identified in prostate cancer cells undergoing apoptosis and its product Par-4 showed cancer specific pro-apoptotic activity. Particularly, the SAC domain of Par-4 (SAC-Par-4) selectively kills cancer cells leaving normal cells unaffected. The therapeutic significance of bioactive SAC-Par-4 is enormous in cancer biology; however, its large scale production is still a matter of concern. Here we report the production of SAC-Par-4-GFP fusion protein coupled to translational enhancer sequence (5′ AMV) and apoplast signal peptide (aTP) in transgenic Nicotiana tabacum cv. Samsun NN plants under the control of a unique recombinant promoter M24. Transgene integration was confirmed by genomic DNA PCR, Southern and Northern blotting, Real-time PCR, and Nuclear run-on assays. Results of Western blot analysis and ELISA confirmed expression of recombinant SAC-Par-4-GFP protein and it was as high as 0.15% of total soluble protein. In addition, we found that targeting of plant recombinant SAC-Par-4-GFP to the apoplast and endoplasmic reticulum (ER) was essential for the stability of plant recombinant protein in comparison to the bacterial derived SAC-Par-4. Deglycosylation analysis demonstrated that ER-targeted SAC-Par-4-GFP-SEKDEL undergoes O-linked glycosylation unlike apoplast-targeted SAC-Par-4-GFP. Furthermore, various in vitro studies like mammalian cells proliferation assay (MTT), apoptosis induction assays, and NF-κB suppression suggested the cytotoxic and apoptotic properties of plant-derived SAC-Par-4-GFP against multiple prostate cancer cell lines. Additionally, pre-treatment of MAT-LyLu prostate cancer cells with purified SAC-Par-4-GFP significantly delayed the onset of tumor in a syngeneic rat prostate cancer model. Taken altogether, we proclaim that plant made SAC-Par-4 may become a useful alternate therapy for effectively alleviating cancer in the new era. PMID:26500666

  7. Project Plan 7930 Cell G PaR Remote Handling System Replacement

    SciTech Connect

    Kinney, Kathryn A

    2009-10-01

    For over 40 years the US Department of Energy (DOE) and its predecessors have made Californium-252 ({sup 252}Cf) available for a wide range of industries including medical, nuclear fuels, mining, military and national security. The Radiochemical Engineering Development Center (REDC) located within the Oak Ridge National Laboratory (ORNL) processes irradiated production targets from the High Flux Isotope Reactor (HFIR). Operations in Building 7930, Cell G provide over 70% of the world's demand for {sup 252}Cf. Building 7930 was constructed and equipped in the mid-1960s. Current operations for {sup 252}Cf processing in Building 7930, Cell G require use of through-the-wall manipulators and the PaR Remote Handling System. Maintenance and repairs for the manipulators is readily accomplished by removal of the manipulator and relocation to a repair shop where hands-on work can be performed in glove boxes. Contamination inside cell G does not currently allow manned entry and no provisions were created for a maintenance area inside the cell. There has been no maintenance of the PaR system or upgrades, leaving operations vulnerable should the system have a catastrophic failure. The Cell G PaR system is currently being operated in a run to failure mode. As the manipulator is now 40+ years old there is significant risk in this method of operation. In 2006 an assessment was completed that resulted in recommendations for replacing the manipulator operator control and power centers which are used to control and power the PaR manipulator in Cell G. In mid-2008 the chain for the bridge drive failed and subsequent examinations indicated several damaged links (see Figure 1). To continue operations the PaR manipulator arm is being used to push and pull the bridge as a workaround. A retrieval tool was fabricated, tested and staged inside Cell G that will allow positioning of the bridge and manipulator arm for removal from the cell should the PaR system completely fail. A fully

  8. La structure de l'eau liquide: Une etude thermique par spectroscopie infrarouge

    NASA Astrophysics Data System (ADS)

    Larouche, Pascal

    Le probleme de la structure de l'eau liquide est important car l'eau est le liquide le plus present sur Terre, et complexe, la quete d'un modele precis pour decrire comment fonctionne ce liquide ayant debute des la fin du dix-neuvieme siecle. Cette etude aborde ce probleme en etudiant l'effet de l'augmentation de la temperature sur H2O et D 2O purs a l'aide de la spectroscopie infrarouge. L'intervalle de temperatures scrute est 29--93.1°C. Les spectres enregistres sont des spectres MIR-ATR entre 650 et 6000 cm-1 . L'analyse par facteurs de ces donnees permet de montrer que deux et seulement deux facteurs principaux sont necessaires pour decomposer tous les spectres experimentaux. Ces resultats sont confirmes grace a l'analyse par facteurs de spectres de la region FIR. Par la suite, la transformation en spectres de la partie reelle n et imaginaire k de l'indice de refraction permet de combiner les donnees des regions MIR et FIR. Une fois ce calcul termine, les spectres de transmission complets de H 2O et D2O entre 25 et 90°C sont connus. Ils sont ensuite utilises pour calculer par extrapolation le spectre des especes constituant l'eau liquide, puis leur abondance en fonction de la temperature. L'extrapolation de ces abondances montre que les especes correspondent a des temperatures limites de --18 et 122°C. Par la suite, la decomposition gaussienne des spectres d'especes met en evidence la riche structure de ces objets et permet de demontrer que l'apparent deplacement du massif d'absorption OH (OD) est produit par une variation de l'intensite des bandes et non pas de leur deplacement. L'examen attentif des spectres des especes prouve qu'il n'y a pas de OH libres crees par l'augmentation de la temperature: meme a 93.1°C, chaque molecule possede quatre liens-H. Ces conclusions sont de plus confirmees par une analyse thermodynamique du passage des molecules de la phase solide a la phase gazeuse. Pour diversifier la nature des resultats experimentaux utilises, des

  9. Water quality, phytoplankton and zooplankton of Par Pond and Pond B. Volume 2. Phytoplankton. Final report, January 1984-June 1985

    SciTech Connect

    Chimney, M.J.; Cody, W.R.; Starkel, W.M.

    1985-08-01

    This document reports on the Par Pond and Pond B phytoplankton community. The objectives of this study were to (1) characterize the biological communities and environmental conditions in Par Pond and Pond B; (2) assess the impact and significance of entrainment losses of plankton at the Par Pond pumphouse; (3) assess the impact of heated discharge on the biotic communities throughout the reservoir; and (4) help determine if Par Pond maintains an indigenous balanced biological community as defined in state and federal regulations. A total of 368 phytoplankton taxa, representing all the major taxonomic groups characteristic of North American freshwaters, were identified from Par Pond and Pond B during this study (73 Bacillariophyta, 166 Chlorophyta, 30 Chrysophyta, 5 Cryptophyta, 47 Cyanophyta, 18 Euglenophyta, 11 phytoflaggelates and 18 Pyrrophyta).

  10. ParFit: A Python-Based Object-Oriented Program for Fitting Molecular Mechanics Parameters to ab Initio Data

    DOE PAGES

    Zahariev, Federico; De Silva, Nuwan; Gordon, Mark S.; ...

    2017-02-23

    Here, a newly created object-oriented program for automating the process of fitting molecular-mechanics parameters to ab initio data, termed ParFit, is presented. ParFit uses a hybrid of deterministic and stochastic genetic algorithms. ParFit can simultaneously handle several molecular-mechanics parameters in multiple molecules and can also apply symmetric and antisymmetric constraints on the optimized parameters. The simultaneous handling of several molecules enhances the transferability of the fitted parameters. ParFit is written in Python, uses a rich set of standard and nonstandard Python libraries, and can be run in parallel on multicore computer systems. As an example, a series of phosphine oxides,more » important for metal extraction chemistry, are parametrized using ParFit.« less

  11. PAR2 exerts local protection against acute pancreatitis via modulation of MAP kinase and MAP kinase phosphatase signaling.

    PubMed

    Namkung, Wan; Yoon, Jae Seok; Kim, Kyung Hwan; Lee, Min Goo

    2008-11-01

    During acute pancreatitis, protease-activated receptor 2 (PAR2) can be activated by interstitially released trypsin. In the mild form of pancreatitis, PAR2 activation exerts local protection against intrapancreatic damage, whereas, in the severe form of pancreatitis, PAR2 activation mediates some systemic complications. This study aimed to identify the molecular mechanisms of PAR2-mediated protective effects against intrapancreatic damage. A mild form of acute pancreatitis was induced by an intraperitoneal injection of caerulein (40 microg/kg) in rats. Effects of PAR2 activation on intrapancreatic damage and on mitogen-activated protein (MAP) kinase signaling were assessed. Caerulein treatment activated extracellular signal-regulated kinase (ERK) and c-Jun NH(2)-terminal kinase (JNK) within 15 min and maintained phosphorylation of ERK and JNK for 2 h in the rat pancreas. Although PAR2 activation by the pretreatment with PAR2-activating peptide (AP) itself increased ERK phosphorylation in rat pancreas, the same treatment remarkably decreased caerulein-induced activation of ERK and JNK principally by accelerating their dephosphorylation. Inhibition of ERK and JNK phosphorylation by the pretreatment with MAP/ERK kinase (MEK) or JNK inhibitors decreased caerulein-induced pancreatic damage that was similar to the effect induced by PAR2-AP. Notably, in caerulein-treated rats, PAR2-AP cotreatment highly increased the expression of a group of MAP kinase phosphatases (MKPs) that deactivate ERK and JNK. The above results imply that downregulation of MAP kinase signaling by MKP induction is a key mechanism involved in the protective effects of PAR2 activation on caerulein-induced intrapancreatic damage.

  12. Activation of PAR2 receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint

    PubMed Central

    Russell, FA; Schuelert, N; Veldhoen, VE; Hollenberg, MD; McDougall, JJ

    2012-01-01

    Background and Purpose The PAR2 receptors are involved in chronic arthritis by mechanisms that are as yet unclear. Here, we examined PAR2 activation in the rat knee joint. Experimental Approach PAR2 in rat knee joint dorsal root ganglia (DRG) cells at L3-L5, retrogradely labelled with Fluoro-gold (FG) were demonstrated immunohistochemically. Electrophysiological recordings from knee joint nerve fibres in urethane anaesthetized Wistar rats assessed the effects of stimulating joint PAR2 with its activating peptide, 2-furoyl-LIGRLO-NH2 (1–100 nmol·100 μL−1, via close intra-arterial injection). Fibre firing rate was recorded during joint rotations before and 15 min after administration of PAR2 activating peptide or control peptide. Leukocyte kinetics in the synovial vasculature upon PAR2 activation were followed by intravital microscopy for 60 min after perfusion of 2-furoyl-LIGRLO-NH2 or control peptide. Roles for transient receptor potential vanilloid-1 (TRPV1) or neurokinin-1 (NK1) receptors in the PAR2 responses were assessed using the selective antagonists, SB366791 and RP67580 respectively. Key Results PAR2 were expressed in 59 ± 5% of FG-positive DRG cells; 100 nmol 2-furoyl-LIGRLO-NH2 increased joint fibre firing rate during normal and noxious rotation, maximal at 3 min (normal; 110 ± 43%, noxious; 90 ± 31%). 2-Furoyl-LIGRLO-NH2 also significantly increased leukocyte rolling and adhesion over 60 min. All these effects were blocked by pre-treatment with SB366791 and RP67580 (P < 0.05 compared with 2-furoyl-LIGRLO-NH2 alone). Conclusions and Implications PAR2 receptors play an acute inflammatory role in the knee joint via TRPV1- and NK1-dependent mechanisms involving both PAR2-mediated neuronal sensitization and leukocyte trafficking. PMID:22849826

  13. Simulation de l'accretion de glace sur un obstacle bidimensionnel par la methode des bissectrices et par la modelisation des ruisselets et des gouttes de surface

    NASA Astrophysics Data System (ADS)

