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1

Pharmacogenetics of FSH action  

PubMed Central

Purpose of the review To review the current knowledge of genetic variants in the two genes affecting the individual responsiveness to follicle-stimulating hormone (FSH) action—the FSH beta-subunit (FSHB) and the FSH receptor (FSHR), as well as the pharmacogenetic ramifications of the findings. Recent findings Four common variants in FSHB/FSHR were shown to exhibit significant effect on FSH action: linked FSHR variants Thr307Ala and Asn680Ser determining common receptorisoforms, andgene expression affecting polymorphisms FSHR –29G/A and FSHB–211G/T. In women, the FSHR Thr307Ala/Asn680Ser polymorphisms show consistent predictive value for estimating the most optimal rFSH dosage in controlled ovarian hyperstimulation(COH).The same variants exhibit a potential for the pharmacogenetic assessment of the treatment ofPCOS. The FSHR–29G/A variant was also shown to contribute to ovarian response to COH. Pilot studies have suggestedthe FSHB–211TT-homozygous oligozoospermicmen with genetically determined low concentration of FSH, as potentially the best responders to FSH treatment; furthermore, modulation of this response by FSHR polymorphisms is possible. Summary Genetic variants in FSHB/FSHRexhibit a potential for pharmacogenetic applications in selecting appropriate treatment options (timing and dosage) in male and female conditions requiring or benefitting from FSH therapy. PMID:22499219

Laan, Maris; Grigorova, Marina; Huhtaniemi, Ilpo T.

2012-01-01

2

Blocking FSH Action Attenuates Osteoclastogenesis  

PubMed Central

A direct effect of FSH on bone turnover via stimulation of osteoclast formation has been reported. Here we show that monoclonal or polyclonal antibodies to FSH inhibit osteoclast formation induced by FSH to an extent similar to that noted in FSH receptor (FSHR) knockout cells. Furthermore, we document the amplification of FSHR cDNA from well-characterized human CD14+ osteoclast precursors and osteoclasts, and the direct sequencing of the PCR products to definitively establish the expression of FSHRs. At these sites, the FSHR was expressed predominantly as an isoform that omits exon 9, a linker between the FSH-binding region and a long, invariant signaling domain of the receptor. These data provide compelling evidence for expression of a FSH receptor isoform in osteoclasts and their precursors. PMID:22561017

Zhu, Ling-Ling; Tourkova, Irina; Yuen, Tony; Robinson, Lisa J.; Bian, Zhuan; Zaidi, Mone; Blair, Harry C.

2014-01-01

3

Follicle-stimulating hormone (FSH) blood test  

MedlinePLUS

... blood. FSH is a hormone released by the pituitary gland , located on the underside of the brain. ... Due to certain types of tumor in the pituitary gland Due to Turner syndrome Low FSH levels in ...

4

Pulsatile release of FSH for superovulation in cattle.  

PubMed

The studies reported here were directed towards the development of an implantable microcapsule which "pulses" release of follicle stimulating hormone, FSH, for application to superovulating cows. Final dose forms were administered using membrane-coated cylinders. The "pulse" of the FSH is achieved by membrane encapsulation of an effervescent/swelling core containing citric acid, sodium bicarbonate, glucose and FSH. Entry of water results in sufficient pressure increase (by gas generation) to rupture ("burst") the membrane. Time to rupture is dependent upon several factors, such as membrane permeability and thickness, and core composition and loading. The final dose forms were implanted by means of a trochar. This system was tested in sheep to substantiate in vivo "burst" times and then tested in cows to determine efficacy. In vivo burst times in sheep varied from 8 to 96 hr, based upon maximal FSH values in blood serum, and generally paralled the planned times resulting from in vitro tests. Multiple capsules designed to release FSH as a pulse or steady state were tested on a limited number of cows plus a control (n = 10). Four of the combinations resulted in 11, 11, 14 and 16 ovulations, indicating that further development has promise of providing a one-injection system using FSH for superovulating cattle. PMID:16727656

Jimoh, A G; Wise, D L; Gresser, J D; Foote, R H; Rhodes, R C; Underbill, L H; Trantolo, D J

1995-02-01

5

Possible existence of a long-loop feedback system between FSH and inhibin in female rats.  

PubMed

Experiments were designed in which peripheral plasma inhibin levels were presumably altered in an attempt to investigate an interdependency between pituitary follicle-stimulating hormone (FSH) and ovarian inhibin secretion. In the first study, unilateral ovariectomy (ULO) was performed on 4-day cycling female rats under ether anesthesia at 0800 h on diestrous day 1 (D1). Inhibin-like activity [FSH-inhibiting activity(FSH-IA)] in untreated ovarian venous plasma (OVP) collected from the remaining ovary was assessed by an in vitro pituitary bioassay system. Both plasma FSH levels and FSH-IA significantly increased between 4 and 12 h after ULO. Thereafter, plasma FSH declined between 12 and 32 h after ULO, whereas FSH-IA remained elevated during this same time interval. Compared to sham-operated rats, plasma FSH was significantly elevated 4, 12, and 24 h after ULO, whereas FSH-IA was statistically higher only at 32 h after ULO. In a second experiment, rats were injected with charcoal-treated porcine follicular fluid (PFF) on proestrus and estrus. Control rats received saline. The data indicate that increased plasma FSH levels on D1 in PFF-treated rats (FSH rebound) may be a consequence of reduced endogenous inhibin secretion on estrus. As well, return of FSH to control levels on D2 in PFF-treated rats may have resulted from an FSH-associated increase in FSH-IA on D1 and D2. PMID:6786105

DePaolo, L V; Anderson, L D; Hirshfield, A N

1981-05-01

6

Superovulation of holstein heifers by a single subcutaneous injection of FSH dissolved in polyvinylpyrrolidone  

Microsoft Academic Search

This study was undertaken to determine whether a single injection of porcine FSH (pFSH) would induce a superovulatory response in cattle. Holstein heifers were given a single injection of pFSH (30mg, sc) dissolved in saline (Group 1, n = 5); 50% polyvinylpyrrolidone (PVP; Group 2, n = 5); or 25% PVP (Group 3, n = 4). Group-4 heifers (n =

T. Takedomi; Y. Aoyagi; M. Konishi; H. Kishi; K. Taya; G. Watanabe; S. Sasamoto

1995-01-01

7

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

PubMed

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 ?4- 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 ?4-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 ?4-steroid-independent regulatory functions on many genes which are highly relevant for the onset of spermatogenesis. PMID:24194844

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

2013-01-01

8

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

PubMed Central

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

2013-01-01

9

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

PubMed

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. PMID:24805832

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

2014-06-01

10

Follicle Stimulating Hormone (FSH) Dosage Based on Body Weight Enhances Ovulatory Responses and Subsequent Embryo Production in Goats  

PubMed Central

An experiment was conducted to evaluate the efficacy of porcine follicle stimulating hormone (pFSH) dosage based on body weight (BW) on ovarian responses of crossbred does. Thirty donor does were divided into 3 groups getting pFSH dosages of 3, 5, and 8 mg pFSH per kg BW, respectively, and were named as pFSH-3, pFSH-5 and pFSH-8, respectively. Estrus was synchronized by inserting a controlled internal drug release (CIDR) device and a single injection of prostaglandin F2? (PGF2?). The pFSH treatments were administered twice a day through 6 decreasing dosages (25, 25, 15, 15, 10, and 10% of total pFSH amount; decreasing daily). Ovarian responses were evaluated on Day 7 after CIDR removal. After CIDR removal, estrus was observed 3 times in a day and pFSH treatments were initiated at 2 days before the CIDR removal. All does in pFSH-5 and pFSH-8 showed estrus signs while half of the does in pFSH-3 showed estrus signs. No differences (p>0.05) were observed on the corpus luteum and total ovarian stimulation among the treatment groups, while total and transferable embryos were higher (p<0.05) in pFSH-5 (7.00 and 6.71) than pFSH-3 (3.00 and 2.80) and pFSH-8 (2.00 and 1.50), respectively. In conclusion, 5 mg pFSH per kg BW dosage gave a higher number of embryos than 3 and 8 mg pFSH per kg BW dosages. The results indicated that the dosage of pFSH based on BW is an important consideration for superovulation in goats. PMID:25178370

Rahman, M. R.; Rahman, M. M.; Wan Khadijah, W. E.; Abdullah, R. B.

2014-01-01

11

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

PubMed

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. PMID:22877941

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

2012-10-01

12

Identification of Smad Response Elements in the Promoter of Goldfish FSH? Gene and Evidence for Their Mediation of Activin and GnRH Stimulation of FSH? Expression  

PubMed Central

As an essential hormone regulating gonads in vertebrates, the biosynthesis and secretion of follicle-stimulating hormone (FSH) is controlled by a variety of endocrine and paracrine factors in both mammalian and non-mammalian vertebrates. Activin was initially discovered in the ovary for its specific stimulation of FSH secretion by the pituitary cells. Our earlier studies in fish have shown that activin stimulates FSH? but suppresses LH? expression in both the goldfish and zebrafish. Further experiments showed that the regulation of FSH? in fish occurred at the promoter level involving Smads, in particular Smad3. To further understand the mechanisms by which activin/Smad regulates FSH? transcription, the present study was undertaken to analyze the promoter of goldfish FSH? gene (fshb) with the aim to identify potential cis-regulatory elements responsible for activin/Smad stimulation. Both serial deletion and site-directed mutagenesis were used, and the promoter activity was tested in the L?T-2 cells, a murine gonadotroph cell line. The reporter constructs of goldfish FSH? promoter-SEAP (secreted alkaline phosphatase) were co-transfected with an expression plasmid for Smads (2 or 3) followed by measurement of SEAP activity in the medium. Two putative Smad responsive elements were identified in the promoter at distal and proximal regions, respectively. The distal site contained a consensus Smad binding element (AGAC, ?1675/?1672) whereas the proximal site (GACCTTGA, ?212/?205) was identical to an SF-1 binding site reported in humans, which was preceded by a sequence (AACACTGA) highly conserved between fish and mammals. The proximal site also seemed to be involved in mediating stimulation of FSH? expression by gonadotropin-releasing hormone and its potential interaction with activin. In conclusion, we have identified two potential cis-regulatory elements in the promoter of goldfish FSH? that are responsible for activin-induced expression of the gene. Since activin stimulation of FSH? expression is functionally conserved in fish and mammals, our findings contribute to the understanding of the fundamental mechanisms of this regulation across vertebrates. PMID:22645522

Lau, Man-Tat; Lin, Sze-Wah; Ge, Wei

2012-01-01

13

Ovarian stimulation with FSH reduces phosphorylation of gonadotrope progesterone receptor and LH secretion in the rat.  

PubMed

Administration of human FSH (hFSH) to cyclic rats during the dioestrous phase attenuates progesterone receptor (PR)-dependent events of the preovulatory LH surge in pro-oestrus. The increased bioactivity of the putative ovarian gonadotropin surge inhibiting/attenuating factor induced by hFSH treatment is not associated with a decrease in PR protein expression, and the possibility of its association at a PR posttranslational effect has been raised. The present experiments aimed to analyse PR phosphorylation status in the gonadotrope of rats with impaired LH secretion induced by in vivo hFSH injection. Two experimental approaches were used. First, incubated pro-oestrous pituitaries from hFSH-injected cycling and oestrogen-treated ovariectomized (OVX) rats were used to analyze the effect of calyculin, an inhibitor of intracellular phosphatases, on PR-dependent LH release, which was measured in the incubation medium by RIA. Second, pituitaries taken from hFSH-injected intact cycling and OVX rats and later incubated with P or GNRH1 were used to assess the phosphorylation rate of gonadotrope. The latter was analysed in formalin-fixed, paraffin-embedded tissue sections by immunohistochemistry using a MAB that recognizes the phosphorylated (p) form of PR at Ser294. Calyculin reduced the ovary-mediated inhibition of hFSH in GNRH1-stimulated LH secretion. In addition, the immunohistochemical expression of pSer294 PR was significantly reduced after ovarian stimulation with hFSH in pituitaries from pro-oestrous rats incubated with P or GNRH1. Altogether, these results suggested that the ovarian-dependent inhibitory effect of FSH injection on the preovulatory LH secretion in the rat may involve an increase in dephosphorylation of PR. PMID:18936085

Gordon, Ana; Garrido-Gracia, José C; Aguilar, Rafaela; Guil-Luna, Silvia; Millán, Yolanda; de Las Mulas, Juana Martín; Sánchez-Criado, José E

2009-01-01

14

Granulosa cells are refractory to FSH action in individuals with a low antral follicle count.  

PubMed

The reason ovarian function and fertility are diminished in women with a low antral follicle count (AFC), despite significant numbers of follicles remaining in ovaries, is unknown. The bovine model is unique to address this question because cattle and women with a low AFC exhibit similar phenotypic characteristics including a diminished ovarian reserve, reduced circulating concentrations of anti-Müllerian hormone (AMH) but heightened FSH secretion during reproductive cycles. Because women and cattle with a low AFC respond minimally to gonadotropin stimulation during IVF cycles or superovulation, granulosa cells in individuals with a low AFC are hypothesised to be refractory to FSH. The present study evaluates this hypothesis by testing whether capacity of granulosa cells to respond to FSH differs between cattle with a low and a high AFC. Granulosa cells from cattle with a low (?15 follicles ?3 mm in diameter) or a high (?25 follicles) AFC were cultured with different doses of FSH. Treatments were evaluated by measurement of oestradiol (E), progesterone (P) and AMH in media and abundance of mRNAs for aromatase (CYP19A1), AMH, FSH receptor (FSHR) and oxytocin (OXT). Progesterone and OXT mRNA are well-established markers of granulosa cell luteinisation. Although high doses of FSH induced granulosa cell luteinisation, basal and FSH-induced increases in E and AMH production and expression of mRNAs for CYP19A1, FSHR and AMH in granulosa cells were much lower, while P production and OXT mRNA expression were higher in non-luteinised and luteinised granulosa cells from the low than the high AFC group. Granulosa cells in cattle with a low AFC are refractory to FSH action, which could explain why ovarian function, responsiveness to gonadotropin stimulation and fertility are diminished in individuals with a low versus a high AFC. PMID:22281079

Scheetz, Danielle; Folger, Joseph K; Smith, George W; Ireland, James J

2012-01-01

15

FSH: One Hormone with Multiple Forms, or a Family of Multiple Hormones  

Microsoft Academic Search

Follicle stimulating hormone (FSH) is produced within pituitary gonadotroph cells and is a critical component of the reproductive\\u000a process. It has a wide variety of activities in both male and female reproductive tissues including growth, division, and\\u000a differentiation of Sertoli and granulosa cells. As a result, FSH is directly involved in the production of both male and female\\u000a gametes, as

Tim G. Rozell; Rena J. Okrainetz

16

Structural and functional characterisation of hFSH and hLH isoforms  

Microsoft Academic Search

Human follicle-stimulating hormone (hFSH) and luteinizing hormone (hLH) are gonadotropins which are secreted as multiple forms by the pituitary. Evidence supporting the structural and functional heterogeneity of 15 purified hFSH isoforms and 20 purified hLH isoforms from pituitary extracts will be presented. Gonadotropin isoforms were purified by a combination of preparative isoelectric focusing and ion-exhange chromatography. The protein mass of

P. G. Stanton; P. G. Burgon; M. T. W. Hearn; D. M. Robertson

1996-01-01

17

Pharmacokinetics and follicular dynamics of corifollitropin alfa versus recombinant FSH during ovarian stimulation for IVF.  

PubMed

A single injection of corifollitropin alfa can replace seven daily injections of recombinant FSH (rFSH) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection. This double-blind randomized controlled trial assessed the pharmacokinetics and pharmacodynamics of 150 ?g corifollitropin alfa versus daily 200 IU rFSH in 1509 patients. Comparative analyses were performed on serum concentrations of FSH immunoreactivity (pharmacokinetics), and the number and size of growing follicles, and inhibin B and oestradiol concentrations as biomarkers of ovarian response (pharmacodynamics). The rate of follicular development was similar in both treatment groups. By stimulation day 8, 33% of patients treated with corifollitropin alfa reached the criterion for human chorionic gonadotrophin (HCG) injection. The number of follicles ?11 mm was slightly higher after corifollitropin alfa compared with daily rFSH at stimulation day 8 (difference, 1.2; 95% confidence interval (Cl) 0.5-1.8; P < 0.01) and on the day of HCG injection (difference, 2.1; 95% Cl 1.4-2.8; P < 0.01). The rise of inhibin B and oestradiol concentrations was similar in both treatment groups. Although the pharmacokinetics of corifollitropin alfa and rFSH are quite different their pharmacodynamic profiles at the dosages used are similar. PMID:21575846

Fauser, Bart C J M; Alper, Michael M; Ledger, William; Schoolcraft, William B; Zandvliet, Anthe; Mannaerts, Bernadette M J L

2011-02-01

18

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

PubMed Central

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

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

2014-01-01

19

Expression of FSH receptor in the hamster ovary during perinatal development.  

PubMed

FSH plays an important role in ovarian follicular development, and it functions via the G-protein coupled FSH receptor. The objectives of the present study were to determine if full-length FSHR mRNA and corresponding protein were expressed in fetal through postnatal hamster ovaries to explain the FSH-induced primordial follicle formation, and if FSH or estrogen (E) would affect the expression. A full-length and two alternately spliced FSHR transcripts were expressed from E14 through P20. The level of the full-length FSHR mRNA increased markedly through P7 before stabilizing at a lower level with the formation and activation of primordial follicles. A predicted 87?kDa FSHR protein band was detected in fetal through P4 ovaries, but additional bands appeared as ovary developed. FSHR immunosignal was present in undifferentiated somatic cells and oocytes in early postnatal ovaries, but was granulosa cells specific after follicles formed. Both eCG and E significantly up-regulated full-length FSHR mRNA levels. Therefore, FSHR is expressed in the hamster ovary from the fetal life to account for FSH-induced primordial follicle formation and cAMP production. Further, FSH or E regulates the receptor expression. PMID:25462586

Chakraborty, Prabuddha; Roy, Shyamal K

2015-01-15

20

Evaluation of the role of FSH in regulation of Leydig cell function during different stages of its differentiation.  

PubMed

The role of follicle stimulating hormone (FSH) in Leydig cell function was evaluated by a passive neutralization approach at different stages of Leydig cell development. Neutralization of endogenous FSH in neonatal rats (10-day-old) resulted in reduction of testes weight, however the testicular testosterone levels and in vitro testosterone production by purified Leydig cells were elevated. Administration of FSH antiserum to immature (25-28-day-old) and adult (90-day-old) rats did not have any effect on testes weight, serum testosterone and testicular testosterone. Interestingly, there was a significant reduction in testosterone production by isolated Leydig cells under hCG stimulated and 22-R-hydroxycholesterol (22-R-OH CHOL) saturated conditions. In support of this observation administration of recombinant FSH to immature and adult rats resulted in significant increase in testosterone production by Leydig cells following incubations in presence of hCG and saturating concentrations of 22-R-OH CHOL, although there was no change in serum and testicular testosterone levels. The role of FSH in immature rats was also confirmed employing FSH receptor antiserum which was raised against the unique domains of FSH receptor. RT-PCR analysis revealed a significant reduction in the mRNA levels of StAR and IGF-1 following blockade of FSH action by FSH receptor antiserum. The results of our studies suggest a stage specific function for FSH in regulation of Leydig cell development by modulating the LH responsiveness and steroidogenesis. PMID:15353182

Sriraman, Venkataraman; Jagannadha Rao, A

2004-09-30

21

Blocking antibody to the ?-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis  

PubMed Central

Low estrogen levels undoubtedly underlie menopausal bone thinning. However, rapid and profuse bone loss begins 3 y before the last menstrual period, when serum estrogen is relatively normal. We have shown that the pituitary hormone FSH, the levels of which are high during late perimenopause, directly stimulates bone resorption by osteoclasts. Here, we generated and characterized a polyclonal antibody to a 13-amino-acid-long peptide sequence within the receptor-binding domain of the FSH ?-subunit. We show that the FSH antibody binds FSH specifically and blocks its action on osteoclast formation in vitro. When injected into ovariectomized mice, the FSH antibody attenuates bone loss significantly not only by inhibiting bone resorption, but also by stimulating bone formation, a yet uncharacterized action of FSH that we report herein. Mesenchymal cells isolated from mice treated with the FSH antibody show greater osteoblast precursor colony counts, similarly to mesenchymal cells isolated from FSH receptor (FSHR)?/? mice. This suggests that FSH negatively regulates osteoblast number. We confirm that this action is mediated by signaling-efficient FSHRs present on mesenchymal stem cells. Overall, the data prompt the future development of an FSH-blocking agent as a means of uncoupling bone formation and bone resorption to a therapeutic advantage in humans. PMID:22908268

Zhu, Ling-Ling; Blair, Harry; Cao, Jay; Yuen, Tony; Latif, Rauf; Guo, Lida; Tourkova, Irina L.; Li, Jianhua; Davies, Terry F.; Sun, Li; Bian, Zhuan; Rosen, Clifford; Zallone, Alberta; New, Maria I.; Zaidi, Mone

2012-01-01

22

Premature Luteinization in In Vitro Fertilization Cycles Using Gonadotropin-Releasing Hormone Agonist (GnRH-a) and Recombinant Follicle-Stimulating Hormone (FSH) and GnRH-a and Urinary FSH  

Microsoft Academic Search

Objective: To determine if premature luteinization can occur in GnRH agonist (GnRH-a) and FSH (recombinant FSH and human urinary FSH) IVF cycles and whether premature luteinization affects IVF and clinical outcome.Design: Retrospective evaluation of 171 IVF-ET cycles. The cycles were divided into two groups according to the P level on the day of hCG: group I (serum P ? 0.9

Filippo Ubaldi; Michel Camus; Johan Smitz; Herjan J. T Coelingh Bennink; André Van Steirteghem; Paul Devroey

1998-01-01

23

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

PubMed Central

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

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

24

The BET protein FSH functionally interacts with ASH1 to orchestrate global gene activity in Drosophila  

PubMed Central

Background The question of how cells re-establish gene expression states after cell division is still poorly understood. Genetic and molecular analyses have indicated that Trithorax group (TrxG) proteins are critical for the long-term maintenance of active gene expression states in many organisms. A generally accepted model suggests that TrxG proteins contribute to maintenance of transcription by protecting genes from inappropriate Polycomb group (PcG)-mediated silencing, instead of directly promoting transcription. Results and discussion Here we report a physical and functional interaction in Drosophila between two members of the TrxG, the histone methyltransferase ASH1 and the bromodomain and extraterminal family protein FSH. We investigated this interface at the genome level, uncovering a widespread co-localization of both proteins at promoters and PcG-bound intergenic elements. Our integrative analysis of chromatin maps and gene expression profiles revealed that the observed ASH1-FSH binding pattern at promoters is a hallmark of active genes. Inhibition of FSH-binding to chromatin resulted in global down-regulation of transcription. In addition, we found that genes displaying marks of robust PcG-mediated repression also have ASH1 and FSH bound to their promoters. Conclusions Our data strongly favor a global coactivator function of ASH1 and FSH during transcription, as opposed to the notion that TrxG proteins impede inappropriate PcG-mediated silencing, but are dispensable elsewhere. Instead, our results suggest that PcG repression needs to overcome the transcription-promoting function of ASH1 and FSH in order to silence genes. PMID:23442797

2013-01-01

25

Genetic Analysis of Zebrafish Gonadotropin (FSH and LH) Functions by TALEN-Mediated Gene Disruption.  

PubMed

Vertebrate reproduction is controlled by two gonadotropins (FSH and LH) from the pituitary. Despite numerous studies on FSH and LH in fish species, their functions in reproduction still remain poorly defined. This is partly due to the lack of powerful genetic approaches for functional studies in adult fish. This situation is now changing with the emergence of genome-editing technologies, especially Transcription Activator-Like Effector Nuclease (TALEN) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR). In this study, we deleted the hormone-specific ?-genes of both FSH and LH in the zebrafish using TALEN. This was followed by a phenotype analysis for key reproductive events, including gonadal differentiation, puberty onset, gametogenesis, final maturation, and fertility. FSH-deficient zebrafish (fshb(-/-)) were surprisingly fertile in both sexes; however, the development of both the ovary and testis was significantly delayed. In contrast, LH-deficient zebrafish (lhb(-/-)) showed normal gonadal growth, but the females failed to spawn and were therefore infertile. Using previtellogenic follicles as the marker, we observed a significant delay of puberty onset in the fshb mutant but not the lhb mutant females. Interestingly, FSH seemed to play a role in maintaining the female status because we repeatedly observed sexual reversal in the fshb mutant. Neither the fshb nor lhb mutation alone seemed to affect gonadal differentiation; however, the double mutation of the two genes led to all males, although the development of the testis was significantly delayed. In summary, our data confirmed some well-known functions of FSH and LH in fish while also providing evidence for novel functions, which would be difficult to reveal using traditional biochemical and physiological approaches. PMID:25396299

Zhang, Zhiwei; Zhu, Bo; Ge, Wei

2015-01-01

26

Expression Profiles of Fsh-Regulated Ovarian Genes during Oogenesis in Coho Salmon  

PubMed Central

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. PMID:25485989

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

2014-01-01

27

Comparison of highly purified urinary versus recombinant FSH: Effect on ART outcomes in polycystic ovary syndrome  

PubMed Central

Background: Polycystic ovary syndrome (PCOS) is a common cause of ovulatory disorders and infertility with high LH to FSH ratio. In order to prevent further increase of LH and follicle atresia, different regimens for ovulation induction have been recommended using FSH alone. Objective: This study was performed in PCOS patients to compare ART outcomes in cycles induced by FSH alone, using either recombinant or urinary products. Materials and Methods: In a randomized trial, from 623 patients who underwent down regulation with GnRH analogue in a long protocol, 160 PCOS patients were randomly divided into two groups of 80. Group A received 150 IU/d recombinant FSH (Gonal-F) and group B 150 IU/d urinary FSH (Fostimon). Results: 33 cases (41.2%) in group A and 36 (45%) in group B achieved clinical pregnancy, which was not significantly different (p=0.67). Total number of oocytes retrieved (13.03±5.56 vs. 14.17±4.89, p=0.17), quality and number of embryos (7.42±3.35 vs. 7.63±3.28, p=0.68) and OHSS rate were similar in group A compared to group B. Endometrial thickness which was 9.66±1.67 mm in group A and 10.36±1.35 mm in group B, showed a significant difference (p=0.004). Conclusion: It seems that in PCOS patients, both pure FSH products used for controlled ovarian hyperstimulation have similar effects on ART outcome and can be used according to availability and patient acceptance without significant difference. PMID:25242998

Sohrabvand, Farnaz; Sheikhhassani, Shahrzad; Bagheri, Maryam; Haghollahi, Fedyeh; Shabihkhani, Maryam; Shariat, Mamak; Nasr Esfahani, Manijeh

2012-01-01

28

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

PubMed

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. PMID:23803162

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

2014-05-01

29

Synthetic releasing hormones LH/FSH-RH and LH-RH : effect of intracerebral and intramuscular injections on female carp  

E-print Network

of synthetic LH/FSH-RH at a dose of1[Jog/kg of body weight proved effective in accelerating oocyte maturity injections on female carp (Cyprinus carpio L.) maturation Miroslawa SOKOLOWSKA W. POPEK K. BIENIARZ Institute and intramuscular injections of synthetic LH/FSH-RH on the maturation of female carp was investigated. The results

Paris-Sud XI, Université de

30

Cloning and gene expression of a cDNA for the chicken follicle-stimulating hormone (FSH)-beta-subunit.  

PubMed

Follicle-stimulating hormone (FSH) is a member of pituitary glycoprotein hormones that are composed of two dissimilar subunits, alpha and beta. Very little information is available regarding the nucleotide and amino acid sequence of FSH-beta in avian species. For better understanding of the phylogenic diversity and evolution of FSH molecule, we have isolated and sequenced the complete complementary DNA (cDNA) encoding chicken FSH-beta precursor molecule by reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA end (RACE) methods. The cloned chicken FSH-beta cDNA consists of 2457-bp nucleotides, including 44-bp nucleotides of the 5'-untranslated region (UTR), 396 bp of the open reading frame, and an extraordinarily long 3'-UTR of 2001-bp nucleotides followed by a poly(A)((16)) tail. It encodes a 131-amino-acid precursor molecule of FSH-beta-subunit with a signal peptide of 20 amino acids followed by a mature protein of 111 amino acids. Twelve cysteine residues, forming six disulfide bonds within beta-subunit and two putative asparagine-linked glycosylation sites, are also conserved in the chicken FSH-beta-subunit. Four proline residues, presumably responsible for changing the backbone direction of protein structure, are conserved in chicken FSH-beta-subunit as well. The nucleotide sequence of chicken FSH-beta cDNA shows high homology with quail FSH-beta cDNA, 97% homology in the open reading frame, and 85% homology in the 3'-UTR. The deduced amino acid sequence of chicken FSH-beta-subunit shows a remarkable similarity to other avian FSH-beta-subunits, 98% homology with quail, and 93% homology with ostrich, whereas a lower similarity (66 to 70%) is noted when compared with mammalian FSH-beta-subunits. By contrast, when comparing with the beta-subunits of chicken luteinizing hormone and thyroid-stimulating hormone, the homologies are as low as 37 and 40%, respectively. FSH-beta mRNA was only expressed in pituitary gland out of various tissues examined and can be up-regulated by gonadotropin-releasing hormone in pituitary tissue culture as estimated by real-time quantitative PCR. PMID:11884082

Shen, San-Tai; Yu, John Yuh-Lin

2002-02-15

31

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

PubMed Central

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. PMID:16827936

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

2006-01-01

32

GnRH Pulse Frequency-Dependent Stimulation of FSH? Transcription Is Mediated via Activation of PKA and CREB  

PubMed Central

Expression of pituitary FSH and LH, under the control of pulsatile GnRH, is essential for fertility. cAMP response element-binding protein (CREB) has been implicated in the regulation of FSH? gene expression, but the molecular mechanisms by which pulsatile GnRH regulates CREB activation remain poorly understood. We hypothesized that CREB is activated by a distinct signaling pathway in response to pulsatile GnRH in a frequency-dependent manner to dictate the FSH? transcriptional response. GnRH stimulation of CREB phosphorylation (pCREB) in the gonadotrope-derived L?T2 cell line was attenuated by a protein kinase A (PKA) inhibitor, H89. A dominant negative PKA (DNPKA) reduced GnRH-stimulated pCREB and markedly decreased GnRH stimulation of FSH? mRNA and FSH?LUC activity, but had little effect on LH?LUC activity, indicating relative specificity of this pathway. In perifusion studies, FSH? mRNA levels and FSH?LUC activities were increased by pulsatile GnRH, with significantly greater increases at low compared with high pulse frequencies. DNPKA markedly reduced these GnRH-stimulated FSH? responses at both low and high pulse frequencies. Correlating with FSH? activation, both PKA activity and levels of pCREB were increased to a greater extent by low compared with high GnRH pulse frequencies, and the induction of pCREB was also attenuated by overexpression of DNPKA at both low and high pulse frequencies. Taken together, these data indicate that a PKA-mediated signaling pathway mediates GnRH activation of CREB at low-pulse frequencies, playing a significant role in the decoding of the hypothalamic GnRH signal to result in frequency-dependent FSH? activation. PMID:23393127

Thompson, Iain R.; Ciccone, Nick A.; Xu, Shuyun; Zaytseva, Sofiya; Carroll, Rona S.

2013-01-01

33

Comparisons of estradiol, LH and FSH patterns in pregnant and nonpregnant beagle bitches  

Microsoft Academic Search

To characterize plasma estradiol, LH and FSH patterns of secretion during the bitch estrous cycle, blood samples were obtained daily from 15 days before until 135 days after the LH surge in 10 pregnant and 10 nonpregnant beagle bitches. After an initial increase between days 15 and 10 and an expected proestrous peak, estradiol concentrations increased again from days 9–12

K. Onclin; B. Murphy; J. P. Verstegen

2002-01-01

34

Fsh Controls Gene Expression in Fish both Independently of and through Steroid Mediation  

E-print Network

for genes encoding key factors of steroidogenesis (star, hsd3b1, cyp11b2-2) or for genes of the Igf system interaction with their cognate receptors present on the Leydig cells. In this context, it is crucial due to the exclusive presence of FSH receptors in the seminiferous epithelium, mostly on Sertoli cells

Paris-Sud XI, Université de

35

Progesterone, estrogen, LH, FSH and PRL concentrations in plasma during the estrous cycle in goat  

E-print Network

Progesterone, estrogen, LH, FSH and PRL concentrations in plasma during the estrous cycle in goat G in plasma were measured in 7 goats by RIA. Mean progesterone level was 0.0-0.8 ng/ml in estrus and 1-4 ng were seen around estrus. Introduction. Studies on hormonal control of the estrous cycle in the goat

Paris-Sud XI, Université de

36

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

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 1.01–1.67; ITT population); the observed difference was more pronounced in poor responders. Conclusions These data suggest that there is a relative increase in the clinical pregnancy rates of 9% in the overall population and 30% in poor responders. In conclusion, this meta-analysis suggests that the addition of r-hLH to r-hFSH may be beneficial for women with POR. PMID:24555766

2014-01-01

37

Roles of binding elements, FOXL2 domains, and interactions with cJUN and SMADs in regulation of FSH?.  

PubMed

We previously identified FOXL2 as a critical component in FSH? gene transcription. Here, we show that mice deficient in FOXL2 have lower levels of gonadotropin gene expression and fewer LH- and FSH-containing cells, but the same level of other pituitary hormones compared to wild-type littermates, highlighting a role of FOXL2 in the pituitary gonadotrope. Further, we investigate the function of FOXL2 in the gonadotrope cell and determine which domains of the FOXL2 protein are necessary for induction of FSH? transcription. There is a stronger induction of FSH? reporter transcription by truncated FOXL2 proteins, but no induction with the mutant lacking the forkhead domain. Specifically, FOXL2 plays a role in activin induction of FSH?, functioning in concert with activin-induced SMAD proteins. Activin acts through multiple promoter elements to induce FSH? expression, some of which bind FOXL2. Each of these FOXL2-binding sites is either juxtaposed or overlapping with a SMAD-binding element. We determined that FOXL2 and SMAD4 proteins form a higher order complex on the most proximal FOXL2 site. Surprisingly, two other sites important for activin induction bind neither SMADs nor FOXL2, suggesting additional factors at work. Furthermore, we show that FOXL2 plays a role in synergistic induction of FSH? by GnRH and activin through interactions with the cJUN component of the AP1 complex that is necessary for GnRH responsiveness. Collectively, our results demonstrate the necessity of FOXL2 for proper FSH production in mice and implicate FOXL2 in integration of transcription factors at the level of the FSH? promoter. PMID:25105693

Roybal, Lacey L; Hambarchyan, Arpi; Meadows, Jason D; Barakat, Nermeen H; Pepa, Patricia A; Breen, Kellie M; Mellon, Pamela L; Coss, Djurdjica

2014-10-01

38

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

PubMed Central

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 ?-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 ?-subunit of hFSH under a Lansbury aspartylation protocol. The proposed strategy for incorporating the prepared N-linked dodecasaccharide-containing 20–27aa domain into ?-hFSH subunit was validated in the context of a model system providing, protected ?-hFSH subunit functionalized with chitobiose at positions 7 and 24. PMID:19341309

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

2009-01-01

39

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

PubMed

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/EBP?, ?, ? and ? 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. PMID:24514953

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

2014-04-01

40

ParAB-mediated intermolecular association of plasmid P1 parS sites.  

PubMed

The P1 plasmid partition system depends on ParA-ParB proteins acting on centromere-like parS sites for a faithful plasmid segregation during the Escherichia coli cell cycle. In vivo we placed parS into host E. coli chromosome and on a Sop(+) F plasmid and found that the stability of a P1 plasmid deleted for parA-parB could be partially restored when parB was expressed in trans. In vitro, parS, conjugated to magnetic beads could capture free parS DNA fragment in presence of ParB. In vitro, ParA stimulated ParB-mediated association of intermolecular parS sites in an ATP-dependent manner. However, in the presence of ADP, ParA reduced ParB-mediated pairing to levels below that seen by ParB alone. ParB of P1 pairs the parS sites of plasmids in vivo and fragments in vitro. Our findings support a model whereby ParB complexes P1 plasmids, ParA-ATP stimulates this interaction and ParA-ADP inhibits ParB pairing activity in a parS-independent manner. PMID:22018490

Kaur, Tranum; Al Abdallah, Qusai; Nafissi, Nafiseh; Wettig, Shawn; Funnell, Barbara E; Slavcev, Roderick A

2011-12-20

41

FSHR polymorphism p.N680S mediates different responses to FSH in vitro.  

PubMed

The single nucleotide polymorphism p.N680S of the follicle-stimulating hormone (FSH) receptor (FSHR) is a discrete marker of ovarian response but previous in vitro studies failed to demonstrate differences in the response to FSH between N and S carrier cells. Here we demonstrate that p.N680S mediates different kinetics of the response to FSH in vitro. Intracellular cAMP production is faster in p.N680S N than in S homozygous human granulosa cells (45 versus 90 min to achieve the plateau, respectively; Mann-Whitney's U-test; p < 0.005; n = 4). Reflecting the cAMP kinetics, phospho-ERK1/2 and -CREB activation, AREG and STARD1 gene expressions and progesterone production were qualitatively and quantitatively different in N versus S homozygous cells. Finally, the blockade of ERK pathway by U0126 abolishes the genotype-mediated different effects on gene expression and progesterone production (Mann-Whitney's U-test; p ? 0.005; n = 3). PMID:24970684

Casarini, Livio; Moriondo, Valeria; Marino, Marco; Adversi, Francesca; Capodanno, Francesco; Grisolia, Chiarina; La Marca, Antonio; La Sala, Giovanni Battista; Simoni, Manuela

2014-08-01

42

LH concentrations do not correlate with pregnancy in rFSH/GnRH antagonist cycles.  

PubMed

The possible relationship between endogenous LH concentrations and clinical outcome was evaluated in 750 patients treated with a standardized gonadotrophin-releasing hormone (GnRH) antagonist and recombinant FSH (rFSH)-only protocol. Serum LH concentrations were measured during stimulation by a central laboratory and patients were stratified into quantiles of P75. The P25 values were 3.38 IU/l, 0.93 IU/l, and 0.91 IU/l on stimulation days 1, 5, and 8, respectively. The ongoing pregnancy rates per started cycle of patients within the P75 subsets and ranged in the various subsets between 35.0% and 39.5%. In keeping with previous, smaller studies, these findings demonstrate that in good prognosis, non-obese patients endogenous LH in a GnRH antagonist protocol is able to support treatment with rFSH only. PMID:20133200

Doody, Kevin; Devroey, Paul; Gordon, Keith; Witjes, Han; Mannaerts, Bernadette

2010-04-01

43

GnRH pulse frequency-dependent differential regulation of LH and FSH gene expression.  

PubMed

The pituitary gonadotropin hormones, FSH and LH, are essential for fertility. Containing an identical ?-subunit (CGA), they are comprised of unique ?-subunits, FSH? and LH?, respectively. These two hormones are regulated by the hypothalamic decapeptide, GnRH, which is released in a pulsatile manner from GnRH neurons located in the hypothalamus. Varying frequencies of pulsatile GnRH stimulate distinct signaling pathways and transcriptional machinery after binding to the receptor, GnRHR, on the cell surface of anterior pituitary gonadotropes. This ligand-receptor binding and activation orchestrates the synthesis and release of FSH and LH, in synergy with other effectors of gonadotropin production, such as activin, inhibin and steroids. Current research efforts aim to discover the mechanisms responsible for the decoding of the GnRH pulse signal by the gonadotrope. Modulating the response to GnRH has the potential to lead to new therapies for patients with altered gonadotropin secretion, such as those with hypothalamic amenorrhea or polycystic ovarian syndrome. PMID:24056171

Thompson, Iain R; Kaiser, Ursula B

2014-03-25

44

PKC? and ? possibly mediate FSH-induced mouse oocyte maturation via NOX-ROS-TACE cascade signaling pathway.  

PubMed

In mammals, gonadotropins stimulate oocyte maturation via the epidermal growth factor (EGF) network, and the protein kinase C (PKC) signaling pathway mediates this process. Tumor necrosis factor-? converting enzyme (TACE) is an important protein responding to PKC activation. However, the detailed signaling cascade between PKC and TACE in follicle-stimulating hormone (FSH)-induced oocyte maturation in vitro remains unclear. In this study, we found that rottlerin (mallotoxin, MTX), the inhibitor of PKC ? and ?, blocked FSH-induced maturation of mouse cumulus-oocyte complexes (COCs) in vitro. We further clarified the relationship between two molecules downstream of PKC ? and ? and TACE in COCs: nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and its products, reactive oxygen species (ROS). We proved that the respective inhibitors of NOX, ROS and TACE could block FSH-stimulated oocyte maturation dose-dependently, but these inhibitory effects could be reversed partially by amphiregulin (Areg), an EGF family member. Notably, inhibition of PKC ? and ? prevented FSH-induced translocation of two cytosolic components of NOX, p47phox and p67phox, to the plasma membrane in cumulus cells. Moreover, FSH-induced TACE activity in cumulus cells was decreased markedly by inhibition of NOX and ROS. In conclusion, PKC ? and ? possibly mediate FSH-induced meiotic resumption in mouse COCs via NOX-ROS-TACE signaling pathway. PMID:25350560

Chen, Qian; Zhang, Wenqiang; Ran, Hao; Feng, Lizhao; Yan, Hao; Mu, Xinyi; Han, Yingying; Liu, Wei; Xia, Guoliang; Wang, Chao

2014-01-01

45

Molecular cloning of follicle-stimulating hormone (FSH)-beta subunit cDNA from duck pituitary.  

PubMed

We have cloned FSH-beta cDNA from duck pituitary gland by reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA end (RACE) methods. The cloned duck FSH-beta cDNA contains 1909-bp nucleotides including 396-bp of open-reading frame and 1491-bp of 3'-untranslational region. The open-reading frame encodes a 131-amino acid protein with a putative 20-amino acid signal peptide and a putative 111-amino acid mature protein. The deduced amino acid sequence shows a remarkable similarity (94-98%) to those of other avian FSH-beta subunits; while it exhibits lower similarities with those of turtles (82-84%), mammals (63-71%), and amphibians (53-57%). The structural model analysis of duck FSH suggests that the cysteine-knot and beta-strands for maintaining the specific structural frame, and the "seat-belt" loop for specific binding to FSH receptor have been conserved in tetrapodian FSH-betas. PMID:16674957

Shen, San-Tai; Cheng, Yi-Sheng; Shen, Tzu-Yun; Yu, John Yuh-Lin

2006-09-15

46

Trisomic pregnancy and elevated FSH: implications for the oocyte pool hypothesis  

PubMed Central

BACKGROUND Some studies, but not all, support the hypothesis that trisomy frequency is related to the size of the oocyte pool, with the risk increased for women with fewer oocytes (older ovarian age). We tested this hypothesis by comparing hormonal indicators of ovarian age among women who had trisomic pregnancy losses with indicators among women with non-trisomic losses or chromosomally normal births. The three primary indicators of advanced ovarian age were low level of anti-Müllerian hormone (AMH), high level of follicle-stimulating hormone (FSH) and low level of inhibin B. METHODS The analysis drew on data from two hospital-based case–control studies. Data were analyzed separately and the evidence from the two sites was combined. We compared 159 women with trisomic pregnancy losses to three comparison groups: 60 women with other chromosomally abnormal losses, 79 women with chromosomally normal losses and 344 women with live births (LBs) age-matched to women with losses. We analyzed the hormone measures as continuous and as categorical variables. All analyses adjust for age in single years, day of blood draw, interval in storage and site. RESULTS AMH and inhibin B did not differ between women with trisomic losses and any of the three comparison groups. Mean ln(FSH) was 0.137 units (95% confidence interval (CI): 0.055, 0.219) higher for trisomy cases compared with LB controls; it was also higher, though not significantly so, for trisomy cases compared with women with other chromosomally abnormal losses or chromosomally normal losses. The adjusted odds ratio in relation to high FSH (?10 mIU/ml) was significantly increased for trisomy cases versus LB controls (adjusted odds ratio (OR): 3.8, 95% CI: 1.6, 8.9). CONCLUSIONS The association of trisomy with elevated FSH is compatible with the oocyte pool hypothesis, whereas the absence of an association with AMH is not. Alternative interpretations are considered, including the possibility that elevated FSH may disrupt meiotic processes or allow recruitment of abnormal follicles. PMID:21467203

Kline, J.K.; Kinney, A.M.; Levin, B.; Kelly, A.C.; Ferin, M.; Warburton, D.

