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Long-acting-FSH (FSH-CTP) in der Reproduktionsmedizin  

Microsoft Academic Search

Zusammenfassung  Die ovarielle Stimulation ist integraler Bestandteil der In-vitro-Fertilisation- (IVF-)Behandlung und trägt wesentlich zur\\u000a Effizienz des Verfahrens bei. Sie ist eine komplexe und häufig für die Patientin als Belastung empfundene Modalität der IVF-Behandlung,\\u000a da sie gewöhnlich die tägliche Selbstinjektion von follikelstimulierendem Hormon (FSH) beinhaltet. Das jüngst entwickelte\\u000a FSH-Präparat, FSH-CTP (Corifollitropin alfa), ist ein rekombinantes, lang wirksames Derivat des FSH-Moleküls. Es besteht

A. Schultze-Mosgau; K. Diedrich; G. Griesinger



Both recombinant African catfish LH and FSH are able to activate the African catfish FSH receptor  

Microsoft Academic Search

LH and FSH are heterodimeric glycoprotein hormones, composed of a common ?-subunit non-covalently associated with a hormone-specific ?-subunit. Repeated efforts to isolate catfish FSH (cfFSH) have not been successful and only catfish LH (cfLH) has been purified from catfish pituitaries. Recently, however, we succeeded in cloning the cDNA encoding the putative cfFSH?; the cDNAs for the ?- and ?-subunit of

H. F. Vischer; J. C. M. Granneman; M. H. K. Linskens; R. W. Schulz; J. Bogerd



Sequential (hFSH + recFSH) vs homogenous (hFSH or recFSH alone) stimulation: clinical and biochemical (cumulus cell gene expression) aspects.  


FSH is a key hormone in the regulation of follicular development. Together with the EGF network, these molecules mediate oocyte maturation and competence in preparation for the action of LH. FSH isoforms regulate distinct biological pathways and have specific effects on granulosa cell function and maturation of the ovarian follicle. Their dynamic interactions occur during the follicular cycle; short-living forms are predominant in the pre-ovulatory phase, whereas long-acting molecules characterize the luteal-follicular transition. Recombinant FSH (rFSH) molecules have a reduced number of isoforms and are less acidic, with a shorter half-life. We have investigated sequential stimulation, comparing hFSH + rFSH, vs. rFSH alone and hFSH alone for the entire stimulation phase. Sequential stimulation leads to an E2 per MII oocyte ratio that is much lower than is seen during treatment with the two drugs individually. Although there is a positive tendency in favor of the sequential treatment, there was no significant difference in pregnancy rates, even taking frozen embryos into consideration. The cumulus cell transcriptome varies considerably between the treatments, although with no clear significance. When comparing pregnant vs. non-pregnant patients, in general a decrease in mRNA expression can be observed in the pregnant patients, especially in expression of folic acid receptor 1 and ovostatin 2. This indicates that material has been transferred from CC to the oocyte. However, a common observation in the literature is that variations in the transcriptome of the cumulus cells are highly dependent upon the patient genotype; the potential for applying this strategy as a basis for selecting embryos is, at the very least, questionable. PMID:24639041

Gurgan, Timur; Montjean, Debbie; Demirol, Aygul; Menezo, Yves J R



Hypo-glycosylated human follicle-stimulating hormone (hFSH(21/18)) is much more active in vitro than fully-glycosylated hFSH (hFSH(24)).  


Hypo-glycosylated hFSH(21/18) (possesses FSH?(21) and FSH?(18)bands) was isolated from hLH preparations by immunoaffinity chromatography followed by gel filtration. Fully-glycosylated hFSH(24) was prepared by combining the fully-glycosylated FSH?(24) variant with hCG? and isolating the heterodimer. The hFSH(21/18) glycoform preparation was significantly smaller than the hFSH(24) preparation and possessed 60% oligomannose glycans, which is unusual for hFSH. Hypo-glycosylated hFSH(21/18) was 9- to 26-fold more active than fully-glycosylated hFSH(24) in FSH radioligand assays. Significantly greater binding of (125)I-hFSH(21/18) tracer than hFSH(24) tracer was observed in all competitive binding assays. In addition, higher binding of hFSH(21/18) was noted in association and saturation binding assays, in which twice as much hFSH(21/18) was bound as hFSH(24). This suggests that more ligand binding sites are available to hFSH(21/18) in FSHR than to hFSH(24). Hypo-glycosylated hFSH(21/18) also bound rat FSHRs more rapidly, exhibiting almost no lag in binding, whereas hFSH(24) specific binding proceeded very slowly for almost the first hour of incubation. PMID:24291635

Bousfield, George R; Butnev, Vladimir Y; Butnev, Viktor Y; Hiromasa, Yasuaki; Harvey, David J; May, Jeffrey V



Further evidence for direct pro-resorptive actions of FSH.  


We confirm that FSH stimulates osteoclast formation, function and survival to enhance bone resorption. It does so via the activation of a pertussis toxin-sensitive G(i)-coupled FSH receptor that we and others have identified on murine and human osteoclast precursors and mature osteoclasts. FSH additionally enhances the production of several osteoclastogenic cytokines, importantly TNFalpha, likely within the bone marrow microenvironment, to augment its pro-resorptive action. FSH levels in humans rise before estrogen falls, and this hormonal change coincides with the most rapid rates of bone loss. On the basis of accumulating evidence, we reaffirm that FSH contributes to the rapid peri-menopausal and early post-menopausal bone loss, which might thus be amenable to FSH blockade. PMID:20171951

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



Purification of a bioactive FSH-releasing factor (FSHRF).  


Before the advent of radioimmunoassay (RIA), FSH-releasing factor (FSHRF) appeared to be separable from LH-releasing hormone (LHRH) by chromatography followed by bioassay for FSH. In this study, we re-examined hypothalamic extracts for the existence of an FSHRF distinct from LHRH, utilizing the Steelman-Pohley bioassay as well as RIA for identification of FSH. Acid extracts of rat hypothalamic fragments were chromatographed on Sephadex G-25. LH- and FSH-releasing activities of each fraction were assessed by bio- and immunoassay of FSH and immunoassay of LH released after incubation with hemipituitaries from adult male rats. The immunoreactive LHRH(IR-LHRH) concentration of each fraction was also measured by RIA. In order to evaluate the FSH-releasing activity of LHRH, three doses of synthetic LHRH were tested and FSH-releasing activity determined by bio- and immunoassay. By RIA, the FSH-releasing activity of each column fraction could be accounted for by IR-LHRH contamination. However, greater FSH-releasing activity than could be predicted by IR-LRH contamination was detected by Steelman-Pohley assay in fractions eluted prior to the LHRH peak in 2 separate fractionations. These fractions from the second fractionation were pooled and eluted from a CMC column with ammonium acetate buffers. Again greater FSH-releasing activity than could be accounted for by IR-LHRH was detected prior to the IR-LHRH peak by Steelman-Pohley assay. These results agree with early work from our laboratory and suggest the presence of a bioactive FSHRF in hypothalamic extracts. PMID:6347345

Mizunuma, H; Samson, W K; Lumpkin, M D; Moltz, H J; Fawcett, C P; McCann, S M



Neuroendocrine Control of FSH Secretion: IV. Hypothalamic Control of Pituitary FSH-Regulatory Proteins and Their Relationship to Changes in FSH Synthesis and Secretion1  

PubMed Central

ABSTRACT The current dogma is that the differential regulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) synthesis and secretion is modulated by gonadotropin-releasing hormone (GnRH) pulse frequency and by changes in inhibins, activins, and follistatins both at the pituitary and at the peripheral level. To date no studies have looked at the overlapping function of these regulators in a combined setting. We tested the hypothesis that changes in GnRH pulse frequency alter the relative abundance of these regulators at the pituitary and peripheral levels in a manner consistent with changes in pituitary and circulating concentrations of FSH; that is, an increase in FSH will be accompanied by increased stimulatory input (activin) and/or reduced follistatin and inhibin. Ovariectomized ewes were subjected to a combination hypothalamic pituitary disconnection (HPD)-hypophyseal portal blood collection procedure. Hypophyseal portal and jugular blood samples were collected for a 6-h period from non-HPD ewes, HPD ewes, or HPD ewes administered GnRH hourly or every 3 h for 4 days. In the absence of endogenous hypothalamic and ovarian hormones that regulate gonadotropin secretion, 3-hourly pulses of GnRH increased pituitary content of FSH more than hourly GnRH, although these differences were not evident in the peripheral circulation. The results failed to support the hypothesis in that the preferential increase of pituitary content of FSH by the lower GnRH pulse frequency could be explained by changes in the pituitary content of inhibin A, follistatin, or activin B. Perhaps the effects of GnRH pulse frequency on FSH is due to changes in the balance of free versus bound amounts of these FSH regulatory proteins or to the involvement of other regulators not monitored in this study.

Sharma, Tejinder P.; Nett, Terry M.; Karsch, Fred J.; Phillips, David J.; Lee, James S.; Herkimer, Carol; Padmanabhan, Vasantha



Spermatid count as a predictor of response to FSH therapy.  


This study evaluated the predictive power of spermatid count and cytology for assisted reproduction outcome after FSH therapy. A total of 174 men with severe oligozoospermia and normal plasma FSH concentration underwent semen analysis including spermatid count, TUNEL test, FISH analysis for sperm aneuploidies and testicular fine-needle aspiration cytology. Ninety-two men with hypospermatogenesis received FSH therapy for 3months and 82 patients with maturative disturbance or partial obstruction served as controls. Semen was analysed at baseline, after FSH therapy and after 3- and 9-month follow up, and pregnancies were recorded. Subjects not reaching pregnancy at 3-month follow up were recommended assisted reproduction treatment. Spermatid count was related to testicular cytology: spermatid concentrations <0.01, 0.01-0.3 and >0.3×10(6)/ml were predictive of partial obstruction, hypospermatogenesis and maturative disturbance. FSH therapy patients showed increases in sperm number and motility (both P<0.001), allowing some couples to undergo intrauterine insemination instead of IVF. Cumulative pregnancy rate after 12months was higher with FSH therapy (44.6%) than without (22.0%; P=0.002). FSH therapy improved pregnancy rate and sometimes allowed less invasive assisted reproduction treatment in well-selected patients. Spermatid count could represent a new parameter to predict response to FSH therapy. One-hundred seventy-four patients with severe reduction of sperm count and normal sex hormones plasma levels underwent semen analysis with spermatid count, and testicular fine needle aspiration cytologiy (FNAC). Ninety-two men infertile men with reduced sperm production (hypospermatogenesis) were treated with highly purified urofollitropin and 82 patients with sperm maturative defects or partial obstruction of the seminal tract served as controls. After treatment and after the following 3 and 9months all subjects performed a new semen analysis and pregnancies were recorded. Subjects who had not reached spontaneous pregnancy were suggested to undergo assisted reproductive techniques (ARTs). Spermatid count was strongly related to testicular cytology: spermatid concentrations were predictive of partial obstruction, hypospermatogenesis and maturative disturbance respectively. Treated patients showed significant increase in sperm number and motility allowing some couples to undergo easier and less invasive assisted reproductive techniques. The number of pregnancies was significantly higher among treated (44.6%) than untreated couples (22.0%). Our data confirmed that FSH treatment can induce a significant improvemet of pergnancy rate and sometimes allows less invasive ARTs use in well selected severe oligozoospermic patients. Moreover, we suggest that spermatid count can be useful to define tubular status and could represent a new parameter to predict response to FSH therapy. PMID:24816256

Garolla, Andrea; Selice, Riccardo; Engl, Bruno; Bertoldo, Alessandro; Menegazzo, Massimo; Finos, Livio; Lenzi, Andrea; Foresta, Carlo



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


Clinical efficacy of human-derived follicle-stimulating hormone (FSH) versus recombinant FSH (rFSH) in IVF-ICSI cycles has long been compared, but no clear evidence of the superiority of a preparation over the other has been found. Human gonadotropins have been often grouped together, but a different glycosylation may be present in each preparation, therefore influencing the specific bioactivity. To exclude confounding factors, a meta-analysis and a cost-effectiveness analysis were designed to compare effectiveness and cost-effectiveness of a specific highly purified human FSH (HP-hFSH) (Fostimon®) versus rFSH (Gonal-F®) in IVF/ICSI cycles. Research methodology filters were applied in MEDLINE, Current Contents and Web of Science from 1980 to February 2012. Eight randomized trials met selection criteria. The meta-analysis showed no significant differences between rFSH and HP-hFSH treatment in live-birth rate (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.63-1.11), clinical pregnancy rate (OR 0.85, 95% CI 0.68-1.07), number of oocytes retrieved, number of mature oocytes and days of stimulation. The cost-effectiveness ratio was € 7174 in the rFSH group and € 2056 in the HP-hFSH group. HP-hFSH is as effective as rFSH in ovarian stimulation for IVF-ICSI cycles, but the human preparation is more cost-effective. PMID:23356335

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



FSH stimulates ovarian cancer cell growth by action on growth factor variant receptor  

PubMed Central

Summary A number of FSH Receptor (FSH-R) isoforms with distinct structural motifs and signaling paradigms have been described, including a single transmembrane domain variant that functions as a growth factor type receptor (FSH-R3). This study tested the hypothesis that FSH can stimulate ovarian cancer cell proliferation by acting on FSH-R3, using the tumorigenic mouse ovarian surface epithelial cell (MOSEC) line ID8. FSH enhanced ID8 proliferation in a concentration-dependent fashion. Moreover, FSH-treatment of ID8 elicited intracellular events consistent with activation of FSH-R3 and distinct from those associated with activation of the canonical G-protein coupled FSH-R isoform (FSH-R1). Specifically, the FSH-R3 signaling pathway included cAMP-independent activation of ERK downstream of an SNX-482 sensitive component likely to be the Cav2.3 calcium channel. Northern analysis using probes specific for exons 7 and 11 of FSH-R identified consistently only one 1.9 kb transcript. Immunoblot analysis confirmed expression of FSH-R3 but not FSHR-1 in ID8. Together, these data suggest that FSH-R3 signaling promotes proliferation of ovarian cancer cells.

Li, Y; Ganta, S; Cheng, C; Craig, R; Ganta, RR; Freeman, LC



FSH immunoneutralization acutely impairs spermatogonial development in normal adult rats.  


Follicle-stimulating hormone (FSH) plays an important part in testicular development. Its role in the regulation of spermatogenesis in the adult, however, remains controversial. This study aimed to explore the role of FSH in the maintenance of adult rat spermatogenesis by using immunoneutralization to selectively withdraw FSH action for periods of up to 8.5 days and then assessing the outcome by quantification of germ cell number. Adult rats received either an ovine polyclonal rat FSH antibody (FSHAb, 2 mg/kg subcutaneous daily-a dosage known to neutralize >90% of FSH in serum) for 2, 4, 7, or 8.5 days or a control sheep immunoglobulin (ConAb, 2 mg/kg) for 8.5 days. Testes were perfusion fixed, and germ cell numbers per testis were quantified using the optical disector (sic) stereological method. The percentage of seminiferous tubules displaying apoptotic cells was determined by the in situ end labeling method (TUNEL). FSHAb treatment for 4, 7, or 8.5 days significantly reduced the number of type A/intermediate spermatogonia (approximately 74% of control values) associated with stages I-IV. Similar reductions were seen in type B spermatogonial and preleptotene spermatocyte numbers after 8.5 days of FSHAb treatment (approximately 69% of control values; P < 0.05). Decreases (P < 0.05) in the numbers of pachytene spermatocytes in stages I-III and VIII, round spermatids in stages I-III, VII, and VIII (approximately 70% of control values), and step 19 elongated spermatids in stage VII (51% of control values) were achieved after 8.5 days of FSHAb treatment. Compared with control, FSHAb treatment increased the percentage of stage XIV-III tubules containing TUNEL-positive cells by about twofold after 7 days of FSHAb treatment (P < 0.05). This study supports a role for FSH in the maintenance of quantitatively normal adult rat spermatogenesis, specifically by regulating A3 and A4 spermatogonial subtypes. FSH may act on these spermatogonia by enhancing the stage-dependent survival of type A spermatogonia. Effects at other sites in spermatogenesis are suggested by the changes in spermatocyte and spermatid populations. However, to clarify these effects, selective FSH withdrawal would need to be prolonged until steady state had been achieved. PMID:10591615

Meachem, S J; Mclachlan, R I; Stanton, P G; Robertson, D M; Wreford, N G



Diagnostic role of follicle-stimulating hormone (FSH) measurements during the menopausal transition--an analysis of FSH, oestradiol and inhibin.  


This review examines the role of follicle-stimulating hormone (FSH) measurement in assessing the significance of symptoms and possible continuing fertility during the menopausal transition. Follicle-stimulating hormone measurement is advocated frequently as a useful diagnostic tool in perimenopausal patients. Several investigators have shown that the serum FSH level increases in the early--mid-follicular and early postovulatory phases in women over the age of 40 years who continue to experience regular menstrual cycles. The serum oestradiol level may fall (although this is controversial) and the immunoreactive inhibin level falls, being inversely correlated with the rising FSH level. When alterations in menstrual cyclicity or flow commence, signalling the onset of the menopausal transition, FSH levels may change abruptly, rising into the normal postmenopausal range and falling again into the range normally seen in young fertile women. Oestradiol and inhibin generally fluctuate in parallel with each other but inversely to FSH, although at times oestradiol in particular may be increased markedly. Postmenopausal FSH levels may be followed by endocrine evidence compatible with normal ovulation. After the menopause, FSH levels rise 10-15-fold, with low oestradiol and undetectable inhibin levels. It is concluded that FSH measurement is of little value, if any in the assessment of women during the menopausal transition because it cannot be interpreted reliably and because, apparently, ovulatory (and, presumably, potentially fertile) cycles may occur subsequent to the observation of postmenopausal FSH levels. Both oestradiol and inhibin are important negative feedback regulators of circulating FSH. PMID:8124478

Burger, H G



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



In vitro fertilizing capacity of sperm from FSH-treated photoinhibited Djungarian hamsters (Phodopus sungorus)  

Microsoft Academic Search

In hypogonadal male Djungarian hamsters FSH alone can induce normal spermatogenesis. However, for the induc- tion of mating behavior, supplementation with testoster- one is necessary. We have here investigated, by in vitro fertilization, whether sperm produced by photoinhibited hamsters treated with FSH alone can fertilize without tes- tosterone. Photoinhibited hypogonadal male Djungarian hamsters were injected daily with human FSH (10

P Niklowitz; A Lerchl; E Nieschlag



Development of a sensitive enzymeimmunoassay (EIA) for FSH determination in bovine plasma.  


A highly sensitive enzymeimmunoassay (EIA) procedure for FSH determination in bovine plasma on microtiterplates using the biotin-streptavidin amplification system and the second antibody coating was developed. Biotin was coupled to FSH and used to bridge between streptavidin-peroxidase and the immobilized antiserum in the competitive assay. The EIA was carried out directly in 50 microl of bovine plasma and compared with an established radioimmunoassay (RIA) employing 100 microl plasma. Same FSH standards and FSH specific antiserum were used in both procedures. FSH standards prepared in hormone free plasma were used. The sensitivity of the EIA procedure was 6.25 pg/well FSH which corresponded to 125 pg/ml plasma; the 50% relative binding sensitivity was seen at 200 pg/well. In comparison to RIA, the EIA was at least four times more sensitive besides requiring 6 times less FSH specific antiserum. Plasma volumes for the EIA ranging from 12.5 to 50 microl did not influence the shape of the standard curve even though a slight drop in the OD450 was seen with higher plasma volumes. When both EIA and RIA methods were used to measure FSH in cows, the levels were detectable only by the EIA procedure. The assay detects high and low plasma FSH levels within the physiological variation as well as changes in plasma FSH after stimulation with a GnRH analog. In conclusion, in addition to being non-radioactive and low cost in nature, the method offers several advantages over the conventional FSH RIA procedure; these are (a) higher sensitivity, (b) less labour and time saving, (c) more economical use of precious FSH antiserum and (d) long shelf-life of the biotinyl-FSH label (in contrast to the short half life of iodinated FSH in RIA). PMID:10379671

Prakash, B S; Wallenhorst, S; Metten, M; Holtz, W; Wuttke, W


Increased Prevalance of the -211 T Allele of Follicle Stimulating Hormone (FSH) ? Subunit Promoter Polymorphism and Lower Serum FSH in Infertile Men  

PubMed Central

Context: The human FSHB promoter polymorphism (rs10835638; ?211 G/T) has been associated with serum FSH in a cohort of young Estonian men. The minor allele carriers had reduced serum FSH (15.7% in GT heterozygotes; 40% in TT homozygotes) compared with GG homozygotes. Objective: Because FSH is essential for normal spermatogenesis and fertility, we speculated that abnormalities in FSH action could contribute to male infertility. We sought to study whether genetically inherited constitutively reduced FSH levels may affect male reproduction and replicate the association between rs10835638 and serum FSH among infertile male patients. Design: Genotyping of rs10835638 in a cohort of infertile men (n = 1029; Andrology Center of the Tartu University Clinics, Estonia), including idiopathic infertility cases (IIFC; n = 750). Patients: Patients included male partners (sperm concentration <20 × 106/ml) of infertile couples failing to conceive a child for 12 months or longer. Results: A significant excess of TT homozygotes (1.1 vs. 2.4%) as well as GT heterozygotes (22.4 vs. 25.1%) was detected among infertile men compared with the young male cohort (?2 test, P < 0.05). The T allele of rs10835638 was associated with reduced serum FSH (analysis of covariance; full cohort: P = 1.20 × 10?6, F = 13.8; IIFC: P = 7.70 × 10?7, F = 14.3) as well as with low FSH to LH ratio (full cohort: P = 1.52 × 10?11, F = 25.6; IIFC: P = 3.25 × 10?9, F = 20.4). The median serum FSH levels differed between the GG and TT carriers by 48.5%. All IIFC with TT genotype exhibited low (<1.8) FSH to LH ratio. Conclusions: In perspective, this genetic marker may have clinical significance in molecular diagnostics of male reproductive success and a potential to identify positive responders to FSH treatment.

Grigorova, Marina; Punab, Margus; Poolamets, Olev; Kelgo, Piret; Ausmees, Kristo; Korrovits, Paul; Vihljajev, Vladimir; Laan, Maris



Regulation of seminiferous tubular function by FSH and androgen.  


Seminiferous tubules contain a cytoplasmic androgen receptor similar to the receptors in the epididymis and ventral prostate. The presence of a cytoplasmic receptor indicates that androgens maintain spermatogenesis by a direct action on certain types of cells within the seminiferous tubule. The Sertoli cell appears to be one of the cell types containing androgen receptors and the receptor might also be present in spermatogonia, primary spermatocytes, or peritubular cells. The Sertoli cell is stimulated by FSH to produce an androgen-binding protein which may serve to increase the accumulation of androgen in the seminiferous epithelium and make it available for binding by intracellular androgen receptors. This may be a way in which FSH enhances the action of androgen on spermatogenesis. Androgens act on the Sertoli cell to increase its response to FSH. This action of androgens on the Sertoli cell results in increased production of androgen-binding protein and may enhance the production of other substances which exert trophic effects on spermatogenesis. PMID:169349

Hansson, V; Weddington, S C; McLean, W S; Smith, A A; Nayfeh, S N; French, F S; Ritzén, E M



Effect of urinary versus recombinant FSH on clinical outcomes after frozen–thawed embryo transfers: a systematic review  

Microsoft Academic Search

Recent randomized trials, systematic reviews and cost-effectiveness analyses have demonstrated the relative efficacy, and in some cases superiority, of urinary gonadotrophins (uFSH, human menopausal gonadotrophin) compared with recombinant FSH (rFSH). However, the effectiveness of frozen-embryo transfers (FET) following ovarian stimulation with uFSH versus rFSH in the fresh cycle has not been well investigated. The objective of this study was to

Hesham G. Al-Inany; Pieter van Gelder



Discordances between follicle stimulating hormone (FSH) and anti-M?llerian hormone (AMH) in female infertility  

PubMed Central

Background Follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) represent the two most frequently utilized laboratory tests in determining ovarian reserve (OR). This study determined the clinical significance of their concordance and discordance in female infertility patients. Methods We investigated 366 consecutive infertility patients (350 reached IVF), excluding women with polycystic ovarian syndrome (PCOS). They were considered to have normal FSH and AMH if values fell within age-specific (as-) 95% confidence intervals (CI), and to suffer from diminished ovarian reserve (DOR) if FSH exceeded and/or AMH fell below those. The two hormones, thus, could be concordant (Group I), both normal (IA) or abnormal (IB), show normal AMH/abnormal FSH (Group II) or normal FSH/abnormal AMH (Group III). Oocyte yields, stratified for age categories, were then studied in each group as reflection of OR. Results Oocyte yields significantly decreased from groups IA to II to III and IB. Predictive values of as-FSH/AMH patterns changed, however, at different ages. Except at very young and very old ages, normal as-AMH better predicted higher oocytes yields than normal as-FSH, though above age 42 years normal as-FSH predicts good oocyte yields even with abnormally low AMH. Under age 42 discrepancies between as- FSH and as-AMH remain similarly predictive of oocyte yields at all ages. Discussion Concordances and discordances between as-FSH and as-AMH improve OR assessments and predictability of oocyte yields in IVF.



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

PubMed Central

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.

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



FSH enhances the proliferation of ovarian cancer cells by activating transient receptor potential channel C3.  


Recent studies have suggested that FSH plays an important role in ovarian epithelial carcinogenesis. We demonstrated that FSH stimulates the proliferation and invasion of ovarian cancer cells, inhibits apoptosis and facilitates neovascularisation. Our previous work has shown that transient receptor potential channel C3 (TRPC3) contributes to the progression of human ovarian cancer. In this study, we further investigated the interaction between FSH and TRPC3. We found that FSH stimulation enhanced the expression of TRPC3 at both the mRNA and protein levels. siRNA-mediated silencing of TRPC3 expression inhibited the ability of FSH to stimulate proliferation and blocked apoptosis in ovarian cancer cell lines. FSH stimulation was associated with the up-regulation of TRPC3, while also facilitating the influx of Ca(2)(+) after treatment with a TRPC-specific agonist. Knockdown of TRPC3 abrogated FSH-stimulated Akt/PKB phosphorylation, leading to decreased expression of downstream effectors including survivin, HIF1-? and VEGF. Ovarian cancer specimens were analysed for TRPC3 expression; higher TRPC3 expression levels correlated with early relapse and worse prognosis. Association with poor disease-free survival and overall survival remained after adjusting for clinical stage and grade. In conclusion, TRPC3 plays a significant role in the stimulating activity of FSH and could be a potential therapeutic target for the treatment of ovarian cancer, particularly in postmenopausal women with elevated FSH levels. PMID:23580589

Tao, Xiang; Zhao, Naiqing; Jin, Hongyan; Zhang, Zhenbo; Liu, Yintao; Wu, Jian; Bast, Robert C; Yu, Yinhua; Feng, Youji



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


Abstract 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



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.



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


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 200IU 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 ?11mm was slightly higher after corifollitropin alfa compared with daily rFSH at stimulation day 8 (difference, 1.2; 95% confidence interval (CI) 0.5-1.8; P<0.01) and on the day of HCG injection (difference, 2.1; 95% CI 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. 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. The objective of this study was to compare the pharmacokinetics and pharmacodynamics of corifollitropin alfa versus daily rFSH. A total of 1509 patients were randomized in a double-blind, controlled trial to either a single injection of 150?g corifollitropin alfa or to daily injections of 200IU rFSH for the first 7 days of ovarian stimulation. Serum levels of FSH immunoreactivity were analysed (pharmacokinetic analysis), together with the number and size of growing follicles and serum inhibin B and oestradiol concentrations as biomarkers of the ovarian response (pharmacodynamic analysis). Serum FSH immunoreactivity levels were higher up to stimulation day 5 for corifollitropin alfa compared with the daily rFSH regimen but were similar from day 8 onwards, when patients started rFSH if the criteria for human chorionic gonadotrophin were not yet reached. Corifollitropin alfa treatment resulted in a similar growth rate of follicles though a slightly higher number of follicles were recruited compared with daily rFSH. It is concluded that the pharmacokinetics of corifollitropin alfa and rFSH are quite different but their induced pharmacodynamic effects at the dosages used are similar. PMID:20843746

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



LH- and FSH-stimulating of adenylate cyclase in seminiferous tubules from young rats: functional FSH and LH receptors unmasked by homogenization.  


LH- and FSH-sensitive adenylate cyclase activity was present in homogenates of whole testis tissue as well as in microdissected seminiferous tubules derived from young rats. In homogenates of seminiferous tubules a single adenylate cyclase appears to interact with both LH and FSH through separate hormone-specific receptors. Disruption of testis tissue by homogenization exposes functional FSH and LH receptors which are inaccessible to the hormones in intact cell preparations. These results indicate that in certain seminiferous tubule cell types only a fraction of the total functional receptors present is accessible to the cell surface for interaction with hormone. PMID:174966

Braun, T; Sepsenwol, S



Immunization with FSH? fusion protein antigen prevents bone loss in a rat ovariectomy-induced osteoporosis model  

SciTech Connect

Highlights: •A GST-FSH fusion protein was successfully expressed in E. coli. •Immunization with GST-FSH antigen can raise high-titer anti-FSH polyclonal sera. •Anti-FSH polyclonal sera can neutralize osteoclastogenic effect of FSH in vitro. •FSH immunization can prevent bone loss in a rat osteoporosis model. -- Abstract: Osteoporosis, a metabolic bone disease, threatens postmenopausal women globally. Hormone replacement therapy (HTR), especially estrogen replacement therapy (ERT), is used widely in the clinic because it has been generally accepted that postmenopausal osteoporosis is caused by estrogen deficiency. However, hypogonadal ? and ? estrogen receptor null mice were only mildly osteopenic, and mice with either receptor deleted had normal bone mass, indicating that estrogen may not be the only mediator that induces osteoporosis. Recently, follicle-stimulating hormone (FSH), the serum concentration of which increases from the very beginning of menopause, has been found to play a key role in postmenopausal osteoporosis by promoting osteoclastogenesis. In this article, we confirmed that exogenous FSH can enhance osteoclast differentiation in vitro and that this effect can be neutralized by either an anti-FSH monoclonal antibody or anti-FSH polyclonal sera raised by immunizing animals with a recombinant GST-FSH? fusion protein antigen. Moreover, immunizing ovariectomized rats with the GST-FSH? antigen does significantly prevent trabecular bone loss and thereby enhance the bone strength, indicating that a FSH-based vaccine may be a promising therapeutic strategy to slow down bone loss in postmenopausal women.

Geng, Wenxin; Yan, Xingrong; Du, Huicong; Cui, Jihong; Li, Liwen, E-mail:; Chen, Fulin, E-mail:



A study on superovulation using FSH and eCG in Awassi ewes.  


The present study was conducted to evaluate superovulatory treatments in Awassi ewes by eCG and FSH. High number of unovulated follicles (P < 0.05) was observed in ewes treated with eCG in non-breeding season. It could be concluded that using FSH to induce superovulation in Awassi ewes is better than eCG. PMID:19882226

Azawi, Osama Ibrahim; Al-Mola, M K M A



Par Pond water balance  

SciTech Connect

A water budget for the Par Pond hydrologic system was established in order to estimate the rate of groundwater influx to Par Pond. This estimate will be used in modeling exercises to predict Par Pond reservoir elevation and spillway discharge in the scenario where Savannah River water is no longer pumped and discharged into Par Pond. The principal of conservation of mass was used to develop the water budget, where water inflow was set equal to water outflow. Components of the water budget were identified, and the flux associated with each was determined. The water budget was considered balanced when inflow and outflow summed to zero. The results of this study suggest that Par Pond gains water from the groundwater system in the upper reaches of the reservoir, but looses water to the groundwater system near the dam. The rate of flux of groundwater from the water table aquifer into Par Pond was determined to be 13 cfs. The rate of flux from Par Pond to the water table aquifer near the dam was determined to be 7 cfs.

Hiergesell, R.A.; Dixon, K.L.



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

SciTech Connect

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

Grasso, P.; Santa-Coloma, T.A.; Reichert, L.E. Jr. (Department of Biochemistry, Albany Medical College, New York, NY (USA))



Individual differences in LH and FSH responses to orchidectomy and testosterone replacement therapy in rams.  


Profiles of LH and FSH levels and pituitary LH responses to exogenous luteinizing hormone releasing hormone (LHRH) have been characterized in rams, castrated rams (wethers), and wethers implanted with testosterone. Rams were castrated when adult, and, at the time of castration, two groups of wethers were implanted with either four or eight testosterone capsules. Rams showed random pulses of LH and testosterone which were temporally related. The number of LH and testosterone pulses per 24 hours differed among rams, giving rise to large differences in the mean levels of these hormones. Mean FSH levels and pituitary LH responses to LHRH also differed among rams and were positively correlated to differences in LH levels. All three nonimplanted wethers showed a rhythmic pulsatile pattern of LH secretion and had elevated mean LH and FSH levels. There were, however, appreciable differences between wethers with regard to mean LH and FSH levels and pituitary LH responses to LHRH. Both four and eight testosterone capsules were effective in suppressing pulsatile LH secretion and mean LH and FSH levels in two out of three wethers. In a third animal within each of these groups, however, LH and FSH profiles and LH responses to LHRH were characteristic of nonimplanted wethers. These data suggest that individual rams have different inherent capacities to secrete gonadotropins which influence LH and FSH responses to castration and testosterone replacement therapy. PMID:6409867

D'Occhio, M J; Schanbacher, B D; Kinder, J E



Estrogen inhibition of LH and FSH secretion: effects of a GnRH antagonist.  


Follicle-stimulating hormone (FSH) levels are not suppressed as rapidly or to the same degree as luteinizing hormone (LH) levels in ovariectomized rats treated with either gonadotropin-releasing hormone (GnRH) antagonist or estrogen. The acute inhibitory effects of various doses of estrogen on FSH and LH secretion were examined in cannulated, 2-wk ovariectomized rats. No dose of 17 beta-estradiol, up to 2,500 ng injected intravenously, suppressed FSH, although LH secretion was inhibited 50% within 1 h by 100 ng. In another experiment, estradiol benzoate (EB; 10 or 250 micrograms; sc injection in oil) was only marginally effective in suppressing FSH, compared with LH, levels in serum. Treatment with EB 24 h before or after a 500 micrograms dose of a GnRH antagonist did not reduce LH or FSH to levels lower than those achieved with antagonist alone. These results indicate that the GnRH-dependent component of FSH release and the GnRH-independent component that is unmasked in the presence of GnRH antagonist are sensitive to negative feedback by estrogen, indicating that this steroid is not the primary inhibitory ovarian factor regulating FSH in the rat. PMID:3083691

Charlesworth, M C; Schwartz, N B



Characterization of sea bass FSH? 5' flanking region: transcriptional control by 17?-estradiol.  