    Fortin, Guy

    Le LIMA (Laboratoire International des Materiaux Antigivre) en collaboration avec le CIRA (Italian Aerospace Research Centre) a developpe un logiciel simulant l'accretion de la glace en regimes sec et humide sur un objet bidimensionnel fixe. L'approche utilisee s'appuie sur les travaux de Lozowski pour les bilans energetiques, sur une etude du comportement du film d'eau, des ruisselets et des gouttes de surface pour le calcul des rugosites et des masses d'eau residuelle, ainsi que sur une methode de bissectrice pour l'evolution de la surface de glace. La contribution du CIRA a ete de fournir le logiciel pour le calcul des ecoulements et de la captation. Le bilan energetique base sur la conservation de l'energie est la sommation de la chaleur latente de fusion, d'evaporation et de sublimation, du rechauffement adiabatique et cinetique, et des pertes de chaleur par convection et conduction, ainsi que de l'evolution thermodynamique de l'eau de son etat initial a son etat final. La densite de la glace, qui a un impact important sur la simulation, est calculee a partir d'une correlation empirique developpee avec les cylindres tournants. En se basant sur les travaux de Al-Khalil et Hansman, le comportement des gouttes en regimes sec et humide a ete decrit analytiquement, ce qui a mene a determiner la hauteur maximale que peuvent atteindre les gouttes avant mouvement. Cette hauteur, appelee hauteur de mouvement, permet de determiner l'etat de l'eau sur la surface (film, ruisselets ou gouttes), ainsi que la hauteur des rugosites lorsque l'eau existe sous forme de gouttes ou de ruisselets. La hauteur de mouvement est determinee par l'equilibre entre les forces de cisaillement, induites par les effets aerodynamiques et gravitationnels evalues pour une goutte non deformee, et la force de cisaillement, induite par la tension de surface et la deformation de la goutte. Elle a ete validee en laboratoire et la precision obtenue pour la partie aerodynamique et gravitationnelle est

  14. Etude par spectroscopie de Coulomb de points quantiques lateraux individuels et couples

    NASA Astrophysics Data System (ADS)

    Pioro-Ladriere, Michel

    Des points quantiques contenant un nombre discret et variable d'electrons sont formes dans un gaz bi-dimensionnel d'electrons a l'aide de grilles metalliques. Le transport electrique, le blocage de spin et la detection de charge sont employes comme outils spectroscopiques permettant de sonder les proprietes de ces nanostructures. Ces techniques permettent aussi de controler exactement le nombres d'electrons confines dans des points quantiques individuels et couples en utilisant un patron de grille judicieux. Une technique de refroidissement en tension est developpee afin de minimiser les effets parasites du bruit telegraphique. Ce type de bruit de charge deteriore la stabilite des nanostructures laterales par l'activation d'un minuscule courant de fuite entre les grilles et le gaz bi-dimensionnel. Un modele expliquant le role du refroidissement en tension sur le courant de fuite est presente. L'activation du courant de fuite est confirmee par detection de charge. Les effets des interactions entre les electrons pieges dans un point quantique sont ensuite etudies dans un regime ou il est possible de comparer les resulats experimentaux avec ceux obtenus par diagonalisation exacte. L'etude demontre que la phase associee au facteur de remplissage nu = 2 est instable au-dessus d'un nombre critique d'electrons. Cette instabilite est confirmee experimentalement par blocage de spin. On demontre aussi l'existence d'etats correles dans le regime des renversements de spin, associe au passage de la phase nu = 2 a nu = 1. Les etats correles sont identifies par spectroscopie en transport non lineaire. Cette caracterisation du diagramme de phase de points individuels permet de coupler deux points quantiques configures a nu = 2. Pour ce regime, la nanostructure se comporte comme un systeme a deux niveaux pouvant contenir entre un et quatre electrons de valence et ce, meme si le nombre total d'electrons est plus eleve. Les degres de liberte de charge et de spin des deux points

  15. Impacts of Light Use Efficiency and fPAR Parameterization on Gross Primary Production Modeling

    NASA Technical Reports Server (NTRS)

    Cheng, Yen-Ben; Zhang, Qingyuan; Lyapustin, Alexei I.; Wang, Yujie; Middleton, Elizabeth M.

    2014-01-01

    This study examines the impact of parameterization of two variables, light use efficiency (LUE) and the fraction of absorbed photosynthetically active radiation (fPAR or fAPAR), on gross primary production(GPP) modeling. Carbon sequestration by terrestrial plants is a key factor to a comprehensive under-standing of the carbon budget at global scale. In this context, accurate measurements and estimates of GPP will allow us to achieve improved carbon monitoring and to quantitatively assess impacts from cli-mate changes and human activities. Spaceborne remote sensing observations can provide a variety of land surface parameterizations for modeling photosynthetic activities at various spatial and temporal scales. This study utilizes a simple GPP model based on LUE concept and different land surface parameterizations to evaluate the model and monitor GPP. Two maize-soybean rotation fields in Nebraska, USA and the Bartlett Experimental Forest in New Hampshire, USA were selected for study. Tower-based eddy-covariance carbon exchange and PAR measurements were collected from the FLUXNET Synthesis Dataset. For the model parameterization, we utilized different values of LUE and the fPAR derived from various algorithms. We adapted the approach and parameters from the MODIS MOD17 Biome Properties Look-Up Table (BPLUT) to derive LUE. We also used a site-specific analytic approach with tower-based Net Ecosystem Exchange (NEE) and PAR to estimate maximum potential LUE (LUEmax) to derive LUE. For the fPAR parameter, the MODIS MOD15A2 fPAR product was used. We also utilized fAPAR chl, a parameter accounting for the fAPAR linked to the chlorophyll-containing canopy fraction. fAPAR chl was obtained by inversion of a radiative transfer model, which used the MODIS-based reflectances in bands 1-7 produced by Multi-Angle Implementation of Atmospheric Correction (MAIAC) algorithm. fAPAR chl exhibited seasonal dynamics more similar with the flux tower based GPP than MOD15A2 fPAR, especially

  16. Developpement d'algorithmes de reconstruction statistique appliques en tomographie rayons-X assistee par ordinateur

    NASA Astrophysics Data System (ADS)

    Thibaudeau, Christian

    La tomodensitometrie (TDM) permet d'obtenir, et ce de facon non invasive, une image tridimensionnelle de l'anatomie interne d'un sujet. Elle constitue l'evolution logique de la radiographie et permet l'observation d'un volume sous differents plans (sagittal, coronal, axial ou n'importe quel autre plan). La TDM peut avantageusement completer la tomographie d'emission par positrons (TEP), un outil de predilection utilise en recherche biomedicale et pour le diagnostic du cancer. La TEP fournit une information fonctionnelle, physiologique et metabolique, permettant la localisation et la quantification de radiotraceurs a l'interieur du corps humain. Cette derniere possede une sensibilite inegalee, mais peut neanmoins souffrir d'une faible resolution spatiale et d'un manque de repere anatomique selon le radiotraceur utilise. La combinaison, ou fusion, des images TEP et TDM permet d'obtenir cette localisation anatomique de la distribution du radiotraceur. L'image TDM represente une carte de l'attenuation subie par les rayons-X lors de leur passage a travers les tissus. Elle permet donc aussi d'ameliorer la quantification de l'image TEP en offrant la possibilite de corriger pour l'attenuation. L'image TDM s'obtient par la transformation de profils d'attenuation en une image cartesienne pouvant etre interpretee par l'humain. Si la qualite de cette image est fortement influencee par les performances de l'appareil, elle depend aussi grandement de la capacite de l'algorithme de reconstruction a obtenir une representation fidele du milieu image. Les techniques de reconstruction standards, basees sur la retroprojection filtree (FBP, filtered back-projection), reposent sur un modele mathematiquement parfait de la geometrie d'acquisition. Une alternative a cette methode etalon est appelee reconstruction statistique, ou iterative. Elle permet d'obtenir de meilleurs resultats en presence de bruit ou d'une quantite limitee d'information et peut virtuellement s'adapter a toutes formes

  17. 1,25-Dihydroxyvitamin D(3) Inhibits Podocyte uPAR Expression and Reduces Proteinuria

    PubMed Central

    Liu, Shuangxin; Xie, Shaoting; Yang, Yun; Ma, Juan; Deng, Yujun; Wang, Wenjian; Xu, Lixia; Li, Ruizhao; Zhang, Li; Yu, Chunping; Shi, Wei

    2013-01-01

    Background Accumulating studies have demonstrated that 1,25-Dihydroxyvitamin D(3) (1,25(OH)2D3) reduces proteinuria and protects podocytes from injury. Recently, urokinase receptor (uPAR) and its soluble form have been shown to cause podocyte injury and focal segmental glomerulosclerosis (FSGS). Here, our findings showed that 1,25(OH)2D3 did inhibit podocyte uPAR expression and attenuate proteinuria and podocyte injury. Methodology/Principal Findings In this study, the antiproteinuric effect of 1,25(OH)2D3 was examined in the lipopolysaccharide mice model of transient proteinuria (LPS mice) and in the 5/6 nephrectomy rat FSGS model(NTX rats). uPAR protein expression were tested by flow cytometry, immune cytochemistry and western blot analysis, and uPAR mRNA expression by real-time quantitative PCR in cultured podocytes and kidney glomeruli isolated from mice and rats. Podocyte motility was observed by transwell migration assay and wound healing assay. Podocyte foot processes effacement was identified by transmission electron microscopy. We found that 1,25(OH)2D3 inhibited podocyte uPAR mRNA and protein synthesis in LPS-treated podocytes, LPS mice and NTX rats, along with 1,25(OH)2D3 reducing proteinuria in NTX rats and LPS mice.1,25(OH)2D3 reduced glomerulosclerosis in NTX rats and alleviated podocyte foot processes effacement in LPS mice. Transwell migration assay and wound healing assay showed that LPS-induced podocyte motility, irrespective of random or directed motility, were substantially reduced by 1,25(OH)2D3. Conclusions/Significance Our results demonstrated that 1,25(OH)2D3 inhibited podocyte uPAR expression in vitro and in vivo, which may be an unanticipated off target effect of 1,25(OH)2D3 and explain its antiproteinuric effect in the 5/6 nephrectomy rat FSGS model and the LPS mouse model of transient proteinuria. PMID:23741418

  18. Monomer–dimer dynamics and distribution of GPI-anchored uPAR are determined by cell surface protein assemblies

    PubMed Central

    Caiolfa, Valeria R.; Zamai, Moreno; Malengo, Gabriele; Andolfo, Annapaola; Madsen, Chris D.; Sutin, Jason; Digman, Michelle A.; Gratton, Enrico; Blasi, Francesco; Sidenius, Nicolai

    2007-01-01

    To search for functional links between glycosylphosphatidylinositol (GPI) protein monomer–oligomer exchange and membrane dynamics and confinement, we studied urokinase plasminogen activator (uPA) receptor (uPAR), a GPI receptor involved in the regulation of cell adhesion, migration, and proliferation. Using a functionally active fluorescent protein–uPAR in live cells, we analyzed the effect that extracellular matrix proteins and uPAR ligands have on uPAR dynamics and dimerization at the cell membrane. Vitronectin directs the recruitment of dimers and slows down the diffusion of the receptors at the basal membrane. The commitment to uPA–plasminogen activator inhibitor type 1–mediated endocytosis and recycling modifies uPAR diffusion and induces an exchange between uPAR monomers and dimers. This exchange is fully reversible. The data demonstrate that cell surface protein assemblies are important in regulating the dynamics and localization of uPAR at the cell membrane and the exchange of monomers and dimers. These results also provide a strong rationale for dynamic studies of GPI-anchored molecules in live cells at steady state and in the absence of cross-linker/clustering agents. PMID:18056417

  19. Characterization of a point mutation in the parC gene of Mycoplasma bovirhinis associated with fluoroquinolone resistance.

    PubMed

    Hirose, K; Kawasaki, Y; Kotani, K; Abiko, K; Sato, H

    2004-05-01

    Quinolone-resistant (QR) mutants of Mycoplasma bovirhinis strain PG43 (type strain) were generated by stepwise selection in increasing concentrations of enrofloxacin (ENR). An alteration was found in the quinolone resistance-determining region (QRDR) of the parC gene coding for the ParC subunit of topoisomerase IV from these mutants, but not in the gyrA, gyrB, and parE gene coding for the GyrA and GyrB subunits of DNA gyrase and the ParE subunit of topoisomerase IV. Similarly, such an alteration in QRDR of parC was found in the field isolates of M. bovirhinis, which possessed various levels of QR. The substitution of leucine (Leu) by serine (Ser) at position 80 of QRDR of ParC was observed in both QR-mutants and QR-isolates. This is the first report of QR based on a point mutation of the parC gene in M. bovirhinis.