2011-01-01

47

Reactive oxygen species regulate FSH-induced expression of vascular endothelial growth factor via Nrf2 and HIF1? signaling in human epithelial ovarian cancer.  

PubMed

Follicle-stimulating hormone (FSH) and the FSH receptor contribute to tumor angiogenesis and are acknowledged risk factors for ovarian epithelial cancer (OEC). Accumulating evidence suggests that FSH can induce vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1? (HIF1?) expression. We previously demonstrated that FSH induces reactive oxygen species (ROS) production and activates Nrf2 signaling. This study was performed to investigate whether FSH induces VEGF expression via a ROS-mediated Nrf2 signaling pathway. In the current study, OET cells were treated with FSH; dichlorofluorescein staining was used to determine ROS generation, western blotting was used to quantify Nrf2 expression and VEGF expression was measured using an ELISA. Nrf2 and HIF1? were knocked down using siRNAs to investigate the role of the Nrf2 and HIF1? signaling pathways in FSH-induced VEGF expression. The chromatin immunoprecipitation assay (ChIP) was used to determine HIF1? binding to the VEGF promoter. Finally, it was found that FSH induced ROS production and activated Nrf2 signaling; elimination of ROS or knockdown of Nrf2 blocked FSH-induced VEGF expression. Knockdown of Nrf2 impaired HIF1? signaling activation. Blockage of the FSH-ROS-Nrf2-HIF1? signaling pathway attenuated FSH-induced binding of HIF1? to the VEGF promoter. Collectively, this study indicates that ROS and aberrant expression of Nrf2 play an important role in FSH-induced angiogenesis in OEC, and provides insight into the mechanisms of FSH-induced VEGF expression. Elimination of ROS or inhibition of Nrf2 may represent potential therapeutic targets for the treatment of ovarian cancer. PMID:23404377

Zhang, Zhenbo; Wang, Qianqian; Ma, Jie; Yi, Xiaofang; Zhu, Yaping; Xi, Xiaowei; Feng, Youji; Jin, Zhijun

2013-04-01

48

BERKELEY PAR LABBERKELEY PAR LAB Where we ended up  

E-print Network

, David Wessel, and Kathy Yelick UC Berkeley Par Lab End-of-Project Party May 30, 2013 #12;BERKELEY PAR LAB Par Lab Timeline 2 Initial Meetings "Berkeley View" Techreport Win UPCRC Competition UPCRC PhaseBERKELEY PAR LABBERKELEY PAR LAB Par Lab: Where we ended up Krste Asanovic, Ras Bodik, Jim Demmel

California at Berkeley, University of

49

FSH-FSHR3-stem cells in ovary surface epithelium: basis for adult ovarian biology, failure, aging, and cancer.  

PubMed

Despite extensive research, genetic basis of premature ovarian failure (POF) and ovarian cancer still remains elusive. It is indeed paradoxical that scientists searched for mutations in FSH receptor (FSHR) expressed on granulosa cells, whereas more than 90% of cancers arise in ovary surface epithelium (OSE). Two distinct populations of stem cells including very small embryonic-like stem cells (VSELs) and ovarian stem cells (OSCs) exist in OSE, are responsible for neo-oogenesis and primordial follicle assembly in adult life, and are modulated by FSH via its alternatively spliced receptor variant FSHR3 (growth factor type 1 receptor acting via calcium signaling and the ERK/MAPK pathway). Any defect in FSH-FSHR3-stem cell interaction in OSE may affect folliculogenesis and thus result in POF. Ovarian aging is associated with a compromised microenvironment that does not support stem cell differentiation into oocytes and further folliculogenesis. FSH exerts a mitogenic effect on OSE and elevated FSH levels associated with advanced age may provide a continuous trigger for stem cells to proliferate resulting in cancer, thus supporting gonadotropin theory for ovarian cancer. Present review is an attempt to put adult ovarian biology, POF, aging, and cancer in the perspective of FSH-FSHR3-stem cell network that functions in OSE. This hypothesis is further supported by the recent understanding that: i) cancer is a stem cell disease and OSE is the niche for ovarian cancer stem cells; ii) ovarian OCT4-positive stem cells are regulated by FSH; and iii) OCT4 along with LIN28 and BMP4 are highly expressed in ovarian cancers. PMID:25269615

Bhartiya, Deepa; Singh, Jarnail

2015-01-01

50

Effects of recombinant LH supplementation in women undergoing assisted reproduction with GnRH agonist down-regulation and stimulation with recombinant FSH: an opening study  

Microsoft Academic Search

Circulating endogenous concentrations of LH are reduced in women undergoing down-regulation with gonadotrophin-releasing hormone agonists (GnRHa) and ovarian stimulation with recombinant human FSH (r-hFSH). The effect of recombinant human LH (r-hLH) supplementation on ovarian response and pregnancy outcome was evaluated in a prospective randomized study (sealed envelopes) including 231 cycles. Normogonadotrophic women were stimulated with either r-hFSH or a combination

P Humaidan; M Bungum; L Bungum; C Yding Andersen

2004-01-01

51

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

PubMed

Gonadotropin-releasing hormone (GnRH) is secreted in brief pulses from the hypothalamus and regulates follicle-stimulating hormone ?-subunit (FSH?) gene expression in pituitary gonadotropes in a frequency-sensitive manner. The mechanisms underlying its preferential and paradoxical induction of FSH? by low frequency GnRH pulses are incompletely understood. Here, we identify growth differentiation factor 9 (GDF9) as a GnRH-suppressed autocrine inducer of FSH? gene expression. GDF9 gene transcription and expression were preferentially decreased by high frequency GnRH pulses. GnRH regulation of GDF9 was concentration-dependent and involved ERK and PKA. GDF9 knockdown or immunoneutralization reduced FSH? mRNA expression. Conversely, exogenous GDF9 induced FSH? expression in immortalized gonadotropes and in mouse primary pituitary cells. GDF9 exposure increased FSH secretion in rat primary pituitary cells. GDF9 induced Smad2/3 phosphorylation, which was impeded by ALK5 knockdown and by activin receptor-like kinase (ALK) receptor inhibitor SB-505124, which also suppressed FSH? expression. Smad2/3 knockdown indicated that FSH? induction by GDF9 involved Smad2 and Smad3. FSH? mRNA induction by GDF9 and GnRH was synergistic. We hypothesized that GDF9 contributes to a regulatory loop that tunes the GnRH frequency-response characteristics of the FSH? gene. To test this, we determined the effects of GDF9 knockdown on FSH? induction at different GnRH pulse frequencies using a parallel perifusion system. Reduction of GDF9 shifted the characteristic pattern of GnRH pulse frequency sensitivity. These results identify GDF9 as contributing to an incoherent feed-forward loop, comprising both intracellular and secreted components, that regulates FSH? expression in response to activation of cell surface GnRH receptors. PMID:24778184

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

2014-06-01

52

Crystalline dihydrotestosterone implants in the lateral septum of male rats. A positive effect on LH and FSH.  

PubMed

Previous investigations in our laboratory have shown that testosterone implanted into the lateral septum in male rats increases LH and FSH secretion. However, it was unclear whether the effect of testosterone was direct via androgen receptor, or indirect via the estrogen receptor after conversion by aromatization to estradiol. To answer this question, we implanted either testosterone or the non-aromatizable androgen 5 alpha-dihydrotestosterone (DHT), into the lateral septum of adult male rats and measured plasma levels of LH and FSH by radioimmunoassay 2 days after implantation. Both testosterone and DHT significantly increased the plasma LH and FSH concentrations. Mean concentration of LH in control animals was 0.21 +/- 0.06 ng/ml, a figure that increased to 0.7 +/- 0.12 and 0.55 +/- 0.1 ng/ml after DHT or testosterone implantation respectively. Mean concentration of FSH in control animals was 1.5 +/- 0.3 ng/ml; this figure increased to 3 +/- 0.3 and 2.9 +/- 0.3 ng/ml after DHT or testosterone implantation. Neither plasma DHT (64.0 +/- 5.6 vs. 52 +/- 5 ng/100ml) nor plasma testosterone levels (4.1 +/- 0.38 vs. 3.3 +/- 0.18 ng/ml) were significantly affected by the implants. We conclude that androgens independently of conversion to estrogen acting in the lateral septum facilitates the release of LH and FSH. PMID:11428719

Roca, G; Torres, J M; Ruiz, E; Ortega, E

2001-01-01

53

Recombinant LH administration in subsequent cycle after "unexpected" poor response to recombinant FSH monotherapy.  

PubMed

Abstract Poor ovarian response (POR) is most frequently linked to the condition known as diminished ovarian reserve, but it can also occur in the absence of pathological ovarian reserve tests ("unexpected" POR). Because possible explanations include theca cells function deficiency, our aim was to evaluate the effect of r-LH administration in "unexpected" poor responders. A retrospective, single-centre, cohort study was conducted on 65 patients with AMH >0.5?ng/ml and/or AFC >5 with POR in their first cycle. Patients underwent a second IVF cycle with same protocol (long- or antagonist) and same starting dose of r-FSH used in the first cycle, plus daily addiction of 150?IU of r-LH from day 1. Compared to the first cycle, r-LH addition in the second cycle determined an increase in number of oocytes retrieved (p?FSH starting dose, possibly due to an underlying occult theca cells deficiency. PMID:24968088

Papaleo, Enrico; Vanni, Valeria Stella; Viganò, Paola; La Marca, Antonio; Pagliardini, Luca; Vitrano, Rossella; Zanirato, Mara; Marsiglio, Elena; Privitera, Laura; Candiani, Massimo

2014-11-01

54

FSH different regimes affect the developmental capacity and cryotolerance of embryos derived from oocytes collected by ovum pick-up in donor sheep  

Microsoft Academic Search

The objective of the present study was to compare the developmental capacity of sheep oocytes obtained by OPU after two different ovarian stimulations, and cryotolerance to vitrification procedures of in vitro derived embryos after in vitro maturation, fertilisation and culture of these oocytes. Sheep were divided into three groups: (A) no treatment (control); (B) constant doses of FSH (FSH-c); (C)

F. Berlinguer; G. Leoni; L. Bogliolo; P. P. Pintus; I. Rosati; S. Ledda; S. Naitana

2004-01-01

55

Toward fully synthetic homogeneous beta-human follicle-stimulating hormone (beta-hFSH) with a biantennary N-linked dodecasaccharide. synthesis of beta-hFSH with chitobiose units at the natural linkage sites.  

PubMed

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 beta-domain of human Follicle-Stimulating Hormone (hFSH) are described. The synthesis highlights the use of the Sinay 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 the beta-subunit of hFSH under a Lansbury aspartylation protocol. The proposed strategy for incorporating the prepared N-linked dodecasaccharide-containing 20-27aa domain into beta-hFSH subunit was validated in the context of a model system, providing protected beta-hFSH subunit functionalized with chitobiose at positions 7 and 24. PMID:19341309

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

2009-04-29

56

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

PubMed

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. PMID:23515285

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

57

Effects of injections and/or subcutaneous implants of melatonin on pituitary and plasma levels of LH, FSH and PRL  

E-print Network

gland while pituitary PRL levels fell. Plasma levels of LH and FSH also rose while PRL titers remainedEffects of injections and/or subcutaneous implants of melatonin on pituitary and plasma levels. After 56 days of treatment the animals were killed and pituitary and plasma levels of luteinizing

Paris-Sud XI, Université de

58

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

SciTech Connect

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.

Bruheim, Kjersti [Cancer Center, Ullevaal University Hospital, Oslo (Norway)], E-mail: Kjersti.Bruheim@medisin.uio.no; Svartberg, Johan [Institute of Clinical Medicine, University of Tromso, Tromso (Norway); Department of Medicine, University Hospital of North Norway, Tromso (Norway); Carlsen, Erik [Department of Gastrointestinal Surgery, Ullevaal University Hospital, Oslo (Norway); Dueland, Svein [Department of Oncology, Norwegian Radium Hospital, Oslo (Norway); Haug, Egil [Hormone Laboratory, Aker University Hospital, Oslo (Norway); Skovlund, Eva [School of Pharmacy, University of Oslo, Oslo (Norway); Tveit, Kjell Magne; Guren, Marianne G. [Cancer Center, Ullevaal University Hospital, Oslo (Norway)

2008-03-01

59

Effects and Interactions of Tachykinins and Dynorphin on FSH and LH Secretion in Developing and Adult Rats.  

PubMed

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 ?-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 ?-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 KNDy node and related factors (ie, other tachykinins) differentially participate in the control of gonadotropins at different stages of rat postnatal maturation. PMID:25490143

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

60

Recombinant FSH-induced follicle development in immature rats treated with an LHRH antagonist:a direct effect of RU486 on follicular atresia.  

PubMed

To investigate whether the progesterone antagonist RU486 has a direct effect on ovarian function, it was administered to immature female rats rendered hypogonadotrophic by administration of an LHRH antagonist and in which follicle development was stimulated by recombinant human FSH (recFSH). In the first experiments the effects of LHRH antagonist and recFSH on follicle growth were evaluated. Female rats of 22 days of age were injected with an LHRH antagonist (Org 30276; 500 micrograms/100 g body weight) every other day. This treatment resulted in a tenfold decrease in serum LH concentrations and a twofold decrease in serum FSH concentrations at day 30 and caused a reduction in the number and size of antral follicles. Treatment with recFSH (Org 32489) twice daily from day 26 for 4 days in a total dose ranging from 5 to 20 IU/animal increased the number and size of antral follicles in a dose-related manner and resulted after 20 IU recFSH in a tenfold increase in the concentration of inhibin in serum and ovaries at day 30. Once it was established that LHRH antagonist treatment in immature rats could be used to study the effects of gonadotrophins or steroids on follicle function, this animal model was used to study the effects of RU486 on the ovary. RU486 was administered (twice daily for 4 days, 1 mg/injection) to LHRH antagonist-treated rats in which follicular growth and differentiation were stimulated by 10 IU recFSH or by 10 IU recFSH plus 0.5 IU human chorionic gonadotrophin (hCG). RU486 had no effect on circulating levels of LH and FSH, but stimulated follicular atresia both in rats treated with recFSH alone and in rats treated with recFSH and hCG. Inhibin concentrations both in serum and ovaries were significantly increased after hCG treatment. RU486, however, did not increase inhibin in the rats treated with recFSH and in those treated with recFSH and hCG. In summary, the present study has demonstrated that (1) immature rats treated with an LHRH antagonist can be used to study the effects of gonadotrophins and steroids on follicular function and (2) RU486 has a direct stimulatory effect on follicular atresia. PMID:8708566

Uilenbroek, J T; Kramer, P; van Leeuwen, E C; Karels, B; Timmerman, M A; de Jong, F H; de Leeuw, R

1996-07-01

61

Involvement of rat gonadotrope progesterone receptor in the ovary-mediated inhibitory action of FSH on LH synthesis.  

PubMed

Rat ovaries stimulated with human follicle-stimulating hormone (hFSH) overexpress a factor that attenuates the LH surge in the rat: the putative gonadotropin surge-attenuating factor (GnSAF). A reduced gondadotrope progesterone receptor (PR) phosphorylation/activation is likely to be the main causative factor involved in GnSAF bioactivity on LH release. Besides, GnSAF reduces LH synthesis as well as LH secretion, and it is not known whether PR is involved in the inhibitory action of GnSAF on LH synthesis. Thus, the purpose of the present work was to evaluate the involvement of PR in the inhibitory effects of GnSAF on LH synthesis in cycling rats. To this end we used a specific radioimmunoassay and reverse transcription-polymerase chain reaction (RT-PCR) to study the effect on LH pituitary content and LH? mRNA expression of PR occupancy with P (3 mg/0.2 ml oil in diestrus) on the inhibitory effects of hFSH (0, 0.1, 1, and 10 IU) in metestrus (day 2) and diestrus (day 3) on LH synthesis on proestrus in intact and on day 4 in day 2 ovariectomized (OVX) rats injected with 5 and 10 ?g of estradiol benzoate (EB) on days 2 and 3, respectively. Results showed that (1) hFSH decreased pituitary LH content in intact, but not in OVX rats injected with EB, without affecting LH? mRNA levels, and (2) PR occupancy with P annulled the inhibitory action of hFSH on pituitary LH content. These results indicate that PR is involved in ovarian GnSAF effect on LH content probably at a post-transcriptional level. PMID:21086199

Gordon, Ana; Garrido-Gracia, José Carlos; Sánchez-Criado, José E; Aguilar, Rafaela

2011-06-01

62

Whole brain-pituitary in vitro preparation of the transgenic medaka (Oryzias latipes) as a tool for analyzing the differential regulatory mechanisms of LH and FSH release.  

PubMed

Two types of gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), are important pituitary hormones for sexual maturation and reproduction, and both of them are centrally regulated by gonadotropin-releasing hormone (GnRH) from the hypothalamus. In mammals, these two gonadotropins are secreted from a single type of gonadotrope. The mechanisms of differential regulation by GnRH of the release of two types of gonadotropins with different secretory profiles are still unknown. In teleosts, however, LH and FSH are secreted from separate cellular populations, unlike in mammals. This feature makes them useful for studying the regulatory mechanisms of LH and FSH secretions independently. Here, we generated transgenic medaka lines that express Ca(2+) indicator protein, inverse-pericam, specifically in the LH or FSH cells. We performed cell-type-specific Ca(2+) imaging of LH and FSH cells, respectively, using the whole brain-pituitary preparations of these transgenic fish in which all neural circuits and GnRH neuronal projection to the pituitary are kept intact. LH and FSH cells showed different Ca(2+) responses to GnRH. The results suggest differential regulation mechanisms for LH and FSH release by GnRH. Moreover, we also succeeded in detecting the effect on LH cells of endogenous GnRH peptide, which was released by electrical stimulation of the axons of GnRH1 neurons. Thus, our newly developed experimental model system using the whole brain-pituitary in vitro preparation of the transgenic medaka is a powerful tool for analyzing the differential regulatory mechanisms of the release of LH and FSH by multisynaptic neural inputs to the pituitary. PMID:24248459

Karigo, Tomomi; Aikawa, Masato; Kondo, Chika; Abe, Hideki; Kanda, Shinji; Oka, Yoshitaka

2014-02-01

63

Cost-effectiveness analysis on the use of rFSH + rLH for the treatment of anovulation in hypogonadotropic hypogonadal women  

PubMed Central

Background Hypogonadotropic hypogonadal women are characterized by ovarian functionality deficiency, caused by low concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). To recover reproduction functionality, recommended therapies for ovarian induction involve injections of FSH and LH medications. Objective Since important differences exist between recombinant and urinary gonadotropin therapies in terms of efficacy and cost, the objective of this study was to develop a cost-effectiveness model to compare recombinant FSH (rFSH) + recombinant LH (rLH) and highly purified human menopausal gonadotropin (HP-HMG). Methods A Markov model was developed, considering three cycles of therapy; probability of pregnancy and miscarriage were considered, and the efficacy was evaluated in terms of pregnancy occurrence. The perspective of the model was that of the Italian Health Service, so only direct cost (drugs, specialist visits, patient examinations, and hospitalizations) were included. Results rFSH + rLH is associated with a higher total cost (€3,453.50) and higher efficacy (0.87) compared with HP-HMG (€2,719.70 and 0.50). rFSH + rLH generated an incremental cost effectiveness ratio equal to €2,007.30 compared to HP-HMG; the average cost per pregnancy is estimated to be €3,990.00 for recombinant strategy and €5,439.80 for urinary strategy. Results of probabilistic sensitivity analysis were consistent with the abovementioned findings. Conclusion Despite the higher acquisition cost in comparison to HP-HMG, rFSH + rLH resulted in a higher pregnancy rate, which makes it the recommended choice when considering cost-effectiveness of LH in supporting FSH-induced follicular gonadotropins in hypogonadotropic hypogonadal women. PMID:25028553

Papaleo, Enrico; Alviggi, Carlo; Colombo, Giorgio Lorenzo; Pisanelli, Claudio; Ripellino, Claudio; Longobardi, Salvatore; Canonico, Pier Luigi

2014-01-01

64

Protease-activated Receptor 1 (PAR1) and PAR4 Heterodimers Are Required for PAR1-enhanced Cleavage of PAR4 by ?-Thrombin*  

PubMed Central

Thrombin is a potent platelet agonist that activates platelets and other cells of the cardiovascular system by cleaving its G-protein-coupled receptors, protease-activated receptor 1 (PAR1), PAR4, or both. We now show that cleaving PAR1 and PAR4 with ?-thrombin induces heterodimer formation. PAR1-PAR4 heterodimers were not detected when unstimulated; however, when the cells were stimulated with 10 nm ?-thrombin, we were able to detect a strong interaction between PAR1 and PAR4 by bioluminescence resonance energy transfer. In contrast, activating the receptors without cleavage using PAR1 and PAR4 agonist peptides (TFLLRN and AYPGKF, respectively) did not enhance heterodimer formation. Preventing PAR1 or PAR4 cleavage with point mutations or hirugen also prevented the induction of heterodimers. To further characterize the PAR1-PAR4 interactions, we mapped the heterodimer interface by introducing point mutations in transmembrane helix 4 of PAR1 or PAR4 that prevented heterodimer formation. Finally, we show that mutations in PAR1 or PAR4 at the heterodimer interface prevented PAR1-assisted cleavage of PAR4. These data demonstrate that PAR1 and PAR4 require allosteric changes induced via receptor cleavage by ?-thrombin to mediate heterodimer formation, and we have determined the PAR1-PAR4 heterodimer interface. Our findings show that PAR1 and PAR4 have dynamic interactions on the cell surface that should be taken into account when developing and characterizing PAR antagonists. PMID:24097976

Arachiche, Amal; Mumaw, Michele M.; de la Fuente, María; Nieman, Marvin T.

2013-01-01

65

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

SciTech Connect

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 prevents hCG-induced expression of the ovulatory genes. • ERK1/2 activation is required for atrazine action in granulosa cells. • Atrazine does not interfere with FSH-stimulated ERK1/2 phosphorylation.

Fa, Svetlana; Pogrmic-Majkic, Kristina; Samardzija, Dragana; Glisic, Branka; Kaisarevic, Sonja; Kovacevic, Radmila; Andric, Nebojsa, E-mail: nebojsa.andric@dbe.uns.ac.rs

2013-07-01

66

Different pharmacokinetic and pharmacodynamic properties of recombinant follicle-stimulating hormone (rFSH) derived from a human cell line compared with rFSH from a non-human cell line.  

PubMed

Pharmacokinetic and pharmacodynamic properties of a novel recombinant follicle-stimulating hormone (rFSH) preparation (FE 999049), expressed by a human cell line (PER.C6), was compared with an rFSH preparation (follitropin ?) expressed by a Chinese hamster ovary (CHO) cell line in healthy pituitary-suppressed women. Following single intravenous administration of 225 IU (Steelman-Pohley assay), the clearance was lower, 0.31 versus 0.44 L/h, for FE 999049 than for follitropin ?. Likewise, the apparent clearance after repeated daily subcutaneous administrations was lower, 0.58 versus 0.99 L/h, and AUC and C(max) higher, 1.7- and 1.6-fold. The absolute bioavailability after a single subcutaneous dose of 450 IU was similar for both preparations, 60-65%. After repeated subcutaneous administration the elimination half-life was approximately 30 and 24 hours for FE 999049 and follitropin ?. The ovarian responses by number of follicles and serum concentrations of inhibin B and estradiol, were higher with FE 999049 than with follitropin ?, AUC and C(max) for the two latter being >1.6-fold greater with FE 999049 than with follitropin ?. These results indicate that administration of equal doses of FE 999049, expressed in a human cell line, and follitropin ?, expressed in a CHO cell line, display different pharmacokinetic and pharmacodynamic properties in humans. PMID:24800998

Olsson, Håkan; Sandström, Rikard; Grundemar, Lars

2014-11-01

67

Production of recombinant orange-spotted grouper (Epinephelus coioides) follicle-stimulating hormone (FSH) in single-chain form and dimer form by Pichia pastoris and their biological activities.  

PubMed

FSH is a key regulator of steroidogenesis and gonadal growth in teleosts. However, function of FSH is elusive in grouper due to the lack of purified and native FSH. In the present study, we reported production of bioactive orange-spotted grouper (Epinephelus coioides) FSH in dimer form and single-chain form by Pichia pastoris. Dimer form of recombinant grouper FSH (rgFSHba) was accomplished by co-expressing mature FSHb-subunit and a-subunit genes. Fusion of mature FSHb-subunit and a-subunit genes together linking with a polypeptide (4×(Gly-Ser)-Gly-Thr) gene generated single-chain form of recombinant grouper FSH (rgFSHb-a). Recombinant grouper common ?-subunit (rgCga) and FSHb-subunit (rgFSHb) were also separately produced. Recombinant proteins were verified by Western blot and mass spectrometry assays, and characterized by deglycosylation analysis. Deglycosylation assay suggested that glycosylation of recombinant FSH mainly occurred on common a-subunit. Bioactivities of recombinant proteins were initially evaluated by activating grouper FSH receptor, and further demonstrated by incubating ovarian fragments of adult grouper and intraperitoneal injection in juvenile female grouper. Two forms of recombinant FSH presented similar biological activities of activating FSH receptor and stimulating in vitro testosterone (T) and estradiol-17? (E2) secretion, though the dimer form functioned slightly weaker than the single-chain form. However, injections of rgFSHb-a or rgFSHba could significantly increase serum T and E2 levels, induce early ovarian development, reduce hypothalamic gnrh1 mRNA level, and increase hypothalamic cyp19a1b mRNA level. Data in this study suggested that recombinant gonadotropin could be produced in dimer form or single-chain form by P. pastoris, and FSH could regulate steroidogenesis and early ovarian development in juvenile grouper. PMID:22684083

Chen, Jun; Zhang, Yanhong; Tang, Zhiguo; Mao, Jiewei; Kuang, Zhonglei; Qin, Chaobin; Li, Wensheng

2012-09-01

68

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

PubMed

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 48h 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. PMID:23583632

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

2013-07-01

69

A common polymorphic allele of the LH beta-subunit gene is associated with higher exogenous FSH consumption during controlled ovarian stimulation for assisted reproductive technology  

PubMed Central

Background V-betaLH is a common genetic variant of LH caused by two polymorphic base changes in the beta subunit gene, altering the amino acid sequence (Trp8Arg and Ile15Thr). In a previous-preliminary trial performed in women undergoing IVF, it was demonstrated that carriers of v-betaLH show sub-optimal ovarian response to a standard long GnRH-agonist down -regulation protocol when stimulated with pure recombinant FSH (r-hFSH). The aim of this study was to confirm the hypothesis that women with v-betaLH display hypo-sensitivity to exogenous FSH in a larger IVF population and to explore the frequency of this variant in a Danish female population. Methods In the present study, the effect of v-betaLH was retrospectively investigated in a larger series of women undergoing controlled ovarian stimulation (COS) and, for the first time, in a Danish IVF population. A total of 220 normogonadotrophic women following a long GnRH-agonist down-regulation protocol received an individualized dose of r-hFSH (100 IU and 375 IU s.c. daily) according to antral follicle count, baseline FSH, body mass index and age. The LH genotype was assessed in all patients by immunofluorometric assay. Results V-betaLH was present in 11% of patients, whereas the allelic frequency was 12%. The study population was divided into two groups according to their LH genotype. Group A consisted of 196 wt/wt women. Group B included 24 individuals with v-betaLH (21 heterozygous and 3 homozygous). No statistically significant differences in the mean number of oocytes retrieved, fertilization rate and pregnancy rate per cycle were observed between groups. However, Group B received a significantly higher cumulative-dose of r-hFSH than Group A (2435.86 +/? 932.8 IU versus 1959.8 +/? 736.45 p?=?0.048). When one-way ANOVA in a within design was applied, the LH genotype had a statistically significant effect (p?FSH, showing a progressive increase from wt/wt (1959.8 +/? 736.45 IU) to v-betaLH hetero- (2267.5 +/? 824.3) and homozygotic women (3558.3 +/? 970.9). Conclusions These results confirm that carriers exhibit hypo-sensitivity to exogenous FSH during COS, documenting that the frequency of v-betaLH in Denmark is similar to a number of European countries. PMID:23725475

2013-01-01

70

Brulures par Diluant  

PubMed Central

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

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

2009-01-01

71

UNIVERSITE OUVERTE Voyage accompagn par  

E-print Network

l'empereur Auguste. Fin de la visite par les remparts (pas de promenade sur les remparts cela est'architecture religieuse de Catalogne. Il fut fondé par Raimond Bérenger IV, comte de Barcelone, qui le céda à l'ordre de

Jeanjean, Louis

72

Comparing clomiphen citrate plus HMG with clomiphen citrate plus rFSH in IUI cycles in couples with unexplained or male factor infertility: A prospective randomized study  

PubMed Central

Background: Different protocols are used for controlled ovarian hyper stimulation (COH), but the optimal method has not yet been determined. Objective: The aim of this study was to compare the outcome of controlled ovarian stimulation (COS) using clomiphen citrate (CC) plus HMG versus CC plus rFSH in intra uterine insemination cycles (IUI). Materials and Methods: 144 women with unexplained or male factor infertility undergoing IUI cycles were randomized (72 patients in CC plus rFSH group and 72 patients in CC plus HMG group) and included in this single blind study from October 2006 to June 2010. The primary outcomes were clinical and ongoing pregnancy rates. The number of dominant follicles, mean of follicular size, endometrial thickness on the day of HCG administration, total dose of gonadotropins and duration of stimulation with gonadotropins were secondary outcomes. Results: Clinical and ongoing pregnancy rates were not significantly different in the two groups .There was a significant higher multiple pregnancy rate in CC plus rFSH group (33.3%) versus CC plus HMG group (12.5%; p<0.005). There were no statistically significant differences in the secondary outcomes between the two groups. Conclusion: According to our results it seems that CC plus HMG is a more suitable and cost-effective regimen than CC plus rFSH in IUI cycles in patients with unexplained or male factor infertility. PMID:24639752

Azargoon, Azam; Bahrami, Marjan; Alavy Toussy, Jafar

2013-01-01

73

The evaluation of recombinant LH supplementation in patients with suboptimal response to recombinant FSH undergoing IVF treatment with GnRH agonist down-regulation.  

PubMed

Abstract We aimed to evaluate the clinical efficacy of r-LH supplementation to r-FSH in patients with suboptimal response to ovarian stimulation undergoing assisted reproduction with GnRH-a downregulation and stimulation with r-FSH. One-hundred thirty-seven patients were included in the study; among them 52 showed normal ovarian response to stimulation and composed the control group (Group 1), and 85 showed suboptimal response to stimulation and were divided into two groups. For Group 2 (n?=?50), 75?IU/L r-LH was added to the treatment, for Group 3 (n?=?35) r-FSH dose was increased by 75?IU/L. IVF results were compared between the groups. Implantation rates were 34.8% in control group, and 36.1% and 15% in LH supplementation group and increased-dose r-FSH group, respectively. Implantation rates were statistically significantly higher in Groups 1 and 2 compared to Group 3 (p?FSH during GnRH agonist down-regulation. Particularly, r-LH is recommended as it may have a beneficial action on implantation in selected group. PMID:25237892

Yaz?c? Y?lmaz, Fatma; Görkemli, Hüseyin; Çolako?lu, Mehmet Cengiz; Aktan, Murat; Gezginç, Kaz?m

2015-02-01

74

Effects of recombinant LH supplementation in women undergoing assisted reproduction with GnRH agonist down-regulation and stimulation with recombinant FSH: an opening study.  

PubMed

Circulating endogenous concentrations of LH are reduced in women undergoing down-regulation with gonadotrophin-releasing hormone agonists (GnRHa) and ovarian stimulation with recombinant human FSH (r-hFSH). The effect of recombinant human LH (r-hLH) supplementation on ovarian response and pregnancy outcome was evaluated in a prospective randomized study (sealed envelopes) including 231 cycles. Normogonadotrophic women were stimulated with either r-hFSH or a combination of r-hFSH and r-hLH in a ratio of 2:1. LH supplementation was started from day 8 of the cycle. Blood samples for oestradiol, LH and androstendione were prospectively collected on days 1, 8 and on the day of aspiration and analysed retrospectively. Overall, the two groups did not differ with respect to pregnancy rate. In contrast, women aged > or =35 years responded to exogenous LH supplementation with significantly increased implantation rates and significantly reduced total FSH consumption as compared with the non-supplemented group. In addition, the implantation rate for a subgroup of patients with the highest endogenous LH concentrations (i.e. > or =1.99 IU/l) on day 8 was significantly increased by LH supplementation. Exogenous LH supplementation from day 8 has no detrimental effect on ovarian response and pregnancy outcome. On the contrary supplementation with r-hLH seems to benefit treatment outcome for women above 35 years of age and for the subgroup of women exhibiting LH concentrations above 1.99 IU/l on stimulation day 8. PMID:15169576

Humaidan, P; Bungum, M; Bungum, L; Yding Andersen, C

2004-06-01

75

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

PubMed

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

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

2014-11-21

76

Atrazine enhances progesterone production through activation of multiple signaling pathways in FSH-stimulated rat granulosa cells: evidence for premature luteinization.  

PubMed

Premature luteinization is a possible cause of infertility in women. It is currently unknown whether environmental chemicals can induce changes associated with premature luteinization. Using rat granulosa cells (GC) in vitro, we demonstrated that exposure to atrazine (ATR), a widely used herbicide, causes GC phenotype that resembles that of human premature luteinization. At the end of the 48-h stimulation with FSH, ATR-exposed GC showed (1) higher levels of progesterone, (2) overexpression of luteal markers (Star and Cyp11a1), and (3) an increase in progesterone:estradiol ratio above 1. Mechanistic experiments were conducted to understand the signaling events engaged by ATR that lead to this phenotype. Western blot analysis revealed prolonged phosphorylation of protein kinase B (AKT) and cAMP response element-binding protein (CREB) in ATR- and FSH-exposed GC. An increased level of ERK1/2-dependent transcriptional factor CCATT/enhancer-binding protein beta (CEBPB) was observed after 4 h of ATR exposure. Inhibitors of PI3K (wortmannin) and MEK (U0126) prevented ATR-induced rise in progesterone level and expression of luteal markers in FSH-stimulated GC. Atrazine intensified AKT and CEBPB signaling and caused Star overexpression in forskolin-stimulated GC but not in epidermal growth factor (EGF)-stimulated GC. In the presence of rolipram, a specific inhibitor of phosphodiesterase 4 (PDE4), ATR was not able to further elevate AKT phosphorylation, CEBPB protein level, and Star mRNA in FSH-stimulated GC, suggesting that ATR inhibits PDE4. Overall, this study showed that ATR acts as a FSH sensitizer leading to enhanced cAMP, AKT, and CEBPB signaling and progesterone biosynthesis, which promotes premature luteinization phenotype in GC. PMID:25253736

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

2014-11-01

77

Transactivation of the PAR1-PAR2 heterodimer by thrombin elicits ?-arrestin-mediated endosomal signaling.  

PubMed

Thrombin cleaves the N terminus of PAR1, generating a new N-terminal domain that functions as a tethered ligand that binds intermolecularly to activate PAR2 in trans. The mechanisms that regulate PAR1-PAR2 heterodimer signaling and trafficking are not known. We now report that PAR1 and PAR2 form a heterodimer that exhibits unique trafficking and signaling behaviors compared with receptor protomers. Using bioluminescence resonance energy transfer, immunofluorescence microscopy, co-immunoprecipitation, and cells expressing receptors exogenously and endogenously, we show that PAR1 and PAR2 specifically interact and form stable dimers. Intriguingly, the PAR1-PAR2 heterodimer displays constitutive internalization that is driven by PAR1 C-terminal tail sorting motifs and is a process that enhances dimer formation. Upon thrombin activation, PAR1-PAR2 dimers co-internalize and recruit ?-arrestins to endosomes. Remarkably, PAR1-PAR2 heterodimers appear to utilize a distinct interface for ?-arrestin interaction compared with receptor protomers. Moreover, thrombin-activated PAR1-PAR2 heterodimers enhance ?-arrestin-mediated ERK1/2 activation in the cytoplasm, whereas activated ERK1/2 induced by the thrombin-activated PAR1 protomer redistributes to the nucleus. Thus, the formation of PAR1-PAR2 heterodimers provides additional modes of thrombin-stimulated signaling responses that appear to be distinctly regulated compared with the receptor protomer. PMID:23476015

Lin, Huilan; Trejo, JoAnn

2013-04-19

78

Par Pond vegetation status 1996  

SciTech Connect

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.

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

1996-12-01

79

Regulation of FSH? induction in L?T2 cells by BMP2 and an Activin A/BMP2 chimera, AB215.  

PubMed

Activins and bone morphogenetic proteins (BMPs) share activin type 2 signaling receptors but utilize different type 1 receptors and Smads. We designed AB215, a potent BMP2-like Activin A/BMP2 chimera incorporating the high-affinity type 2 receptor-binding epitope of Activin A. In this study, we compare the signaling properties of AB215 and BMP2 in HEK293T cells and gonadotroph L?T2 cells in which Activin A and BMP2 synergistically induce FSH?. In HEK293T cells, AB215 is more potent than BMP2 and competitively blocks Activin A signaling, while BMP2 has a partial blocking activity. Activin A signaling is insensitive to BMP pathway antagonism in HEK293T cells but is strongly inhibited by constitutively active (CA) BMP type 1 receptors. By contrast, the potencies of AB215 and BMP2 are indistinguishable in L?T2 cells and although AB215 blocks Activin A signaling, BMP2 has no inhibitory effect. Unlike HEK293T, Activin A signaling is strongly inhibited by BMP pathway antagonism in L?T2 cells but is largely unaffected by CA BMP type 1 receptors. BMP2 increases phospho-Smad3 levels in L?T2 cells, in both the absence and the presence of Activin A treatment, and augments Activin A-induced FSH?. AB215 has the opposite effect and sharply decreases basal phospho-Smad3 levels and blocks Smad2 phosphorylation and FSH? induction resulting from Activin A treatment. These findings together demonstrate that while AB215 activates the BMP pathway, it has opposing effects to those of BMP2 on FSH? induction in L?T2 cells apparently due to its ability to block Activin A signaling. PMID:25100748

Jung, Jae Woo; Ahn, Chihoon; Shim, Sun Young; Gray, Peter C; Kwiatkowski, Witek; Choe, Senyon

2014-10-01

80

Immunocytochemical applications of specific antisera raised against synthetic fragment peptides of mummichog GtH subunits: examining seasonal variations of gonadotrophs (FSH cells and LH cells) in the mummichog and applications to other acanthopterygian fishes  

Microsoft Academic Search

Two distinct types of gonadotrophs, FSH (GtH I) cells and LH (GtH II) cells, were immunocytochemically identified from mummichog (Fundulus heteroclitus; Cyprinodontiformes, Acanthopterygii) pituitary using antisera raised against synthetic fragment peptides of FSH? and LH?. Both cell types were abundant during the spawning period (spring and early summer) and decreased in number during the post-spawning immature period. The number of

Akio Shimizu; Hideki Tanaka; Hirohiko Kagawa

2003-01-01

81

Immediate and delayed effects of heat stress on follicular development and its association with plasma FSH and inhibin concentration in cows.  

PubMed

The aim of this study was to characterize the immediate effects of heat stress on plasma FSH and inhibin concentrations, and its involvement in follicular dynamics during a complete oestrous cycle, and to examine a possible delayed effect of heat stress on follicular development. Holstein dairy cows were oestrous synchronized and randomly assigned to either cooled (n = 7) or heat-stressed (n = 6) treatment groups. During a complete oestrous cycle, control cows, which were cooled, maintained normothermia, whereas heat-stressed cows, which were exposed to direct solar radiation, developed hyperthermia. At the end of this oestrous cycle (treated cycle), both groups were cooled and maintained normothermia for the first 10 days of the subsequent oestrous cycle. Throughout this period, follicular development was examined by ultrasonography, and plasma samples were collected. During the second follicular wave of the treated oestrous cycle, a significantly larger cohort of medium sized follicles (6-9 mm) was found in heat-stressed cows than in cooled cows (P < 0.05). The enhanced growth of follicles in this wave in heat-stressed cows was associated with a higher plasma FSH increase which lasted 4 more days (days 8-13 of the oestrous cycle; P < 0.05), and coincided with a decrease in the plasma concentration of immunoreactive inhibin (days 5-18 of the oestrous cycle; P < 0.05). During the follicular phase (days 17-20 of the treated cycle), heat-stressed cows showed an increase in the number of large follicles (>/= 10 mm), and the preovulatory plasma FSH surge was significantly higher in heat-stressed cows than in cooled cows (P < 0.01). The effect of heat stress was also observed during the first follicular wave of the subsequent cycle: the postovulatory plasma FSH concentration was higher (P < 0.01), but fewer medium follicles developed, and the first follicular wave decreased at a slower rate in previously heat-stressed cows than in cooled cows (0.40 and 0.71 follicles per day, respectively). This study shows both immediate and delayed effects of heat stress on follicular dynamics, which were associated with high FSH and low inhibin concentrations in plasma. These alterations may have physiological significance that could be associated with low fertility of cattle during the summer and autumn. PMID:11006149

Roth, Z; Meidan, R; Braw-Tal, R; Wolfenson, D

2000-09-01

82

FRQUENCEMETRE RADIOLECTRIQUE Par Z. CARRIRE.  

E-print Network

'un stroboscope réglé sur les stries de la flamme. On peut obtenir, pour la fréquence 10 000, des stries espacées'éclairage sensible au son émis par le haut-parleur et d'un stroboscope réglé sur les franges qu'engendre le haut'analyseur par excellence des phénomènes périodiques : le stroboscope. Avec cet appareil, dans une flamme qui, au

Boyer, Edmond

83

BERKELEY PAR LABBERKELEY PAR LAB Three Challenges and Three  

E-print Network

Compiler/runtime infrastructure Domain-specific libraries, languages, and specializers 2 #12;BERKELEY PAR Domain-specific solutions in libraries, languages, and specializers Expert programmers solve) span 4 (global) Program Start Barrier Barrier Bar Exchange Bar Bar Bar 0, 1, 2, 3, 4, 5, 6, 7 0, 1, 2

California at Berkeley, University of

84

DSEXCITATION DE NOYAUX DE DYSPROSIUM OBTENUS PAR BOMBARDEMENT DE TERBIUM PAR DES PROTONS  

E-print Network

833 D�SEXCITATION DE NOYAUX DE DYSPROSIUM OBTENUS PAR BOMBARDEMENT DE TERBIUM PAR DES PROTONS Par M (p, 9n) (p, 10n) induites sur le terbium-159. La comparaison avec un calcul fondé sur les Simonoff [6] ont récemment exa- miné la désexcitation de noyaux de terbium et de dysprosium obtenus par

Paris-Sud XI, Université de

85

PAR and Supply Distribution System The PAR Program is administered by Materials Logistics (Central Distribution)  

E-print Network

Logistics (Central Distribution) Services, a division of Materials Management. · The PAR Program is focused, except in the OR and NICU. (Materials Management will be reviewing a PAR system for the multiple units#12;PAR and Supply Distribution System OVERVIEW · The PAR Program is administered by Materials

Oliver, Douglas L.

86

Par Pond Fish, Water, and Sediment Chemistry  

SciTech Connect

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.

Paller, M.H. [Westinghouse Savannah River Company, AIKEN, SC (United States); Wike, L.D.

1996-06-01

87

NOUVEAU SPECTROSCOPE; PAR M. THOLLON.  