The sea bass follicle-stimulating hormone 5' flanking region (sbFSH? 5' FR) was cloned and characterized in order to study the molecular mechanisms underlying transcriptional regulation of the sbFSH? gene. Analysis of the ~3.5 kb of this region revealed the presence of several putative cis-acting elements, including steroid hormone response elements, cAMP response elements, pituitary-specific transcription factor response elements, activator protein-1 response elements and TATA sequence. Deleted constructs containing ~3.5 kb of the sbFSH? 5' FR fused to a luciferase reporter gene were transiently transfected into human embryonic kidney (HEK 293) and mouse mature gonadotrope (L?T2) cell lines. The sbFSH? 5' FR was efficiently expressed under basal conditions in L?T2 but not in HEK 293, pointing to both positive and negative regulatory elements. In order to elucidate the estrogen-mediated sbFSH? transcriptional activity, in vitro treatments with 17?-estradiol were carried out on primary cultures of pituitary cells and L?T2 cells transiently expressing luciferase under the control of sbFSH? 5' FR. Overall, these results demonstrate that 17?-estradiol inhibits sbFSH? gene expression directly at the level of the pituitary. However, it was also shown that estrogen did not induce changes of the sbFSH promoter-directed luciferase activity, suggesting that sbFSH? 5'FR (~3.5 kb) activity is cell type dependent and its estrogen regulation could require cis-acting elements located upstream of the promoter region, which is characterized in this article. PMID:24271878

Muriach, Borja; Carrillo, Manuel; Zanuy, Silvia; Cerdá-Reverter, José Miguel



Further evidence for differential regulation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH): increased FSH and decreased LH levels in a patient with familial pure gonadal dysgenesis.  

PubMed Central

There is experimental evidence that a portion of follicle-stimulating hormone (FSH) secretion is independent of hypothalamic influences. A 29 year old woman with familial pure gonadal dysgenesis developed myelodysplastic syndrome. Endocrine investigations showed discrepancy between serum FSH and luteinizing hormone (LH) levels. FSH levels remained elevated while LH levels decreased. The FSH to LH ratio was 10 (normal 2-2.5). The fall in LH is likely to be due to factor(s) involved directly and specifically in LH synthesis and release. Exogenous LH releasing hormone administration as well as hormonal replacement treatment increased LH levels. The FSH to LH ratio decreased to 7. This case supports the hypothesis of differential regulation of FSH and LH, and that FSH secretion is at least partly autonomous.

Popovic, V.; Micic, D.; Damjanovic, S.; Calovic, L.; Rolovic, Z.; Mijovic, A.; Petakov, M.; Manojlovic, D.; Micic, J.



Pituitary follicle-stimulating hormone (FSH) induces CREM gene expression in Sertoli cells: involvement in long-term desensitization of the FSH receptor.  

PubMed Central

Transcription factor CREM (cAMP-responsive element modulator) plays a pivotal role in the nuclear response to cAMP in neuroendocrine cells. We have previously shown that follicle-stimulating hormone (FSH) directs CREM expression in male germ cells. The physiological importance of FSH in Sertoli cell function prompted us to analyze its effect on CREM expression in these cells. We observed a dramatic and specific increase in the CREM isoform ICER (inducible cAMP early repressor) expression, with a peak 4 h after FSH treatment of primary Sertoli cells. Interestingly, induced levels of ICER protein persist for a considerably longer time. Induction of the repressor ICER accompanies early down-regulation of the FSH receptor transcript, which leads to long-term desensitization. Here we show that ICER represses FSH receptor expression by binding to a CRE-like sequence in the regulatory region of the gene. Our results confirm the crucial role played by CREM in hormonal control and suggest its role in the long-term desensitization phenomenon of peptide membrane receptors. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6

Monaco, L; Foulkes, N S; Sassone-Corsi, P



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

SciTech Connect

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

Kangasniemi, M.; Kaipia, A.; Toppari, J.; Perheentupa, A.; Huhtaniemi, I.; Parvinen, M. (Univ. of Turku (Finland))



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

Microsoft Academic Search

Stage-specific binding of follicle-stimulating hormone (FSH) was measured in rat seminiferous tubules. The binding in single-point assays was over 3-fold higher (P less than 0.05) in stages XIII to I than in stages VI to VII of the epithelial cycle. No difference was found between the equilibrium association constants (Ka) of FSH binding in stages XIV to IV (10 +\\/-




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

SciTech Connect

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

Kangasniemi, M.; Kaipia, A.; Toppari, J.; Mali, P.; Huhtaniemi, I.; Parvinen, M. (Univ. of Turku (Finland))



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

Microsoft Academic Search

Basal and follicle-stimulating hormone (FSH)-stimulated cyclic AMP (cAMP) productions by seminiferous tubular segments from irradiated adult rats were investigated at defined stages of the epithelial cycle when specific spermatogenic cells were low in number. Seven days post-irradiation, depletion of spermatogonia did not influence the basal cAMP production, but FSH response increased in stages II-VIII. Seventeen days post-irradiation when spermatocytes were

Marko Kangasniemi; Antti Kaipia; Jorma Toppari; Pekka Mali; Ilpo Huhtaniemi; Martti Parvinen



Superovulation using recombinant human FSH and ultrasound-guided transabdominal follicular aspiration in baboon ( Papio anubis)  

Microsoft Academic Search

The response of baboon females to a modified human ovarian stimulation protocol incorporating start of pituitary suppression in the luteal phase of the cycle with a GnRH agonist (GnRHa) and recombinant human FSH (rhFSH) was studied. A long-acting GnRHa implant supplying goserelin acetate was administered s.c. to six adult female baboons experiencing regular menstrual cycles (33–34 days) on days 22–24

S. Cseh; J. Corselli; P. Chan; L. Bailey



Dynamic changes in glycosylation and glycan composition of serum FSH and LH during natural ovarian stimulation  

PubMed Central

Background Glycosylation and glycan composition are of fundamental importance for the biological properties of FSH and LH. The aim of this study was to determine the glycosylation, sialylation, and sulfonation of serum FSH and LH throughout the normal menstrual cycle. Methods Serum samples were collected from 79 healthy women with regular menstrual cycles. The mean numbers of anionic monosaccharide (AMS), sialic acid (SA), and sulfonated N-acetylgalactosamine (SU) residues per FSH and LH molecule were estimated for all sera with methods based on electrophoreses, neuraminidase treatments, and fluoroimmunoassays of the gonadotrophins. Results Di-glycosylated glycoforms (FSHdi, LHdi) were detected in serum in addition to tetra-glycosylated FSH (FSHtetra) and tri-glycosylated LH (LHtri). FSHdi exhibited two peaks: one on day 5 to 7 and one, more pronounced, at midcycle. FSHtetra plateaued at a high concentration from day 5 to 15, without a midcycle peak. There were lower concentrations of LHdi than LHtri, except at midcycle when the opposite occurred. The mean numbers of SA and SU residues per molecule of FSH and LH in serum showed four different patterns during the cycle, all with highly significant (P < 0.0001) differences between levels at different phases of the cycle. The pattern of SA residues on FSH was ‘M’-shaped, and that of SU on LH ‘V’-shaped. Conclusion Serum FSH and LH governing the natural ovarian stimulation process exhibited dynamic changes of glycosylation and glycan composition. This new information on the FSH and LH molecular structures may lead to more successful mono-ovulatory treatment regimens for ovulation induction in anovulatory women.

Eriksson, Karin



Improved FSH sensitisation and aromatase assay in human granulosa-lutein cells  

Microsoft Academic Search

Granulosa-lutein (GL) cells from follicular aspirates from women undergoing in-vitro fertilization (IVF) treatment are usually refractory to follicle stimulating hormone (FSH) regarding the induction and\\/or maintenance of aromatase activity which converts androgens (e.g. testosterone) to oestrogens. The normal method of assaying FSH-stimulated aromatase activity in GL cell cultures is to add exogenous testosterone throughout the cell culture period and measure

A. Lambert; S. D. Harris; P. Knaggs; W. R. Robertson



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



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


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




NASA Astrophysics Data System (ADS)

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

Frouin, R. J.; Franz, B.



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

PubMed Central

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

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



Effect of cyproterone acetate on cells of the pars distalis of the adenohypophysis in the beagle bitch.  


The effects of oral administration of 100 mg per kg per day cyproterone acetate (CPA) for four weeks on cells of the pars distalis, as revealed by the immunoperoxidase technique and chemical staining, were studied in the ovariectomized beagle bitch. For immunochemical staining antisera to the following hormones were used: canine GH, canine PRL, procine ACHT, bovine TSH beta, bovine LH beta and human FSH beta1. The most striking effects of the treatment were an overall increase in the relative proportion of GH cells and a marked morphological indication of high secretory activity in these cells. In contrast, PRL cells were not affected significantly. In all ovariectomized control bitches a marked atrophy of the cells stained for FSH beta (FSH cells) and hypertrophy of the cells shown to contain LH beta (LH cells) were observed. FSH cells became enlarged, while LH cells appeared reduced in size by administration of CPA. In some treated bitches ACTH/MSH cells showed atrophy and regressive changes, whereas TSH cells seemed to become enlarged and were more densely arranged. These structural responses indicate that, in addition to its partial antigonadotropic properties, CPA as a synthetic progesterone derivative may stimulate GH secretion and possibly suppress CRH-ACTH activity in the ovariectomized beagle bitch. PMID:200363

El Etreby, M F; Fath El BaB, M R



Regulation and Regulatory Role of WNT Signaling in Potentiating FSH Action during Bovine Dominant Follicle Selection.  


Follicular development occurs in wave like patterns in monotocous species such as cattle and humans and is regulated by a complex interaction of gonadotropins with local intrafollicular regulatory molecules. To further elucidate potential mechanisms controlling dominant follicle selection, granulosa cell RNA harvested from F1 (largest) and F2 (second largest) follicles isolated at predeviation (PD) and onset of diameter deviation (OD) stages of the first follicular wave was subjected to preliminary RNA transcriptome analysis. Expression of numerous WNT system components was observed. Hence experiments were performed to test the hypothesis that WNT signaling modulates FSH action on granulosa cells during follicular waves. Abundance of mRNA for WNT pathway members was evaluated in granulosa cells harvested from follicles at emergence (EM), PD, OD and early dominance (ED) stages of the first follicular wave. In F1 follicles, abundance of CTNNB1 and DVL1 mRNAs was higher and AXIN2 mRNA was lower at ED versus EM stages and DVL1 and FZD6 mRNAs were higher and AXIN2 mRNA was lower in F1 versus F2 follicle at the ED stage. Bovine granulosa cells were treated in vitro with increasing doses of the WNT inhibitor IWR-1+/- maximal stimulatory dose of FSH. IWR-1 treatment blocked the FSH-induced increase in granulosa cell numbers and reduced the FSH-induced increase in estradiol. Granulosa cells were also cultured in the presence or absence of FSH +/- IWR-1 and hormonal regulation of mRNA for WNT pathway members and known FSH targets determined. FSH treatment increased CYP19A1, CCND2, CTNNB1, AXIN2 and FZD6 mRNAs and the stimulatory effect on CYP19A1 mRNA was reduced by IWR-1. In contrast, FSH reduced CARTPT mRNA and IWR-1 partially reversed the inhibitory effect of FSH. Results support temporal and hormonal regulation and a potential role for WNT signaling in potentiating FSH action during dominant follicle selection. PMID:24936794

Gupta, P S P; Folger, Joseph K; Rajput, Sandeep K; Lv, Lihua; Yao, Jianbo; Ireland, James J; Smith, George W



Regulation and Regulatory Role of WNT Signaling in Potentiating FSH Action during Bovine Dominant Follicle Selection  

PubMed Central

Follicular development occurs in wave like patterns in monotocous species such as cattle and humans and is regulated by a complex interaction of gonadotropins with local intrafollicular regulatory molecules. To further elucidate potential mechanisms controlling dominant follicle selection, granulosa cell RNA harvested from F1 (largest) and F2 (second largest) follicles isolated at predeviation (PD) and onset of diameter deviation (OD) stages of the first follicular wave was subjected to preliminary RNA transcriptome analysis. Expression of numerous WNT system components was observed. Hence experiments were performed to test the hypothesis that WNT signaling modulates FSH action on granulosa cells during follicular waves. Abundance of mRNA for WNT pathway members was evaluated in granulosa cells harvested from follicles at emergence (EM), PD, OD and early dominance (ED) stages of the first follicular wave. In F1 follicles, abundance of CTNNB1 and DVL1 mRNAs was higher and AXIN2 mRNA was lower at ED versus EM stages and DVL1 and FZD6 mRNAs were higher and AXIN2 mRNA was lower in F1 versus F2 follicle at the ED stage. Bovine granulosa cells were treated in vitro with increasing doses of the WNT inhibitor IWR-1+/? maximal stimulatory dose of FSH. IWR-1 treatment blocked the FSH-induced increase in granulosa cell numbers and reduced the FSH-induced increase in estradiol. Granulosa cells were also cultured in the presence or absence of FSH +/? IWR-1 and hormonal regulation of mRNA for WNT pathway members and known FSH targets determined. FSH treatment increased CYP19A1, CCND2, CTNNB1, AXIN2 and FZD6 mRNAs and the stimulatory effect on CYP19A1 mRNA was reduced by IWR-1. In contrast, FSH reduced CARTPT mRNA and IWR-1 partially reversed the inhibitory effect of FSH. Results support temporal and hormonal regulation and a potential role for WNT signaling in potentiating FSH action during dominant follicle selection.

Gupta, P. S. P.; Folger, Joseph K.; Rajput, Sandeep K.; Lv, Lihua; Yao, Jianbo; Ireland, James J.; Smith, George W.



Spondylolisthésis par lyse isthmique  

Microsoft Academic Search

Spondylolisthesis refers to a permanent forward slippage of the vertebral body, in most cases L5, more rarely L4 or higher lumbar vertebrae. Spondylolisthesis by isthmic spondylolysis or fractures of the pars interarticularis - acquired most of the time by repeated microtrauma during childhood – differ from congenital spondylolisthesis in which developmental abnormalities of the posterior arch are often associated to

J.-M. Vital; M. Pedram



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



Joint Basal and Pulsatile Hypersecretory Mechanisms Drive the Monotropic Follicle-Stimulating Hormone (FSH) Elevation in Healthy Older Men: Concurrent Preservation of the Orderliness of the FSH Release Process: A General Clinical Research Center Study  

Microsoft Academic Search

To appraise the neuroendocrine mechanisms that underlie a selective (monotropic) elevation of serum FSH concentrations in healthy older men, we sampled blood in 11 young (ages 21-34) and 8 older men (ages 62-72) men every 2.5 min overnight. Serum FSH concentrations were quantitated in an automated, high-sensitivity, chemiluminescence-based assay. Rates of basal and pulsatile FSH secretion were estimated by deconvolution




Basal follicle stimulating hormone (FSH) predicts response to controlled ovarian hyperstimulation (COH)intrauterine insemination (IUI) therapy  

Microsoft Academic Search

Purpose: This work investigates the relationship of basal follicle stimulating hormone (FSH) measurements and age to ovarian responsiveness and pregnancy occurrence following controlled ovarian hyperstimulation and intrauterine insemination (COH-IUI). Method: Basal FSH was measured retrospectively in sera from infertility patients obtained on cycle day 2, 3, or4 of a COH-IUI treatment cycle. Basal FSH was then correlated with COH response

Thomas H. Burwinkel; John E. Buster; Janet L. Scoggan; Sandra A. Carson



Effects of estradiol and FSH on maturation of the testis in the hypogonadal (hpg) mouse  

PubMed Central

Background The hypogonadal (hpg) mouse is widely used as an animal model with which to investigate the endocrine regulation of spermatogenesis. Chronic treatment of these GnRH-deficient mice with estradiol is known to induce testicular maturation and restore qualitatively normal spermatogenesis. The aim of the current studies was to investigate whether these effects of estradiol are direct effects in the testis, or indirect actions via paradoxical stimulation of FSH secretion from the pituitary gland. Methods Initially, Western blot and immunohistochemistry were used to analyse tissues from hpg mice to identify potential sites of action of estradiol. In the main study, hpg mice were treated for 50 days with either an estradiol implant or daily injections of recombinant human FSH, or a combination of both, to determine whether estradiol would have an additive or synergistic effect with FSH on testis development, as assessed by histological analysis and stereological quantification of Leydig, Sertoli and germ cell proliferation. Results Western blot analysis revealed ER? immunoreactive bands of appropriate molecular weight in extracts of testis and pituitary glands from hpg mice, and immunohistochemical studies confirmed ER? in nuclei of anterior pituitary cells and Leydig and peritubular cells in hpg mice. Histological and morphometric analyses revealed that estradiol treatment alone was as effective as FSH in promoting Sertoli cell production and proliferation of the seminiferous epithelium, resulting in the production of elongating spermatids. Combined estradiol and FSH treatment did not produce a greater effect than either treatment alone, though an increased dose of FSH significantly increased seminiferous tubule volume and testis weight and increase Sertoli cell numbers further within the same time frame. In contrast, estradiol caused substantial increases in the wet weight of the seminal vesicles, whereas FSH was without effect on this tissue, and did not augment the actions of estradiol. Conclusion As ERalpha receptor is abundantly expressed in the pituitary gland of hpg mice, and estradiol did not exert effects on testis development over and above those of FSH, we conclude that the action of estradiol on testis development in hpg mice is predominantly via the stimulation of pituitary FSH release.

Baines, Helen; Nwagwu, Margaret O; Hastie, Graham R; Wiles, Roman A; Mayhew, Terry M; Ebling, Francis JP



Evaluation of the degree of satisfaction in oocyte donors using sustained-release FSH corifollitropin ?.  


Ovarian stimulation treatment is recognized as placing a physical and psychological burden on patients and oocyte donors. The introduction of sustained follicle stimulants will reduce the number of injections and may improve the overall patient experience. This study aimed to evaluate the degree of satisfaction in oocyte donors undergoing treatment with corifollitropin ?, a synthetic recombinant rFSH which replaces daily FSH injections for the first week of ovarian stimulation. The results showed no significant differences in clinical parameters between the two protocols (recombinant FSH versus corifollitropin ?). Implantation rates for the corifollitropin ? and daily FSH protocol groups were 39.1% and 38.4%, respectively, while ongoing pregnancy rates were 45.9% and 44.4%. There were no statistical between-group differences in the responses to the questionnaires. However, donors treated with corifollitropin ? who had undergone a previous cycle with daily FSH reported greater satisfaction with the corifollitropin ? protocol. In conclusion, no significant differences were found in any analysed parameters between treatments. However, when donors who had undergone both treatments chose which treatment they preferred, the results clearly showed a positive trend towards choosing corifollitropin ?, confirming that this protocol may reduce treatment burden and increase donor compliance. PMID:23352098

Requena, Antonio; Cruz, María; Collado, Diana; Izquierdo, Alexandra; Ballesteros, Agustín; Muñoz, Manuel; García-Velasco, Juan Antonio



Use of a single injection of long-acting recombinant bovine FSH to superovulate Holstein heifers: A preliminary study.  


Our objective was to compare several experimental preparations of a single injection of long-acting recombinant bovine FSH (rbFSH; types A and B) to a porcine pituitary-derived FSH (Folltropin) to superovulate Holstein dairy heifers. Nonlactating, nonpregnant virgin Holstein heifers (n = 56) aged 12 to 15 months were randomly assigned to one of four superstimulatory treatments. Beginning at a random stage of the estrous cycle, all follicles greater than 5 mm were aspirated. Thirty-six hours later, heifers received an intravaginal P4 device and superstimulatory treatments were initiated. Treatments were (1) 300 mg of pituitary-derived FSH (Folltropin) administered in eight decreasing doses over a period of 3.5 days; (2) a single injection of 50 ?g of A-rbFSH; (3) a single injection of 100 ?g of A-rbFSH; and (4) a single injection of 50 ?g of B-rbFSH. All heifers received 25 mg PGF2? at 48 and 72 hours after the insertion of P4 device. At 84 hours after insertion, P4 devices were removed, and ovulation was induced 24 hours later with hCG (2500 IU). Heifers were inseminated at 12 and 24 hours after hCG treatment. The number of ovulatory follicles was greatest for heifers treated with Folltropin and B50-rbFSH, least for heifers treated with A50-rbFSH, and was intermediate for heifers treated with A100-rbFSH (25.7 ± 3.2, 18.9 ± 3.2, 5.9 ± 0.9, and 16.6 ± 3.1, respectively; P < 0.001). The number of corpora lutea was greatest for heifers treated with Folltropin, B50-rbFSH, and A100-rbFSH, and least for heifers treated with A50-rbFSH (19.1 ± 2.4, 16.1 ± 3.0, 15.9 ± 2.9, and 2.6 ± 0.9, respectively; P < 0.001). The number of good-quality embryos differed among treatments and was greatest for heifers treated with B50-rbFSH, Folltropin, and A100-rbFSH and least for heifers treated with A50-rbFSH (7.6 ± 2.4, 6.5 ± 1.7, 4.3 ± 1.5, and 0.8 ± 0.5, respectively; P < 0.001). In conclusion, a single injection of a preparation of long-acting rbFSH (either 100 ?g of A-rbFSH or 50 ?g of B-rbFSH but not 50 ?g of A-rbFSH) produced similar superovulatory responses resulting in the production of good-quality embryos when compared with a pituitary-derived FSH preparation administered twice daily for 4 days. More studies using different types of cattle and different doses of rbFSH are needed to confirm the findings reported in this preliminary study. PMID:24938802

Carvalho, Paulo D; Hackbart, Katherine S; Bender, Robb W; Baez, Giovanni M; Dresch, Ana R; Guenther, Jerry N; Souza, Alex H; Fricke, Paul M



Evidence for gene transcription of adenohypophyseal hormones in the ovine pars tuberalis.  


Specific cells of the hypophyseal pars tuberalis (PT) have been associated with the transmission of photoperiodic stimuli to the endocrine system. However, their principal secretory products have not been identified yet. Therefore we studied the expression of several adenohypophyseal hormones and their subunits (TSH, FSH, LH, common alpha-chain, GH, ACTH, PRL, alpha- and gamma-MSH, beta-lipotropin) by immunocytochemistry, Northern blot analysis and in situ hybridization in the sheep pituitary. Only the common alpha-chain of glycoprotein hormones could be detected in ovine PT-specific cells by immunocytochemistry while antibodies directed against the beta-chains of LH, FSH, TSH and beta-lipotropin labeled single cells in the PT but failed to detect these antigens in PT-specific cells. In situ hybridization and Northern blot analysis with antisense oligonucleotides against the common alpha-chain, beta-LH, beta-FSH, beta-TSH, PRL and POMC revealed the expression of these subunits in the ovine PT. The mRNA of the common alpha-chain, beta-TSH and, to a far lower extent, PRL and POMC were found throughout the entire pars tuberalis while beta-FSH and beta-LH could only be detected in cells of the caudal PT. Hence, GH-mRNA and GH immunoreactivity were exclusively found in the pituitary pars distalis. Compared to these results--obtained under the short photoperiod (winter)--we found clear ultrastructural signs of altered secretory activity in PT-specific cells of animals exposed to the long photoperiod (summer); the common alpha-chain immunoreactivity was nearly absent in PT-specific cells of summer animals. However, no seasonal influence on gene transcription or translation for other adenohypophyseal hormone was observed. These findings suggest that ovine PT-specific cells, which are only immunopositive for the common alpha-chain, are capable to express different mRNAs of adenohypophyseal hormones. Although it remains elusive how gene transcription and translation are related in this cell type, the presence of an mRNA pool for hormone subunits leads to the speculation that--at least in the sheep--hormone synthesis is mainly regulated at the translational level and that secretion of hormones may be primarily constitutive. PMID:8839351

Böckers, T M; Bockmann, J; Fauteck, J D; Wittkowski, W; Sabel, B A; Kreutz, M R



Roles of PAR1 and PAR2 in viral myocarditis.  


Viral myocarditis is estimated to cause ~20% of sudden death in people under the age of 40. A variety of viruses have been found to cause myocarditis including coxsackievirus B3 (CVB3). Many studies have been performed with CVB3 because there is a mouse model of CVB3-induced myocarditis. Studies have shown that the TLR3-IFN? pathway plays a central role in the innate immune response to CVB3 infection. Our laboratory studies the role of protease activated receptors (PAR) in different biological responses including viral infection. We examined the effect of a deficiency in either PAR1 or PAR2 on CVB3-induced myocarditis. Interestingly, we found that PAR1 knockout mice had increased cardiac injury whereas PAR2 knockout mice had decreased cardiac injury. Our studies support the notion that PARs modulate the innate immune response and can have both positive and negative effects on TLR-dependent responses. PMID:24759133

Mackman, Nigel; Antoniak, Silvio



Comparative incidence of ovarian hyperstimulation syndrome following ovarian stimulation with corifollitropin alfa or recombinant FSH.  


Corifollitropin alfa is a novel recombinant gonadotrophin with sustained follicle-stimulating activity. A single injection can replace seven daily injections of recombinant follicle-stimulating hormone (rFSH) during the first week of ovarian stimulation. All cases of ovarian hyperstimulation syndrome (OHSS) with corifollitropin alfa intervention in a gonadotrophin-releasing hormone antagonist protocol have been assessed in three large trials: Engage, Ensure and Trust. Overall, 1705 patients received corifollitropin alfa and 5.6% experienced mild, moderate or severe OHSS. In the randomized controlled trials, Engage and Ensure, the pooled incidence of OHSS with corifollitropin alfa was 6.9% (71/1023 patients) compared with 6.0% (53/880 patients) in the rFSH group. Adjusted for trial, the odds ratio for OHSS was 1.18 (95% CI 0.81-1.71) indicating that the risk of OHSS for corifollitropin alfa was similar to that for rFSH. The incidence of mild, moderate and severe OHSS was 3.0%, 2.2% and 1.8%, respectively, with corifollitropin alfa, with 1.9% requiring hospitalization, and 3.5%, 1.3% and 1.3%, respectively, in the rFSH arms, with 0.9% requiring hospitalization. Despite a higher ovarian response with corifollitropin alfa compared with rFSH for the first 7days of ovarian stimulation, the incidence of OHSS was similar. Corifollitropin alfa is a new agent used in ovarian stimulation treatment for IVF fertilization. One injection of corifollitropin alfa can replace seven injections of recombinant FSH (rFSH). In three studies of corifollitropin alfa treatment, we assessed all cases of ovarian hyperstimulation syndrome (OHSS), a potentially serious complication of ovarian stimulation treatment. Overall, 5.6% of the patients (95/1701) experienced OHSS. Two of the trials compared corifollitropin alfa versus rFSH. Because OHSS is relatively rare, we pooled the results of these trials to give a more reliable estimate of the incidence of OHSS. In the pooled analysis, 6.9% (71/1023) of patients receiving corifollitropin alfa had signs or symptoms of OHSS, compared with 6.0% in the rFSH group (53/880). The risk of OHSS with corifollitropin alfa treatment was similar to the risk of OHSS in patients who received rFSH: the incidence of mild, moderate and severe OHSS was 3.0%, 2.2% and 1.8%, respectively, in patients in the corifollitropin alfa treatment groups, with 1.9% requiring hospitalisation, and 3.5%, 1.3% and 1.3%, respectively, in patients in the rFSH treatment groups, with 0.9% requiring hospitalization. Although the ovaries respond more to corifollitropin alfa than to rFSH for the first 7days of ovarian stimulation, neither treatment regimen was significantly more likely to cause OHSS. PMID:22386594

Tarlatzis, Basil C; Griesinger, Georg; Leader, Arthur; Rombauts, Luk; Ijzerman-Boon, Pieta C; Mannaerts, Bernadette M J L



FSHB promoter polymorphism within evolutionary conserved element is associated with serum FSH level in men  

PubMed Central

BACKGROUND No polymorphisms affecting serum FSH levels have been described in the human FSHB gene. We have identified a potential regulatory single nucleotide polymorphism (SNP, rs10835638; G/T) 211 bp upstream from the FSHB mRNA transcription start-site, located within a highly conserved region among placental mammals. We aimed to determine the correlation of carrier status of rs10835638 alternative alleles with serum FSH level in men, and testicular and hormonal parameters. METHODS A quantitative genetic association study using a cohort of healthy men (n = 554; age 19.2 ± 1.7 years) visiting the Centre of Andrology, Tartu University Hospital, Estonia. RESULTS Rs10835638 (allele frequencies: G 87.6%, T 12.4%) was significantly associated with serum FSH level (analysis of variance: F = 13.0, P = 0.0016, df = 1; regression testing for a linear trend: P = 0.0003). Subjects with the GG genotype exhibited higher FSH levels (3.37 ± 1.79 IU/l, n = 423) compared with heterozygotes (2.84 ± 1.54 IU/l, n = 125) (P = 0.0005), the group of T-allele carriers (GT+TT, 2.78 ± 1.51 IU/l, n = 131) (P = 0.0005) and TT-homozygotes (2.02 ± 0.81 IU/L, n = 6) (P = 0.031). Rs10835638 was also associated with significant (P < 0.05) reduction in free testosterone index and testes volume, but increased semen volume, sex hormone-binding globulin, serum testosterone and estradiol. LH and inhibin-B levels did not differ significantly between groups. CONCLUSIONS The identification of a regulatory SNP in FSHB promoter paves the way to study the effect of constitutively low FSH on male health and fertility. As FSH contributes to follicular development and sex steroid production in women, the role of this FSHB variant in female reproductive success is still to be addressed.

Grigorova, Marina; Punab, Margus; Ausmees, Kristo; Laan, Maris



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.



Weak evidence of bright light effects on human LH and FSH  

PubMed Central

Background Most mammals are seasonal breeders whose gonads grow to anticipate reproduction in the spring and summer. As day length increases, secretion increases for two gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH). This response is largely controlled by light. Light effects on gonadotropins are mediated through effects on the suprachiasmatic nucleus and responses of the circadian system. There is some evidence that seasonal breeding in humans is regulated by similar mechanisms, and that light stimulates LH secretion, but primate responses seem complex. Methods To gain further information on effects of bright light on LH and FSH secretion in humans, we analyzed urine samples collected in three experiments conducted for other goals. First, volunteers ages 18-30 years and 60-75 commenced an ultra-short 90-min sleep-wake cycle, during which they were exposed to 3000 lux light for 3 hours at balanced times of day, repeated for 3 days. Urine samples were assayed to explore any LH phase response curve. Second, depressed participants 60-79 years of age were treated with bright light or dim placebo light for 28 days, with measurements of urinary LH and FSH before and after treatment. Third, women of ages 20-45 years with premenstrual dysphoric disorder (PMDD) were treated to one 3-hour exposure of morning light, measuring LH and FSH in urine before and after the treatments. Results Two of the three studies showed significant increases in LH after light treatment, and FSH also tended to increase, but there were no significant contrasts with parallel placebo treatments and no significant time-of-day treatment effects. Conclusions These results gave some support for the hypothesis that bright light may augment LH secretion. Longer-duration studies may be needed to clarify the effects of light on human LH and FSH.



GnRH Increases c-Fos Half-Life Contributing to Higher FSH? Induction  

PubMed Central

GnRH is a potent hypothalamic regulator of gonadotropin hormones, LH and FSH, which are both expressed within the pituitary gonadotrope and are necessary for the stimulation of gametogenesis and steroidogenesis in the gonads. Differential regulation of LH and FSH, which is essential for reproductive fitness, is achieved, in part, through the varying of GnRH pulse frequency. However, the mechanism controlling the increase in FSH during the periods of low GnRH has not been elucidated. Here, we uncover another level of regulation by GnRH that contributes to differential expression of the gonadotropins and may play an important role for the generation of the secondary rise of FSH that stimulates folliculogenesis. GnRH stimulates LH? and FSH? subunit transcription via induction of the immediate early genes, Egr1 and c-Fos, respectively. Here, we determined that GnRH induces rapidly both Egr1 and c-Fos, but specifically decreases the rate of c-Fos degradation. In particular, GnRH modulates the rate of c-Fos protein turnover by inducing c-Fos phosphorylation through the ERK1/2 pathway. This extends the half-life of c-Fos, which is normally rapidly degraded. Confirming the role of phosphorylation in promoting increased protein activity, we show that a c-Fos mutant that cannot be phosphorylated by GnRH induces lower expression of the FHS? promoter than wild-type c-Fos. Our studies expand upon the role of GnRH in the regulation of gonadotropin gene expression by highlighting the role of c-Fos posttranslational modification that may cause higher levels of FSH during the time of low GnRH pulse frequency to stimulate follicular growth.

Reddy, Gaddameedi R.; Xie, Changchuan; Lindaman, Lacey L.



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


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



FSH and TSH in the Regulation of Bone Mass: The Pituitary/Immune/Bone Axis  

PubMed Central

Recent evidences have highlighted that the pituitary hormones have profound effects on bone, so that the pituitary-bone axis is now becoming an important issue in the skeletal biology. Here, we discuss the topical evidence about the dysfunction of the pituitary-bone axis that leads to osteoporotic bone loss. We will explore the context of FSH and TSH hormones arguing their direct or indirect role in bone loss. In addition, we will focus on the knowledge that both FSH and TSH have influence on proinflammatory and proosteoclastogenic cytokine expression, such as TNF? and IL-1, underlining the correlation of pituitary-bone axis to the immune system.