  20. The Clinical Value of Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels in Autoimmune Connective Tissue Disorders

    PubMed Central

    Toldi, Gergely; Balog, Attila

    2016-01-01

    The assessment of the general inflammatory condition of patients with autoimmune connective tissue disorders (ACTD) is a major challenge. The use of traditional inflammatory markers including CRP-levels and erythrocyte sedimentation rate (ESR) is limited by several preanalytical factors and their low specificities. Soluble urokinase plasminogen activator receptor (suPAR) is one of the novel candidate markers that is increasingly used in immune mediated disorders. In our studies we compared suPAR levels of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and ankylosing spondylitis with those of healthy controls. suPAR provided valuable clinical information on disease activity in RA, SLE and SSc. We identified a subgroup of remitted RA patients, who presented still clinical symptoms of inflammatory activity which correlated to high plasma suPAR (while ESR and CRP were normal). In SLE we established specific suPAR cut-off values that support the discrimination between patients with high and those with moderate SLE activity. In patients with SSc suPAR correlated with objective measures of lung and other complications. In the majority of ACTDs including SLE, SSc or RA, suPAR is seemingly a good biomarker that would provide valuable clinical information. However, before the introduction of this novel parameter in laboratory repertoire important issues should be elucidated. These include the establishment of appropriate and disease specific cutoff values, clarification of interfering preanalytical values and underlying conditions and declaration of age- and gender-specific reference ranges. PMID:27683525

  1. The Par3/aPKC interaction is essential for end bud remodeling and progenitor differentiation during mammary gland morphogenesis

    PubMed Central

    McCaffrey, Luke Martin; Macara, Ian G.

    2009-01-01

    Mammalian polarity proteins have been studied predominantly in cell culture systems, and little is known about their functions in vivo. To address this issue, we used a shRNA lentiviral system to manipulate gene expression in mouse mammary stem/progenitor cells. Transplantation of Par3-depleted stem/progenitor cells into the mammary fat pad severely disrupted mammary development, and glands were characterized by ductal hyperplasia, luminal filling, and highly disorganized end bud structures that were unable to remodel into normal ductal structures. Unexpectedly, Par3-depleted mammary glands also had an expanded progenitor population. We identified a novel function for the atypical protein kinase C (aPKC)-binding domain of Par3 in restricting Par3 and aPKC to the apical region in mammary epithelia in vivo, and found that mammary morphogenesis is dependent on the ability of Par3 to directly bind aPKC. These results reveal a new function for Par3 in the regulation of progenitor differentiation and epithelial morphogenesis in vivo and demonstrate for the first time an essential requirement for the Par3–aPKC interaction. PMID:19528321

  2. Graded hedgehog and fibroblast growth factor signaling independently regulate pituitary cell fates and help establish the pars distalis and pars intermedia of the zebrafish adenohypophysis.

    PubMed

    Guner, Burcu; Ozacar, A Tuba; Thomas, Jeanne E; Karlstrom, Rolf O

    2008-09-01

    The vertebrate adenohypophysis forms as a placode at the anterior margin of the neural plate, requiring both hedgehog (Hh) and fibroblast growth factor (Fgf) mediated cell-cell signaling for induction and survival of endocrine cell types. Using small molecule inhibitors to modulate signaling levels during zebrafish development we show that graded Hh and Fgf signaling independently help establish the two subdomains of the adenohypophysis, the anteriorly located pars distalis (PD) and the posterior pars intermedia (PI). High levels of Hh signaling are required for formation of the PD and differentiation of anterior endocrine cell types, whereas lower levels of Hh signaling are required for formation of the PI and differentiation of posterior endocrine cell types. In contrast, high Fgf signaling levels are required for formation of the PI and posterior endocrine cell differentiation, whereas anterior regions require lower levels of Fgf signaling. Based on live observations and marker analyses, we show that the PD forms first at the midline closest to the central nervous system source of Sonic hedgehog. In contrast the PI appears to form from more lateral/posterior cells close to a central nervous system source of Fgf3. Together our data show that graded Hh and Fgf signaling independently direct induction of the PD and PI and help establish endocrine cell fates along the anterior/posterior axis of the zebrafish adenohypophysis. These data suggest that there are distinct origins and signaling requirements for the PD and PI.

  3. PET imaging of urokinase-type plasminogen activator receptor (uPAR) in prostate cancer: current status and future perspectives.

    PubMed

    Skovgaard, Dorthe; Persson, Morten; Kjaer, Andreas

    2016-01-01

    Overexpression of urokinase-type plasminogen activator receptors (uPAR) represents an important biomarker for aggressiveness in most common malignant diseases, including prostate cancer (PC). Accordingly, uPAR expression either assessed directly in malignant PC tissue or assessed directly in plasma (intact/cleaved forms)-provides independent additional clinical information to that contributed by PSA, Gleason score, and other relevant pathological and clinical parameters. In this respect, non-invasive molecular imaging by positron emission tomography (PET) offers a very attractive technology platform, which can provide the required quantitative information on the uPAR expression profile, without the need for invasive procedures and the risk of missing the target due to tumor heterogeneity. These observations support non-invasive PET imaging of uPAR in PC as a clinically relevant diagnostic and prognostic imaging method. In this review, we will focus on the recent development of uPAR PET and the relevance within prostate cancer imaging. Novel antibody and small-molecule radiotracers-targeting uPAR, including a series of uPAR-targeting PET ligands, based on the high affinity peptide ligand AE105, have been synthesized and tested in vitro and in vivo in preclinical murine xenograft models and, recently, in a first-ever clinical uPAR PET study in cancer patients, including patients with PC. In this phase I study, a high and specific uptake of the tracer (64)Cu-DOTA-AE105 was found in both primary tumors and lymph node metastases. The results are encouraging and support large-scale clinical trials to determine the utility of uPAR PET in the management of patients with PC with the goal of improving outcome.

  4. Ground validation of Dual Precipitation Radar (DPR) on GPM by rapid scan Phased Array weahter Radar (PAR)

    NASA Astrophysics Data System (ADS)

    Hirano, Y.; Mega, T.; Shimamura, S.; Wu, T.; Kikuchi, H.; Ushio, T.; Yoshikawa, E.; Chandra, C. V.

    2014-12-01

    The core observatory satellite of the Global Precipitation Measurement (GPM) mission was launched on February 27th 2014. The Dual-frequency Precipitation Radar (DPR) on the GPM core observatory is the succession of the TRMM Precipitation Radar (PR). The DPR consists of a Ku-band precipitation radar and a Ka-band precipitation radar. The DPR is expected to be more sensitive than the PR especially in the measurement of light rainfall and snowfall in high latitude regions. Because of the difference of spatial and temporal resolutions, Space Radar (SR) and conventional type of Ground Radar (GR) are hard to compare.The SR observes each point of earth in short time, for example one footprint is an observation in some microseconds. Rain-gauge measurements have accurate rainfall rate, but rain-gage observes small area and accumulated rainfall in some minutes. The conventional GR can cover a wide area, however, a volume scan requires several minutes. The Phased Array weather Radar (PAR) is developed by Osaka University, Toshiba, and NICT. The PAR is a weather-radar on X-band within 100m range sampling. High spatial and temporal resolution is achieved by the PAR with pulse compression and the digital beam-forming technique. The PAR transmits a wide beam and receives narrow beams by using digital beam forming. Then, the PAR observes many elevation angles from a single pulse. The time of each volume scan is 10-30 seconds in operation, typically 30 seconds. The study shows comparisons between the DPR and the PAR by more similar spatial and temporal resolution. The rainfall region of DPR is similar to the one of PAR. Correlation coefficient of both radar reflectivity suggests more than 0.8 in the 20km range of PAR. As a result, it is considered that DPR can observe with high accuracy. We present the case study which DPR overpassed the PAR observation region in detail.

  5. Physical activity on prescription schemes (PARS): do programme characteristics influence effectiveness? Results of a systematic review and meta-analyses

    PubMed Central

    Arsenijevic, Jelena; Groot, Wim

    2017-01-01

    Background Physical activity on prescription schemes (PARS) are health promotion programmes that have been implemented in various countries. The aim of this study was to outline the differences in the design of PARS in different countries. This study also explored the differences in the adherence rate to PARS and the self-reported level of physical activity between PARS users in different countries. Method A systematic literature review and meta-analyses were conducted. We searched PubMed and EBASCO in July 2015 and updated our search in September 2015. Studies that reported adherence to the programme and self-reported level of physical activity, published in the English language in a peer-reviewed journal since 2000, were included. The difference in the pooled adherence rate after finishing the PARS programme and the adherence rate before or during the PARS programme was 17% (95% CI 9% to 24%). The difference in the pooled physical activity was 0.93 unit score (95 CI −3.57 to 1.71). For the adherence rate, a meta-regression was conducted. Results In total, 37 studies conducted in 11 different countries met the inclusion criteria. Among them, 31 reported the adherence rate, while the level of physical activity was reported in 17 studies. Results from meta-analyses show that PARS had an effect on the adherence rate of physical activity, while the results from the meta-regressions show that programme characteristics such as type of chronic disease and the follow-up period influenced the adherence rate. Conclusions The effects of PARS on adherence and self-reported physical activity were influenced by programme characteristics and also by the design of the study. Future studies on the effectiveness of PARS should use a prospective longitudinal design and combine quantitative and qualitative data. Furthermore, future evaluation studies should distinguish between evaluating the adherence rate and the self-reported physical activity among participants with different

  6. Agrobacterium tumefaciens pTAR parA promoter region involved in autoregulation, incompatibility and plasmid partitioning.

    PubMed

    Gallie, D R; Kado, C I

    1987-02-05

    The locus responsible for directing proper plasmid partitioning of Agrobacterium tumefaciens pTAR is contained within a 1259 base-pair region. Insertions or deletions within this locus can result in the loss of the plasmid's ability to partition properly. One protein product (parA), approximately 25,000 Mr, is expressed from the par locus in Escherichia coli and A. tumefaciens protein analysis systems in vitro. DNA sequence analysis of the locus revealed a single 23,500 Mr open reading frame, confirming the protein data. A 248 base-pair region immediately upstream from the 23,500 Mr open reading frame, containing an array of 12 seven-base-pair palindromic repeats each of which are separated by exactly ten base-pairs of A + T-rich (75%) sequence, not only serves to provide the promoter but is also involved in parA autoregulation. In addition, this region containing a set of 12 seven-base-pair palindromic repeats, is responsible for plasmid-associated incompatibility within Inc Ag-1 and also functions as the cis-acting recognition site at which parA interacts to bring about partitioning. Transcriptional analysis indicated that only the DNA strand responsible for parA is actively transcribed, and that active transcription of the opposite strand of par can inhibit the production of parA, resulting in plasmid destabilization. The presence of the par locus in a plasmid results in stable inheritance within a wide range of members of Rhizobiaceae. Segregation rates of par-defective derivatives can be influenced by the host.

  7. Comparative analysis of a plant pseudoautosomal region (PAR) in Silene latifolia with the corresponding S. vulgaris autosome

    PubMed Central

    2012-01-01

    Background The sex chromosomes of Silene latifolia are heteromorphic as in mammals, with females being homogametic (XX) and males heterogametic (XY). While recombination occurs along the entire X chromosome in females, recombination between the X and Y chromosomes in males is restricted to the pseudoautosomal region (PAR). In the few mammals so far studied, PARs are often characterized by elevated recombination and mutation rates and high GC content compared with the rest of the genome. However, PARs have not been studied in plants until now. In this paper we report the construction of a BAC library for S. latifolia and the first analysis of a > 100 kb fragment of a S. latifolia PAR that we compare to the homologous autosomal region in the closely related gynodioecious species S. vulgaris. Results Six new sex-linked genes were identified in the S. latifolia PAR, together with numerous transposable elements. The same genes were found on the S. vulgaris autosomal segment, with no enlargement of the predicted coding sequences in S. latifolia. Intergenic regions were on average 1.6 times longer in S. latifolia than in S. vulgaris, mainly as a consequence of the insertion of transposable elements. The GC content did not differ significantly between the PAR region in S. latifolia and the corresponding autosomal region in S. vulgaris. Conclusions Our results demonstrate the usefulness of the BAC library developed here for the analysis of plant sex chromosomes and indicate that the PAR in the evolutionarily young S. latifolia sex chromosomes has diverged from the corresponding autosomal region in the gynodioecious S. vulgaris mainly with respect to the insertion of transposable elements. Gene order between the PAR and autosomal region investigated is conserved, and the PAR does not have the high GC content observed in evolutionarily much older mammalian sex chromosomes. PMID:22681719

  8. Comparison of the effects of pretreatment with Veramix sponge (medroxyprogesterone acetate) or CIDR (natural progesterone) in combination with an injection of estradiol-17β on ovarian activity, endocrine profiles, and embryo yields in cyclic ewes superovulated in the multiple-dose Folltropin-V (porcine FSH) regimen.