E-print Network

I4I NOUVEAU SPECTROSCOPE; PAR M. THOLLON. J'ai eu l'honneur de présenter récemment à l'Académie et qu'on fasse varier la position du couple sur le trajet d'un rayon d'une certaine réfrangibilité, il y

Boyer, Edmond

88

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

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 consistent with our previous observation of elevated plasma triiodothyronine concentrations in hyperleptinemic horses (later shown to be insulin insensitive as well). PMID:23571008

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

2013-05-01

89

Par proteins and neuronal polarity  

PubMed Central

A hallmark of neurons is their ability to polarize with dendrite and axon specification to allow the proper flow of information through the nervous system. Over the past decade, extensive research has been performed in an attempt to understand the molecular and cellular machinery mediating this neuronal polarization process. It has become evident that many of the critical regulators involved in establishing neuronal polarity are evolutionarily conserved proteins that had previously been implicated in controlling the polarization of other cell types. At the forefront of this research are the partition defective (Par) proteins. In this review, we will provide a commentary on the progress of work regarding the central importance of Par proteins in the establishment of neuronal polarity. PMID:21557502

Insolera, Ryan; Chen, She; Shi, Song-Hai

2011-01-01

90

prsente par Pierre Niainarivony ZOKIMILA  

E-print Network

stockage des déchets radioactifs : Approche par homogénéisation Date de soutenance : 7 octobre 2005 Frédéric Pellet Université Joseph Fourier - Grenoble I Rapporteurs Denis Fabre Conservatoire National des à l'accomplissement de cette thèse. Tout d'abord, je veux remercier Monsieur Frédéric Pellet, Maître

Paris-Sud XI, Université de

91

PHONOPTOMTRE ; PAR M. J. LISSAJOUS.  

E-print Network

265 PHONOPTOM�TRE ; PAR M. J. LISSAJOUS. (Société de Physique; séance du I3 mars I87 4.) Le'une couche d'alcool : ce godet se meut verticalement au moyen d une vis de réglage R. Le courant de la pile façon à produire lim" des figures si- b Il al é e spa r nous clalm 1 étude optique des sons. () Il

Boyer, Edmond

92

Prsente par M. J CORNEBISE  

E-print Network

T 'U P M C Spécialité M Option S M Présentée par M. J CORNEBISE Pour obtenir le grade de D 'U P M C Effectuée sous la direction de M. E MOULINES, M. P DEHEUVELS M M C S A A S M C M Soutenue le 25 Juin 2009 Devant le jury composé de : M. Paul DEHEUVELS (Directeur) M. Eric MOULINES (Directeur) M. Fabien CAMPILLO

Cornebise, Julien

93

ParB spreading requires DNA bridging  

PubMed Central

The parABS system is a widely employed mechanism for plasmid partitioning and chromosome segregation in bacteria. ParB binds to parS sites on plasmids and chromosomes and associates with broad regions of adjacent DNA, a phenomenon known as spreading. Although essential for ParB function, the mechanism of spreading remains poorly understood. Using single-molecule approaches, we discovered that Bacillus subtilis ParB (Spo0J) is able to trap DNA loops. Point mutants in Spo0J that disrupt DNA bridging are defective in spreading and recruitment of structural maintenance of chromosomes (SMC) condensin complexes in vivo. DNA bridging helps to explain how a limited number of Spo0J molecules per parS site (?20) can spread over many kilobases and suggests a mechanism by which ParB proteins could facilitate the loading of SMC complexes. We show that DNA bridging is a property of diverse ParB homologs, suggesting broad evolutionary conservation. PMID:24829297

Graham, Thomas G.W.; Wang, Xindan; Song, Dan; Etson, Candice M.; van Oijen, Antoine M.; Rudner, David Z.; Loparo, Joseph J.

2014-01-01

94

The Par3-Like Polarity Protein, Par3L, is Essential for Mammary Stem Cell Maintenance  

PubMed Central

The Par polarity proteins play key roles in asymmetric division of Drosophila stem cells; however, whether the same mechanisms control stem cells in mammals is controversial. Although necessary for mammary gland morphogenesis, Par3 is not essential for mammary stem cell function. We discovered that, instead, a previously uncharacterized protein, Par3-Like (Par3L), is vital for mammary gland stem cell maintenance. Par3L function has been mysterious because unlike Par3 it does not interact with atypical protein kinase C or the Par6 polarity protein. We found that Par3L is expressed by multipotent stem cells in the terminal end buds of murine mammary glands. Ablation of Par3L resulted in rapid and profound stem cell loss. Unexpectedly, Par3L, but not Par3, binds to the tumor suppressor protein LKB1 and inhibits its kinase activity. This interaction is key for the function of Par3L in mammary stem cell maintenance. Our data reveal insights into a linkage between cell polarity proteins and stem cell survival, and uncover the first known biological function for Par3L. PMID:24859006

Huo, Yongliang; Macara, Ian G.

2014-01-01

95

Seasonal expression of KiSS-1 and the pituitary gonadotropins LH? and FSH? in adult male Libyan jird (Meriones libycus).  

PubMed

The molecular mechanisms operating on a seasonal time-scale and regulating functions such as reproduction are poorly understood in animals living in desert environments. Kisspeptin, the product of the KiSS-1 gene, plays a critical role in control of the hypothalamic-pituitary-gonad axis that orchestrates the reproductive system in vertebrates. We report a sequence analysis of KiSS-1 and the pituitary luteinising hormone-beta (LH?) and follicle-stimulating hormone-beta (FSH?) in the Libyan jird (Meriones libycus), a seasonal breeding rodent that is sexually active during spring and quiescent in fall. We also assessed gene expression by quantitative real-time reverse transcription-polymerase chain reaction during the non-breeding and breeding seasons. The KiSS-1 cDNA sequence analysis showed high homology between M. libycus and all other rodents (94%) and humans (92%). KiSS-1 expression was higher during the breeding season than that during the non-breeding season. In contrast, LH? and FSH? expression levels were higher during the non-breeding season in autumn and varied in an opposite manner with testicular, seminal vesicle weights and plasma testosterone levels. Our results extend the role for KiSS-1 in activating the HPG axis in this desert rodent in its natural biotope by relaying environmental cues as in other seasonal non-desert rodent models. PMID:24786546

Boufermes, R; Richard, N; Le Moguen, K; Amirat, Z; Khammar, F; Kottler, M L

2014-06-10

96

Reconstructing the Discontinuous and Conformational ?1/?3-Loop Binding Site on hFSH/hCG by Using Highly Constrained Multicyclic Peptides.  

PubMed

Making peptide-based molecules that mimic functional interaction sites on proteins remains a challenge in biomedical sciences. Here, we present a robust technology for the covalent assembly of highly constrained and discontinuous binding site mimics, the potential of which is exemplified for structurally complex binding sites on the "Cys-knot" proteins hFSH and hCG. Peptidic structures were assembled by Ar(CH2 Br)2 -promoted peptide cyclizations, combined with oxime ligation and disulfide formation. The technology allows unprotected side chain groups and is applicable to peptides of different lengths and nature. A tetracyclic FSH mimic was constructed, showing >600-fold improved binding compared to linear or monocyclic controls. Binding of a tricyclic hCG mimic to anti-hCG mAb 8G5 was identical to hCG itself (IC50 =260 vs. 470 pM), whereas this mimic displayed an IC50 value of 149 nM for mAb 3468, an hCG-neutralizing antibody with undetectable binding to either linear or monocyclic controls. PMID:25469830

Smeenk, Linde E J; Timmers-Parohi, Drohpatie; Benschop, Joris J; Puijk, Wouter C; Hiemstra, Henk; van Maarseveen, Jan H; Timmerman, Peter

2015-01-01

97

Exploring the cyclooxygenase 2 (COX2)/15d-?(12,14)PGJ(2) system in hamster Sertoli cells: regulation by FSH/testosterone and relevance to glucose uptake.  

PubMed

We have previously described a stimulatory effect of testosterone on cyclooxygenase 2 (COX2) expression and prostaglandin (PG) synthesis, and the involvement of PGs in the modulation of testosterone production in Leydig cells of the seasonal breeder Syrian hamster. In this study, we investigated the existence of a COX2/PGs system in hamster Sertoli cells, its regulation by testosterone and FSH, and its effect on glucose uptake. COX2 expression was observed in Sertoli cells of both reproductively active and inactive adult hamsters. Testosterone and the plasma membrane-impermeable testosterone-BSA significantly induced COX2 expression, mitogen activated protein kinases 1/2 (MAPK1/2) phosphorylation and 15d-?(12,14)PGJ(2) production in Sertoli cells purified from photoperiodically regressed hamsters. These actions were abolished by the antiandrogen bicalutamide and by the inhibitor of MAPK kinase (MEK1/2) U0126, suggesting that testosterone exerts its stimulatory effect on COX2/PGs through a non-classical mechanism that involves the presence of androgen receptors and MAPK1/2 activation. FSH also stimulated COX2/PGs via MAPK1/2 phosphorylation. FSH and testosterone stimulate, whereas 15d-?(12,14)PGJ(2) via PPAR? inhibits, [2,6-(3)H]-2-deoxy-d-glucose ([(3)H]-2-DOG) uptake. Meloxicam, a selective COX2 inhibitor, further increases [(3)H]-2-DOG uptake in the presence of FSH or testosterone. Thus, in addition to their positive effect, FSH and testosterone may also exert an indirect negative regulation on glucose uptake which involves the COX2/15d-?(12,14)PGJ(2)/PPAR? system. Overall, these results demonstrate the presence of a COX2/PG system in hamster Sertoli cells which might act as a local modulator of FSH and testosterone actions. PMID:22974512

Matzkin, María Eugenia; Pellizzari, Eliana Herminia; Rossi, Soledad Paola; Calandra, Ricardo Saúl; Cigorraga, Selva Beatriz; Frungieri, Mónica Beatriz

2012-11-01

98

A double-blind, non-inferiority RCT comparing corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol  

PubMed Central

BACKGROUND Corifollitropin alfa, a fusion protein lacking LH activity, has a longer elimination half-life and extended time to peak levels than recombinant FSH (rFSH). A single injection of corifollitropin alfa may replace seven daily gonadotrophin injections during the first week of ovarian stimulation. METHODS In this large, double-blind, randomized, non-inferiority trial the ongoing pregnancy rates were assessed after one injection of 150 µg corifollitropin alfa during the first week of stimulation and compared with daily injections of 200 IU rFSH using a standard GnRH antagonist protocol. RESULTS The study population comprised 1506 treated patients with mean age of 31.5 years and body weight of 68.6 kg. Ongoing pregnancy rates of 38.9% for the corifollitropin alfa group and 38.1% for rFSH were achieved, with an estimated non-significant difference of 0.9% [95% confidence interval (CI): ?3.9; 5.7] in favor of corifollitropin alfa. Stratified analyses of pregnancy rates confirmed robustness of this primary outcome by showing similar results regardless of IVF or ICSI, or number of embryos transferred. A slightly higher follicular response with corifollitropin alfa resulted in a higher number of cumulus–oocyte-complexes compared with rFSH [estimated difference 1.2 (95% CI: 0.5; 1.9)], whereas median duration of stimulation was equal (9 days) and incidence of (moderate/severe) ovarian hyperstimulation syndrome was the same (4.1 and 2.7%, respectively P = 0.15). CONCLUSION Corifollitropin alfa is a novel and effective treatment option for potential normal responder patients undergoing ovarian stimulation with GnRH antagonist co-treatment for IVF resulting in a high ongoing pregnancy rate, equal to that achieved with daily rFSH. The trial was registered under ClinicalTrials.gov identifier NTC00696800. PMID:19684043

Devroey, P.; Boostanfar, R.; Koper, N.P.; Mannaerts, B.M.J.L.; IJzerman-Boon, P.C.; Fauser, B.C.J.M.

2009-01-01

99

Apprentissage par Renforcement JER EMIE MARY  

E-print Network

Apprentissage par Renforcement J´ER ´EMIE MARY ´equipe TAO LRI 27 f´evrier 2006 J´ER ´EMIE MARY MDPs 5 R´ef´erences J´ER ´EMIE MARY Apprentissage par Renforcement #12;Introduction Apprendre et'influer sur l'environnement, 5 Le monde est stochastique et bruit´e. J´ER ´EMIE MARY Apprentissage par

Mary, Jeremie - Groupe de Recherche sur l'Apprentissage Automatique, Université Charles de Gaulle

100

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

ERIC Educational Resources Information Center

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…

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

2005-01-01

101

PHOTOLUMINESCENCE DU MTAANTIMONIATE DE CALCIUM ACTIV PAR LE BISMUTH Par ROGER BERNARD et JOSEPH JANIN,  

E-print Network

616. PHOTOLUMINESCENCE DU M�TAANTIMONIATE DE CALCIUM ACTIV� PAR LE BISMUTH Par ROGER BERNARD et différentes concentrations en bismuth ; les courbes corres- pondantes sont reproduites sur la figure 1. FiG. 1 concentrations en activateur. présentent pas de modification par addition de bismuth. Il semble plus

Paris-Sud XI, Université de

102

PAR  

E-print Network

La diffusion de ce mémoire se fait dans le ' respect des droits de son auteur, qui a signé le formulaire Autorisation de reproduire. et de diffuser un travail de recherche de cycles $Upérieurs (SDU-522- Rév.01-2006). Cette autorisation.stipule que «conformément · à l'article 11 du Règlement no 8 des études de cycles supérieurs, [l'auteur] concède à l'Université du Québec à Montréal une licence non exclusive d'utilisation et de. publication pe la totalité ou d'une partie importante de [son] travail de recherche pour 'des fins pédagogiques et non commerciales. Plus précisément, [l'auteur] autorise l'Université du Québec à Montréal à reproduire, diffuser, prêter, distribuer ou vendre des.· copies de. [son] travail de recherche à des fins non commerciales sur quelque support que ce soit, y compris l'Internet. Cette licence et cette autorisation n'entraînent pas une renonciation de [la] part [de l'auteur] à [ses] droits moraux ni à [ses] droits de propriété intellectuelle. Sauf entente contraire, [l'auteur] conserve la liberté de diffuser et de commercialiser ou non ce travail dont [il] possède un exemplaire..» AVANT-PROPOS Ce mémoire est constitué de deux chapitres sous la forme d'articles scientifiques

Persistance Et; Activité Reproductrice; Des Oiseaux; De La; Maîtrise En Biologie; Maxime Allard; Février Université; Du Québec; À Montréal; Service Des Bibliothèques

103

Par Pond vegetation status Summer 1995 -- Summary  

SciTech Connect

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.

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

1996-01-01

104

Immunocytochemical applications of specific antisera raised against synthetic fragment peptides of mummichog GtH subunits: examining seasonal variations of gonadotrophs (FSH cells and LH cells) in the mummichog and applications to other acanthopterygian fishes.  

PubMed

Two distinct types of gonadotrophs, FSH (GtH I) cells and LH (GtH II) cells, were immunocytochemically identified from mummichog (Fundulus heteroclitus; Cyprinodontiformes, Acanthopterygii) pituitary using antisera raised against synthetic fragment peptides of FSHbeta and LHbeta. Both cell types were abundant during the spawning period (spring and early summer) and decreased in number during the post-spawning immature period. The number of FSH cells increased again during the early phases of gonadal development (cortical alveoli accumulation in the oocytes and basal spermatogenesis) in early winter, whereas the number of LH cells did not. Only FSH cells were abundant during the latter phases of gonadal development (vitellogenesis and active spermatogenesis) in early spring. These observations suggest that both GtHs have important yet different roles for reproduction in this species. Antisera against the conservative region of the FSHbeta and the LHbeta subunits immunostained FSH cells and LH cells, respectively, also in red seabream (Pagrus major; Perciformes, Acanthopterygii) and small mouth bass (Micropterus dolomieu; Perciformes, Acanthopterygii), suggesting the possibility of their use for other acanthopterygian fishes. PMID:12765642

Shimizu, Akio; Tanaka, Hideki; Kagawa, Hirohiko

2003-06-01

105

Bone morphogenetic protein 2 stimulates noncanonical SMAD2/3 signaling via the BMP type 1A receptor in gonadotrope-like cells: implications for FSH synthesis.  

PubMed

FSH is an essential regulator of mammalian reproduction. Its synthesis by pituitary gonadotrope cells is regulated by multiple endocrine and paracrine factors, including TGF? superfamily ligands, such as the activins and inhibins. Activins stimulate FSH synthesis via transcriptional regulation of its ?-subunit gene (Fshb). More recently, bone morphogenetic proteins (BMPs) were shown to stimulate murine Fshb transcription alone and in synergy with activins. BMP2 signals via its canonical type I receptor, BMPR1A (or activin receptor-like kinase 3 [ALK3]), and SMAD1 and SMAD5 to stimulate transcription of inhibitor of DNA binding proteins. Inhibitor of DNA binding proteins then potentiate the actions of activin-stimulated SMAD3 to regulate the Fshb gene in the gonadotrope-like L?T2 cell line. Here, we report the unexpected observation that BMP2 also stimulates the SMAD2/3 pathway in these cells and that it does so directly via ALK3. Indeed, this novel, noncanonical ALK3 activity is completely independent of ALK4, ALK5, and ALK7, the type I receptors most often associated with SMAD2/3 pathway activation. Induction of the SMAD2/3 pathway by ALK3 is dependent upon its own previous activation by associated type II receptors, which phosphorylate conserved serine and threonine residues in the ALK3 juxtamembrane glycine-serine-rich domain. ALK3 signaling via SMAD3 is necessary for the receptor to stimulate Fshb transcription, whereas its activation of the SMAD1/5/8 pathway alone is insufficient. These data challenge current dogma that ALK3 and other BMP type I receptors signal via SMAD1, SMAD5, and SMAD8 and not SMAD2 or SMAD3. Moreover, they suggest that BMPs and activins may use similar intracellular signaling mechanisms to activate the murine Fshb promoter in immortalized gonadotrope-like cells. PMID:24601881

Wang, Ying; Ho, Catherine C; Bang, EunJin; Rejon, Carlis A; Libasci, Vanessa; Pertchenko, Pavel; Hébert, Terence E; Bernard, Daniel J

2014-05-01

106

[Pars plana phacoemulsification. Technics, indications and results].  

PubMed

Pars plana phacoemulsification allows cataract extraction through a 3 mm posterior sclerotomy. The indications of these technics are the combined cataract-vitrectomy, the cataracts on vitrectomised eyes and cataracts on eyes filled with silicone oil. The alteration of corneal endothelium is very reduced with the endocapsular pars plana phacoemulsification. After the emulsification, the capsular bag is extracted with a microforceps through the pars plana. It is also possible to save the anterior capsule to reduce corneal alteration during endocular surgery. We present the indications and the advantages of these technics. PMID:2641077

Furia, M; Puech, M; Elalouf, M; Boulley-Duparc, A

1989-01-01

107

Comparative cactus architecture and par interception  

SciTech Connect

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.

Geller, G.N.; Nobel, P.S. (Univ. of California, Los Angeles (USA))

1987-07-01

108

Techniques for measuring intercepted and absorbed PAR in corn canopies  

NASA Technical Reports Server (NTRS)

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.

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

1984-01-01

109

Protease-Activated Receptor (PAR) 1 and PAR4 Differentially Regulate Factor V Expression from Human Platelets  

PubMed Central

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. PMID:23307185

Duvernay, Matthew; Young, Summer; Gailani, David; Schoenecker, Jonathan

2013-01-01

110

par Elias Sanbar Ambassadeur de Palestine  

E-print Network

par Elias Sanbar Ambassadeur de Palestine auprès de l'UNESCO l'église de la Nativité au Patrimoi PatrimoiNe moNdial Portée et enjeux par Elias Sanbar Ambassadeur de Palestine auprès de l'UNESCO Considérée que s'exprimera Elias Sanbar. mardi 4 mars 2014 | 18h30, uni dufour l'eglise de la Nativité au

Citi, Sandra

111

Céphalées par abus médicamenteux et addiction  

Microsoft Academic Search

Résumé  \\u000a Objectifs: étude de la comorbidité pour les troubles liés à l’utilisation de substances psychoactives chez les patients souffrant de\\u000a céphalées par abus médicamenteux.Méthode: étude comparative de quarante et un migraineux (MIG) et quarante et un patients souffrant de céphalées par abus médicamenteux\\u000a issus de migraines (CAM).Résultats: les CAM ulilisant des médicaments contenant des substances psychoactives (caféine et codéine) remplissent

F. Radat; C. Creac'h; M. Lafitau; S. Irachabal; V. Dousset; P. Henry

2005-01-01

112

Ovarian response and pregnancy outcome related to mid-follicular LH levels in women undergoing assisted reproduction with GnRH agonist down-regulation (GnRHa) and recombinant FSH stimulation  

Microsoft Academic Search

BACKGROUND: The effect of LH levels on stimulation day 8 on ovarian response and pregnancy outcome were evaluated in women receiving pituitary down-regulation with GnRH agonists (0.8 mg Suprefact® s.c. daily until pituitary down-regulation and 0.4 mg\\/day during ovarian stimulation) and ovarian stimulation with recombinant FSH. METHODS: Blood samples were prospectively collected from a total of 207 normal women undergoing

Peter Humaidan; Leif Bungum; Mona Bungum; Claus Yding Andersen

2002-01-01

113

ERK2-mediated phosphorylation of Par3 regulates neuronal polarization.  

PubMed

Axon formation is one of the most important events in neuronal polarization and is regulated by signaling molecules involved in cytoskeletal rearrangement and protein transport. We previously found that Partition-defective 3 (Par3) is associated with KIF3A (kinesin-2) and is transported into the nascent axon in a KIF3A-dependent fashion. Par3 interacts with the Rac-specific guanine nucleotide-exchange factors (GEFs) Tiam1/2, which activate Rac1, and participates in axon formation in cultured hippocampal neurons. However, the regulatory mechanism of the Par3-KIF3A interaction is poorly understood, and the role of Par3 in neuronal polarization in vivo remains elusive. Here, we found that extracellular signal-regulated kinase 2 (ERK2) directly interacts with Par3, that ERK2 phosphorylates Par3 at Ser-1116, and that the phosphorylated Par3 accumulates at the axonal tips in a manner dependent upon ERK2 activity. The phosphorylation of Par3 by ERK2 inhibited the interaction of Par3 with KIF3A but not with the other Par3 partners, including Par6 and aPKC. The phosphomimic mutant of Par3 (Par3-S1116D) showed less binding activity with the KIF3s and slower transport in the axons. The knockdown of Par3 by RNA interference impaired neuronal polarization, which was rescued with RNAi-resistant Par3, but not with the phosphomimic Par3 mutant, in cultured rat hippocampal neurons and mouse cortical projection neurons in vivo. These results suggest that ERK2 phosphorylates Par3 and inhibits its binding with KIF3A, thereby controlling Par3 transport and neuronal polarity. PMID:23946386

Funahashi, Yasuhiro; Namba, Takashi; Fujisue, Shin; Itoh, Norimichi; Nakamuta, Shinichi; Kato, Katsuhiro; Shimada, Akiko; Xu, Chundi; Shan, Wei; Nishioka, Tomoki; Kaibuchi, Kozo

2013-08-14

114

ParCAT: Parallel Climate Analysis Toolkit  

SciTech Connect

Climate science is employing increasingly complex models and simulations to analyze the past and predict the future of Earth s climate. This growth in complexity is creating a widening gap between the data being produced and the ability to analyze the datasets. Parallel computing tools are necessary to analyze, compare, and interpret the simulation data. The Parallel Climate Analysis Toolkit (ParCAT) provides basic tools to efficiently use parallel computing techniques to make analysis of these datasets manageable. The toolkit provides the ability to compute spatio-temporal means, differences between runs or differences between averages of runs, and histograms of the values in a data set. ParCAT is implemented as a command-line utility written in C. This allows for easy integration in other tools and allows for use in scripts. This also makes it possible to run ParCAT on many platforms from laptops to supercomputers. ParCAT outputs NetCDF files so it is compatible with existing utilities such as Panoply and UV-CDAT. This paper describes ParCAT and presents results from some example runs on the Titan system at ORNL.

Smith, Brian E [ORNL; Steed, Chad A [ORNL; Shipman, Galen M [ORNL; Ricciuto, Daniel M [ORNL; Thornton, Peter E [ORNL; Wehner, Michael [Lawrence Berkeley National Laboratory (LBNL); Williams, Dean N. [Lawrence Livermore National Laboratory (LLNL)

2013-01-01

115

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

PubMed Central

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 its released soluble molecules (factors, mediators, chemokines, cytokines, neurotransmitters) locally increase oocyte maturation and hormone secretion. Therefore we suggest that platelets are not only a small participant but may be the conductor or active mediator of this complex regulatory system which has several unrevealed mechanisms. In other words platelets are corpuscular messengers, or are more than a member of the family providing hemostasis. PMID:24883111

2014-01-01

116

PAR polarity: from complexity to design principles.  

PubMed

The par-titioning-defective or PAR proteins comprise the core of an essential cell polarity network that underlies polarization in a wide variety of cell types and developmental contexts. The output of this network in nearly every case is the establishment of opposing and complementary membrane domains that define a cell?s polarity axis. Yet, behind this simple pattern is a complex system of interactions, regulation and dynamic behaviors. How these various parts combine to generate polarized patterns of protein localization in cells is only beginning to become clear. This review, part of the Special Issue on Cell Polarity, aims to highlight several emerging themes and design principles that underlie the process of cell polarization by components of the PAR network. PMID:25128809

Goehring, Nathan W

2014-11-01

117

Les Brulures Chimiques Par Le Laurier Rose  

PubMed Central

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

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

2010-01-01

118

-calcul et dualite : appel par nom et appel par valeur Jer^ome ROCHETEAU  

E-print Network

µ-calcul et dualit´e : appel par nom et appel par valeur J´er^ome ROCHETEAU R´esum´e L'extension `a r´eduction avec appel par valeur. On ´etudie cette dualit´e, d'une part `a travers le µ-calcul dont'autre part `a travers le ¯µ~µ-calcul dont les r´eductions reposent sur une sym´etrie gauche/droite du calcul

Paris-Sud XI, Université de

119

Systemic Par-4 inhibits non-autochthonous tumor growth  

PubMed Central

The tumor suppressor protein Par-4 (prostate apoptosis response-4) is spontaneously secreted by normal and cancer cells. Extracellular Par-4 induces caspase-dependent apoptosis in cancer cell cultures by binding, via its effector SAC domain, to cell surface GRP78 receptor. However, the functional significance of extracellular Par-4/SAC has not been validated in animal models. We show that Par-4/SAC-transgenic mice express systemic Par-4/SAC protein and are resistant to the growth of non-autochthonous tumors. Consistently, secretory Par-4/SAC pro-apoptotic activity can be transferred from these cancer-resistant transgenic mice to cancer-susceptible mice by bone marrow transplantation. Moreover, intravenous injection of recombinant Par-4 or SAC protein inhibits metastasis of cancer cells. Collectively, our findings indicate that extracellular Par-4/SAC is systemically functional in inhibition of tumor growth and metastasis progression, and may merit investigation as a therapy. PMID:21613819

Brandon, Jason; Qiu, Shirley; Shelton, Brent J; Spear, Brett; Bondada, Subbarao; Bryson, Scott

2011-01-01

120

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

SciTech Connect

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.

Chaudhuri, Barnali [University of Buffalo, The State University of New York; Gupta, Sayan [Case Western Reserve University; Urban, Volker S [ORNL; Chance, Mark [Case Western Reserve University; D'Mello, Rhijuta [Case Western Reserve University; Smith, Lauren [University of Buffalo, The State University of New York; Lyons, Kelly [University of Buffalo, The State University of New York; Gee, Jessica [University of Buffalo, The State University of New York

2010-01-01

121

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

SciTech Connect

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.

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

2011-12-31

122

CHAMBRE A TINCELLES CYLINDRIQUE A FILS AVEC ENREGISTREMENT PAR FERRITES  

E-print Network

304. CHAMBRE A �TINCELLES CYLINDRIQUE A FILS AVEC ENREGISTREMENT PAR FERRITES A. E. TAYLOR, I fils, avec enregistrement par ferrites, présentant l'avantage d'une quantité de matériau réduite pour assurée par des chambres à étincelles à ferrites. Les électrodes sont constituées par des feuilles d

Boyer, Edmond

123

Asservissement par PID Application du PWM au pont en H  

E-print Network

Plan Asservissement par PID PWM Ponts en H Application du PWM au pont en H Bibliographie Asservissement par PID, PWM et Ponts en H Siwar, Cédric, Samuel Télécom Paristech 4 mars 2011 Siwar, Cédric, Samuel ROSE 1 / 33 4 mars 2011 #12;Plan Asservissement par PID PWM Ponts en H Application du PWM au pont

Tardieu, Samuel

124

235 -2010 Anne : 2010 Dlivre par  

E-print Network

Sandrine ISOARD-GAUTHEUR LE BURNOUT SPORTIF CHEZ DES ADOLESCENTS(TES) EN POLE ESPOIR HANDBALL : APPROCHE tel-00842944,version1-9Jul2013 #12;Le Burnout Sportif chez des Adolescents(tes) en Pôle Espoir premier chapitre présente une revue de littérature sur le burnout sportif. Par la suite trois axes de

125

Historic macrophyte development in Par Pond  

Microsoft Academic Search

Aerial photographs from 1975, 1980, and 1983 were examined to evaluate the changes that have occurred in the wetland vegetation of Par Pond, a reactor-cooling reservoir. Evaluation of the aerial photographs was based on comparisons with ground-level vegetation maps made during July 1984. Comparisons of photographs from August and December of 1983 revealed the main seasonal change in the aerial

1985-01-01

126

NOUVEAU SYSTME TLGRAPHIQUE; PAR M. ESTIENNE.  

E-print Network

conformément au code Morse. Le trait peut occuper, en hauteur, la largeur du ruban de papier, quelle que soit volume du Morse. L'avan- cement du papier se produit par un mécanisme analogue à celui de ce dernier

Paris-Sud XI, Université de

127

Intramural Sports Par 3 Golf League  

E-print Network

The Department of Recreational Sports does not provide health or accident insurance that covers intramural sports participants. The Intramural Sports Program encourages each participant to maintain health and accidentIntramural Sports Par 3 Golf League Summer 2014 Intramural Sports Calendar of Events Summer 2014

Escher, Christine

128

suPAR and Team Nephrology  

PubMed Central

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

2014-01-01

129

CARTOGRAPHIE DES ACCIDENTS GOLOGIQUES PAR IMAGERIE  

E-print Network

119 CARTOGRAPHIE DES ACCIDENTS G�OLOGIQUES PAR IMAGERIE SATELLITAIRE LANDSAT-7 ETM+ ET ANALYSE DES cartographier les réseaux de fractures dans les roches cristallines et métamorphiques à l'aide des images les images brutes, permettant une meilleure cartographie des accidents géologiques. La carte

Paris-Sud XI, Université de

130

pr esent ee par Boubakeur BOUFAMA  

E-print Network

#12;ERES 3 Table des mati#12;eres Introduction 6 1 G eom etrie et vision par ordinateur 11 1.1 G eom : : : : : : : : : : : : : : : : : : 13 1.1.3 Invariants projectifs : : : : : : : : : : : : : : : : : : : : : : : 14 1.1.4 G eom etrie a ne : : : : : : : : : : : : : : : : : : : : : : : : : 17 1.1.5 G eom etrie euclidienne

Boyer, Edmond

131

L'ABSORPTION DES ULTRASONS PAR CERTAINES CTONES Par S. PARTHASARATHY et V. NARASIMHAN,  

E-print Network

957. L'ABSORPTION DES ULTRASONS PAR CERTAINES C�TONES Par S. PARTHASARATHY et V. NARASIMHAN coefficient d'absorption ont été mesurés dans plusieurs cétones à différentes températures et les résultats variation de l'absorption avec la température était positif dans l'intervalle considéré dans ce travail

Paris-Sud XI, Université de

132

Comptes Rendus des JNC 17 -Poitiers 2011 Simulation par lments finis des procds par infusion de rsine  

E-print Network

Comptes Rendus des JNC 17 - Poitiers 2011 Simulation par éléments finis des procédés par infusion de résine Finite Simulation of the liquid infusion processes G. Pacquaut, J. Bruchon, N. Moulin, S permettant de simuler par éléments finis les procé- dés par infusion de résine au travers de renforts fibreux

Paris-Sud XI, Université de

133

Mechanisms of Apoptosis by the Tumor Suppressor Par-4  

PubMed Central

Par-4 is a pro-apoptotic, tumor suppressor protein that induces apoptosis selectively in cancer cells. Endoplasmic reticulum-stress and higher levels of protein kinase A in tumor cells confer the coveted feature of cancer selective response to extracellular and intracellular Par-4, respectively. Recent studies have shown that systemic Par-4 confers resistance to tumor growth in mice, and that tumor-resistance is transferable by bone marrow transplantation. Moreover, recombinant Par-4 inhibits the growth of tumors in mice. As systemic Par-4 induces apoptosis via cell surface GRP78, strategies that promote GRP78 trafficking to the cell surface are expected sensitize cancer cells to circulating levels of Par-4. This review illustrates the domains and mechanisms by which Par-4 orchestrates the apoptotic process in both cell culture models and in physiological settings. PMID:22552839

Hebbar, Nikhil; Wang, Chi; Rangnekar, Vivek M.

2012-01-01

134

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

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. PMID:18802725

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

2008-11-01

135

UNIVERSIT DE GRENOBLE attribu par la bibliothque  

E-print Network

, for offering me a great place to stay during my thesis writing and for making sure that I am always properly the writing of my thesis. Finally, I woulkd like to thank my friends Vasil, Fabio, Pierre, Gaetan, Amael l'imiter avec de la stéréo-vision par ordinateur. Cela se fait à l'aide de deux caméras, une pour

Paris-Sud XI, Université de

136

Review of PAR parameterizations in ocean ecosystem models  

NASA Astrophysics Data System (ADS)

Commonly-used empirical equations for calculating downward 'photosynthetically available radiation' or PAR were reviewed in order to identify a more theoretically-sound parameterization for application to ocean biogeochemical models. Three different forms of broadband PAR parameterization are currently employed in biogeochemical models, each of them originating from the downward irradiance formulations normally applied to ocean circulation models, which produce poor attenuation estimates for PAR. Two of the PAR formulations, a single-exponential function and a double-exponential function, are parameterized by multiplying surface irradiance by a coefficient determining the portion of underwater PAR. The third formulation uses the second term of the double-exponential function. After elucidating the theoretical problems of modeling PAR using these parameterizations, we suggest an improved, R-modified double-exponential PAR formulation, including Paulson and Simpson's (1977) parameter values. We also newly estimate PAR penetration via least-squares fitting of values digitized from Jerlov's (1976) observations in different oceanic water types, and compare this PAR-observation derived parameterization with our new, theoretical, R-modified parameterization. Finally, we discuss a universal limitation inherent in current theoretical approaches to PAR parameterization.

Byun, Do-Seong; Wang, Xiao Hua; Hart, Deirdre E.; Zavatarelli, Marco

2014-12-01

137

A Conserved Mode of Protein Recognition and Binding in a ParD?ParE Toxin?Antitoxin Complex  

SciTech Connect

Toxin-antitoxin (TA) systems form a ubiquitous class of prokaryotic proteins with functional roles in plasmid inheritance, environmental stress response, and cell development. ParDE family TA systems are broadly conserved on plasmids and bacterial chromosomes and have been well characterized as genetic elements that promote stable plasmid inheritance. We present a crystal structure of a chromosomally encoded ParD-ParE complex from Caulobacter crescentus at 2.6 {angstrom} resolution. This TA system forms an {alpha}{sub 2}{beta}{sub 2} heterotetramer in the crystal and in solution. The toxin-antitoxin binding interface reveals extensive polar and hydrophobic contacts of ParD antitoxin helices with a conserved recognition and binding groove on the ParE toxin. A cross-species comparison of this complex structure with related toxin structures identified an antitoxin recognition and binding subdomain that is conserved between distantly related members of the RelE/ParE toxin superfamily despite a low level of overall primary sequence identity. We further demonstrate that ParD antitoxin is dimeric, stably folded, and largely helical when not bound to ParE toxin. Thus, the paradigmatic model in which antitoxin undergoes a disorder-to-order transition upon toxin binding does not apply to this chromosomal ParD-ParE TA system.

Dalton, Kevin M.; Crosson, Sean (UC)

2010-05-06

138

A new model for estimating boreal forest fPAR  

NASA Astrophysics Data System (ADS)

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.

Majasalmi, Titta; Rautiainen, Miina; Stenberg, Pauline

2014-05-01

139

Sur le rayonnement du polonium Par B. KUCERA,  

E-print Network

75 Sur le rayonnement du polonium Par B. KUCERA, [Laboratoire de l'Institut de physique de l avec B Ma- sek sur le le polonium. Il s'agit de la nature du rayonnemet émis par par le plonium , de du polonium. Le dispositif de mesure se comprend sans cxplica- 1 ion d'après la figure 1. V est un

Boyer, Edmond

140

IRRADIATION DES MTAUX Par R. M. WALKER 1  

E-print Network

474. IRRADIATION DES M�TAUX Par R. M. WALKER 1 Laboratoire de Chimie Physique de la Faculté des Sciences de Paris. Résumé. 2014 On montre que la théorie simple du seuil pour les défauts par irradiation donne une description excellente des principales caractéristiques des modifications induites par l'irradiation

Boyer, Edmond

141

DSINTGRATION DU TERBIUM 164 Par E. MONNAND et A. MOUSSA,  

E-print Network

D�SINT�GRATION DU TERBIUM 164 Par E. MONNAND et A. MOUSSA, Laboratoire de Chimie Nucléaire, Centre terbium 164 produit par la réaction nucléaire 164Dy(n, p)164Tb avec des neutrons de 14 MeV. L'isotope 164 du terbium n'a 6t6 signal6 jusqu'ici que par Alstad et Pappas [1] qui l'ont obtenu a partir de

Paris-Sud XI, Université de

142

SUR LA THORIE OSMOTIQUE DES PILES ; Par M. M. COUETTE.  

E-print Network

200 SUR LA TH�ORIE OSMOTIQUE DES PILES ; Par M. M. COUETTE. 1 Introduction. - La théorie osmotique des forces électromotrice créée par M. T~TTalther Nernst (~ ), en 1889, est devenue, ce me semble déterminer séparément les diffé- rences de potentiel aux divers contacts. M. Pellat a demandé cette dernière

Boyer, Edmond

143

Regulation of cell signalling by uPAR  

Microsoft Academic Search

Urokinase-type plasminogen activator receptor (uPAR) expression is elevated during inflammation and tissue remodelling and in many human cancers, in which it frequently indicates poor prognosis. uPAR regulates proteolysis by binding the extracellular protease urokinase-type plasminogen activator (uPA; also known as urokinase) and also activates many intracellular signalling pathways. Coordination of extracellular matrix (ECM) proteolysis and cell signalling by uPAR underlies

Harvey W. Smith; Chris J. Marshall

2010-01-01

144

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

PubMed Central

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

2013-01-01

145

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

146

NOMBRE DE RAYONS 03B1 MIS PAR UNE PRPARATION DE DPOT ACTIF DU THORIUM MESURE PAR SON RAYONNEMENT PNTRANT  

E-print Network

NOMBRE DE RAYONS 03B1 �MIS PAR UNE PR�PARATION DE D�POT ACTIF DU THORIUM MESUR�E PAR SON cm de Pb. Résultats. 1. But du travail. - Le Radiothorium, le Thorium X et le dépôt actif du Thorium sont généralement dosés par leur rayonnement y provenant de Thorium (C + Cfl). A cet effet, à l

Paris-Sud XI, Université de

147

CONTOUR DES RAIES D'ARC DU SODIUM ELARGIES PAR L'EFFET STARK INTERMOLCULAIRE Par S. WENIGER,  

E-print Network

37 CONTOUR DES RAIES D'ARC DU SODIUM ELARGIES PAR L'EFFET STARK INTERMOL�CULAIRE Par S. WENIGER le contour théorique d'une raie uni- quem'ent élargie par l'effet Stark, on procède de la façon observé permet de déterminer les valeurs approchées des constantes Stark pour les raies qui n'avaient pas

Boyer, Edmond

148

ETUDE DES RADIATIONS IONISANTES MISES PAR LES DCHARGES LECTRIQUES DANS L'AIR Par M. GEORGES DCHNE.  

E-print Network

l'étude, à la chambre d'ionisation, des radiations ionisantes très absor- bables émises par lesETUDE DES RADIATIONS IONISANTES �MISES PAR LES D�CHARGES �LECTRIQUES DANS L'AIR Par M. GEORGES décharges électriques non condensées dans l'air (aigrettes, étincelles en tension alternative avec

Boyer, Edmond

149

Diet-induced obesity, adipose inflammation, and metabolic dysfunction correlating with PAR2 expression are attenuated by PAR2 antagonism.  

PubMed

Excessive uptake of fatty acids and glucose by adipose tissue triggers adipocyte dysfunction and infiltration of immune cells. Altered metabolic homeostasis in adipose tissue promotes insulin resistance, type 2 diabetes, hypertension, and cardiovascular disease. Inflammatory and metabolic processes are mediated by certain proteolytic enzymes that share a common cellular target, protease-activated receptor 2 (PAR2). This study showed that human and rat obesity correlated in vivo with increased expression of PAR2 in adipose tissue, primarily in stromal vascular cells (SVCs) including macrophages. PAR2 was expressed more than other PARs on human macrophages and was increased by dietary fatty acids (palmitic, stearic, and myristic). A novel PAR2 antagonist, GB88 (5-isoxazoyl-Cha-Ile-spiroindene-1,4-piperidine), given orally at 10 mg/kg/d (wk 8-16) reduced body weight by ?10% in obese rats fed a high-carbohydrate high-fat (HCHF) diet for 16 wk, and strongly attenuated adiposity, adipose tissue inflammation, infiltrated macrophages and mast cells, insulin resistance, and cardiac fibrosis and remodeling; while reversing liver and pancreatic dysfunction and normalizing secretion of PAR2-directed glucose-stimulated insulin secretion in MIN6 ? cells. In summary, PAR2 is a new biomarker for obesity, and its expression is stimulated by dietary fatty acids; PAR2 is a substantial contributor to inflammatory and metabolic dysfunction; and a PAR2 antagonist inhibits diet-induced obesity and inflammatory, metabolic, and cardiovascular dysfunction. PMID:23964081

Lim, Junxian; Iyer, Abishek; Liu, Ligong; Suen, Jacky Y; Lohman, Rink-Jan; Seow, Vernon; Yau, Mei-Kwan; Brown, Lindsay; Fairlie, David P

2013-12-01

150

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

PubMed

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

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

2014-06-17

151

78 FR 42584 - Additional Designation of Aluminat, Pars Amayesh Sanaat Kish, Parviz Khaki, Pishro Systems...  

Federal Register 2010, 2011, 2012, 2013, 2014

...Additional Designation of Aluminat, Pars Amayesh Sanaat Kish, Parviz Khaki, Pishro...General, has determined that Aluminat, Pars Amayesh Sanaat Kish, Parviz Khaki, Pishro...Arak Road, Parcham Street, Arak, Iran PARS Amayesh Sanaat Kish AKA: PASK AKA:...

2013-07-16

152

Historic macrophyte development in Par Pond  

SciTech Connect

Aerial photographs from 1975, 1980, and 1983 were examined to evaluate the changes that have occurred in the wetland vegetation of Par Pond, a reactor-cooling reservoir. Evaluation of the aerial photographs was based on comparisons with ground-level vegetation maps made during July 1984. Comparisons of photographs from August and December of 1983 revealed the main seasonal change in the aerial coverage of wetland vegetation to be the wintertime loss of non-persistent emergent species such as Nelumbo lutea and Nymphaea odorata. Comparisons between September 1980 and August 1983 revealed that the lakeward extent of non-persistent macrophytes has increased by an average of 8.2 m, though not all sites have changed equally. For persistent macrophytes (principally Typha), the average increase in lakeward extent between December 1975 and August 1983 was 3.48 m. The extensive development of wetland vegetation in Par Pond as well as the substantial spread of vegetation over only a few years time indicates the high suitability of this habitat for the growth of wetland plants.

Grace, J.B.