Cuscito, Concetta; Colucci, Silvia



Falling FSH levels predict poor IVF pregnancy rates in patients whom the gonadotropins are withheld  

Microsoft Academic Search

Aim  To determine whether monitoring follicle stimulating hormone (FSH) levels in over-responding patients whom the gonadotropins\\u000a were withheld would predict \\u000a pregnancy outcome.\\u000a \\u000a \\u000a \\u000a Methods  A group of 33 female infertility patients aged between 20–40 years who had to be coasted during controlled ovarian hyperstimulation\\u000a were recruited for this study. The FSH concentrations on human chorionic gonadotropin (HCG) day and on the four preceding\\u000a days

Munire Erman Akar; Kutluk Oktay



Molecular Analysis of a Mutated FSH Receptor Detected in a Patient with Spontaneous Ovarian Hyperstimulation Syndrome  

PubMed Central

Spontaneous ovarian hyperstimulation syndrome (sOHSS) is a rare event that may result from a FSH-producing pituitary adenoma (FSHoma), activating mutations of the FSH receptor (FSHR), and cross-reactivity of the FSHR to elevated hCG and TSH in the setting of pregnancy or hypothyroidism. The objective of this study was to investigate whether an aberrant FSHR was present in a woman with sOHSS and a non-surgically diagnosed FSHoma whose serum FSH levels and FSH bioactivity were nearly normal. Sequencing of the patient’s FSHR gene revealed a heterozygous novel missense mutation c. 1536G>A resulting in an amino acid substitution M512I. We asked whether this mutant FSHR affected FSHR-mediated signaling pathways involving cAMP/protein kinase A (PKA), phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) and v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog kinase (SRC)/ p42/p44 extracellular signal-regulated protein kinases (ERK1/2). Thus, 293T cells expressing wild-type (FSHRwt), the mutant FSHR (FSHRmt), or both (FSHRwt/mt) were treated with FSH and subjected to measurements of intracellular cAMP, cAMP-induced CRE (cAMP response element)-mediated luciferase assays and immunoblot analyses of phosphorylated PI3K and ERK1/2. There were no differences in luciferase activities or phosphorylation levels of ERK1/2 among FSHRwt, FSHRmt cells and FSHwt/mt cells. However, FSHRmt cells showed a significant reduction in both cAMP production and PI3K phosphorylation levels with unchanged phosphorylation of ERK1/2 upon FSH stimulation in comparison to FSHwt cells. Also, FSH treatment did not provoke PI3K phosphorylation in FSHwt/mt cells. These results indicate that the novel missense M512I FSHR mutation identified herein did not participate in hyperactivation of FSHR-mediated signaling pathways but rather in hypoactivation of the FSH-mediated PI3K/AKT pathway. Thus, this study demonstrates a new functional property of this novel mutatnt FSHR, which, however, might not be involved in the pathogenesis of sOHSS in this FSHoma patient.

Uchida, Sayaka; Uchida, Hiroshi; Maruyama, Tetsuo; Kajitani, Takashi; Oda, Hideyuki; Miyazaki, Kaoru; Kagami, Maki; Yoshimura, Yasunori



A Naturally Occurring Basically Charged Human Follicle-Stimulating Hormone (FSH) Variant Inhibits FSH-Induced Androgen Aromatization and Tissue-Type Plasminogen Activator Enzyme Activity in vitro  

Microsoft Academic Search

It is well known that deglycosylation of gonadotropins by enzymatic or chemical procedures or by deletion of sites for N-linked glycosylation produces antagonistic analogs which are able to interact strongly with the receptor and to inhibit binding of the wild-type hormone. In the present study, we analyzed the antagonistic properties of a naturally occurring basic follicle-stimulating hormone (FSH) charge isoform

Carlos M. Timossi; Jorgelina Barrios de Tomasi; Elena Zambrano; Roberto González; Alfredo Ulloa-Aguirre



IGF-I Signaling Is Essential for FSH Stimulation of AKT and Steroidogenic Genes in Granulosa Cells  

PubMed Central

FSH and IGF-I synergistically stimulate gonadal steroid production; conversely, silencing the FSH or the IGF-I genes leads to infertility and hypogonadism. To determine the molecular link between these hormones, we examined the signaling cross talk downstream of their receptors. In human and rodent granulosa cells (GCs), IGF-I potentiated the stimulatory effects of FSH and cAMP on the expression of steroidogenic genes. In contrast, inhibition of IGF-I receptor (IGF-IR) activity or expression using pharmacological, genetic, or biochemical approaches prevented the FSH- and cAMP-induced expression of steroidogenic genes and estradiol production. In vivo experiments demonstrated that IGF-IR inactivation reduces the stimulation of steroidogenic genes and follicle growth by gonadotropins. FSH or IGF-I alone stimulated protein kinase B (PKB), which is also known as AKT and in combination synergistically increased AKT phosphorylation. Remarkably, blocking IGF-IR expression or activity decreased AKT basal activity and abolished AKT activation by FSH. In GCs lacking IGF-IR activity, FSH stimulation of Cyp19 expression was rescued by overexpression of constitutively active AKT. Our findings demonstrate, for the first time, that in human, mouse, and rat GCs, the well-known stimulatory effect of FSH on Cyp19 and AKT depends on IGF-I and on the expression and activation of the IGF-IR.

Zhou, Ping; Baumgarten, Sarah C.; Wu, Yanguang; Bennett, Jill; Winston, Nicola; Hirshfeld-Cytron, Jennifer



Neonatal androgenization of hypogonadal (hpg) male mice does not abolish estradiol-induced FSH production and spermatogenesis  

Microsoft Academic Search

BACKGROUND: Testicular development is arrested in the hypogonadal (hpg) mouse due to a congenital deficiency in hypothalamic gonadotropin-releasing hormone (GnRH) synthesis. Chronic treatment of male hpg mice with estradiol induces FSH synthesis and secretion, and causes testicular maturation and qualitatively normal spermatogenesis. As estradiol negative feedback normally inhibits FSH production in the male, this study tested whether this paradoxical response

Margaret O Nwagwu; Helen Baines; Jeffrey B Kerr; Francis JP Ebling



Repeated superovulation using a simplified FSH\\/eCG treatment for in vivo embryo production in sheep  

Microsoft Academic Search

This study investigated the efficacy of a simplified repeated superovulation treatment (eCG plus FSH in a single dose, rather than the usual protocol of six decreasing doses of FSH) in the in vivo embryo production in Ojalada donor ewes during the breeding season. In vitro viability after vitrification and warming of embryos recovered from both treatments was also assessed. In

F. Forcada; M. Ait Amer-Meziane; J. A. Abecia; M. C. Maurel; J. A. Cebrián-Pérez; T. Muiño-Blanco; B. Asenjo; M. I. Vázquez; A. Casao



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.

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



Effects of hyper- and hypothyroidism on serum LH and FSH levels in intact and gonadectomized male and female rats.  


The effects of hypo- and hyper-thyroidism on serum LH and FSH were determined in both intact and castrated male and female rats. Thyro-parathyroidectomy (Tx) for 30 days in rats with intact gonads resulted in a significant reduction in serum LH and FSH, and also in a decrease in serum testosterone in males. Administration of 2.5 mug thyroxine (T4)/100 g BW to Tx rats of both sexes returned serum LH and FSH levels to those of intact rats, and in males also restored normal serum testosterone levels. Tx superimposed upon castration resulted in a significantly greater increase in serum LH and FSH than produced by castration alone. Administration of 2.5 mug T4/100 g body weight to castrate-Tx rats reduced serum LH and FSH values to those of castrate rats, whereas 10 mug T4/100 g BW evoked a further decrease in serum LH but no additional reduction in serum FSH. When both 2.5 mug T4/100 g BW and 2 mug estradiol benzoate were injected into Tx-ovariectomized rats, the decrease in serum LH and FSH was much greater than produced by T4 alone. These observations indicate that hypothyroidism results in decreased release of LH and FSH in rats with intact gonads, and in increased release of LH and FSH in castrate rats of both sexes. Administration of a replacement dose of T4 can restore LH and FSH release to normal in Tx rats with intact gonads, and to castration levels in Tx-castrate rats. PMID:1175507

Bruni, J F; Marshall, S; Dibbet, J A; Meites, J



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.

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




Microsoft Academic Search

Summary Plasma prolactin (PRL), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured by radioimmunoassay in groups of eight gilts sampled every 20 min for 6 h at about 2-wk intervals between 15 and 192 d of age. The PRL levels were high at 15 and 28 d, declined at 40 d just after weaning and then rose slowly

S. Camous; A. Prunier; J. Pelletier


Plasma estradiol,fsh and lh concentration after dominant follicle aspiration in the cow  

Microsoft Academic Search

This work investigates the estrogenic role of the dominant follicle with regard to regulation of plasma FSH and LH concentration. Eight Holstein-Friesian cows were used for aspiration of the dominant follicle using ultrasound guidance during the early, mid and late stages of the luteal phase. Blood samples were collected at 15-min intervals from 4 h before until 7 h after

G. S. Amiridis; L. Robertson; S. Reid; J. S. Boyd; P. J. O'Shaughnessy; I. A. Jeffcoate



Stress inhibits seasonal and FSH-induced ovarian recrudescence in the lizard,Mabuya carinata.  


Stressors (handling, chasing, and noise) applied randomly five times per day for one month to lizards during the recrudescence phase of the ovarian cycle caused a significant reduction in mean number of oocytes and primordial follicles when compared to those of controls. Further, vitellogenic follicles were absent in the ovary of lizards subjected to stressors. Administration of bovine FSH during post-breeding regression phase of the ovarian cycle induced ovarian recrudescence as shown by significant increases in the mean number of oogonia, oocytes, and primordial follicles compared to controls, as well as vitellogenic growth of follicles. However, lizards treated with FSH and exposed to stressors did not exhibit ovarian recrudescence. Furthermore, FSH administration during the post-breeding regression phase caused a significant increase in serum levels of estradiol compared to controls, which was accompanied by significant increases in the relative weight of the liver and oviduct, as well as vitellogenic growth of follicles. Despite administration of FSH to lizards subjected to stressors, there was neither any increase in serum levels of estradiol and weight of the liver nor vitellogenic growth of follicles. The results indicate that repeated application of stressors inhibits vitellogenic growth of follicles by suppression of steroidogenic activity in M. carinata. This is the first report revealing that the ovary does not respond to gonadotrophin treatment under stressful conditions in reptiles. PMID:12115929

Ganesh, C B; Yajurvedi, H N



Expression of endothelial nitric oxide synthase gene in cultured porcine granulosa cells after FSH stimulation  

Microsoft Academic Search

The present study was designed to investigate nitric oxide (NO) synthesis and the expression of endothelial NO synthase (eNOS) gene in cultured porcine granulosa cells. Granulosa cells prepared from small follicles (1-4 mm diameter) were cultured in plastic dishes coated with fibronectin in chemically defined medium, and matured after 48 h of stimulation with FSH. The concentrations of nitrite and

K Takesue; M-A Hattori; N Nishida; Y Kato; N Fujihara



Endogenous LH Surge Versus hCG as Ovulation Trigger After Low-Dose Highly Purified FSH in IUI: A Comparison of 761 Cycles  

Microsoft Academic Search

Purpose: The results obtained with a protocol consisting of ovarian stimulation with low doses of highly purified FSH (FSH HP), administration of a GnRH analogue to induce an endogenous surge of gonadotropins, and IUI were evaluated. These results were compared with those seen with similar FSH stimulation and hCG administration followed by IUI.

A. Romeu; A. Monzó; T. Peiró; E. Diez; J. A. Peinado; L. A. Quintero



Phosphoinositide 3-kinase p110? mediates estrogen- and FSH-stimulated ovarian follicle growth.  


In the mammalian ovary, primordial follicles are generated early in life and remain dormant for prolonged periods. Their growth resumes via primordial follicle activation, and they continue to grow until the preovulatory stage under the regulation of hormones and growth factors, such as estrogen, FSH, and IGF-1. Both FSH and IGF-1 activate the phosphatidylinositol-3 kinase (PI3K)/Akt (acute transforming retrovirus thymoma protein kinase) signaling pathway in granulosa cells (GCs), yet it remains inconclusive whether the PI3K pathway is crucial for follicle growth. In this study, we investigated the p110? isoform (encoded by the Pik3cd gene) of PI3K catalytic subunit expression in the mouse ovary and its function in fertility. Pik3cd-null females were subfertile, exhibited fewer growing follicles and more atretic antral follicles in the ovary, and responded poorly to exogenous gonadotropins compared with controls. Ovary transplantation showed that Pik3cd-null ovaries responded poorly to FSH stimulation in vitro; this confirmed that the follicle growth defect was intrinsically ovarian. In addition, estradiol (E2)-stimulated follicle growth and GC proliferation in preantral follicles was impaired in Pik3cd-null ovaries. FSH and E2 substantially activated the PI3K/Akt pathway in GCs of control mice but not in those of Pik3cd-null mice. However, primordial follicle activation and oocyte meiotic maturation were not affected by Pik3cd knockout. Taken together, our findings indicate that the p110? isoform of the PI3K catalytic subunit is a key component of the PI3K pathway for both FSH and E2-stimulated follicle growth in ovarian GCs; however, it is not required for primordial follicle activation and oocyte development. PMID:23820902

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



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.



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


Studies were conducted to characterize the chicken (c) FSH receptor (R) cDNA, and to evaluate expression of cFSH-R mRNA in the hen ovary at known stages during follicle development. A total of 2.5 kb of nucleic acid sequence including the complete cFSH-R coding region was isolated by a combination of the reverse-transcription polymerase chain reaction and 5'- and 3'-rapid amplification of cDNA ends techniques. Overall, the nucleic acid sequence homology of the cFSH-R cDNA coding region is 71.8% and 72.2% compared to the rat and bovine FSH-R, respectively, while the deduced amino acid sequence identity for the receptor protein (693 amino acids) is 71.9% and 72.4%, respectively. By comparison, the cFSH-R nucleic acid and amino acid sequences are 60.1% and 49.4% identical to the respective cLH-R sequences. Northern blot analysis detected a single 4.3-kb cFSH-R mRNA transcript, which was selectively expressed in ovarian (granulosa, theca, and stromal) tissues, but not the oviduct, adrenal, liver, muscle, or brain. As the follicle developed from the prehierarchical (6- to 8-mm diameter) to the largest preovulatory (F1 follicle) stage, cFSH-R mRNA levels progressively declined within both the granulosa and theca layers (p < 0.05). Moreover, cFSH-R mRNA levels were lower in whole atretic than in morphologically normal 3- to 5-mm follicles (p = 0.0015). The pattern of cFSH-R mRNA expression within the granulosa layer during follicle development was notably different from that of the recently reported cLH-R, in that cLH-R mRNA levels increase to become readily detectable coincident with dramatically increased steroidogenic capacity during the last few days before ovulation of the follicle. On the other hand, highest levels of cFSH-R mRNA in 6- to 8-mm (prehierarchical) follicles were consistent with a role for the cFSH-R in maintaining the viability of prehierarchical follicles and in initiating granulosa cell differentiation at the time when follicles are selected into the preovulatory hierarchy. PMID:8902217

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



Serum FSH Levels in Coasting Programmes on the hCG Day and Their Clinical Outcomes in IVF ? ICSI Cycles  

PubMed Central

Introduction. Coasting is the most commonly used strategy in prevention of severe OHSS. Serum FSH levels measurements during coasting may aid in optimizing the duration of coasting. Objective(s). To study live birth rates (LBRs), clinical pregnancy rates (CPRs), and optimal duration of coasting based on serum FSH levels on the hCG day. Materials and Methods. It is a retrospective study performed between 2005 and 2008 at Barts and The London Centre for Reproductive Medicine, NHS Trust, London, UK, on 349-coasted women undergoing controlled ovarian stimulation (COS) for IVF ± ICSI. The serum FSH level measurements on the hCG day during coasting programme were analysed to predict the LBR and CPR. Result(s). LBR and CPR were significantly higher when the FSH levels on the hCG day were >2.5?IU/L (LBR: 32.5%, P = 0.045 and CPR: 36.9%, P = 0.027) compared to FSH <2.5?IU/L. The optimal FSH cut-off level for LBR and CPR is 5.6?IU/L on the hCG day. The optimal cutoff for coasting is 4 days. Conclusion(s). Coasting may be continued as long as either serum FSH level is > 2.5?IU/L on the hCG day without compromising the LBR and CPR or to maximum of 4 days.

Vitthala, Srisailesh; Bouaziz, Jerome; Tozer, Amanda; Zosmer, Ariel; Al-Shawaf, Talha



Increased basal and pulsatile secretion of FSH and LH in young men with 47,XXY or 46,XX karyotypes  

PubMed Central

Objective The regulation of normal sexual maturation and reproductive function is dependent on a precise hormonal regulation at hypothalamic, pituitary, and gonadal levels. The aim of this study was to investigate the neuroendocrine integrity of the pituitary-gonadal axis in patients with primary testicular failure due to supernumerary X chromosomes. Design Cross-sectional study. Methods In this study, 7 untreated patients with primary gonadal insufficiency due to SRY-positive 46,XX (n=4) and 46,XXY karyotypes (n=3) aged 18.8 years and 25 age-matched healthy controls participated. Reproductive hormones, testicular size, and overnight LH and FSH serum profiles and overnight urine LH and FSH excretion were determined. Results Basal LH and FSH secretion was elevated 6.3- and 25.4-fold respectively in the patients and the amount of LH and FSH secreted per burst were 2.0- and 6.6-fold elevated. We found significantly more LH but not FSH peaks per 24 h, as estimated by the Weibull ? analysis. There was no difference between approximate entropy ratios or Weibull ? analyses indicating comparable orderliness and regularity of LH and FSH secretion. Overnight urinary LH and FSH excretion was significantly elevated in patients compared with controls and correlated significantly with calculated total overnight LH and FSH secretion respectively, thus validating deconvolution. Conclusion In this group of patients with severe hypergonadotropic hypogonadism due to a supernumerary X chromosome, higher basal, pulsatile, and total LH and FSH secretion were associated with significantly more LH peaks per 24 h in comparison with healthy controls. Thus, our data indicate that in patients with Klinefelter syndrome and XX male karyotypes the entire hypothalamic-pituitary-gonadal axis has undergone functional changes.

Aksglaede, Lise; Jensen, Rikke Beck; Carlsen, Elisabeth; Kok, Petra; Keenan, Daniel M; Veldhuis, Johannes; Skakkebaek, Niels E; Juul, Anders



Elucidation of the role of LH and FSH during neonatal testicular development and growth in the boar.  


The aim was to elucidate the role of LH and FSH in testicular development and growth in the neonatal boar. On Day 10 after birth (Day 0 of study), animals were assigned to one of nine groups (n=6): Group 1, control, no treatment; Group 2, hemicastrated (H); Group 3, H and implanted with GnRH agonist (H+GnRH); Group 4, H+GnRH+FSH 200?g/kg daily from Days 0 to 14 (D0-14); Group 5, H+GnRH+FSH 400?g/kg D0-14; Group 6, H+GnRH+FSH 400?g/kg in PVP D0-14; Group 7, H+GnRH+LH 200?g/kg D0-14; Group 8, H+GnRH+LH 400?g/kg D0-14; Group 9, H+GnRH+LH and FSH 200?g/kg D0-14. The right testis in control and hemicastrated boars was removed on Day 15. Hemicastrated boars had greater (P<0.05) testicular growth than control boars and testicular growth was prevented in boars treated with GnRH agonist. FSH induced Sertoli cell proliferation but not testicular growth whilst LH induced Leydig cell proliferation and testicular growth was similar to control boars but less than hemicastrated boars. LH+FSH induced similar testicular growth as LH alone and neither LH and/or FSH supported testicular hypertrophy in hemicastrated boars. The findings show conclusively for the first time that LH and FSH respectively induce Leydig cell and Sertoli cell proliferation in the neonatal boar. LH additionally supports a normal increase in testicular size in the neonatal boar. PMID:23276544

Wells, R; Kenny, A L; Duckett, R; Wreford, N G; Johnston, S D; D'Occhio, M J



Beta-endorphin disrupts seasonal and FSH-induced ovarian recrudescence in the lizard Mabuya carinata.  


Administration (ip) of an opioid peptide, beta-endorphin (beta-EP) (0.1, 0.5, or 1 microg beta-EP/day/lizard for 30 days) during seasonal recrudescence phase of the ovarian cycle inhibited ovarian recrudescence as shown by the absence of vitellogenic follicles in the ovary in contrast to their presence in treatment controls in the lizard Mabuya carinata. In the germinal bed, treatment of 0.1 microg beta-EP did not affect primordial follicles, whereas their mean number was significantly lower in lizards treated with 0.5 or 1 microg beta-EP compared to those of treatment controls. There was also suppression of oviductal development as shown by a significantly lower relative weight of the oviduct and regressed oviductal glands in lizards treated with all the dosages of beta-EP compared to treatment controls. In another experiment, administration of FSH (10 IU FSH/alternate day/lizard for 30 days) during the regression phase of the ovarian cycle induced development of vitellogenic follicles, whereas the treatment controls showed only previtellogenic follicles. In addition, there was a significant increase in the ovarian and oviductal weights compared to initial and treatment controls. However, simultaneous administration of similar dosage of FSH and beta-EP (0.5 microg/day/lizard) did not induce ovarian recrudescence as shown by the absence of vitellogenic follicles in the ovary and significantly lower weight of the ovary and the oviduct and the mean number of oogonia, oocytes, and primordial follicles compared to those of FSH-treated lizards. The results indicate that beta-EP inhibits seasonal as well as FSH-induced ovarian recrudescence. Inhibitory effect of beta-EP on follicular development despite FSH administration implies its effect at the ovarian level in M. carinata. While adversely affecting the ovarian follicular development, beta-EP did not affect the adrenal gland as there was no significant variation in the mean nuclear diameter of the adrenocortical cells of treatment controls and beta-EP-treated lizards. Furthermore, administration of beta-EP caused a significant decrease in the mean number of islands of white pulp of the spleen indicating its adverse effect on immunity. PMID:12957474

Ganesh, C B; Yajurvedi, H N



Prokaryotic ParA-ParB-parS system links bacterial chromosome segregation with the cell cycle.  


While the essential role of episomal par loci in plasmid DNA partitioning has long been appreciated, the function of chromosomally encoded par loci is less clear. The chromosomal parA-parB genes are conserved throughout the bacterial kingdom and encode proteins homologous to those of the plasmidic Type I active partitioning systems. The third conserved element, the centromere-like sequence called parS, occurs in several copies in the chromosome. Recent studies show that the ParA-ParB-parS system is a key player of a mitosis-like process ensuring proper intracellular localization of certain chromosomal regions such as oriC domain and their active and directed segregation. Moreover, the chromosomal par systems link chromosome segregation with initiation of DNA replication and the cell cycle. PMID:21924286

Mierzejewska, Jolanta; Jagura-Burdzy, Gra?yna



Transactivation of the PAR1-PAR2 Heterodimer by Thrombin Elicits ?-Arrestin-mediated Endosomal Signaling*  

PubMed Central

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.

Lin, Huilan; Trejo, JoAnn



Protease-activated receptor-3 (PAR3) regulates PAR1 signaling by receptor dimerization  

PubMed Central

Thrombin activates endothelial cell signaling by cleaving the protease-activated receptor-1 (PAR1). However, the function of the apparently nonsignaling receptor PAR3 also expressed in endothelial cells is unknown. We demonstrate here the crucial role of PAR3 in potentiating the responsiveness of PAR1 to thrombin. We tested the hypothesis that PAR1/PAR3 heterodimerization and its effect in modifying G protein selectivity was responsible for PAR3 regulation of PAR1 sensitivity. Using bioluminescent resonance energy transfer-2, we showed that PAR1 had comparable dimerization affinity for PAR3 as for itself. We observed increased G?13 coupling between the PAR1/3 heterodimer compared with the PAR1/1 homodimer. Moreover, knockdown of PAR3 moderated the PAR1-activated increase in endothelial permeability. These results demonstrate a role of PAR3 in allosterically regulating PAR1 signaling governing increased endothelial permeability. Because PAR3 is a critical determinant of PAR1 function, targeting of PAR3 may mitigate the effects of PAR1 in activating endothelial responses such as vascular inflammation.

McLaughlin, Joseph N.; Patterson, Myla M.; Malik, Asrar B.



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.



Expression of mRNA for the LH and FSH receptors in mouse oocytes and preimplantation embryos.  


The gonadotrophins LH and FSH are known to regulate gonadal growth, and differentiation, endocrine function and gametogenesis. The LH receptor is expressed in ovarian theca, granulosa and luteal cells, and in testicular Leydig cells. The FSH receptor is expressed only in ovarian granulosa cells and in testicular Sertoli cells. The expression of the FSH and LH receptors was analysed by RT-PCR to study the role of these receptors in early mouse development. After reverse transcription, strategically designed nested primers were used for amplification from cDNA. Transcripts for the receptors were present in mouse oocytes and preimplantation embryos. The presence of mRNA for FSH and LH receptors in oocytes, zygotes and preimplantation embryos indicates a potential role for the gonadotrophins in the modulation of meiotic resumption and completion of oocyte maturation, as well as a beneficial effect on early embryonic development in mice. PMID:11226072

Patsoula, E; Loutradis, D; Drakakis, P; Kallianidis, K; Bletsa, R; Michalas, S



Evaluation of two oestrus synchronization regimens in eFSH-treated donor mares  

Microsoft Academic Search

Reliable methods for regulating oestrus and superovulation in equine embryo transfer (ET) programs are desirable. The objective in this study was to compare two oestrus synchronization methods combined with equine follicle-stimulating hormone (eFSH) treatment in an ET program. In the progesterone and estradiol-17? (P&E) group, mares (n=12) were given progesterone and estradiol-17?, daily for 10days, followed by prostaglandin (PG)F2? on

Tal Raz; Sylvia D. Carley; Jodyne M. Green; Claire E. Card



The relationship between plasma leptin and FSH concentrations with ovulation rate in Iranian native sheep.  


The aim of this study was to determine the relationship between plasma leptin and FSH concentration in Iranian sheep. Forty female Mehraban and Sanjabi sheep were used. All ewes were cyclic and synchronized with cloprestenol. The ewes were divided into two breed groups: Mehraban breed (n = 20) and Sanjabi breed (n = 20), feeding at maintenance level. On the first and second days of estrus cycle, blood samples were collected from the jugular vein. Ovulation number was determined by endoscopy 7 days after the second injection. Mean Plasma leptin concentrations on second day (4.74 +/- 0.15 and 4.68 +/- 0.10 ng mL(-1)) were significantly higher than those on first day (2.64 +/- 0.11 and 2.56 +/- 0.04 ng mL(-1)) for Mehraban and Sanjabi sheep, respectively (p<0.01). Mean plasma FSH concentrations on second day (2.75 +/- 0.17 and 2.74 +/- 0.15 ng mL(-1)) were also significantly greater than those on first day (1.19 +/- 0.05 and 1.19 +/- 0.04 ng mL(-1)) for Mehraban and Sanjabi ewes, respectively (p<0.01). In the present study, positive relationship has been shown between plasma Leptin and FSH concentrations (p<0.01) in Mehraban and Sanjabi sheep. Ovulation rate had a significant difference between Mehraban (1.20 +/- 0.33) and Sanjabi (1.07 +/- 0.1) ewes. Significant differences were not observed between concentrations of FSH and leptin with ovulation rate in both breeds (p < or = 0.01). PMID:19070042

Towhidi, A; Masoumi, R; Moeini, M M; Solgi, H; Moravej, H



In vivo oocyte recovery and in vitro embryo production from bovine oocyte donors treated with progestagen, oestradiol and FSH  

Microsoft Academic Search

The effect of treatment of donor cattle with progestagen and oestradiol or FSH on in vivo oocyte recovery and in vitro embryo production was studied. Forty-eight beef×Friesian cows formed eight replicates of six treatments in a 2 (no steroid versus steroid)×3 (none, single or multiple dose(s) of FSH) factorial design in which follicles were aspirated once weekly for 3 weeks.

K. L Goodhand; M. E Staines; J. S. M Hutchinson; P. J Broadbent



Effect of Serotoninergic System on FSH Secretion in Male and Female Rats: Evidence for Stimulatory and Inhibitory Actions  

Microsoft Academic Search

The present experiments were designed to assess the effect of the serotoninergic system on FSH secretion in prepubertal (16-, 18-, 20-, 26- and 30-day-old) and adult (60-day-old) male and female rats. The intraperitoneal administration of 5-hydroxytryptophan (5-HTP), a serotonin (5-HT) precursor, induced a significant increase of FSH levels in male rats at 16, 26, 30 and 60 days of age

Sergio N. Justo; Graciela L. Rossano; Berta Szwarcfarb; Modesto C. Rubio; Jaime A. Moguilevsky



Differential gene expression in human granulosa cells from recombinant FSH versus human menopausal gonadotropin ovarian stimulation protocols  

Microsoft Academic Search

BACKGROUND: The study was designed to test the hypothesis that granulosa cell (GC) gene expression response differs between recombinant FSH and human menopausal gonadotropin (hMG) stimulation regimens. METHODS: Females < 35 years-old undergoing IVF for tubal or male factor infertility were prospectively randomized to one of two stimulation protocols, GnRH agonist long protocol plus individualized dosages of (1) recombinant (r)FSH

John Brannian; Kathleen Eyster; Breanne A Mueller; Mandi G Bietz; Keith Hansen



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

Microsoft Academic Search

The economic implications of the choice of gonadotrophin influence decision making but their cost-effectiveness in frozen-embryo transfer cycles has not been adequately studied. An economic evaluation was performed comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) using individual patient data (n=986) from two large randomized controlled trials using a long agonist IVF protocol. The simulation model incorporated

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



Serum levels of LH, FSH, estradiol and progesterone in female rats experimentally infected by Trypanosoma evansi.  


The goal of this study was to evaluate reproductive hormones in sera samples of female rats experimentally infected by Trypanosoma evansi during different phases of the estrous cycle. For that, 64 animals were divided into two groups: 24 rats for the control group (uninfected), and 40 animals were infected by T. evansi. These groups were divided into subgroups according to the time of infection (days 5 and 15 post-infection; PI) and the phase of the estrous cycle (proestrus, estrus, metestrus and diestrus). Serum was collected at days 5 and 15 PI and the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), progesterone and estradiol were assessed by enzyme immunoassay technique. The concentration of nitrite/nitrate (NOx), advanced oxidation protein products (AOPP), and thiobarbituric acid reactive substances (TBARS) were measured in ovaries and uteruses in these same periods. Infected females showed significant decrease (P<0.05) of LH, FSH, estradiol and progesterone in different periods and phases of the estrous cycle when compared to uninfected rats. In addition, it was observed an increase in the concentration of NOx, AOPP, and TBARS in the ovaries, which is indicative of cell damage. Therefore, our experimental study showed that T. evansi infection in female rats may cause changes in LH, FSH, estradiol, and progesterone levels regardless of the time of infection or phase of the estrous cycle. PMID:23816642

Faccio, Luciana; Da Silva, Aleksandro S; Tonin, Alexandre A; França, Raqueli T; Gressler, Lucas T; Copetti, Maíra M; Oliveira, Camila B; Sangoi, Manuela B; Moresco, Rafael N; Bottari, Nathieli B; Duarte, Marta M M F; Monteiro, Silvia G



Predicting the FSH threshold dose in women with WHO Group II anovulatory infertility failing to ovulate or conceive on clomiphene citrate  

PubMed Central

BACKGROUND The objective of this investigation was to establish independent predictors of follicle-stimulating hormone (FSH) threshold dose in anovulatory women undergoing ovulation induction with FSH preparations. METHODS One hundred and fifty-one patients with WHO Group II anovulatory infertility failing to ovulate or conceive on clomiphene citrate underwent ovarian stimulation with FSH-only preparations following a low-dose step-up protocol. The individual FSH threshold dose was defined as the FSH dose when meeting the human chorionic gonadotrophin criteria (one follicle ?17 mm, or 2–3 follicles ?15 mm). The influence of demographics, physical characteristics, obstetric and infertility and menstrual cycle history, ovarian ultrasonography, endocrine parameters and type of gonadotrophin preparation on the FSH threshold dose was assessed through multiple regression analysis. RESULTS In the univariate analysis, age, body mass index (BMI), failure to ovulate with clomiphene citrate, menstrual cycle history (amenorrhea, oligomenorrhea or anovulatory cycles of 21–35 days), mean ovarian volume, LH/FSH ratio, testosterone and free androgen index were significant (P < 0.05) predictors of FSH threshold dose. In the multivariate analysis, menstrual cycle history, mean ovarian volume and BMI remained significant (P < 0.001). CONCLUSIONS The individual FSH threshold dose for ovulation induction in anovulatory women can be predicted based on three variables easily determined in clinical practice: menstrual cycle history, mean ovarian volume and BMI. A FSH dosage nomogram was constructed based on these parameters.

Nyboe Andersen, Anders; Balen, Adam; Platteau, Peter; Devroey, Paul; Helmgaard, Lisbeth; Arce, Joan-Carles



Genetically Determined Dosage of Follicle-Stimulating Hormone (FSH) Affects Male Reproductive Parameters  

PubMed Central

Context: The detailed role of FSH in contributing to male testicular function and fertility has been debated. We have previously identified the association between the T-allele of the FSHB promoter polymorphism (rs10835638; G/T, ?211 bp from the mRNA start) and significantly reduced male serum FSH. Objective: In the current study, the T-allele carriers of the FSHB ?211 G/T single nucleotide polymorphism represented a natural model for documenting downstream phenotypic consequences of insufficient FSH action. Design and Subjects: We genotyped rs10835638 in the population-based Baltic cohort of young men (n = 1054; GG carriers, n = 796; GT carriers, n = 244; TT carriers, n = 14) recruited by Andrology Centres in Tartu, Estonia; Riga, Latvia; and Kaunas, Lithuania. Marker-trait association testing was performed using linear regression (additive, recessive models) adjusted by age, body mass index, smoking, and recruitment center. Results: Serum hormones directly correlated with the T-allele dosage of rs10835638 included FSH (additive model, P = 1.11 × 10?6; T-allele effect, ?0.41 IU/liter), inhibin-B (P = 2.16 × 10?3; T-allele effect, ?14.67 pg/ml), and total testosterone (P = 9.30 × 10?3; T-allele effect, ?1.46 nmol/liter). Parameters altered only among TT homozygotes were reduced testicular volume (recessive model, P = 1.19 × 10?4; TT genotype effect, ?9.47 ml) and increased serum LH (P = 2.25 × 10?2; TT genotype effect, 1.07 IU/liter). The carrier status of rs10835638 alternative genotypes did not affect sperm motility and morphology, calculated free testosterone, serum SHBG, and estradiol concentrations. Conclusion: We showed for the first time that genetically determined low FSH may have wider downstream effects on the male reproductive system, including impaired testes development, altered testicular hormone levels (inhibin-B, total testosterone, LH), and affected male reproductive potential.

Grigorova, Marina; Punab, Margus; Zilaitiene, Birute; Erenpreiss, Juris; Ausmees, Kristo; Matulevicius, Valentinas; Tsarev, Igor; J?rgensen, Niels



Correlation between testicular sperm extraction outcomes and clinical, endocrine and testicular histology parameters in 120 azoospermic men with normal serum FSH levels.  