    PubMed

    Bartlewski, Pawel M; Seaton, Patricia; Szpila, Patrycja; Oliveira, Maria E F; Murawski, Maciej; Schwarz, Tomasz; Kridli, Rami T; Zieba, Dorota A

    2015-10-15

    Follicular wave status at the beginning of exogenous FSH administration is an important contributor to variability in superovulatory responses in ruminants. Studies in ewes have shown a decrease in the number of ovulations when superovulation is initiated in the presence of ostensibly ovulatory-sized ovarian follicles. Hormonal ablation of large antral follicles with the progestin-estradiol (E2-17β) treatment significantly reduces this variability in superovulated anestrous ewes, but the effects of the treatment in cycling ewes have not yet been assessed. Sixteen Rideau Arcott × Polled Dorset ewes (November-December) received either medroxyprogesterone acetate (MAP)-releasing intravaginal sponges (60 mg) or controlled internal drug release (CIDR) devices (containing 300 mg of natural progesterone) for 14 days (Days 0-14), with a single intramuscular injection of 350 μg of E2-17β on Day 6. The superovulatory treatment consisted of six injections of porcine FSH (Folltropin-V) given twice daily, followed by a bolus GnRH injection (50 μg intramuscular) on Day 15. There were no differences (P < 0.05) in the ovulatory responses and embryo yields between the two groups of ewes. In both subsets of animals, the next follicular wave emerged ∼2.5 days after an E2-17β injection (P > 0.05). A decline in maximum follicle size after an E2-17β injection was more abrupt in CIDR- compared with MAP-treated animals, and the ewes pretreated with exogenous progesterone had significantly more 3-mm follicles at the start of the superovulatory treatment. The metabolic clearance rate of exogenous E2-17β appeared to be greater in MAP-treated ewes, but circulating concentrations of porcine FSH failed to increase significantly after each Folltropin-V injection in CIDR-treated animals. The CIDR-treated ewes exceeded (P < 0.05) their MAP-treated counterparts in serum E2-17β concentrations during superovulation. In spite of differences in antral follicle numbers and endocrine profiles

  9. Estimation of Downstream Cesium Concentrations Following a Postulated PAR Pond Dam Break

    SciTech Connect

    Chen, K.F.

    2002-07-08

    Following a postulated PAR Pond dam break, some of the PAR Pond sediment including the cesium could be eroded and be transported downstream to the Savannah River through the Lower Three Runs Creek. Studies showed that most of the eroded sediment including the cesium would deposit in the Lower Three Runs Creek and the remainder would discharge to the Savannah River from the mouth of Lower Three Runs Creek. A WASP5 model was developed to simulate the eroded sediment and cesium transport from the Lower Three Runs Creek mouth to the Atlantic coast. The dissolved cesium concentrations at the Highway 301 bridge and near the City of Savannah Industrial and Domestic Water Supply Plant are 30 and 27 pCi/l, respectively. The concentrations at both locations are less than the U. S. Environmental Protection Agency drinking water standard of 200 pCi/l.

  10. Corneal modeling using conic section fits of PAR corneal topography system measurements

    NASA Astrophysics Data System (ADS)

    Zipper, Stanley; Manns, Fabrice; Fernandez, Viviana; Sandadi, Samith; Ho, Arthur; Parel, Jean-Marie A.

    2001-06-01

    The purpose of this study was to measure the average shape and variability of human corneas and to develop a tool for analyzing, height, curvature, and aberrations based on a conic section model. Fresh Eye Bank Eyes were placed in Dextran until the corneal thickness reached a physiological value. The eyes were placed in a custom made holder and measured using an intraoperative PAR Corneal Topography System (CTS) mounted on an operation microscope. Topography was measured before and after removal of the epithelium. A series of MATLAB functions were written to analyze the raw-z (height) data in polar coordinates. The functions fit conic sections to the PAR CTS data along hemi-meridians at 5 degree(s) intervals. The conic shape factor and apical radius were used to calculate and display the curvature. The dependence of these parameters with meridional position was examined.

  11. Manipulation quantique de la lumière par un amplificateur non linéaire

    NASA Astrophysics Data System (ADS)

    Symul, T.; Bencheikh, K.; Levenson, J. A.

    2002-06-01

    Nous proposons un dispositif original, appelé Amplificateur Non Linéaire (ANL), permettant la génération et la manipulation d'états quantiques de la lumière. Ce dispositif permet une compression du bruit quantique de la lumière en dessous de la limite quantique standard plus efficace que celle obtenue par interactions non linéaires du second ordre ou du troisième ordre. Il permet également d'inverser les fluctuations quantiques en intensité de la lumière, et de produire des photons jumeaux ayant des corrélations quantiques plus élevées et plus robustes que ceux produits par un amplificateur paramétrique seul.

  12. Laser Nd:YVO{4} impulsionnel à 914 nm pompé par diode

    NASA Astrophysics Data System (ADS)

    Blandin, P.; Druon, F.; Balembois, F.; Georges, P.; Lévêque-Fort, S.; Fontaine-Aupart, M. P.

    2006-10-01

    Nous présentons ici le premier laser impulsionnel à verrouillage de modes en phase passif directement pompé par diode, utilisant la transition 4F{3 / 2}-4I{9/2} de l'ion néodyme à 914 nm. Le système de pompage utilisé permet d'obtenir un dispositif simple. Le train d'impulsions est obtenu grâce à un miroir à absorbant saturable, l'émission laser à 914 nm étant privilégiée par l'introduction dans la cavité de fortes pertes à 1064 nm. Nous obtenons avec notre dispositif des impulsions à 913.8 nm, de durée 8.8 ps à une cadence de 94 MHz et à une puissance de 86 mW.

  13. Youth empowerment in context: exploring tensions in school-based yPAR.

    PubMed

    Kohfeldt, Danielle; Chhun, Lina; Grace, Sarah; Langhout, Regina Day

    2011-03-01

    In much of the youth empowerment literature, researchers focus on the relationship between youth and adults involved in empowerment programs while neglecting the broader social framework in which these relationships and the program itself functions. Utilizing an ecological model, the current research examines the tensions that surfaced in attempts to create an empowering setting in an after-school PAR program with fifth-graders. Challenging assumptions about youth, structural challenges, and conflicting theories of change are highlighted. Results examine the role of sociocultural context as PAR researchers attempt to create a setting in which students gain skills to become change agents within their school. The study suggests that youth empowerment is a context dependent process that requires attention to a multiplicity of factors that influence possibilities for empowerment via second order change.

  14. BOREAS TE-9 PAR and Leaf Nitrogen Data for NSA Species

    NASA Technical Reports Server (NTRS)

    Hall, Forrest G. (Editor); Curd, Shelaine (Editor); Dang, Qinglai; Margolis, Hank; Coyea, Marie

    2000-01-01

    The Boreal Ecosystem-Atmospheric Study (BOREAS) TE-9 (Terrestrial Ecology) team collected several data sets related to chemical and photosynthetic properties of leaves in boreal forest tree species. This data set describes the relationship between photosynthetically active radiation (PAR) levels and foliage nitrogen in samples from six sites in the BOREAS Northern Study Area (NSA) collected during the three 1994 intensive field campaigns (IFCs). This information is useful for modeling the vertical distribution of carbon fixation for these different forest types in the boreal forest. The data were collected to quantify the relationship between PAR and leaf nitrogen of black spruce, jack pine, and aspen. The data are available in tabular ASCII files. The data files are available on a CD-ROM (see document number 20010000884), or from the Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC).

  15. Perianesthetic development of diaphragmatic hernia in a horse with equine pituitary pars intermedia dysfunction (PPID)

    PubMed Central

    Shepard, Molly K.; Lee, Wesley L.; Eggleston, Randy B.

    2015-01-01

    A 21-year-old Thoroughbred gelding with a history of equine pituitary pars intermedia dysfunction (PPID) presented with priapism of 2 days’ duration. The horse received a caudal morphine epidural and then underwent corpus cavernosum lavage and phallectomy under general anesthesia. The patient’s recovery featured multiple unsuccessful attempts to stand and his respiratory distress persisted for several hours until he acutely developed severe colic and was euthanized. Necropsy findings revealed a pituitary adenoma of the pars intermedia, bilateral adrenal cortical hyperplasia, and diaphragmatic herniation. This report suggests that horses with PPID may present a greater risk for diaphragmatic hernia under general anesthesia or during procedures placing stress on the diaphragm, including anesthetic recovery. PMID:25565714

  16. Disrupting the right pars opercularis with electrical stimulation frees the song: case report.

    PubMed

    Herbet, Guillaume; Lafargue, Gilles; Almairac, Fabien; Moritz-Gasser, Sylvie; Bonnetblanc, François; Duffau, Hugues

    2015-12-01

    The authors report the first case of a strikingly unusual speech impairment evoked by intraoperative electrostimulation in a 36-year-old right-handed patient, a well-trained singer, who underwent awake surgery for a right fronto-temporo-insular low-grade glioma. Functionally disrupting the pars opercularis of the right inferior frontal gyrus led the patient to automatically switch from a speaking to a singing mode of language production. Given the central role of the right pars opercularis in the inhibitory control network, the authors propose that this finding may be interpreted as possible evidence for a competitive and independent neurocognitive subnetwork devoted to the melodically intoned articulation of words (normal language-based vs singing-based) in subjects with high expertise. From a more clinical perspective, such data may have implications for awake neurosurgery, especially to preserve the quality of life for singers.

  17. Hydraulic and hydrologic evaluation of PAR Pond Dam. Technical evaluation report

    SciTech Connect

    Reich, M.; Wang, P.C.; Khanbilvardi, R.; Bezler, P.

    1993-10-01

    The PAR Pond Dam at Savannah River Plant was constructed in 1958--1959. Seepage, depressions, boils and spring flow were observed in varying locations on the dam in the last few years. Comprehensive geotechnical and hydraulic investigations pertaining to the effects of the above observations on the abilities of the dam to withstand future floods were made in 1991 and early 1993 where dam capacity to survive flooding and seismic events were evaluated. Brookhaven National Laboratory (BNL) was asked by the Department of Energy (EH) to carry out an independent review of the PAR Pond Dam response to future flooding and seismic events. This report addresses the studies made to evaluate the capacity of the dam to survive floods. A companion report will summarize the evaluations performed to assess the seismic capacity of the dam.

  18. Case series of equine pituitary pars intermedia dysfunction in a tropical climate.

    PubMed

    Spelta, C W; Axon, J E

    2012-11-01

    The clinical manifestations of equine pituitary pars intermedia dysfunction (PPID) in temperate climates are well described. The classic presentation is that of an older animal with hirsutism, laminitis, poor muscle tone, pendulous abdomen and weight loss. This case series highlights the additional clinical signs of anhidrosis and heat stress with secondary exercise intolerance that were seen as primary presenting problems in equids with PPID in the hot, humid conditions of a tropical climate. The clinical signs resolved with medical treatment for PPID.

  19. Magnétométrie à hélium par pompage laser: le bilan

    NASA Astrophysics Data System (ADS)

    Gilles, H.; Hamel, J.; Monfort, Y.

    2002-06-01

    Depuis 1986, l'équipe Physique Atomique et Capteurs du CIRIL-ISMRA de Caen étudie les magnétomètres à hélium par pompage laser. On présente ici le bilan de ces travaux de recherche et les performances des deux prototypes (hélium4 et hélium3) réalisés au Laboratoire.

  20. Endophthalmitis following pars plana vitrectomy: a literature review of incidence, causative organisms, and treatment outcomes

    PubMed Central

    Dave, Vivek Pravin; Pathengay, Avinash; Schwartz, Stephen G; Flynn, Harry W

    2014-01-01

    Endophthalmitis following pars plana vitrectomy is a very uncommon cause of endophthalmitis. Cases reported over the last decade show a decrease in incidence over time. To optimize visual outcome, early diagnosis and treatment are essential. In this review we report a summary of the incidence of endophthalmitis following vitrectomy, various risk factors for their occurrence, the microbiological profile and the visual outcomes post treatment. PMID:25382968

  1. K-Area and Par Pond Sewage Sludge Application Sites groundwater monitoring report, Third quarter 1992

    SciTech Connect

    Thompson, C.Y.

    1993-01-01

    During third quarter 1992, the three wells at the K-Area Sewage Sludge Application Site (KSS wells) and the three wells at the Par Pond Sewage Sludge Application Site (PSS wells) were sampled for analyses required each quarter or annually by South Carolina Department of Health and Environmental Control Construction Permit 13,173 and for base-neutral/acid semivolatile constituents. None of the analytical results exceeded standards.

  2. L'analyse par activation de neutrons de réacteur

    NASA Astrophysics Data System (ADS)

    Meyer, G.