1985-08-01

153

Par Pond vegetation status summer 1995 - July survey descriptive summary  

Microsoft Academic Search

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

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

1995-01-01

154

Clinical and immunopathological studies of pars planitis in a family  

Microsoft Academic Search

We examined a family in which two brothers with identical HLA typing have pars planitis with snowbanking. Immunopathological studies of one of their eyes showed that in the area of snowbanking over the pars plana there was mild to moderate inflammatory cell infiltration, consisting of mostly Pan T (Leu 4+) lymphocytes. The ratio of T helper\\/inducer to T suppressor\\/cytotoxic cells

R P Wetzig; C C Chan; R B Nussenblatt; A G Palestine; D O Mazur; K K Mittal

1988-01-01

155

Pars plana incisions of four patients: histopathology and electron microscopy  

Microsoft Academic Search

The pathology of pars plana incisions of four patients is described: three with light microscopy and one with light and electron microscopy. Two eyes were removed because of choroidal melanoma, immediately and 8 days after vitrectomy and transvitreous retinal biopsy. Considerable disruption of tissues surrounding the pars plana incisions was observed. Vitreous was incarcerated in the wounds, which healed with

F H Koch; A E Kreiger; M Spitznas; B Glasgow; R Y Foos; M O Yoshizumi

1995-01-01

156

The pattern of cervical penetration and the effect of topical treatment with prostaglandin and/or FSH and oxytocin on the depth of cervical penetration in the ewe during the peri-ovulatory period.  

PubMed

Artificial insemination in sheep has two major limiting factors: the poor quality of frozen-thawed ram semen and the convoluted anatomy of the sheep cervix that does not allow transcervical passage of an inseminating catheter. It has been demonstrated that in the ewe during estrus, there is a degree of cervical relaxation mediated by ovarian and possibly gonadotrohic hormones, and we set out to investigate factors that might enhance cervical relaxation. Five experiments were conducted on ewes of different breeds to determine: 1) the pattern of cervical penetration during the periovulatory period in ewes of several breeds (Welsh Mountain, Île-de-France, Vendéenne, Romanov and Sarda); 2) the effect of the "ram effect" a socio-sexual stimulus, on cervical penetration; and 3) the effects of the intracervical administration of follicle-stimulating hormone (FSH), oxytocin and a prostaglandin E agonist (misoprostol) on the depth of cervical penetration during the periovulatory period. The results showed that during the periovulatory period in all breeds examined, there was increased penetration of the cervical canal (P<0.05) by an inseminating catheter. Cervical penetration increased to a maximum 54 h after the removal of progestagen sponges and then gradually declined. Furthermore, the depth of cervical penetration but not its pattern, was affected (P<0.05) by the breed of ewe. The maximum depth of cervical penetration was lower (P<0.05) in the Vendéenne breed compared to the Île-de-France and Romanov breeds, which did not differ from one another. In the presence of rams, the depth of cervical penetration was increased at 48 and 54 h after removal of sponges (P<0.05) and reduced at 72 h (P<0.05). The local administration of hormones FSH, misoprostol (a PGE agonist) and oxytocin alone and in various combinations did not have any significant effect on the depth of cervical penetration during the periovulatory period. In conclusion, the natural relaxation of the cervix observed in ewes of several breeds occurs at a time during estrus, 54 h after the removal of progestagen sponges, which is the most suitable for artificial insemination. The effect was enhanced by the presence of a ram but not by the local intracervical administration of FSH, misoprostol and oxytocin even though oxytocin and PGE2 are involved in cervical function. The time of maximum cervical penetration in the preovulatory period (54 h) coincides with high LH and estradiol concentrations suggesting they might be responsible for the relaxation of the cervix probably through an oxytocin-PGE mediated pathway. PMID:22537999

Falchi, L; Taema, M; La Clanche, S; Scaramuzzi, R J

2012-07-15

157

Dissection of the region of Pseudomonas aeruginosa ParA that is important for dimerization and interactions with its partner ParB.  

PubMed

Pseudomonas aeruginosa ParA belongs to a large subfamily of Walker-type ATPases acting as partitioning proteins in bacteria. ParA has the ability to both self-associate and interact with its partner ParB. Analysis of the deletion mutants defined the part of the protein involved in dimerization and interactions with ParB. Here, a set of ParA alanine substitution mutants in the region between E67 and L85 was created and analysed in vivo and in vitro. All mutants impaired in dimerization (substitutions at positions M74, H79, Y82 and L84) were also defective in interactions with ParB, suggesting that ParA-ParB interactions depend on the ability of ParA to dimerize. Mutants with alanine substitutions at positions E67, C68, L70, E72, F76, Q83 and L85 were not impaired in dimerization, but were defective in interactions with ParB. The dimerization interface partly overlapped the pseudo-hairpin, involved in interactions with ParB. ParA mutant derivatives tested in vitro showed no defects in ATPase activity. Two parA alleles (parA84, whose product can neither self-interact nor interact with ParB, and parA67, whose product is impaired in interactions with ParB, but not in dimerization) were introduced into the P. aeruginosa chromosome by homologous gene exchange. Both mutants showed defective separation of ParB foci, but to different extents. Only PAO1161 parA84 was visibly impaired in terms of chromosome segregation, growth rate and motility, similar to a parA-null mutant. PMID:25139949

Bartosik, Aneta A; Glabski, Krzysztof; Jecz, Paulina; Lasocki, Krzysztof; Mikosa, Malgorzata; Plochocka, Danuta; Thomas, Christopher M; Jagura-Burdzy, Grazyna

2014-11-01

158

Recombination in the Human Pseudoautosomal Region PAR1  

PubMed Central

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

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

2014-01-01

159

Amlioration de l'utilisation par les bovins des chaumes de Sorghum bicolor par le hachage et la complmentation  

E-print Network

Amélioration de l'utilisation par les bovins des chaumes de Sorghum bicolor par le hachage et la and Leng, 1986 ILCA/Addis Ababa). Un essai d'amélioration de pailles de Sorghum bicolor complémenté à l

Boyer, Edmond

160

SPRY1 promotes the degradation of uPAR and inhibits uPAR-mediated cell adhesion and proliferation  

PubMed Central

Urokinase plasminogen activator receptor (uPAR) is a GPI anchored cell surface protein that is closely associated with invasion, migration, and metastasis of cancer cells. Many functional extracellular proteins and transmembrane receptors interact with uPAR. However, few studies have examined the association of uPAR with cytoplasm proteins. We previously used yeast two-hybrid screening to isolate several novel uPAR-interacting cytoplasmic proteins, including Sprouty1 (SPRY1), an inhibitor of the (Ras-mitogen-activated protein kinase) MAPK pathway. In this study, we show that SPRY1 interacts with uPAR and directs it toward lysosomal-mediated degradation. Overexpression of SPRY1 decreased the cell surface and cytoplasmic uPAR protein level. Moreover, SPRY1 overexpression augmented uPAR-induced cell adhesion to vitronectin as well as proliferation of cancer cells. Our results also further support the critical role of SPRY1 contribution to tumor growth. In a subcutaneous tumor model, overexpression of SPRY1 in HCT116 or A549 xenograft in athymic nude mice led to great suppression of tumor growth. These results show that SPRY1 may affect tumor cell function through direct interaction with uPAR and promote its lysosomal degradation. PMID:25520860

Liu, Xiufeng; Lan, Yan; Zhang, Di; Wang, Kai; Wang, Yao; Hua, Zi-Chun

2014-01-01

161

Species and Incompatibility Determination within the P1par Family of Plasmid Partition Elements  

PubMed Central

The P1par family of active plasmid partition systems consists of at least six members, broadly distributed in a variety of plasmid types and bacterial genera. Each encodes two Par proteins and contains a cis-acting parS site. Individual par systems can show distinct species specificities; the proteins from one type cannot function with the parS site of another. P1par-versus-P7par specificity resides within two hexamer BoxB repeats encoded by parS that contact the ParB protein near the carboxy terminus. Here, we examine the species specificity differences between Yersinia pestis pMT1parS and Escherichia coli P1 and P7parS. pMT1parS site specificity could be altered to that of either P1 or P7 by point mutation changes in the BoxB repeats. Just one base change in a single BoxB repeat sometimes sufficed. The BoxB sequence appears to be able to adopt a number of forms that define exclusive interactions with different ParB species. The looped parS structure may facilitate this repertoire of interaction specificities. Different P1par family members have different partition-mediated incompatibility specificities. This property defines whether two related plasmids can coexist in the same cell and is important in promoting the evolution of new plasmid species. BoxB sequence changes that switch species specificity between P1, P7, and pMT1 species switched partition-mediated plasmid incompatibility in concert. Thus, there is a direct mechanistic link between species specificity and partition-mediated incompatibility, and the BoxB-ParB interaction can be regarded as a special mechanism for facilitating plasmid evolution. PMID:16109939

Dabrazhynetskaya, Alena; Sergueev, Kirill; Austin, Stuart

2005-01-01

162

Protease-Activated Receptor (PAR)2, but Not PAR1, Is Involved in Collateral Formation and Anti-Inflammatory Monocyte Polarization in a Mouse Hind Limb Ischemia Model  

PubMed Central

Aims In collateral development (i.e. arteriogenesis), mononuclear cells are important and exist as a heterogeneous population consisting of pro-inflammatory and anti-inflammatory/repair-associated cells. Protease-activated receptor (PAR)1 and PAR2 are G-protein-coupled receptors that are both expressed by mononuclear cells and are involved in pro-inflammatory reactions, while PAR2 also plays a role in repair-associated responses. Here, we investigated the physiological role of PAR1 and PAR2 in arteriogenesis in a murine hind limb ischemia model. Methods and Results PAR1-deficient (PAR1-/-), PAR2-deficient (PAR2-/-) and wild-type (WT) mice underwent femoral artery ligation. Laser Doppler measurements revealed reduced post-ischemic blood flow recovery in PAR2-/- hind limbs when compared to WT, while PAR1-/- mice were not affected. Upon ischemia, reduced numbers of smooth muscle actin (SMA)-positive collaterals and CD31-positive capillaries were found in PAR2-/- mice when compared to WT mice, whereas these parameters in PAR1-/- mice did not differ from WT mice. The pool of circulating repair-associated (Ly6C-low) monocytes and the number of repair-associated (CD206-positive) macrophages surrounding collaterals in the hind limbs were increased in WT and PAR1-/- mice, but unaffected in PAR2-/- mice. The number of repair-associated macrophages in PAR2-/- hind limbs correlated with CD11b- and CD115-expression on the circulating monocytes in these animals, suggesting that monocyte extravasation and M-CSF-dependent differentiation into repair-associated cells are hampered. Conclusion PAR2, but not PAR1, is involved in arteriogenesis and promotes the repair-associated response in ischemic tissues. Therefore, PAR2 potentially forms a new pro-arteriogenic target in coronary artery disease (CAD) patients. PMID:23637930

Nossent, Anne Yael; van Oeveren-Rietdijk, Annemarie M.; de Vries, Margreet R.; Spek, C. Arnold; van Zonneveld, Anton Jan; Reitsma, Pieter H.; Hamming, Jaap F.; de Boer, Hetty C.; Versteeg, Henri H.; Quax, Paul H. A.

2013-01-01

163

TUDE PAR MESURE DE CONDUCTIBILIT LECTRIQUE ET PAR RSONANCE PARAMAGNTIQUE LECTRONIQUE DU MANGANSE  

E-print Network

MANGAN�SE DANS LE FLUORURE DE LITHIUM Par M. P. BERGE, C. GAGO (1), G. BLANC, Mmes M. ADAM-BENVENISTE et M étendu de température le processus de conduc- tibilité est lié aux paires Mn2+-lacunes lithium. Analysis of superhyperfine spectra confirms the presence of Mn2+ surrounded by an octahedron of fluorine

Paris-Sud XI, Université de

164

Taare Zameen Par and dyslexic savants  

PubMed Central

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

Chakravarty, Ambar

2009-01-01

165

Control of Cleavage Spindle Orientation in Caenorhabditis Elegans: The Role of the Genes Par-2 and Par-3  

PubMed Central

Polarized asymmetric divisions play important roles in the development of plants and animals. The first two embryonic cleavages of Caenorhabditis elegans provide an opportunity to study the mechanisms controlling polarized asymmetric divisions. The first cleavage is unequal, producing daughters with different sizes and fates. The daughter blastomeres divide with different orientations at the second cleavage; the anterior blastomere divides equally across the long axis of the egg, whereas the posterior blastomere divides unequally along the long axis. We report here the results of our analysis of the genes par-2 and par-3 with respect to their contribution to the polarity of these division. Strong loss-of-function mutations in both genes lead to an equal first cleavage and an altered second cleavage. Interestingly, the mutations exhibit striking gene-specific differences at the second cleavage. The par-2 mutations lead to transverse spindle orientations in both blastomeres, whereas par-3 mutations lead to longitudinal spindle orientations in both blastomeres. The spindle orientation defects correlate with defects in centrosome movements during both the first and the second cell cycle. Temperature shift experiments with par-2(it5ts) indicate that the par-2(+) activity is not required after the two-cell stage. Analysis of double mutants shows that par-3 is epistatic to par-2. We propose a model wherein par-2(+) and par-3(+) act in concert during the first cell cycle to affect asymmetric modification of the cytoskeleton. This polar modification leads to different behaviors of centrosomes in the anterior and posterior and leads ultimately to blastomere-specific spindle orientations at the second cleavage. PMID:7713417

Cheng, N. N.; Kirby, C. M.; Kemphues, K. J.

1995-01-01

166

Prostate Apoptosis Response 4 (Par-4), a Novel Substrate of Caspase-3 during Apoptosis Activation  

PubMed Central

Prostate apoptosis response 4 (Par-4) is a ubiquitously expressed proapoptotic tumor suppressor protein. Here, we show for the first time, that Par-4 is a novel substrate of caspase-3 during apoptosis. We found that Par-4 is cleaved during cisplatin-induced apoptosis in human normal and cancer cell lines. Par-4 cleavage generates a C-terminal fragment of ?25 kDa, and the cleavage of Par-4 is completely inhibited by a caspase-3 inhibitor, suggesting that caspase-3 is directly involved in the cleavage of Par-4. Caspase-3-deficient MCF-7 cells do not show Par-4 cleavage in response to cisplatin treatment, and restoration of caspase-3 in MCF-7 cells produces a decrease in Par-4 levels, with the appearance of a cleaved fragment. Additionally, knockdown of Par-4 reduces caspase-3 activation and apoptosis induction. Site-directed mutagenesis reveals that Par-4 cleavage by caspase-3 occurs at an unconventional site, EEPD131?G. Interestingly, overexpression of wild-type Par-4 but not the Par-4 D131A mutant sensitizes cells to cisplatin-induced apoptosis. Upon caspase-3 cleavage, the cleaved fragment of Par-4 accumulates in the nucleus and displays increased apoptotic activity. Overexpression of the cleaved fragment of Par-4 inhibits I?B? phosphorylation and blocks NF-?B nuclear translocation. We have identified a novel specific caspase-3 cleavage site in Par-4, and the cleaved fragment of Par-4 retains proapoptotic activity. PMID:22184067

Chaudhry, Parvesh; Singh, Mohan; Parent, Sophie

2012-01-01

167

GABA, Receptor-Mediated Inhibition of Rat Substantia Nigra Dopaminergic Neurons by Pars Reticulata Projection Neurons  

Microsoft Academic Search

Evidence from electrophysiological studies has suggested an inhibitory interaction between GABAergic neurons in substantia nigra pars reticulata and dopaminergic neurons in pars compacta. However, that this inhibitory interaction is due to a projection from pars reticulata to pars compacta has never been demonstrated directly, nor has the GA- BAergic neuron that mediates the interaction been identi- fied either electrophysiologically or

J. M. Tepper; L. P. Martin; D. R. Anderson

1995-01-01

168

View from southeast to northwest of PAR site bachelor officers' ...  

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

View from southeast to northwest of PAR site bachelor officers' quarters - Stanley R. Mickelsen Safeguard Complex, Bachelor Officers' Quarters, North of Second Avenue; South of Metal & Woodworking Shop No. 706, Nekoma, Cavalier County, ND

169

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

170

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

NASA Technical Reports Server (NTRS)

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.

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

1979-01-01

171

Universit de Grenoble N attribu par la bibliothque  

E-print Network

.1. Scriptural Translation, Transliteration and Transcription traduction (Methods and Tools for Weak Problems of Translation) Thèse dirigée par M. Christian BOITET...................................................................................................................... 7 Scriptural Translation and other Weak Translation Problems ...................... 7 Chapter 1

Boyer, Edmond

172

Description des alignements forms par DTW Franois Petitjean  

E-print Network

distance de Levenshtein, également appe- lée distance d'édition, et a été introduite par [2, 3] dans le'autre séquence en minimisant les coûts d'association. Le coût d'une association correspond à la distance entre séquence par rapport à une autre, et parvient ainsi à saisir des similarités que la distance euclidienne ne

Paris-Sud XI, Université de

173

StePar: an automatic code for stellar parameter determination  

NASA Astrophysics Data System (ADS)

We introduce a new automatic code (StePar) for determinig stellar atmospheric parameters (T_{eff}, log{g}, ? and [Fe/H]) in an automated way. StePar employs the 2002 version of the MOOG code (Sneden 1973) and a grid of Kurucz ATLAS9 plane-paralell model atmospheres (Kurucz 1993). The atmospheric parameters are obtained from the EWs of 263 Fe I and 36 Fe II lines (obtained from Sousa et al. 2008, A&A, 487, 373) iterating until the excitation and ionization equilibrium are fullfilled. StePar uses a Downhill Simplex method that minimizes a quadratic form composed by the excitation and ionization equilibrium conditions. Atmospheric parameters determined by StePar are independent of the stellar parameters initial-guess for the problem star, therefore we employ the canonical solar values as initial input. StePar can only deal with FGK stars from F6 to K4, also it can not work with fast rotators, veiled spectra, very metal poor stars or Signal to noise ratio below 30. Optionally StePar can operate with MARCS models (Gustafson et al. 2008, A&A, 486, 951) instead of Kurucz ATLAS9 models, additionally Turbospectrum (Alvarez & Plez 1998, A&A, 330, 1109) can replace the MOOG code and play its role during the parameter determination. StePar has been used to determine stellar parameters for some studies (Tabernero et al. 2012, A&A, 547, A13; Wisniewski et al. 2012, AJ, 143, 107). In addition StePar is being used to obtain parameters for FGK stars from the GAIA-ESO Survey.

Tabernero, H. M.; González Hernández, J. I.; Montes, D.

2013-05-01

174

Analyse structurale des matriaux carbons trs dsordonns par microspectroscopie Raman  

E-print Network

Analyse structurale des matériaux carbonés très désordonnés par microspectroscopie Raman'organisation de la matière organique dans les métasédiments peut être quantifié par microspectroscopie Raman. De'organisation et les pics de température du métamorphisme, et ont calibré le géothermomètre RSCM (Raman

Boyer, Edmond

175

Article original Diffrenciation par le systme API 50 CH  

E-print Network

Article original Différenciation par le système API 50 CH et électrophorèse des mycoplasmes Marcy-l'Ã?toile, France (Reçu le 15 janvier 1991; accepté le 11 juin 1991) Résumé ― Le système API'aspect des colonies lors de l'isolement, ainsi que les résultats fournis par le système API 50 CH ont permis

Paris-Sud XI, Université de

176

Par reduction in ofdm via active constellation extension  

Microsoft Academic Search

The high peak-to-average power ratio (PAR) in orthogonal frequency division multiplexing (OFDM) modulation systems can significantly reduce power efficiency and performance. Methods exist which alter or introduce new signal constellations to combat large signal peaks. We present a new PAR-reduction method that dynamically extends outer constellation points in active (data-carrying) channels, within margin-preserving constraints, in order to minimize the peak

Brian Scott Krongold; Douglas L. Jones

2003-01-01

177

DTERMINATION DE L'NERGIE CINTIQUE MAXIMUM DES NEUTRONS MIS PAR LE GLUCINIUM BOMBARD PAR LES RAYONS a DU POLONIUM  

E-print Network

RAYONS a DU POLONIUM Par L. WINAND. Sommaire. 2014 L'auteur détermine les énergies cinétiques des noyaux envisagée. En admettant que c'est l'isotope 11 du Bore irradié par les particules alpha du Polonium qui est'énergie maximum observés. Ce noyau, sous l'action des rayons alpha du Polonium peut émettre, soit un proton, soit

Boyer, Edmond

178

Vaissire, J, 2010, Le franais, langue frontires par excellence , dans FRONTIRES, DU LINGUISTIQUE AU SMIOTIQUE, ouvrage collectif initi par  

E-print Network

segmentation du continuum vocal. Les résultats issus des expérimentations contrôlées ont mis à jour la de la parole, les pauses respiratoires et les différences d'effort articulatoire (mesurables par les discours. Cet effort peut augmenter, par exemple, sur un élément du message à focaliser. Le niveau

Paris-Sud XI, Université de

179

Platelet protease-activated receptor (PAR)4, but not PAR1, associated with neutral sphingomyelinase responsible for thrombin-stimulated ceramide-NF-?B signaling in human platelets.  

PubMed

Thrombin activates platelets mainly through protease-activated receptor (PAR)1 and PAR4. However, downstream platelet signaling between PAR1 and PAR4 is not yet well understood. This study investigated the relationship between nSMase/ceramide and the NF-?B signaling pathway in PARs-mediated human platelet activation. The LC-MS/MS, aggregometry, flow cytometry, immunoprecipitation, and mesenteric microvessels of mice were used in this study. Human platelets stimulated by thrombin, 3-OMS (a neutral sphingomyelinase [nSMase] inhibitor) and Bay11-7082 (an NF-?B inhibitor) significantly inhibited platelet activation such as P-selectin expression. Thrombin also activated I?B kinase (IKK)? and I?B? phosphorylation; such phosphorylation was inhibited by 3-OMS and SB203580 (a p38 MAPK inhibitor). Moreover, 3-OMS abolished platelet aggregation, IKK?, and p38 MAPK phosphorylation stimulated by PAR4-AP (a PAR4 agonist) but not by PAR1-AP (a PAR1 agonist). Immunoprecipitation revealed that nSMase was directly associated with PAR4 but not PAR1 in resting platelets. In human platelets, C24:0-ceramide is the predominant form of ceramides in the LC/MS-MS assay; C24:0-ceramide increases after stimulation by thrombin or PAR4-AP, but not after stimulation by PAR1-AP. We also found that C2-ceramide (a cell-permeable ceramide analog) activated p38 MAPK and IKK? phosphorylation in platelets and markedly shortened the occlusion time of platelet plug formation in vivo. This study demonstrated that thrombin activated nSMase by binding to PAR4, but not to PAR1, to increase the C24:0-ceramide level, followed by the activation of p38 MAPK-NF-?B signaling. Our results showed a novel physiological significance of PAR4-nSMase/ceramide-p38 MAPK-NF-?B cascade in platelet activation. PMID:23065519

Chen, Wei-Fan; Lee, Jie-Jen; Chang, Chao-Chien; Lin, Kuan-Hong; Wang, Shwu-Huey; Sheu, Joen-Rong

2013-05-01

180

ACCLRATEUR DE 340 KV DESTIN A TUDIER LES RACTIONS INDUITES PAR TRITONS Par Mme D. MAGNAC-VALETTE, MM. M. SUFFERT, M. LIESS et P. CER,  

E-print Network

88. ACC�L�RATEUR DE 340 KV DESTIN� A �TUDIER LES R�ACTIONS INDUITES PAR TRITONS Par Mme D. MAGNAC électrostatique et spécialement construit pour étudier les réactions induites par tritons. Il donne un faisceau working with an electrostatic high tension is described. It is specially designed for triton acceleration

Paris-Sud XI, Université de

181

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

SciTech Connect

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.

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

1995-06-01

182

Bacillus subtilis Soj (ParA): The involvement of DNA binding and dynamic localization in plasmid partitioning  

E-print Network

The ParA family of ATPases encompasses proteins with a wide variety of functions. The prototype of this family is the ParA ATPase from the P1 prophage plasmid, which, along with ParB and the parS binding site, is required for the faithful...

Hester, Christina Marie

2008-05-08

183

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

SciTech Connect

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.

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

1995-09-01

184

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

SciTech Connect

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.

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

1995-11-01

185

Emerging Roles for the FSH Receptor Adapter Protein APPL1 and Overlap of a Putative 14-3-3? Interaction Domain with a Canonical G-protein Interaction Site  

PubMed Central

The interaction of cytoplasmic proteins with intracellular domains of membrane receptors can occur at several opportunities, including: during biosynthesis, while in membrane residency and during internalization and recycling following ligand binding. Since the initial discovery that it interacts with the FSH receptor (FSHR) together with additional members of a potential signaling complex, APPL1 has been shown to interact with a variety of membrane receptors. Recent subcellular localizations of APPL1 place it in dynamic and varied venues in the cell, including at the cell membrane, the nucleus and the early endosomes. Another adapter protein family the 14-3-3 proteins, are largely recognized as binding to phosphorylation sites but recent work demonstrated that in the case of FSHR, the 14-3-3 site overlaps with the canonical G-protein binding site. G-proteins appear to sample the environment and exchange between the membrane and intracellular locales and this binding could be mediated by or modulated by receptor interactions at the 14-3-3 binding site. Observations that multiple proteins can interact with cytoplasmic domains of GPCRs leads to the inescapable conclusion that either the interactions occur via orderly replacement or exchange, or that receptors are simultaneously occupied by a variety of adapters and effectors or even that oligomers of dimeric GPCRs provide for platforms that can simultaneously interact with effectors and adaptors. PMID:20600589

Mahale, Smita D.; Nechamen, Cheryl A.; Davydenko, Olga; Thomas, Richard M.; Ulloa-Aguirre, Alfredo

2010-01-01

186

PAR-3 Oligomerization May Provide an Actin-Independent Mechanism to Maintain Distinct Par Protein Domains in the Early Caenorhabditis elegans Embryo  

PubMed Central

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. PMID:21943422

Dawes, Adriana T.; Munro, Edwin M.

2011-01-01

187

The Pars Interarticularis Stress Reaction, Spondylolysis, and Spondylolisthesis Progression  

PubMed Central

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

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

1998-01-01

188

PAR-1 phosphorylates Mind bomb to promote vertebrate neurogenesis  

PubMed Central

Summary Generation of neurons in the vertebrate central nervous system requires complex transcriptional regulatory network and signaling processes in polarized neuroepithelial progenitor cells. Here we demonstrate that neurogenesis in the Xenopus neural plate in vivo and mammalian neural progenitors in vitro involves intrinsic antagonistic activities of the polarity proteins PAR-1 and aPKC. Furthermore, we show that Mind bomb (Mib), a ubiquitin ligase that promotes Notch ligand trafficking and activity, is a crucial molecular substrate for PAR-1. The phosphorylation of Mib by PAR-1 results in Mib degradation, repression of Notch signaling and stimulation of neuronal differentiation. These observations suggest a conserved mechanism for neuronal fate determination that might operate during asymmetric divisions of polarized neural progenitor cells. PMID:19686683

Ossipova, Olga; Ezan, Jerome; Sokol, Sergei Y.

2010-01-01

189

Effect of trans pars plana surgery on the corneal endothelium.  

PubMed

Endothelial cell density and thickness of the cornea do not appear to be affected by long-standing diabetes mellitus. Standard intra- or extracapsular cataract surgery results in a statistically significant reduction of endothelial cell density, but not in a long-term change of corneal thickness. Endothelial cell loss after trans pars plana surgery averages 8.5%. Differences in endothelial cell loss between phakic eyes of diabetics and phakic and aphakic eyes of nondiabetics subjected to lens removal and/or vitrectomy are not statistically significant. Corneal thickness is increased to a statistically significant degree in all eyes after trans pars plana surgery. Although the cornea in diabetics requires more time to recover after trans pars plana surgery, we found no evidence that it suffers significantly more damage than the cornea in nondiabetics. PMID:7262410

Buettner, H; Bourne, W M

1981-01-01

190

Competing ParA Structures Space Bacterial Plasmids Equally over the Nucleoid.  

PubMed

Low copy number plasmids in bacteria require segregation for stable inheritance through cell division. This is often achieved by a parABC locus, comprising an ATPase ParA, DNA-binding protein ParB and a parC region, encoding ParB-binding sites. These minimal components space plasmids equally over the nucleoid, yet the underlying mechanism is not understood. Here we investigate a model where ParA-ATP can dynamically associate to the nucleoid and is hydrolyzed by plasmid-associated ParB, thereby creating nucleoid-bound, self-organizing ParA concentration gradients. We show mathematically that differences between competing ParA concentrations on either side of a plasmid can specify regular plasmid positioning. Such positioning can be achieved regardless of the exact mechanism of plasmid movement, including plasmid diffusion with ParA-mediated immobilization or directed plasmid motion induced by ParB/parC-stimulated ParA structure disassembly. However, we find experimentally that parABC from Escherichia coli plasmid pB171 increases plasmid mobility, inconsistent with diffusion/immobilization. Instead our observations favor directed plasmid motion. Our model predicts less oscillatory ParA dynamics than previously believed, a prediction we verify experimentally. We also show that ParA localization and plasmid positioning depend on the underlying nucleoid morphology, indicating that the chromosomal architecture constrains ParA structure formation. Our directed motion model unifies previously contradictory models for plasmid segregation and provides a robust mechanistic basis for self-organized plasmid spacing that may be widely applicable. PMID:25521716

Ietswaart, Robert; Szardenings, Florian; Gerdes, Kenn; Howard, Martin

2014-12-01

191

Competing ParA Structures Space Bacterial Plasmids Equally over the Nucleoid  

PubMed Central

Low copy number plasmids in bacteria require segregation for stable inheritance through cell division. This is often achieved by a parABC locus, comprising an ATPase ParA, DNA-binding protein ParB and a parC region, encoding ParB-binding sites. These minimal components space plasmids equally over the nucleoid, yet the underlying mechanism is not understood. Here we investigate a model where ParA-ATP can dynamically associate to the nucleoid and is hydrolyzed by plasmid-associated ParB, thereby creating nucleoid-bound, self-organizing ParA concentration gradients. We show mathematically that differences between competing ParA concentrations on either side of a plasmid can specify regular plasmid positioning. Such positioning can be achieved regardless of the exact mechanism of plasmid movement, including plasmid diffusion with ParA-mediated immobilization or directed plasmid motion induced by ParB/parC-stimulated ParA structure disassembly. However, we find experimentally that parABC from Escherichia coli plasmid pB171 increases plasmid mobility, inconsistent with diffusion/immobilization. Instead our observations favor directed plasmid motion. Our model predicts less oscillatory ParA dynamics than previously believed, a prediction we verify experimentally. We also show that ParA localization and plasmid positioning depend on the underlying nucleoid morphology, indicating that the chromosomal architecture constrains ParA structure formation. Our directed motion model unifies previously contradictory models for plasmid segregation and provides a robust mechanistic basis for self-organized plasmid spacing that may be widely applicable. PMID:25521716

Gerdes, Kenn; Howard, Martin

2014-01-01

192

Subcellular Localization and Characterization of the ParAB System from Corynebacterium glutamicum?  

PubMed Central

Faithful segregation of chromosomes and plasmids is a vital prerequisite to produce viable and genetically identical progeny. Bacteria use a specialized segregation system composed of the partitioning proteins ParA and ParB to segregate certain plasmids. Strikingly, homologues of ParA and ParB are found to be encoded in many chromosomes. Although mutations in the chromosomal Par system have effects on segregation efficiency, the exact mechanism by which the chromosomes are segregated into the daughter cells is not fully understood. We describe the polar localization of the ParB origin nucleoprotein complex in the actinomycete Corynebacterium glutamicum. ParB and the origin of replication were found to be stably localized to the cell poles. After replication, the origins move toward the opposite pole. Purified ParB was able to bind to the parS consensus sequence in vitro. C. glutamicum possesses two ParA-like partitioning ATPase proteins. Both proteins interact with ParB but show a slightly different subcellular localization and phenotype. While ParA might be part of a conventional partitioning system, PldP seems to play a role in division site selection. PMID:20435732

Donovan, Catriona; Schwaiger, Astrid; Krämer, Reinhard; Bramkamp, Marc

2010-01-01

193

Modelling the Establishment of PAR Protein Polarity in the One-Cell C. elegans Embryo  

E-print Network

At the one-cell stage, the C. elegans embryo becomes polarized along the anterior-posterior axis. The PAR proteins form complementary anterior and posterior domains in a dynamic process driven by cytoskeletal rearrangement. Initially, the PAR proteins are uniformly distributed throughout the embryo. Following a cue from fertilization, cortical actomyosin contracts towards the anterior pole. PAR-3/PAR-6/PKC-3 (the anterior PAR proteins) become restricted to the anterior cortex. PAR-1 and PAR-2 (the posterior PAR proteins) become enriched in the posterior cortical region. We present a mathematical model of this polarity establishment process, in which we take a novel approach to combine reaction-diffusion dynamics of the PAR proteins coupled to a simple model of actomyosin contraction. We show that known interactions between the PAR proteins are sufficient to explain many aspects of the observed cortical PAR dynamics in both wild-type and mutant embryos. However, cytoplasmic PAR protein polarity, which is vital for generating daughter cells with distinct molecular components, cannot be properly explained within such a framework. We therefore consider additional mechanisms that can reproduce the proper cytoplasmic polarity. In particular we predict that cytoskeletal asymmetry in the cytoplasm, in addition to the cortical actomyosin asymmetry, is a critical determinant of PAR protein localization.

Filipe Tostevin; Martin Howard

2008-11-20

194

Urokinase Plasminogen Activator Receptor (uPAR) Targeted Nuclear Imaging and Radionuclide Therapy  

PubMed Central

Urokinase-type plasminogen activator receptor (uPAR) is a glycosylphosphatidylinositol (GPI)-anchored protein. Besides regulating proteolysis, uPAR could also activate many intracellular signaling pathways that promote cell motility, invasion, proliferation, and survival through cooperating with transmembrane receptors. uPAR is overexpressed across a variety of tumors and is associated with cancer invasion and metastasis. In order to meet the demand for a rapid development and potential clinical application of anti-cancer therapy based on uPA/uPAR system, it is desirable to develop non-invasive imaging methods to visualize and quantify uPAR expression in vivo. In this review, we will discuss recent advances in the development of uPAR-targeted nuclear imaging and radionuclide therapy agents. The successful development of molecular imaging probes to visualize uPAR expression in vivo would not only assist preclinical researches on uPAR function, but also eventually impact patient management. PMID:23843898

Li, Dan; Liu, Shuanglong; Shan, Hong; Conti, Peter; Li, Zibo

2013-01-01

195

Par-4 Down-regulation Promotes Breast Cancer Recurrence by Preventing Multinucleation following Targeted Therapy  

PubMed Central

Summary Most deaths from breast cancer result from tumor recurrence, but the mechanisms underlying tumor relapse are largely unknown. We now report that Par-4 is down-regulated during tumor recurrence and that Par-4 down-regulation is necessary and sufficient to promote recurrence. Tumor cells with low Par-4 expression survive therapy by evading a program of Par-4-dependent multinucleation and apoptosis that is otherwise engaged following treatment. Low Par-4 expression is associated with poor response to neoadjuvant chemotherapy and an increased risk of relapse in breast cancer patients, and Par-4 is down-regulated in residual tumor cells that survive neoadjuvant chemotherapy. Our findings identify Par-4-induced multinucleation as a mechanism of cell death in oncogene-addicted cells and establish Par-4 as a negative regulator of breast cancer recurrence. PMID:23770012

Alvarez, James V.; Pan, Tien-chi; Ruth, Jason; Feng, Yi; Zhou, Alice; Pant, Dhruv; Grimley, Joshua S.; Wandless, Thomas J.; DeMichele, Angela; Chodosh, Lewis A.

2013-01-01

196

Class 8. Telomeres and PAR October 5, 2009 Boyd, et al., 1996  

E-print Network

Class 8. Telomeres and PAR October 5, 2009 1 Telomeres A model Boyd, et al., 1996 #12;Class 8. Telomeres and PAR October 5, 2009 2 Spatial cue -> polarity Cuenca, A. A. et al. Development 2003://ftp.wormbase.org/pub/wormbase/datasets/seydoux_2003/MOVIE02%20PAR-6.mov #12;Class 8. Telomeres and PAR October 5, 2009 3 Cuenca, A. A. et al

Devoto, Stephen H.

197

Etude de la prvision de la digestibilit des fourrages par une mthode enzymatique  

E-print Network

pepsine dans l'acide chlorhydrique 1 N, 24 heures à 40°, suivi d'un traitement par une cellulase « Onozuka celle par la pepsine-cellulase était améliorée par la présence de pepsine (SR = 0,036 avec pepsine) ; toutefois avec la valeur de 1 N choisie, la valeur de la digestibilité par la pepsine-cellulase se rapproche

Paris-Sud XI, Université de

198

Alternative 3' UTR selection controls PAR-5 homeostasis and cell polarity in C. elegans embryos.  

PubMed

Cell polarity in one-cell C. elegans embryos guides asymmetric cell division and cell-fate specification. Shortly after fertilization, embryos establish two antagonistic cortical domains of PAR proteins. Here, we find that the conserved polarity factor PAR-5 regulates PAR domain size in a dose-dependent manner. Using quantitative imaging and controlled genetic manipulation, we find that PAR-5 protein levels reflect the cumulative output of three mRNA isoforms with different translational efficiencies mediated by their 3' UTRs. 3' UTR selection is regulated, influencing PAR-5 protein abundance. Alternative splicing underlies the selection of par-5 3' UTR isoforms. 3' UTR splicing is enhanced by the SR protein kinase SPK-1, and accordingly, SPK-1 is required for wild-type PAR-5 levels and PAR domain size. Precise regulation of par-5 isoform selection is essential for polarization when the posterior PAR network is compromised. Together, strict control of PAR-5 protein levels and feedback from polarity to par-5 3' UTR selection confer robustness to embryo polarization. PMID:25199833

Mikl, Martin; Cowan, Carrie R

2014-09-11

199

TUDE COMPARATIVE DES VIBRATIONS DE BASSES FRQUENCES DE LA 03B2-HYDROQUINONE PAR INFRAROUGE  

E-print Network

amorcee par ensemencement avec un monocristal de clathrate d'hydroquinone pr6sentant un taux eleve de H2S ET PAR DIFFUSION IN�LASTIQUE DES NEUTRONS J. S. HIGGINS Institut Laue-Langevin, 38000 Grenoble 1976, accepté le 23 aofit 1976Jj Résumé. 2014 La diffusion des neutrons lents par l'hydroquinone 03B2

Boyer, Edmond

200

SUR UN SILICATE DE CADMIUM LUMINESCENT Par A. LEVIALDI et V. LUZZATI.  

E-print Network

SUR UN SILICATE DE CADMIUM LUMINESCENT Par A. LEVIALDI et V. LUZZATI. Sommaire. - �tude de quelques propriétés d'un silicate de cadmium (1) luminescent. Leur interpré- tation par la théorie des trappes de silicate de cadmium par des radiations ultra- violettes de longueur d'onde voisine de ), = 2537 A

Boyer, Edmond

201

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

ERIC Educational Resources Information Center

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…

Lorenzetti, Liza; Walsh, Christine Ann

2014-01-01

202

Reconstruction 3D du bti partir d'une seule image par naissances et morts multiples  

E-print Network

Reconstruction 3D du bâti à partir d'une seule image par naissances et morts multiples Jean ne conserver que les plus pertinentes par un algorithme de type naissances et morts multiples. Nous plus pertinents. Ce principe est décliné par un algorithme de type naissances et morts mul- tiples

Boyer, Edmond

203

TUDE OPTIQUE ET LECTRIQUE SUR LE TELLURURE DE BISMUTH Bi2Te3 Par J. LAGRENAUDIE,  

E-print Network

39 A �TUDE OPTIQUE ET �LECTRIQUE SUR LE TELLURURE DE BISMUTH Bi2Te3 Par J. LAGRENAUDIE, C. N. E. T, PAGE Le tellurure de bismuth Bi2 Te 3 a été préparé par cofusion des éléments, vers 600 °C, et purifié

Boyer, Edmond

204

05 Novembre 2012 IPNO-T-12-05 Prsente par  

E-print Network

and nitrilotriacetic acids was studied using liquid-liquid extraction with the element at tracer scale (CPa en Sciences De l'Université Paris Sud Complexation des actinides (III, IV et V) par des acides/11/2012 par Sébastien LEGUAY Complexation des actinides (III, IV et V) par des acides organiques Directeur de

Boyer, Edmond

205

The pars intermedia of the mink, Mustela vison  

Microsoft Academic Search

The pars intermedia of intact and experimental female minks has been studied by light, electron and fluorescence microscopy. The general structure of the mink intermediate lobe is described. Two main cell types are recognized. One, termed glandular cell, predominates in number and is characterized by the presence of electron-dense granules about 200 nm in diameter and numerous large vesicles up

B. Weman; A. Nobin

1973-01-01

206

QUELQUES PROPRITS DES PARTICULES ANORMALEMENT LONGUES MISES PAR DES RADIOLMENTS  

E-print Network

de France. Résumé. 2014 Les sources de polonium naturel et de polonium artificiel provenant de. On constate également une émission de neutrons par les deux sources. Abstract. 2014 Natural polonium sources and artificial polonium sources from bismuth irradiated by neutrons, emit a same radiation, abormally long

Paris-Sud XI, Université de

207

ParFlow User's Manual GMWI 2010-01  

E-print Network

. Smith3 , Carol S. Woodward4 , Robert D. Falgout5 , Ian M. Ferguson6 , Chuck Baldwin, William J. Bosl 7.M. Ferguson, C. Baldwin, W.J. Bosl, R. Hornung, S. Ashby, ParFlow User's Manual. International Ground Water. Kollet, Ian M. Ferguson, Steven G. Smith, Carol S. Woodward. Permission is granted to copy, distribute

208

La simulation pour les systmes pilots par le produit  

E-print Network

résolution du problème, vieux de 50 ans, de synchronisation, de lien entre les flux Chapitre rédigé par celle-ci les hauts niveaux de décision ont une vision globale de tout le système. La plupart des

Paris-Sud XI, Université de

209

INCIDENCE DU DOPAGE PAR LES TRANQUILLISANTS SUR L'ACTIVIT  

E-print Network

OF TRANQUILLIZER DOPING ON THE MUSCULAR ACTIVITY ON THE SPORT HORSE. I. - ACEPROMAZINE Doping with tranquillizersINCIDENCE DU DOPAGE PAR LES TRANQUILLISANTS SUR L'ACTIVITÃ? MUSCULAIRE DU CHEVAL DE SPORT I has appeared recently in horse-back riding sports. In this paper we study the effects of acepromazine

Paris-Sud XI, Université de

210

INSTITUT NATIONAL POLYTECHNIQUE DE GRENOBLE N attribu par la bibliothque  

E-print Network

, Myriam, Alexis ainsi que l'équipe de la ligne D2AM pour leur aide lors des expériences de diffusion aux ou friction stir welding (FSW) 4 A-1 Principe du soudage par friction malaxage (friction stir welding

Paris-Sud XI, Université de

211

DIFFUSION STIMULE INDUITE PAR UNE ABSORPTION A DEUX PHOTONS  

E-print Network

harmonique d'un laser a Rubis déclenché. L'impulsion a 3 471 A avait une duree de 8 ns a mi-hauteur. Le faisceau, monomode longitudinal et spatial a la sortie de l'oscillateur, étant degrade par la chaine d

Boyer, Edmond

212

INFECTION EXPRIMENTALE DU BLIER PAR SALMONELLA ABORTUS OVIS  

E-print Network

INFECTION EXPÃ?RIMENTALE DU BÃ?LIER PAR SALMONELLA ABORTUS OVIS R. SANCHIS P. PARDON2 Georgette, France Summary EXPERIMENTAL INFECTION OF RAM WITH SALMONELLA ABORTUS OVIS. - The susceptibility of rams to experimental challenge with Salmonella abortus ovis was investigated by subcutaneous, conjunctival or preputial

Paris-Sud XI, Université de

213

L'analyse par activation de neutrons de réacteur  

NASA Astrophysics Data System (ADS)

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,?), (n,p), (n,?), (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...

Meyer, G.

2003-02-01

214

Par Pond vegetation status summer 1995 - July survey descriptive summary  

SciTech Connect

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.