We retrospectively evaluated the clinical and hormonal profiles, sperm extraction outcomes and testicular histology parameters in 120 azoospermic men with normal serum follicle-stimulating hormone (FSH) level. Microsurgical epididymal sperm aspiration (MESA) and testicular sperm extraction (TESE) were performed in 33 and 87 cases, respectively. Sperm were successfully retrieved in all the MESA procedures and in 65 of the TESE procedures. The mean serum FSH and inhibin B levels and the testicular volume differed significantly according to whether or not sperm were retrieved. The threshold serum inhibin B value for predicting successful TESE was 123.5pg/mL (sensitivity: 69.7%; specificity: 66.7%). The 13 patients with Sertoli cell only syndrome (SCOS) had a higher mean serum FSH level and a lower mean serum inhibin B level than the other phenotypes. TESE was negative for 11 of the 13 SCOS men. The mean±SD inhibin B level was significantly lower in patients with 5-10IU/L of FSH than those with 2-5IU/L of FSH (108.30±53.86 vs. 175.23±70.17pg/mL, respectively). The sperm retrieval rates were 71.42% for the group with 5-10IU/L of FSH and 87.32% for the group with 2-5IU/L of FSH. Ten of the 13 SCOS men had a FSH level between 5 and 10IU/L. The clinical pregnancy rate was significantly lower (p=0.04) in the group with 5-10IU/L (50%) of FSH than in the group with 2-5IU/L (77.5%) of FSH. In conclusion, there is no FSH value below which spermatogenesis is always found. Inhibin B assays and clinical assessments are thus of particular value in men with normal serum FSH levels. PMID:20695924

Mitchell, V; Robin, G; Boitrelle, F; Massart, P; Marchetti, C; Marcelli, F; Rigot, J-M



Growth Differentiation Factor 9 (GDF9) Forms an Incoherent Feed-forward Loop Modulating Follicle-stimulating Hormone ?-Subunit (FSH?) Gene Expression.  


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



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


Follicle-stimulating hormone has been widely used to induce superovulation in buffaloes and cows and usually triggers functional and morphologic alterations in the corpus luteum (CL). Several studies have shown that FSH is involved in regulating vascular development and that adequate angiogenesis is essential for normal luteal development. Angiogenesis is regulated by many growth factors, of which vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) have an established central role. Therefore, we have used a combination of in vitro and in vivo studies to assess the effects of FSH on the expression of VEGF and FGF2 and their receptors in buffalo luteal cells. The in vivo model consisted of 12 buffalo cows, divided into control (n = 6) and superovulated (n = 6) groups, and CL samples were collected on day 6 after ovulation. In this model, we analyzed the gene and protein expression of FGF2 and its receptors and the protein expression of VEGFA systems with the use of real-time PCR, Western blot analysis, and immunohistochemistry. In the in vitro model, granulosa cells were collected from small follicles (diameter, 4-6 mm) of buffaloes and cultured for 4 d in serum-free medium with or without FSH (10 ng/mL). To induce in vitro luteinization, LH (250 ng/mL) and fetal bovine serum (10%) were added to the medium, and granulosa cells were maintained in culture for 4 d more. The progesterone concentration in the medium was measured at days 4, 5, and 8 after the beginning of cell culture. Cells were collected at day 8 and subjected to real-time PCR, Western blot analysis, and immunofluorescence for assessment of the expression of FGF2, VEGF, and their receptors. To address the percentage of steroidogenic and growth factor-expressing cells in the culture, flow cytometry was performed. We observed that in superovulated buffalo CL, the FGF2 system mRNA expression was decreased even as protein expression was increased and that the VEGF protein was increased (P < 0.05). In vitro experiments with granulosa cells showed an increase in the mRNA expression of VEGF and FGF2 and its receptors 1 and 2 and protein expression of VEGF, kinase insert domain receptor, FGF receptor 2, and FGF receptor 3 in cells treated with FSH (P < 0.05), in contrast to the in vivo experiments. Moreover, the progesterone production by FSH-treated cells was elevated compared with untreated cells (P < 0.05). Our findings indicate that VEGF, FGF2, and their receptors were differentially regulated by FSH in vitro and in vivo in buffalo luteal cells, which points toward a role of CL environment in modulating cellular answers to gonadotropins. PMID:24209507

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



Evaluation of two oestrus synchronization regimens in eFSH-treated donor mares.  


Reliable methods for regulating oestrus and superovulation in equine embryo transfer (ET) programs are desirable. The objective in this study was to compare two oestrus synchronization methods combined with equine follicle-stimulating hormone (eFSH) treatment in an ET program. In the progesterone and estradiol-17? (P&E) group, mares (n=12) were given progesterone and estradiol-17?, daily for 10 days, followed by prostaglandin (PG)F(2?) on the last day. In the PG group, mares (n=12) were given PGF(2?) 5 days post-ovulation. In both groups donor mares were allocated to eFSH therapy, and were subsequently bred. Embryo recovery and transfer were performed routinely. The interval to ovulation (mean ± SEM, range) was not statistically different between donor mares in the P&E group (10.2±0.3, 9-12 days) and donor mares in the PG group (8.7±0.7, 4-12 days). Among donor mares, the synchrony of ovulations was higher following the P&E regimen (P<0.05); however, there was a tendency (P<0.06) for fewer ovulations than in the PG group (1.5±0.3 vs. 2.5±0.4 ovulations, respectively). Embryo recovery (0.9±0.3 vs. 1.4±0.3 embryo/recovery) and recipient pregnancy rate per transferred embryo (4/9, 44% vs. 4/15, 27%) were similar. It was concluded that the P&E regimen was more reliable for synchronization of oestrus in eFSH-treated mares but the fewer ovulations may curtail any advantage of this regimen. PMID:20392656

Raz, Tal; Carley, Sylvia D; Green, Jodyne M; Card, Claire E



Pharmacological Estrogen Administration Causes a FSH-Independent Osteo-Anabolic Effect Requiring ER Alpha in Osteoblasts  

PubMed Central

Postmenopausal osteoporosis is characterized by declining estrogen levels, and estrogen replacement therapy has been proven beneficial for preventing bone loss in affected women. While the physiological functions of estrogen in bone, primarily the inhibition of bone resorption, have been studied extensively, the effects of pharmacological estrogen administration are still poorly characterized. Since elevated levels of follicle-stimulating hormone (FSH) have been suggested to be involved in postmenopausal bone loss, we investigated whether the skeletal response to pharmacological estrogen administration is mediated in a FSH-dependent manner. Therefore, we treated wildtype and FSH?-deficicent (Fshb?/?) mice with estrogen for 4 weeks and subsequently analyzed their skeletal phenotype. Here we observed that estrogen treatment resulted in a significant increase of trabecular and cortical bone mass in both, wildtype and Fshb?/? mice. Unexpectedly, this FSH-independent pharmacological effect of estrogen was not caused by influencing bone resorption, but primarily by increasing bone formation. To understand the cellular and molecular nature of this osteo-anabolic effect we next administered estrogen to mouse models carrying cell specific mutant alleles of the estrogen receptor alpha (ER?). Here we found that the response to pharmacological estrogen administration was not affected by ER? inactivation in osteoclasts, while it was blunted in mice lacking the ER? in osteoblasts or in mice carrying a mutant ER? incapable of DNA binding. Taken together, our findings reveal a previously unknown osteo-anabolic effect of pharmacological estrogen administration, which is independent of FSH and requires DNA-binding of ER? in osteoblasts.

Jeschke, Anke; Marshall, Robert P.; Stride, Brenda D.; Wintermantel, Tim; Beil, Frank T.; Amling, Michael; Schutz, Gunther; Tuckermann, Jan; Schinke, Thorsten



Dysregulation of ovarian follicular development in female rat: LH decreases FSH sensitivity during preantral-early antral transition.  


Several clinical studies have shown a correlation of hypersecretion of LH and polycystic ovary syndrome (PCOS), infertility, and miscarriage in women, suggesting that chronically elevated LH impairs fertility. Growth arrest of small antral follicles in PCOS is also assumed to be associated with an abnormal endocrine environment involving increased LH stimulation, a hyperandrogenic milieu, and subsequent dysregulated FSH action in the ovarian follicles. In this study, we examined whether and how LH modulates follicular development and steroid production during preantral-early antral follicle transition by using a rat preantral follicle culture system. LH augments testosterone and estradiol production in preantral follicles via up-regulating mRNA abundance of CYP17A1 and CYP19A1. LH promotes rat preantral follicle growth, and the follicular size reaches that of early antral follicles in vitro, a response attenuated by the specific androgen receptor antagonist and a targeted disruption of androgen receptor gene. Sustained follicle stimulation by LH, but not by androgen, decreases FSH receptor mRNA levels and FSH receptor signaling and inhibits FSH-induced follicular growth. The data suggest that LH promotes preantral-early antral transition via the increased synthesis and growth-promoting action of androgen. However, chronic LH stimulation impairs FSH-dependent antral follicle growth by suppressing granulosa cell FSHR expression via the modulation of intraovarian regulators, including LH-induced thecal factors. PMID:23709086

Orisaka, Makoto; Hattori, Katsushige; Fukuda, Shin; Mizutani, Tetsuya; Miyamoto, Kaoru; Sato, Takashi; Tsang, Benjamin K; Kotsuji, Fumikazu; Yoshida, Yoshio



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.



Effects of FSH on the expression of receptors for oocyte-secreted factors and members of the EGF-like family during in vitro maturation in cattle.  


FSH induces expansion of bovine cumulus-oocyte complexes (COCs) in cattle, which can be enhanced by oocyte-secreted factors (OSFs). In this study it was hypothesised that FSH stimulates COC expansion in part from direct stimulation of the epidermal growth factor (EGF)-like ligands amphiregulin (AREG), epiregulin (EREG) and betacellulin (BTC), but also in part through regulation of OSFs or their receptors in cumulus cells. Bovine COCs were cultured in defined medium with graded doses of FSH. In the absence of FSH, COCs did not expand. FSH caused cumulus expansion, and increased the abundance of AREG and EREG mRNA in a time- and dose-dependent manner, but decreased BTC mRNA levels. FSH had modest stimulatory effects on the levels of mRNA encoding the bone morphogenetic protein 15 (BMP15) receptor, BMPR1B, in cumulus cells, but did not alter mRNA expression of the growth and differentiation factor 9 (GDF9) receptor, TGFBR1. More interestingly, FSH dramatically stimulated levels of mRNA encoding two receptors for fibroblast growth factors (FGF), FGFR2C and FGFR3C, in cumulus cells. FSH also stimulated mRNA expression of FGFR1B, but not of FGFR2B in cumulus cells. Based on dose-response studies, FGFR3C was the receptor most sensitive to the influence of FSH. This study demonstrates that FSH stimulates the expression of EGF-like factors in bovine cumulus cells, and provides evidence that FSH differently regulates the expression of distinct receptors for OSFs in cumulus cells. PMID:23021259

Caixeta, Ester Siqueira; Machado, Mariana Fernandes; Ripamonte, Paula; Price, Christopher; Buratini, José



Regulation of Par-4 by oncogenic Ras.  


Oncogenic Ras causes down-regulation of the proapoptotic tumor suppressor gene Par-4. Replenishment of the basal levels of Par-4 results in inhibition of Ras-inducible cellular transformation. Moreover, overexpression of Par-4 (twofold to fourfold over basal levels) results in apoptosis of cells expressing oncogenic Ras. Par-4 does not, on its own, induce apoptosis in immortalized or nontransformed cells. This chapter describes the key methods used for analysis of Par-4 down-regulation by oncogenic Ras, which can be extended to study most genes whose down-regulation by oncogenic Ras is critical for oncogenic transformation and cell survival. PMID:16757343

Vasudevan, Krishna Murthi; Ranganathan, Padhma; Rangnekar, Vivek M



Effect of the alpha subunit of equine LH on the FSH induced cAMP production in rat seminiferous tubule cells.  


Previous observations from our laboratory have shown that equine LH can suppress the FSH induced cyclic AMP production in rat seminiferous tubule cells in vitro. The present investigation was carried out to determine the effect of various subunits in this system. The ratios (w/w) of subunits to equine FSH tested was 1:3, 3:1 and 30:1 with a standard dose of 0.3 microgram of the FSH. It was noted that equine LH-beta was not effective up to a 10 microgram concentration in inhibiting the cyclic AMP production induced by equine FSH. Under these conditions, equine LH-alpha suppressed the FSH activity in a dose dependent manner. However, alpha subunits derived from several other species of LH were without any effect on FSH action. Histidine modified derivative of equine LH and its alpha subunit, both of which lack biological activity in the rat Leydig cell assay for LH, were found to be inactive as inhibitors of the equine FSH response. Thus, these results show that the suppressive effect of equine LH on FSH action in the rat seminiferous tubule is a function of the equine LH alpha subunit. PMID:6262061

Aggarwal, B B; Papkoff, H; Licht, P



Differences in clinical characteristics of fallopian canal dehiscence associated with pars flaccida and pars tensa cholesteatomas.  


This study investigated the difference in clinical characteristics of fallopian canal dehiscence associated with pars flaccida and pars tensa cholesteatomas for the purpose of increasing the preoperative detectability of dehiscence. A total of 189 ears of patients 7-80 years of age (mean 42 years) with pars flaccida cholesteatoma and 63 ears of patients 9-84 years of age (mean 50 years) with pars tensa cholesteatoma were studied. All patients had undergone prior surgical management at our institution from January 2006 to April 2012. The incidence of fallopian canal dehiscence and its location were compared between pars flaccida and pars tensa cholesteatomas. Intraoperative findings of coexistent pathologies, including destruction of the stapes superstructure, labyrinthine fistula, and dural exposure, were compared between the dehiscence and no-dehiscence groups for the two types of cholesteatomas. The incidence of dehiscence was significantly higher in patients with pars tensa cholesteatoma (55.6 %) than in patients with pars flaccida cholesteatoma (26.5 %). Dehiscence located posterior to the cochleariform process occurred slightly more frequently in patients with pars tensa cholesteatoma than in those with pars flaccida cholesteatoma. In patients with pars flaccida cholesteatoma, labyrinthine fistulas and dural exposure were significantly more frequent in the dehiscence group than in the no-dehiscence group. Fallopian canal dehiscence is more frequent in patients with pars tensa cholesteatoma than in those with pars flaccida cholesteatoma. Especially in patients with pars flaccida cholesteatoma, paying special attention to these coexisting pathologies is important to increase preoperative detectability of dehiscence. PMID:24071859

Shinnabe, Akihiro; Yamamoto, Hiroki; Hara, Mariko; Hasegawa, Masayo; Matsuzawa, Shingo; Kanazawa, Hiromi; Yoshida, Naohiro; Iino, Yukiko



Obtencion de anticuerpos anti-globulinas de conejo en carnero para su utilizacion en los radioinmunoanalisis de LH, FSH, y prolactina. (Production of anti-IgG antibodies in sheep for using in the radioimmunoassays of LH, FSH and prolactin).  

National Technical Information Service (NTIS)

In this work described the production of second antibodies in sheep against rabbit IgG for being used in radioimmunoassays for determination LH, FSH and Prolactin. There was made the comparison between the results obtained using the Kits-RIA produced by u...

R. Caso E. Perez M. Mosquera C. Arranz



Décontamination nucléaire par laser UV  

NASA Astrophysics Data System (ADS)

Le développement et l'utilisation de procédés propres pour le nettoyage ou la préparation de surfaces est l'une des priorités du milieu industriel. Cet intérêt est d'autant plus grand dans le domaine du nucléaire pour lequel la réduction des déchets est un axe de recherche important. Un dispositif de décontamination nucléaire par laser UV impulsionnel a été développé et testé. Il est composé. d'un laser à excimères de 1kW, d'un faisceau de fibres optiques et d'un dispositif de récupération des particules. Les essais réalisés en milieu actif ont démontré sa capacité à nettoyer des surfaces métalliques polluées par différents radioéléments avec des facteurs de décontamination généralement supérieurs à 10. Ce dispositif permet de décontaminer de grandes surfaces de géométrie simple en réduisant fortement la génération de déchets secondaires. Il est, à ce jour et dans ces conditions d'utilisations, le procédé de décontamination par voie sèche le plus efficace.

Delaporte, Ph.; Gastaud, M.; Marine, W.; Sentis, M.; Uteza, O.; Thouvenot, P.; Alcaraz, J. L.; Le Samedy, J. M.; Blin, D.



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


One of the primary limiting factors to superovulation and embryo transfer in cattle has been the large variability in response, both between and within animals. It appears that the primary source of this problem is the variability in the population of gonadotropin-responsive follicles present in ovaries at the time of stimulation. We have shown that treatment of heifers with recombinant bovine somatotropin (rbGH) increases the number of small antral follicles (2 to 5 mm) and, therefore, enhances the subsequent superovulatory response to eCG. To investigate further the potential of using this approach to improve superovulatory regimens in cattle, the effect of rbGH pretreatment on the response to pituitary FSH was studied. The estrous cycles of 16 heifers were synchronized using PGF2alpha. On Day 7 of the synchronized cycle, half of the animals were injected with 320 mg sustained-release formulated rbGH, while the other half received 10 ml saline. Five days later, all heifers were given a decreasing-dose regimen of twice daily injections of oFSH for 4 d, incorporating an injection of PGF2alpha with the fifth FSH treatment, to induce superovulation. All animals were artificially inseminated twice with semen from the same bull during estrus. Ova/embryos were recovered nonsurgically on Days 6 to 8 of the following estrous cycle, and the ovulation rate assessed on Day 9 by laparoscopy. Using the same animals as described above, the experiment was repeated twice, 3 and 6 mo later, with no laparoscopy in the third experiment. The animals were randomized both between experiments and for the day of ova/embryo collection. Pretreatment of heifers with rbGH significantly (P < 0.01) increased the number of ovulations, total number of ova/embryos recovered and the number of transferable embryos. The percentage of transferable embryos was significantly (P < 0.05) increased by rbGH pretreatment. In addition, the incidence (2/16) of follicular cysts with a poor ovulatory response (< 6 ovulations) for the rbGH-pretreated heifers was significantly lower (P < 0.05) when compared with the incidence (7/16) in the control animals. It is concluded that pretreatment with rbGH may provide a useful approach for improving superovulatory response in cattle. PMID:16727823

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



Carbaryl inhibits basal and FSH-induced progesterone biosynthesis of primary human granulosa-lutein cells.  


Carbaryl is known to impede female reproductive function, however, the mechanisms through which the adverse effects are mediated are not clearly elucidated. In order to get insight into the mechanisms, this study was conducted to raise fresh concerns about the potential effects of carbaryl on steroidogenesis by primary human granulosa-lutein cells (hGLCs) and explore the possible nature of this action. hGLCs were co-incubated with various concentrations of carbaryl at 0, 1, 5, 25, 125 micromol/L for 24 h to examine effects of this carbamate pesticide on progesterone accumulation. We observed that the carbaryl inhibited basal and FSH-induced progesterone production in a dose-dependent manner. We also investigated the effects of carbaryl on 22(R)-hydroxycholesterol (22R-HC)-stimulated progesterone yield, basal and FSH-stimulated StAR gene expression and cyclic adenosine monophosphate (cAMP) production, as well as forskolin (non-specific activator of adenylyl cyclase)-induced progesterone and cAMP production of hGLCs. We found that the decreased progesterone biosynthesis was accompanied with a reduced cAMP abundance on both basal and FSH-induced condition. Furthermore, our results demonstrated that the 22R-HC could remove the carbaryl-induced restraint of progesterone biosynthesis, suggesting that carbaryl caused a disruption of cholesterol transport across mitochondrial membranes, which was further confirmed by the observation that carbaryl inhibited the gene expression of steroidogenic acute regulatory protein (StAR). In addition, the inhibitory effects of carbaryl on progesterone and cAMP production were completely reversed by addition of forskolin to the cell culture, which indicated a repaired site on the upstream components of adenylate cyclase or adenylate cyclase per se by carbaryl in the cAMP-mediated signal pathway. All the effects mentioned above were not due to a detrimental action of carbaryl on cell viability by MTS assay. In conclusion, carbaryl may inhibit steroidogenesis, at least in part, by obstructing the delivery of cholesterol over mitochondrial membranes and attenuating cAMP generation. PMID:16413094

Cheng, Senping; Chen, Jianfeng; Qiu, Yang; Hong, Xia; Xia, Yankai; Feng, Ting; Liu, Jiayin; Song, Lin; Zhang, Zhengdong; Wang, Xinru



Shortened Estrous Cycle Length, Increased FSH Levels, FSH Variance, Oocyte Spindle Aberrations, and Early Declining Fertility in Aging Senescence-Accelerated Mouse Prone-8 (SAMP8) Mice: Concomitant Characteristics of Human Midlife Female Reproductive Aging.  


Women experience a series of specific transitions in their reproductive function with age. Shortening of the menstrual cycle begins in the mid to late 30s and is regarded as the first sign of reproductive aging. Other early changes include elevation and increased variance of serum FSH levels, increased incidences of oocyte spindle aberrations and aneuploidy, and declining fertility. The goal of this study was to investigate whether the mouse strain senescence-accelerated mouse-prone-8 (SAMP8) is a suitable model for the study of these midlife reproductive aging characteristics. Midlife SAMP8 mice aged 6.5-7.85 months (midlife SAMP8) exhibited shortened estrous cycles compared with SAMP8 mice aged 2-3 months (young SAMP8, P = .0040). Midlife SAMP8 mice had high FSH levels compared with young SAMP8 mice, and mice with a single day of high FSH exhibited statistically elevated FSH throughout the cycle, ranging from 1.8- to 3.6-fold elevation on the days of proestrus, estrus, metestrus, and diestrus (P < .05). Midlife SAMP8 mice displayed more variance in FSH than young SAMP8 mice (P = .01). Midlife SAMP8 ovulated fewer oocytes (P = .0155). SAMP8 oocytes stained with fluorescently labeled antitubulin antibodies and scored in fluorescence microscopy exhibited increased incidence of meiotic spindle aberrations with age, from 2/126 (1.59%) in young SAMP8 to 38/139 (27.3%) in midlife SAMP8 (17.2-fold increase, P < .0001). Finally, SAMP8 exhibited declining fertility from 8.9 pups/litter in young SAMP8 to 3.5 pups/litter in midlife SAMP8 mice (P < .0001). The age at which these changes occur is younger than for most mouse strains, and their simultaneous occurrence within a single strain has not been described previously. We propose that SAMP8 mice are a model of midlife human female reproductive aging. PMID:24654787

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



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

SciTech Connect

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

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



Influence of DDT, DDVP and malathion on FSH, LH and testosterone serum levels and testosterone concentration in testis  

Microsoft Academic Search

Summary Groups of adult male rats were treated with DDT, DDVP or malathion orally for two or three weeks. Body weight and testis weight did not change. FSH and LH levels in serum also remained unchanged, whereas that of testosterone was decreased by DDT. This substance also diminished the concentration of testosterone in the testis. Therefore, the previously observed damage

Walter Krause



Ovarian Response to Different Dose Levels of Follicle Stimulating Hormone (FSH) in Different Genotypes of Bangladeshi Cattle  

PubMed Central

The experiment was conducted under the Department of Animal Breeding and Genetics, Bangladesh Agricultural University (BAU), Mymensingh from June, 2001 to December, 2005 in two different locations (Central Cattle Breeding and Dairy Farm and Bangladesh Livestock Research Institute in Savar, Dhaka) to observe ovarian response to different doses of FSH in three different genotypes of cattle- indigenous Local, Pabna cattle and Friesian×Local cross. Five different dose levels used were 200, 240, 280, 320 and 360 mg. Ovarian response as corpus luteum (CL), recovered embryo (RE) and of transferable embryos (TE) count in Local were significant for 320, 280 and 280 mg respectively. In Pabna cattle CL, RE and TE count were found significant for 360, 320 and 320 mg respectively. In Friesian×Local cross CL, RE and TE count were found significant for 360, 320 and 320 mg respectively. The excellent quality embryos showed significantly the highest yield (1.80±0.20) in the 240 and 280 mg FSH levels in Local genotype. In Pabna cattle, the highest yield (2.00±0.32) was found at FSH level 320 mg. In Friesian×Local, the highest yield (2.20±0.20) was found at FSH level 280 mg.

Ali, M. S.; Khandoker, M. A. M. Y.; Afroz, M. A.; Bhuiyan, A. K. F. H.



Differential Expression of Claudin Family Proteins in Mouse Ovarian Serous Papillary Epithelial Adenoma in Aging FSH Receptor–Deficient Mutants  

Microsoft Academic Search

Ovarian cancer is a deadly disease with long latency. To understand the consequences of loss of follicle- stimulating hormone receptor (FSH-R) signaling and to explore why the atrophic and anovulatory ovaries of follitropin receptor knockout (FORKO) mice develop different types of ovarian tumors, including serous papillary epithelial adenoma later in life, we used mRNA expression profiling to gain a comprehensive

Jayaprakash Aravindakshan; Xinlei Chen; M. Ram Sairam



Value of measuring serum FSH in addition to serum estradiol in a coasting programme to prevent severe OHSS  

Microsoft Academic Search

BACKGROUND: Withholding gonadotrophins (coasting) can reduce the risk of severe ovarian hyperstimulation syndrome (OHSS) in patients having assisted reproduction therapy. This requires daily serum estradiol (E2) measurements, which occasionally have been seen to decline suddenly and sharply. METHODS: To increase the sensitivity of the coasting programme we measured serum FSH in parallel with E2 in patients at risk of developing

T. Al-Shawaf; A. Zosmer; A. Tozer; C. Gillott; A. M. Lower; J. G. Grudzinskas



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:; 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)



Metformin Inhibits Follicle-Stimulating Hormone (FSH) Action in Human Granulosa Cells: Relevance to Polycystic Ovary Syndrome  

PubMed Central

Background: Women with anovulatory polycystic ovary syndrome (PCOS) are generally insulin-resistant and as a consequence are often treated with the biguanide metformin. Results with metformin have, however, been variable with some studies demonstrating induction of regular cycles and an increase in ovulation, whereas others do not. Hence more understanding is needed regarding the mechanism of metformin's actions in ovarian granulosa cells especially in light of previous demonstrations of direct actions. Objective: The aim of this study was to investigate metformin's interaction with the FSH/cAMP/protein kinase A pathway, which is the primary signaling pathway controlling CYP19A1 (aromatase) expression in the ovary. Methods: The effect of metformin on FSH and forskolin-stimulated aromatase expression in human granulosa cells was measured by quantitative real-time PCR. Activity was assessed after transfection with a promoter II-luciferase construct, and by an RIA measuring conversion of androgen to estrogens. The effect on FSH receptor (FSHR) mRNA was assessed by quantitative PCR. Levels of phosphorylated cAMP response element binding protein (CREB) and CREB-regulated transcription coactivator 2 (CRTC2) were measured by Western blotting and cAMP by a bioluminescent assay. Results: Metformin markedly reduced FSH but not forskolin-stimulated aromatase expression and activity. This effect was exerted by inhibition of basal and ligand-induced up-regulation of FSHR expression. Metformin also reduced FSH-induced phosphorylation of CREB and hence CRE activity, which could potentially disrupt the CREB–CREB-binding protein–CRTC2 coactivator complex that binds to CRE in promoter II of the aromatase gene. This is mediated in an AMP-activated protein kinase-independent manner, and does not involve alteration of cAMP levels. Conclusion: These finding have implications for the use of metformin in the treatment of anovulation in women with PCOS.

Elia, Androulla; Jawad, Zara; Pellatt, Laura; Mason, Helen D.



Does higher starting dose of FSH stimulation with letrozole improve fertility preservation outcomes in women with breast cancer?  

PubMed Central

Objective To evaluate the efficacy of ovarian stimulation with higher doses of gonadotropins in fertility preservation (FP) cycles with the intention to maximize the likelihood of future pregnancies. Design Retrospective (secondary analysis). Setting Academic medical centers. Patient(s) Low-dose (LD, 150 IU; n = 34) versus high-dose (HD, >150 IU; n = 117) FSH start in 151 patients with breast cancer (BCa) undergoing ovarian stimulation for embryo cryopreservation with letrozole (LE) before cancer treatment. Intervention(s) None. Main Outcome Measure(s) FP cycle outcomes. Result(s) Mean total FSH dose (2,037 ± 679 IU vs. 1,128 ± 381 IU) and FSH level on trigger day (21.1 ± 8.9 vs. 10.6 ± 4.5 mIU/mL) were higher in the HD group, confirming the receipt of higher-dose FSH. There was no difference in other patient characteristics. Despite the larger number of follicles >17 mm in diameter in the HD group (5.0 ± 2.0 vs. 3.4 ± 1.4), neither peak E2 (498.0 ± 377.5 vs. 397.9 ± 320.3), number of oocytes (13.3 ± 8.7 vs. 12.3 ± 8.0), nor number of embryos (6.3 ± 4.7 vs. 5.4 ± 3.8) were significantly different from the LD group. Of those undergoing frozen embryo transfer (ET), live birth rate (LBR)/ET trended higher in the LD (9/15) compared with HD (2/11) group, with 2.1 ± 0.8 vs. 1.9 ± 0.3 embryos transferred, respectively. Conclusion(s) Higher-dose FSH stimulation in LE cycles does not improve outcomes and may be associated with lower LBR. Our findings may support minimal stimulation in young noninfertile women with BCa.

Lee, Sanghoon; Oktay, Kutluk



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



Identification of ovarian genes regulated by follicle-stimulating hormone (Fsh) in vitro during early secondary oocyte growth in coho salmon.  


Follicle-stimulating hormone (Fsh) function in fishes is poorly understood. This study aimed to reveal Fsh-regulated genes in coho salmon previtellogenic ovarian follicles in vitro. Four suppression subtractive hybridization libraries were generated with RNA isolated from Fsh-treated and control follicles or follicle cell-enriched tissue fractions. Fsh induced steroidogenesis and dynamically upregulated several genes predominantly expressed in follicle cells, including WAP domain-containing protease, connexin 34.3, clusterin (clu1, clu2), fibronectin, wilms tumor 2-like, and influenza virus NS1A-binding protein a. Genes downregulated by Fsh included connective tissue growth factor, alcohol dehydrogenase 8-like, and serine/threonine-protein kinase pim-1. This study demonstrates for the first time in fishes that Fsh influences the expression of a unique suite of ovarian genes involved in processes like cell communication, survival and differentiation, and extracellular matrix remodeling. Collectively, these findings suggest that Fsh and/or steroids induce differentiation of granulosa cells and remodeling of the follicle in preparation for onset of vitellogenesis. PMID:23200633

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



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

PubMed Central

Background Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. Methods/Design Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged?FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT. Discussion The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines. Trial registration NTR2657



Ablation de matériaux par laser femtoseconde  

NASA Astrophysics Data System (ADS)

L'ablation de métaux par laser impulsionnel ultrabref (femtoseconde) est étudiée en analysant les cratères par microscopie optique. La profondeur du cratère a été mesurée en fonction du nombre d'impulsions et de la fluence. Les résultats sont comparés à un modèle analytique décrivant l'interaction laser-matière en régime femtoseconde.

Bruneau, S.; Hermann, J.; Itina, T.; Sentis, M.; Semerok, A.; Marine, W.



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.



Age, FSH dose and follicular aspiration frequency affect oocyte yield from juvenile donor lambs.  


Experiments were conducted to determine the effects of lamb age, frequency of follicular aspirations, and hormone stimulation by fixed or variable FSH dose, on the number of collected oocytes and their maturational competence. In trial 1, the characteristics of follicular population (number and diameter of follicles) were studied in 40 lambs which were slaughtered at the age of 30 days (S1), 42 days (S2), 60 days (S3) and 5-6 months (S4), each n = 10. In trial 2, 27 lambs were divided into four groups. group MF lambs (n = 6) had follicular aspiration (OPU) in four monthly intervals commencing from the age of 8-9 weeks (sessions MF1, MF2, MF3 and MF4). In groups SF2, SF3 and SF4 (each n = 6), OPU was conducted once during the 12-13, 16-17 and 20-21 week of age, respectively. Ovarian stimulation was conducted with fixed FSH dose (3.52 mg/animal). In trial 3, 10 lambs (group MV) were treated as those of group MF apart from the FSH dose, which was administered according to the body weight in a dose of 0.27 mg/kg. The number and the size of follicles, the number and the quality of collected oocytes and the maturational competence of the oocytes were compared between and within groups. In trial 1, the total number and the number of small follicles were greater in groups S1 and S2 compared with those of S3 and S4 (p < 0.01). Similarly, the follicular population was greater in group MF1 than in group SF3 (p < 0.01). In sessions MF2, MF3, MV2, MV3 and MV4, more oocytes were collected in comparison with those from the respective once-aspirated age mates (groups SF2, SF3 and SF4). In total, more (p = 0.02) oocytes per donor were collected from group MV (15.2 +/- 5.5) than from group MF (9.0 +/- 3.2). An absolute maturational failure was observed in oocytes collected from groups SF2 and SF3. Maturational competence varied between 16.7% and 58.3% (p = 0.017) among sessions of group MF, but it was more uniform among sessions of group MV (range 12.5-42.9%, p > 0.05). Our results indicate that firstly, the number and the quality of harvested oocytes from juvenile lambs can be much improved if follicular stimulation regime is adjusted to the body weight. Secondly, in terms of follicular population and oocyte quality, 3 and 4-month-old lambs are naturally bad oocyte donors, but this characteristic can be reversed by a previous follicular ablation. PMID:17506799

Valasi, I; Leontides, L; Papanikolaou, Th; Amiridis, G S



Segrosome assembly at the pliable parH centromere  

PubMed Central

The segrosome of multiresistance plasmid TP228 comprises ParF, which is a member of the ParA ATPase superfamily, and the ParG ribbon–helix–helix factor that assemble jointly on the parH centromere. Here we demonstrate that the distinctive parH site (?100-bp) consists of an array of degenerate tetramer boxes interspersed by AT-rich spacers. Although numerous consecutive AT-steps are suggestive of inherent curvature, parH lacks an intrinsic bend. Sequential deletion of parH tetramers progressively reduced centromere function. Nevertheless, the variant subsites could be rearranged in different geometries that accommodated centromere activity effectively revealing that the site is highly elastic in vivo. ParG cooperatively coated parH: proper centromere binding necessitated the protein's N-terminal flexible tails which modulate the centromere binding affinity of ParG. Interaction of the ParG ribbon–helix–helix domain with major groove bases in the tetramer boxes likely provides direct readout of the centromere. In contrast, the AT-rich spacers may be implicated in indirect readout that mediates cooperativity between ParG dimers assembled on adjacent boxes. ParF alone does not bind parH but instead loads into the segrosome interactively with ParG, thereby subtly altering centromere conformation. Assembly of ParF into the complex requires the N-terminal flexible tails in ParG that are contacted by ParF.