    2003-02-01

    Quand les neutrons traversent la matière, certains sont transmis sans interaction, les autres interagissent avec le milieu traversé par diffusion et par absorption. Ce phénomène d'absorption est utilisé pour se protéger des neutrons, mais aussi pour les détecter; il peut également être utilisé pour identifier les noyaux “absorbants" et ainsi analyser le milieu traversé. En effet par différentes réactions nucléaires (n,γ), (n,p), (n,α), (n,fission), on obtient des noyaux résiduels qui sont souvent radioactifs; on dit que l'échantillon est “activé". Si l'on connaît le rendement d'activation et donc le pourcentage de noyaux ainsi “transmutés", les mesures de radioactivité induite vont permettre de déterminer la composition de l'échantillon irradié. Cette méthode dite d'analyse par activation neutronique est pratiquée depuis la découverte du neutron. Elle a permis grâce à sa sélectivité et à sa sensibilité d'avoir accès au domaine des traces et des ultra-traces dans des champs d'application très divers comme la métallurgie, l'archéologie, la biologie, la géochimie etc...

  3. CALiPER Application Summary Report 20. LED PAR38 Lamps

    SciTech Connect

    none,

    2012-11-01

    This report analyzes the independently tested photometric performance of 38 LED PAR38 lamps. The test results indicate substantial improvement versus earlier CALiPER testing of similar products, and performance comparable to recent data from LED Lighting Facts and ENERGY STAR. Additional testing that focuses on performance attributes beyond those covered by LM-79-08 is planned for this group of lamps, and will be presented in subsequent reports.

  4. La fracture de Hahn Steinthal traitée par vissage d'Herbert: 3 cas

    PubMed Central

    Bienvenu, Bouhelo-Pam Kevin Parfait; Amine, El Rhazi; Khalid, Chmali; Mohamed, Azarkane; Mohamed, El Idrissi; Mohamed, Shimi; Abdelhalim, El Ibrahimi; Abdelmajid, El Mrini

    2015-01-01

    Les fractures du capitulum sont rares. Leur prise en charge initiale doit être précoce et efficace en raison des risques engendrés sur le coude: rigidité, instabilité, arthrose. De nombreux traitements ont été proposés. Notre étude décrit le vissage par vis d'Herbert pratiqué chez trois patientes recensées entre 2012 et 2013. Elles ont été inclues selon les critères de traumatisme du coude avec douleur exquise externe avec un trait de fracture radiologique frontal du condyle huméral externe emportant la joue externe de la trochlée. Le diagnostic a été orienté par l'examen clinique et confirmé à la radiographie de face, de profil et des ¾ internes. Les lésions ont été classées selon Bryan et Morrey. Les patients ont été opérés en urgence par abord postéro-latéral de Kocher, réduction à ciel ouvert puis stabilisation par vis de Herbert enfouies. Le recul moyen a été de un an. La récupération fonctionnelle totale moyenne a été de 3,6 mois. L’évaluation fonctionnelle a été jugée excellente selon le score MEPI (Mayo Elbow Performance Index) pour les trois patients. Il n'y a pas eu de démontage de matériel. La consolidation osseuse moyenne a été de 2,6 mois. PMID:26015850

  5. Inflammation in Prostate Carcinogenesis: Role of the Tumor Suppressor Par-4

    DTIC Science & Technology

    2012-09-01

    which they coordinate with each other to form an intricate regula- tory network to protect against tumorigenesis. The Tumor Suppressor Par-4 at the...that integrates signals to coordinate molecular events that protect cells against tumorigenesis. Understanding the cross talks among each compo- nent...with the atypical isoforms of protein kinase C. Cell. 1996;86(5):777-86. 8. Sells SF, Wood DP, Jr., Joshi-Barve SS, Muthukumar S, Jacob RJ, Crist SA

  6. Seismic analysis of the Par Pond Dam: Study of slope failure and liquefaction. Technical evaluation report

    SciTech Connect

    Simos, N.; Reich, M.

    1994-07-01

    Stability concerns of the Par Pond Dam, an embankment structure in the Savannah River Site complex, resulted in a comprehensive evaluation of the state of its integrity. Specifically, excessive seepage through the embankment, slope failure due to an earthquake event as well as liquefaction potential of the embankment and the foundation are addressed and the potential of failure is evaluated. Lastly, remedial benefits of the addition of a berm structure are also assessed.

  7. Pars planitis is associated with an increased frequency of effector‐memory CD57+ T cells

    PubMed Central

    Pedroza‐Seres, Miguel; Linares, Marisela; Voorduin, Stephanie; Enrique, Rojas‐Ramos; Lascurain, Ricardo; Garfias, Yonathan; Jimenez‐Martinez, Maria Carmen

    2007-01-01

    Aim To evaluate the frequency, phenotype and the potential function of CD57+ T cell subsets in patients with pars planitis. Methods CD4+CD57+ and CD8+CD57+ T cells were quantitated in peripheral blood from 15 patients with pars planitis and 15 healthy controls. To evaluate the phenotype and potential function of CD57+ T cell subsets CCR7, CD27, CD28, CD45RA, CD45RO, intracellular IFN‐γ, IL‐4, perforin and granzyme‐A expression were assessed by flow cytometry. Results CD57+ T cells subsets were increased in patients with pars planitis (p = 0.002). The majority of CD4+CD57+ T cells were CCR7−CD27−CD28−CD45RO+, while the most CD8+CD57+ T cells were CCR7−CD27−CD28−CD45RA+. The number of cells positive for intracellular IFN‐γ and IL‐4 was higher in the CD57+ T cell populations. A greater number of CD8+CD57+ T cells than CD8+CD57− T cells were positive to perforin (p = 0.006) and granzyme‐A (p = 0.01). Conclusions CD57+ T cells had a phenotype associated with peripheral memory (CCR7−CD27−CD28−). Cytokine production by CD57+ T cells suggests that these cells may play a role in helper cell regulation. High expression of intracellular proteins involved in cytotoxicity suggests that CD8+CD57+ T cells may play an effector role. Taken together, this study proposes that CD57+ T cells function as memory‐effector T cell subsets during pars planitis pathogenesis. PMID:17475702

  8. Visual Outcomes and Prognostic Factors after Pars Plana Vitrectomy for Traumatic Endophthalmitis.

    PubMed

    Jiang, Tao; Jiang, Jing; Wang, Renping; Lei, Jianlin; Zhou, Yang

    2017-01-01

    Purpose. To evaluate visual outcomes and identify prognostic factors after pars plana vitrectomy (PPV) surgery for traumatic endophthalmitis. Methods. Medical records of 121 consecutive patients (121 eyes) diagnosed with traumatic endophthalmitis that had undergone pars plana vitrectomy were retrospectively reviewed. Results. 121 patients, aged from 6 to 71 years, all underwent PPV surgery. 113 cases had improved best corrected visual acuity (BCVA) after surgery and 60% of them obtained BCVA better than fingers counting (FC). Good final visual prognosis was significantly associated with time between trauma and initial treatment less than 12 hrs (40% versus 98%; P < 0.001), time between trauma and PPV treatment less than 24 hrs (62% versus 98%; P < 0.001), laceration length less than 10 mm (63% versus 96%; P < 0.001), and presenting VA better than LP (42% versus 96%; P < 0.001), while gender, type of laceration, presence of IOFB or retinal detachment, and the use of silicone oil tamponade were not significant factors resulting in better BCVA. Bacteria were identified in 43.8% of specimens and most of the microorganisms were identified as nonvirulent ones. Conclusions. Pars plana vitrectomy surgery was preferred as a primary treatment option for traumatic endophthalmitis. A good final visual prognosis was significantly associated with timely treatment, prompt vitrectomy surgery, shorter length of laceration, and better presenting visual acuity.

  9. Pituitary pars intermedia dysfunction (Equine Cushing's disease) in an onager (Equus hemionus onager).

    PubMed

    Peel, Alison J; Bouts, Tim; Flach, Edmund; Rivers, Sonja; Routh, Andrew

    2009-12-01

    Pituitary pars intermedia dysfunction (PPID), also known as Equine Cushing's disease, is most often diagnosed in older horses and ponies. To the authors' knowledge, there have been no reports of its diagnosis in captive nondomestic equids. A 13-yr old onager (Equus hemionus onager) at the Zoological Society of London (ZSL) Whipsnade Zoo showed clinical signs suggestive of PPID, including hirsutism, fat redistribution, weight loss, laminitis, and chronic infections. A dexamethasone suppression test was performed to confirm PPID. Subsequently, adenomatous hyperplasia and microadenoma of the pars intermedia were identified postmortem. Four months later, this onager's dam died suddenly, and adenomatous hyperplasia of the pars intermedia was diagnosed following necropsy. The dam had shown no clinical signs of PPID. Examination of archives identified eight other adult onagers that died or were euthanized between 1993 and 2007. The brain was not examined in four of these, but pituitary glands were described as enlarged during necropsy in three animals based on the subjective assessment of an experienced zoo and wildlife pathologist, making an overall prevalence of enlargement of 83.3%. Hyperplastic pituitary changes are positively correlated with age in domestic equids, and this may also be the case in onagers. Alternative etiologies are also discussed.

  10. K-Area and Par Pond Sewage Sludge Application Sites Groundwater Monitoring Report

    SciTech Connect

    Thompson, C.Y.

    1993-04-01

    During fourth quarter 1992, samples from the three monitoring wells at the K-Area site (KSS series) and the three monitoring wells at the Par Pond site (PSS series) were analyzed for constituents required by South Carolina Department of Health and Environmental Control Construction Permit 13, 173 and for other constituents as part of the Savannah River Site (SRS) Groundwater Monitoring Program. This report describes monitoring results that exceeded the final Primary Drinking Water Standards (PDWS) or the SRS flagging criteria. During fourth quarter 1992, no constituents analyzed exceeded the PDWS or the SRS Flag 2 criteria at the K-Area and Par Pond Sewage Sludge Application Sites. In the KSS well series, the field measurement for alkalinity ranged as high as 26 mg/L in well KSS 1D. Alkalinity measurements were zero in the PSS wells. Historical and current water-level elevations at the K-Area and Par Pond Sewage Sludge Application Site indicate that the groundwater flow directions are south to southwest (SRS grid coordinates).

  11. Impacts of active urea secretion into pars recta on urine concentration and urea excretion rate

    PubMed Central

    Layton, Anita T; Bankir, Lise

    2013-01-01

    It has been observed experimentally that early distal tubular urea flow exceeds urea delivery by the proximal convoluted tubule to the pars recta and loop of Henle. Moreover, the fractional excretion of urea in the urine may exceed values compatible with the reabsorption known to occur in the proximal convoluted tubule in the cortex. A likely explanation for these observations is that urea may be actively secreted into the pars recta, as proposed in a few studies. However, this hypothesis has yet to be demonstrated experimentally. In this study, we used a mathematical model of the renal medulla of the rat kidney to investigate the impacts of active urea secretion in the intrarenal handling of urea and in the urine concentrating ability. The model represents only the outer and inner medullary zones, with the actions taking place in the cortex incorporated via boundary conditions. Blood flow in the model vasculature is divided into plasma and red blood cell compartments. We compared urea flow rates and other related model variables without and with the hypothetical active urea secretion in the pars recta. The simulation suggests that active urea secretion induces a “urea-selective” improvement in urine concentrating ability by enhancing the efficiency of urea excretion without requiring a higher urine flow rate, and with only modest changes in the excretion of other solutes. These results should encourage experimental studies in order to assess the existence of an active urea secretion in the rodent kidney. PMID:24058732

  12. Visual Outcomes and Prognostic Factors after Pars Plana Vitrectomy for Traumatic Endophthalmitis

    PubMed Central

    2017-01-01

    Purpose. To evaluate visual outcomes and identify prognostic factors after pars plana vitrectomy (PPV) surgery for traumatic endophthalmitis. Methods. Medical records of 121 consecutive patients (121 eyes) diagnosed with traumatic endophthalmitis that had undergone pars plana vitrectomy were retrospectively reviewed. Results. 121 patients, aged from 6 to 71 years, all underwent PPV surgery. 113 cases had improved best corrected visual acuity (BCVA) after surgery and 60% of them obtained BCVA better than fingers counting (FC). Good final visual prognosis was significantly associated with time between trauma and initial treatment less than 12 hrs (40% versus 98%; P < 0.001), time between trauma and PPV treatment less than 24 hrs (62% versus 98%; P < 0.001), laceration length less than 10 mm (63% versus 96%; P < 0.001), and presenting VA better than LP (42% versus 96%; P < 0.001), while gender, type of laceration, presence of IOFB or retinal detachment, and the use of silicone oil tamponade were not significant factors resulting in better BCVA. Bacteria were identified in 43.8% of specimens and most of the microorganisms were identified as nonvirulent ones. Conclusions. Pars plana vitrectomy surgery was preferred as a primary treatment option for traumatic endophthalmitis. A good final visual prognosis was significantly associated with timely treatment, prompt vitrectomy surgery, shorter length of laceration, and better presenting visual acuity. PMID:28246599

  13. Modifications vibrationnelles induites par différentes vapeurs acides sur les polyanilines

    NASA Astrophysics Data System (ADS)

    Cochet, M.; Quillard, S.; Buisson, J. P.; Lefrant, S.; Louarn, G.