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

1995-07-01

215

Histoire(de(l'Astronomie( par(Thomas(Widemann((  

E-print Network

(ses(observations.(Dans(son(oeuvre,( "l'Almageste",(ainsi(dénommée(par(les( Arabes,(il(présente(son(système( géocentrique(du(centre(de(l'épicycle(est(uniforme.(( Almageste (grec, IXe siècle)! Almageste (latin, XIII-XIVe siècle)! L'astronomie(araboIislamique( ( Parmi

Demoulin, Pascal

216

Acetylcholinesterase in der Pars distalis von Zonotrichia leucophrys gambelii (Aves)  

Microsoft Academic Search

Photoperiodic stimulation of photosensitive male white-crowned sparrows, Zonotrichia leucophrys gambelii, causes the appearance of acetylcholinesterase activity in the cephalic and caudal lobes of the pars distalis. In photosensitive birds held on short daily photoperiods little or no activity can he demonstrated histochemically. The enzyme is restricted to PAS-positive cells. After attaining a maximum between 31 and 52 days after the

Eberhard Haase; Donald S. Farner

1969-01-01

217

BOREAS RSS-10 TOMS Circumpolar One-Degree PAR Images  

NASA Technical Reports Server (NTRS)

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).

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

2000-01-01

218

Cartographie des graphes de terrain par une approche proxmique  

E-print Network

Cartographie des graphes de terrain par une approche proxémique Bruno Gaume 10 décembre 2009 1 des particules qui cartographient les propriétés structurelles des graphes étudiés. Cette méthode). Cartographier la forme du sens dans les petits mondes lexicaux. JADT. [Watts and Strogatz, 1998] Watts, D. J

Grigoras, .Romulus

219

The Pars Triangularis in Dyslexia and ADHD: A Comprehensive Approach  

ERIC Educational Resources Information Center

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…

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

2009-01-01

220

TUDE DE LA TRANSMUTATION DU CUIVRE PAR L'AZOTE, L'OXYGNE ET LE NON Par Mmes H. FARAGGI, J. OLKOWSKY, Mlles J. BEYDON, M. CRUT  

E-print Network

519. �TUDE DE LA TRANSMUTATION DU CUIVRE PAR L'AZOTE, L'OXYG�NE ET LE N�ON Par Mmes H. FARAGGI, J. Abstract. 2014 We have studied the relative yields of the radioelement formed in the transmutation »).° Nous avons étudié, à Saclay, la transmutation du cuivre par l'azote et l'oxygène [2]. Nous avons pu

Paris-Sud XI, Université de

221

PRODUCTION DE TRITIUM DANS LE THORIUM PAR DES PROTONS DE 135 MeV Par M. LEFORT, G. SIMONOFF et X. TARRAGO  

E-print Network

959 PRODUCTION DE TRITIUM DANS LE THORIUM PAR DES PROTONS DE 135 MeV Par M. LEFORT, G. SIMONOFF et thorium par des protons de 135 MeV accélérés au synchro-cyclotron d'Orsay. Le tritium était extrait des measured the cross-section of tritium production by bombardement of thorium by 135 MeV protons in the Orsay

Paris-Sud XI, Université de

222

DTERMINATION PRCISE DE L'NERGIE DES RAYONS 03B1 EMIS PAR LE THORIUM Par M. GEORGES PHILBERT, Mme JEANNINE GNIN et M. LOPOLD VIGNERON,  

E-print Network

16 D�TERMINATION PR�CISE DE L'�NERGIE DES RAYONS 03B1 EMIS PAR LE THORIUM Par M. GEORGES PHILBERT. Sommaire. 2014 Du thorium, de l'ionium et du polonium ont été introduits ensemble dans une émulsion, les et autres nous ont permis de ne pas être gênés par les dérivés radioactifs du thorium. L

Paris-Sud XI, Université de

223

Etudes par spectroscopie Raman et par RMN des verres du système B2O3SiO2Li2O  

Microsoft Academic Search

Une approche structurale par spectroscopie Raman des verres du système B2O3-SiO2-Li2O a été effectuée. D'autre part une étude de l'environment du bore par RMN a été entreprise. Les résultats obtenus semblent indiquer que ces verres sont constitués de deux phases vitreuses distinctes, respectivement boratée et silicatée. Des phénomènes de démixtion ont d'ailleurs été mis en évidence par microscopie électronique à

Jean-Claude Brethous; Alain Levasseur; Gerard Villeneuve; Patrick Echegut; Paul Hagenmuller; Michel Couzi

1981-01-01

224

The physical association of the P2Y12 receptor with PAR4 regulates arrestin-mediated Akt activation.  

PubMed

It is now well accepted that protease activated receptor (PAR) 1 and PAR4 have differential roles in platelet activation. PAR4, a low-affinity thrombin receptor in human platelets, participates in sustained platelet activation in a P2Y12-dependent manner; however, the mechanisms are not defined. Our previous studies demonstrated that thrombin induces the association of PAR4 with P2Y12, together with arrestin recruitment to the complex. Here we show that PAR4 and P2Y12 directly interact to coregulate Akt signaling after PAR4 activation. We observed direct and specific interaction of P2Y12 with PAR4 but not PAR1 by bioluminescent resonance energy transfer when the receptors were coexpressed in human embryonic kidney 293T cells. PAR4-P2Y12 dimerization was promoted by PAR4-AP and inhibited by P2Y12 antagonist. By using sequence comparison of the transmembrane domains of PAR1 and PAR4, we designed a mutant form of PAR4, "PAR4SFT," by replacing LGL194-196 at the base of transmembrane domain 4 with the corresponding aligned PAR1 residues SFT 220-222. PAR4SFT supported only 8.74% of PAR4-P2Y12 interaction, abolishing P2Y12-dependent arrestin recruitment to PAR4 and Akt activation. Nonetheless, PAR4SFT still supported homodimerization with PAR4. PAR4SFT failed to induce a calcium flux when expressed independently; however, coexpression of increasing concentrations of PAR4SFT, together with PAR4 potentiated PAR4-mediated calcium flux, suggested that PAR4 act as homodimers to signal to Gq-coupled calcium responses. In conclusion, PAR4 LGL (194-196) governs agonist-dependent association of PAR4 with P2Y12 and contributes to Gq-coupled calcium responses. PAR4-P2Y12 association supports arrestin-mediated sustained signaling to Akt. Hence, PAR4-P2Y12 dimerization is likely to be important for the PAR4-P2Y12 dependent stabilization of platelet thrombi. PMID:24723492

Khan, Aasma; Li, Dongjun; Ibrahim, Salam; Smyth, Emer; Woulfe, Donna S

2014-07-01

225

Proteinase-Activated Receptor 1 (PAR1) Regulates Leukemic Stem Cell Functions  

PubMed Central

External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1?/? hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1?/? leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance. PMID:24740120

Bäumer, Nicole; Krause, Annika; Köhler, Gabriele; Lettermann, Stephanie; Evers, Georg; Hascher, Antje; Bäumer, Sebastian; Berdel, Wolfgang E.

2014-01-01

226

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

PubMed

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

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

2015-01-30

227

Structure of the ParM filament at 8.5 Å resolution  

PubMed Central

The actin-like protein ParM forms the cytomotive filament of the ParMRC system, a type II plasmid segregation system encoded by Escherichia coli R1 plasmid. We report an 8.5 Å resolution reconstruction of the ParM filament, obtained using cryo-electron microscopy. Fitting of the 3D density reconstruction with monomeric crystal structures of ParM provides insights into dynamic instability of ParM filaments. The structural analysis suggests that a ParM conformation, corresponding to a metastable state, is held within the filament by intrafilament contacts. This filament conformation of ParM can be attained only from the ATP-bound state, and induces a change in conformation of the bound nucleotide. The structural analysis also provides a rationale for the observed stimulation of hydrolysis upon polymerisation into the filament. PMID:23462100

Gayathri, Pananghat; Fujii, Takashi; Namba, Keiichi; Löwe, Jan

2013-01-01

228

Par3 functions in the biogenesis of the primary cilium in polarized epithelial cells.  

PubMed

Par3 is a PDZ protein important for the formation of junctional complexes in epithelial cells. We have identified an additional role for Par3 in membrane biogenesis. Although Par3 was not required for maintaining polarized apical or basolateral membrane domains, at the apical surface, Par3 was absolutely essential for the growth and elongation of the primary cilium. The activity reflected its ability to interact with kinesin-2, the microtubule motor responsible for anterograde transport of intraflagellar transport particles to the tip of the growing cilium. The Par3 binding partners Par6 and atypical protein kinase C interacted with the ciliary membrane component Crumbs3 and we show that the PDZ binding motif of Crumbs3 was necessary for its targeting to the ciliary membrane. Thus, the Par complex likely serves as an adaptor that couples the vectorial movement of at least a subset of membrane proteins to microtubule-dependent transport during ciliogenesis. PMID:18070914

Sfakianos, Jeff; Togawa, Akashi; Maday, Sandra; Hull, Mike; Pypaert, Marc; Cantley, Lloyd; Toomre, Derek; Mellman, Ira

2007-12-17

229

[Resonance light scattering of 4-(2-pyridylazo)-resorcinol (PAR)].  

PubMed

Mechanism and influence factors of resonance light scattering (RLS) spectra of 4-(2-pyridylazo)-resorcinol (PAR) aqueous solution were studied. In weak acidic solutions, strong RLS of PAR can be observed. The spectral feature of RLS is related to the absorption spectra of PAR. Acidity of the solutions influenced the acid-base equilibrium of PAR and its existing state, thereby influenced the RLS intensity. At pH 3.1 to pH 6.2, PAR exists as neutral molecule, which may assemble into molecular aggregates by hydrophobic force giving a light scattering enhancement. By a light polarization experiment, the RLS of PAR was demonstrated to be complete polarized light. The relationship between RLS intensity and PAR concentration was examined to be linear at a given set of experimental conditions. PMID:16329503

Wei, Yong-Ju; Qi, Xiu-ju; Dun, Hui-juan; Wang, Hui-ying; Lan, Rui-jia

2005-08-01

230

ParCAT: A Parallel Climate Analysis Toolkit  

NASA Astrophysics Data System (ADS)

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. ParCAT is implemented in C to provide efficient file IO. The file IO operations in the toolkit use the parallel-netcdf library; this enables the code to use the parallel IO capabilities of modern HPC systems. Analysis that currently requires an estimated 12+ hours with the traditional CCSM Land Model Diagnostics Package can now be performed in as little as 30 minutes on a single desktop workstation and a few minutes for relatively small jobs completed on modern HPC systems such as ORNL's Jaguar.

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

2012-12-01

231

Anterior PAR Proteins Function During Cytokinesis and Maintain DYN-1 at the Cleavage Furrow in Caenorhabditis elegans  

PubMed Central

PAR proteins are key regulators of cellular polarity and have links to the endocytic machinery and the actin cytoskeleton. Our data suggest a unique role for PAR proteins in cytokinesis. We have found that at the onset of cytokinesis, anterior PAR-6 and posterior PAR-2 proteins are redistributed to the furrow membrane in a temporal and spatial manner. PAR-6 and PAR-2 localize to the furrow membrane during ingression but PAR-2-GFP is distinct in that it is excluded from the extreme tip of the furrow. Once the midbody has formed, PAR-2-GFP becomes restricted to the midbody region (the midbody plus the membrane flanking it). Depletion of both anterior PAR proteins, PAR-3 and PAR-6, led to an increase in multinucleate embryos, suggesting that the anterior PAR proteins are necessary during cytokinesis and that PAR-3 and PAR-6 function in cytokinesis may be partially redundant. Lastly, anterior PAR proteins play a role in the maintenance of DYN-1 in the cleavage furrow. Our data indicate that the PAR proteins are involved in the events that occur during cytokinesis and may play a role in promoting the membrane trafficking and remodeling events that occur during this time. PMID:22887994

Pittman, Kelly J.; Skop, Ahna R.

2013-01-01

232

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

ERIC Educational Resources Information Center

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…

Papay, John P.; Johnson, Susan Moore

2012-01-01

233

LES MICROBES ET LE LAIT, par le Dl' VIOLLE.  

E-print Network

LES MICROBES ET LE LAIT, par le Dl' VIOLLE. d'e l'Institut Pasteur. Le lait est, à lui seul, la,originellement.snin, vierge de tout microbe et de tout corps toxique. Mai,s s'il parvient à maintenir la vie de l'adulte, à milieu qui contient les trois grands principes 'alimentaires, des sels minéraux et de l'eau, les microbes

Paris-Sud XI, Université de

234

SUR LES PRISMES A DVIATION CONSTANTE; Par M. EUGNE BLOCH.  

E-print Network

145 SUR LES PRISMES A D�VIATION CONSTANTE; Par M. EUG�NE BLOCH. 1. MM. Pellin et Broca (') ont signalé les premiers les intéres- santes propriétés d'un prisme à déviation constante, dans lequel les'angle A du prisme (fig. 1) est de 90°, FIG. 1. l'angle B de -;5°; les angles A' et B' sont respectivement de

Boyer, Edmond

235

Mesure de Variations D'indice par Polarimetrie  

Microsoft Academic Search

Pour mesurer de faibles variations d'indice de réfraction (10 -6 ) nous nous proposons d'utiliser la variation de l'état de polarisation d'une vibration lumineuse par réflexion sur le matériau à étudier. On sait en effet qu'une vibration polarisée rectilignement d'azimut alphai , arrivant sous l'incidence i sur le milieu d'indice relatif n , possède après réflexion, un azimut alphar différent

Jean-Claude Canit; Denise Berger; Michel Billardon

1966-01-01

236

LES MOLCULES DANS UN CHAMP CENTRIFUGE INTENSE; par T. SVEDBERG.  

E-print Network

LES MOL�CULES DANS UN CHAMP CENTRIFUGE INTENSE; par T. SVEDBERG. Université d'Upsala (Suède). Sommaire. 2014 De l'étude du comportement des molécules dans des champs centrifuges intenses on peut tirer exposée. L'auteur décrit la réalisation des champs centrifuges allant jusqu'à 200 000 fois la pesanteur

Paris-Sud XI, Université de

237

ANOMALIE DE LONGUEUR DES FERRITES Par LOUIS WEIL.  

E-print Network

ferrites de cuivre, de nickel, de cobalt, de zinc et de magnésium, entre la température ordinaire et 900° CANOMALIE DE LONGUEUR DES FERRITES Par LOUIS WEIL. Sommaire. - L'auteur a étudié la dilatation des étudié au dilatomètre Chevenard divers ferrites. Lorsqu'on fait varier la température assez lentement

Paris-Sud XI, Université de

238

AIMANTATION SPONTANE DES FERRITES Par REN PAUTHENET et L. BOCHIROL.  

E-print Network

également étudié la variation thermique de l'aimantation spontanée des ferrites de nickel, de cobalt et deAIMANTATION SPONTAN�E DES FERRITES Par REN� PAUTHENET et L. BOCHIROL. Sommaire. 2014 Les auteurs ont étudié les variations de l'aimantation à saturation des ferrites de magnésium et de cuivre en

Paris-Sud XI, Université de

239

Parli-Pro: A Fun Guide for Learning Parliamentary Procedures  

E-print Network

Parliamentary Procedure Classification and Summary of Motions (in order of rank) Classification of Motion Second Required Debatable Amendable Vote Required Can Be Reconsidered Privileged Motions 26 Adjourn (when unqualified) Yes No No Majority No 27 Orders..../Mrs. President, I second the motion. President: It has been moved and seconded that?The floor is now open for discussion. ................19 Mission: Parli-Pro/A Fun Guide for Learning Parliamentary Procedure MISSION 5: Amend a Motion You may amend a motion...

Davis, Brad

2007-07-23

240

APPLICATION DES PALIERS A GAZ AUX GYROSCOPES Par G. GOBERT,  

E-print Network

43 APPLICATION DES PALIERS A GAZ AUX GYROSCOPES Par G. GOBERT, Centre d'�tudes Nucléaires de Saclay gyroscope dont le rotor de 4 cm de diamètre pesant plusieurs centaines de grammes tourne à une vitesse to the construction of a gyroscope. The rotor is 4 cm in diameter and runs at 180 000 r. p. m. Its weight is 500 g. LE

Paris-Sud XI, Université de

241

Vectorial bicarbonate transport by Par-C10 salivary cells.  

PubMed

Salivary glands produce a HCO(3)(-)-rich fluid that is important for the neutral milieu in the upper gastrointestinal tract. The molecular mechanism of this secretion is poorly understood. Par-C10, an immortalized rat parotid acinar line, has been shown to secrete Cl(-)- in response to Ca(2+-)-mobilizing stimuli. Our aim was to assess the capacity of polarized monolayers of Par-C10 cells to transport and secrete HCO(3)(-)-. Transepithelial electrolyte movement was evaluated by short-circuit current measurements. Intracellular pH (pH(i)) was measured by microfluorometry in cells loaded with BCECF. Monolayers of Par-C10 cells, grown on Transwell membranes, developed high transepithelial resistance and exhibited vectorial anion secretion which was activated by both ATP and forskolin. The currents were partially inhibited by bumetanide and by withdrawal of HCO(3)(-) indicating the dependence of ion movements on NKCC and on HCO(3)(-) ions, respectively. In HCO(3)(-)-free solutions the recovery of pH(i) from acid loading was abolished by EIPA. In the presence of HCO(3)(-) there was a strong EIPA-insensitive recovery from acid loading which was inhibited by H(2)DIDS. ATP and forskolin stimulated HCO(3)(-) efflux from the cells. Furthermore, HCl(-) withdrawal experiments showed the presence of DNDS-sensitive basolateral anion exchange. In conclusion Par-C10 cells achieve transepithelial transport that is sensitive to both intracellular Ca(2+)- and cAMP-dependent stimulation. We identified Na(+)/H(+) exchange, Na(+)-HCO(3)(-) cotransport and anion exchange at the basolateral side of the cells as being involved in intracellular pH regulation and vectorial HCO(3)(-) secretion. This cell line offers a good model for further studies to understand the molecular mechanisms of salivary HCO(3)(-) secretion. PMID:20388965

Demeter, I; Szucs, A; Hegyesi, O; Foldes, A; Racz, G Z; Burghardt, B; Steward, M C; Varga, G

2009-12-01

242

d'ordre: 780 attribue par la biblioth`eque : | | | | | | | | | | |  

E-print Network

No d'ordre: 780 No attribu´e par la biblioth`eque : | | | | | | | | | | | Th`ese de doctorat de l obtenir le grade de Docteur de l'Universit´e d'Angers Titre de la th`ese : Matrice de r´esistance et du La- boratoire Proc´ed´e Mat´eriau Instrumentation du Centre d'Enseignement et de Recherche de l

Boyer, Edmond

243

Valid par CA du 31 janvier 2012 COMMISSIONS CULTURE  

E-print Network

Validé par CA du 31 janvier 2012 1 COMMISSIONS CULTURE Fonctionnement des commissions culture et actions dans le domaine de la culture. Afin de mener une politique culturelle cohérente avec les différents acteurs bourguignons de la culture, l'université de Bourgogne a décidé d'appuyer sa stratégie

Herrmann, Samuel

244

Aide apporte par la tldtection la cartographie des prairies permanentes  

E-print Network

Aide apportée par la télédétection à la cartographie des prairies permanentes Colette M. GIRARD I mise au point d'une méthode de diagnostic et de cartographie des prairies et pâturages appliquée à la guident le seuillage des données satellitaires. Un exemple de cartographie est donné et discuté. Mots clés

Paris-Sud XI, Université de

245

LES PROBLEMES DE LA GRANULOMTRIE Par M. JEAN VILLEY.  

E-print Network

éléments en fonction des dimensions du moule, mais elle fournit aussi la base d'une théorie rationnelle des similitude des deux grains. Dans un moule donné, l'altération relative de la compacité moyenne, par (1 le nom de rayon moyen du moule. Cette altération relative varie proportionnellement à la dimension

Paris-Sud XI, Université de

246

Abandon des terres par l'agriculture et colonisation par les ligneux : quelles consquences sur la vgtation pour diffrents cosystmes europens ?  

E-print Network

1 Abandon des terres par l'agriculture et colonisation par les ligneux : quelles conséquences sur analyser les conséquences de l'abandon et de la colonisation ligneuse dans des habitats semi stades d'abandon. Les résultats montrent que bien que la composition de la végétation change fortement

Paris-Sud XI, Université de

247

Nucleotide exchange factor ECT2 interacts with the polarity protein complex Par6/Par3/protein kinase Czeta (PKCzeta) and regulates PKCzeta activity.  

PubMed

Regulation of cell polarity is an important biological event that governs diverse cell functions such as localization of embryonic determinants and establishment of tissue and organ architecture. The Rho family GTPases and the polarity complex Par6/Par3/atypical protein kinase C (PKC) play a key role in the signaling pathway, but the molecules that regulate upstream signaling are still not known. Here we identified the guanine nucleotide exchange factor ECT2 as an activator of the polarity complex. ECT2 interacted with Par6 as well as Par3 and PKCzeta. Coexpression of Par6 and ECT2 efficiently activated Cdc42 in vivo. Overexpression of ECT2 also stimulated the PKCzeta activity, whereas dominant-negative ECT2 inhibited the increase in PKCzeta activity stimulated by Par6. ECT2 localization was detected at sites of cell-cell contact as well as in the nucleus of MDCK cells. The expression and localization of ECT2 were regulated by calcium, which is a critical regulator of cell-cell adhesion. Together, these results suggest that ECT2 regulates the polarity complex Par6/Par3/PKCzeta and possibly plays a role in epithelial cell polarity. PMID:15254234

Liu, Xiu-Fen; Ishida, Hiroshi; Raziuddin, Razi; Miki, Toru

2004-08-01

248

Collective cell migration requires suppression of actomyosin at cell-cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6.  

PubMed

Collective cell migration occurs in a range of contexts: cancer cells frequently invade in cohorts while retaining cell-cell junctions. Here we show that collective invasion by cancer cells depends on decreasing actomyosin contractility at sites of cell-cell contact. When actomyosin is not downregulated at cell-cell contacts, migrating cells lose cohesion. We provide a molecular mechanism for this downregulation. Depletion of discoidin domain receptor 1 (DDR1) blocks collective cancer-cell invasion in a range of two-dimensional, three-dimensional and 'organotypic' models. DDR1 coordinates the Par3/Par6 cell-polarity complex through its carboxy terminus, binding PDZ domains in Par3 and Par6. The DDR1-Par3/Par6 complex controls the localization of RhoE to cell-cell contacts, where it antagonizes ROCK-driven actomyosin contractility. Depletion of DDR1, Par3, Par6 or RhoE leads to increased actomyosin contactility at cell-cell contacts, a loss of cell-cell cohesion and defective collective cell invasion. PMID:21170030

Hidalgo-Carcedo, Cristina; Hooper, Steven; Chaudhry, Shahid I; Williamson, Peter; Harrington, Kevin; Leitinger, Birgit; Sahai, Erik

2011-01-01

249

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

PubMed

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-? 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-? 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-? expression and contributes to the innate immune response during single-stranded RNA viral infection. PMID:23391721

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

2013-03-01

250

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

NASA Astrophysics Data System (ADS)

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.

Broedersz, Chase; Wingreen, Ned

2013-03-01

251

The Role of Neurosecretory Neurons in the Pars Intercerebralis and Pars Lateralis in Reproductive Diapause of the Blowfly, Protophormia terraenovae  

NASA Astrophysics Data System (ADS)

Microlesions of the brain were made to examine the role of neurosecretory neurons in the pars intercerebralis (PI) and pars lateralis (PL) in the induction of reproductive diapause of the female blowfly Protophormia terraenovae. Under both diapause-inducing (LD 12 : 12, 20° C) and diapause-averting conditions (LD 18 : 6, 25° C), the ovaries invariably failed to develop when the PI was removed. When the PL was removed bilaterally, the ovaries developed in most of the females, irrespective of the rearing conditions. Removal of the PL prevented females from entering reproductive diapause. These results show that certain neurosecretory neurons in the PI are necessary for vitellogenesis, and that the PL contains inhibitory neurons which suppress vitellogenesis during reproductive diapause.

Shiga, S.; Numata, H.

252

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

NASA Technical Reports Server (NTRS)

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.

Frouin, Robert

1993-01-01

253

SUR LES RAYONNEMENTS 03B3 ET X MIS PAR LE POLONIUM 210  

E-print Network

244 SUR LES RAYONNEMENTS 03B3 ET X �MIS PAR LE POLONIUM 210 Par MICHEL RIOU, Institut du Radium essentiellement par les rayons x dans les atomes de plomb contenus dans les sources de polonium. Des travaux r6 polonium 210 (RaF) 6met en faible intensité les rayonnements et L du plomb, et une raie y de 800 keV. Nous

Paris-Sud XI, Université de

254

LE DBIT DE CHALEUR DU POLONIUM; DTERMINATION PAR VOIE CALORIMTRIQUE DE SES CONSTANTES RADIOACTIVES  

E-print Network

LE D�BIT DE CHALEUR DU POLONIUM; D�TERMINATION PAR VOIE CALORIM�TRIQUE DE SES CONSTANTES du Po est k = 1,533.105. 1. Introduction. - La mesure du débit de chaleur du polonium a fait l chaleur d'un tel sel, par accumulation du polonium par l'intermédiaire de RaD- Ra !!J1, peut être calculée

Boyer, Edmond

255

ESTIMATION DES INCERTITUDES DE MESURE DE VISCOSITE PAR CHUTE DE BILLE  

E-print Network

to the expression of Uncertainty in Measurement), c'est à dire, par propagation des variances. Ensuite, et parce que méthodes distinctes. Tout d'abord le calcul est effectué en suivant la démarche décrite par le GUM (Guide donnée par l'expression : g U18 d b 2 )( -= (1) avec : : Viscosité dynamique du fluide (Pa.s) d

Paris-Sud XI, Université de

256

The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi  

Microsoft Academic Search

The causative agent of Lyme borreliosis, the spirochete Borrelia burgdorferi, has been shown to induce expression of the urokinase receptor (uPAR); however, the role of uPAR in the immune response against Borrelia has never been investigated. uPAR not only acts as a proteinase receptor, but can also, dependently or independently of ligation to uPA, directly affect leukocyte function. We here

Joppe W. R. Hovius; Maarten F. Bijlsma; Windt van der G. J. W; W. Joost Wiersinga; Bastiaan J. D. Boukens; Jeroen Coumou; Anneke Oei; Regina de Beer; Vos de A. F; Cornelis van't Veer; Dam van A. P; Penghua Wang; Erol Fikrig; Marcel M. Levi; Joris J. T. H. Roelofs; Tom van der Poll

2009-01-01

257

The Urokinase Receptor (uPAR) Facilitates Clearance of Borrelia burgdorferi  

Microsoft Academic Search

The causative agent of Lyme borreliosis, the spirochete Borrelia burgdorferi, has been shown to induce expression of the urokinase receptor (uPAR); however, the role of uPAR in the immune response against Borrelia has never been investigated. uPAR not only acts as a proteinase receptor, but can also, dependently or independently of ligation to uPA, directly affect leukocyte function. We here

Joppe W. R. Hovius; Maarten F. Bijlsma; Gerritje J. W. van der Windt; W. Joost Wiersinga; Bastiaan J. D. Boukens; Jeroen Coumou; Anneke Oei; Regina de Beer; Alex F. de Vos; Cornelis van t Veer; Alje P. van Dam; Penghua Wang; Erol Fikrig; Marcel M. Levi; Joris J. T. H. Roelofs; Tom van der Poll

2009-01-01

258

Convergence de la dynamique des dislocations vers le mouvement par courbure moyenne  

E-print Network

Origine variationnelle du mouvement par courbure moyenne anisotrope 4 Sch´ema num´erique Sch´ema num´erique pour la dynamique des dislocations Sch´ema num´erique pour le mouvement par courbure moyenne mouvement par courbure moyenne anisotrope 4 Sch´ema num´erique Sch´ema num´erique pour la dynamique des

Forcadel, Nicolas

259

Cathepsin S causes inflammatory pain via biased agonism of PAR2 and TRPV4.  

PubMed

Serine proteases such as trypsin and mast cell tryptase cleave protease-activated receptor-2 (PAR2) at R(36)?S(37) and reveal a tethered ligand that excites nociceptors, causing neurogenic inflammation and pain. Whether proteases that cleave PAR2 at distinct sites are biased agonists that also induce inflammation and pain is unexplored. Cathepsin S (Cat-S) is a lysosomal cysteine protease of antigen-presenting cells that is secreted during inflammation and which retains activity at extracellular pH. We observed that Cat-S cleaved PAR2 at E(56)?T(57), which removed the canonical tethered ligand and prevented trypsin activation. In HEK and KNRK cell lines and in nociceptive neurons of mouse dorsal root ganglia, Cat-S and a decapeptide mimicking the Cat-S-revealed tethered ligand-stimulated PAR2 coupling to G?s and formation of cAMP. In contrast to trypsin, Cat-S did not mobilize intracellular Ca(2+), activate ERK1/2, recruit ?-arrestins, or induce PAR2 endocytosis. Cat-S caused PAR2-dependent activation of transient receptor potential vanilloid 4 (TRPV4) in Xenopus laevis oocytes, HEK cells and nociceptive neurons, and stimulated neuronal hyperexcitability by adenylyl cyclase and protein kinase A-dependent mechanisms. Intraplantar injection of Cat-S caused inflammation and hyperalgesia in mice that was attenuated by PAR2 or TRPV4 deletion and adenylyl cyclase inhibition. Cat-S and PAR2 antagonists suppressed formalin-induced inflammation and pain, which implicates endogenous Cat-S and PAR2 in inflammatory pain. Our results identify Cat-S as a biased agonist of PAR2 that causes PAR2- and TRPV4-dependent inflammation and pain. They expand the role of PAR2 as a mediator of protease-driven inflammatory pain. PMID:25118282

Zhao, Peishen; Lieu, TinaMarie; Barlow, Nicholas; Metcalf, Matthew; Veldhuis, Nicholas A; Jensen, Dane D; Kocan, Martina; Sostegni, Silvia; Haerteis, Silke; Baraznenok, Vera; Henderson, Ian; Lindström, Erik; Guerrero-Alba, Raquel; Valdez-Morales, Eduardo E; Liedtke, Wolfgang; McIntyre, Peter; Vanner, Stephen J; Korbmacher, Christoph; Bunnett, Nigel W

2014-09-26

260

SPALLATION (1) DU TERBIUM PAR DES PROTONS DE 170 MEV. PREMIRE PARTIE QUALITATIVE  

E-print Network

549. SPALLATION (1) DU TERBIUM PAR DES PROTONS DE 170 MEV. PREMI�RE PARTIE QUALITATIVE Par J le terbium pour plusieurs raisons : 1) c'est un mono-isotope ; 2) les isotopes très déficients en- TIONS. - Les cibles, constituées par de l'oxyde de terbium très pur (Johnson-Matthey), étaient irra

Paris-Sud XI, Université de

261

Segmentation d'images par coupe de graphe avec a priori de forme Damien Grosgeorge1  

E-print Network

Segmentation d'images par coupe de graphe avec a priori de forme Damien Grosgeorge1 Caroline.grosgeorge@univ-rouen.fr Résumé La segmentation d'images par coupe de graphe permet d'obtenir très rapidement, par minimisation informations des niveaux de gris. Mots Clef Segmentation d'image, coupe de graphe, a priori de forme, analyse

Paris-Sud XI, Université de

262

DISPOSITIF MCANIQUE PERMETTANT LA MESURE PAR COMPENSATION D'UNE CONSTANTE DE KERR  

E-print Network

176 A DISPOSITIF M�CANIQUE PERMETTANT LA MESURE PAR COMPENSATION D'UNE CONSTANTE DE KERR Par Mlle M'une constante de Kerr inconnue on peut opérer par la compen- sation de 2 biréfringences égales en valeur absolue it is necessary to measure an unknown Kerr constant by a compensation method, one must be able rigorously to align

Paris-Sud XI, Université de

263

MISSION MOLCULAIRE ET RECOMBINAISON ATOMIQUE DANS L'AZOTE Par J. AKRICHE, L. HERMAN,  

E-print Network

celui de (3). Le déclin de l'ionisation serait déter- miné par (1) et non par (4). Les mesures PHYSIQUE ET LE RADIUM TOME 19, JUILLET 1958, Introduction. - Le déclin de l'ionisation et de la (le la recombinaison radiative, est très faible par rapport à celui de (1). Le rapport des

Boyer, Edmond

264

Activation of protease-activated receptors (PARs)-1 and -2 promotes alpha-smooth muscle actin expression and release of cytokines from human lung fibroblasts.  

PubMed

Previous studies have shown that protease-activated receptors (PARs) play an important role in various physiological processes. In the present investigation, we determined the expression of PARs on human lung fibroblasts (HLF-1) and whether they were involved in cellular differentiation and pro-inflammatory cytokine and prostaglandin (PGE2) secretion. PAR-1, PAR-2, PAR-3, and PAR-4 were detected in fibroblasts using RT-PCR, immunocytochemistry, and flow cytometry. Increased expression of PAR-4, but not other PARs, was observed in fibroblasts stimulated with phorbol myristate acetate. The archetypical activators of PARs, namely, thrombin and trypsin, as well as PAR-1 and PAR-2 agonist peptides, stimulated transient increases in intracellular Ca(2+), and promoted increased ?-smooth muscle actin expression. The proteolytic and peptidic PAR activators also stimulated the release of IL-6 and IL-8, as well as PGE2, with a rank order of potency of PAR-1 > PAR-2. The combined stimulation of PAR-1 and PAR-2 resulted in an additive release of both IL-6 and IL-8. In contrast, PAR-3 and PAR-4 agonist peptides, as well as all the PAR control peptides examined, were inactive. These results suggest an important role for PARs associated with fibroblasts in the modulation of inflammation and remodeling in the airway. PMID:25663523

Asokananthan, Nithiananthan; Lan, Rommel S; Graham, Peter T; Bakker, Anthony J; Tokanovi?, Ana; Stewart, Geoffrey A

2015-02-01

265

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

PubMed Central

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

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

266

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

PubMed

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-? 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-? 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-? and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-? 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. PMID:24726923

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

2014-07-01

267

The two Cis-acting sites, parS1 and oriC1, contribute to the longitudinal organisation of Vibrio cholerae chromosome I.  

PubMed

The segregation of bacterial chromosomes follows a precise choreography of spatial organisation. It is initiated by the bipolar migration of the sister copies of the replication origin (ori). Most bacterial chromosomes contain a partition system (Par) with parS sites in close proximity to ori that contribute to the active mobilisation of the ori region towards the old pole. This is thought to result in a longitudinal chromosomal arrangement within the cell. In this study, we followed the duplication frequency and the cellular position of 19 Vibrio cholerae genome loci as a function of cell length. The genome of V. cholerae is divided between two chromosomes, chromosome I and II, which both contain a Par system. The ori region of chromosome I (oriI) is tethered to the old pole, whereas the ori region of chromosome II is found at midcell. Nevertheless, we found that both chromosomes adopted a longitudinal organisation. Chromosome I extended over the entire cell while chromosome II extended over the younger cell half. We further demonstrate that displacing parS sites away from the oriI region rotates the bulk of chromosome I. The only exception was the region where replication terminates, which still localised to the septum. However, the longitudinal arrangement of chromosome I persisted in Par mutants and, as was reported earlier, the ori region still localised towards the old pole. Finally, we show that the Par-independent longitudinal organisation and oriI polarity were perturbed by the introduction of a second origin. Taken together, these results suggest that the Par system is the major contributor to the longitudinal organisation of chromosome I but that the replication program also influences the arrangement of bacterial chromosomes. PMID:25010199

David, Ariane; Demarre, Gaëlle; Muresan, Leila; Paly, Evelyne; Barre, François-Xavier; Possoz, Christophe

2014-07-01

268

A systematic computation scheme of PAR-WIG cruising performance  

NASA Astrophysics Data System (ADS)

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.

Ando, Shigenori

1993-08-01

269

Inflammation and Macular Oedema after Pars Plana Vitrectomy  

PubMed Central

Cystoid macular oedema (CMO) is a major cause of reduced vision following intraocular surgery. Although the aetiology of CMO is not completely clarified, intraocular inflammation is known to play a major role in its development. The macula may develop cytotoxic oedema when the primary lesion and fluid accumulation occur in the parenchymatous cells (intracellular oedema) or vasogenic oedema when the primary defect occurs in the blood-retinal barrier and leads to extracellular fluid accumulation (extracellular oedema). We report on the mechanisms of CMO formation after pars plana vitrectomy and associated surgical procedures and discuss possible therapeutic approaches. PMID:24288446

Romano, Vito; Angi, Martina; del Grosso, Renata; Romano, Davide; Vinciguerra, Paolo; Romano, Mario R.

2013-01-01

270

BOREAS TE-12 Incoming PAR Through the Forest Canopy Data  

NASA Technical Reports Server (NTRS)

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).

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

2000-01-01

271

Glycosylation and the activation of proteinase-activated receptor 2 (PAR2) by human mast cell tryptase  

PubMed Central

Human mast cell tryptase appears to display considerable variation in activating proteinase-activated receptor 2 (PAR2). We found tryptase to be an inefficient activator of wild-type rat-PAR2 (wt-rPAR2) and therefore decided to explore the factors that may influence tryptase activation of PAR2.Using a 20 mer peptide (P20) corresponding to the cleavage/activation sequence of wt-rPAR2, tryptase was as efficient as trypsin in releasing the receptor-activating sequence (SLIGRL…). However, in the presence of either human-PAR2 or wt-r PAR2 expressing cells, tryptase could only activate PAR2 by releasing SLIGRL from the P20 peptide, suggesting that PAR2 expressed on the cells was protected from tryptase activation.Three approaches were employed to test the hypothesis that PAR2 receptor glycosylation restricts tryptase activation. (a) pretreatment of wt-rPAR2 expressing cells or human embryonic kidney cells (HEK293) with vibrio cholerae neuraminidase to remove oligosaccharide sialic acid, unmasked tryptase-mediated PAR2 activation. (b) Inhibiting receptor glycosylation in HEK293 cells with tunicamycin enabled tryptase-mediated PAR2 activation. (c) Wt-rPAR2 devoid of the N-terminal glycosylation sequon (PAR2T25?), but not rPAR2 devoid of the glycosylation sequon located on extracellular loop-2 (PAR2T224A), was selectively and substantially (>30 fold) more sensitive to tryptase compared with the wt-rPAR2.Immunocytochemistry using antisera that specifically recognized the N-terminal precleavage sequence of PAR2 demonstrated that tryptase released the precleavage domain from PAR2T25? but not from wt-rPAR2.Heparin?:?tryptase molar ratios of greater than 2?:?1 abrogated tryptase activation of PAR2T25?.Our results indicate that glycosylation of PAR2 and heparin-inhibition of PAR2 activation by tryptase could provide novel mechanisms for regulating receptor activation by tryptase and possibly other proteases. PMID:11606310

Compton, Steven J; Renaux, Bernard; Wijesuriya, Suranga J; Hollenberg, Morley D

2001-01-01

272

A method for estimating the incident PAR on inclined surfaces  

NASA Astrophysics Data System (ADS)

A new simple model has been developed that incorporates Digital Elevation Model (DEM) and Moderate Resolution Imaging Spectroradiometer (MODIS) products to produce incident photosynthetically active radiation (PAR) for tilted surface. The method is based on a simplification of the general radiative transfer equation, which considers five major processes of attenuation of solar radiation: 1) Rayleigh scattering, 2) absorption by ozone and water vapor, 3) aerosol scattering, 4) multiple reflectance between surface and atmosphere, and 5) three terrain factors: slope and aspect, isotropic sky view factor, and additional radiation by neighbor reflectance. A comparison of the model results with observational data from the Yucheng and Changbai Mountain sites of the Chinese Ecosystem Research Network (CERN) shows the correlation coefficient as 0.929 and 0.904, respectively. A comparison of the model results with the 2006 filed measured PAR in the Yucheng and Changbai sites shows the correlation coefficient as 0.929 and 0.904, respectively, and the average percent error as 10% and 15%, respectively.

Xie, Xiaoping; Gao, Wei; Gao, Zhiqiang

2008-08-01

273

Phosphorylation of the Par Polarity Complex Protein Par3 at Serine 962 Is Mediated by Aurora A and Regulates Its Function in Neuronal Polarity*  

PubMed Central

The Aurora kinases are a family of serine/threonine protein kinases that perform important functions during the cell cycle. Recently, it was shown that Drosophila Aurora A also regulates the asymmetric localization of Numb to the basal and the partitioning-defective (Par) complex to the apical cortex of neuroblasts by phosphorylating Par6. Here, we show that Aurora A is required for neuronal polarity. Suppression of Aurora A by RNA interference results in the loss of neuronal polarity. Aurora A interacts directly with the atypical protein kinase C binding domain of Par3 and phosphorylates it at serine 962. The phosphorylation of Par3 at serine 962 contributes to its function in the establishment of neuronal polarity. PMID:19812038

Khazaei, Mohammad R.; Püschel, Andreas W.

2009-01-01

274

Par-1 regulates tissue growth by influencing hippo phosphorylation status and hippo-salvador association.  

PubMed

The evolutionarily conserved Hippo (Hpo) signaling pathway plays a pivotal role in organ size control by balancing cell proliferation and cell death. Here, we reported the identification of Par-1 as a regulator of the Hpo signaling pathway using a gain-of-function EP screen in Drosophila melanogaster. Overexpression of Par-1 elevated Yorkie activity, resulting in increased Hpo target gene expression and tissue overgrowth, while loss of Par-1 diminished Hpo target gene expression and reduced organ size. We demonstrated that par-1 functioned downstream of fat and expanded and upstream of hpo and salvador (sav). In addition, we also found that Par-1 physically interacted with Hpo and Sav and regulated the phosphorylation of Hpo at Ser30 to restrict its activity. Par-1 also inhibited the association of Hpo and Sav, resulting in Sav dephosphorylation and destabilization. Furthermore, we provided evidence that Par-1-induced Hpo regulation is conserved in mammalian cells. Taken together, our findings identified Par-1 as a novel component of the Hpo signaling network. PMID:23940457

Huang, Hong-Ling; Wang, Shimin; Yin, Meng-Xin; Dong, Liang; Wang, Chao; Wu, Wei; Lu, Yi; Feng, Miao; Dai, Chuanyang; Guo, Xiaocan; Li, Li; Zhao, Bin; Zhou, Zhaocai; Ji, Hongbin; Jiang, Jin; Zhao, Yun; Liu, Xin-Yuan; Zhang, Lei

2013-01-01

275

LECTRONS DE MATRIALISATION ET DE TRANSMUTATION Par I. CURIE et F. JOLIOT.  

E-print Network

�LECTRONS DE MAT�RIALISATION ET DE TRANSMUTATION Par I. CURIE et F. JOLIOT. Sommaire. - Les auteurs on observe l'émission d'électrons positifs lors de la transmutation par les rayons 03B1 de cer- tains

Boyer, Edmond

276

RECHERCHES SUR LES COURBES DE SCINTILLATIONS DONNES PAR LES RAYONS 03B1 DU POLONIUM;  

E-print Network

RECHERCHES SUR LES COURBES DE SCINTILLATIONS DONN�ES PAR LES RAYONS 03B1 DU POLONIUM; par G probable d'un rayon, K et p deux constantes (p = 0,0165 pour le polonium). Ces prévisions théoriques furent

Paris-Sud XI, Université de

277

Recherche dans les banques d'ADN par indexation parall`ele  

E-print Network

Recherche dans les banques d'ADN par indexation parall`ele Van Hoa Nguyen Institut Francophone d banques d'ADN. Une recherche rapide passe par une mise en oeuvre parall`ele des algorithmes. Les m directement sur le temps d'ex´ecution. Or les banques d'ADN croissent exponentiellement. Cet article propose

Boyer, Edmond

278

Modeling the Establishment of PAR Protein Polarity in the One-Cell C. elegans Embryo  

E-print Network

Modeling the Establishment of PAR Protein Polarity in the One-Cell C. elegans Embryo Filipe ABSTRACT At the one-cell stage, the C. elegans embryo becomes polarized along the anterior-posterior axis by cytoskeletal rearrangement. Initially, the PAR proteins are uniformly distributed throughout the embryo. After

Howard, Martin

279

LUMINESCENCE ET CONDUCTIBILIT DE MONOCRISTAUX DE ZnS(Cu) Par D. R. HAMILTON,  

E-print Network

de H2S. L'auteur a préféré utiliser leur méthode de préparation, modifiée par l'utilisation d, on introduisait le cuivre par diffusion : on chauffait pendant 2 heures à 1 000° C, dans une bombe en quartz, les

Boyer, Edmond

280

Ultrastructure of the pituitary gland (pars distalis) in sockeye salmon ( Oncorhynchus nerka ) during gonad maturation  

Microsoft Academic Search

The fine structure of the various hormone-producing cell types (with the exclusion of the prolactin cells) in the pituitary gland (pars distalis) of migratory sockeye salmon is described. All fish were in an advanced stage of sexual maturation. In the proximal pars distalis five cell types were distinguished: growth hormone cells, ACTH cells, gonadotrops, “vesicular cells”, and “chromophobe cells”. Gonadotrops

H. Cook; A. P. van Overbeeke

1972-01-01

281

12 CFR 1263.19 - Par value and price of stock.  

Code of Federal Regulations, 2011 CFR

...2011-01-01 false Par value and price of stock. 1263.19 Section... Banks and Banking FEDERAL HOUSING FINANCE AGENCY FEDERAL HOME... § 1263.19 Par value and price of stock. The capital...the Director has fixed a higher...