Wu, Meiyi; Zampini, Massimiliano; Bussiek, Malte; Hoischen, Christian; Diekmann, Stephan; Hayes, Finbarr



Toward drugs for protease-activated receptor 2 (PAR2).  


PAR2 has a distinctive functional phenotype among an unusual group of GPCRs called protease activated receptors, which self-activate after cleavage of their N-termini by mainly serine proteases. PAR2 is the most highly expressed PAR on certain immune cells, and it is activated by multiple proteases (but not thrombin) in inflammation. PAR2 is expressed on many types of primary human cells and cancer cells. PAR2 knockout mice and PAR2 agonists and antagonists have implicated PAR2 as a promising target in inflammatory conditions; respiratory, gastrointestinal, metabolic, cardiovascular, and neurological dysfunction; and cancers. This article summarizes salient features of PAR2 structure, activation, and function; opportunities for disease intervention via PAR2; pharmacological properties of published or patented PAR2 modulators (small molecule agonists and antagonists, pepducins, antibodies); and some personal perspectives on limitations of assessing their properties and on promising new directions for PAR2 modulation. PMID:23895492

Yau, Mei-Kwan; Liu, Ligong; Fairlie, David P



Effect of FSH and cell localization on dimeric inhibin-A secretion from bovine granulosa cells in culture  

Microsoft Academic Search

We tested the hypotheses that the secretion of dimeric inhibin-A from cultured bovine granulosa cells is stimu- lated by FSH, and that antral cells secrete more inhibin-A than do mural cells. Cells from the antral or mural compartment of follicles were cultured in defined medium in two culture systems, and dimeric inhibin-A was measured by two-site ELISA or by Western

M L Boudjemaâ; P Rouillier; B Bhatia; J M Silva; L A Guilbault



Pueraria tuberosa DC extract improves androgenesis and sexual behavior via FSH LH cascade.  


The aim of this study was to investigate the effects of ethanolic extract of Pueraria tuberosa (PT) on sexual behaviour and androgenic activity. Male albino rats were divided into four groups of six animals each: control group 1 (2% acacia solution), PT-treated group 2 (50 mg/Kg), PT-treated group 3 (100?mg/Kg), and PT-treated group 4 (150?mg/Kg). Sexual behavior of male rats in the presence of a female rat was recorded. The treated groups were evaluated for sexual parameters. The extract was characterized using LC-MS. The effect of treatment on anabolic and weight of secondary sexual organs was determined. The histological changes in section of testis and epididymis after treatment were observed. Sperm count in epididymis and fructose content in seminal vesicles were also measured. Levels of hormones like FSH, LH, and T were determined. A dose-dependent increase in sexual behaviors was evidenced in the animals of extract treated groups. Increase in testis weight was recorded in PT. At the highest dose PT also affects the hormones level. The four compounds namely puerarin, daidzein, biochanin-A and formononetin were identified in ethanolic extract using LC-MS. It concluded that PT extract possesses androgenic effect and it significantly increased the sexual behaviour and hormones level. PMID:24489512

Chauhan, Nagendra Singh; Sharma, Vikas; Thakur, Mayank; Christine Helena Frankland Sawaya, Alexandra; Dixit, V K



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


The present study aims to determine the role of the specific residues of the extracellular loops (ELs) of the FSH receptor (FSHR) in hormone binding and receptor activation. By substituting the sequences of each of the ELs of human FSHR with those of the luteinizing hormone/choriogonadotropin receptor (LH/CGR), we generated three mutant constructs where the three ELs were individually replaced. A fourth construct had all the three substituted ELs. The receptor expression and hormone binding ability of the mutants were comparable to that of the wild type. Hormone-induced signaling and internalization were lower in the EL2 substitution mutant (EL2M). In this mutant, the EL2 of FSHR was substituted with the corresponding loop of LH/CGR. Interestingly, homology modeling revealed a change in the orientation of EL2 in the mutant receptor. Thus, disruption of EL2 affected overall receptor function, suggesting the role of FSHR specific residues of the loop in ligand mediated signaling. PMID:22641019

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



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.  


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



Impact of the GPX5, FUT1, FSH? and PRLR Genes on Individual Weight at Birth and 30 Days in Hybrid Pig  

Microsoft Academic Search

Zhang, D.J., Liu, D., Yang, G.W., Fu, X.K. and He, X.M. 2010. Impact of the GPX5, FUT1, FSH? and PRLR genes on individual weight at birth and 30 days in hybrid pig. J. Appl. Anim. Res., 38: 239–243.To analyse polymorphisms and genetic associations of glutathione peroxidase 5 (GPX5), ?1-fucosyltransferase (FUT1), follicle stimulating hormone ? subunit (FSH?) and prolactin receptor (PRLR)

D. J. Zhang; D. Liu; G. W. Yang; X. K. Fu; X. M. He



Superstimulation of ovarian follicular growth with FSH oocyte recovery, and embryo production from Zebu (Bos indicus) calves: effects of treatment with a GnRH agonist or antagonist.  


The capacity of heifer calves of a late sexually maturing Zebu (Bos indicus) genotype to respond to superstimulation with FSH at a young age and in vitro oocyte development were examined. Some calves were treated with a GnRH agonist (deslorelin) or antagonist (cetrorelix) to determine whether altering plasma concentrations of LH would influence follicular responses to FSH and oocyte developmental competency. Brahman calves (3-mo-old; 140 +/- 3 kg) were randomly assigned to 3 groups: control (n = 10); deslorelin treatment from Day -8 to 3 (n = 10); and cetrorelix treatment from Day -3 to 2 (n = 10). All calves were stimulated with FSH from Day 0 to 2, and were ovariectomized on Day 3 to determine follicular responses to FSH and to recover oocytes for in vitro procedures. Before treatment with FSH, heifers receiving deslorelin had greater (P < 0.001) plasma LH (0.30 +/- 0.01 ng/ml) than control heifers (0.17 +/- 0.02 ng/ml), while plasma LH was reduced (P < 0.05) in heifers treated with cetrorelix (0.13 +/- 0.01 ng/ml). Control heifers had a surge release of LH during treatment with FSH, but this did not occur in heifers treated with deslorelin or cetrorelix. All heifers had large numbers of follicles > or = 2 mm (approximately 60 follicles) after superstimulation with FSH, and there were no differences (P > 0.10) between groups. Total numbers of oocytes recovered and cultured also did not differ (P > 0.05) for control heifers and heifers treated with deslorelin or cetrorelix. Fertilization and cleavage rates were similar for the 3 groups, and developmental rates to blastocysts were also similar. Zebu heifers respond well to superstimulation with FSH at a young age, and their oocytes are developmentally competent. PMID:10732069

Maclellan, L J; Whyte, T R; Murray, A; Fitzpatrick, L A; Earl, C R; Aspden, W J; Kinder, J E; Grotjan, H E; Walsh, J; Trigg, T E; D'Occhio, M J



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.

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



Differential expression of claudin family proteins in mouse ovarian serous papillary epithelial adenoma in aging FSH receptor-deficient mutants.  


Ovarian cancer is a deadly disease with long latency. To understand the consequences of loss of follicle-stimulating hormone receptor (FSH-R) signaling and to explore why the atrophic and anovulatory ovaries of follitropin receptor knockout (FORKO) mice develop different types of ovarian tumors, including serous papillary epithelial adenoma later in life, we used mRNA expression profiling to gain a comprehensive view of misregulated genes. Using real-time quantitative reverse transcription-polymerase chain reaction, protein analysis, and cellular localization, we show, for the first time, in vivo evidence that, in the absence of FSH-R signaling, claudin-3, claudin-4, and claudin-11 are selectively upregulated, whereas claudin-1 decreases in ovarian surface epithelium and tumors in comparison to wild type. In vitro experiments using a mouse ovarian surface epithelial cell line derived from wild-type females reveal direct hormonal influence on claudin proteins. Although recent studies suggest that cell junction proteins are differentially expressed in ovarian tumors in women, the etiology of such changes remains unclear. Our results suggest an altered hormonal environment resulting from FSH-R loss as a cause of early changes in tight junction proteins that predispose the ovary to late-onset tumors that occur with aging. More importantly, this study identifies claudin-11 overexpression in mouse ovarian serous cystadenoma. PMID:17217615

Aravindakshan, Jayaprakash; Chen, Xinlei; Sairam, M Ram



Proteinase-activated receptor-1 (PAR1) and PAR2 mediate relaxation of guinea pig internal anal sphincter.  


Activation of proteinase-activated receptor-1 (PAR1) and PAR2 stimulates contraction of the rat but relaxation of the guinea pig colon. The aim of the present study was to investigate PAR effects on internal anal sphincter (IAS) motility. We measured relaxation of isolated muscle strips from the guinea pig IAS caused by PAR agonists using isometric transducers. Reverse transcription polymerase chain reaction (RT-PCR) was performed to determine the existence of PAR. In the IAS, thrombin and PAR1 peptide agonists TFLLR-NH2 and SFLLRN-NH2 evoked moderate to marked relaxation in a concentration-dependent manner. In addition, trypsin and PAR2 peptide agonists 2-furoyl-LIGRLO-NH2, SLIGRL-NH2 and SLIGKV-NH2 produced relaxation. In contrast, both PAR1 and PAR2 inactive control peptides did not elicit relaxation. Furthermore, the selective PAR1 antagonist vorapaxar and PAR2 antagonist GB 83 specifically inhibited thrombin and trypsin-induced relaxations, respectively. RT-PCR revealed the presence of PAR1 and PAR2 in the IAS. This indicates that PAR1 and PAR2 mediate the IAS relaxation. The relaxant responses of TFLLR-NH2 and trypsin were attenuated by N(omega)-Nitro-L-arginine (L-NNA), indicating involvement of NO. These responses were not affected by tetrodotoxin, implying that the PAR effects are not neurally mediated. On the other hand, PAR4 agonists GYPGKF-NH2, GYPGQV-NH2 and AYPGKF-NH2 did not cause relaxation or contraction, suggesting that PAR4 is not involved in the sphincter motility. Taken together, these results demonstrate that both PAR1 and PAR2 mediate relaxation of the guinea pig IAS through the NO pathway. PAR1 and PAR2 may regulate IAS tone and might be potential therapeutic targets for anal motility disorders. PMID:24631471

Huang, Shih-Che



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.



Melphalan, alone or conjugated to an FSH-? peptide, kills murine testicular cells in vitro and transiently suppresses murine spermatogenesis in vivo.  


New approaches to sterilizing male animals are needed to control captive and wild animal populations. We sought to develop a nonsurgical method of permanent sterilization for male animals by administering the gonadotoxicant melphalan conjugated to peptides derived from the ?-chain of FSH?. We hypothesized that conjugating melphalan to FSH? peptides would magnify the gonadotoxic effects of melphalan while minimizing systemic toxicity. The ability of conjugates of melphalan and FSH? peptides to kill murine testicular cells was first tested in vitro in a three-dimensional testicular cell coculture system. In this system, melphalan caused considerable cell death as measured both by increases in lactate dehydrogenase concentrations in the culture supernatant and direct visualization of the cultures. Of the conjugates tested, melphalan conjugated to a 20-amino acid peptide derived from human FSH? consisting of amino acids 33 to 53 (FSH? (33-53)-melphalan) was very potent, with cell cytotoxicity and lactate dehydrogenase release roughly one-half that of melphalan. The effects of melphalan and FSH? (33-53)-melphalan on spermatogenesis were then tested in vivo in mature C56Bl/6 male mice. Four weeks after intraperitoneal injection, all mice treated with either FSH? (33-53)-melphalan or melphalan had approximately 75% reductions in testicular spermatid counts compared with control animals. Testicular histology revealed significant reduction in mature spermatids and spermatocytes in most tubules. However, 12 weeks after the injection, testicular spermatid counts and histology were similar to controls, except in one animal receiving FSH? (33-53)-melphalan that had no apparent spermatogenesis. We conclude that melphalan and FSH? (33-53)-melphalan are potent gonadotoxicants in male mice resulting in marked suppression of spermatogenesis 4 weeks after a single intraperitoneal injection. However, this effect is transient in most mice as spermatogenesis is similar to control animals 12 weeks after drug administration. Melphalan or FSH? (33-53)-melphalan may be useful for the temporary control of fertility in male animals, but additional research will be needed to develop a single dose method of permanent sterilization for male animals. PMID:24746827

Amory, John K; Hong, SungWoo; Yu, Xiaozhong; Muller, Charles H; Faustman, Elaine; Goldstein, Alex



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.

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



Direct actions of the luteinizing hormone-releasing hormone agonist, deslorelin, on anterior pituitary contents of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), LH and FSH subunit messenger ribonucleic acid, and plasma concentrations of LH and FSH in castrated male cattle.  


The objective in this study was to characterize direct effects of the LHRH agonist, deslorelin, on anterior pituitary gland function in male cattle in the absence of gonadal feedback. Castrated bulls (steers), 30 mo old, were allocated to four groups: group 1, control, no treatment (n = 8); group 2, five deslorelin implants (approximately 250 micrograms total deslorelin/day) for 42 days (n = 8); group 3, control+ LHRH (50 micrograms i.m.) at weekly intervals (n = 3); group 4, five deslorelin implants+LHRH as for group 3 (n = 3). Plasma LH was similar (p > 0.05) for steers in groups 1 and 2 on Day 0 and lower (p < 0.05) for steers in group 2 on Day 4, and continued to decrease to Day 41 (group 1, 1.71 +/- 0.20 ng/ml [mean +/- SEM]; group 2, 0.38 +/- 0.03 ng/ml [p < 0.001]). Mean plasma concentrations of FSH were similar (p > 0.05) for steers in groups 1 and 2 on Day 0 and lower (p < 0.05) for steers in group 2 on Day 7, and declined to Day 41 (group 1, 43.5 +/- 3.9 ng/ml; group 2, 17.5 +/- 1.5 ng/ml [p < 0.001]). Steers in group 3 showed increases in plasma LH after injection of LHRH on all occasions, while steers in group 4 did not show increases in plasma LH from Day 14 onward. Mean relative pituitary contents (arbitrary units) of LH beta- and FSH beta-subunit mRNAs were reduced on Day 42 in steers treated with deslorelin (LH beta: groups 1 and 3, 1.56 +/- 0.27; groups 2 and 4, 0.08 +/- 0.01 [p < 0.001]; FSH beta: groups 1 and 3, 1.01 +/- 0.08; groups 2 and 4, 0.34 +/- 0.07 [p < 0.001]). However, alpha-subunit mRNA was similar for control steers and steers treated with deslorelin (groups 1 and 3, 1.00 +/- 0.11; groups 2 and 4, 0.86 +/- 0.12 [p > 0.1]). Pituitary content of LH, but not FSH, was reduced in steers treated with deslorelin. In summary, steers treated with deslorelin showed desensitization to natural LHRH, and this was associated with reduced pituitary contents of LH and FSH beta-subunit mRNAs, a reduction in pituitary content of LH, and decreases in plasma concentrations of LH and FSH. This demonstrated, for the first time, a direct action of LHRH agonist on LH and FSH beta-subunit gene expression in cattle, independent of gonadal feedback. Also, there was a differential effect of treatment with deslorelin on gonadotropin alpha- and beta-subunit mRNA contents in the anterior pituitary. PMID:8828844

Aspden, W J; Rao, A; Scott, P T; Clarke, I J; Trigg, T E; Walsh, J; D'Occhio, M J



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

PubMed Central

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

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



The horse pseudoautosomal region (PAR): characterization and comparison with the human, chimp and mouse PARs.  


The pseudoautosomal region (PAR) is a genomic segment on mammalian sex chromosomes where sequence homology mimics that seen between autosomal homologues. The region is essential for pairing and proper segregation of sex chromosomes during male meiosis. As yet, only human/chimp and mouse PARs have been characterized. The two groups of species differ dramatically in gene content and size of the PAR and therefore do not provide clues about the likely evolution and constitution of PAR among mammals. Here we characterize the equine PAR by i) isolating and arranging 71 BACs containing 129 markers (110 STS and 19 genes) into two contigs spanning the region, ii) precisely localizing the pseudoautosomal boundary (PAB), and iii) describing part of the contiguous X- and Y-specific regions. We also report the discovery of an approximately 200 kb region in the middle of the PAR that is present in the male-specific region of the Y (MSY) as well. Such duplication is a novel observation in mammals. Further, comparison of the equine PAR with the human counterpart shows that despite containing orthologs from an additional 1 Mb region beyond the human PAR1, the equine PAR is around 0.9 Mb smaller than the size of the human PAR. We theorize that the PAR varies in size and gene content across evolutionarily closely as well as distantly related mammals. Although striking differences like those observed between human and mouse may be rare, variations similar to those seen between horse and human may be prevalent among mammals. PMID:18544933

Raudsepp, T; Chowdhary, B P



FSH-induced phosphoprotein phosphatase 2A-mediated deactivation of particulate phosphodiesterase-4 activities is abolished after alteration in proteoglycan synthesis in immature rat Sertoli cells.  


Cessation of rat testicular Sertoli cells proliferation around days 15-20 post partum is associated in vitro with the highest rise in rolipram-sensitive cAMP-catabolizing phosphodiesterase-4 activities (PDE4s) triggered by FSH during the early postnatal period. The transient nature of FSH-induced increase in PDE4s suggests concomitant changes in both PKA-mediated activation and subsequent deactivation of these activities. In this study, we demonstrated that the deactivation of FSH-stimulated particulate, but not soluble, PDE4s in cultured Sertoli cells from 20-day-old rats was inhibited by phosphoprotein phosphatase (PP) inhibitors, okadaïc acid, and calyculin A. Moreover, the deactivation of FSH-stimulated particulate PDE4s was timely related with the gonadotropin-induced increase in both particulate PP2A activity and particulate PP2A catalytic subunit immunoreactive expression independently of any transcriptional regulation of that subunit. Both the FSH-induced increase in recruitment/activation of particulate PP2A and the subsequent deactivation of particulate PDE4 were abolished when Sertoli cell proteoglycans (PGs) synthesis was altered by sodium chlorate. Sodium chlorate effect was developmentally regulated as evidenced by its ability to silence particulate PDE4 deactivation only in non-proliferating (from 20- to 30-day-old rats) but not in proliferating (from 10-day-old rats) Sertoli cells. All these data suggested that PGs could be involved in the FSH-induced recruitment/activation of PP2A. Particularly, developmentally regulated transmembrane syndecans, the most abundant PGs in Sertoli cells, by targeting PP2A at the membrane level could allow developmental control of activated particulate PDE4s and, potentially, other signaling phosphoproteins, including the FSH receptor, during the early postnatal period. PMID:18372231

Levallet, Guénaëlle; Levallet, Jérôme; Bonnamy, Pierre-Jacques



Corifollitropin alfa or rFSH treatment flexibility options for controlled ovarian stimulation: a post hoc analysis of the Engage trial  

PubMed Central

Background We sought to determine the impact of treatment flexibility on clinical outcomes in either a corifollitropin alfa or recombinant follicle-stimulating hormone (rFSH) protocol. Methods Post hoc analysis of a prospective, multicenter, randomized, double-blind, double-dummy non-inferiority clinical trial (Engage). Efficacy outcomes were assessed on patients from the Engage trial who started treatment on menstrual cycle day 2 versus menstrual cycle day 3, patients who received rFSH step-down or fixed-dose rFSH, patients who received rFSH on the day of human chorionic gonadotropin (hCG) compared with those who did not, and patients who received hCG when the criterion was reached versus those with a 1-day delay. Results The effect of each of the treatment flexibility options on ongoing pregnancy rate was not significant. The estimated difference (95% confidence interval) in ongoing pregnancy rate was -4.3% (-9.4%, 0.8%) for patients who started ovarian stimulation on cycle day 2 versus day 3, 1.8% (-4.1%, 7.6%) for patients who received hCG on the day the hCG criterion was met versus 1 day after, 3.2% (-2.1%, 8.6%) for patients who received rFSH on the day of hCG administration versus those who did not, and -5.8% (-13.0%, 1.4%) for patients who received a reduced versus fixed-dose of rFSH from day 8. Conclusions Treatment flexibility of ovarian stimulation does not substantially affect the clinical outcome in patients’ treatment following initiation of ovarian stimulation with either corifollitropin alfa or with daily rFSH in a gonadotropin-releasing hormone antagonist protocol. Trial registration Trial was registered under identifier NCT00696800.



Corifollitropin alfa or rFSH treatment flexibility options for controlled ovarian stimulation: a post hoc analysis of the engage trial.  


BACKGROUND: We sought to determine the impact of treatment flexibility on clinical outcomes in either a corifollitropin alfa or recombinant follicle-stimulating hormone (rFSH) protocol. METHODS: Post hoc analysis of a prospective, multicenter, randomized, double-blind, double-dummy non-inferiority clinical trial (Engage). Efficacy outcomes were assessed on patients from the Engage trial who started treatment on menstrual cycle day 2 versus menstrual cycle day 3, patients who received rFSH step-down or fixed-dose rFSH, patients who received rFSH on the day of human chorionic gonadotropin (hCG) compared with those who did not, and patients who received hCG when the criterion was reached versus those with a 1-day delay. RESULTS: The effect of each of the treatment flexibility options on ongoing pregnancy rate was not significant. The estimated difference (95% confidence interval) inongoing pregnancy rate was -4.5% (-9.6%, 0.6%) for patients who started ovarian stimulation on cycle day 2 versus day 3, 1.9% (-4.0%, 7.7%) for patients who received hCG on the day the hCG criterion was met versus 1 day after, 3.9% (-2.4%, 8.3%) for patients who received rFSH on the day of hCG administration versus those who did not, and -5.8% (-13.0%, 1.4%) for patients who received a reduced versus fixed-dose of rFSH from day 8. CONCLUSIONS: Treatment flexibility of ovarian stimulation does not substantially affect the clinical outcome in patients' treatment following initiation of ovarian stimulation with either corifollitropin alfa or with daily rFSH in a gonadotropin-releasing hormone antagonist protocol.Trial registration number: Trial was registered under identifier NCT00696800. PMID:23758821

Leader, Arthur; Devroey, Paul; Witjes, Han; Gordon, Keith



Bazooka and PAR6 are required with PAR1 for the maintenance of oocyte fate in Drosophila  

Microsoft Academic Search

The anterior-posterior axis of C. elegans is defined by the asymmetric division of the one-cell zygote, and this is controlled by the PAR proteins, including PAR-3 and PAR-6, which form a complex at the anterior of the cell, and PAR-1, which localizes at the posterior [1–4]. PAR-1 plays a similar role in axis formation in Drosophila: the protein localizes to

Jean-René Huynh; Mark Petronczki; Juergen A. Knoblich; Daniel St Johnston



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


Genes critical for fertility are highly conserved in mammals. Interspecies DNA sequence variation, resulting in amino acid substitutions and post-transcriptional modifications, including alternative splicing, are a result of evolution and speciation. The mammalian follicle-stimulating hormone receptor (FSHR) gene encodes distinct species-specific forms by alternative splicing. Skipping of exon 2 of the human FSHR was reported in women of North American origin and correlated with low response to ovarian stimulation with exogenous follicle-stimulating hormone (FSH). To determine whether this variant correlated with low response in women of different genetic backgrounds, we performed a blinded retrospective observational study in a Turkish cohort. Ovarian response was determined as low, intermediate or high according to retrieved oocyte numbers after classifying patients in four age groups (<35, 35-37, 38-40, >40). Cumulus cells collected from 96 women undergoing IVF/ICSI following controlled ovarian hyperstimulation revealed four alternatively spliced FSHR products in seven patients (8%): exon 2 deletion in four patients; exon 3 and exons 2 + 3 deletion in one patient each, and a retention of an intron 1 fragment in one patient. In all others (92%) splicing was intact. Alternative skipping of exons 2, 3 or 2 + 3 were exclusive to low responders and was independent of the use of agonist or antagonist. Interestingly, skipping of exon 3 occurs naturally in the ovaries of domestic cats-a good comparative model for human fertility. We tested the signaling potential of human and cat variants after transfection in HEK293 cells and FSH stimulation. None of the splicing variants initiated cAMP signaling despite high FSH doses, unlike full-length proteins. These data substantiate the occurrence of FSHR exon skipping in a subgroup of low responders and suggest that species-specific regulation of FSHR splicing plays diverse roles in mammalian ovarian function. PMID:24670307

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



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

NASA Astrophysics Data System (ADS)

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

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



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)



Development of a homologous enzyme-linked immunosorbent assay for European sea bass FSH. Reproductive cycle plasma levels in both sexes and in yearling precocious and non-precocious males.  


Since the late 1980s, gonadotropins have been isolated and characterized in several fish species, but specific immunoassays for the follicle-stimulating hormone (FSH) have only been developed for a few. The present study reports the development and use of a specific and homologous competitive ELISA for measuring FSH in European sea bass (Dicentrarchus labrax) using a recombinant FSH and its specific antiserum. Recombinant European sea bass FSH? and FSH heterodimer were produced in the methylotrophic yeast Pichia pastoris and a baculovirus expression system, respectively. Specific polyclonal antibodies, generated by rabbit immunization against recombinant FSH?, were used at a final dilution of 1:8000. Recombinant FSH heterodimer was used to generate a standard curve and for coating of microplates (166 ?g/ml). The sensitivity of the assay was 0.5 ng/ml [B(0)-2SD], and the intra- and inter-assay coefficients of variation were 2.12% (n=10) and 5.44% (n=16) (B(i)/B(0) ?45%), respectively. A high degree of parallelism was observed between the standard curve and serially diluted plasma and pituitary samples of European sea bass. The ELISA developed was used to study the plasma FSH profiles of mature males and females during the reproductive cycle, and those of immature juvenile males under different light regimes. The analysis showed that FSH increased significantly during the intermediate stages of spermatogenesis and during vitellogenesis. Analyses in immature juvenile males showed that the continuous light photoperiod significantly reduced plasma FSH levels, and consequently, testicular growth and precocious puberty. In conclusion, the immunoassay developed has proven to be sensitive, specific and accurate for measuring European sea bass FSH, and it represents a valuable tool for future studies on the reproductive endocrinology of this species. PMID:22227219

Molés, Gregorio; Gómez, Ana; Carrillo, Manuel; Zanuy, Silvia



An unbalanced translocation unmasks a recessive mutation in the follicle-stimulating hormone receptor (FSHR) gene and causes FSH resistance  

PubMed Central

Follicle-stimulating hormone (FSH) mediated by its receptor (FSHR) is pivotal for normal gametogenesis. Inactivating FSHR mutations are known to cause hypergonadotropic hypogonadism with disturbed follicular maturation in females. So far, only very few recessive point mutations have been described. We report on a 17-year-old female with primary amenorrhea, hypergonadotropic hypogonadism and disturbed folliculogenesis. Chromosome analysis detected a seemingly balanced translocation 46,XX,t(2;8)(p16.3or21;p23.1)mat. FSHR sequence analysis revealed a novel non-synonymous point mutation in exon 10 (c.1760C>A, p.Pro587His), but no wild-type allele. The mutation was also found in the father, but not in the mother. Furthermore, molecular-cytogenetic analyses of the breakpoint region on chromosome 2 showed the translocation to be unbalanced, containing a deletion with one breakpoint within the FSHR gene. The deletion size was narrowed down by array analysis to approximately 163?kb, involving exons 9 and 10 of the FSHR gene. Functional studies of the mutation revealed the complete lack of signal transduction presumably caused by a changed conformational structure of transmembrane helix 6. To our knowledge, this is the first description of a compound heterozygosity of an inactivating FSHR point mutation unmasked by a partial deletion. This coincidence of two rare changes caused clinical signs consistent with FSH resistance.

Kuechler, Amla; Hauffa, Berthold P; Koninger, Angela; Kleinau, Gunnar; Albrecht, Beate; Horsthemke, Bernhard; Gromoll, Jorg



Peroxisome Proliferator-Activated Receptor-? Mediates Bisphenol A Inhibition of FSH-Stimulated IGF-1, Aromatase, and Estradiol in Human Granulosa Cells  

PubMed Central

Background Bisphenol A (BPA), a chemical used as a plasticizer, is a potent endocrine disruptor that, even in low concentrations, disturbs normal development and functions of reproductive organs in different species. Objectives We investigated whether BPA affects human ovarian granulosa cell function. Methods We treated KGN granulosa cells and granulosa cells from subjects undergoing in vitro fertilization (IVF) with follicle-stimulating hormone (FSH), BPA, or BPA plus FSH in a dose- and time-dependent manner. We then evaluated expression of insulin-like growth factor 1 (IGF-1), aromatase, and transcription factors known to mediate aromatase induction by FSH [including steroidogenic factor-1 (SF-1), GATA4, cAMP response element binding protein-1 (CREB-1), and peroxisome proliferator–activated receptor-? (PPAR?)], as well as 17?-estradiol (E2) secretion. KGN cells were transfected with a PPAR?-containing vector, followed by assessment of aromatase and IGF-I expression. Results BPA reduced FSH-induced IGF-1 and aromatase expression and E2 secretion in a dose-dependent fashion. Similar effects on aromatase were observed in IVF granulosa cells. SF-1 and GATA4, but not CREB-1, were reduced after BPA treatment, although PPAR?, an inhibitor of aromatase, was significantly up-regulated by BPA in a dose-dependent manner, with simultaneous decrease of aromatase. Overexpression of PPAR? in KGN cells reduced FSH-stimulated aromatase and IGF-1 mRNAs, with increasing concentrations of the transfected expression vector, mimicking BPA action. Also, BPA reduced granulosa cell DNA synthesis without changing DNA fragmentation, suggesting that BPA does not induce apoptosis. Conclusions Overall, the data demonstrate that BPA induces PPAR?, which mediates down-regulation of FSH-stimulated IGF-1, SF-1, GATA4, aromatase, and E2 in human granulosa cells. These observations support a potential role of altered steroidogenesis and proliferation within the ovarian follicular compartment due to this endocrine disruptor.

Kwintkiewicz, Jakub; Nishi, Yoshihiro; Yanase, Toshihiko; Giudice, Linda C.



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


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



Systemic Par-4 inhibits non-autochthonous tumor growth.  


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

Zhao, Yanming; Burikhanov, Ravshan; Brandon, Jason; Qiu, Shirley; Shelton, Brent J; Spear, Brett; Bondada, Subbarao; Bryson, Scott; Rangnekar, Vivek M



View from east to west of PAR site storage building; ...  

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

View from east to west of PAR site storage building; formerly PAR dispensary - Stanley R. Mickelsen Safeguard Complex, Storage Building, Across street from Family Housing Units 110 & 111, Nekoma, Cavalier County, ND


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



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



A combined global and local approach to elucidate spatial organization of the mycobacterial ParB-parS partition assembly  

PubMed Central

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 pre-divisional 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. 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 N.; Gupta, Sayan; Urban, Volker S.; Chance, Mark R.; D'Mello, Rhijuta; Smith, Lauren; Lyons, Kelly; Gee, Jessica



Apoptosis Mediated by a Novel Leucine Zipper Protein Par4  

Microsoft Academic Search

The prostate apoptosis response-4 (par-4) gene was isolated in a differential screen for immediate-early genes that are up-regulated during apoptosis of prostate cancer cells. Unlike most other immediate-early genes, par-4 is exclusively induced during apoptosis. The expression or induction of par-4 is not restricted to prostatic cells. The par-4 gene is widely expressed in diverse normal tissues and cell types

V. M. Rangnekar



Par(-4)oxysm in breast cancer.  


Women suffering from breast cancer often succumb to incurable recurrent disease resulting from therapy-resistant cancer cells. In this issue of Cancer Cell, Alvarez and colleagues identify downregulation of the tumor suppressor Par-4 as the key determinant in apoptosis evasion, which leads to tumor recurrence in breast cancer. PMID:23845436

Shrestha-Bhattarai, Tripti; Hebbar, Nikhil; Rangnekar, Vivek M



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



Induction of multiple follicular development by a single dose of long-acting recombinant follicle-Stimulating hormone (FSH-CTP, corifollitropin alfa) for controlled ovarian stimulation before in vitro fertilization.  


In a first feasibility study, the efficacy and safety of a single dose of recombinant long-acting FSH (FSH-CTP) were investigated in in vitro fertilization (IVF) patients undergoing controlled ovarian stimulation with a flexible GnRH antagonist protocol. Eligible subjects were randomized to receive a single dose of 120 micro g (n = 25), 180 microg (n = 24), or 240 microg (n = 25) corifollitropin alfa (FSH-CTP) or to start daily fixed doses of 150 IU recombinant FSH (rFSH) (n = 24, reference). Subjects who received a single dose of FSH-CTP continued 1 wk after injection (treatment d 8) with fixed daily doses of 150 IU rFSH (Puregon/Follistim) until the day of triggering final oocyte maturation. The terminal half-life of FSH-CTP was, on average, 65 h and dose independent. Cycle cancellation before human chorionic gonadotropin (hCG) administration occurred in only three subjects treated with FSH-CTP. The median duration of stimulation was 10.0 d in each FSH-CTP group and 9.0 d in the daily rFSH group. The total number of follicles at least 11 mm at stimulation d 8 and at the day of hCG administration tended to increase with dose of FSH-CTP, although a significant dose-response relationship was revealed only for the number of follicles at least 15 mm on the day of hCG (P = 0.03). Serum estradiol levels and inhibin-B levels were not significantly different between the four groups on d 8 and on the day of hCG. In total, 12 subjects (17.6%) in the FSH-CTP groups and two subjects (8.3%) in the rFSH group experienced a premature LH rise (defined as LH >or= 10 IU/liter) before the start of the GnRH antagonist (P value not significant between groups). This relatively high incidence of women demonstrating an early LH rise in the FSH-CTP groups may be related to the higher initial rises of serum estradiol and the use of a flexible GnRH antagonist protocol. The mean number of oocytes recovered per started cycle was higher in FSH-CTP-treated subjects compared with rFSH-treated subjects (significant at P = 0.03 for the 240- microg FSH-CTP group), but no difference could be noted between the number of good quality embryos (range of means, 3.8-4.8 per attempt), and equal numbers of embryos were available for embryo transfer. In summary, FSH-CTP appeared to be a potent inducer of multiple follicular growth; additional research will be needed to select the optimal FSH-CTP dose and treatment time interval. PMID:15126522

Devroey, P; Fauser, B C; Platteau, P; Beckers, N G; Dhont, M; Mannaerts, B M



Effect of prior FSH treatment on the estrus and ovulation responses to eCG in prepubertal gilts.  