    1998-06-01

    We present a comparative study of conductive form of polyaniline, i.e, polyemeraldine doped with HCl vapor or with HCSA upon m-cresol vapor. UV-Vis.-nir absorption measurements on polyaniline thin films, vs acid vapors time exposure, have been made. In the same way, Raman spectra have been recorded with different excitation lines from the blue and red ranges to the infrared region. Finally, an assignment of Raman bands observed, is proposed and confirmed by vibrational calculations based on valence-force-field. Nous présentons une étude comparative de la forme conductrice de la polyaniline, c'est-à-dire de la polyéméraldine dopée par des vapeurs d'HCl ou dopée par l'acide camphre sulfonique (HCSA) sous vapeurs de m-crésol. Des mesures d'absorption UV-Vis-proche infrarouge sur des films minces de polyaniline, en fonction du temps d'exposition aux vapeurs acides, ont été réalisées. Parallèlement, les spectres Raman ont été obtenus pour différentes longueurs d'onde d'excitation allant du visible jusqu'au proche infrarouge. Finalement, une attribution des bandes Raman observées est proposée et confirmée par des calculs vibrationnels basés sur des champs de force de valence.

  14. Phosphorylation of LKB1/Par-4 Establishes Schwann Cell Polarity to Initiate and Control Myelin Extent

    PubMed Central

    Shen, Yun-An A.; Chen, Yan; Dao, Dang Q.; Mayoral, Sonia R.; Wu, Laiman; Meijer, Dies; Ullian, Erik M.; Chan, Jonah R.; Lu, Q. Richard

    2014-01-01

    The Schwann cell (SC)-axon interface represents a membrane specialization that integrates axonal signals to coordinate cytoskeletal dynamics resulting in myelination. Here we show that LKB1/Par-4 is asymmetrically localized to the SC-axon interface and colocalizes with the polarity protein Par-3. Using purified SCs and myelinating cocultures, we demonstrate that localization is dependent on the phosphorylation of LKB1 at serine-431. SC-specific deletion of LKB1 significantly attenuates developmental myelination, delaying the initiation and altering the myelin extent into adulthood, resulting in a 30% reduction in the conduction velocity along adult sciatic nerves. Phosphorylation of LKB1 by protein kinase A is essential to establish the asymmetric localization of LKB1 and Par-3 and rescues the delay in myelination observed in the SC-specific knockout of LKB1. Our findings suggest that SC polarity may coordinate multiple signaling complexes that couple SC-axon contact to the redistribution of specific membrane components necessary to initiate and control myelin extent. PMID:25255972

  15. Pars plana vitrectomy for malignant glaucoma in nonglaucomatous and in filtered glaucomatous eyes

    PubMed Central

    Matlach, Juliane; Slobodda, Joerg; Grehn, Franz; Klink, Thomas

    2012-01-01

    Purpose To assess the outcomes of pars plana vitrectomy for the treatment of malignant glaucoma in patients with and without previous filtration surgery. Patients and methods Data of 15 patients developing malignant glaucoma after trabeculectomy (60%) or following ophthalmic interventions other than filtration surgery (40%) were recorded retrospectively. Pars plana vitrectomy was performed in case of failed medical or laser treatment recreating the normal pathway of aqueous humor. The main outcome measures were the postoperative intraocular pressure (IOP), the frequency of complications, and success rate based on the following criteria: IOP reduction by ≥20% and to ≤21 mmHg (definition one) or an IOP < 18 mmHg (definition two) with (qualified success) and without (complete success) glaucoma medication. Results Vitrectomy reduced IOP from baseline in eyes with and without previous trabeculectomy during a median follow-up of 16.4 months (range 7 days to 58 months); although the majority of patients required glaucoma medication to reach desired IOP. The complete success rates were 11% (both definitions) for patients with filtering blebs and none of the patients without previous trabeculectomy had complete success at the 12-month visit. Complications were few and included transient shallowing of the anterior chamber, choroidal detachment, corneal decompensation, filtering bleb failure, and need for further IOP-lowering procedures. Conclusion Pars plana vitrectomy is equally effective for malignant glaucoma caused by trabeculectomy or interventions other than filtration surgery, although IOP-lowering medication is necessary in nearly all cases to maintain target IOP. PMID:23226000

  16. On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1

    PubMed Central

    Luo, Xin; Kraus, W. Lee

    2012-01-01

    Cellular stress responses are mediated through a series of regulatory processes that occur at the genomic, transcriptional, post-transcriptional, translational, and post-translational levels. These responses require a complex network of sensors and effectors from multiple signaling pathways, including the abundant and ubiquitous nuclear enzyme poly(ADP-ribose) (PAR) polymerase-1 (PARP-1). PARP-1 functions at the center of cellular stress responses, where it processes diverse signals and, in response, directs cells to specific fates (e.g., DNA repair vs. cell death) based on the type and strength of the stress stimulus. Many of PARP-1's functions in stress response pathways are mediated by its regulated synthesis of PAR, a negatively charged polymer, using NAD+ as a donor of ADP-ribose units. Thus, PARP-1's functions are intimately tied to nuclear NAD+ metabolism and the broader metabolic profile of the cell. Recent studies in cell and animal models have highlighted the roles of PARP-1 and PAR in the response to a wide variety of extrinsic and intrinsic stress signals, including those initiated by oxidative, nitrosative, genotoxic, oncogenic, thermal, inflammatory, and metabolic stresses. These responses underlie pathological conditions, including cancer, inflammation-related diseases, and metabolic dysregulation. The development of PARP inhibitors is being pursued as a therapeutic approach to these conditions. In this review, we highlight the newest findings about PARP-1's role in stress responses in the context of the historical data. PMID:22391446

  17. Higher incidence of Gastrospirillum sp. in swine with gastric ulcer of the pars oesophagea.

    PubMed

    Barbosa, A J; Silva, J C; Nogueira, A M; Paulino Júnior, E; Miranda, C R

    1995-03-01

    Gastric ulcer in swine is characterized by an area of acid-peptic digestion, occurs usually in the pars oesophagea of the stomach, and has unknown etiopathogenesis. The present work was carried out to investigate the prevalence of the newly described spiral-shaped microorganism Gastrospirillum sp. ("Gastrospirillum suis") in stomachs of abattoir pigs with and without gastric ulcer. Stomachs were removed from 32 consecutive pigs presenting apparently normal mucosa and from 32 additional consecutive pigs presenting frank, chronic gastric ulcer of the pars oesophagea. Fragments of antral, oxyntic, cardiac and pars oesophagea regions were taken from each stomach and processed for histology and for identification of Gastrospirillum sp. in tissue sections. The microorganisms were identified mainly in the mucous layer and in gastric foveolas of the antral and oxyntic mucosa. Forty pigs (62.5%) were positive for Gastrospirillum sp.; among them, 27 (67.5%) had gastric ulcer, and 13 (32.5%) had no ulcer. Twenty-four pigs (37.5%) were negative for Gastrospirillum sp.; among them, five (20.8%) presented with gastric ulcer, and 19 (79.2%) had no ulcer. There was a significant difference between pigs with and without gastric ulcer in regard to the presence of Gastrospirillum sp. (P < 0.01). The spiral-shaped microorganism Gastrospirillum sp. that inhabits the stomach of pigs should be considered a possible factor connected with the etiopathogenesis of swine gastric ulcer.

  18. Polycystin-1 binds Par3/aPKC and controls convergent extension during renal tubular morphogenesis

    NASA Astrophysics Data System (ADS)

    Castelli, Maddalena; Boca, Manila; Chiaravalli, Marco; Ramalingam, Harini; Rowe, Isaline; Distefano, Gianfranco; Carroll, Thomas; Boletta, Alessandra

    2013-10-01

    Several organs, including the lungs and kidneys, are formed by epithelial tubes whose proper morphogenesis ensures correct function. This is best exemplified by the kidney, where defective establishment or maintenance of tubular diameter results in polycystic kidney disease, a common genetic disorder. Most polycystic kidney disease cases result from loss-of-function mutations in the PKD1 gene, encoding Polycystin-1, a large receptor of unknown function. Here we demonstrate that PC-1 has an essential role in the establishment of correct tubular diameter during nephron development. Polycystin-1 associates with Par3 favouring the assembly of a pro-polarizing Par3/aPKC complex and it regulates a programme of cell polarity important for oriented cell migration and for a convergent extension-like process during tubular morphogenesis. Par3 inactivation in the developing kidney results in defective convergent extension and tubular morphogenesis, and in renal cyst formation. Our data define Polycystin-1 as central to cell polarization and to epithelial tube morphogenesis and homeostasis.

  19. Recuit thermique rapide de semi-conducteur par énergie micro-onde

    NASA Astrophysics Data System (ADS)

    Covas, M.; Gay, H. C.

    1993-05-01

    This paper proposes a new technique for rapid thermal annealing of semi-conductors. This technique is based on microwave energy, and offers the same advantages as the rapid thermal annealing by incoherent light, in terms of rapidity, and contamination. However, our technique reduces considerably the required energy for the annealing process. This technique has been compared to the rapid thermal by incoherent light: lab experiments, carried out on boron implanted silicon samples, showed that a power gain ratio of about 10 can be achieved. Nous proposons une méthode de recuit thermique rapide du silicium par énergie micro-onde. Cette technique offre les mêmes avantages que les traitements thermiques rapides par lumière incohérente, c'est-à-dire des durées de chauffage très brèves, limitant ainsi la diffusion des dopants, et un traitement plaquette par plaquette : les risques de contamination de tout un lot sont ainsi éliminés. De plus notre méthode requiert une faible énergie : pour parvenir à des recuits de qualité similaire à celle obtenue dans des fours de recuit rapide à lampes il faut un flux de puissance 10 fois plus faible.

  20. MPDZ EXPRESSION IN THE CAUDOLATERAL SUBSTANTIA NIGRA PARS RETICULATA IS CRUCIALLY INVOLVED IN ALCOHOL WITHDRAWAL

    PubMed Central

    Kruse, L.C.; Walter, N.A.R.; Buck, K.J.

    2014-01-01

    Association studies implicate the multiple PDZ domain protein (MUPP1/MPDZ) gene in risk for alcoholism in humans and alcohol withdrawal in mice. Although manipulation of the Mpdz gene by homologous recombination and bacterial artificial chromosome transgenesis has suggested that its expression affects alcohol withdrawal risk, the potential confounding effects of linked genes and developmental compensation currently limit interpretation. Here, using RNA interference, we directly test the impact of Mpdz expression on alcohol withdrawal severity and provide brain regional mechanistic information. Lentiviral-mediated delivery of Mpdz short hairpin RNA (shRNA) to the caudolateral substantia nigra pars reticulata significantly reduces Mpdz expression and exacerbates alcohol withdrawal convulsions compared to control mice delivered a scrambled shRNA. Neither baseline nor pentylenetetrazol enhanced convulsions differed between Mpdz shRNA and control animals, indicating that Mpdz expression in the caudolateral substantia nigra pars reticulata does not generally affect seizure susceptibility. To our knowledge, these represent the first in vivo Mpdz RNA interference analyses, and provide the first direct evidence that Mpdz expression impacts behavior. Our results confirm that Mpdz is a quantitative trait gene for alcohol withdrawal and demonstrate that its expression in the caudolateral substantia nigra pars reticulata is crucially involved in risk for alcohol withdrawal. PMID:25109596

  1. Approaching Long Genomic Regions and Large Recombination Rates with msParSm as an Alternative to MaCS

    PubMed Central

    Montemuiño, Carlos; Espinosa, Antonio; Moure, Juan C.; Vera, Gonzalo; Hernández, Porfidio; Ramos-Onsins, Sebastián

    2016-01-01

    The msParSm application is an evolution of msPar, the parallel version of the coalescent simulation program ms, which removes the limitation for simulating long stretches of DNA sequences with large recombination rates, without compromising the accuracy of the standard coalescence. This work introduces msParSm, describes its significant performance improvements over msPar and its shared memory parallelization details, and shows how it can get better, if not similar, execution times than MaCS. Two case studies with different mutation rates were analyzed, one approximating the human average and the other approximating the Drosophila melanogaster average. Source code is available at https://github.com/cmontemuino/msparsm. PMID:27721650

  2. Genome-wide protein QTL mapping identifies human plasma kallikrein as a post-translational regulator of serum uPAR levels.