2011-01-01

282

12 CFR 925.19 - Par value and price of stock.  

Code of Federal Regulations, 2010 CFR

...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...Requirements § 925.19 Par value and price of stock. The capital stock...

2010-01-01

283

LED Lighting Flicker and Potential Health Concerns: IEEE Standard PAR1789 Update  

E-print Network

LED Lighting Flicker and Potential Health Concerns: IEEE Standard PAR1789 Update Arnold Wilkins Working Group, IEEE PAR1789 "Recommending practices for modulating current in High Brightness LEDsStar and other standards groups about the emerging concern of flicker in LED lighting. This paper introduces

Lehman, Brad

284

Modelisation et analyse des syst`emes Duree: 4h. Une feuille par question.  

E-print Network

- bies et un groupe d'^etres humains "normaux" (non zombies). Il est bien connu que lorsqu'un zombie touche un ^etre humain, ce dernier se transforme en zombie. Par ailleurs, la panique provoqu´ee dans le camp des humains par la pr´esence des zombies cr´ee un rapprochement entre les humains, rapprochement

Catholique de Louvain, Université

285

Fbxo45-mediated degradation of the tumor-suppressor Par-4 regulates cancer cell survival.  

PubMed

Prostate apoptosis response protein 4 (Par-4) also known as PRKC apoptosis WT1 regulator is a tumor suppressor that selectively induces apoptosis in cancer cells. However, its post-translational regulation by ubiquitin-mediated proteolysis and the cellular machinery that is responsible for its proteasomal degradation are unknown. Using immunopurification and an unbiased mass spectrometry-based approach, we show that Par-4 interacts with the SPRY-domain containing E3 ubiquitin ligase Fbxo45 through a short consensus sequence motif. Fbxo45 interacts with Par-4 in the cytoplasm and mediates its ubiquitylation and proteasomal degradation. Fbxo45 silencing results in stabilization of Par-4 with increased apoptosis. Importantly, a Par-4 mutant that is unable to bind Fbxo45 is stabilized and further enhances staurosporine-induced apoptosis. Co-expression of Fbxo45 with Par-4 protects cancer cells against Par-4-induced apoptosis. Our studies reveal that Fbxo45 is the substrate-receptor subunit of a functional E3 ligase for Par-4 that has a critical role in cancer cell survival. PMID:24992930

Chen, X; Sahasrabuddhe, A A; Szankasi, P; Chung, F; Basrur, V; Rangnekar, V M; Pagano, M; Lim, M S; Elenitoba-Johnson, K S J

2014-10-01

286

Paternal age related schizophrenia (PARS): latent subgroups detected by k-means clustering analysis  

E-print Network

1 Paternal age related schizophrenia (PARS): latent subgroups detected by k-means clustering.antonius@nyumc.org #12;2 Abstract Background: Paternal age related schizophrenia (PARS) has been proposed as a subgroup of schizophrenia with distinct etiology, pathophysiology and symptoms. This study uses a k-means clustering

Ahn, Hongshik

287

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

ERIC Educational Resources Information Center

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…

Grace, Sarah; Langhout, Regina Day

2014-01-01

288

Par3 controls neural crest migration by promoting microtubule catastrophe during contact inhibition of locomotion  

PubMed Central

There is growing evidence that contact inhibition of locomotion (CIL) is essential for morphogenesis and its failure is thought to be responsible for cancer invasion; however, the molecular bases of this phenomenon are poorly understood. Here we investigate the role of the polarity protein Par3 in CIL during migration of the neural crest, a highly migratory mesenchymal cell type. In epithelial cells, Par3 is localised to the cell-cell adhesion complex and is important in the definition of apicobasal polarity, but the localisation and function of Par3 in mesenchymal cells are not well characterised. We show in Xenopus and zebrafish that Par3 is localised to the cell-cell contact in neural crest cells and is essential for CIL. We demonstrate that the dynamics of microtubules are different in different parts of the cell, with an increase in microtubule catastrophe at the collision site during CIL. Par3 loss-of-function affects neural crest migration by reducing microtubule catastrophe at the site of cell-cell contact and abrogating CIL. Furthermore, Par3 promotes microtubule catastrophe by inhibiting the Rac-GEF Trio, as double inhibition of Par3 and Trio restores microtubule catastrophe at the cell contact and rescues CIL and neural crest migration. Our results demonstrate a novel role of Par3 during neural crest migration, which is likely to be conserved in other processes that involve CIL such as cancer invasion or cell dispersion. PMID:24173803

Moore, Rachel; Theveneau, Eric; Pozzi, Sara; Alexandre, Paula; Richardson, Joanna; Merks, Anne; Parsons, Maddy; Kashef, Jubin; Linker, Claudia; Mayor, Roberto

2013-01-01

289

SUR LA CONSTANTE DE KERR DES LIQUIDES CONDUCTEURS Par M. PAUTHENIER  

E-print Network

SUR LA CONSTANTE DE KERR DES LIQUIDES CONDUCTEURS Par M. PAUTHENIER Nous avons réalisé une nouvelle la constante de Kerr de liquides assez bons conducteurs. Principe. - Le liquide à étudier, compris pratique. - La mesure de la cons- tante de Kerr se fait par une méthode de compensation. Le liquide de

Paris-Sud XI, Université de

290

EXPOSE ET MISE AU POINT BIBLIOGRAPHIQUE TUDE DE L'ADSORPTION PHYSIQUE PAR SPECTROSCOPIE INFRAROUGE  

E-print Network

719. EXPOSE ET MISE AU POINT BIBLIOGRAPHIQUE �TUDE DE L'ADSORPTION PHYSIQUE PAR SPECTROSCOPIE INFRAROUGE Par A. SAVARY et S. ROBIN, Laboratoire de Spectroscopie, Faculté des Sciences de Rennes. Résumé ainsi obtenus sont incomplets. La spectroscopie infrarouge per- met de suivre les perturbations, qui

Boyer, Edmond

291

Spectroscopie par impulsions priodiques sur un jet molculaire. Probabilit de transition. Effets de rsonance  

E-print Network

2777 Spectroscopie par impulsions périodiques sur un jet moléculaire. Probabilité de transition. Effets de résonance J. C. Chardon, C. Genty et J. C. Labrune Laboratoire de Spectroscopie Hertzienne et d spectroscopique par impulsions en résonance électrique sur des jets moléculaires (spectroscopie MBER). Cette

Boyer, Edmond

292

Par-1 Regulates Tissue Growth by Influencing Hippo Phosphorylation Status and Hippo-Salvador Association  

PubMed Central

The evolutionarily conserved Hippo (Hpo) signaling pathway plays a pivotal role in organ size control by balancing cell proliferation and cell death. Here, we reported the identification of Par-1 as a regulator of the Hpo signaling pathway using a gain-of-function EP screen in Drosophila melanogaster. Overexpression of Par-1 elevated Yorkie activity, resulting in increased Hpo target gene expression and tissue overgrowth, while loss of Par-1 diminished Hpo target gene expression and reduced organ size. We demonstrated that par-1 functioned downstream of fat and expanded and upstream of hpo and salvador (sav). In addition, we also found that Par-1 physically interacted with Hpo and Sav and regulated the phosphorylation of Hpo at Ser30 to restrict its activity. Par-1 also inhibited the association of Hpo and Sav, resulting in Sav dephosphorylation and destabilization. Furthermore, we provided evidence that Par-1-induced Hpo regulation is conserved in mammalian cells. Taken together, our findings identified Par-1 as a novel component of the Hpo signaling network. PMID:23940457

Yin, Meng-Xin; Dong, Liang; Wang, Chao; Wu, Wei; Lu, Yi; Feng, Miao; Dai, Chuanyang; Guo, Xiaocan; Li, Li; Zhao, Bin; Zhou, Zhaocai; Ji, Hongbin; Jiang, Jin; Zhao, Yun; Liu, Xin-Yuan; Zhang, Lei

2013-01-01

293

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...

294

IONISATION MULTIPLE ET TRANSITIONS AUGER DANS L'INDIUM ET L'ARGENT PAR IMPACT LECTRONIQUE  

E-print Network

radiative, donnant naissance au spectre de fluorescence X, soit de façon non radiative, un élec- tron plus603 IONISATION MULTIPLE ET TRANSITIONS AUGER DANS L'INDIUM ET L'ARGENT PAR IMPACT �LECTRONIQUE par au cours de l'ionisation primaire (In5+, In6+, Ag5+, Ag6+), soit au cours de la cascade de

Paris-Sud XI, Université de

295

Couches nanostructures par embossage pour l'extraction de lumire dans des systmes luminescents  

E-print Network

'un moule en silicium Film solgel de TiO2 déposé par spin coating Couche solgel condensée structurée Couche luminescente #12;Exemple de moule (Si par e-beam) a=320 nm #12;The Nanonex NX 2500 for NIL

van Tiggelen, Bart

296

COUCHES PITAXIALES D'ARSNIURE DE GALLIUM OBTENUES PAR LA TECHNIQUE DE TRANSPORT EN PHASE VAPEUR  

E-print Network

161. COUCHES �PITAXIALES D'ARS�NIURE DE GALLIUM OBTENUES PAR LA TECHNIQUE DE TRANSPORT EN PHASE gallium sur des supports de germanium réalisée par la technique de transport en phase vapeur. Cette étude mobilité. Abstract. 2014 We have studied the epitaxy of gallium arsenide deposited by the vapor phase

Paris-Sud XI, Université de

297

Local-scale heterogeneity of photosynthetically active radiation (PAR), absorbed PAR and net radiation as a function of topography, sky conditions and leaf area index  

Microsoft Academic Search

The local-scale spatial distribution of photosynthetically active radiation (PAR), absorbed PAR (APAR) and net all-wave radiation (Q?) across the top of a forest canopy was investigated as a function of topography, sky conditions and forest heterogeneity for a forested hilly study site located in south-central Indiana, USA that is part of the FLUXNET and SpecNet networks. The method to estimate

Andrew Oliphant; C. Susan; B. Grimmond; Hans-Peter Schmid; Craig A. Wayson

2006-01-01

298

Rsultats obtenus chez la truite Arc-en-ciel concernant l'absorption du glycocolle par l'intestin moyen et par l'intestin  

E-print Network

Résultats obtenus chez la truite Arc-en-ciel concernant l'absorption du glycocolle par l'intestin moyen et par l'intestin postérieur : rôle du sodium dans les différences observées G. BOG�, A. RIGAL, G and distal intestinal absorption of glycocolle in trout. Role of sodium in the differences observed

Paris-Sud XI, Université de

299

Neph-Nephrin Proteins Bind the Par3-Par6-Atypical Protein Kinase C (aPKC) Complex to Regulate Podocyte Cell Polarity*S?  

PubMed Central

The kidney filter represents a unique assembly of podocyte epithelial cells that tightly enwrap the glomerular capillaries with their foot processes and the interposed slit diaphragm. So far, very little is known about the guidance cues and polarity signals required to regulate proper development and maintenance of the glomerular filtration barrier. We now identify Par3, Par6, and atypical protein kinase C (aPKC) polarity proteins as novel Neph1-Nephrin-associated proteins. The interaction was mediated through the PDZ domain of Par3 and conserved carboxyl terminal residues in Neph1 and Nephrin. Par3, Par6, and aPKC localized to the slit diaphragm as shown in immunofluorescence and immunoelectron microscopy. Consistent with a critical role for aPKC activity in podocytes, inhibition of glomerular aPKC activity with a pseudosubstrate inhibitor resulted in a loss of regular podocyte foot process architecture. These data provide an important link between cell recognition mediated through the Neph1-Nephrin complex and Par-dependent polarity signaling and suggest that this molecular interaction is essential for establishing the three-dimensional architecture of podocytes at the kidney filtration barrier. PMID:18562307

Hartleben, Björn; Schweizer, Heiko; Lübben, Pauline; Bartram, Malte P.; Möller, Clemens C.; Herr, Ronja; Wei, Changli; Neumann-Haefelin, Elke; Schermer, Bernhard; Zentgraf, Hanswalter; Kerjaschki, Dontscho; Reiser, Jochen; Walz, Gerd; Benzing, Thomas; Huber, Tobias B.

2008-01-01

300

uPAR and cathepsin B inhibition enhanced radiation-induced apoptosis in gliomainitiating cells  

PubMed Central

Glioblastomas present as diffuse tumors with invasion into normal brain tissue and frequently recur or progress after radiation as focal masses because of glioma-initiating cells. The role of the urokinase-type plasminogen activator receptor (uPAR) and cathepsin B in stem-like phenotype has been extensively studied in several solid tumors. In the present study, we demonstrated that selection of glioma-initiating cells using CD133 expression leads to a specific enrichment of CD133+ cells in both U87 and 4910 cells. In addition, CD133+ cells exhibited a considerable amount of other stem cell markers, such as Nestin and Sox-2. Radiation treatment significantly enhanced uPAR and cathepsin B levels in glioma-initiating cells. To downregulate radiation-induced uPAR and cathepsin B expression, we used a bicistronic shRNA construct that simultaneously targets both uPAR and cathepsin B (pCU). Downregulation of uPAR and cathepsin B using pCU decreased radiation-enhanced uPAR and cathepsin B levels and caused DNA damage-induced apoptosis in glioma cell lines and glioma-initiating cells. The most striking finding of this study is that knockdown of uPAR and cathepsin B inhibited ongoing transcription by suppressing BrUTP incorporation at ?H2AX foci. In addition, uPAR and cathepsin B gene silencing inversely regulated survivin and H2AX expression in both glioma cells and glioma-initiating cells. Pretreatment with pCU reduced radiation-enhanced expression of uPAR, cathepsin B, and survivin and enhanced DNA damage in pre-established glioma in nude mice. Taken together, our in vitro and in vivo findings suggest that uPAR and cathepsin B inhibition might serve as an adjunct to radiation therapy to target glioma-initiating cells and, therefore, for the treatment of glioma. PMID:22573309

Malla, Rama Rao; Gopinath, Sreelatha; Alapati, Kiranmai; Gorantla, Bharathi; Gondi, Christopher S.; Rao, Jasti S.

2012-01-01

301

COMPTITION FISSION-SPALLATION DANS LES CIBLES DE THORIUM BOMBARDES PAR PROTONS DE 155 MeV  

E-print Network

338. COMPÃ?TITION FISSION-SPALLATION DANS LES CIBLES DE THORIUM BOMBARDÃ?ES PAR PROTONS DE 155 Me isotopes du thorium et de l'actinium, par bombardement de Th 232 par des protons de 155 MeV. Ces sections were made on the formation of several isotopes of thorium, and actinium, by bombarding Th 232 by 155 Me

Paris-Sud XI, Université de

302

MMOIRES ORIGINAUX Sur l'ionisation de la vapeur d'eau par les rayons 03B1 du polonium  

E-print Network

M�MOIRES ORIGINAUX Sur l'ionisation de la vapeur d'eau par les rayons 03B1 du polonium Par B. BIANU faire des expériences directes sur l'ionisation produite par les rayons y du polonium dans la vapeur d

Boyer, Edmond

303

Proteinase-activated receptors (PARs) – focus on receptor-receptor-interactions and their physiological and pathophysiological impact  

PubMed Central

Proteinase-activated receptors (PARs) are a subfamily of G protein-coupled receptors (GPCRs) with four members, PAR1, PAR2, PAR3 and PAR4, playing critical functions in hemostasis, thrombosis, embryonic development, wound healing, inflammation and cancer progression. PARs are characterized by a unique activation mechanism involving receptor cleavage by different proteinases at specific sites within the extracellular amino-terminus and the exposure of amino-terminal “tethered ligand“ domains that bind to and activate the cleaved receptors. After activation, the PAR family members are able to stimulate complex intracellular signalling networks via classical G protein-mediated pathways and beta-arrestin signalling. In addition, different receptor crosstalk mechanisms critically contribute to a high diversity of PAR signal transduction and receptor-trafficking processes that result in multiple physiological effects. In this review, we summarize current information about PAR-initiated physical and functional receptor interactions and their physiological and pathological roles. We focus especially on PAR homo- and heterodimerization, transactivation of receptor tyrosine kinases (RTKs) and receptor serine/threonine kinases (RSTKs), communication with other GPCRs, toll-like receptors and NOD-like receptors, ion channel receptors, and on PAR association with cargo receptors. In addition, we discuss the suitability of these receptor interaction mechanisms as targets for modulating PAR signalling in disease. PMID:24215724

2013-01-01

304

La prévention des infections par le virus respiratoire syncytial  

PubMed Central

RÉSUMÉ L’infection par le virus respiratoire syncytial (VRS) est la principale cause d’infections des voies respiratoires inférieures chez les jeunes enfants. Le palivizumab, un anticorps monoclonal anti-VRS, réduit le taux d’hospitalisation des enfants à haut risque mais est très coûteux. Le présent document de principes remplace les trois précédents documents de principes de la Société canadienne de pédiatrie sur le sujet et est mis à jour principalement pour traiter des récentes modifications aux lignes directrices de l’American Academy of Pediatrics dans le contexte canadien. Il contient une analyse des publications ainsi que des recommandations au sujet de l’utilisation du palivizumab chez les enfants à haut risque

Robinson, JL

2011-01-01

305

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

SciTech Connect

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.

Hickey, H.M. [Westinghouse Savannah River Co., Aiken, SC (United States); Matthews, S.S.; Neal, L.W. [Rust Environment and Infrastructure, Inc., Greenville, SC (United States); Weiss, W.R. [Rust Environment and Infrastructure, Inc., Aiken, SC (United States)

1993-11-01

306

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

PubMed Central

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 PMID:24859756

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

2014-01-01

307

Novel animal models of acute and chronic cancer pain: a pivotal role for PAR2  

PubMed Central

Targeted therapy to prevent the progression from acute to chronic pain in cancer patients remains elusive. We developed three novel cancer models in mice that together recapitulate the anatomical, temporal and functional characteristics of acute and chronic head and neck cancer pain in humans. Using pharmacologic and genetic approaches in these novel cancer models, we identified the interaction between protease-activated receptor 2 (PAR2) and serine proteases to be of central importance. We show serine proteases such as trypsin induce acute cancer pain in a PAR2-dependent manner. Chronic cancer pain is associated with elevated serine proteases in the cancer microenvironment and PAR2 up-regulation in peripheral nerves. Serine protease inhibition greatly reduces the severity of persistent cancer pain in wild-type mice but most strikingly, the development of chronic cancer pain is prevented in PAR2-deficient mice. Our results demonstrate a direct role for PAR2 in acute cancer pain and suggest that PAR2 up-regulation may favor the development and maintenance of chronic cancer pain. Targeting the PAR2—serine protease interaction is a promising approach to the treatment of acute cancer pain and prevention of chronic cancer pain. PMID:23055487

LAM, D.K.; DANG, D.; ZHANG, J.; DOLAN, J.C.; SCHMIDT, B.L.

2012-01-01

308

Characterization and function of human Ly-6/uPAR molecules  

PubMed Central

Human Ly-6/uPAR molecules are a superfamily composed of two subfamilies; one is the membrane bound proteins with a GPI-anchor and the other are secreted proteins without the GPI-anchor. Ly-6/uPAR molecules have remarkable amino acid homology through a distinctive 8-10 cysteine-rich domain that is associated predominantly with O-linked glycans. These molecules are encoded by multiple tightly linked genes located on Chr. 8q23, and have a conserved genomic organization. Ly-6/uPAR molecules have an interesting expression pattern during hematopoiesis and on specific tumors indicating that Ly-6/uPAR molecules are associated with development of the immune system and carcinogenesis. Thus, Ly-6/uPAR molecules are useful antigens for diagnostic and therapeutic targets. This review summarizes our understanding of human Ly-6/uPAR molecules with regard to molecular structure as well as what is known about their function in normal and malignant tissues and suggest Ly-6/uPAR molecules as target antigens for cancer immunotherapy. [BMB Reports 2012; 45(11): 595-603] PMID:23186997

Kong, Hyun Kyung; Park, Jong Hoon

2012-01-01

309

MMP-1/PAR-1 signal transduction axis and its prognostic impact in esophageal squamous cell carcinoma  

PubMed Central

The matrix metalloprotease-1 (MMP-1)/protease-activated receptor-1 (PAR-1) signal transduction axis plays an important role in tumorigenesis. To explore the expression and prognostic value of MMP-1 and PAR-1 in esophageal squamous cell carcinoma (ESCC), we evaluated the expression of two proteins in resected specimens from 85 patients with ESCC by immunohistochemistry. Sixty-two (72.9%) and 58 (68.2%) tumors were MMP-1- and PAR-1-positive, respectively, while no significant staining was observed in normal esophageal squamous epithelium. MMP-1 and PAR-1 overexpression was significantly associated with tumor node metastasis (TNM) stage and regional lymph node involvement. Patients with MMP-1- and PAR-1-positive tumors, respectively, had poorer disease-free survival (DFS) than those with negative ESCC (P = 0.002 and 0.003, respectively). Univariate analysis showed a significant relationship between TNM stage [hazard ratio (HR) = 2.836, 95% confidence interval (CI) = 1.866-4.308], regional lymph node involvement (HR = 2.955, 95%CI = 1.713-5.068), MMP-1 expression (HR = 2.669, 95%CI = 1.229-6.127), and PAR-1 expression (HR = 1.762, 95%CI = 1.156-2.883) and DFS. Multivariate analysis including the above four parameters identified TNM stage (HR = 2.035, 95%CI = 1.167-3.681), MMP-1 expression (HR = 2.109, 95%CI = 1.293-3.279), and PAR-1 expression (HR = 1.967, 95%CI = 1.256-2.881) as independent and significant prognostic factors for DFS. Our data suggest for the first time that MMP-1 and PAR-1 were both overexpressed in ESCC and are novel predictors of poor patient prognosis after curative resection. The MMP-1/PAR-1 signal transduction axis might be a new therapeutic target for future therapies tailored against ESCC. PMID:22086466

Peng, Hong-hua; Zhang, Xi; Cao, Pei-guo

2011-01-01

310

Thrombin induces rapid PAR1-mediated non-classical FGF1 release  

SciTech Connect

Thrombin induces cell proliferation and migration during vascular injury. We report that thrombin rapidly stimulated expression and release of the pro-angiogenic polypeptide fibroblast growth factor 1 (FGF1). Thrombin failed to induce FGF1 release from protease-activated receptor 1 (PAR1) null fibroblasts, indicating that this effect was dependent on PAR1. Similarly to thrombin, FGF1 expression and release were induced by TRAP, a specific oligopeptide agonist of PAR1. These results identify a novel aspect of the crosstalk between FGF and thrombin signaling pathways which both play important roles in tissue repair and angiogenesis.

Duarte, Maria [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Kolev, Vihren [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Soldi, Raffaella [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Kirov, Alexander [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Graziani, Irene [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Oliveira, Silvia Marta [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Kacer, Doreen [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Friesel, Robert [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Maciag, Thomas [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Prudovsky, Igor [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States)]. E-mail: prudoi@mmc.org

2006-11-24

311

Functional characterization of rose phenylacetaldehyde reductase (PAR), an enzyme involved in the biosynthesis of the scent compound 2-phenylethanol.  

PubMed

2-Phenylethanol (2PE) is a prominent scent compound released from flowers of Damask roses (Rosa×damascena) and some hybrid roses (Rosa 'Hoh-Jun' and Rosa 'Yves Piaget'). 2PE is biosynthesized from l-phenylalanine (l-Phe) via the intermediate phenylacetaldehyde (PAld) by two key enzymes, aromatic amino acid decarboxylase (AADC) and phenylacetaldehyde reductase (PAR). Here we describe substrate specificity and cofactor preference in addition to molecular characterization of rose-PAR and recombinant PAR from R.×damascena. The deduced amino acid sequence of the full-length cDNA encoded a protein exhibiting 77% and 75% identity with Solanum lycopersicum PAR1 and 2, respectively. The transcripts of PAR were higher in petals than calyxes and leaves and peaking at the unfurling stage 4. Recombinant PAR and rose-PAR catalyzed reduction of PAld to 2PE using NADPH as the preferred cofactor. Reductase activity of rose-PAR and recombinant PAR were higher for aromatic and aliphatic aldehydes than for keto-carbonyl groups. Both PARs showed that (S)-[4-(2)H] NADPH was preferentially used over the (R)-[4-(2)H] isomer to give [1-(2)H]-2PE from PAld, indicating that PAR can be classified as short-chain dehydrogenase reductase (SDR). PMID:20650544

Chen, Xiao-Min; Kobayashi, Hiromi; Sakai, Miwa; Hirata, Hiroshi; Asai, Tatsuo; Ohnishi, Toshiyuki; Baldermann, Susanne; Watanabe, Naoharu

2011-01-15

312

EXPLOITATION DE L'AUTOGLISSEMENT FREQUENTIELSOLITON LIMITE PAR DES RADIATIONS DE CHERENKOV  

E-print Network

EXPLOITATION DE L'AUTOGLISSEMENT FREQUENTIELSOLITON LIMITE PAR DES RADIATIONS DE CHERENKOV POUR'apparition de radiations de Cherenkov qui limitent l'autoglissement fréquentiel d'une impulsion soliton pour

Paris-Sud XI, Université de

313

Comptage par pifluorescence des bactries du rumen, cultives in vitro. Estimation de leur tat physiologique  

E-print Network

used for direct count of fluorescent bacteria gave an estimate of microflora biomass and physiological %) (Jones, 1974), et pour le dosage des nucléotides adényliques par bioluminescence, après extraction au

Boyer, Edmond

314

Mice lacking the thrombin receptor, PAR1, have normal skin wound healing.  

PubMed Central

Thrombin's actions on platelets, macrophages, fibroblasts, and endothelial cells have prompted the hypothesis that thrombin may be important for inflammatory and fibroproliferative processes in wound healing. Protease-activated receptor 1 (PAR1) is a G-protein-coupled receptor that mediates many of the cellular activities of thrombin. To test the role of this receptor in vivo, we generated PAR1-deficient mice. Despite the observation that fibroblasts cultured from these mice lacked responsiveness to thrombin in vitro, we now report that there was no difference detected between wild-type and PAR1-deficient mice in skin wound healing assays including time to closure of open wounds, tensile strength of healed incisional wounds, wound histology, and hydroxyproline/DNA content of wound implants. We conclude that PAR1 is not necessary for normal skin wound healing in mice. Images Figure 2 PMID:9358744

Connolly, A. J.; Suh, D. Y.; Hunt, T. K.; Coughlin, S. R.

1997-01-01

315

LA CAT'EGORIE DE JOYAL EST UNE CAT'EGORIE TEST par  

E-print Network

________________________________________________________________________ LA CAT'EGORIE DE JOYAL EST UNE CAT'EGORIE TEST par Denis but principal de cet article est de prouver que la cat'eg* *orie cellulaire de Joyal est une cat

Maltsiniotis, Georges - Institut de Mathématiques de Jussieu, Université Paris 7

316

Le Lait (1981), 61, 481-493 Donnes sur la contamination par l'aflatoxine Ml  

E-print Network

Le Lait (1981), 61, 481-493 Données sur la contamination par l'aflatoxine Ml du lait et des,2,3] et de Iongh [5], il est connu que les aflatoxines B, ingérées par une vache en lactation, se retrou aflatoxines Ml et Mz (fig. 1) présentent une toxicité comparable à celle des aflatoxines BI et Br, dont elles

Paris-Sud XI, Université de

317

La perception des changements comptables par les acteurs : le cas du Vit-Nam  

E-print Network

1 La perception des changements comptables par les acteurs : le cas du Viêt-Nam Nhu Tuyên Lê déterminants de la perception des changements comptables par les acteurs mêmes de la Comptabilité, dans le produit à cet effet, l'étude conduit à quatre résultats : (1) les perceptions des changements sont

Paris-Sud XI, Université de

318

Volatilit du dpt actif du thorium Par T. BARRATT et A. B. WOOD  

E-print Network

198 Volatilité du dépôt actif du thorium Par T. BARRATT et A. B. WOOD [Woolwich Polytechnic]. Marsden et Darwini avaient proposé pour la série de transformations du thorium A le schéma suivant, Cet et thoriums C faites par Mlle Meitner 2 et Marsden et Wilson3ayant donné des résultats contradictoires, les

Paris-Sud XI, Université de

319

MESURE DU PARCOURS MOYEN DES RAYONS 03B1 DU THORIUM PAR LA MTHODE PHOTOGRAPHIQUE  

E-print Network

MESURE DU PARCOURS MOYEN DES RAYONS 03B1 DU THORIUM PAR LA M�THODE PHOTOGRAPHIQUE Par Mme HENRIETTE thorium dans l'émulsion des plaques photo- graphiques, on déduit leur parcours moyen dans l'air à150 thorium a déjà fait l'objet de plusieurs mesures dont les résultats ne sont pas toujours concordants. Les

Paris-Sud XI, Université de

320

LES NEUTRONS LENTS MIS PAR LE GLUCINIUM SOUS L'ACTION DES RAYONS 03B1  

E-print Network

, chocs inélastiques) par le glucinium sous l'action des rayons 03B1 du polonium ou du radon et forment un Bothe et Becker (glucinium métal bombardé par les rayons a du polonium) l'atmosphère d'une chambre à de glucinium métal accolé à une préparation de polonium (cette source nous a été prêtée obligeamment

Paris-Sud XI, Université de

321

liement du radium tait influenc par un champ lectrique ont donn des rsultats ngatifs.  

E-print Network

rayonnement du polonium préparé par M. eu M~ Curie n'a nlanifesté, dans les conditions des expériences polonium donnait des ombres géométriques très nettes, comme, du reste, je l'avais reconnu dèpuis longtemps. Giesel avait observé une déviation magnétique avec une de ses préparations de polonium. Article published

Paris-Sud XI, Université de

322

HORIZON GYROSCOPIQUE DANS LE VIDE DU CONTRE-AMIRAL FLEURIAIS ; Par M. ED. CASPARI.  

E-print Network

citerons : le sextant à niveau du contre-amiral Lejeune, dans lequel l'image réfléchie de la bulle est mise'horizon gyroscopique. L'instrument employé pour la mesure des hauteurs est le sextant ordinaire complété par l nous allons décrire. Un tore 1) est porté par un pivot i reposant sur un godet fixé au sextant. Deux

Paris-Sud XI, Université de

323

Recherche de sentiments opposes par une approche floue `a partir de textes libres  

E-print Network

Recherche de sentiments oppos´es par une approche floue `a partir de textes libres A fuzzy approach for determining opposite sentiments from free text Dong (Haoyuan) Li1 Anne Laurent2 Mathieu Roche2 Pascal Poncelet´ecideur est ´egalement de plus en plus int´eress´e par des remarques qui sont repr´esentatives d'un sentiment

Paris-Sud XI, Université de

324

CONTRIBUTION A L'TUDE DE LA MAGNTO-CHIMIE DU VANADIUM; par M. NICOLAS PERRAKIS.  

E-print Network

CONTRIBUTION A L'�TUDE DE LA MAGN�TO-CHIMIE DU VANADIUM; par M. NICOLAS PERRAKIS. Sommaire. 2014 Au Curie des sels du vanadium que j'ai étudiés se déplacent dans le temps, même en dehors de toute 43,7 10-6 par atome de vanadium. ' . Introduction. - Il y a une dizaine d'années, Kossel remarquait

Paris-Sud XI, Université de

325

Condensation d'ADN plasmidique par des diamines sur un substrat de graphite HOPG.  

E-print Network

Condensation d'ADN plasmidique par des diamines sur un substrat de graphite HOPG. Ce travail vise à améliorer notre connaissance des effets produits par les électrons de basse énergie (EBEs) sur l'ADN. Parmi]. Ce type d'étude requiert un bon étalement et un contrôle des dépôts d'ADN plasmidique sur des

Paris-Sud XI, Université de

326

ParCYCLIC: finite element modelling of earthquake liquefaction response on parallel computers  

Microsoft Academic Search

This paper presents the computational procedures and solution strategy employed in ParCYCLIC, a parallel non-linear finite element program developed based on an existing serial code CYCLIC for the analysis of cyclic seismically-induced liquefaction problems. In ParCYCLIC, finite elements are employed within an incremental plasticity, coupled solid-fluid formulation. A constitutive model developed for simulating liquefaction-induced deformations is a main component of

Jun Peng; Jinchi Lu; Kincho H. Law; Ahmed Elgamal

2004-01-01

327

ParCYCLIC: Finite Element Modeling of Earthquake Liquefaction Response on Parallel Computers  

Microsoft Academic Search

This paper presents the computational procedures and solution strategy employed in ParCYCLIC, a parallel nonlinear finite element program developed based on an existing serial code CYCLIC for the analysis of cyclic seismically-induced liquefaction problems. In ParCYCLIC, finite elements are employed within an incremental plasticity, coupled solid-fluid formulation. A constitutive model developed for simulating liquefaction-induced deformations is a main component of

Jun Peng; Jinchi Lu; Kincho H. Law; Ahmed Elgamal

328

PAR-WIG performance prediction during acceleration from water-borne to air-borne  

Microsoft Academic Search

Take-off performance is calculated for PAR-WIG which utilizes propeller-slipstream. For this purpose, a quick automatic computation scheme is developed for performance of 'engine-propeller combination system'. Example calculations are presented, which show that the hump drag is completely removed with PAR effect. It is noted that variable-geometry of wing-end-plates is desirable and variable-camber of main-wing is essential.

Shigenori Ando; Michiyo Kato

1991-01-01

329

PAR-WIG performance prediction during acceleration from water-borne to air-borne  

NASA Astrophysics Data System (ADS)

Take-off performance is calculated for PAR-WIG which utilizes propeller-slipstream. For this purpose, a quick automatic computation scheme is developed for performance of 'engine-propeller combination system'. Example calculations are presented, which show that the hump drag is completely removed with PAR effect. It is noted that variable-geometry of wing-end-plates is desirable and variable-camber of main-wing is essential.

Ando, Shigenori; Kato, Michiyo

1991-11-01

330

Laser verre codop Erbium et Ytterbium pomp par une diode laser de puissance  

E-print Network

Laser verre codopé Erbium et Ytterbium pompé par une diode laser de puissance Eric Tanguy CL lean proposé est fondé sur l'utilisation d'un verre codopé erbium et ytterbium pompé optiquement par unediode laser fibrée de puissanceet émettantvers 980 nm. Les lasers exploitant les propriétés de l'erbium et

Paris-Sud XI, Université de

331

DOSAGE DU RADON DANS L'AIR. Par Mme G. DELIBRIAS,  

E-print Network

78 A. DOSAGE DU RADON DANS L'AIR. Par Mme G. DELIBRIAS, Commissariat à l'�nergie atomique. Centre d'�tudes Nucléaires, à Saclay. Sommaire. 2014 On décrit une méthode de dosage de traces de radon dans l'atmosphère. La. Introduction. - L'air contient normalement une certaine quantité de Radon, de l'ordre de i o-1° Curie par m3 d

Paris-Sud XI, Université de

332

ABSORPTION INFRA-ROUGE DANS LES ALLIAGES NORMAUX Par B. CAROLI (1),  

E-print Network

884. ABSORPTION INFRA-ROUGE DANS LES ALLIAGES NORMAUX Par B. CAROLI (1), Résumé. - L'absorption de'électrons de Bloch, par une méthode quantique. On en déduit pour les fréquences faibles un coefficient d'absorption sont estimées sur un exemple simple. Abstract. 2014 Infra-red absorption by dilute alloys is studied

Boyer, Edmond

333

ETUDE DU CYCLE DE RESPIRATION A PARTIR DE DONNEES 4D GENEREES PAR UN SCANNER  

E-print Network

ETUDE DU CYCLE DE RESPIRATION A PARTIR DE DONNEES 4D GENEREES PAR UN SCANNER DYNAMIQUE 3D STUDY cycle de respiration à partir de données 4D générées par un scanner dynamique 3D Résumé Le laboratoire préliminaires sur l'étude du cycle de respiration de quelques individus. Cette recherche s'intéresse à l

Nebel, Jean-Christophe

334

Le Lait (1982),62, 113-125 Effets de la concentration par vaporation  

E-print Network

était ultrafiltré soit sur un module Amicon équipé de membranes Hollow Fiber HIO P50 de surface 0,9 m2 pendant l'évaporation. La concentration des protéines par ultrafiltration avant évapo- ration et séchage séchage du lait préalablement concentré par ultrafiltration présente, comme l'ont montré Maubois et

Paris-Sud XI, Université de

335

SPECTRE DE L'THYLAMINE C2H5NH2 Par M. MATRICON,  

E-print Network

. Le spectroscope utilisé est du type maintenant classique à modulation par effet Stark. On sait que d'absorption déplacées par effet Stark. Dans le cas de l'éthylamine, les conditions expérimentales alternative appliquée pour la modulation Stark : 200 à 30o V sur une électrode placée au centre d'une cellule

Paris-Sud XI, Université de

336

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

PubMed Central

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. PMID:25053432

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

2014-01-01

337

THERMOLUMINESCENCE DE LiF A BASSE TEMPRATURE Par J. TOURNON et P. BERGE,  

E-print Network

147. THERMOLUMINESCENCE DE LiF A BASSE TEMP�RATURE Par J. TOURNON et P. BERGE, Service de Physique thermoluminescence ont montré l'existence de deux niveaux métastables à 78 °K, produits par l'excitation des centres centres, de la durée d'excitation dans la bande F et aussi du nombre d'expériences de thermoluminescence

Boyer, Edmond

338

CARACTRISATION DU PHOTO-NOIRCISSEMENT DES FIBRES OPTIQUES DOPES YTTERBIUM PAR THERMOLUMINESCENCE  

E-print Network

CARACT�RISATION DU PHOTO-NOIRCISSEMENT DES FIBRES OPTIQUES DOP�ES YTTERBIUM PAR THERMOLUMINESCENCE thermoluminescence, une technique particulièrement adaptée à la caractérisation des défauts et centres ionisés par-noircissement ; Thermoluminescence 1. INTRODUCTION Les fibres optiques en silice dopées ytterbium (FDY) utilisées dans les

Boyer, Edmond

339

STOCKAGE DU METHANE PAR ADSORPTION SUR CHARBON ACTIF ASSOCIEE A LA FORMATION  

E-print Network

STOCKAGE DU METHANE PAR ADSORPTION SUR CHARBON ACTIF ASSOCIEE A LA FORMATION D'HYDRATES M.L. Zanota. Nous présentons des résultats expérimentaux concernant les capacités de stockage du méthane sur des stockage par l'intermédiaire de la formation d'hydrates de méthane. Les courbes de stockage et de

Boyer, Edmond

340

Improved phase factor computation for the PAR reduction of an OFDM signal using PTS  

Microsoft Academic Search

The peak-to-average power ratio (PAR) of an orthogonal frequency-division multiplexing (OFDM) signal can be substantially larger than that of a single carrier system. Partial transmit sequence (PTS) combining can improve the PAR statistics of an OFDM signal. As PTS requires an exhaustive search over all combinations of allowed phase factors, the search complexity increases exponentially with the number of subblocks.

Chintha Tellambura

2001-01-01

341

ALERTEES PAR LA MORT CELLULAIRE, NOS DEFENSES ANTIVIRALES METTENT LE TURBO  

E-print Network

MORT CELLULAIRE, NOS DEFENSES ANTIVIRALES METTENT LE TURBO Genève, le 9 février 2012 SOUS EMBARGO JUSQU marche après que certaines cellules ont été détruites par l'ennemi viral. A leur mort, elles relâchent associated molecular pattern). Ces DAMP se distinguent du reste des débris de la cellule morte par leur

Loewith, Robbie

342

SCELLEMENT TANCHE AU VIDE, DU VERRE ET DU MICA Par JACQUES LABEYRIE.  

E-print Network

20. SCELLEMENT �TANCHE AU VIDE, DU VERRE ET DU MICA Par JACQUES LABEYRIE. Commissariat à l'énergie atomique. Sommaire. - Les feuilles de mica, même minces (0,01mm), peuvent être scellées au verre par l 354°. Le même émail peut servir pour sceller le mica sur un métal de coefficient de dila- tation

Paris-Sud XI, Université de

343

Breaking the epithelial polarity barrier in cancer: the strange case of LKB1/PAR-4  

PubMed Central

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

Partanen, Johanna I.; Tervonen, Topi A.; Klefström, Juha

2013-01-01

344

Examining relational empowerment for elementary school students in a yPAR program.  

PubMed

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. PMID:24356900

Langhout, Regina Day; Collins, Charles; Ellison, Erin Rose

2014-06-01

345

Par-4, a Gene Required for Cytoplasmic Localization and Determination of Specific Cell Types in Caenorhabditis Elegans Embryogenesis  

PubMed Central

Specification of some cell fates in the early Caenorhabditis elegans embryo is mediated by cytoplasmic localization under control of the maternal genome. Using nine newly isolated mutations, and two existing mutations, we have analyzed the role of the maternally expressed gene par-4 in cytoplasmic localization. We recovered seven new par-4 alleles in screens for maternal effect lethal mutations that result in failure to differentiate intestinal cells. Two additional par-4 mutations were identified in noncomplementation screens using strains with a high frequency of transposon mobility. All 11 mutations cause defects early in development of embryos produced by homozygous mutant mothers. Analysis with a deficiency in the region indicates that it33 is a strong loss-of-function mutation. par-4(it33) terminal stage embryos contain many cells, but show no morphogenesis, and are lacking intestinal cells. Temperature shifts with the it57ts allele suggest that the critical period for both intestinal differentiation and embryo viability begins during oogenesis, about 1.5 hr before fertilization, and ends before the four-cell stage. We propose that the primary function of the par-4 gene is to act as part of a maternally encoded system for cytoplasmic localization in the first cell cycle, with par-4 playing a particularly important role in the determination of intestine. Analysis of a par-4;par-2 double mutant suggests that par-4 and par-2 gene products interact in this system. PMID:1582558

Morton, D. G.; Roos, J. M.; Kemphues, K. J.

1992-01-01

346

Analyses par diffraction de rayons X sur des revêtements barrières thermiques réalisés par un procédé hybride plasma-laser  

NASA Astrophysics Data System (ADS)

Les revêtements barrières thermiques (BTs) constitués de zircone yttriée partiellement stabilisée (ZrO{2} + 7% en masse d'Y{2}O{3}) et d'une sous-couche métallique (MCrAlY où M représente une combinaison de nickel et de cobalt) sont extrêmement utilisés afin d'améliorer les performances des composants des parties chaudes des turbines à gaz. La projection plasma sous atmosphère ambiante et l'irradiation laser in situ (au moyen d'un laser à diodes) sont associés ici afin de modifier les caractéristiques structurales des BTs. Les phases présentes au sein de la BT ont un rôle important. Des analyses par diffraction de rayons X ont été menées pour étudier les changements de phase possibles après traitement laser. Aucun changement de phase n'a été remarqué : la phase tétragonale métastable (t') demeure la phase prépondérante aussi bien pour les dépôts projetés que les dépôts post-traités au laser et refondus in situ. La formation de cette phase semble être liée à la solidification et au refroidissement rapide découlant de la projection plasma ainsi que de la refusion laser. Ce résultat est prometteur, car :

Antou, G.; Hlawka, F.; Montavon, G.; Bach, M.; Cornet, A.; Coddet, C.