The objective of this study was to determine the effect of pre-treatment of prepubertal gilts with FSH on the estrus and ovulatory responses to eCG injection at two ages. A total of 149 prepubertal Hypor gilts were selected at 150 days (n=76) or 180 days (n=73) of age and assigned to injection of 400 IU eCG plus 200 IU hCG (PG600), 600IU eCG alone (Folligon), pre-treatment with 72 mg FSH (Folltropin) administered as 6 x 12 mg injections at 12 h intervals with 600 IU Folligon 12h after last FSH injection, or non-injected controls. To facilitate detection of estrus, gilts were exposed to a mature boar for 15 min daily for 7 days. To determine ovulatory responses, blood samples were obtained on the day of injection and 10 days later and assayed for progesterone content. Following treatment at 150 days, one control gilt (5.3%) was deemed estrus but ovulation did not occur. Compared to treatment with Folligon alone, PG600 injection tended (P=0.1) to increase the estrus response (52.6% compared with. 26.3%) and increased (P<0.01) the ovulatory response (89.5% compared with. 47.4%). The estrous response in gilts pretreated with Folltropin was intermediate (42.1%) but the ovulatory response (47.4%) was the same as for Folligon alone. Following treatment at 180 days, two control gilts (10.5%) were deemed estrus and ovulation did occur in these gilts. There was no difference between hormone-treated groups for estrus or ovulatory responses, although the ovulatory response of PG600-treated gilts tended (P=0.1) to be greater than for the Folligon-treated group (89.5% compared with 66.7%), with Folltropin-pretreated gilts being intermediate (76.5%). These data demonstrate that the estrus and ovulatory responses of gilts were greater for PG600 than for Folligon and that while responses to PG600 were not affected by gilt age, for the combined Folligon groups, estrous response (P<0.02) and ovulatory response (P<0.05) improved with increased gilt age. PMID:18282669

Manjarin, R; Dominguez, J C; Castro, M J; Vallado, B; Rodriguez, S; Sprecher, D J; Cassar, G; Friendship, R M; Kirkwood, R N



Differential expression levels of Par-4 in melanoma.  


The pro-apoptotic prostate apoptosis response-4 gene product Par-4 sensitizes prostate cells to the induction of programmed cell death. In this study we examined Par-4 expression in human melanoma cell lines and melanoma metastases. The heterogeneous expression detected prompted us to investigate the biological relevance of Par-4 in a human melanoma xenotransplantation model. Overexpression of Par-4 by transfection decreased tumour development in xenotransplanted A375-C6 melanoma cells in SCID mice and correlated to an increase in tumour cell apoptosis. These data suggest that high expression of the pro-apoptotic protein Par-4 could qualify as a prognostic marker in human melanoma. PMID:11479426

Lucas, T; Pratscher, B; Krishnan, S; Fink, D; Günsberg, P; Wolschek, M; Wacheck, V; Muster, T; Romirer, I; Wolff, K; Pehamberger, H; Eichler, H G; Rangnekar, V M; Jansen, B



Superovulation in ewes by a single injection of pFSH dissolved in polyvinylpyrrolidone (PVP): effects of PVP molecular weight, concentration and schedule of treatment  

Microsoft Academic Search

Three experiments were carried out to evaluate induction in ewes of superovulation and embryo production by a single injection of a porcine pituitary extract (pFSH) dissolved in polyvinylpyrrolidone (PVP), investigating the effects of PVP molecular weight and its concentration (Experiment I), time and method of treatment (Experiments II and III). All ewes were synchronized for estrus by vaginal sponges impregnated

A. G D’Alessandro; G Martemucci; M. A Colonna; A Borghese; M. G Terzano; A Bellitti



Basal serum levels of FSH and estradiol in ovulatory and anovulatory women undergoing treatment by in-vitro maturation of immature oocytes  

Microsoft Academic Search

BACKGROUND: The study aim was to establish whether basal serum levels of FSH and estradiol are predictive of outcome in women undergoing treatment by in-vitro maturation (IVM) of immature oocytes. METHODS: Data were obtained from 123 unstimulated IVM cycles. Serum was taken between cycle days 2-4 for analysis. Patients received 10 000 IU of HCG 36 h before immature oocyte

Tim J. Child; Camille Sylvestre; Imran Pirwany; Seang Lin Tan


Development of non-competitive enzyme-linked immunosorbent assays for mummichog Fundulus heteroclitus gonadotropins - examining seasonal variations in plasma FSH and LH levels in both sexes.  


The mummichog Fundulus heteroclitus is an excellent experimental fish for reproductive physiology because of its adequate size, easiness for rearing, and controllable reproduction under laboratory conditions. Furthermore, it is the only species that the native GtHs and their subunits have been purified among small experimental fishes. In this study, homologous non-competitive enzyme-linked immunosorbent assays (ELISAs) for the mummichog FSH and LH were developed by raising monoclonal and polyclonal antibodies against the purified GtHs or their subunits, and the plasma hormone levels in various seasons were examined. The cross-reactivity of LH in the FSH ELISA and the cross-reactivity of FSH in the LH ELISA were low, 2.3% and 0.2% respectively, indicating high specificities of both GtH assays. The practical detection limits were 10 pg/well (0.125 ng/ml plasma) for the FSH ELISA and 8 pg/well (0.1 ng/ml plasma) for the LH ELISA. Plasma FSH levels in females indicated distinct correlations with ovarian stages: they were almost undetectable (<0.125 ng/ml) during the post-spawning immature phase (September), low values (0.3 ng/ml) during the cortical alveoli accumulation phase (December), considerably high (1.8 ng/ml) in the vitellogenic phase (February), and very high values (12 ng/ml) during the spawning season (June). The male FSH levels showed similar pattern of changes to that of females, also indicating distinct correlations with testicular activities. Plasma LH levels were considerably high during the spawning period in both sexes (3.3 ng/ml in females and 4.5 ng/ml in males). They were low or undetectable values in non-spawning seasons, and clear correlation with the gonadal stages was not observed. These results indicate the importance of FSH for various reproductive events in multiple spawning fishes, and are consistent with the general understanding that the LH is responsible for final gametes maturation in both sexes. Nonetheless, they further suggest that the role of LH for various reproductive events other than the final maturation may be limited. PMID:22819935

Shimizu, Akio; Ohkubo, Makoto; Hamaguchi, Masami



Mechanisms of apoptosis by the tumor suppressor Par-4.  


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



Apoptosis and tumor resistance conferred by Par-4.  


Par-4 is a tumor suppressor protein with a pro-apoptotic function. Epigenetic silencing of Par-4 is seen in diverse tumors and Par-4 knockout mice develop spontaneous tumors in various tissues. Endogenous Par-4 is essential for sensitization of cells to diverse apoptotic stimuli, whereas ectopic expression of Par-4 can selectively induce apoptosis in cancer cells. The cancer-specific pro-apoptotic action of Par-4 resides in its centrally located SAC domain. This review emphasizes the role of Par-4/SAC in apoptosis and tumor resistance. SAC transgenic mice display normal development and life span, and, most importantly, are resistant to spontaneous, as well as oncogene-induced, autochthonous tumors. The tumor resistant phenotype and undetectable toxicity of SAC in vivo suggests the SAC domain possesses tremendous therapeutic potential. PMID:18836307

Zhao, Yanming; Rangnekar, Vivek M



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.

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



Acute follicular response to FSH in heifers downregulated long term with a GnRH agonist and with suppressed ovarian follicular growth.  


The objectives of this study were to (1) ascertain ovarian follicular status in heifers where the pituitary gonadotrope cells producing LH and FSH were downregulated by long-term treatment with a GnRH agonist and (2) characterize the acute superstimulation of follicular growth in response to FSH in heifers where the pituitary was downregulated with a GnRH agonist. At the start of the study, heifers (3 year old) were implanted with GnRH agonist (n = 20) or received no treatment (control, n = 5). After 6 months, follicular growth in heifers implanted with GnRH agonist was restricted to early antral follicles (2-4 mm). At this time, these heifers were allocated to four groups and follicular development was superstimulated with FSH as follows: group 1 (n = 5) and group 2 (n = 5), a conventional FSH protocol with injections over 4 days (Days 0-3) with Group 2 receiving two times the normal dose of FSH; group 3 (n = 5), a single injection of FSH in saline on Day 0; group 4 (n = 5), a single injection of FSH in slow-release polyvinylpyrrolidone on Day 0. Follicular growth in the control heifers (n = 5) was superstimulated using the conventional 4-day FSH protocol. On Day 5, heifers in groups 1 and 2 had similar (P > 0.05) numbers of follicles in the size categories 6 to 7 mm (12.8 ± 3.0 follicles) and 8 to 9 mm (6.5 ± 1.0) as control heifers (6-7 mm, 14.6 ± 2.2; 8-9 mm, 6.2 ± 2.2) and six of the former heifers had follicles 10 mm (3.2 ± 1.4). Also on Day 5, follicular growth for heifers in group 3 was restricted to 4 to 5 mm (11.6 ± 3.0) and 6 to 7 mm (7.6 ± 3.7), whereas four out of five heifers in group 4 had follicles of 6 to 7 mm (8.2 ± 2.3) and three heifers had follicles of 8 to 9 mm (4.6 ± 2.2) and 10 mm (2.2 ± 0.9). Injection of exogenous LH on Day 5 induced ovulation in 9 out of 10 heifers in groups 1 and 2, no heifers in group 3, and 2 of 5 heifers in group 4. Plasma concentrations of progesterone 6 days after ovulation were the same (P > 0.05) for heifers in groups 1 and 2 (8.9 ± 0.9 ng/mL) and control heifers (10.0 ± 0.9 ng/mL). This study has shown that heifers treated chronically with a GnRH agonist have suppressed ovarian follicular growth but are able to respond to acute superstimulation with FSH. Furthermore, follicles in heifers treated with a GnRH agonist undergo morphologically normal growth in response to FSH and can ovulate and develop into a CL. The long-term GnRH agonist-treated heifer provides a practical model for repeated ovarian follicular superstimulation, multiple ovulation, and embryo transfer, without the need to control stage of the estrous cycle. PMID:23998741

D'Occhio, M J; Cremonesi, F; Trigg, T E; Aspden, W J; Baruselli, P S



[The physiological significance of the hippocampus on the inhibitory effects of corticosterone upon the estradiol-induced LH and FSH surges in rats].  


The effects of corticosterone (CS) on the gonadotropin surge induced by estradiol-benzoate (E2) were studied in adrenalectomized and ovariectomized (ADRX-OVEX) rats. The results are as follows. In ADRX-OVEX rats implanted with E2-tablets in the bilateral axillae, LH and FSH surges occurred 4 days after the implantation of E2, peaking at 17:00 h. The levels of these surges were markedly higher than those in OVEX rats similarly treated but were attenuated significantly by the subcutaneous injection of CS (25 micrograms in sesame oil) given at 12:00 h. The CS implantation (0.5 micrograms in 2 microliters sesame oil) into the dorsal hippocampus at 15:00 h significantly inhibited the levels of LH and FSH surges in ADRX-OVEX rats with E2-tablets. The effect of the CS implant in the lateral septal nucleus was also inhibitory but not statistically significant. The CS administration in the ventral part of the midbrain tegmentum did not elicit any change in the surge of LH and FSH. In animals with the dorsal fornix-section at the post-anterior-commissural level, surges of LH and FSH also occurred in the afternoon of the 4th day after the E2-tablets implantation, but the levels of LH and FSH were not significantly altered by an intravenous injection of CS (5 micrograms in saline) at 15:30 h. It was suggested the CS circulating in the blood would induce a rise of hippocampal activity which would exert a suppressive influence on the gonadotropin release. PMID:6440814

Nagase, M



Divergent immunomodulatory effects of recombinant and urinary-derived FSH, LH, and hCG on human CD4+ T cells.  


This study investigated the in vitro immune-modulating activities of recombinant versus highly purified urinary follicle-stimulating hormone (FSH), luteinizing hormone (LH), and human chorionic gonadotropin (hCG) at the cellular level. CD4(+) T cells were isolated from peripheral blood mononuclear cells obtained from ten healthy women (aged 19-30 years) with regular menstrual cycles during the follicular phase of their cycle. CD4(+) T cells were stimulated with anti-CD3/CD28 monoclonal antibodies as a T cell-specific mitogen. Proliferative and cytokine responses were analyzed at standard time points (72h). Recombinant FSH (r-FSH) and LH (r-LH) alone showed a modest capacity to influence proliferation and cytokine release by CD4(+) T cells. Conversely, their addition to T cells in combination with recombinant hCG (r-hCG) induced a powerful down-modulation of T cell proliferation, decreased interferon-gamma (IFN-gamma) secretion and increased interleukin-10 (IL-10) production. These immune-modulating activities were not present when CD4(+) T cells were stimulated either in the presence of urinary-purified FSH (u-FSH) or human menopausal gonadotropin (HMG), alone or in combination with recombinant hCG. We are the first to suggest that urinary-purified gonadotropins do not display profound immune-modulating activities as compared with the recombinant preparations, despite their endocrine effects. Therefore, the use of the recombinant preparations in assisted reproductive techniques might be relevant not only for their well-documented endocrine actions but also for their impact on the transient immune tolerance known to favour embryo implantation and progression of pregnancy. PMID:20452035

Carbone, Fortunata; Procaccini, Claudio; De Rosa, Veronica; Alviggi, Carlo; De Placido, Giuseppe; Kramer, Daniel; Longobardi, Salvatore; Matarese, Giuseppe



Par-4 prevents breast cancer recurrence.  


Therapy resistance and disease recurrence are two of the most challenging aspects in breast cancer treatment. A recent article in Cancer Cell makes a significant contribution toward a better understanding of this therapeutic problem by establishing downregulation of the tumor suppressor Par-4 as the primary determinant of breast cancer recurrence. This viewpoint brings forth the importance of their findings and its implications on future research and therapy. PMID:24164776

Hebbar, Nikhil; Shrestha-Bhattarai, Tripti; Rangnekar, Vivek M



Enlèvement de particules par laser impulsionnel  

NASA Astrophysics Data System (ADS)

L'enlèvement de particules par laser impulsionnel (ns) est étudié expérimentalement. Des efficacités supérieures à 90% sont obtenues pour l'enlèvement de particules de polystyrene (PS) de diamètre 385 nm sur des surfaces de Si et Cu. Les fluences seuils d'enlèvement sont déterminées et comparées à une modélisation de l'expansion thermique du substrat. L'interprétation est discutée en terme de mécanismes fondamentaux envisageables responsables de l'éjection des particules.

Grojo, D.; Delaporte, P.; Cros, A.



Par Pond refill water quality sampling  

SciTech Connect

This study was designed to document anoxia and its cause in the event that the anoxia caused a fish kill. However, no fish kill was observed during this study, and dissolved oxygen and nutrient concentrations generally remained within the range expected for southeastern reservoirs. Par Pond water quality monitoring will continue during the second summer after refill as the aquatic macrophytes become reestablished and nutrients in the sediments are released to the water column.

Koch, J.W. II; Martin, F.D.; Westbury, H.M.



Par-4 prevents breast cancer recurrence  

PubMed Central

Therapy resistance and disease recurrence are two of the most challenging aspects in breast cancer treatment. A recent article in Cancer Cell makes a significant contribution toward a better understanding of this therapeutic problem by establishing downregulation of the tumor suppressor Par-4 as the primary determinant of breast cancer recurrence. This viewpoint brings forth the importance of their findings and its implications on future research and therapy.



La modélisation par Reverse Monte Carlo (RMC)  

NASA Astrophysics Data System (ADS)

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

McGreevy, R. L.



Distinct PAR\\/IQGAP expression patterns during murine development: implications for thrombin-associated cytoskeletal reorganization  

Microsoft Academic Search

Thrombin has a critical role in many adult and embryologic cellular processes, exerting its effects through two high-affinity thrombin receptor systems: protease-activated receptor 1 (PAR1) and the PAR3\\/PAR4 system. Both hPAR1 and hPAR3 are coclustered in the human genome, with hPAR3 encompassed within hIQGAP2, a putative GTPase activating protein with actin polymerizing functions linked to cytoskeletal reorganization. Since hPARs colocalize

Lisa D. Cupit; Valentina A. Schmidt; Frederick Miller; Wadie F. Bahou



Apoptosis mediated by a novel leucine zipper protein Par-4.  


The prostate apoptosis response-4 (par-4) gene was isolated in a differential screen for immediate-early genes that are up-regulated during apoptosis of prostate cancer cells. Unlike most other immediate-early genes, par-4 is exclusively induced during apoptosis. The expression or induction of par-4 is not restricted to prostatic cells. The par-4 gene is widely expressed in diverse normal tissues and cell types and conserved during evolution. Par-4 protein contains a leucine zipper domain that is essential for sensitization of cells to apoptosis. Functional studies indicate that par-4 expression is necessary to induce apoptosis. Par-4 protein may induce apoptosis by a p53-independent pathway that involves cytoplasmic inactivation of atypical protein kinase C isoforms resulting in down-regulation of MAP kinase activity and an up-regulation of p38 kinase activity. However, Par-4 is detected in the cytoplasm and in the nucleus, suggesting both cytoplasmic and nuclear roles for the pro-apoptotic protein. Interestingly, Par-4 is predicted to contain a death domain homologous to that of Fas or TRADD, and may therefore trigger a death cascade analogous to that of the death domain proteins. Par-4-dependent apoptosis is abrogated by Bcl-2 and by caspase inhibitors. Identification of the components of the p53-independent apoptosis pathway induced by Par-4 may help to further elucidate the mechanism of Par-4 action. Moreover, in view of the pro-apoptotic function of Par-4, its role in diseases, such as cancer and neurogenerative disorders, whose pathophysiology involves apoptotic cell death needs further investigation. PMID:14646502

Rangnekar, V M



"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.



A conserved mode of protein recognition and binding in a ParD-ParE toxin-antitoxin complex†  

PubMed Central

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 Å resolution. This TA system forms an ?2?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 sub-domain that is conserved between distantly-related members of the RelE/ParE toxin superfamily despite low 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



The protease activated receptor 2 (PAR2) polymorphic variant F240S constitutively activates PAR2 receptors and potentiates responses to small-molecule PAR2 agonists.  


AC-55541 [N-[[1-(3-bromo-phenyl)-eth-(E)-ylidene-hydrazinocarbonyl]-(4-oxo-3,4-dihydro-phthalazin-1-yl)-methyl]-benzamide] and AC-264613 [2-oxo-4-phenylpyrrolidine-3-carboxylic acid [1-(3-bromo-phenyl)-(E/Z)-ethylidene]-hydrazide] are the first two small-molecule agonists described for the G protein-coupled receptor protease-activated receptor 2 (PAR2), but whether they activate PAR2 through a similar mechanism as its tethered peptide ligand or soluble peptide mimetics of its tethered peptide ligand is unclear. Extracellular loop 2 (ECL2) has been shown to play a critical role in the activation mechanism of PAR2. Therefore, we constructed a series of PAR2 receptors mutated in ECL2, including a previously described polymorphic variant of PAR2 (F240S), and compared AC-55541 and AC-264613 to SLIGRL and a potent analog of SLIGRL called 2-furoyl LIGRLO in a series of functional assays, including cellular proliferation, phosphatidylinositol hydrolysis, and ?-arrestin recruitment assays. Surprisingly, receptors with the F240S mutation were constitutively active in all functional assays tested. Furthermore, AC-55541 and AC-264613 were potentiated over 30-fold at the receptors with the F240S mutation, whereas SLIGRL and 2-furoyl LIGRLO were much less affected. In contrast, mutagenesis of charged residues in ECL2 confirmed their important role in the actions of peptide agonists of PAR2, whereas these mutations did not significantly affect activation of PAR2 by AC-55541 or AC-264613. These results suggest that F240S PAR2 receptors may be useful in screens to detect novel small-molecule PAR2 modulators and that further work on the biological importance of the F240S PAR2 variant is warranted. PMID:24078870

Ma, Jian-Nong; Burstein, Ethan S



Apoptosis by Par4 in cancer and neurodegenerative diseases  

Microsoft Academic Search

Prostate apoptosis response-4 (par-4) is a pro-apoptotic gene identified in prostate cancer cells undergoing apoptosis. Par-4 protein, which contains a leucine zipper domain at the carboxy-terminus, functions as a transcriptional repressor in the nucleus. Par-4 selectively induces apoptosis in androgen-independent prostate cancer cells and Ras-transformed cells but not in androgen-dependent prostate cancer cells or normal cells. Cells that are resistant

Nadia El-Guendy; Vivek M Rangnekar



Regulation of cancer cell survival by Par-4.  


Prostate apoptosis response-4 (Par-4) is a unique pro-apoptotic protein that selectively induces apoptosis in cancer cells. Moreover, Par-4 sensitizes cells to the action of diverse apoptotic stimuli and causes tumor regression. This review discusses the prominent structural and functional features of Par-4 and the multiple levels of regulation of its apoptotic function, all of which can be utilized to develop targeted cancer therapy. PMID:16382046

Ranganathan, Padhma; Rangnekar, Vivek M



A new method for PAR reduction in baseband DMT systems  

Microsoft Academic Search

The high peak-to-average power ratio (PAR) in real-baseband discrete multitone modulation (DMT) systems can significantly limit performance. Tone reservation techniques use unavailable or reserved tones to design a peak-cancelling signal that lowers the PAR of a transmit data block. Previous methods converge very slowly to a good solution. Our new active-set method converges much faster toward a minimum-PAR solution at

Brian S. Krongold; Douglas L. Jones



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



ParABS system in chromosome partitioning in the bacterium Myxococcus xanthus.  


Chromosome segregation is an essential cellular function in eukaryotic and prokaryotic cells. The ParABS system is a fundamental player for a mitosis-like process in chromosome partitioning in many bacterial species. This work shows that the social bacterium Myxococcus xanthus also uses the ParABS system for chromosome segregation. Its large prokaryotic genome of 9.1 Mb contains 22 parS sequences near the origin of replication, and it is shown here that M. xanthus ParB binds preferentially to a consensus parS sequence in vitro. ParB and ParA are essential for cell viability in M. xanthus as in Caulobacter crescentus, but unlike in many other bacteria. Absence of ParB results in anucleate cells, chromosome segregation defects and loss of viability. Analysis of ParA subcellular localization shows that it clusters at the poles in all cells, and in some, in the DNA-free cell division plane between two chromosomal DNA masses. This ParA localization pattern depends on ParB but not on FtsZ. ParB inhibits the nonspecific interaction of ParA with DNA, and ParA colocalizes with chromosomal DNA only when ParB is depleted. The subcellular localization of ParB suggests a single ParB-parS complex localized at the edge of the nucleoid, next to a polar ParA cluster, with a second ParB-parS complex migrating after the replication of parS takes place to the opposite nucleoid edge, next to the other polar ParA cluster. PMID:24466283

Iniesta, Antonio A



ParABS System in Chromosome Partitioning in the Bacterium Myxococcus xanthus  

PubMed Central

Chromosome segregation is an essential cellular function in eukaryotic and prokaryotic cells. The ParABS system is a fundamental player for a mitosis-like process in chromosome partitioning in many bacterial species. This work shows that the social bacterium Myxococcus xanthus also uses the ParABS system for chromosome segregation. Its large prokaryotic genome of 9.1 Mb contains 22 parS sequences near the origin of replication, and it is shown here that M. xanthus ParB binds preferentially to a consensus parS sequence in vitro. ParB and ParA are essential for cell viability in M. xanthus as in Caulobacter crescentus, but unlike in many other bacteria. Absence of ParB results in anucleate cells, chromosome segregation defects and loss of viability. Analysis of ParA subcellular localization shows that it clusters at the poles in all cells, and in some, in the DNA-free cell division plane between two chromosomal DNA masses. This ParA localization pattern depends on ParB but not on FtsZ. ParB inhibits the nonspecific interaction of ParA with DNA, and ParA colocalizes with chromosomal DNA only when ParB is depleted. The subcellular localization of ParB suggests a single ParB-parS complex localized at the edge of the nucleoid, next to a polar ParA cluster, with a second ParB-parS complex migrating after the replication of parS takes place to the opposite nucleoid edge, next to the other polar ParA cluster.

Iniesta, Antonio A.



Modelisation par elements finis du muscle strie  

NASA Astrophysics Data System (ADS)

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

Leonard, Mathieu


Childhood Pars Planitis; Clinical Features and Outcomes  

PubMed Central

Purpose To evaluate the demographic and clinical features of childhood pars planitis, and to determine the therapeutic and visual outcomes of the disease. Methods Medical records of pediatric patients (less than 16 years of age at diagnosis) with pars planitis and at least 6 months of follow-up who were referred to Labbafinejad Medical Center, Tehran, Iran over a 22 year period were reviewed. Results Overall, 117 eyes of 61 patients including 51 (83.6%) male subjects were included. Mean age at the time of diagnosis was 7.8±3.2 (range, 3–16) years. Mean best corrected visual acuity (BCVA) was 0.88±0.76 logMAR at presentation which improved to 0.39±0.51 logMAR at final visit (P<0.001). Endotheliitis was present in 23 (19.6%) eyes and was significantly more prevalent in subjects younger than 9 years (P=0.025). Cataract formation (41.9%) and cystoid macular edema (19.7%) were the most prevalent complications. Univariate regression analysis showed that better baseline visual acuity (OR=0.38, 95%CI 0.21–0.70, P=0.002), age older than 5 years at disease onset (OR=0.36, 95%CI 0.14–0.9, P=0.029), absence of endotheliitis (OR=0.39, 95%CI 0.15–0.99, P=0.047) and female gender (OR=3.77, 95%CI 1.03–13.93, P=0.046) were significantly associated with final BCVA of 20/40 or better. Conclusion Childhood pars planitis was much more common among male subjects. Endotheliitis may be a sign of inflammation spillover and is more prevalent in younger patients. Visual prognosis is favorable in most patients with appropriate treatment.

Nikkhah, Homayoon; Ramezani, Alireza; Ahmadieh, Hamid; Soheilian, Masoud; Azarmina, Mohsen; Dehghan, Mohammad-Hossein; Moradian, Siamak; Nourinia, Ramin



L’endoscopie vue par le malade  

Microsoft Academic Search

Résumé  Les auteurs se proposent de vérifier si et en quelle mesure un examen œsophago-gastro-duodenoscopique altère ou modifie le\\u000a schéma corporel de l’individu.\\u000a \\u000a Comme instrument de recherche les A.A. ont employé le dessin, en tant que moins sujet à des modifications conscientes ou inconscientes.\\u000a \\u000a \\u000a On a examiné 30 malades hétérogènes par sexe, âge, culture et condition socio-économique. A l’intérieur de cet

G. Schelotto; F. Molinari; E. Bovero



[Vision loss after uncomplicated pars plana vitrectomy].  


Every eye surgery has its pitfalls and possible complications. Even after properly and noncomplicated orbital or intraocular surgery there can develop a loss of visual acuity or visual field. In the perioperative period was on the operated eye for epimacular membrane (23G pars plana vitrectomy) retinal arterial occlusion with fatal consequences for visual function. Entrance visual acuity decreased from 20/63 to counting fingers. Risk factors for age-related and underlying diseases were accompanied by systemic hypotension and mild anemia. Commonly available topical and general therapy did not lead to any significant improvement. PMID:24697538

Hejsek, L; Dusová, J; Stepanov, A; Rozsíval, P



True and Sham Acupuncture Produced Similar Frequency of Ovulation and Improved LH to FSH Ratios in Women with Polycystic Ovary Syndrome  

PubMed Central

Context: Acupuncture may represent a nonpharmaceutical treatment for women with polycystic ovary syndrome (PCOS), based on four studies. Objective: The objective of the study was to determine whether true, as compared with sham, acupuncture normalizes pituitary gonadotropin hormones and increases ovulatory frequency in women with PCOS. Design: This was a randomized, double-blind, sham-controlled clinical trial (5 month protocol). Setting: The study was conducted in central Virginia. Participants: Eighty-four reproductive-aged women completed the intervention. Eligibility required a PCOS diagnosis and no hormonal intervention 60 d before enrollment. Interventions: Intervention included 12 sessions of true or sham acupuncture (Park sham device) for 8 wk. Main Outcome Measures: Serum LH and FSH at baseline, after intervention, and 3 months later were measured. Ovulation was measured with weekly urine or blood samples. Results: Both arms demonstrated a similar mean ovulation rate over the 5 months (0.37/month among n = 40 true acupuncture and 0.40/month among n = 44 sham participants, P = 0.6), similar LH to FSH ratio improvement (?0.5 and ?0.8 true and sham, respectively, P < 0.04 after intervention vs. baseline) and a similar decline in LH over the 5-month protocol (P < 0.05). Neither arm experienced a change in FSH. There were seven pregnancies (no difference by intervention, P = 0.7). Lower fasting insulin and free testosterone were highly correlated with a higher ovulation rate within the true acupuncture group only (P = 0.03), controlling for prestudy menstrual frequency and body mass index. Conclusion: We were unable to discern a difference between the true and sham acupuncture protocols for these women with PCOS, and both groups had a similar improvement in their LH/FSH ratio.

Williams, Christopher D.; Jenkins, Jeffrey; Patrie, James T.



Follicle-stimulating hormone (FSH) stimulates the expression of Pin1, a peptidyl-prolyl isomerase, in the bovine granulosa cells.  


A peptidyl-prolyl isomerase, Pin 1, has been shown to play a role in the regulation of cell cycle progression, both in vitro and in vivo. However, the involvement of Pin 1 during follicular development is not well understood. The aim of this study was first to investigate the expression of Pin 1 mRNA in the granulosa and theca cells of the follicle at different developmental stages of follicles in the bovine ovary, and second, to examine the effects of follicle-stimulating hormone (FSH) and estradiol (E2) on the expression of Pin 1 in the cultured bovine granulosa cells. Follicles were classified into four groups based on the diameter (dominant follicles >8.5mm in diameter, subordinate follicles <8.5mm in diameter) and the relative levels of E2 and progesterone (P4) (E2:P4>1, estrogen active; E2:P4<1, estrogen inactive): i.e. preovulatory dominant follicles (POFs); E2 active dominant follicles (EADs); E2 inactive dominant follicles (EIDs); small follicles (SFs). The expression of the Pin 1 gene was significantly increased in the granulosa cells of EADs as compared with those of other follicles, whereas its expression in theca cells did not differ among follicles at different developmental stages. The concentration of 5 ng/ml FSH alone and the combination of 1 ng/ml E2 and 5 ng/ml FSH stimulated the expression of the Pin 1 gene in bovine granulosa cells. Our data provide the first evidence that Pin 1 expression in the granulosa cells but not the theca cells changes during follicular development, and that FSH stimulate the expression of the Pin 1 gene. These results suggest that Pin 1 regulates the timing of cell proliferation and may act as an intracellular signal responder in the granulosa cells during bovine follicle development. PMID:16621422

Shimizu, Takashi; Tetsuka, Masafumi; Miyamoto, Akio; Uchida, Takafumi



Ovulation induction in women with polycystic ovary syndrome: randomized trial of clomiphene citrate versus low-dose recombinant FSH as first line therapy  

Microsoft Academic Search

This single centre randomized controlled trial was undertaken to compare the efficacy and safety of clomiphene citrate and lowdose recombinant FSH as first line pharmacological therapy for anovulatory infertility associated with polycystic ovary syndrome (PCOS). Seventy-six infertile patients with PCOS were randomized to receive clomiphene citrate (50–150 mg\\/day for 5 days) (clomiphene citrate group, n = 38) or recombinant human

Eugenio López; Gunby Joanne; Salim Daya; Juan J Parrilla; Lorenzo Abad; Juan Balasch



Pediatric reference intervals for FSH, LH, estradiol, T3, free T3, cortisol, and growth hormone on the DPC IMMULITE 1000  

Microsoft Academic Search

BackgroundWe studied serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), triiodothyronine (T3), free T3 (FT3), cortisol and growth hormone (GH) concentrations in a population of pediatric patients. The reference intervals were determined separately for females and males stratified by age groups to assess age- and sex-related differences. Our objective was to obtain reference intervals for the 7 serum analytes

Offie P. Soldin; Eve G. Hoffman; Michael A. Waring; Steven J. Soldin



Co-administration of metformin during rFSH treatment in patients with clomiphene citrate-resistant polycystic ovarian syndrome: a prospective randomized trial  

Microsoft Academic Search

BACKGROUND: This study aims to evaluate the impact of metformin on ovarian response when co-administered during recombinant (r)FSH using the low-dose step-up protocol in clomiphene citrate-resistant polycystic ovarian syndrome (PCOS) patients with normal glucose tolerance. METHODS AND RESULTS: Thirty-two patients were randomized to metformin (n 16) and placebo (n 16) groups. Hormonal assessment, a 75 g oral glucose tolerance test

Hakan Yaralõ; Aygul Demirol; Hulusi B. Zeynelog; Nuray Yig; Orhan Bukulmez; Zehra Koray



Expression and regulation of SNAP-25 and synaptotagmin VII in developing mouse ovarian follicles via the FSH receptor.  