    PubMed

    Portelli, Michael A; Siedlinski, Mateusz; Stewart, Ceri E; Postma, Dirkje S; Nieuwenhuis, Maartje A; Vonk, Judith M; Nurnberg, Peter; Altmuller, Janine; Moffatt, Miriam F; Wardlaw, Andrew J; Parker, Stuart G; Connolly, Martin J; Koppelman, Gerard H; Sayers, Ian

    2014-02-01

    The soluble cleaved urokinase plasminogen activator receptor (scuPAR) is a circulating protein detected in multiple diseases, including various cancers, cardiovascular disease, and kidney disease, where elevated levels of scuPAR have been associated with worsening prognosis and increased disease aggressiveness. We aimed to identify novel genetic and biomolecular mechanisms regulating scuPAR levels. Elevated serum scuPAR levels were identified in asthma (n=514) and chronic obstructive pulmonary disease (COPD; n=219) cohorts when compared to controls (n=96). In these cohorts, a genome-wide association study of serum scuPAR levels identified a human plasma kallikrein gene (KLKB1) promoter polymorphism (rs4253238) associated with serum scuPAR levels in a control/asthma population (P=1.17 × 10(-7)), which was also observed in a COPD population (combined P=5.04 × 10(-12)). Using a fluorescent assay, we demonstrated that serum KLKB1 enzymatic activity was driven by rs4253238 and is inverse to scuPAR levels. Biochemical analysis identified that KLKB1 cleaves scuPAR and negates scuPAR's effects on primary human bronchial epithelial cells (HBECs) in vitro. Chymotrypsin was used as a proproteolytic control, while basal HBECs were used as a control to define scuPAR-driven effects. In summary, we reveal a novel post-translational regulatory mechanism for scuPAR using a hypothesis-free approach with implications for multiple human diseases.

  3. PAR-2, LGL-1 and the CDC-42 GAP CHIN-1 act in distinct pathways to maintain polarity in the C. elegans embryo.

    PubMed

    Beatty, Alexander; Morton, Diane G; Kemphues, Kenneth

    2013-05-01

    In the one-cell C. elegans embryo, polarity is maintained by mutual antagonism between the anterior cortical proteins PAR-3, PKC-3, PAR-6 and CDC-42, and the posterior cortical proteins PAR-2 and LGL-1 on the posterior cortex. The mechanisms by which these proteins interact to maintain polarity are incompletely understood. In this study, we investigate the interplay among PAR-2, LGL-1, myosin, the anterior PAR proteins and CDC-42. We find that PAR-2 and LGL-1 affect cortical myosin accumulation by different mechanisms. LGL-1 does not directly antagonize the accumulation of cortical myosin and instead plays a role in regulating PAR-6 levels. By contrast, PAR-2 likely has separate roles in regulating cortical myosin accumulation and preventing the expansion of the anterior cortical domain. We also provide evidence that asymmetry of active CDC-42 can be maintained independently of LGL-1 and PAR-2 by a redundant pathway that includes the CDC-42 GAP CHIN-1. Finally, we show that, in addition to its primary role in regulating the size of the anterior cortical domain via its binding to PAR-6, CDC-42 has a secondary role in regulating cortical myosin that is not dependent on PAR-6.

  4. Remote estimation of Kd (PAR) using MODIS and Landsat imagery for turbid inland waters in Northeast China

    NASA Astrophysics Data System (ADS)

    Song, Kaishan; Ma, Jianhang; Wen, Zhidan; Fang, Chong; Shang, Yingxin; Zhao, Ying; Wang, Ming; Du, Jia

    2017-01-01

    Light availability for photosynthetically active radiation (PAR) is one of the major factors governing photosynthesis in aquatic ecosystems. Conventional measurements of light attenuation in the PAR domain (Kd(PAR)) is representative for only small areas of water body. Remotely sensed optical imagery can be utilized to monitor Kd(PAR) in large areas of water bodies, based on the relationship between water leaving radiance and Kd(PAR). In this study, six field surveys were conducted over 20 lakes (or reservoirs) across Northeast China from April to September 2015. In order to derive the Kd(PAR) at regional scale, the Landsat/TM/ETM+/OLI and the MODIS daily surface reflectance data (MOD09GA ∼500 m, Bands 1-7) were used to establish empirical inversion models. Through multiple stepwise regression analysis, the band difference (Red-Blue) and band ratio (NIR/Red) were used in Landsat imagery modeling, and the band difference (Red-Blue) and ratio (Red/Blue) were used in MODIS imagery modeling. The accuracy of the two models was evaluated by 10-fold cross-validation in ten times. The results indicate that the models performed well for both Landsat (R2 = 0.83, RMSE = 0.95, and MRE = 0.33), and MODIS (R2 = 0.86, RMSE = 0.91, and MRE = 0.19) imagery. However, the Kd(PAR) derived by MODIS is slightly higher than that estimated by Landsat (slope = 1.203 and R2 = 0.972). Consistency of model performance between the MODIS daily (MYD09G A) and the 8-Day composite reflectance (MYD09A1) data was verified by Kd(PAR) estimations and regression analysis (slope = 1.044 and R2 = 0.966). Finally, the spatial and temporal distribution of Kd(PAR) in Northeast China indicated that specific geographical characteristics as well as meteorological alterations can influence Kd(PAR) calibrations. Specifically, we have revealed that the wind speed and algal bloom are the major determinants of Kd(PAR) in Lake Hulun (2050 km2) and Xingkai (4412 km2).

  5. Disentangling the confounding effects of PAR and air temperature on net ecosystem exchange in time and scale

    NASA Astrophysics Data System (ADS)

    yang, Z.; Chen, J.; Becker, R.; Chu, H.; Xie, J.; Shao, C.

    2013-12-01

    Net ecosystem exchange of CO2 (NEE) in temperate forests is modulated by microclimatic factors. The effects of those factors differ at different time scales and during different time periods. Some of them are correlated across a number of time scales, so their effects on NEE are confounded by each other. PAR and air temperature (Ta) are among the two most important drivers of NEE in temperate forests, and among the two most correlated microclimatic factors. PAR and Ta have similar daily, seasonal, and annual cycles. Their influence on NEE is confounded by each other and entangled together especially at those scales. In this study, we tried to disentangle the confounding effects of them on NEE at different time scales and during different time periods. To accomplish this objective, we applied the innovative spectral analysis techniques including Continuous Wavelet Transformation (CWT), Cross Wavelet Transformation (XWT), Wavelet Coherent (WTC), and Partial Wavelet Coherence (PWC) on seven years time series (2004-2010) of PAR, Ta and NEE from the Ohio Oak Openings site (N 41.5545°, W 83.8438°), USA for spectral analysis. We found that PAR is the major driver at short time scales (e.g. semidiurnal and daily) and Ta is the major driver at long time scales (e.g. seasonal and annual). At daily scale during growing seasons, PAR is anti-phase with NEE with no time delay while Ta lagged PAR about 2-3 hours, which could be explained by the strong dependence of photosynthesis on PAR and a 2-3 hours lags of the daily course of Ta to PAR. At daily scale during non-growing season, NEE has little variation and thus neither Ta nor PAR has high common wavelet power and significant coherence with NEE. At annual scale, Ta is anti-phase with NEE and PAR leads NEE about 34 days, which could be explained by the strong dependence of LAI dynamics on Ta and the lag between the LAI/biomass development and the progress of sunlight. We also found that NEE distributes most of its variation

  6. Molecular networks implicated in speech-related disorders: FOXP2 regulates the SRPX2/uPAR complex

    PubMed Central

    Roll, Patrice; Vernes, Sonja C.; Bruneau, Nadine; Cillario, Jennifer; Ponsole-Lenfant, Magali; Massacrier, Annick; Rudolf, Gabrielle; Khalife, Manal; Hirsch, Edouard; Fisher, Simon E.; Szepetowski, Pierre

    2010-01-01

    It is a challenge to identify the molecular networks contributing to the neural basis of human speech. Mutations in transcription factor FOXP2 cause difficulties mastering fluent speech (developmental verbal dyspraxia, DVD), whereas mutations of sushi-repeat protein SRPX2 lead to epilepsy of the rolandic (sylvian) speech areas, with DVD or with bilateral perisylvian polymicrogyria. Pathophysiological mechanisms driven by SRPX2 involve modified interaction with the plasminogen activator receptor (uPAR). Independent chromatin-immunoprecipitation microarray screening has identified the uPAR gene promoter as a potential target site bound by FOXP2. Here, we directly tested for the existence of a transcriptional regulatory network between human FOXP2 and the SRPX2/uPAR complex. In silico searches followed by gel retardation assays identified specific efficient FOXP2-binding sites in each of the promoter regions of SRPX2 and uPAR. In FOXP2-transfected cells, significant decreases were observed in the amounts of both SRPX2 (43.6%) and uPAR (38.6%) native transcripts. Luciferase reporter assays demonstrated that FOXP2 expression yielded a marked inhibition of SRPX2 (80.2%) and uPAR (77.5%) promoter activity. A mutant FOXP2 that causes DVD (p.R553H) failed to bind to SRPX2 and uPAR target sites and showed impaired down-regulation of SRPX2 and uPAR promoter activity. In a patient with polymicrogyria of the left rolandic operculum, a novel FOXP2 mutation (p.M406T) was found in the leucine-zipper (dimerization) domain. p.M406T partially impaired the FOXP2 regulation of SRPX2 promoter activity, whereas that of the uPAR promoter remained unchanged. Together with recently described FOXP2-CNTNAP2 and SRPX2/uPAR links, the FOXP2-SRPX2/uPAR network provides exciting insights into molecular pathways underlying speech-related disorders. PMID:20858596

  7. Protease-Activated Receptor 2 (PAR2) Is Upregulated by Acanthamoeba Plasminogen Activator (aPA) and Induces Proinflammatory Cytokine in Human Corneal Epithelial Cells

    PubMed Central

    Tripathi, Trivendra; Abdi, Mahshid; Alizadeh, Hassan

    2014-01-01

    Purpose. Acanthamoeba plasminogen activator (aPA) is a serine protease elaborated by Acanthamoeba trophozoites that facilitates the invasion of trophozoites to the host and contributes to the pathogenesis of Acanthamoeba keratitis (AK). The aim of this study was to explore if aPA stimulates proinflammatory cytokine in human corneal epithelial (HCE) cells via the protease-activated receptors (PARs) pathway. Methods. Acanthamoeba castellanii trophozoites were grown in peptone-yeast extract glucose for 7 days, and the supernatants were collected and centrifuged. The aPA was purified using the fast protein liquid chromatography system, and aPA activity was determined by zymography assays. Human corneal epithelial cells were incubated with or without aPA (100 μg/mL), PAR1 agonists (thrombin, 10 μM; TRAP-6, 10 μM), and PAR2 agonists (SLIGRL-NH2, 100 μM; AC 55541, 10 μM) for 24 and 48 hours. Inhibition of PAR1 and PAR2 involved preincubating the HCE cells for 1 hour with the antagonist of PAR1 (SCH 79797, 60 μM) and PAR2 (FSLLRY-NH2, 100 μM) with or without aPA. Human corneal epithelial cells also were preincubated with PAR1 and PAR2 antagonists and then incubated with or without PAR1 agonists (thrombin and TRAP-6) and PAR2 agonists (SLIGRL-NH2 and AC 55541). Expression of PAR1 and PAR2 was examined by quantitative RT-PCR (qRT-PCR), flow cytometry, and immunocytochemistry. Interleukin-8 expression was quantified by qRT-PCR and ELISA. Results. Human corneal epithelial cells constitutively expressed PAR1 and PAR2 mRNA. Acanthamoeba plasminogen activator and PAR2 agonists significantly upregulated PAR2 mRNA expression (1- and 2-fold, respectively) (P < 0.05). Protease-activated receptor 2 antagonist significantly inhibited aPA, and PAR2 agonists induced PAR2 mRNA expression in HCE cells (P < 0.05). Protease-activated receptor 1 agonists, but not aPA, significantly upregulated PAR1 mRNA expression, which was significantly inhibited by PAR1 antagonist in HCE cells

  8. Effet Hall et Magnetisme des Alliages Amorphes Nickel-Zirconium Fabriques Par Pulverisation

    NASA Astrophysics Data System (ADS)

    Morel, Robert

    Cette these se situe dans le cadre d'une etude des proprietes electroniques et structurales des alliages metalliques amorphes, en cours depuis quelques annees a l'Universite de Montreal. Ce programme nous a entre autres amene a caracteriser la magnetoresistivite et l'effet Hall d'alliages FeZr, CoZr et NiZr, ce qui a permis de mettre en evidence deux caracteristiques de l'effet Hall: Dans les alliages amorphes ferromagnetiques, la resistivite elevee engendre un effet Hall extraordinaire beaucoup plus important que celui enregistre dans les metaux cristallins. La polarisation des spins entrai ne une asymetrie de la diffusion qui, tant dans les phases cristalline et amorphe, est tenue responsable de cette contribution. L'autre particularite du comportement de Hall de ces systemes est le renversement de signe du coefficient de Hall ordinaire, qui passe du negatif au positif dans les echantillons plus riches en zirconium. Dans les metaux cristallins, un modele d'electrons libres predit un signe negatif a moins que la conduction ne soit dominee par les trous. Or, dans un milieu desordonne les memes concepts sont difficilement applicables et de nouvelles theories ont du etre elaborees pour expliquer ce phenomene. Jusqu'a maintenant, l'etude des alliages amorphes nickel-zirconium s'est faite surtout a partir d'echantillons fabriques par trempe sur roue. Malheureusement cette technique ne permet pas la fabrication d'alliages contenant plus de 70% de nickel, a l'exception du seul compose Ni _{90}Zr_{10 }. Pour pallier a cette lacune et etendre nos connaissance a l'ensemble de la gamme de compositions, nous avons fabrique par pulverisation cathodique des echantillons NiZr amorphes--et quelques alliages cristallins tres riches en nickel--couvrant une bonne partie de la gamme interdite par la technique de trempe sur roue. Dans un premier temps, par comparaison avec les resultats connus nous avons mis en evidence les similitudes et les differences entre les alliages obtenus par

  9. Apparent PS II absorption cross-section and estimation of mean PAR in optically thin and dense suspensions of Chlorella.