2004-11-01

347

Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells  

NASA Astrophysics Data System (ADS)

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 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. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr32922d

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

348

SPECIATION DES METAUX Pb, Zn, Cd DANS LES POUSSIERES EN SUSPENSION DANS L'AIR AMBIANT PAR EXTRACTIONS CHIMIQUES ET PAR ESEM-EDS AUTOMATISE.  

E-print Network

SPECIATION DES METAUX Pb, Zn, Cd DANS LES POUSSIERES EN SUSPENSION DANS L'AIR AMBIANT PAR.Delalain@ineris.fr TITLE Speciation of lead, zinc and cadmium in ambient air dust combining selective chemical extractions the speciation of these elements, i.e their main physico-chemical species. A chemical extraction procedure has

Paris-Sud XI, Université de

349

Detecting Plant Photoprotective Response to Water Stress Through Variation In PAR Reflectance  

NASA Astrophysics Data System (ADS)

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.

Zygielbaum, A. I.; Arkebauer, T. J.; Walter-Shea, E.

2012-12-01

350

PAR2-mediated upregulation of BDNF contributes to central sensitization in bone cancer pain  

PubMed Central

Background Bone cancer pain is currently a major clinical challenge for the management of cancer patients, and the cellular and molecular mechanisms underlying the spinal sensitization remain unclear. While several studies demonstrated the critical role of proteinase-activated receptor (PAR2) in the pathogenesis of several types of inflammatory or neuropathic pain, the involvement of spinal PAR2 and the pertinent signaling in the central sensitization is not determined yet in the rodent model of bone cancer pain. Findings Implantation of tumor cells into the tibias induced significant thermal hyperalgesia and mechanical allodynia, and enhanced glutamatergic strength in the ipsilateral dorsal horn. Significantly increased brain-derived neurotrophic factor (BDNF) expression was detected in the dorsal horn, and blockade of spinal BDNF signaling attenuated the enhancement of glutamatergic strength, thermal hyperalgesia and mechanical allodynia in the rats with bone cancer pain. Significantly increased spinal PAR2 expression was also observed, and inhibition of PAR2 signaling ameliorated BDNF upsurge, enhanced glutamatergic strength, and thermal hyperalgesia and mechanical allodynia. Inhibition of NF-?B pathway, the downstream of PAR2 signaling, also significantly decreased the spinal BDNF expression, glutamatergic strength of dorsal horn neurons, and thermal hyperalgesia and mechanical allodynia. Conclusion The present study demonstrated that activation of PAR2 triggered NF-?B signaling and significantly upregulated the BDNF function, which critically contributed to the enhancement of glutamatergic transmission in spinal dorsal horn and thermal and mechanical hypersensitivity in the rats with bone cancer. This indicated that PAR2 - NF-?B signaling might become a novel target for the treatment of pain in patients with bone cancer. PMID:24886294

2014-01-01

351

Benthic primary productivity on the Georgia midcontinental shelf: Benthic flux measurements and high-resolution, continuous in situ PAR records  

Microsoft Academic Search

Continuous, 7 year records of above-water, near-surface water column and near-bottom measurements of photosynthetically active radiation (PAR) were used in conjunction with in situ chamber measurements to estimate magnitude and seasonal variations in benthic primary productivity (BPP) on the Georgia continental shelf. Correlation between BPP and PAR flux was established with 19 light\\/dark benthic chamber and PAR flux measurements at

R. A. Jahnke; J. R. Nelson; M. E. Richards; C. Y. Robertson; A. M. F. Rao; D. B. Jahnke

2008-01-01

352

SUR LA THORIE DE L'COULEMENT DES LIQUIDES PAR LES ORIFICES EN MINCE PAROI, CIRCULAIRES OU RECTANGULAIRES ALLONGS; CALCUL  

E-print Network

265 SUR LA TH�ORIE DE L'�COULEMENT DES LIQUIDES PAR LES ORIFICES EN MINCE PAROI, CIRCULAIRES OU DE L'ORIFICE; PAR M. J. BOUSSINESQ. 1' 1. (.orsqu'un vase plein de liquide est percé, à travers une partie plane et mince de sa paroi, d'un orifice cr, de dimensions très petites par rapport à ses

Boyer, Edmond

353

Proteolytic Activation of the Protease-activated Receptor (PAR)-2 by the Glycosylphosphatidylinositol-anchored Serine Protease Testisin.  

PubMed

Protease-activated receptors (PARs) are a family of seven-transmembrane, G-protein-coupled receptors that are activated by multiple serine proteases through specific N-terminal proteolytic cleavage and the unmasking of a tethered ligand. The majority of PAR-activating proteases described to date are soluble proteases that are active during injury, coagulation, and inflammation. Less investigation, however, has focused on the potential for membrane-anchored serine proteases to regulate PAR activation. Testisin is a unique trypsin-like serine protease that is tethered to the extracellular membrane of cells through a glycophosphatidylinositol (GPI) anchor. Here, we show that the N-terminal domain of PAR-2 is a substrate for testisin and that proteolytic cleavage of PAR-2 by recombinant testisin activates downstream signaling pathways, including intracellular Ca(2+) mobilization and ERK1/2 phosphorylation. When testisin and PAR-2 are co-expressed in HeLa cells, GPI-anchored testisin specifically releases the PAR-2 tethered ligand. Conversely, knockdown of endogenous testisin in NCI/ADR-Res ovarian tumor cells reduces PAR-2 N-terminal proteolytic cleavage. The cleavage of PAR-2 by testisin induces activation of the intracellular serum-response element and NF?B signaling pathways and the induction of IL-8 and IL-6 cytokine gene expression. Furthermore, the activation of PAR-2 by testisin results in the loss and internalization of PAR-2 from the cell surface. This study reveals a new biological substrate for testisin and is the first demonstration of the activation of a PAR by a serine protease GPI-linked to the cell surface. PMID:25519908

Driesbaugh, Kathryn H; Buzza, Marguerite S; Martin, Erik W; Conway, Gregory D; Kao, Joseph P Y; Antalis, Toni M

2015-02-01

354

Loss of Par-1a/MARK3/C-TAK1 Kinase Leads to Reduced Adiposity, Resistance to Hepatic Steatosis, and Defective Gluconeogenesis ?  

PubMed Central

Par-1 is an evolutionarily conserved protein kinase required for polarity in worms, flies, frogs, and mammals. The mammalian Par-1 family consists of four members. Knockout studies of mice implicate Par-1b/MARK2/EMK in regulating fertility, immune homeostasis, learning, and memory as well as adiposity, insulin hypersensitivity, and glucose metabolism. Here, we report phenotypes of mice null for a second family member (Par-1a/MARK3/C-TAK1) that exhibit increased energy expenditure, reduced adiposity with unaltered glucose handling, and normal insulin sensitivity. Knockout mice were protected against high-fat diet-induced obesity and displayed attenuated weight gain, complete resistance to hepatic steatosis, and improved glucose handling with decreased insulin secretion. Overnight starvation led to complete hepatic glycogen depletion, associated hypoketotic hypoglycemia, increased hepatocellular autophagy, and increased glycogen synthase levels in Par-1a?/? but not in control or Par-1b?/? mice. The intercrossing of Par-1a?/? with Par-1b?/? mice revealed that at least one of the four alleles is necessary for embryonic survival. The severity of phenotypes followed a rank order, whereby the loss of one Par-1b allele in Par-1a?/? mice conveyed milder phenotypes than the loss of one Par-1a allele in Par-1b?/? mice. Thus, although Par-1a and Par-1b can compensate for one another during embryogenesis, their individual disruption gives rise to distinct metabolic phenotypes in adult mice. PMID:20733003

Lennerz, Jochen K.; Hurov, Jonathan B.; White, Lynn S.; Lewandowski, Katherine T.; Prior, Julie L.; Planer, G. James; Gereau, Robert W.; Piwnica-Worms, David; Schmidt, Robert E.; Piwnica-Worms, Helen

2010-01-01

355

Matrix metalloproteinase-10 is a critical effector of protein kinase C?-Par6?-mediated lung cancer  

PubMed Central

Protein kinase C? (PKC?) drives transformed growth of non-small cell lung cancer (NSCLC) cells through the Rho family GTPase Rac1. We show here that PKC? activates Rac1 in NSCLC cells by formation of a PKC?–Par6? complex that drives anchorage-independent growth and invasion through activation of matrix metalloproteinase-10 (MMP-10) expression. RNAi-mediated knockdown of PKC?, Par6? or Rac1 expression inhibits NSCLC transformation and MMP-10 expression in vitro. Expression of wild-type Par6? in Par6?-deficient cells restores transformation and MMP-10 expression, whereas expression of Par6? mutants that either cannot bind PKC? (Par6?-K19A) or couple to Rac1 (Par6?-?CRIB) do not. Knockdown of MMP-10 expression blocks anchorage-independent growth and invasion of NSCLC cells and addition of catalytically active MMP-10 to PKC?- or Par6?-deficient cells restores anchorage-independent growth and invasion. Dominant-negative PKC? inhibits tumorigenicity and MMP-10 expression in subcutaneous NSCLC tumors. MMP-10 and PKC? are coordinately overexpressed in primary NSCLC tumors, and tumor MMP-10 expression predicts poor survival in NSCLC patients. Our data define a PKC?–Par6?–Rac1 signaling axis that drives anchorage-independent growth and invasion of NSCLC cells through induction of MMP-10 expression. PMID:18427549

Frederick, LA; Matthews, JA; Jamieson, L; Justilien, V; Thompson, EA; Radisky, DC; Fields, AP

2009-01-01

356

Tumour Microenvironments Induce Expression of Urokinase Plasminogen Activator Receptor (uPAR) and Concomitant Activation of Gelatinolytic Enzymes  

PubMed Central

Background The urokinase plasminogen activator receptor (uPAR) is associated with poor prognosis in oral squamous cell carcinoma (OSCC), and increased expression of uPAR is often found at the invasive tumour front. The aim of the current study was to elucidate the role of uPAR in invasion and metastasis of OSCC, and the effects of various tumour microenvironments in these processes. Furthermore, we wanted to study whether the cells’ expression level of uPAR affected the activity of gelatinolytic enzymes. Methods The Plaur gene was both overexpressed and knocked-down in the murine OSCC cell line AT84. Tongue and skin tumours were established in syngeneic mice, and cells were also studied in an ex vivo leiomyoma invasion model. Soluble factors derived from leiomyoma tissue, as well as purified extracellular matrix (ECM) proteins, were assessed for their ability to affect uPAR expression, glycosylation and cleavage. Activity of gelatinolytic enzymes in the tissues were assessed by in situ zymography. Results We found that increased levels of uPAR did not induce tumour invasion or metastasis. However, cells expressing low endogenous levels of uPAR in vitro up-regulated uPAR expression both in tongue, skin and leiomyoma tissue. Various ECM proteins had no effect on uPAR expression, while soluble factors originating from the leiomyoma tissue increased both the expression and glycosylation of uPAR, and possibly also affected the proteolytic processing of uPAR. Tumours with high levels of uPAR, as well as cells invading leiomyoma tissue with up-regulated uPAR expression, all displayed enhanced activity of gelatinolytic enzymes. Conclusions Although high levels of uPAR are not sufficient to induce invasion and metastasis, the activity of gelatinolytic enzymes was increased. Furthermore, several tumour microenvironments have the capacity to induce up-regulation of uPAR expression, and soluble factors in the tumour microenvironment may have an important role in the regulation of posttranslational modification of uPAR. PMID:25157856

Magnussen, Synnøve; Hadler-Olsen, Elin; Latysheva, Nadezhda; Pirila, Emma; Steigen, Sonja E.; Hanes, Robert; Salo, Tuula; Winberg, Jan-Olof; Uhlin-Hansen, Lars; Svineng, Gunbjørg

2014-01-01

357

Participatory Action Research (PAR) in Middle School: Opportunities, Constraints, and Key Processes  

PubMed Central

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

Ritterman, Miranda L.; Wanis, Maggie G.

2010-01-01

358

Lipid nanoparticles as delivery vehicles for the Parietaria judaica major allergen Par j 2  

PubMed Central

Parietaria pollen is one of the major causes of allergic reaction in southern Europe, affecting about 30% of all allergic patients in this area. Specific immunotherapy is the only treatment able to modify the natural outcome of the disease by restoring a normal immunity against allergens. The preparation of allergen-solid lipid nanoparticles as delivery vehicles for therapeutic proteins, P. judaica major allergen Par j 2, was investigated. The Par j 2 allergen was expressed in a large amount in Escherichia coli and purified to homogeneity. Its immunological properties were studied by western blotting and enzyme-linked immunosorbent assay inhibition. Solid lipid nanoparticles were obtained by water-in-oil-in-water multiple emulsion method and characterized in terms of mean size and surface charge. These systems (approximately 250 nm diameter and negative surface charge) incorporated recombinant Par j 2 with 40% or greater efficiency. Moreover, the endotoxin level and anaphylactic activity of the empty solid lipid nanoparticles and recombinant Par j 2-loaded solid lipid nanoparticles were evaluated by looking at the overexpression of CD203c marker on human basophils. These results demonstrate that recombinant Par j 2-nanoparticles could be proposed as safe compositions for the development of new therapeutic dosage forms to cure allergic reactions. PMID:22162654

Bondì, Maria Luisa; Montana, Giovanna; Craparo, Emanuela Fabiola; Di Gesù, Roberto; Giammona, Gaetano; Bonura, Angela; Colombo, Paolo

2011-01-01

359

Ablation de ZnO par laser UV (193 nm) : nano-agrégats en phase gazeuse  

NASA Astrophysics Data System (ADS)

La condensation de nano-agrégats d'oxyde de zinc en phase gazeuse est mise en évidence lors de l'ablation de ZnO massif par laser ArF pulsé. Nous comparons l'évolution spatio-temporelle de la forme du panache d'ablation (plume) de ZnO sous vide et sous atmosphère de gaz de couverture (oxygène et/ou hélium) à partir des images CCD et des résultats issus d'analyses spectroscopiques. L'expansion du plasma et la croissance des nano-clusters sont influencées par l'effet du confinement de la plume dû aux collisions entre les particules ablatées et les molécules de gaz ambiant ainsi que par les réactions chimiques dans le cas de l'oxygène. Le spectre de rayonnement du plasma est constitué principalement par l'émission d'atomes excités de Zn neutre. Nous avons observé la photoluminescence des nano-agrégats en suspension dans le gaz ainsi que leur décomposition par laser ArF.

Ozerov, I.; Bulgakov, A.; Nelson, D.; Castell, R.; Sentis, M.; Marine, W.

2003-06-01

360

Nanomechanical recognition of prognostic biomarker suPAR with DVD-ROM optical technology  

NASA Astrophysics Data System (ADS)

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.

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

361

Co-expression of uPAR and CXCR4 promotes tumor growth and metastasis in small cell lung cancer  

PubMed Central

Urokinase-type plasminogen activator receptor (uPAR) and C-X-C-chemokine receptor-4 (CXCR4) are considered as key molecules in invasion and metastasis of several cancers via extracellular matrix degeneration and assist tumor metastasis to specific sites by chemotaxis. However, the combined effect of uPAR and CXCR4 on small cell lung cancer (SCLC), the most aggressive type of lung cancer, is not clear. In this study, we detected the expression of uPAR and CXCR4 in SCLC tissue samples (n = 50) by immunohistochemistry. The tumors with high expression of both uPAR and CXCR4 (12/50) had larger size, higher lymph node (LN) metastasis and worse prognosis of patients than those with low expression of uPAR and CXCR4 (38/50) (P < 0.05). We further identified and isolated the both uPAR and CXCR4 positive expression subpopulation cells (uPAR+CXCR4+ cells) from the SCLC cell line H446 by flow cytometry. The uPAR+CXCR4+ cancer cells showed a higher invasive and migrating capacity in the transwell and wound healing assays compared with other subpopulation cells (P < 0.05). uPAR+CXCR4+ cells injected subcutaneously in nude mice markedly increased tumor growth and induced lung metastasis, while other subpopulation cells did not. In conclusion, these data suggest that uPAR and CXCR4 co-expression predicts worse prognosis of SCLC patients. uPAR+CXCR4+ cells promote the tumor growth and play a potential role in metastasis of SCLC. PMID:25120753

Li, Yanlei; Shen, Yao; Miao, Yajing; Luan, Yajing; Sun, Baocun; Qiu, Xiaofei

2014-01-01

362

Potential Ecological Effects of Contaminants in the Exposed Par Pond Sediments  

SciTech Connect

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.

Paller, M.H. [Westinghouse Savannah River Company, AIKEN, SC (United States); Wike, L.D.

1996-08-01

363

PAR-4/LKB1 regulates DNA replication during asynchronous division of the early C. elegans embryo  

PubMed Central

Regulation of cell cycle duration is critical during development, yet the underlying molecular mechanisms are still poorly understood. The two-cell stage Caenorhabditis elegans embryo divides asynchronously and thus provides a powerful context in which to study regulation of cell cycle timing during development. Using genetic analysis and high-resolution imaging, we found that deoxyribonucleic acid (DNA) replication is asymmetrically regulated in the two-cell stage embryo and that the PAR-4 and PAR-1 polarity proteins dampen DNA replication dynamics specifically in the posterior blastomere, independently of regulators previously implicated in the control of cell cycle timing. Our results demonstrate that accurate control of DNA replication is crucial during C. elegans early embryonic development and further provide a novel mechanism by which PAR proteins control cell cycle progression during asynchronous cell division. PMID:24841566

Descoteaux, Catherine; Chartier, Nicolas T.; Pintard, Lionel; Labbé, Jean-Claude

2014-01-01

364

Rullier A et al. PAR-1 knock-out protects against liver fibrosis1 Protease-activated receptor 1 (PAR-1) knock-out reduces experimentally-induced liver  

E-print Network

Rullier A et al. PAR-1 knock-out protects against liver fibrosis1 Protease-activated receptor 1 (PAR-1) knock-out reduces experimentally-induced liver fibrosis. Anne Rullier1, 2 , Jennifer Gillibert Victor Segalen Bordeaux 2, Bordeaux, F-33076 France. Key words : liver fibrosis, hemostasis, thrombin

Paris-Sud XI, Université de

365

PAR2 activation alters colonic paracellular permeability in mice via IFN-?-dependent and -independent pathways  

PubMed Central

Activation of colonic proteinase-activated receptor-2 (PAR2) caused inflammation and increased mucosal permeability in mouse colon. The present study was aimed at characterizing the possible links between these two phenomena. We evaluated the effects of intracolonic infusion of PAR2-activating peptide, SLIGRL, on colonic paracellular permeability and inflammation at two different doses, 5 and 100 ?g per mouse, in an attempt to discriminate between both PAR2-mediated effects. We further investigated the possible involvement of interferon ? (IFN-?) and calmodulin-dependent activation of myosin light chain kinase (MLCK), and alterations of zonula occludens-1 (ZO-1) localization in PAR2-induced responses. Thus, at the lower dose, SLIGRL increased colonic permeability without causing inflammation. Western blotting showed phosphorylation of mucosal myosin light chain (MLC) expression after both doses of SLIGRL. Moreover, while the MLCK inhibitor, ML-7, abolished the permeability effects of the low dose of SLIGRL, it only partially inhibited that of the high dose. In IFN-?-deficient mice (B6 ifng?/?), the increases in permeability were similar for both doses of SLIGRL and prevented by ML-7. In addition, MLCK immunoprecipitation revealed an increase of calmodulin binding to MLCK in the mucosa of mice treated with either dose of SLIGRL. Finally, we have shown that direct activation of PAR2 on enterocytes is responsible for increased permeability and ZO-1 disruption. Moreover, SLIGRL at a dose that does not produce inflammation increases permeability via calmodulin activation, which binds and activates MLCK. The resulting tight junction opening does not depend upon IFN-? secretion, while the increased permeability in response to the high dose of PAR2 agonist involves IFN-? secretion. PMID:15194744

Cenac, Nicolas; Chin, Alex C; Garcia-Villar, Rafael; Salvador-Cartier, Christel; Ferrier, Laurent; Vergnolle, Nathalie; Buret, André G; Fioramonti, Jean; Bueno, Lionel

2004-01-01

366

K-Area and Par Pond Sewage Sludge Application Sites groundwater monitoring reports, second quarter 1992  

SciTech Connect

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.

Not Available

1992-10-01

367

NOUVELLES RECHERCHES SUR L'MISSION DES NEUTRONS Par Mme IRNE CURIE et F. JOLIOT.  

E-print Network

On étudie le rayonnement nucléaire pénétrant excité par les rayons 03B1 du polonium dans les éléments légers du polonium. L'émission des neutrons de Li commence seulement pour une énergie de 5 106 eV des rayons rayonnement 'y nucléaire sous l'action des particules a du polonium. Il a été prouvé par la suite que la

Paris-Sud XI, Université de

368

A review of "La Rochefoucauld par quatre chemins. Les Maximes et leurs ambivalence" by Eric Turcat  

E-print Network

82 seventeenth-century news Eric Turcat. La Rochefoucauld par quatre chemins. Les Maximes et leurs ambivalence. Biblio 17, v. 206. Tübingen: Gunter Narr Verlag, 2013. 220 pp. ISBN 978-63-8233-6803-8. $65.91. Review by denis d. grélé, university...(s). For his part, Eric Turcat does not recoil from the challenge and offers in La Rochefoucauld par quatre chemins, not one but four possible methods of understanding apparent disparate fragments of thoughts. Each chapter of his book is devoted to one...

Grele, Denis D.

2014-01-01

369

Un premier schéma de l’inconscient par Charcot dès 1892  

Microsoft Academic Search

Résumé  Nous rapportons ici un schéma de l’inconscient tracé en juin 1892 par Jean-Martin Charcot qui s’avère être un inédit du fonds\\u000a légué par son fils, Jean-Baptiste, à la bibliothèque de La Salpêtrière, aujourd’hui Fonds Charcot de l’université Pierre-et-Marie-Curie.\\u000a Ce schéma est lié au travail clinique de Jean-Martin Charcot sur l’hystérie et à sa conceptualisation progressive de la place\\u000a de l’affect

C. Bouchara; P. Mazet; D. Cohen

2010-01-01

370

Rglage du PID numrique par rduction de la complexit du rgulateur  

E-print Network

Réglage du PID numérique par réduction de la complexité du régulateur Zito Gianluca*, Landau Ioan procédure de synthèse des régulateurs PID numériques pour les systèmes d'ordre élevé est présentée. Cette modèle du système. L'estimation des paramètres du PID est faite par un algorithme du type identication en

Paris-Sud XI, Université de

371

MESURE D'ACTIVIT DES METTEURS 03B1 PAR CIN-NUCLOGRAPHIE Par Mme O. R0152HRICH-GOUSSU,  

E-print Network

polonium par le ciné- nucléographe. Pour des sources de quelques dizièmes à quelques centièmes de avait porté sur des sources de polonium d'environ 200 FC et les résultats avaient été concordants avec'une activité résiduelle de l'appareil, toujours possible en raison de la diffusion du polonium. Ce mouvement

Paris-Sud XI, Université de

372

Caractristiques spectrales de l'lectrogastrogramme chez l'homme par drivations externes. Incidence de la pathologie gastrique et en particulier des noplasies, par  

E-print Network

évidence par analyse multivariée entre les dérivations, les jours d'enregistrement, le sexe et l'âge. Chez plus basse, et d'autres une fréquence plus élevée que la normale. L'amplitude Y du pic fréquentiel'analyse du pic d'amplitude montre cependant que 25 % des néoplasiques présentent une amplitude pseudonormale

Paris-Sud XI, Université de

373

difficile par le trs faible flux de neutrons disponible. Grce la trs faible dure des impulsions issues  

E-print Network

energy distribution of the fission fragments in binary fission of 235U and in tripartition. (2 pré- cision dans la détermination de la section efficace de fission du 239Pu réclamée par les physiciens des piles. BALANCE D'�NERGIE POUR LA FISSION TERNAIRE DE 235U INDUITE PAR LES NEUTRONS LENTS (1

Paris-Sud XI, Université de

374

Racial Difference in Human Platelet PAR4 Reactivity Reflects Expression of PCTP and miR-376c  

PubMed Central

Racial differences in the pathophysiology of atherothrombosis are poorly understood. We explored the function and transcriptome of platelets in healthy black (n = 70) and white (n = 84) subjects. PAR4 thrombin receptor induced platelet aggregation and calcium mobilization were significantly greater in black subjects. Numerous differentially expressed (DE) RNAs were associated with both race and PAR4 reactivity, including phosphatidylcholine transfer protein (PCTP), and platelets from blacks expressed higher levels of PC-TP protein. PC-TP inhibition or depletion blocked activation of platelets or megakaryocytic cell lines through PAR4 but not PAR1. MiR-376c levels were DE by race and PAR4 reactivity, and were inversely correlated with PCTP mRNA levels, PC-TP protein levels and PAR4 reactivity. MiR-376c regulated expression of PC-TP in human megakaryocytes. A disproportionately high number of miRNAs DE by race and PAR4 reactivity, including miR-376c, are encoded in the DLK1-DIO3 locus, and were lower in platelets from blacks. These results support PC-TP as a regulator of the racial difference in PAR4-mediated platelet activation, indicate a genomic contribution to platelet function that differs by race, and emphasize a need to consider race effects when developing anti-thrombotic drugs. PMID:24216752

Edelstein, Leonard C.; Simon, Lukas M.; Montoya, Raúl Teruel; Holinstat, Michael; Chen, Edward S.; Bergeron, Angela; Kong, Xianguo; Nagalla, Srikanth; Mohandas, Narla; Cohen, David E.; Dong, Jing-fei; Shaw, Chad; Bray, Paul F.

2013-01-01

375

AP-3 regulates PAR1 ubiquitin-independent MVB/lysosomal sorting via an ALIX-mediated pathway.  

PubMed

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

Dores, Michael R; Paing, May M; Lin, Huilan; Montagne, William A; Marchese, Adriano; Trejo, JoAnn

2012-09-01

376

The distribution and nature of gonadotropic cells in the rostral pars distalis of the Atlantic salmon, Salmo salar  

E-print Network

salmon, Salmo salar B. EKENGREN J. PEUTE G. FRIDBERG University of Stockholm, Department of Zoology, Box the gonadotropic (GTH) cells in the rostral pars distalis (RPD) of the pituitary in the Atlantic salmon in phases are generally distributed in the proximal pars distalis. In the sockeye salmon the GTH cells also occur

Paris-Sud XI, Université de

377

The Product of par-4, a Gene Induced during Apoptosis, Interacts Selectively with the Atypical Isoforms of Protein Kinase C  

Microsoft Academic Search

The atypical PKCs are involved in a number of important cellular functions, including cell proliferation. We report here that the product of the par-4 gene specifically interacts with the regulatory domains of ?PKC and ?\\/?PKC, which dramatically inhibits their enzymatic activity. This is particularly challenging, because expression of par-4 has been shown to correlate with growth inhibition and apoptosis. Results

María T Díaz-Meco; María M Municio; Sonia Frutos; Pilar Sanchez; José Lozano; Laura Sanz; Jorge Moscat

1996-01-01

378

The Rac-GAP Bcr is a novel regulator of the Par complex that controls cell polarity  

PubMed Central

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 PKC?) 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 PKC? signaling. Loss of Bcr results in faster, more random migration and striking polarity defects in astrocytes. These polarity defects are rescued by reducing PKC? 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 PKC? function. PMID:24152735

Narayanan, Anjana S.; Reyes, Steve B.; Um, Kyongmi; McCarty, Joseph H.; Tolias, Kimberley F.

2013-01-01

379

6th International OFDM-Workshop (InOWo) 2001, Hamburg 31-1 PAR reduction revisited  

E-print Network

6th International OFDM-Workshop (InOWo) 2001, Hamburg 31-1 PAR reduction revisited: an extension to #12;31-2 6th International OFDM-Workshop (InOWo) 2001, Hamburg y should grow with the PAR limit. High

Henkel, Werner

380

A light and electron microscopic study of the healing of pars plana incisions in the rhesus monkey  

Microsoft Academic Search

Pars plana incisions were made in 11 rhesus monkey eyes. Six animals had injections of 0.1 ml of blood into the vitreous cavity with a 25-gauge needle and five animals had vitrectomy through a 4-mm incision with a multifunction vitrectomy probe. Six to 13 years later the scars in the pars plana were found to consist of fibrous tissue and

Frank Koch; Allan Kreiger; Manfred Spitznas

1994-01-01

381

The ratio of transmitted near-infrared radiation to photosynthetically active radiation (PAR) increases in proportion to the adsorbed PAR in the canopy.  

PubMed

The daily total photosynthetically active radiation (400-700 nm, PAR) and near-infrared radiation (700-1000 nm, NIR) were measured in the understory beneath the canopy (PARt and NIRt) and above the canopy (PARi and NIRi) of a Japanese cool-temperate deciduous broad-leaved forest during the snow-free period (May to November). The integration of spectral radiation for NIR and that for PAR, and the daily integrations of instantaneous NIR and PAR, reduced the noises from the optical difference in spectrum and from canopy structure heterogeneity, sky condition and solar elevation. PARi/PARt was linearly related to NIRt/PARt (R² = 0.96). The effect of cloudiness was negligible, because the fluctuation of NIRi/PARi was quite small regardless of season and weather conditions compared with the range of NIRt/PARt in the forest. The ratio of NIRt/PARt beneath the canopy was log-linearly related to the in situ leaf area index (LAI) with a wide range from 0 to 5.25 (R² = 0.97). We conclude that seasonal changes in fAPAR (= 1 - PARt/PARi) and LAI of a canopy can be estimated with high accuracy by transmitted NIRt and PARt beneath the canopy. PMID:20428920

Kume, Atsushi; Nasahara, Kenlo N; Nagai, Shin; Muraoka, Hiroyuki

2011-01-01

382

The interaction of mPar3 with the ubiquitin ligase Smurf2 is required for the establishment of neuronal polarity.  

PubMed

The Par polarity complex consisting of the evolutionarily conserved proteins mPar3, mPar6, and aPKC regulates cell polarity in many cell types including neurons. Here we show that mPar3 is required for the establishment of neuronal polarity and links the Smurf2 to Kinesin-2. The HECT domain E3 ubiquitin ligase Smurf2 ensures that neurons extend only a single axon by initiating the degradation of inactive Rap1B through the ubiquitin/proteasome system. Its interaction with mPar3 is required to localize Smurf2 to growth cones and restrict Rap1B to the axon. Interfering with the binding of mPar3 to Kinesin-2 or Smurf2 to mPar3 and knockdown of mPar3 by RNAi disrupt the establishment of neuronal polarity through the failure to restrict Rap1B to a single neurite. PMID:17906294

Schwamborn, Jens C; Khazaei, Mohammad R; Püschel, Andreas W

2007-11-30

383

IL-32-PAR2 axis is an innate immunity sensor providing alternative signaling for LPS-TRIF axis  

PubMed Central

Interleukin (IL)-32 is known to exert adujvant effects on innate immune response, however, receptors and downstream signaling pathways remain to be clarified. Here we found that IL-32? upregulated serine protease activity of proteinase-3 (PR3), in turn triggering protease-activated receptor 2 (PAR2) signaling. Interestingly, silencing of PR3 or PAR2 using siRNA markedly diminished IL-32?-induced TNF? and IFN-? mRNA expression. IL-32?-PAR2 axis utilized TRIF and Ras-Raf-1 pathways. On stimulation with lipopolysaccharide (LPS), differential activation of protein kinase C isoforms modulated the balance between LPS-TLR4-TRIF and IL-32-PAR2-TRIF axes, because LPS was a strong inducer of IL-32?. IL-32-PAR2-TRIF axis might serve not only as an extracellular sensor of bacterial and autologous proteases, but also as a modulator of innate and adaptive immunity during infection. PMID:24129891

Nakayama, Masanori; Niki, Yasuo; Kawasaki, Toshiki; Takeda, Yuki; Ikegami, Hiroyasu; Toyama, Yoshiaki; Miyamoto, Takeshi

2013-01-01

384

Urine But Not Serum Soluble Urokinase Receptor (suPAR) May Identify Cases of Recurrent FSGS in Kidney Transplant Candidates  

PubMed Central

Introduction Recently serum soluble urokinase receptor (suPAR) has been proposed as a cause of two thirds of cases of focal segmental glomerulosclerosis (FSGS). It was noted to be uniquely elevated in cases of primary FSGS with higher levels noted in cases that recurred post-transplant. It is also suggested as a possible target and marker of therapy. Methods We studied serum and urine suPAR from pre-transplant banked samples from 86 well characterized kidney transplant recipients and 10 healthy controls to determine its prognostic utility. Causes of native kidney disease were; primary focal segmental glomerulosclerosis, diabetic nephropathy, membranous nephropathy, immunoglobulin A nephropathy, and autosomal dominant polycystic kidney disease. suPAR was measured using a commercially available enzyme-linked immunosorbent assay kit. Urinary suPAR was indexed to creatinine. Results Both serum and urine suPAR correlated with proteinuria and albuminuria. Serum suPAR was found to be elevated in all transplant candidates with advanced renal disease compared to healthy controls and could not differentiate disease diagnosis. Urine suPAR was elevated in cases of recurrent focal segmental glomerulosclerosis compared to all other causes of end stage renal disease. Recurrent focal segmental glomerulosclerosis cases had substantially higher proteinuria compared to all other cases. However, elevated urinary suPAR showed a trend in providing additional prognostic information beyond proteinuria in the small cohort of recurrent FSGS cases. Conclusion In advanced renal disease, elevated serum suPAR is not unique to FSGS cases. Urinary suPAR appears to be higher in cases of focal segmental glomerulosclerosis destined for recurrence and merits further evaluation. PMID:23736353

Palacios, Carlos R Franco; Lieske, John C; Wadei, Hani M; Rule, Andrew D; Fervenza, Fernando C.; Voskoboev, Nikolay; Garovic, Vesna D; Zand, Ladan; Stegall, Mark D; Cosio, Fernando G; Amer, Hatem

2014-01-01

385

An Uncleavable uPAR Mutant Allows Dissection of Signaling Pathways in uPA-dependent Cell Migration  

PubMed Central

Urokinase-type plasminogen activator (uPA) binding to uPAR induces migration, adhesion, and proliferation through multiple interactions with G proteins-coupled receptor FPRL1, integrins, or the epidermal growth factor (EGF) receptor (EGFR). At least two forms of uPAR are present on the cell surface: full-length and cleaved uPAR, each specifically interacting with one or more transmembrane proteins. The connection between these interactions and the effects on the signaling pathways activation is not clear. We have exploited an uPAR mutant (hcr, human cleavage resistant) to dissect the pathways involved in uPA-induced cell migration. This mutant is not cleaved by proteases, is glycosylphosphatidylinositol anchored, and binds uPA with a normal Kd. Both wild-type (wt) and hcr-uPAR are able to mediate uPA-induced migration, are constitutively associated with the EGFR, and associate with ?3?1 integrin upon uPA binding. However, they engage different pathways in response to uPA. wt-uPAR requires both integrins and FPRL1 to mediate uPA-induced migration, and association of wt-uPAR to ?3?1 results in uPAR cleavage and extracellular signal-regulated kinase (ERK) activation. On the contrary, hcr-uPAR does not activate ERK and does not engage FPRL1 or any other G protein-coupled receptor, but it activates an alternative pathway initiated by the formation of a triple complex (uPAR-?3?1-EGFR) and resulting in the autotyrosine phosphorylation of EGFR. PMID:16267271

Mazzieri, Roberta; D'Alessio, Silvia; Kenmoe, Richard Kamgang; Ossowski, Liliana; Blasi, Francesco

2006-01-01

386

Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR2) is involved in vascular function  

PubMed Central

Background and Purpose Proteinase-activated receptors (PARs) and toll-like receptors (TLRs) are involved in innate immune responses. The aim of this study was to evaluate the possible cross-talk between PAR2 and TLR4 in vessels in physiological condition and how it varies following stimulation of TLR4 by using in vivo and ex vivo models. Experimental Approach Thoracic aortas were harvested from both naïve and endotoxaemic rats for in vitro studies. Arterial blood pressure was monitored in anaesthetized rats in vivo. LPS was used as a TLR4 agonist while PAR2 activating peptide (AP) was used as a PAR2 agonist. Aortas harvested from TLR4–/– mice were also used to characterize the PAR2 response. Key Results PAR2, but not TLR4, expression was enhanced in aortas of endotoxaemic rats. PAR2AP-induced vasorelaxation was increased in aortic rings of LPS-treated rats. TLR4 inhibitors, curcumine and resveratrol, reduced PAR2AP-induced vasorelaxation and PAR2AP-induced hypotension in both naïve and endotoxaemic rats. Finally, in aortic rings from TLR4–/– mice, the expression of PAR2 was reduced and the PAR2AP-induced vasodilatation impaired compared with those from wild-type mice and both resveratrol and curcumine were ineffective. Conclusions and Implications Cross-talk between PAR2 and TLR4 contributes to vascular homeostasis. PMID:22957757

Bucci, M; Vellecco, V; Harrington, L; Brancaleone, V; Roviezzo, F; Mattace Raso, G; Ianaro, A; Lungarella, G; De Palma, R; Meli, R; Cirino, G

2013-01-01

387

CONVERSION DIRECTE D'NERGIE THERMIQUE EN MOUVEMENT Par C. VERI,  

E-print Network

faibles. Abstract. 2014 A method is proposed for directly converting thermal energy into mechanical energy166 CONVERSION DIRECTE D'�NERGIE THERMIQUE EN MOUVEMENT Par C. VERI�, Laboratoire de Magnétisme et conversion directe d'énergie thermique en énergie mécanique au moyen de thermoéléments. A titre d

Boyer, Edmond

388

Friction dependence of shallow granular flows from discrete par-ticle simulations  

E-print Network

Friction dependence of shallow granular flows from discrete par- ticle simulations Anthony Thornton relation for the macroscopic bed friction or basal roughness obtained from micro-scale discrete particle simulations of steady flows. We systematically vary the bed friction by changing the contact friction

Al Hanbali, Ahmad

389

Comparative validation of the IPAQ and the 7Day PAR among women diagnosed with breast cancer  

Microsoft Academic Search

BACKGROUND: The criterion-related validity and measurement bias of the long form of the International Physical Activity Questionnaire (IPAQ) was compared to the 7-Day Physical Activity Recall (PAR). METHODS: Participants were women who have been diagnosed with breast cancer and enrolled in the ongoing Women's Healthy Eating and Living Study. Women (N = 159, average age 57 years) wore an accelerometer

Marilyn Johnson-Kozlow; James F Sallis; Elizabeth A Gilpin; Cheryl L Rock; John P Pierce

2006-01-01

390

he gypsy moth (Lymantria dis-par) is probably the most de-  

E-print Network

T he gypsy moth (Lymantria dis- par) is probably the most de- structive forest defoliator in the United States. More than 81 million acres of forests have been defoliated by the gypsy moth since 1924). During gypsy moth outbreaks, many species of hard- woods may be defoliated; repeated de- foliation causes

Liebhold, Andrew

391

Split Scenes, Converging Visions: The Ethical Terrains where PAR and Borderlands Scholarship Meet  

ERIC Educational Resources Information Center

This paper examines theoretical linkages between Anzaldua's borderland scholarship, in particular the notion of mestiza consciousness, and participatory action research. Two studies with high school and college co-researchers falling along different points of the PAR spectrum are described to illustrate these conceptual linkages. Points in the…

Ayala, Jennifer

2009-01-01

392

36] thologie Pour la Science -n 420 -Octobre 2012 Les nids construits par les termites  

E-print Network

36] �thologie © Pour la Science - n° 420 - Octobre 2012 Les nids construits par les termites sont Picarougne et Christian Jost 1Les termites Trinervitermes gemina- tus (a plus de 500.Laterredunidestenrichieenargile que les termites prélèvent parfois à plu- sieurs mètres de

Theraulaz, Guy

393

ACARYOCHLORIS EXPLAINING THE RIDDLE OF CHLOROPHYLL D IN RED ALGAE AND EXPANDING PAR FOR OXYGENIC PHOTOSYNTHESIS  

E-print Network

ACARYOCHLORIS ­ EXPLAINING THE RIDDLE OF CHLOROPHYLL D IN RED ALGAE AND EXPANDING PAR FOR OXYGENIC strain is shown to live epi- phytically on the red alga Gelidium caulacantheum, which itself is harvested by the red alga. Availability of far red light, however, is relatively unaffected by DOM or red

Oregon, University of

394

Fine structure of the chromophobe in the pars distalis of the common snapping turtle, Chelydra serpentina  

Microsoft Academic Search

Chromophobes of the pars distalis in young Chelydra serpentina have sparse cytoplasm with no specific granules; however, many cytoplasmic filaments are present. The chromophobes are connected to the other cell types by desmosomes, while different types of junctional specializations occur between adjacent chromophobes. Cytoplasmic filaments traverse the cytoplasm in a random manner and terminate on both the junctional complexes and

Michael T. Tseng; Chester L. Yntema

1976-01-01

395

REMARQUES SUR LES PRISMES A DVIATION CONSTANTE Par M. R. DE MALLEMANN.  

E-print Network

REMARQUES SUR LES PRISMES A D�VIATION CONSTANTE Par M. R. DE MALLEMANN. Faculté des Sciences de (~) : « Dans tout prisme à déviation constante, il existe une droite normale à la section principale, telle que toute rotation finie du prisme, autour de cette droite prise comme axe, ne détermine aucun déplacement

Boyer, Edmond

396

PREUVES EXPRIMENTALES DE L'EXISTENCE DU NEUTRON Par IRNE CURIE et F. JOLIOT.  

E-print Network

lIoffmann de très grande sensibilité (fig. 9, Pl. I, A). Une source de rayons ot du polonium, une irradié par le polonium, et de même pour les autres éléments. (*) Une partie des résultats exposés dans ce

Paris-Sud XI, Université de

397

TUDE DU RYTHME DES MISSIONS DE PARTICULES ALPHA DU POLONIUM Par JEAN BRENET,  

E-print Network

�TUDE DU RYTHME DES �MISSIONS DE PARTICULES ALPHA DU POLONIUM Par JEAN BRENET, Institut de Physique du Polonium (obtenus dans des conditions expérimentales différentes) ont été étudiés du point de vue

Boyer, Edmond

398

SUR LA PNTRATION DU POLONIUM DANS LE PLOMB, par Mlle E. MONTEL.  

E-print Network

SUR LA P�N�TRATION DU POLONIUM DANS LE PLOMB, par Mlle E. MONTEL. Institut du Radium, Paris de polonium ont été faits en solution légèrement chlorhydrique. Il est essentiel d'employer des la forme de leurs contours. Le polonium traverse donc l'épaisseur de feuilles minces de plomb en

Paris-Sud XI, Université de

399

SUR LES VALENCES DU POLONIUM Par MM. HAISSINSKY et M. GUILLOT.  

E-print Network

SUR LES VALENCES DU POLONIUM Par MM. HAISSINSKY et M. GUILLOT. Sommaire. - L'addition de quantités croissantes d'électrolytes aux solutions acides de polonium pro- voque un déplacement du potentiel critique de ions du polonium. La confrontation de ce résultat avec ceux d'expériences antérieures de

Boyer, Edmond

400

LES INTERVALLES EXTRMES ENTRE LES MISSIONS RADIOACTIVES. II. Par E. J. GUMBEL.  