Soluble-NSF attachment protein receptor (SNARE) proteins play a role in vesicle fusion, exocytosis, and intracellular trafficking in neuronal cells as well as in fertilization and embryogenesis. We investigated the expression patterns of two SNARE proteins, SNAP-25 and synaptotagmin VII (SytVII), and their regulation by pregnant mare serum gonadotropin (PMSG) during mouse ovarian follicular development. Ovaries were obtained at 0, 12, 24, 36, and 48 h post-PMSG injection of immature mice. SNAP-25 and SytVII mRNA expression levels increased gradually in a time-dependant manner. However, protein levels revealed different patterns of expression, suggesting different translational regulation following PMSG stimulation. SNAP-25 and SytVII expression was closely associated with thickening of the granulosa cell (GC) layer and follicle morphological changes from a flattened to a cuboidal shape. To explore follicle stimulating hormone receptor (FSHR)-mediated regulation of their expression, GCs from preantral follicles were cultured to examine the effects of FSHR siRNA knockdown. FSHR siRNA abolished upregulation of the SNAREs in both PMSG and FSH-stimulated GCs. This abolished gene expression was rescued by adding dibutyryl cyclic AMP to the cultures. These results suggest that SNAP-25 and SytVII expression is regulated via the FSHR-cAMP pathway during follicular development. PMID:23207584

Choi, Sung Sik; Jung, Joo Young; Lee, Dong Ho; Kang, Ji Yoon; Lee, Sang Ho



GnRH agonist trigger for women with breast cancer undergoing fertility preservation by aromatase inhibitor/FSH stimulation  

PubMed Central

Aromatase inhibitors can be utilized to minimize oestrogen exposure in breast cancer patients undergoing gonadotrophin stimulation. This retrospective-prospective study determined whether using a gonadotrophin-releasing hormone agonist (GnRHa) trigger instead of human chorionic gonadotrophin (HCG) would reduce oestrogen exposure and improve cycle outcomes in aromatase inhibitor cycles. Seventy-four breast cancer patients who desired fertility preservation, with normal ovarian reserve and <45 years of age received letrozole 5 mg/day plus recombinant FSH 150–300 IU/day for ovarian stimulation. Subjects either received HCG 5000–10,000 IU (n = 47) or leuprolide acetate 1 mg (GnRHa, n = 27) as trigger. Oestradiol measurements were repeated 4 days after the trigger and subjects were evaluated for ovarian hyperstimulation syndrome (OHSS). In the GnRHa group, oestradiol concentrations dropped significantly after the trigger than the HCG group (P = 0.013) and there was a lower incidence of OHSS. GnRHa trigger resulted in a higher number and percentage of mature oocytes and a higher number of cryopreserved embryos or oocytes compared with HCG. GnRHa trigger improves outcomes by increasing the yield of mature oocytes and embryos in aromatase inhibitor cycles and also decreases the post-trigger oestradiol exposure as well as OHSS risks in women with breast cancer.

Oktay, Kutluk; Turkcuoglu, Ilg?n; Rodriguez-Wallberg, Kenny A



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


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



Apoptosis by Par-4 in cancer and neurodegenerative diseases.  


Prostate apoptosis response-4 (par-4) is a pro-apoptotic gene identified in prostate cancer cells undergoing apoptosis. Par-4 protein, which contains a leucine zipper domain at the carboxy-terminus, functions as a transcriptional repressor in the nucleus. Par-4 selectively induces apoptosis in androgen-independent prostate cancer cells and Ras-transformed cells but not in androgen-dependent prostate cancer cells or normal cells. Cells that are resistant to apoptosis by Par-4 alone, however, are greatly sensitized by Par-4 to the action of other pro-apoptotic insults such as growth factor withdrawal, tumor necrosis factor, ionizing radiation, intracellular calcium elevation, or those involved in neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and stroke. Apoptosis induction by Par-4 involves a complex mechanism that requires activation of the Fas death receptor signaling pathway and coparallel inhibition of cell survival NF-kappaB transcription activity. The unique ability of Par-4 to induce apoptosis in cancer cells but not normal cells and the ability of Par-4 antisense or dominant-negative mutant to abrogate apoptosis in neurodegenerative disease paradigms makes it an appealing candidate for molecular therapy of cancer and neuronal diseases. PMID:12565819

El-Guendy, Nadia; Rangnekar, Vivek M



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



Mutually exclusive expression patterns of Bcl2 and Par4 in human prostate tumors consistent with down-regulation of Bcl2 by Par4  

Microsoft Academic Search

Par-4 is a widely expressed protein that sensitizes both prostatic and non-prostatic cells to apoptosis. Constitutive- or regulated- overexpression of Par-4 caused a reduction in the levels of the anti-apoptotic protein Bcl-2. Replenishment of Bcl-2 levels abrogated susceptibility to Par-4-dependent apoptosis, suggesting that Par-4-mediated apoptosis requires downmodulation of Bcl-2 levels. The inverse correlation between Par-4 and Bcl-2 expression was recapitulated

Guofang Qiu; Mansoor Ahmed; Stephen F Sells; Mohammed Mohiuddin; Michael H Weinstein; Vivek M Rangnekar



Effect of addition of FSH, LH and proteasome inhibitor MG132 to in vitro maturation medium on the developmental competence of yak (Bos grunniens) oocytes  

PubMed Central

Background The competence for embryonic development after IVF is low in the yak, therefore, we investigated the effects of supplementation of FSH, LH and the proteasome inhibitor MG132 in IVM media on yak oocyte competence for development after IVF. Methods In Experiment 1, yak cumulus-oocyte complexes (COCs) were in vitro matured (IVM) in TCM-199 with 20% fetal calf serum (FCS), 1 microg/mL estradiol-17beta, and different combinations of LH (50 or 100 IU/mL) and FSH (0, 1, 5, 10 microg/mL) at 38.6 degrees C, 5% CO2 in air for 24 h. Matured oocytes were exposed to frozen–thawed, heparin-capacitated yak sperm. Presumptive zygotes were cultured in SOF medium containing 6 mg/ml BSA, 0.5 mg/mL myoinositol, 3% (v/v) essential amino acids, 1% nonessential amino acids and 100 ?g/mL L-glutamine (48 h, 38.5 degrees C, 5% CO2, 5% O2, and 90% N2). In Experiment 2, cumulus cells were collected at the end of IVM to determine FSHR and LHR mRNA expression by real-time PCR. In Experiment 3 and 4, COCs were cultured in the presence or absence of the proteasomal inhibitor MG132 from either 0–6 h or 18–24 h after initiation of maturation. Results The optimum concentration of FSH and LH in IVM media was 5 microg/mL FSH and 50 IU/mL LH which resulted in the greatest cleavage (79.1%) and blastocyst rates (16.1%). Both FSHR and LHR mRNA were detected in yak cumulus cells after IVM. Treatment with MG132 early in maturation reduced (P?FSH and LH in IVM medium, and treatment with MG132 late in maturation can improve yak oocytes competence for development after IVF.



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.

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



TMS suppression of right pars triangularis, but not pars opercularis, improves naming in aphasia.  


This study sought to discover if an optimum 1 cm(2) area in the non-damaged right hemisphere (RH) was present, which could temporarily improve naming in chronic, nonfluent aphasia patients when suppressed with repetitive transcranial magnetic stimulation (rTMS). Ten minutes of slow, 1Hz rTMS was applied to suppress different RH ROIs in eight aphasia cases. Picture naming and response time (RT) were examined before, and immediately after rTMS. In aphasia patients, suppression of right pars triangularis (PTr) led to significant increase in pictures named, and significant decrease in RT. Suppression of right pars opercularis (POp), however, led to significant increase in RT, but no change in number of pictures named. Eight normals named all pictures correctly; similar to aphasia patients, RT significantly decreased following rTMS to suppress right PTr, versus right POp. Differential effects following suppression of right PTr versus right POp suggest different functional roles for these regions. PMID:21864891

Naeser, Margaret A; Martin, Paula I; Theoret, Hugo; Kobayashi, Masahito; Fregni, Felipe; Nicholas, Marjorie; Tormos, Jose M; Steven, Megan S; Baker, Errol H; Pascual-Leone, Alvaro



TMS suppression of right pars triangularis, but not pars opercularis, improves naming in aphasia  

PubMed Central

This study sought to discover if an optimum 1 cm2 area in the non-damaged right hemisphere (RH) was present, which could temporarily improve naming in chronic, nonfluent aphasia patients when suppressed with repetitive transcranial magnetic stimulation (rTMS). Ten minutes of slow, 1 Hz rTMS was applied to suppress different RH ROIs in eight aphasia cases. Picture naming and response time (RT) were examined before, and immediately after rTMS. In aphasia patients, suppression of right pars triangularis (PTr) led to significant increase in pictures named, and significant decrease in RT. Suppression of right pars opercularis (POp), however, led to significant increase in RT, but no change in number of pictures named. Eight normals named all pictures correctly; similar to aphasia patients, RT significantly decreased following rTMS to suppress right PTr, versus right POp. Differential effects following suppression of right PTr versus right POp suggest different functional roles for these regions.

Naeser, Margaret A.; Martin, Paula I.; Theoret, Hugo; Kobayashi, Masahito; Fregni, Felipe; Nicholas, Marjorie; Tormos, Jose M.; Steven, Megan S.; Baker, Errol H.; Pascual-Leone, Alvaro



Novel Role for Proteinase-activated Receptor 2 (PAR2) in Membrane Trafficking of Proteinase-activated Receptor 4 (PAR4)*  

PubMed Central

Proteinase-activated receptors 4 (PAR4) is a class A G protein-coupled receptor (GPCR) recognized through the ability of serine proteases such as thrombin and trypsin to mediate receptor activation. Due to the irreversible nature of activation, a fresh supply of receptor is required to be mobilized to the cell surface for responsiveness to agonist to be sustained. Unlike other PAR subtypes, the mechanisms regulating receptor trafficking of PAR4 remain unknown. Here, we report novel features of the intracellular trafficking of PAR4 to the plasma membrane. PAR4 was poorly expressed at the plasma membrane and largely retained in the endoplasmic reticulum (ER) in a complex with the COPI protein subunit ?-COP1. Analysis of the PAR4 protein sequence identified an arginine-based (RXR) ER retention sequence located within intracellular loop-2 (R183AR ? A183AA), mutation of which allowed efficient membrane delivery of PAR4. Interestingly, co-expression with PAR2 facilitated plasma membrane delivery of PAR4, an effect produced through disruption of ?-COP1 binding and facilitation of interaction with the chaperone protein 14-3-3?. Intermolecular FRET studies confirmed heterodimerization between PAR2 and PAR4. PAR2 also enhanced glycosylation of PAR4 and activation of PAR4 signaling. Our results identify a novel regulatory role for PAR2 in the anterograde traffic of PAR4. PAR2 was shown to both facilitate and abrogate protein interactions with PAR4, impacting upon receptor localization and cell signal transduction. This work is likely to impact markedly upon the understanding of the receptor pharmacology of PAR4 in normal physiology and disease.

Cunningham, Margaret R.; McIntosh, Kathryn A.; Pediani, John D.; Robben, Joris; Cooke, Alexandra E.; Nilsson, Mary; Gould, Gwyn W.; Mundell, Stuart; Milligan, Graeme; Plevin, Robin



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.

Chakravarty, Ambar



Time interval between FSH priming and aspiration of immature human oocytes for in-vitro maturation: a prospective randomized study.  


This prospective randomized controlled study was performed to examine the influence of coasting for 2 days versus 3 days following a fixed daily dose of FSH for 3 days. The outcome was 2-fold. In the first experiment (n = 50 cycles), the incidence of apoptosis in granulosa cells was compared. In the second experiment (n = 28 cycles), the rates of maturation, fertilization, cleavage, pregnancy and implantation were compared. In addition, clinical pregnancy rate per aspiration was registered. Granulosa cells were collected from follicular aspirates and pooled for each patient. The APOPTAG Detection Kit was used for staining of the granulosa cells and detection of apoptosis. Oocytes were matured in vitro for 28-30 h before intracytoplasmic sperm injection. The incidence of apoptosis in granulosa cells did not differ between granulosa cells obtained after 2 days coasting (n = 25 cycles) compared with granulosa cells obtained after 3 days coasting (n = 25 cycles) (26.2 versus 26.2%). When oocytes obtained after coasting for 2 days (n = 12 cycles) were compared with oocytes obtained after coasting for 3 days (n = 16 cycles), no significant difference was found between rates of maturation (63 versus 65%), fertilization (60 versus 68%), cleavage (86 versus 92%) or implantation [5/12; 42 versus 1/12 (8%)]. A higher clinical pregnancy rate per aspiration [5/16 (31%) versus 1/12 (8%)] was obtained after coasting for 3 days compared with coasting for 2 days. The difference was not significant. This randomized study showed no difference in apoptosis of granulosa cells and no difference in developmental competence of oocytes obtained after coasting for 3 days compared with 2 days coasting. PMID:12831585

Mikkelsen, Anne Lis; Høst, Erik; Blaabjerg, Jan; Lindenberg, Svend



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.

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



Mapping Human Protease-activated Receptor 4 (PAR4) Homodimer Interface to Transmembrane Helix 4*  

PubMed Central

Thrombin activates platelets by binding and cleaving protease-activated receptors 1 and 4 (PAR1 and PAR4). Because of the importance of PAR4 activation on platelets in humans and mice and emerging roles for PAR4 in other tissues, experiments were done to characterize the interaction between PAR4 homodimers. Bimolecular fluorescence complementation and bioluminescence resonance energy transfer (BRET) were used to examine the PAR4 homodimer interface. In bimolecular fluorescence complementation experiments, PAR4 formed homodimers that were disrupted by unlabeled PAR4 in a concentration-dependent manner, but not by rhodopsin. In BRET experiments, the PAR4 homodimers showed a specific interaction as indicated by a hyperbolic BRET signal in response to increasing PAR4-GFP expression. PAR4 did not interact with rhodopsin in BRET assays. The threshold maximum BRET signal was disrupted in a concentration-dependent manner by unlabeled PAR4. In contrast, rhodopsin was unable to disrupt the BRET signal, indicating that the disruption of the PAR4 homodimer is not due to nonspecific interactions. A panel of rho-PAR4 chimeras and PAR4 point mutants has mapped the dimer interface to hydrophobic residues in transmembrane helix 4. Finally, mutations that disrupted dimer formation had reduced calcium mobilization in response to the PAR4 agonist peptide. These results link the loss of dimer formation to a loss of PAR4 signaling.

de la Fuente, Maria; Noble, Daniel N.; Verma, Sheetal; Nieman, Marvin T.



Attenuated Vasodilator Effectiveness of Protease-Activated Receptor 2 Agonist in Heterozygous par2 Knockout Mice  

PubMed Central

Studies of homozygous PAR2 gene knockout mice have described a mix of phenotypic effects in vitro and in vivo. However, there have been few studies of PAR2 heterozygous (wild-type/knockout; PAR2-HET) mice. The phenotypes of many hemi and heterozygous transgenic mice have been described as intermediates between those of wild-type and knockout animals. In our study we aimed to determine the effects of intermediary par2 gene zygosity on vascular tissue responses to PAR2 activation. Specifically, we compared the vasodilator effectiveness of the PAR2 activating peptide 2-furoyl-LIGRLO-amide in aortas of wild-type PAR2 homozygous (PAR2-WT) and PAR2-HET mice. In myographs under isometric tension conditions, isolated aortic rings were contracted by alpha 1-adrenoeceptor agonist (phenylephrine), and thromboxane receptor agonist (U46619) and then relaxation responses by the additions of 2-furoyl-LIGRLO-amide, acetylcholine, and nitroprusside were recorded. A Schild regression analysis of the inhibition by a PAR2 antagonist (GB-83) of PAR2 agonist-induced aortic ring relaxations was used to compare receptor expression in PAR2-WT to PAR2-HET. PAR2 mRNA in aortas was measured by quantitative real-time PCR. In aortas contracted by either phenylephrine or U46619, the maximum relaxations induced by 2-furoyl-LIGRLO-amide were less in PAR2-HET than in the gender-matched PAR2-WT. GB-83 was 3- to 4-fold more potent for inhibition of 2fly in PAR2-HET than in PAR2-WT. PAR2 mRNA content of aortas from PAR2-HET was not significantly different than in PAR2-WT. Acetylcholine- and nitroprusside-induced relaxations of aortas from PAR2-HET were not significantly different than in PAR2-WT and PAR2 knockout. An interesting secondary finding was that relaxations induced by agonists of PAR2 and muscarinic receptors were larger in females than in males. We conclude that the lower PAR2-mediated responses in PAR2-HET aortas are consistent with evidence of a lower quantity of functional receptor expression, despite the apparently normal PAR2 mRNA content in PAR2-HET aortas.

Hennessey, John C.; McGuire, John J.



Non-par banking: competition and monopoly in markets for payments services  

Microsoft Academic Search

Once the Federal Reserve Banks started providing par interbank funds transfers, their check collection service was unnecessary to bring nationwide par check collection in competitive banking markets. The survival of non-par banks probably reflected the absence of competition in the markets where they operated. The empirical evidence is consistent with this conclusion, since non-par banks typically were monopolists in isolated

Ed Stevens



Molecular cloning of LIM homeodomain transcription factor Lhx2 as a transcription factor of porcine follicle-stimulating hormone beta subunit (FSH?) gene.  


We cloned the LIM-homeodomain protein LHX2 as a transcription factor for the porcine follicle-stimulating hormone ? subunit gene (Fsh?) by the Yeast One-Hybrid Cloning System using the upstream region of -852/-746 bases (b) from the transcription start site, called Fd2, as a bait sequence. The reporter assay in L?T2 and CHO cells revealed the presence of an LHX2-responsive region other than Fd2. A potential LHX2 binding sequence was confirmed as AATTAAT containing a consensus homeodomain binding core sequence AATT by Systematic Evolution of Ligands by Exponential Enrichment analysis. DNase I footprinting demonstrated three AATTAAT sequences located at regions -835/-829, -818/-812 and -806/-800 b in the Fd2 region and 12 binding sites in the distal and proximal regions mostly containing an AATT-core sequence. RT-PCR analysis of Lhx2 expression during porcine fetal and postnatal pituitary development showed a gradual increase from fetal day (f) 40 to postnatal day (p) 8 followed by a slight decrease to p230, suggesting that LHX2 may play its role largely in the late fetal and postnatal periods. The analyses of Lhx2 expression in pituitary tumor-derived cell lines showed their expressions in cell lines including ?T31, L?T2 and others. Since LHX2 was previously identified as a transcription factor for Cga and the in vitro experiments in the present study suggested that LHX2 regulated the expression of Fsh?, it is possible that LHX2 controls the synthesis of FSH at the transcription level. PMID:22134063

Kato, Takako; Ishikawa, Akio; Yoshida, Saishu; Sano, Yoshiya; Kitahara, Kousuke; Nakayama, Michie; Susa, Takao; Kato, Yukio



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.



Par-4 inducible apoptosis in prostate cancer cells.  


Prostate cancer is associated with the inability of prostatic epithelial cells to undergo apoptosis rather than with increased cell proliferation. Prostate apoptosis response-4 (Par-4) is a unique pro-apoptotic molecule that is capable of selectively inducing apoptosis in cancer cells when over-expressed, sensitizing the cells to diverse apoptotic stimuli and causing regression of tumors in animal models. This review discusses the salient functions of Par-4 that can be harnessed to prostate cancer therapy. PMID:14755681

Gurumurthy, Sushma; Rangnekar, Vivek M



Another application for trellis shaping: PAR reduction for DMT (OFDM)  

Microsoft Academic Search

A bound for the possible reduction of the peak-to-average ratio (PAR) dependent on the rate as well as possible practical procedures are presented. The idea of trellis shaping, originally used to minimize average transmit power in single-carrier systems, is applied to the problem of PAR reduction in multicarrier transmission. Its impact, as a function of code rate, as well as

Werner Henkel; Björn Wagner



Immunohistochemical Analysis of the Proapoptotic Protein Par4 in Normal Rat Tissues1  

Microsoft Academic Search

Prostate apoptosis response 4 (par-4) is a recently identified gene that encodes a transcription factor, Par-4, with a leucine zipper domain. Par-4 protein is constitutively expressed in various cell lines and is functionally required but not sufficient for apoptosis. Induction of Par-4 in cultured cells is found exclusively during apoptosis, and ectopic overexpression of Par-4 enhances the potency of apoptotic

Erwin R Boghaert; Stephen F. Sells; Al-Jumaily Walid; Patricia Malone; Neil M. Williams; Michael H. Weinstein; Robert Strange; Vivek M. Rangnekar


Pars intermedia peptides: studies in adult humans.  


A combination of radioimmunoassays and chromatography under acid-dissociating conditions has been used to obtain profiles of ACTH and LPH-related peptides in human plasma and cerebrospinal fluid. The spectra of peptides observed in these two fluids differ markedly. ACTH, beta-LPH, gamma-LPH and beta-endorphin are observed in the plasma of normal subjects and patients with increased pituitary ACTH secretion, whereas cerebrospinal fluid contains ACTH, beta-LPH, gamma-LPH and beta-endorphin, a 31 000-molecular-weight putative precursor having ACTH, LPH and gamma-MSH immunoreactivities, as well as pro-gamma-MSH(1-77) and smaller immunoreactive gamma-MSH fragments, alpha-MSH was not observed in blood or cerebrospinal fluid but this pars intermedia peptide and corticotropin-like intermediate lobe peptide (CLIP) were both found in tumour tissues obtained from patients with the ectopic ACTH syndrome. In vitro studies of human pituitary tumour tissues confirmed concomitant secretion of ACTH, beta-LPH, gamma-LPH, beta-endorphin and pro-gamma-MSH, which could be stimulated by a preparation of crude stalk median eminence and synthetic arginine vasopressin, from the rat, and could be suppressed by hydrocortisone. Clinical studies in which electroacupuncture was used to alleviate the symptoms of heroin withdrawal or recurrent pain revealed that concentrations of met-enkephalin and beta-endorphin, respectively, may rise in cerebrospinal fluid in association with relief of symptoms. PMID:6268379

Ratter, S J; McLoughlin, L; Gillies, G; Clement-Jones, V; Hope, J; Rees, L H



The pars flaccida middle ear pressure and mastoid pneumatization index.  


The degree of pars flaccida retraction and the levels of mastoid pneumatization were assessed and correlated in 388 adults with intact pars tensa. Poorly pneumatized mastoids were found to be associated with retraction of pars flaccida; the poorer the pneumatization, the deeper the retraction. Well pneumatized mastoids were usually associated with normal position of the pars flaccida. The pars flaccida was previously also shown to retract in face of ME negative pressure--and its degree can be seen to be an index of ME negative pressure. Thus, the correlation of deeper degrees of pars flaccida retractions with mastoid hypopneumatization (and vice versa) lends strength to the studies which show the mastoid pneumatic system to have a function of a passive ME pressure buffer. This observation lends further evidence as to why ears with poorly pneumatized mastoids are a priori at risk to develop complications such as SOM in adults, tympanic membrane retractions and perforations, incus necrosis or retraction pocket cholesteatoma. Ears with a large pneumatic system are hardly at such risk. PMID:8725533

Sadé, J; Fuchs, C; Luntz, M



Par4 Is an Essential Downstream Target of DAP-like Kinase (Dlk) in Dlk\\/Par4-mediated Apoptosis  

Microsoft Academic Search

Prostate apoptosis response-4 (Par-4) was initially identified as a gene product up-regulated in prostate cancer cells undergoing apoptosis. In rat fibroblasts, coexpression of Par-4 and its interaction partner DAP-like kinase (Dlk, which is also known as zipper-interacting protein kinase (ZIPK)) induces relocation of the kinase from the nucleus to the actin filament system, followed by extensive myosin light chain (MLC)

Meike Boosen; Susanne Vetterkind; Jan Kubicek; Karl-Heinz Scheidtmann; Susanne Illenberger; Ute Preuss



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 Central

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.

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



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


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



The actinobacterial signature protein ParJ (SCO1662) regulates ParA polymerization and affects chromosome segregation and cell division during Streptomyces sporulation.  


Bacterial chromosome segregation usually involves cytoskeletal ParA proteins, ATPases which can form dynamic filaments. In aerial hyphae of the mycelial bacterium Streptomyces coelicolor, ParA filaments extend over tens of microns and are responsible for segregation of dozens of chromosomes. We have identified a novel interaction partner of S. coelicolor ParA, ParJ. ParJ negatively regulates ParA polymerization in vitro and is important for efficient chromosome segregation in sporulating aerial hyphae. ParJ-EGFP formed foci along aerial hyphae even in the absence of ParA. ParJ, which is encoded by sco1662, turned out to be one of the five actinobacterial signature proteins, and another of the five is a ParJ paralogue. We hypothesize that polar growth, which is characteristic not only of streptomycetes, but even of simple Actinobacteria, may be interlinked with ParA polymer assembly and its specific regulation by ParJ. PMID:21143314

Ditkowski, Bartosz; Tro?, Paulina; Ginda, Katarzyna; Donczew, Magdalena; Chater, Keith F; Zakrzewska-Czerwi?ska, Jolanta; Jakimowicz, Dagmara



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 identifier NTC00696800.

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



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

NASA Astrophysics Data System (ADS)

La situation energetique et les enjeux environnementaux auxquels la societe est confrontee entrainent un interet grandissant pour la production d'electricite a partir de l'energie solaire. Parmi les technologies actuellement disponibles, la filiere du photovoltaique a concentrateur solaire (CPV pour concentrator photovoltaics) possede un rendement superieur et mi potentiel interessant a condition que ses couts de production soient competitifs. La methode d'epitaxie par faisceaux chimiques (CBE pour chemical beam epitaxy) possede plusieurs caracteristiques qui la rendent interessante pour la production a grande echelle de cellules photovoltaiques a jonctions multiples a base de semi-conducteurs III-V. Ce type de cellule possede la meilleure efficacite atteinte a ce jour et est utilise sur les satellites et les systemes photovoltaiques a concentrateur solaire (CPV) les plus efficaces. Une des principales forces de la technique CBE se trouve dans son potentiel d'efficacite d'utilisation des materiaux source qui est superieur a celui de la technique d'epitaxie qui est couramment utilisee pour la production a grande echelle de ces cellules. Ce memoire de maitrise presente les travaux effectues dans le but d'evaluer le potentiel de la technique CBE pour realiser la croissance de couches de GaAs sur des substrats de Ge. Cette croissance constitue la premiere etape de fabrication de nombreux modeles de cellules solaires a haute performance decrites plus haut. La realisation de ce projet a necessite le developpement d'un procede de preparation de surface pour les substrats de germanium, la realisation de nombreuses sceances de croissance epitaxiale et la caracterisation des materiaux obtenus par microscopie optique, microscopie a force atomique (AFM), diffraction des rayons-X a haute resolution (HRXRD), microscopie electronique a transmission (TEM), photoluminescence a basse temperature (LTPL) et spectrometrie de masse des ions secondaires (SIMS). Les experiences ont permis de confirmer l'efficacite du procede de preparation de surface et d'identifier les conditions de croissance optimales. Les resultats de caracterisation indiquent que les materiaux obtenus presentent une tres faible rugosite de surface, une bonne qualite cristalline et un dopage residuel relativement important. De plus, l'interface GaAs/Ge possede une faible densite de defauts. Finalement, la diffusion d'arsenic dans le substrat de germanium est comparable aux valeurs trouvees dans la litterature pour la croissance a basse temperature avec les autres procedes d'epitaxie courants. Ces resultats confirment que la technique d'epitaxie par faisceaux chimiques (CBE) permet de produire des couches de GaAs sur Ge de qualite adequate pour la fabrication de cellules solaires a haute performance. L'apport a la communaute scientifique a ete maximise par le biais de la redaction d'un article soumis a la revue Journal of Crystal Growth et la presentation des travaux a la conference Photovoltaics Canada 2010 . Mots-cles : Epitaxie par jets chimiques, Chemical beam epitaxy, CBE, MOMBE, Germanium, GaAs, Ge

Belanger, Simon


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.



Expression and function of the leucine zipper protein Par-4 in apoptosis.  


The prostate apoptosis response-4 (par-4) gene was identified by differential screening for genes that are upregulated when prostate cancer cells are induced to undergo apoptosis. The par-4 gene is induced by apoptotic signals but not by growth-arresting, necrotic, or growth-stimulatory signals. The deduced amino acid sequence of par-4 predicts a protein with a leucine zipper domain at its carboxy terminus. We have recently shown that the Par-4 protein binds, via its leucine zipper domain, to the zinc finger domain of Wilms' tumor protein WT1 (R. W. Johnstone et al., Mol. Cell. Biol. 16:6945-6956, 1996). In experiments aimed at determining the functional role of par-4 in apoptosis, an antisense par-4 oligomer abrogated par-4 expression and activator-driven apoptosis in rat prostate cancer cell line AT-3, suggesting that par-4 is required for apoptosis in these cells. Consistent with a functional role for par-4 in apoptosis, ectopic overexpression of par-4 in prostate cancer cell line PC-3 and melanoma cell line A375-C6 conferred supersensitivity to apoptotic stimuli. Transfection studies with deletion mutants of Par-4 revealed that full-length Par-4, but not mutants that lacked the leucine zipper domain of Par-4, conferred enhanced sensitivity to apoptotic stimuli. Most importantly, ectopic coexpression of the leucine zipper domain of Par-4 inhibited the ability of Par-4 to enhance apoptosis. Finally, ectopic expression of WT1 attenuated apoptosis, and coexpression of Par-4 but not a leucine zipperless mutant of Par-4 rescued the cells from the antiapoptotic effect of WT1. These findings suggest that the leucine zipper domain is required for the Par-4 protein to function in apoptosis. PMID:9199316

Sells, S F; Han, S S; Muthukkumar, S; Maddiwar, N; Johnstone, R; Boghaert, E; Gillis, D; Liu, G; Nair, P; Monnig, S; Collini, P; Mattson, M P; Sukhatme, V P; Zimmer, S G; Wood, D P; McRoberts, J W; Shi, Y; Rangnekar, V M



Oncogenic Ras sensitizes cells to apoptosis by Par-4.  


Certain mutations in the mammalian ras gene are oncogenic and are often detected in human cancers. Oncogenic Ras induces the transcription activity of NF-kappaB that confers cell survival. Oncogenic Ras also down-modulates the expression of Par-4, a transcriptional repressor protein, that is essential but not sufficient on its own to induce apoptosis. Here we show that reintroduction of Par-4 by transient transfection leads to apoptosis in cells expressing oncogenic Ras but not in those that lack oncogenic Ras expression. Par-4 abrogates oncogenic Ras-inducible NF-kappaB transcription activity but does not interfere with cytoplasmic activation, or the DNA binding activity, of NF-kappaB. Because abrogation of NF-kappaB transcription activity is sufficient to cause apoptosis in cells expressing oncogenic Ras, our findings identify Par-4 as a novel example of a pro-apoptotic protein that selectively inhibits oncogenic Ras-dependent NF-kappaB function at the transcription level and suggest a mechanism by which Par-4 expression may selectively induce apoptosis in oncogenic Ras-expressing cells. PMID:10514481

Nalca, A; Qiu, S G; El-Guendy, N; Krishnan, S; Rangnekar, V M



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.



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.



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.

Dawes, Adriana T.; Munro, Edwin M.



Two cases of malignant glaucoma unresolved by pars plana vitrectomy  

PubMed Central

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

Hosoda, Yoshikatsu; Akagi, Tadamichi; Yoshimura, Nagahisa



The bacterial chromosome segregation protein Spo0J spreads along DNA from parS nucleation sites.  


Regulation of chromosome inheritance is essential to ensure proper transmission of genetic information. To accomplish accurate genome segregation, cells organize their chromosomes and actively separate them prior to cytokinesis. In Bacillus subtilis the Spo0J protein is required for accurate chromosome segregation and it regulates the developmental switch from vegetative growth to sporulation. Spo0J is a DNA-binding protein that recognizes at least eight identified parS sites located near the origin of replication. As judged by fluorescence microscopy, Spo0J forms discrete foci associated with the oriC region of the chromosome throughout the cell cycle. In an attempt to determine the mechanisms utilized by Spo0J to facilitate productive chromosome segregation, we have investigated the DNA binding activity of Spo0J. In vivo we find Spo0J associates with several kilobases of DNA flanking its specific binding sites (parS) through a parS-dependent nucleation event that promotes lateral spreading of Spo0J along the chromosome. Using purified components we find that Spo0J has the ability to coat non-specific DNA substrates. These 'Spo0J domains' provide large structures near oriC that could potentially demark, organize or localize the origin region of the chromosome. PMID:16925562

Murray, Heath; Ferreira, Henrique; Errington, Jeff



ParA-mediated plasmid partition driven by protein pattern self-organization  

PubMed Central

DNA segregation ensures the stable inheritance of genetic material prior to cell division. Many bacterial chromosomes and low-copy plasmids, such as the plasmids P1 and F, employ a three-component system to partition replicated genomes: a partition site on the DNA target, typically called parS, a partition site binding protein, typically called ParB, and a Walker-type ATPase, typically called ParA, which also binds non-specific DNA. In vivo, the ParA family of ATPases forms dynamic patterns over the nucleoid, but how ATP-driven patterning is involved in partition is unknown. We reconstituted and visualized ParA-mediated plasmid partition inside a DNA-carpeted flowcell, which acts as an artificial nucleoid. ParA and ParB transiently bridged plasmid to the DNA carpet. ParB-stimulated ATP hydrolysis by ParA resulted in ParA disassembly from the bridging complex and from the surrounding DNA carpet, which led to plasmid detachment. Our results support a diffusion-ratchet model, where ParB on the plasmid chases and redistributes the ParA gradient on the nucleoid, which in turn mobilizes the plasmid.

Hwang, Ling Chin; Vecchiarelli, Anthony G; Han, Yong-Woon; Mizuuchi, Michiyo; Harada, Yoshie; Funnell, Barbara E; Mizuuchi, Kiyoshi



Plasma FSH, LH, the positive feedback of oestrogen, ovulation and luteal function in the ewe given bromocriptine to suppress prolactin during seasonal anoestrus.  


The effects of pharmacological reduction of the high plasma prolactin concentration typical of seasonal anoestrus in sheep were assessed with respect to positive feedback of oestrogen on LH release, ovulation, and progesterone secretion. Treatment of 16 Scottish Blackface ewes with 1 mg bromocriptine, i.m. twice daily for 12 days, reduced prolactin concentrations in peripheral plasma from 64 +/- 10 ng/ml before treatment to < 4 ng/ml. This treatment had no effect on the proportion of ewes discharging LH and FSH in response to 12.5 microgram oestradiol benzoate (3/8 before compared with 5/16 during treatment) or the proportion of ewes ovulating in response to oestrogen treatment. Plasma progesterone concentrations remained low even in ovulating ewes. It is concluded that treatment with bromocriptine alone is unlikely to restore oestrous cycles to ewes in seasonal anoestrus. PMID:6772780

Land, R B; Carr, W R; McNeilly, A S; Preece, R D



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

PubMed Central

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

Grigorova, Marina; Punab, Margus; Punab, Anna Maria; Poolamets, Olev; Vihljajev, Vladimir; Zilaitiene, Birute; Erenpreiss, Juris; Matulevicius, Valentinas; Laan, Maris



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.

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



Par-4 downregulation promotes breast cancer recurrence by preventing multinucleation following targeted therapy.  


Most deaths from breast cancer result from tumor recurrence, but mechanisms underlying tumor relapse are largely unknown. We now report that Par-4 is downregulated during tumor recurrence and that Par-4 downregulation 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 patients with breast cancer, and Par-4 is downregulated 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



Bone Morphogenetic Protein 2 Stimulates Noncanonical SMAD2/3 Signaling via the BMP Type 1A Receptor in Gonadotrope-Like Cells: Implications for FSH Synthesis.  