    PubMed

    Klughammer, Christof; Schreiber, Ulrich

    2015-01-01

    Theoretical prediction of effective mean PAR in optically dense samples is complicated by various optical effects, including light scattering and reflections. Direct information on the mean rate of photon absorption by PS II is provided by the kinetics of the fluorescence rise induced upon onset of strong actinic illumination (O-I1 rise). A recently introduced kinetic multi-color PAM fluorometer was applied to study the relationship between initial slope and cell density in the relatively simple model system of suspensions of Chlorella. Use of a curve fitting routine was made which was originally developed for assessment of the wavelength-dependent absorption cross-section of PS II, σ II(λ), in dilute suspensions. The model underlying analysis of the O-I1 rise kinetics is outlined and data on the relationship between fitted values of σ II(λ) and PAR in dilute samples are presented. With increasing cell density, lowering of apparent cross-section, <σ>(λ), with respect to σ II(λ), relates to a decrease of effective mean PAR, <PAR>(λ), relative to incident PAR(λ). When ML and AL are applied in the same direction, the decline of <σ>(λ)/σ II(λ) with increasing optical density is less steep than that of the theoretically predicted <PAR>(λ)/PAR(λ). It approaches a value of 0.5 when the same colors of ML and AL are used, in agreement with theory. These observations open the way for estimating mean PAR in optically dense samples via measurements of <σ>(λ)/σ II(λ)).

  10. Peroxynitrite-induced thymocyte apoptosis: the role of caspases and poly (ADP-ribose) synthetase (PARS) activation.

    PubMed Central

    Virág, L; Scott, G S; Cuzzocrea, S; Marmer, D; Salzman, A L; Szabó, C

    1998-01-01

    The mechanisms by which immature thymocyte apoptosis is induced during negative selection are poorly defined. Reports demonstrated that cross-linking of T-cell receptor leads to stromal cell activation, expression of inducible nitric oxide synthase (iNOS) and, subsequently, to thymocyte apoptosis. Therefore we examined, whether NO directly or indirectly, through peroxynitrite formation, causes thymocyte apoptosis. Immuno-histochemical detection of nitrotyrosine revealed in vivo peroxynitrite formation in the thymi of naive mice. Nitrotyrosine, the footprint of peroxynitrite, was predominantly found in the corticomedullary junction and the medulla of naive mice. In the thymi of mice deficient in the inducible isoform of nitric oxide synthase, considerably less nitrotyrosine was found. Exposure of thymocytes in vitro to low concentrations (10 microM) of peroxynitrite led to apoptosis, whereas higher concentrations (50 microM) resulted in intense cell death with the characteristics of necrosis. We also investigated the effect of poly (ADP-ribose) synthetase (PARS) inhibition on thymocyte apoptosis. Using the PARS inhibitor 3-aminobenzamide (3-AB), or thymocytes from PARS-deficient animals, we established that PARS determines the fate of thymocyte death. Suppression of cellular ATP levels, and the cellular necrosis in response to peroxynitrite were prevented by PARS inhibition. Therefore, in the absence of PARS, cells are diverted towards the pathway of apoptotic cell death. Similar results were obtained with H2O2 treatment, while apoptosis induced by non-oxidative stimuli such as dexamethasone or anti-FAS antibody was unaffected by PARS inhibition. In conclusion, we propose that peroxynitrite-induced apoptosis may play a role in the process of thymocyte negative selection. Furthermore, we propose that the physiological role of PARS cleavage by apopain during apoptosis may serve as an energy-conserving step, enabling the cell to complete the process of apoptosis

  11. Hypersensitivity Induced by Activation of Spinal Cord PAR2 Receptors Is Partially Mediated by TRPV1 Receptors

    PubMed Central

    Mrozkova, Petra; Spicarova, Diana; Palecek, Jiri

    2016-01-01

    Protease-activated receptors 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) receptors in the peripheral nerve endings are implicated in the development of increased sensitivity to mechanical and thermal stimuli, especially during inflammatory states. Both PAR2 and TRPV1 receptors are co-expressed in nociceptive dorsal root ganglion (DRG) neurons on their peripheral endings and also on presynaptic endings in the spinal cord dorsal horn. However, the modulation of nociceptive synaptic transmission in the superficial dorsal horn after activation of PAR2 and their functional coupling with TRPV1 is not clear. To investigate the role of spinal PAR2 activation on nociceptive modulation, intrathecal drug application was used in behavioural experiments and patch-clamp recordings of spontaneous, miniature and dorsal root stimulation-evoked excitatory postsynaptic currents (sEPSCs, mEPSCs, eEPSCs) were performed on superficial dorsal horn neurons in acute rat spinal cord slices. Intrathecal application of PAR2 activating peptide SLIGKV-NH2 induced thermal hyperalgesia, which was prevented by pretreatment with TRPV1 antagonist SB 366791 and was reduced by protein kinases inhibitor staurosporine. Patch-clamp experiments revealed robust decrease of mEPSC frequency (62.8 ± 4.9%), increase of sEPSC frequency (127.0 ± 5.9%) and eEPSC amplitude (126.9 ± 12.0%) in dorsal horn neurons after acute SLIGKV-NH2 application. All these EPSC changes, induced by PAR2 activation, were prevented by SB 366791 and staurosporine pretreatment. Our results demonstrate an important role of spinal PAR2 receptors in modulation of nociceptive transmission in the spinal cord dorsal horn at least partially mediated by activation of presynaptic TRPV1 receptors. The functional coupling between the PAR2 and TRPV1 receptors on the central branches of DRG neurons may be important especially during different pathological states when it may enhance pain perception. PMID:27755539

  12. Row orientation effect on UV-B, UV-A and PAR solar irradiation components in vineyards at Tuscany, Italy

    NASA Astrophysics Data System (ADS)

    Grifoni, D.; Carreras, G.; Zipoli, G.; Sabatini, F.; Dalla Marta, A.; Orlandini, S.

    2008-11-01

    Besides playing an essential role in plant photosynthesis, solar radiation is also involved in many other important biological processes. In particular, it has been demonstrated that ultraviolet (UV) solar radiation plays a relevant role in grapevines ( Vitis vinifera) in the production of certain important chemical compounds directly responsible for yield and wine quality. Moreover, the exposure to UV-B radiation (280-320 nm) can affect plant-disease interaction by influencing the behaviour of both pathogen and host. The main objective of this research was to characterise the solar radiative regime of a vineyard, in terms of photosynthetically active radiation (PAR) and UV components. In this analysis, solar spectral UV irradiance components, broadband UV (280-400 nm), spectral UV-B and UV-A (320-400 nm), the biological effective UVBE, as well as the PAR (400-700 nm) component, were all considered. The diurnal patterns of these quantities and the UV-B/PAR and UV-B/UV-A ratios were analysed to investigate the effect of row orientation of the vineyard in combination with solar azimuth and elevation angles. The distribution of PAR and UV irradiance at various heights of the vertical sides of the rows was also studied. The results showed that the highest portion of plants received higher levels of daily radiation, especially the UV-B component. Row orientation of the vines had a pronounced effect on the global PAR received by the two sides of the rows and, to a lesser extent, UV-A and UV-B. When only the diffused component was considered, this geometrical effect was greatly attenuated. UV-B/PAR and UV-A/PAR ratios were also affected, with potential consequences on physiological processes. Because of the high diffusive capacity of the UV-B radiation, the UV-B/PAR ratio was significantly lower on the plant portions exposed to full sunlight than on those in the shade.

  13. Structure par RMN d'un complexe AlcR(1-60)-ADN: Reconnaissance du petit sillon par la partie N-terminale

    NASA Astrophysics Data System (ADS)

    Cahuzac, B.; Félenbok, B.; Guittet, E.

    1999-10-01

    Aspergillus nidulans is a filamentous fungus able to use ethanol as sole energy source. The activation of the ethanol regulon genes expression is mediated by the AlcR protein. Its DNA-binding domain is located in the N-terminus (residues 1 to 60), and its NMR solution structure shows a global zinc binuclear cluster fold, with two helices in addition to the basic binuclear motif. A small number of crystallographic structures of DNA complexes of binuclear cluster proteins is yet known, and points out the major groove and the first helix as the principal sites of interaction on the DNA and the protein respectively. In this article we show evidences that the N-terminus of the protein is involved in binding to the minor groove. Aspergillus nidulans est un champignon filamenteux capable d'utiliser l'éthanol comme source unique d'énergie. La protéine AlcR est responsable de l'activation de l'expression des gènes du régulon éthanol. Le domaine de liaison à l'ADN est situé dans la partie N-terminale de la protéine (a.a. 1 à 60), et sa structure déterminée par RMN en solution montre un repliement global en bouquet binucléaire à zinc, avec deux hélices supplémentaires par rapport au motif de base. Alors que les structures déjà connues de complexes ADN - bouquets binucléaires permettent de situer dans le grand sillon la quasi-totalité des interactions, nous montrons dans la présente étude l'implication du début de la séquence dans la reconnaissance du petit sillon de l'ADN (a.a. 5 et 6).

  14. Proteinase-activated receptor 2 (PAR(2)) in cholangiocarcinoma (CCA) cells: effects on signaling and cellular level.

    PubMed

    Kaufmann, Roland; Hascher, Alexander; Mussbach, Franziska; Henklein, Petra; Katenkamp, Kathrin; Westermann, Martin; Settmacher, Utz

    2012-12-01

    In this study, we demonstrate functional expression of the proteinase-activated receptor 2 (PAR(2)), a member of a G-protein receptor subfamily in primary cholangiocarcinoma (PCCA) cell cultures. Treatment of PCCA cells with the serine proteinase trypsin and the PAR(2)-selective activating peptide, furoyl-LIGRLO-NH(2), increased migration across a collagen membrane barrier. This effect was inhibited by a PAR(2)-selective pepducin antagonist peptide (P2pal-18S) and it was also blocked with the Met receptor tyrosine kinase (Met) inhibitors SU 11274 and PHA 665752, the MAPKinase inhibitors PD 98059 and SL 327, and the Stat3 inhibitor Stattic. The involvement of Met, p42/p44 MAPKinases and Stat3 in PAR(2)-mediated PCCA cell signaling was further supported by the findings that trypsin and the PAR(2)-selective agonist peptide, 2-furoyl-LIGRLO-NH(2), stimulated activating phosphorylation of these signaling molecules in cholangiocarcinoma cells. With our results, we provide a novel signal transduction module in cholangiocarcinoma cell migration involving PAR(2)-driven activation of Met, p42/p44 MAPKinases and Stat3.

  15. Store-operated CRAC channels regulate PAR2-activated Ca2+ signaling and cytokine production in airway epithelial cells

    PubMed Central

    Jairaman, Amit; Yamashita, Megumi; Schleimer, Robert P.; Prakriya, Murali

    2015-01-01

    The G-protein coupled protease-activated receptor 2 (PAR2) plays an important role in the pathogenesis of various inflammatory and auto-immune disorders. In airway epithelial cells (AECs), stimulation of PAR2 by a