E-print Network

longue telle que le polonium. On sait que les rayons actifs décroissent d'après la formule exponen de quelques heures. Le polonium est de préparation facile par évaporation d'une goutte de solution

Paris-Sud XI, Université de

401

et dtermin exprimentalement par M. Taylor Il semble que la divergence des rsultats doive tre  

E-print Network

polonium m'a amené au résul- tat : 116000 ions par particule. Ce nombre est très inférieur au nombre 164000. I;nfin, au cours de ce travail, j'ai eu l'occasion de déterminer la constante � du polonium et sa

Boyer, Edmond

402

Long-term results of pars plana vitrectomy in the management of complicated uveitis  

Microsoft Academic Search

This retrospective study evaluates the long term efficacy of pars plana vitrectomy on the preservation of vision in complicated chronic uveitis, including endogenous intermediate uveitis and other entities. Combined vitrectomy-lensectomy was performed in 10 eyes with complicated cataracts, and 18 vitrectomies were done without lensectomies. The mean follow up was 45 months. Additional retinal surgery (for example, scleral buckling) was

A Heiligenhaus; N Bornfeld; M H Foerster; A Wessing

1994-01-01

403

Classification dynamique par treillis de concepts pour la recherche d'information  

E-print Network

to their properties and it has been used in recent works to organise answers provided by a search engine accordingClassification dynamique par treillis de concepts pour la recherche d'information sur le web classification pour faire évoluer le treillis et ainsi mieux l'adapter au besoin de l'utilisateur. ABSTRACT

Paris-Sud XI, Université de

404

Crystal Structure of Thrombin Bound to the Uncleaved Extracellular Fragment of PAR1  

SciTech Connect

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.

Gandhi, Prafull S.; Chen, Zhiwei; Di Cera, Enrico (St. Louis-MED)

2010-05-11

405

Vanderbilt Hall Athletic Facility Physical Activity Readiness Questionnaire (PAR-Q)  

E-print Network

Vanderbilt Hall Athletic Facility Physical Activity Readiness Questionnaire (PAR-Q) Name (print _____________________ Regular physical activity is fun and healthy, and increasingly more people are starting to become more with their doctor before they start becoming much more physically active. If you are planning to become much more

Paulsson, Johan

406

Qualit dilectrique de couches minces isolantes de GaN obtenues par pulvrisation cathodique ractive  

E-print Network

fréquence. La conductivité, dominée par l'effet Poole- Frenkel, atteint 10-13 03A9-1cm-1à faible champ. Le. The conductivity is dominated by the Poole-Frenkel effect. Its value can reach 10-13 03A9-1cm-1at low fields

Boyer, Edmond

407

Enfance Violence Exil par Catherine MILKOVITCH-RIOUX et Rose DUROUX  

E-print Network

1 Enfance Violence Exil par Catherine MILKOVITCH-RIOUX et Rose DUROUX CELIS, Université Blaise Pascal Clermont-Ferrand (CELIS) PROGRAMME ANR Enfance Violence Exil (EVE) Vidéo du colloque : http : //www.enfance-violence-exil.net (rubrique « Colloques et séminaires ») L'Enfant Combattant, pratiques et

Paris-Sud XI, Université de

408

Cortactin activation by FVIIa/tissue factor and PAR2 promotes endothelial cell migration.  

PubMed

Cellular migration is a complex process that requires the polymerization of actin filaments to drive cellular extension. Smooth muscle and cancer cell migration has been shown to be affected by coagulation factors, notably the factor VII (FVIIa) and tissue factor (TF) complex. The present studies delineated mediators involved with the process of FVIIa/TF-induced cell migration and utilized a simple, precise, and reproducible, migration assay. Both FVIIa and protease-activated receptor-2 (PAR2)-activating peptide, SLIGRL, increased the migration rate of porcine cerebral microvascular endothelial cells (pCMVECs) overexpressing human TF. Ras homolog gene family member A (RhoA) and cortactin were upregulated during the process; expression of HIF, actin polymerization nuclear diaphanous-related formin-1 and -2 (Dia1, and Dia2) were unaffected. Gene silencing by shRNA to PAR2, RhoA, and cortactin attenuated this gene upregulation and migration induced by FVIIa/TF. Utilizing immunocellular localization, we demonstrate that during FVIIa/TF and PAR2 activation, cortactin molecules translocate from the cytoplasm to the cell periphery and assist in lamellipodia formation of pCMVECs. Overall, we demonstrate a novel regulation and role for cortactin in FVIIa/TF-mediated endothelial cell migration that occurs through a PAR2 and RhoA dependent mechanism. PMID:21160057

Zhu, Tang; Mancini, Joseph A; Sapieha, Przemyslaw; Yang, Chun; Joyal, Jean-Sébastien; Honoré, Jean-Claude; Leduc, Martin; Zaniolo, Karine; Hardy, Pierre; Shao, Zhuo; Fan, Li; Hou, Xin; Rivard, Georges-Etienne; Chemtob, Sylvain

2011-03-01

409

Bayesian Hidden Markov Models to Identify RNA-Protein Interaction Sites in PAR-CLIP  

PubMed Central

Summary The photoactivatable ribonucleoside enhanced cross-linking immunoprecipitation (PAR-CLIP) has been increasingly used for the global mapping of RNA-protein interaction sites. There are two key features of the PAR-CLIP experiments: The sequence read tags are likely to form an enriched peak around each RNA-protein interaction site; and the cross-linking procedure is likely to introduce a specific mutation in each sequence read tag at the interaction site. Several ad hoc methods have been developed to identify the RNA-protein interaction sites using either sequence read counts or mutation counts alone; however, rigorous statistical methods for analyzing PAR-CLIP are still lacking. In this study, we propose an integrative model to establish a joint distribution of observed read and mutation counts. To pinpoint the interaction sites at single base-pair resolution, we developed a novel modeling approach that adopts non-homogeneous hidden Markov models to incorporate the nucleotide sequence at each genomic location. Both simulation studies and data application showed that our method outperforms the ad hoc methods, and provides reliable inferences for the RNA-protein binding sites from PAR-CLIP data. PMID:24571656

Yun, Jonghyun; Wang, Tao; Xiao, Guanghua

2014-01-01

410

Protease Activated Receptor-1 (PAR-1) Mediated Platelet Aggregation is Dependant on Clopidogrel Response  

PubMed Central

Introduction Clopidogrel inhibits ADP mediated platelet aggregation through inhibition of the P2Y12 receptor by its active metabolite. Thrombin induces platelet aggregation by binding to protease activated receptor-1 (PAR-1), and inhibition of PAR-1 has been evaluated in patients treated with clopidogrel to reduce ischemic events after acute coronary syndromes. Residual PAR-1 mediated platelet aggregation may be dependent on extent of clopidogrel response. Material and Methods Platelet aggregation was measured in 55 patients undergoing elective PCI at 16-24 hours after 600mg clopidogrel loading dose by light transmittance aggregometry using ADP 20?M and thrombin receptor agonist peptide (TRAP) at 15 ?M and 25 ?M as agonists. Genomic DNA was genotyped for common CYP2C19 variants. Results Increasing quartiles of 20 ?M ADP induced platelet aggregation after clopidogrel loading were associated with increasing levels of TRAP mediated platelet aggregation. Patients in the highest quartile (clopidogrel non-responders) of post treatment ADP aggregation had significantly higher TRAP mediated aggregation than the patients in the lowest quartile (clopidogrel responders) [TRAP 15 ?M: 79.6±5% vs. 69.5±8%, p<0.001]. Conclusions Non-responders to clopidogrel show increased residual platelet aggregation induced by TRAP, whereas clopidogrel responders exhibit attenuated response to TRAP. Addition of PAR-1 antiplatelet drugs may be most effective in patients with reduced clopidogrel response and high residual TRAP mediated platelet aggregation. PMID:22459907

Kreutz, Rolf P.; Breall, Jeffrey A.; Kreutz, Yvonne; Owens, Janelle; Lu, Deshun; Bolad, Islam; von der Lohe, Elisabeth; Sinha, Anjan; Flockhart, David A.

2012-01-01

411

Substantia nigra pars reticulata neurons code initiation of a serial pattern: implications for natural action sequences  

E-print Network

activity, obsessive±compulsive disorder, Parkinson's disease, rat, serial order, syntax, Tourette ganglia dysfunction, such as Parkinson's disease or Tourette's syndrome. The substantia nigra pars and Tourette's syndrome (Rapoport & Wise, 1988; Toates, 1990), which can sometimes involve speech sequences too

Berridge, Kent

412

Décomposition de Helmholtz par ondelettes : convergence d'un algorithme itératif  

Microsoft Academic Search

R esum e. Dans ce qui suit, on pr esente des ondelettes a divergence nulle et des ondelettes a rotationnel nul, et on d enit des projecteurs associ es : ces projecteurs permettent de construire un algorithme it eratif de d ecomposition de Helmholtz par ondelettes. Cette d ecomposition de Helmholtz est localis ee en espace, contrairement a une d

Erwan Deriaz; Kai Bittner; Valérie Perrier

2007-01-01

413

Mthode d'analyse du mouvement de l'paule par utilisation de nappes de marqueurs  

E-print Network

'un système de caméras VICON. Le suivi du mouvement des nappes par un algorithme de recalage robuste doit, Epaule, Marqueurs, Nappe, Système VICON, signal. 1 Introduction Le membre supérieur humain a été moins

Paris-Sud XI, Université de

414

Introduction Design of Kicker/Bumper Magnet and PFN for PAR  

E-print Network

Introduction LS-156 10/15/90 Design of Kicker/Bumper Magnet and PFN for PAR By JU \\VANG Al. S. Government purposes. Three fast pulsed kicker!bumper magnets are required in the positron identical magnetic fields. Therefore, they will have the same design. Each kicker!bumper magnet is required

Kemner, Ken

415

Essai d'amlioration de la rsistance la scheresse du tournesol (Helianthus annuus) par croisement interspci-  

E-print Network

Essai d'amélioration de la résistance à la sécheresse du tournesol (Helianthus annuus) par Helianthus annuus x H. argophyllus a été effectué en 1977 dans le but d'obtenir de nouveaux cultivars de argophyllus. Methodology and first results. An interspecific cross between Helianthus annuus and Helianthus

Paris-Sud XI, Université de

416

PRODUCTION DE LA PATULINE EN MILIEU LIQUIDE PAR DES MOISISSURES APPARTENANT AUX GENRES  

E-print Network

. expansum, 1 of P. claviforme and P. thomii produced patulin after 9 days of culture. Mycotoxin mycotoxine a été trouvée dans des pommes (Harwig et al., 1973), du cidre doux (Scott et al., 1972 ; Wilson et'analyse qualitative et quantitative de la mycotoxine est également effectuée par chromatographie sur couche mince

Paris-Sud XI, Université de

417

A comparative ultrastructural study of the pars tuberalis of various mammals, the chicken and the newt  

Microsoft Academic Search

The pars tuberalis of the rat, mouse, garden door mouse, European hamster, cat, cattle, chicken and newt is composed of two main cell types: specific secretory cells and follicular cells. The specific cells are characterized by comparable morphologic features in the investigated species, despite differences in the diameter of the secretory granulated vesicles; the ultrastructural morphology of these cells is

Horst-Dieter Dellmann; Marie Elisabeth Stoeckel; Colette Hindelang-Gertner; Aimé Porte; Fred Stutinsky

1974-01-01

418

Prvention de la transmission du VIH par l'allaitement maternel Rsultats 4. RESULTATS  

E-print Network

breastfeeding to reduce HIV transmission through breastmilk in Abidjan, Cote d'Ivoire" J Trop Pediatr 2005 status in Abidjan, Cote d'Ivoire, before the implementation of infant feeding interventions aimed Statistique (Côte d'Ivoire) 2001). L'essai Ditrame a également montré que 98% des femmes infectées par le VIH

Paris-Sud XI, Université de

419

The role of uPAR signaling in lung cancer Background and significance  

E-print Network

The role of uPAR signaling in lung cancer Background and significance Lung cancer is the leading of lung cancer ­ non-small-cell-lung cancer (about 85% of all lung cancer cases) and small- cell-lung cancer (about 15%) (Herbst et al., 2008). Small cell lung carcinoma (SCLC) is rapidly growing and often

Gleeson, Joseph G.

420

Digestion des glucides de la levure d'alcanes par le veau prruminant  

E-print Network

Digestion des glucides de la levure d'alcanes par le veau préruminant J. M. BESLE, Bernadette LASSALAS, P. THIVEND Laboratoire de la Digestion des Ruminanfs, 1.N.R.A., Theix, 63110 Beaumont France. Summary. Digestion of alkane yeast carbohydrates by the preruminant calf. Four 15-day old preruminant

Paris-Sud XI, Université de

421

ED n364 : Sciences Fondamentales et Appliques Nattribu par la bibliothque  

E-print Network

NUMERIQUE DU SOUDAGE PAR FROTTEMENT-MALAXAGE NUMERICAL SIMULATION OF THE FRICTION STIR WELDING PROCESS,version1-8Apr2008 #12;- 4 - ABSTRACT Despite considerable interests in the Friction Stir Welding (FSW the different stages of the Friction Stir Welding (FSW) process. A splitting method is utilized: a) the material

Paris-Sud XI, Université de

422

LUMINESCENCES PROPRES ET PARASITES DU DURNE Par Y. MEYER et R. ASTIER,  

E-print Network

1089. LUMINESCENCES PROPRES ET PARASITES DU DUR�NE Par Y. MEYER et R. ASTIER, Laboratoire de Physique de l'�cole Polytechnique. Résumé. 2014 On a étudié les luminescences propres et parasites du- nescences parasites et on discute les mécanismes correspondants. Abstract. 2014 We have studied the true

Paris-Sud XI, Université de

423

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...

424

Dtection prcoce de maladies sur feuilles par traitement d'images S.Han* F. Cointault*  

E-print Network

imaging techniques: acquisition and image processing. Keywords Early detection, color space, hybride1 Détection précoce de maladies sur feuilles par traitement d'images S.Han* F. Cointault* * Agro agriculture et viticulture, la solution actuelle nécessite l'emploi massif de produits phytosanitaires

Paris-Sud XI, Université de

425

La fondation Rockefeller et la naissance de l'universalisme philanthropique amricain par Ludovic Tourns  

E-print Network

of Philanthropic Foundations in the Reproduction and Production of Hegemony: The Rockefeller Foundation, Inderjeet Parmar, « To Relate Knowledge and Action: The Impact of the Rockefeller Foundation on Foreign1 La fondation Rockefeller et la naissance de l'universalisme philanthropique américain par Ludovic

Boyer, Edmond

426

Par6 is phosphorylated by aPKC to facilitate EMT  

PubMed Central

The conserved polarity proteins Par6 and aPKC regulate cell polarization processes. However, increasing evidence also suggests that they play a role in oncogenic progression. During tumor progression, epithelial to mesenchymal transition (EMT) delineates an evolutionary conserved process that converts stationary epithelial cells into mesenchymal cells, which have an acquired ability for independent migration and invasion. In addition to signaling pathways that alter genetic programes that trigger the loss of cell-cell adhesion, alternative pathways can alter cell plasticity to regulate cell-cell cohesion and increase invasive potential. One such pathway involves TGF?-induced phosphorylation of Par6. In epithelial cells, Par6 phosphorylation results in the dissolution of junctional complexes, cytoskeletal remodelling, and increased metastatic potential. Recently, we found that aPKC can also phosphorylate Par6 to drive EMT and increase the migratory potential of non-small cell lung cancer cells. This result has implications with respect to homeostatic and developmental processes involving polarization, and also with respect to cancer progression—particularly since aPKC has been reported to be an oncogenic regulator in various tumor cells. PMID:23880940

Gunaratne, Adrian; Di Guglielmo, Gianni M.

2013-01-01

427

LARGISSEMENT DES RAIES DE L'ARGON PAR LES ATOMES NEUTRES ET APPLICATION A LA MESURE  

E-print Network

par effet Van der Waals, on obtient un accord satisfaisant entre l'expérience et la théorie en'excellentes conditions (raies intenses, 61argissement Stark n6gligeable), Felar- gissement et le deplacement r6sonnant et

Boyer, Edmond

428

SUR LES TRANSFORMATIONS DE L'ALLIAGE MnSnCu2 Par P. TAGLANG,  

E-print Network

. FIG. 1. - �tude paramagnétique. Take [2], Stark et Haupt [3], Ashworth [4], Ross et Gray [5 seconde 'transformation se produit. En effet la courbe de dilatation se terminé par une parallèle à la

Boyer, Edmond

429

The Utility of Clinicians Ratings of Anxiety Using the Pediatric Anxiety Rating Scale (PARS)  

ERIC Educational Resources Information Center

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…

Ginsburg, Golda S.; Keeton, Courtney P.; Drazdowski, Tess K.; Riddle, Mark A.

2011-01-01

430

Participation and Participatory Action Research (PAR) in Environmental Education Processes: For What Are People Empowered?  

ERIC Educational Resources Information Center

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…

Le Grange, Lesley

2009-01-01

431

NUCLATION PAR LE BORAX DU SULFATE DE SODIUM DISPERS. APPLICATION POSSIBLE AU STOCKAGE THERMIQUE  

E-print Network

L-359 NUCL�ATION PAR LE BORAX DU SULFATE DE SODIUM DISPERS�. APPLICATION POSSIBLE AU STOCKAGE un intérêt pour la réalisation de stockage thermique. Abstract. 2014 The crystallization of droplets stockage thermique. Mais sous forme macroscopique le rendement du stockage baisse a chaque cycle du fait de

Boyer, Edmond

432

Dimensionnement et gestion d'un systme de stockage thermique par hydro-accumulation : application la  

E-print Network

Dimensionnement et gestion d'un système de stockage thermique par hydro-accumulation : application de stockage thermique de type hydro-accumulation destiné à une chaufferie collective multi permettant d'optimiser le dimensionnement de ce système de stockage. L'approche développée est testée sur une

Paris-Sud XI, Université de

433

INHIBITION OF PS II PHOTOCHEMISTRY BY PAR AND UV RADIATION IN NATURAL PHYTOPLANKTON COMMUNITIES  

EPA Science Inventory

The effects of PAR and UV radiation on PS II photochemistry were examined in natural phytoplankton communities from coastal waters off Rhode Island (USA) and the subtropical Pacific. he photochemical energy conversion efficiency, the functional absorption cross section and the ki...

434

Projet SIGFRIED 1 : SIG Facteurs de RIsques Environnementaux et Dcs par cancer. Intgration de bases  

E-print Network

physique, nutrition...). Mais les cancers progressant le plus (cancer du sein, cancer de la prostate) sont1 Projet SIGFRIED 1 : SIG Facteurs de RIsques Environnementaux et Décès par cancer. Intégration de cancer. J. Caudeville, JB. Masson INERIS : Institut National de l'Environnement industriel et des RISques

Paris-Sud XI, Université de

435

les rsultats sont une confirmation de la relation donne par PROCEEDINGS OF THE ROYAL SOCIETY;  

E-print Network

modification de la bande citron. Ce fait avait été signalé pour la première fois par M. Fovvler en 1888 et la bande citron. Le spectre continu s'étend de D à un peu au- dessous de J.~; ~ . Les parties les

Boyer, Edmond

436

Contr^ole par laser de la dynamique de syst`emes quantiques  

E-print Network

Contr^ole par laser de la dynamique de syst`emes quantiques Mamadou NDONG Universit´e Paris Sud XI . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 2 Contr^ole de syst`emes quantiques 28 2.1 Pr´esentation du probl`eme . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 2.2 Formulation math´ematique . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 2.2.1 Contr^ole

Boyer, Edmond

437

DIFFERENT TYPES OF SMECTIC H PHASES by A. DE VRIES Remplacer reference [1] par  

E-print Network

ERRATA « DIFFERENT TYPES OF SMECTIC H PHASES » by A. DE VRIES Remplacer reference [1] par : [1] DE VRIES, A., J. Chem. Phys. 61 (1974) 2367. ERRATA EFFET D'UN CHAMP �LECTRIQUE DANS L'H�LIUM 3 SUPERFLUIDE J. M. DELRIEU Une erreur de signe dans la transformee de Fourier de WD entraine qu'a partir de la

Boyer, Edmond

438

OBTENTION D'IMPULSIONS EN LIMITE DE FOURIER PAR COMPRESSION SPECTRALE REALISEE DANS UNE FIBRE OPTIQUE  

E-print Network

OBTENTION D'IMPULSIONS EN LIMITE DE FOURIER PAR COMPRESSION SPECTRALE REALISEE DANS UNE FIBRE compression spectrale d'impulsions picosecondes dans un montage totalement fibré aux longueurs d'onde des impulsion de forme sécante hyperbolique. MOTS-CLEFS : compression spectrale ; impulsions paraboliques

Paris-Sud XI, Université de

439

Comptes Rendus des JNC 16 Toulouse 2009 Comportement de poutres renforces par composites matrice  

E-print Network

Comptes Rendus des JNC 16 Toulouse 2009 Comportement de poutres renforcées par composites à matrice minérale Behavior of beams made in textile reinforced mineral matrix composites G. Promis 1 , A.gabor@univ-lyon1.fr Résumé Dans cet article, Le comportement en flexion de poutres en composite à matrice minérale

Paris-Sud XI, Université de

440

Protolyse in vitro de casine et de gluten par les enzymes pancratiques  

E-print Network

Protéolyse in vitro de caséine et de gluten par les enzymes pancréatiques Marie-Claire CAMUS, J. C by pancreatic enzymes. The time-course of proteolysis of casein and gluten by pancreatic enzymes (trypsin, chymotrypsin, pancreatic juice) was studied in vitro with various concentrations of enzyme or substrate

Paris-Sud XI, Université de

441

The loss of circadian PAR bZip transcription factors results in epilepsy  

PubMed Central

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

Gachon, Frédéric; Fonjallaz, Philippe; Damiola, Francesca; Gos, Pascal; Kodama, Tohru; Zakany, Jozsef; Duboule, Denis; Petit, Brice; Tafti, Mehdi; Schibler, Ueli

2004-01-01

442

Project Plan 7930 Cell G PaR Remote Handling System Replacement  

SciTech Connect

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 functioning and reliable Par manipulator arm is necessary for uninterrupted {sup 252}Cf operations; a fully-functioning bridge is needed for the system to function as intended.

Kinney, Kathryn A [ORNL

2009-10-01

443

La structure de l'eau liquide: Une etude thermique par spectroscopie infrarouge  

NASA Astrophysics Data System (ADS)

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 mesures de diffraction des rayons X ont aussi ete analysees. Les abondances tirees de l'analyse par facteurs des spectres infrarouges permettent de calculer les fonctions de distributions radiales des deux especes. Ces fonctions offrent la possibilite de connaitre les distances relatives entre les atomes. Avec ces distances en main, l'architecture des deux especes peut etre schematisee. Ces resultats originaux, combines a ceux issus de la spectroscopie infrarouge, permettent de montrer que la premiere espece est bien organisee, c'est-a-dire que le cube defini par un atome d'oxygene et les quatre autres atomes d'oxygene avec lesquels il est en liens-H est regulier, alors que pour l'espece chaude, les dimensions du cubes sont irregulieres. La comparaison entre les deux especes montre qu'elles etablissent toujours quatre liens-H et que leurs differences resident uniquement dans la geometrie des cubes. Finalement, deux hypotheses sont formulees comme fondement d'un modele de la structure de l'eau liquide. Premierement, l'empilement des cubes des deux especes permet de representer l'eau a toutes les temperatures, l'espece froide etant garante de la stabilite du liquide, alors que l'espece chaude a un effet destabilisant; et deuxiemement, le saut du proton stabilise les liens-H, de telle sorte que lorsque l'espece chaude devient trop abondante, ces defauts provoquent un arret des sauts de protons et les liens-H ainsi affaiblis se brisent et le liquide s'evapore.

Larouche, Pascal

444

uPAR-targeted optical imaging contrasts as theranostic agents for tumor margin detection.  

PubMed

Complete removal of tumors by surgery is the most important prognostic factor for cancer patients with the early stage cancers. The ability to identify invasive tumor edges of the primary tumor, locally invaded small tumor lesions, and drug resistant residual tumors following neoadjuvant therapy during surgery should significantly reduce the incidence of local tumor recurrence and improve survival of cancer patients. In this study, we report that urokinase plasminogen activator (uPA) and its receptor (uPAR) are the ligand/cell surface target pair for the development of targeted optical imaging probes for enhancing imaging contrasts in the tumor border. Recombinant peptides of the amino terminal fragment (ATF) of the receptor binding domain of uPA were labeled with near infrared fluorescence (NIR) dye molecules either as peptide-imaging or peptide-conjugated nanoparticle imaging probes. Systemic delivery of the uPAR-targeted imaging probes in mice bearing orthotopic human breast or pancreatic tumor xenografts or mouse mammary tumors led to the accumulation of the probes in the tumor and stromal cells, resulting in strong signals for optical imaging of tumors and identification of tumor margins. Histological analysis showed that a high level of uPAR-targeted nanoparticles was present in the tumor edge or active tumor stroma immediately adjacent to the tumor cells. Furthermore, following targeted therapy using uPAR-targeted theranostic nanoparticles, residual tumors were detectable by optical imaging through the imaging contrasts produced by NIR-dye-labeled theranostic nanoparticles in drug resistant tumor cells. Therefore, results of our study support the potential of the development of uPAR-targeted imaging and theranostic agents for image-guided surgery. PMID:24396518

Yang, Lily; Sajja, Hari Krishna; Cao, Zehong; Qian, Weiping; Bender, Laura; Marcus, Adam I; Lipowska, Malgorzata; Wood, William C; Wang, Y Andrew

2013-01-01

445

Capteur de CO{2} à fibres optiques par absorption moléculaire à 4,3 ?m  

NASA Astrophysics Data System (ADS)

This paper describes a remote optical fibre sensor for the carbon dioxide detection by molecular absorption in the near infrared (4.3 ?m) corresponding to fundamental mode ?3. To overcome the problem of the strong attenuation signal of optical fibre in the near infrared, we have used the opto-suppling technique which changes the working wavelength from 4.3 ?m to 860 nm and permits the use of standard optical fibre 50/125. The simulation of absorption has been obtained by original modelisation of the absorption spectrum and the establishment of the calibration curves takes to the sensor to detect a partial pressures greater than 100 ?bar with a minimal error margin of 100 ?bar, which is acceptable considering the future use of the device. The sensor has been designed to monitor the CO{2} rate in enriched greenhouses. Cet article décrit un capteur à fibres optiques de gaz carbonique par absorption moléculaire dans l'infrarouge moyen (4,3 ?m) correspondant au mode fondamental ?3. La liaison entre le site de mesure et le site de contrôle est assurée par un fibre optique standard 50/125 après une transposition de longueur d'onde de 4,3 ?m à 860 nm par opto-alimentation. La simulation de l'absorption a été obtenue par modélisation originale du spectre d'absorption et l'établissement des courbes d'étalonnage prévoit une marge d'erreur minimale de 100 ?bar, ce qui est suffisant pour l'application du dispositif à la régulation de taux CO{2} dans les serres agricoles enrichies par de gaz.

Bendamardji, S.; Alayli, Y.; Huard, S.

1996-04-01

446

Phospho-dependent ubiquitination and degradation of PAR-1 regulates synaptic morphology and tau-mediated A? toxicity in Drosophila  

PubMed Central

The conserved kinases PAR-1/MARK are critically involved in processes such as asymmetric cell division, cell polarity and neuronal differentiation. Their deregulation has been implicated in diseases including Alzheimer’s disease and cancer. Given the importance of PAR-1/MARK in health and disease, their activities need to be tightly controlled. However, little is known about the molecular mechanisms underlying their regulation in vivo. Here we show that in Drosophila, a phosphorylation-dependent ubiquitination mechanism restrains PAR-1 activation. Active PAR-1 generated by LKB1-controlled phosphorylation is targeted for ubiquitination and degradation by SCF (Skp, Cullin, F-box containing complex) (Slimb), whose action is antagonized by the deubiquitinating enzyme fat facets. This newly identified PAR-1-modifying module critically regulates synaptic morphology and tau-mediated postsynaptic toxicity of amyloid precursor protein (APP)/A?-42, the causative agents of Alzheimer’s disease, at the Drosophila neuromuscular junction. Our results provide new insights into the regulation of PAR-1 in various physiological processes and offer new therapeutic strategies for diseases involving PAR-1/MARK deregulation. PMID:23271647

Lee, Seongsoo; Wang, Ji-Wu; Yu, Wendou; Lu, Bingwei

2015-01-01

447

RAB-5 Controls the Cortical Organization and Dynamics of PAR Proteins to Maintain C. elegans Early Embryonic Polarity  

PubMed Central

In all organisms, cell polarity is fundamental for most aspects of cell physiology. In many species and cell types, it is controlled by the evolutionarily conserved PAR-3, PAR-6 and aPKC proteins, which are asymmetrically localized at the cell cortex where they define specific domains. While PAR proteins define the antero-posterior axis of the early C. elegans embryo, the mechanism controlling their asymmetric localization is not fully understood. Here we studied the role of endocytic regulators in embryonic polarization and asymmetric division. We found that depleting the early endosome regulator RAB-5 results in polarity-related phenotypes in the early embryo. Using Total Internal Reflection Fluorescence (TIRF) microscopy, we observed that PAR-6 is localized at the cell cortex in highly dynamic puncta and depleting RAB-5 decreased PAR-6 cortical dynamics during the polarity maintenance phase. Depletion of RAB-5 also increased PAR-6 association with clathrin heavy chain (CHC-1) and this increase depended on the presence of the GTPase dynamin, an upstream regulator of endocytosis. Interestingly, further analysis indicated that loss of RAB-5 leads to a disorganization of the actin cytoskeleton and that this occurs independently of dynamin activity. Our results indicate that RAB-5 promotes C. elegans embryonic polarity in both dynamin-dependent and -independent manners, by controlling PAR-6 localization and cortical dynamics through the regulation of its association with the cell cortex and the organization of the actin cytoskeleton. PMID:22545101

Hyenne, Vincent; Tremblay-Boudreault, Thierry; Velmurugan, Ramraj; Grant, Barth D.; Loerke, Dinah; Labbé, Jean-Claude

2012-01-01

448

Neutrophil Elastase and Proteinase-3 Trigger G Protein-biased Signaling through Proteinase-activated Receptor-1 (PAR1)*  

PubMed Central

Neutrophil proteinases released at sites of inflammation can affect tissue function by either activating or disarming signal transduction mediated by proteinase-activated receptors (PARs). Because PAR1 is expressed at sites where abundant neutrophil infiltration occurs, we hypothesized that neutrophil-derived enzymes might also regulate PAR1 signaling. We report here that both neutrophil elastase and proteinase-3 cleave the human PAR1 N terminus at sites distinct from the thrombin cleavage site. This cleavage results in a disarming of thrombin-activated calcium signaling through PAR1. However, the distinct non-canonical tethered ligands unmasked by neutrophil elastase and proteinase-3, as well as synthetic peptides with sequences derived from these novel exposed tethered ligands, selectively stimulated PAR1-mediated mitogen-activated protein kinase activation. This signaling was blocked by pertussis toxin, implicating a G?i-triggered signal pathway. We conclude that neutrophil proteinases trigger biased PAR1 signaling and we describe a novel set of tethered ligands that are distinct from the classical tethered ligand revealed by thrombin. We further demonstrate the function of this biased signaling in regulating endothelial cell barrier integrity. PMID:24052258

Mihara, Koichiro; Ramachandran, Rithwik; Renaux, Bernard; Saifeddine, Mahmoud; Hollenberg, Morley D.

2013-01-01

449

Structure and putative signaling mechanism of Protease activated receptor 2 (PAR2) - a promising target for breast cancer.  

PubMed

Experimental evidences have observed enhanced expression of protease activated receptor 2 (PAR2) in breast cancer consistently. However, it is not yet recognized as an important therapeutic target for breast cancer as the primary molecular mechanisms of its activation are not yet well-defined. Nevertheless, recent reports on the mechanism of GPCR activation and signaling have given new insights to GPCR functioning. In the light of these details, we attempted to understand PAR2 structure & function using molecular modeling techniques. In this work, we generated averaged representative stable models of PAR2, using protease activated receptor 1 (PAR1) as a template and selected conformation based on their binding affinity with PAR2 specific agonist, GB110. Further, the selected model was used for studying the binding affinity of putative ligands. The selected ligands were based on a recent publication on phylogenetic analysis of Class A rhodopsin family of GPCRs. This study reports putative ligands, their interacting residues, binding affinity and molecular dynamics simulation studies on PAR2-ligand complexes. The results reported from this study would be useful for researchers and academicians to investigate PAR2 function as its physiological role is still hypothetical. Further, this information may provide a novel therapeutic scheme to manage breast cancer. PMID:25173751

Kakarala, Kavita Kumari; Jamil, Kaiser; Devaraji, Vinod

2014-09-01

450

uPAR and cathepsin B downregulation induces apoptosis by targeting calcineurin A to BAD via Bcl-2 in glioma.  

PubMed

Cathepsin B and urokinase plasminogen activator receptor (uPAR) are postulated to play key roles in glioma invasion. Calcineurin is one of the key regulators of mitochondrial-dependent apoptosis, but its mechanism is poorly understood. Hence, we studied subcellular localization of calcineurin after transcriptional downregulation of uPAR and cathepsin B in glioma. In the present study, efficient downregulation of uPAR and cathepsin B increased the translocation of calcineurin A from the mitochondria to the cytosol, decreased pBAD (S136) expression and its interaction with 14-3-3? and increased the interaction of BAD with Bcl-xl. Co-depletion of uPAR and cathepsin B induced mitochondrial translocation of BAD, activation of caspase 3 as well as PARP and cytochrome c and SMAC release. These effects were inhibited by FK506 (10 ?M), a specific inhibitor of calcineurin. Calcineurin A was co-localized and also co-immunoprecipitated with Bcl-2. This interaction decreased with co-depletion of uPAR and cathepsin B and also with Bcl-2 inhibitor, HA 14-1 (20 ?g/ml). Altered localization and interaction of calcineurin A with Bcl-2 was also observed in vivo when uPAR and cathepsin B were downregulated. In conclusion, downregulation of uPAR and cathepsin B induced apoptosis by targeting calcineurin A to BAD via Bcl-2 in glioma. PMID:21964739

Malla, Rama Rao; Gopinath, Sreelatha; Gondi, Christopher S; Alapati, Kiranmai; Dinh, Dzung H; Tsung, Andrew J; Rao, Jasti S

2012-03-01

451

Monomer–dimer dynamics and distribution of GPI-anchored uPAR are determined by cell surface protein assemblies  

PubMed Central

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

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

452

Etk/Bmx Regulates Proteinase-Activated-Receptor1 (PAR1) in Breast Cancer Invasion: Signaling Partners, Hierarchy and Physiological Significance  

PubMed Central

Background While protease-activated-receptor 1 (PAR1) plays a central role in tumor progression, little is known about the cell signaling involved. Methodology/Principal Findings We show here the impact of PAR1 cellular activities using both an orthotopic mouse mammary xenograft and a colorectal-liver metastasis model in vivo, with biochemical analyses in vitro. Large and highly vascularized tumors were generated by cells over-expressing wt hPar1, Y397Z hPar1, with persistent signaling, or Y381A hPar1 mutant constructs. In contrast, cells over-expressing the truncated form of hPar1, which lacks the cytoplasmic tail, developed small or no tumors, similar to cells expressing empty vector or control untreated cells. Antibody array membranes revealed essential hPar1 partners including Etk/Bmx and Shc. PAR1 activation induces Etk/Bmx and Shc binding to the receptor C-tail to form a complex. Y/A mutations in the PAR1 C-tail did not prevent Shc-PAR1 association, but enhanced the number of liver metastases compared with the already increased metastases obtained with wt hPar1. We found that Etk/Bmx first binds via the PH domain to a region of seven residues, located between C378-S384 in PAR1 C-tail, enabling subsequent Shc association. Importantly, expression of the hPar1-7A mutant form (substituted A, residues 378-384), which is incapable of binding Etk/Bmx, resulted in inhibition of invasion through Matrigel-coated membranes. Similarly, knocking down Etk/Bmx inhibited PAR1-induced MDA-MB-435 cell migration. In addition, intact spheroid morphogenesis of MCF10A cells is markedly disrupted by the ectopic expression of wt hPar1. In contrast, the forced expression of the hPar1-7A mutant results in normal ball-shaped spheroids. Thus, by preventing binding of Etk/Bmx to PAR1 -C-tail, hPar1 oncogenic properties are abrogated. Conclusions/Significance This is the first demonstration that a cytoplasmic portion of the PAR1 C-tail functions as a scaffold site. We identify here essential signaling partners, determine the hierarchy of binding and provide a platform for therapeutic vehicles via definition of the critical PAR1-associating region in the breast cancer signaling niche. PMID:20559570

Cohen, Irit; Maoz, Myriam; Turm, Hagit; Grisaru-Granovsky, Sorina; Maly, Bella; Uziely, Beatrice; Weiss, Einat; Abramovitch, Rinat; Gross, Eithan; Barzilay, Oded; Qiu, Yun; Bar-Shavit, Rachel

2010-01-01

453

Expression of protease activated receptor-2 (PAR-2) in central airways of smokers and non-smokers  

PubMed Central

Background: Protease activated receptor-2 (PAR-2) is a transmembrane G protein coupled receptor preferentially activated by trypsin and tryptase. The protease activated receptors play an important role in most components of injury responses including cell proliferation, migration, matrix remodelling, and inflammation. Cigarette smoking causes an inflammatory process in the central airways, peripheral airways, lung parenchyma, and adventitia of pulmonary arteries. Methods: To quantify the expression of PAR-2 in the central airways of smokers and non-smokers, surgical specimens obtained from 30 subjects undergoing lung resection for localised pulmonary lesions (24 with a history of cigarette smoking and six non-smoking control subjects) were examined. Central airways were immunostained with an antiserum specific for PAR-2 and PAR-2 expression was quantified using light microscopy and image analysis. Results: PAR-2 expression was found in bronchial smooth muscle, epithelium, glands, and in the endothelium and smooth muscle of bronchial vessels. PAR-2 expression was similar in the central airways of smokers and non-smokers. When smokers were divided according to the presence of symptoms of chronic bronchitis and chronic airflow limitation, PAR-2 expression was increased in smooth muscle (median 3.8 (interquartile range 2.9–5.8) and 1.4 (1.07–3.4) respectively); glands (33.3 (18.2–43.8) and 16.2 (11.5–22.2), respectively); and bronchial vessels (54.2 (48.7–56.8) and 40.0 (36–40.4), respectively) of smokers with symptoms of chronic bronchitis with normal lung function compared with smokers with chronic airflow limitation (COPD), but the increase was statistically significant (p<0.005) only for bronchial vessels. Conclusions: PAR-2 is present in bronchial smooth muscle, glands, and bronchial vessels of both smokers and non-smokers. An increased expression of PAR-2 was found in bronchial vessels of patients with bronchitis compared with those with COPD. PMID:11828045

Miotto, D; Hollenberg, M; Bunnett, N; Papi, A; Braccioni, F; Boschetto, P; Rea, F; Zuin, A; Geppetti, P; Saetta, M; Maestrelli, P; Fabbri, L; Mapp, C

2002-01-01

454

Comparative analysis of a plant pseudoautosomal region (PAR) in Silene latifolia with the corresponding S. vulgaris autosome  

PubMed Central

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

2012-01-01

455

Secretory prostate apoptosis response (Par)-4 sensitizes multicellular spheroids (MCS) of glioblastoma multiforme cells to tamoxifen-induced cell death  

PubMed Central

Glioblastoma multiforme (GBM) is the most malignant form of brain tumor and is associated with resistance to conventional therapy and poor patient survival. Prostate apoptosis response (Par)-4, a tumor suppressor, is expressed as both an intracellular and secretory/extracellular protein. Though secretory Par-4 induces apoptosis in cancer cells, its potential in drug-resistant tumors remains to be fully explored. Multicellular spheroids (MCS) of cancer cells often acquire multi-drug resistance and serve as ideal experimental models. We investigated the role of Par-4 in Tamoxifen (TAM)-induced cell death in MCS of human cell lines and primary cultures of GBM tumors. TCGA and REMBRANT data analysis revealed that low levels of Par-4 correlated with low survival period (21.85 ± 19.30 days) in GBM but not in astrocytomas (59.13 ± 47.26 days) and oligodendrogliomas (58.04 ± 59.80 days) suggesting low PAWR expression as a predictive risk factor in GBM. Consistently, MCS of human cell lines and primary cultures displayed low Par-4 expression, high level of chemo-resistance genes and were resistant to TAM-induced cytotoxicity. In monolayer cells, TAM-induced cytotoxicity was associated with enhanced expression of Par-4 and was alleviated by silencing of Par-4 using specific siRNA. TAM effectively induced secretory Par-4 in conditioned medium (CM) of cells cultured as monolayer but not in MCS. Moreover, MCS were rendered sensitive to TAM-induced cell death by exposure to conditioned medium (CM)-containing Par-4 (derived from TAM-treated monolayer cells). Also TAM reduced the expression of Akt and PKC? in GBM cells cultured as monolayer but not in MCS. Importantly, combination of TAM with inhibitors to PI3K inhibitor (LY294002) or PKC? resulted in secretion of Par-4 and cell death in MCS. Since membrane GRP78 is overexpressed in most cancer cells but not normal cells, and secretory Par-4 induces apoptosis by binding to membrane GRP78, secretory Par-4 is an attractive candidate for potentially overcoming therapy-resistance not only in malignant glioma but in broad spectrum of cancers.

Jagtap, Jayashree C.; Parveen, D.; Shah, Reecha D.; Desai, Aarti; Bhosale, Dipali; Chugh, Ashish; Ranade, Deepak; Karnik, Swapnil; Khedkar, Bhushan; Mathur, Aaishwarya; Natesh, Kumar; Chandrika, Goparaju; Shastry, Padma

2014-01-01

456

Inferring total canopy APAR from PAR bidirectional reflectances and vegetation indices in tallgrass prairie. [Absorbed Photosynthetically Active Radiation  

NASA Technical Reports Server (NTRS)

The fraction of photosynthetically active radiation (PAR) absorbed by a vegetated canopy (APARc) or landscape (APARs) is a critical parameter in climate processes. A grassland study examined: 1) whether APARs can be estimated from PAR bidirectional exitance fractions; and 2) whether APARs is correlated with spectral vegetation indices (SVIs). Data were acquired with a high resolution continuous spectroradiometer at 4 sun angles on grassland sites. APARs was computed from the scattered surface PAR exitance fractions. The nadir APARs value was the most variable diurnally; it provided a good estimate of the average surface APARs at 95 percent. APARc was best represented by exitance factors between 30-60* forward.

Middleton, Elizabeth M.

1992-01-01

457

Increased soluble urokinase plasminogen activator receptor (suPAR) is associated with thrombosis and inhibition of plasmin generation in paroxysmal nocturnal hemoglobinuria (PNH) patients.  

PubMed

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired genetic disorder of the bone marrow that produces intravascular hemolysis, proclivity to venous thrombosis, and hematopoietic failure. Mutation in the PIG-A gene of a hematopoietic stem cell abrogates synthesis of glycosylphosphoinositol (GPI) anchors and expression of all GPI-anchored proteins on the surface of progeny erythrocytes, leukocytes, and platelets. Urokinase plasminogen activator receptor (uPAR), a GPI-linked protein expressed on neutrophils, mediates endogenous thrombolysis through a urokinase-dependent mechanism. Here we show that membrane GPI-anchored uPAR is decreased or absent on granulocytes and platelets of patients with PNH, while soluble uPAR (suPAR) levels are increased in patients' plasma. Serum suPAR concentrations correlated with the number of GPI-negative neutrophils and were highest in patients who later develop thrombosis. In vitro, suPAR is released from PNH hematopoietic cells and from platelets upon activation, suggesting that these cells are the probable source of plasma suPAR in the absence of GPI anchor synthesis and trafficking of uPAR to the cell membrane. In vitro, the addition of recombinant suPAR results in a dose-dependent decrease in the activity of single-chain urokinase. We hypothesized that suPAR, prevents the interaction of urokinase with membrane-anchored uPAR on residual normal cells. PMID:18954937

Sloand, Elaine M; Pfannes, Loretta; Scheinberg, Phillip; More, Kenneth; Wu, Colin O; Horne, McDonald; Young, Neal S

2008-12-01

458

Protease-Activated Receptor 2 (PAR2) Is Upregulated by Acanthamoeba Plasminogen Activator (aPA) and Induces Proinflammatory Cytokine in Human Corneal Epithelial Cells  

PubMed Central

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 supe