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



La croissance des PME par le biais des ressources et compétences : quelles voies ?  

Microsoft Academic Search

Les PME sont des organisations particulières, bien différentes par rapport à la grande entreprise. Les PME en croissance sont vues comme des vrais leviers pour la création d'emploi et de richesse dans une économie. La croissance des PME est alimentée soit par les nouvelles ressources générées dans l'entreprise pendant le processus de croissance, soit par l'apport externe des ressources (par

A. E Popa Postariu



p38 Mitogen-Activated Protein Kinase Is Critical for Synergistic Induction of the FSH? Gene by Gonadotropin-Releasing Hormone and Activin through Augmentation of c-Fos Induction and Smad Phosphorylation  

PubMed Central

GnRH and activin independently and synergistically activate transcription of the FSH ?-subunit gene, the subunit that provides specificity and is the limiting factor in the synthesis of the mature hormone. This synergistic interaction, as determined by two-way ANOVA, is specific for FSH? and may, therefore, contribute to differential expression of the two gonadotropin hormones, which is critical for the reproductive cycle. We find that the cross-talk between the GnRH and activin signaling pathways occurs at the level of p38 MAPK, because the synergy is dependent on p38 MAPK activity, which is activated by GnRH, and activin cotreatment augments p38 activation by GnRH. Both the Smad and activator protein-1 binding sites on the FSH? promoter are necessary and sufficient for synergy. After cotreatment, Smad 3 proteins are more highly phosphorylated on the activin-receptor signaling-dependent residues on the C terminus than with activin treatment alone, and c-Fos is more highly expressed than with GnRH treatment alone. Inhibition of p38 by either of two different inhibitors or a dominant-negative p38 kinase abrogates synergy on FSH? expression, reduces c-Fos induction by GnRH, and prevents the further increase in c-Fos levels that occurs with cotreatment. Additionally, p38 is necessary for maximal Smad 3 C-terminal phosphorylation by activin treatment alone and for the further increase caused by cotreatment. Thus, p38 is the pivotal signaling molecule that integrates GnRH and activin interaction on the FSH? promoter through higher induction of c-Fos and elevated Smad phosphorylation.

Coss, Djurdjica; Hand, Cameron M.; Yaphockun, Karen K. J.; Ely, Heather A.; Mellon, Pamela L.



par genes in Mycobacterium bovis and Mycobacterium smegmatis are arranged in an operon transcribed from "SigGC" promoters  

PubMed Central

Background The ParA/Soj and ParB/Spo0J proteins, and the cis-acting parS site, participate actively in chromosome segregation and cell cycle progression. Genes homologous to parA and parB, and two putative parS copies, have been identified in the Mycobacterium bovis BCG and Mycobacterium smegmatis chromosomes. As in Mycobacterium tuberculosis, the parA and parB genes in these two non-pathogenic mycobacteria are located near the chromosomal origin of replication. The present work focused on the determination of the transcriptional organisation of the ~6 Kb orf60K-parB region of M. bovis BCG and M. smegmatis by primer extension, transcriptional fusions to the green fluorescence protein (GFP) and quantitative RT-PCR. Results The parAB genes were arranged in an operon. However, we also found promoters upstream of each one of these genes. Seven putative promoter sequences were identified in the orf60K-parB region of M. bovis BCG, whilst four were identified in the homologous region of M. smegmatis, one upstream of each open reading frame (ORF). Real-time PCR assays showed that in M. smegmatis, mRNA-parA and mRNA-parB levels decreased between the exponential and stationary phases. In M. bovis BCG, mRNA-parA levels also decreased between the exponential and stationary phases. However, parB expression was higher than parA expression and remained almost unchanged along the growth curve. Conclusion The majority of the proposed promoter regions had features characteristic of Mycobacterium promoters previously denoted as Group D. The -10 hexamer of a strong E. coli ?70-like promoter, located upstream of gidB of M. bovis BCG, overlapped with a putative parS sequence, suggesting that the transcription from this promoter might be regulated by the binding of ParB to parS.

Casart, Yveth; Gamero, Elida; Rivera-Gutierrez, Sandra; Gonzalez-y-Merchand, Jorge A; Salazar, Leiria



Biased signalling and proteinase-activated receptors (PARs): targeting inflammatory disease.  


Although it has been known since the 1960s that trypsin and chymotrypsin can mimic hormone action in tissues, it took until the 1990s to discover that serine proteinases can regulate cells by cleaving and activating a unique four-member family of GPCRs known as proteinase-activated receptors (PARs). PAR activation involves the proteolytic exposure of its N-terminal receptor sequence that folds back to function as a 'tethered' receptor-activating ligand (TL). A key N-terminal arginine in each of PARs 1 to 4 has been singled out as a target for cleavage by thrombin (PARs 1, 3 and 4), trypsin (PARs 2 and 4) or other proteases to unmask the TL that activates signalling via Gq , Gi or G12 /13 . Similarly, synthetic receptor-activating peptides, corresponding to the exposed 'TL sequences' (e.g. SFLLRN-, for PAR1 or SLIGRL- for PAR2) can, like proteinase activation, also drive signalling via Gq , Gi and G12 /13 , without requiring receptor cleavage. Recent data show, however, that distinct proteinase-revealed 'non-canonical' PAR tethered-ligand sequences and PAR-activating agonist and antagonist peptide analogues can induce 'biased' PAR signalling, for example, via G12 /13 -MAPKinase instead of Gq -calcium. This overview summarizes implications of this 'biased' signalling by PAR agonists and antagonists for the recognized roles the PARs play in inflammatory settings. PMID:24354792

Hollenberg, M D; Mihara, K; Polley, D; Suen, J Y; Han, A; Fairlie, D P; Ramachandran, R



Molecular cloning of the rat proteinase-activated receptor 4 (PAR4)  

PubMed Central

Background The proteinase-activated receptor 4 (PAR4) is a G-protein-coupled receptor activated by proteases such as thrombin and trypsin. Although activation of PAR4 has been shown to modulate rat gastrointestinal motility, the rat PAR4 sequence was unknown until now. This study aimed to identify the rat PAR4 cDNA. Results The cDNA coding for the rat PAR4 homologue was cloned from the duodenum. Northern blots demonstrated a 3.0 kb transcript in the duodenum. Protein homology with mouse and human counterparts was 90% and 75% respectively. PAR4 is expressed predominantly in the esophagus, stomach, duodenum and the spleen. When expressed in COS cells, PAR4 is activated by trypsin (1 nM), thrombin (50 nM), mouse PAR4 specific peptide (500 ?M) and a putative rat PAR4 specific activating peptide (100 ?M), as measured by intracellular Ca2+-changes. Conclusions We have identified and characterized cDNA encoding the rat PAR4 homologue. PAR4 is expressed predominantly in the upper gastrointestinal tract. It is activated by trypsin, thrombin and its newly identified rat PAR4 specific activating peptide.

Hoogerwerf, Willemijntje A; Hellmich, Helen Lee; Micci, Maria Adelaide; Winston, John H; Zou, Lei; Pasricha, Pankaj J



Laser picoseconde pompé par diode à basse cadence de récurrence  

NASA Astrophysics Data System (ADS)

Nous présentons une étude expérimentale d'un laser Nd:YAG picoseconde à faible cadence de récurrence. Nous comparons les performances obtenues avec un laser de cavité métrique utilisant la même source de pompe. Des gains en énergie et en puissance crête par impulsion de 10 et 7 ont été obtenus.

Albert, A.; Couderc, V.; Louradour, F.; Barthélémy, A.



Pars plana vitrectomy in vitreous haemorrhage due to Eales' disease.  


Repeated vitreous haemorrhage is a common occurrence in Eales disease. 25 eyes of unresolving vitreous haemorrhage were subjected to pars plana vitrectomy. 18 eyes improved to 1/60 or better. Vitreous rebleed was the commonest problem encountered. We discuss our experience, complications and limitations. PMID:1452278

Gadkari, S S; Kamdar, P A; Jehangir, R P; Shah, N A; Adrianwala, S D



Summary of radiological impacts of Par Pond drawdown.  

National Technical Information Service (NTIS)

On March 14, 1991, a ten square foot depression was discovered on the lower downstream slope of Par Pond Dam. The water level in the pond was lowered about 19 feet during the period June 28--September 19, 1991, as a safety precaution to significantly redu...

W. L. Marter A. L. Boni



PhyloPars: estimation of missing parameter values using phylogeny  

Microsoft Academic Search

A wealth of information on metabolic parameters of a species can be inferred from observations on spe- cies that are phylogenetically related. Phylogeny- based information can complement direct empirical evidence, and is particularly valuable if experiments on the species of interest are not feasible. The PhyloPars web server provides a statistically con- sistent method that combines an incomplete set of

Jorn Bruggeman; Jaap Heringa; Bernd W. Brandt



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.



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)



Estimating PAR absorbed by vegetation from bidirectional reflectance measurements  

Microsoft Academic Search

Satellite remote sensing allows estimation, at a global scale, of the photosynthetically active radiation absorbed (APAR) by the vegetation. Current estimates are based on retrieving the fraction (fAPAR) of PAR absorbed by the canopy from spectral vegetation indices (SVI) derived from combinations of spectral reflectance measurements. We show that currently used SVI are strongly affected by the soil reflectance as

Jean-Louis Roujean; François-Marie Breon



Laboratory diagnosis of equine pituitary pars intermedia adenoma  

Microsoft Academic Search

The objective of the study was to determine the sensitivity with which an adenoma of the pars intermedia of the pituitary gland can be predicted in horses by measuring the basal plasma concentrations of glucose, cortisol, adrenocorticotropin (ACTH), and insulin, the urinary concentration of corticoids, the urinary corticoid:creatinine ratio, and the plasma cortisol concentration after the administration of 25 IU

J. H. van der Kolk; T. Wensing; H. C. Kalsbeek; H. J. Breukink



Photoémission de Csl induite par une impulsion laser intense femtoseconde  

NASA Astrophysics Data System (ADS)

Nous avons mesuré pour la première fois les spectres de photoélectrons émis par un cristal isolant à large bande interdite, Csl, avec une dynamique de 10^6 coups/s, excité par la source laser haute cadence du C.E.L.I.A (800 nm, 40 fs, 1 kHz, 1 TW). L'émission d'électrons jusqu'à des énergies de quelques dizaines d'électrons-volts a été observée pour des impulsions d'éclairement compris entre 0.5 et 3 TW/cm^2, relativement faible donc par comparaison aux éclairements utilisés pour accélérer les électrons d'un atome aux mêmes énergies. Ces spectres contiennent tous, en particulier, deux bandes dans le domaine des basses énergies d'électrons (<5 eV), également observées lors d'études précédentes. Les électrons les plus énergétiques forment un plateau intense légèrement structuré et limité par une coupure exponentielle. Pour des impulsions de 3 TW/cm^2 cette coupure est située à 27 eV. L'insuffisance du mécanisme électron-photon-phonon, considéré jusqu'à présent comme le principal processus d'échauffement des électrons dans les solides en interaction non destructrice avec un champ laser, nous a poussé à proposer un mécanisme alternatif. Ce modèle met en évidence les transitions directes multiphotoniques dans la bande de conduction du solide qui sont incontournables du fait de sa structure électronique multi-branches

Belsky, A.; Vasil'Ev, A.; Yatsenko, B.; Bachau, H.; Martin, P.; Geoffroy, G.; Guizard, S.



Radiological impact of Par Pond drawdown from liquid effluent pathways  

SciTech Connect

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

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



Traumatismes Oculaires par Petards: Bilan sur Trois Annees  

PubMed Central

Summary Les accidents dus aux pétards sont des accidents graves. Leur recrudescence ces dernières années en Algérie, essentiellement durant les fêtes du Mawlid Ennabaoui (fête de la naissance du prophète), mérite à notre sens d'entreprendre des bilans exhaustifs dont celui-ci dans le but d'une sensibilisation de toutes les compétences concernées. Nous avons réuni sur trois années consécutives (2002, 2003, 2004) 60 dossiers de malades ayant subi des accidents oculaires par pétards. Nos patients sont répartis en 42 consultations pour blessures légères et 18 hospitalisations pour blessures graves. Parmi ces derniers, neuf ont présenté des complications et séquelles graves (cinq cas de cécité par atrophie du globe oculaire, trois cas de cécité cornéenne et un cas de cécité par trou maculaire). Dans tous ces cas l'incapacité permanente partielle est au minimum de 30%. Au vu de ces données nous proposons des mesures d'éducation sanitaire et une sensibilisation du grand public aux traumatismes oculaires, par le biais de mé dias appropriés: radio, télévision, affiches.

Zouaoui-Kesraoui, N.; Derdour, A.



PAR-5 is a PARty hub in the germline  

PubMed Central

As our understanding of how molecular machineries work expands, an increasing number of proteins that appear as regulators of different processes have been identified. These proteins are hubs within and among functional networks. The 14-3-3 protein family is involved in multiple cellular pathways and, therefore, influences signaling in several disease processes, from neurobiological disorders to cancer. As a consequence, 14-3-3 proteins are currently being investigated as therapeutic targets. Moreover, 14-3-3 protein levels have been associated with resistance to chemotherapies. There are seven 14-3-3 genes in humans, while Caenorhabditis elegans only possesses two, namely par-5 and ftt-2. Among the C. elegans scientific community, par-5 is mainly recognized as one of the par genes that is essential for the asymmetric first cell division in the embryo. However, a recent study from our laboratory describes roles of par-5 in germ cell proliferation and in the cellular response to DNA damage induced by genotoxic agents. In this review, we explore the broad functionality of 14-3-3 proteins in C. elegans and comment on the potential use of worms for launching a drugs/modifiers discovery platform for the therapeutic regulation of 14-3-3 function in cancer.

Aristizabal-Corrales, David; Schwartz Jr, Simo; Ceron, Julian



Management of persistent hyperplastic primary vitreous by pars plana vitrectomy.  

PubMed Central

Two children with persistent hyperplastic primary vitreous (PHPV) underwent vitrectomy and lensectomy via the pars plana to remove the fibrovascular stalk. Postoperatively the eyes were quiet, only a slight vitreous haze obscured the fundus view in the immediate postoperative period, and the stumps of the stalks retracted. Early surgical treatment of PHPV may prevent later serious complications. Images

Peyman, G A; Sanders, D R; Nagpal, K C



The Physical Association of the P2Y12 Receptor with PAR4 Regulates Arrestin-Mediated Akt Activation.  


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



Étude d'un empilement multicouche périodique Mo/Si par spectroscopie d'émission X et par réflectométrie X  

NASA Astrophysics Data System (ADS)

Nous avons étudié par spectroscopie d'émission X induite par électrons (EXES) et par réflectométrie X (RX), un empilement périodique constitué de bicouches Mo/Si, destiné à servir de miroir interférentiel dans le domaine des rayons X mous. Les résultats de RX rasante (? = 0,154 nm) peuvent être interprétés par une succession de couches où les atomes de Si se mélangent aux couches Mo et réciproquement, avec de plus une rugosité interfaciale. D'après l'analyse EXES, les atomes de silicium sont présents dans deux environnements physico-chimiques différents. Au centre des couches Si, se trouve du silicium amorphe et au niveau des interfaces se trouve une interphase sur une épaisseur d'environ 2 nm où les atomes de Si sont sous forme de siliciures (Mo{5}Si{3} et MoSi{2}). La composition de cette interphase a été déterminée et a permis de reproduire d'une manière satisfaisante les mesures de réflectivité absolue effectuées en RX mou (? = 1,33 nm).

Jonnard, P.; André, J.-M.; Gautier, J.; Roulliay, M.; Bridou, F.; Delmotte, F.; Ravet, M.-F.



Decreased expression of the pro-apoptotic protein Par-4 in renal cell carcinoma.  


Par-4 is a widely expressed leucine zipper protein that confers sensitization to apoptosis induced by exogenous insults. Because the expression of genes that promote apoptosis may be down-regulated during tumorigenesis, we sought to examine the expression of Par-4 in human tumors. We present here evidence that Par-4 protein levels were severely decreased in human renal cell carcinoma specimens relative to normal tubular cells. Replenishment of Par-4 protein levels in renal cell carcinoma cell lines conferred sensitivity to apoptosis. Because apoptosis may serve as a defense mechanism against malignant transformation or progression, decreased expression of Par-4 may contribute to the pathophysiology of renal cell carcinoma. PMID:10022126

Cook, J; Krishnan, S; Ananth, S; Sells, S F; Shi, Y; Walther, M M; Linehan, W M; Sukhatme, V P; Weinstein, M H; Rangnekar, V M



Brulure par Plaque de Bistouri Electrique: a Propos de Quatre Cas  

PubMed Central

Summary La brûlure par plaque de bistouri électrique est un accident rare mais grave par la profondeur de la lésion et par sa localisation, surtout quand qu’elle survient dans un contexte chirurgical dont le vécu reste difficile de la part du malade et du chirurgien. Cette brûlure bien que imprévisible reste grave par la profondeur et la localisation de la brûlure et par sa survenue dans un contexte opératoire, chez des patients malades. La prise en charge de la brûlure doit se faire en milieu spécialisé. La prévention reste le seul moyen d’éviter ce type d’accident.

Khales, A.; Achbouk, A.; Belmir, R.; Cherkab, L.; Ennouhi, M.A.; Ababou, K.; Ihrai, H.



Macroinvertebrates of Par Pond and Pond B: Final report, January 1984-June 1985  

SciTech Connect

This document reports on the Par Pond and Pond B macroinvertebrate sampling program from January 1984 through June 1985. It includes data on quantitative and qualitative benthic sampling, quantitative meroplankton sampling and quarterly diel sample. The basic objectives were to: (1) characterize the benthic and meroplankton macroinvertebrate communities of Par Pond and Pond B, with respect to taxonomic composition and diversity, density and relative abundance of functional feeding groups; (2) assess the impact of thermal discharges on the macroinvertebrate community of Par Pond; (3) assess the impact and significance of entrainment losses of macroinvertebrate meroplankton from Par Pond; and (4) compare Par Pond macroninvertebrate communities with those in Pond B.

Kondratieff, B.C.; Chimney, M.J.; Painter, W.B.



Mutually exclusive expression patterns of Bcl-2 and Par-4 in human prostate tumors consistent with down-regulation of Bcl-2 by Par-4.  


Par-4 is a widely expressed protein that sensitizes both prostatic and non-prostatic cells to apoptosis. Constitutive- or regulated- overexpression of Par-4 caused a reduction in the levels of the anti-apoptotic protein Bcl-2. Replenishment of Bcl-2 levels abrogated susceptibility to Par-4-dependent apoptosis, suggesting that Par-4-mediated apoptosis requires downmodulation of Bcl-2 levels. The inverse correlation between Par-4 and Bcl-2 expression was recapitulated in human prostate tumors. Par-4 but not Bcl-2 was detected in the secretory epithelium of benign prostatic tumors and in primary and metastatic prostate cancers that are apt to undergo apoptosis. Moreover, xenografts of human, androgen-dependent CWR22 tumors showed Par-4 but not Bcl-2 expression. By contrast, androgen-independent CWR22R tumors derived from the CWR22 xenografts showed mutually exclusive expression patterns of Par-4 and Bcl-2. These findings suggest a mechanism by which Par-4 may sensitize prostate tumor cells to apoptosis. PMID:9989812

Qiu, G; Ahmed, M; Sells, S F; Mohiuddin, M; Weinstein, M H; Rangnekar, V M



Expression of Partitioning Defective 3 (Par-3) for Predicting Extrahepatic Metastasis and Survival with Hepatocellular Carcinoma  

PubMed Central

Partitioning defective 3 (Par-3), a crucial component of partitioning-defective complex proteins, controls cell polarity and contributes to cell migration and cancer cell epithelial-to-mesenchymal transition. However, the clinical relevance of Par-3 in tumor progression and metastasis has not been well elucidated. In this study, we investigated the impact and association of Par-3 expression and clinical outcomes with hepatocellular carcinoma (HCC). We first confirmed that Par-3 was abundantly expressed in HCC cell lines by Western blot analysis. We used immunohistochemistry to analyze the association of Par-3 expression and clinicopathological characteristics in primary and subsequent metastatic tumors of patients with HCC. Par-3 was overexpressed in 47 of 111 (42.3%) primary tumors. Increased expression of Par-3 in primary tumors predicted an increased five-year cumulative incidence of extrahepatic metastasis. In addition, multivariate analysis revealed that Par-3 overexpression was an independent risk factor of extrahepatic metastasis. Increased Par-3 expression in primary tumors was associated with poor five-year overall survival rates and was an independent prognostic factor on Cox regression analysis. In conclusion, we show for the first time that increased Par-3 expression is associated with distant metastasis and poor survival rates in patients with HCC. Par-3 may be a novel prognostic biomarker and therapeutic target for HCC.

Jan, Yee-Jee; Ko, Bor-Sheng; Liu, Tzu-An; Wu, Yao-Ming; Liang, Shu-Man; Chen, Shyh-Chang; Wang, John; Liou, Jun-Yang



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.

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



Structure of the ParM filament at 8.5 ? 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.

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



A Bipolar Spindle Of Antiparallel ParM Filaments Drives Bacterial Plasmid Segregation  

PubMed Central

To ensure their stable inheritance by daughter cells during cell division, bacterial low copy-number plasmids make simple DNA segregating machines that use an elongating protein filament between sister plasmids. In the ParMRC system of Escherichia coli R1 plasmid, ParM, an actin-like protein, forms the spindle between ParRC complexes on sister plasmids. Using a combination of structural work and total internal reflection fluorescence microscopy, we show that ParRC bound and could accelerate growth at only one end of polar ParM filaments, mechanistically resembling eukaryotic formins. The architecture of ParM filaments enabled two ParRC-bound filaments to associate in an antiparallel orientation, forming a bipolar spindle. The spindle elongated as a bundle of at least two antiparallel filaments, thereby pushing two plasmid clusters towards the poles.

Gayathri, P.; Fujii, T.; M?ller-Jensen, J.; van den Ent, F.; Namba, K.; Lowe, J.



A bipolar spindle of antiparallel ParM filaments drives bacterial plasmid segregation.  


To ensure their stable inheritance by daughter cells during cell division, bacterial low-copy-number plasmids make simple DNA segregating machines that use an elongating protein filament between sister plasmids. In the ParMRC system of the Escherichia coli R1 plasmid, ParM, an actinlike protein, forms the spindle between ParRC complexes on sister plasmids. By using a combination of structural work and total internal reflection fluorescence microscopy, we show that ParRC bound and could accelerate growth at only one end of polar ParM filaments, mechanistically resembling eukaryotic formins. The architecture of ParM filaments enabled two ParRC-bound filaments to associate in an antiparallel orientation, forming a bipolar spindle. The spindle elongated as a bundle of at least two antiparallel filaments, thereby pushing two plasmid clusters toward the poles. PMID:23112295

Gayathri, P; Fujii, T; Møller-Jensen, J; van den Ent, F; Namba, K; Löwe, J



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.



Identification of a Unique Core Domain of Par-4 sufficient for Selective Apoptosis Induction in Cancer Cells.  

National Technical Information Service (NTIS)

The present invention relates to Par-4 mutants which cause apoptosis in cancer cells which are sensitive to Par-4 and also induce apoptosis in cancer cells which are resistant to Par-4. The present invention also relates to methods of using the Par-4 muta...

V. M. Rangnekar



Asymmetrically distributed PAR3 protein contributes to cell polarity and spindle alignment in early C. elegans embryos  

Microsoft Academic Search

The par-3 gene is required for establishing polarity in early C. elegans embryos. Embryos from par-3 homozygous mothers show defects in segregation of cytoplasmic determinants and in positioning of the early cleavage spindles. We report here that the PAR-3 protein is asymmetrically distributed at the periphery of the zygote and asymmetrically dividing blastomeres of the germline lineage. The PAR-3 distribution

Bijan Etemad-Moghadam; Su Guo; Kenneth J. Kemphues



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.

Pittman, Kelly J.; Skop, Ahna R.



Laser UV à semiconducteur nitrure pompé par des micropointes  

NASA Astrophysics Data System (ADS)

Dans un Laser à Semiconducteur Micropointes (LSM), le milieu amplificateur est pompé par un faisceau d'électrons issus de micropointes effet de champ. Ce type de laser est particulièrement adapté aux semi-conducteurs à grands gaps tels que les nitrures GaN et AIN émettant dans l'UltraViolet, pour lesquels le dopage et la prise de contact ohmique deviennent problématiques. Ce papier présente ce dispositif et l'état d'avancement des travaux.

Barjon, J.; Adelmann, C.; Baptist, R.; Brault, J.; Daudin, B.; Dang, Le Si; Molva, E.



ParSyC: An Efficient SystemC Parser  

Microsoft Academic Search

Due to the ever increasing complexity of circuits and systems new methodologies for system design are mandatory. Lan- guages that enable modeling at higher levels of abstraction but also allow for a concise hardware description offer a promising way into this direction. One such language is SystemC. In this paper we propose the SystemC parser ParSyC, that allows to convert

Görschwin Fey; Daniel Große; Tim Cassens; Christian Genz; Tim Warode; Rolf Drechsler



ParSyC: An Efficient SystemC Parser  

Microsoft Academic Search

Abstract— Due to the ever increasing complexity of circuits and systems new methodologies for system design are mandatory. Languages that enable modeling at higher levels of abstraction but also allow for a concise hardware description offer a promising way into this direction. One such language is SystemC. In this paper we propose the SystemC parser ParSyC, that allows to convert

G. Fey; T. Cassens; C. Genz; T. Warode; R. Drechsler




Microsoft Academic Search

Les prépositions sont presque toujours une zone d'ombre dans l'apprentissage d'une langue étrangère, car elles portent non seulement des traits sémantiques, mais aussi des traits culturels, y compris une représentation du monde qu'une description grammaticale n'arrive pas à expliquer. Pour le cas qui nous intéresse, c'est-à-dire, la maîtrise des prépositions du français par des apprenants dont la langue maternelle est

Marta Gonçalves; Sandra de Melo


An Evalutation of Planar-Adaptive Routing (PAR)  

Microsoft Academic Search

Network performance can be improved by allowingadaptive routing, but doing so introduces new possibilitiesof deadlock which can overwhelm the flexibilityadvantages. Planar-adaptive routing (PAR) resolvesthis tension by limiting adaptive routing to a seriesof two-dimensional planes, reducing hardware requirementsfor deadlock prevention.We explore the performance of planar-adaptiverouters for two, three, and four-dimensional networks.Under non-uniform traffic loads, the planar-adaptive...

Jae H. Kim; Andrew A. Chien



Ultrasound biomicroscopy of hyperpressurized eyes following pars plana vitrectomy  

PubMed Central

Early elevated intraocular pressure (IOP) following pars plana vitrectomy is a common complication of vitreoretinal surgery and severe pressure elevation may result in visual loss. To investigate the mechanism of IOP elevation following pars plana vitrectomy, a retrospective review of 119 patients (132 eyes) who had undergone vitreoretinal surgery was performed. Ultrasound biomicroscopy (UBM) was used to observe the changes in the structure of the anterior segment following vitrectomy and to compare various parameters pre- and postsurgery. The UBM examination revealed inflammation within the anterior chamber and hyphema with increased IOP. In certain patients, the iris had adhered to the trabecular meshwork and the anterior chamber angle was closed. Cyclodialysis involving the pars plicata and iris was also observed. Furthermore, silicone oil emulsification in the anterior chamber angle and posterior chamber presurgery were noted in certain cases. Edema and forward rotation of the ciliary body resulted in the closure of the anterior chamber angle. The measured parameters indicated that the anterior chamber became shallower and that the anterior chamber angle was narrowed in phakic eyes with elevated IOP. Eyes with elevated IOP and intraocular lenses were not observed to be different from phakic eyes with elevated IOP. This may be due to the fact that an eye with an intraocular lens is thinner than a phakic eye. This study suggests that UBM examination is useful for investigating the pathogenesis of elevated IOP following vitrectomy, and provides a theoretical basis.




Modifications vibrationnelles induites par différentes vapeurs acides sur les polyanilines  

NASA Astrophysics Data System (ADS)

We present a comparative study of conductive form of polyaniline, i.e, polyemeraldine doped with HCl vapor or with HCSA upon m-cresol vapor. UV-Vis.-nir absorption measurements on polyaniline thin films, vs acid vapors time exposure, have been made. In the same way, Raman spectra have been recorded with different excitation lines from the blue and red ranges to the infrared region. Finally, an assignment of Raman bands observed, is proposed and confirmed by vibrational calculations based on valence-force-field. Nous présentons une étude comparative de la forme conductrice de la polyaniline, c'est-à-dire de la polyéméraldine dopée par des vapeurs d'HCl ou dopée par l'acide camphre sulfonique (HCSA) sous vapeurs de m-crésol. Des mesures d'absorption UV-Vis-proche infrarouge sur des films minces de polyaniline, en fonction du temps d'exposition aux vapeurs acides, ont été réalisées. Parallèlement, les spectres Raman ont été obtenus pour différentes longueurs d'onde d'excitation allant du visible jusqu'au proche infrarouge. Finalement, une attribution des bandes Raman observées est proposée et confirmée par des calculs vibrationnels basés sur des champs de force de valence.

Cochet, M.; Quillard, S.; Buisson, J. P.; Lefrant, S.; Louarn, G.



Being on PAR: Outcomes of a Pilot Trial to Improve Mental Health and Wellbeing in the Workplace With the Promoting Adult Resilience (PAR) Program  

Microsoft Academic Search

There is an urgent need to find strategies to promote positive mental health in the workplace. The current study presents outcomes of a pilot trial of the Promoting Adult Resilience (PAR) program, an innovative mental health promotion pro- gram, which is conducted in the workplace over 11 weekly sessions. The PAR pro- gram is a strengths-based resilience-building program that integrates

Prudence Millear; Poppy Liossis; Ian M. Shochet; Herbert Biggs; Maria Donald



Platelet Specific Promoters Are Insufficient to Express Protease Activated Receptor 1 (PAR1) Transgene in Mouse Platelets  

PubMed Central

The in vivo study of protease activated receptors (PARs) in platelets is complicated due to species specific expression profiles. Human platelets express PAR1 and PAR4 whereas mouse platelets express PAR3 and PAR4. Further, PAR subtypes interact with one another to influence activation and signaling. The goal of the current study was to generate mice expressing PAR1 on their platelets using transgenic approaches to mimic PAR expression found in human platelets. This system would allow us to examine specific signaling from PAR1 and the PAR1-PAR4 heterodimer in vivo. Our first approach used the mouse GPIb? promoter to drive expression of mouse PAR1 in platelets (GPIb?-Tg-mPAR1). We obtained the expected frequency of founders carrying the transgene and had the expected Mendelian distribution of the transgene in multiple founders. However, we did not observe expression or a functional response of PAR1. As a second approach, we targeted human PAR1 with the same promoter (GPIb?-Tg-hPAR1). Once again we observed the expected frequency and distributing of the transgene. Human PAR1 expression was detected in platelets from the GPIb?-Tg-hPAR1 mice by flow cytometry, however, at a lower level than for human platelets. Despite a low level of PAR1 expression, platelets from the GPIb?-Tg-hPAR1 mice did not respond to the PAR1 agonist peptide (SFLLRN). In addition, they did not respond to thrombin when crossed to the PAR4?/? mice. Finally, we used an alternative platelet specific promoter, human ?IIb, to express human PAR1 (?IIb-Tg-hPAR1). Similar to our previous attempts, we obtained the expected number of founders but did not detect PAR1 expression or response in platelets from ?IIb-Tg-hPAR1 mice. Although unsuccessful, the experiments described in this report provide a resource for future efforts in generating mice expressing PAR1 on their platelets. We provide an experimental framework and offer considerations that will save time and research funds.

Arachiche, Amal; de la Fuente, Maria; Nieman, Marvin T.



PAR proteins diffuse freely across the anterior-posterior boundary in polarized C. elegans embryos  

PubMed Central

Polarization of cells by PAR proteins requires the segregation of antagonistic sets of proteins into two mutually exclusive membrane-associated domains. Understanding how nanometer scale interactions between individual PAR proteins allow spatial organization across cellular length scales requires determining the kinetic properties of PAR proteins and how they are modified in space. We find that PAR-2 and PAR-6, which localize to opposing PAR domains, undergo exchange between well mixed cytoplasmic populations and laterally diffusing membrane-associated states. Domain maintenance does not involve diffusion barriers, lateral sorting, or active transport. Rather, both PAR proteins are free to diffuse between domains, giving rise to a continuous boundary flux because of lateral diffusion of molecules down the concentration gradients that exist across the embryo. Our results suggest that the equalizing effects of lateral diffusion are countered by actin-independent differences in the effective membrane affinities of PAR proteins between the two domains, which likely depend on the ability of each PAR species to locally modulate the membrane affinity of opposing PAR species within its domain. We propose that the stably polarized embryo reflects a dynamic steady state in which molecules undergo continuous diffusion between regions of net association and dissociation.

Goehring, Nathan W.; Hoege, Carsten



Phosphorylation of Par-4 by protein kinase A is critical for apoptosis.  


Despite distinct dissimilarities, diverse cancers express several common protumorigenic traits. We present here evidence that the proapoptotic protein Par-4 utilizes one such common tumorigenic trait to become selectively activated and induce apoptosis in cancer cells. Elevated protein kinase A (PKA) activity noted in cancer cells activated the apoptotic function of ectopic Par-4 or its SAC (selective for apoptosis induction in cancer cells) domain, which induces apoptosis selectively in cancer cells and not in normal or immortalized cells. PKA preferentially phosphorylated Par-4 at the T155 residue within the SAC domain in cancer cells. Moreover, pharmacological-, peptide-, or small interfering RNA-mediated inhibition of PKA activity in cancer cells resulted in abrogation of both T155 phosphorylation and apoptosis by Par-4. The mechanism of activation of endogenous Par-4 was similar to that of ectopic Par-4, and in response to exogenous stimuli, endogenous Par-4 induced apoptosis by a PKA- and phosphorylated T155-dependent mechanism. Enforced elevation of PKA activity in normal cells resulted in apoptosis by the SAC domain of Par-4 in a T155-dependent manner. Together, these observations suggest that selective apoptosis of cancer cells by the SAC domain of Par-4 involves phosphorylation of T155 by PKA. These findings uncover a novel mechanism engaging PKA, a procancerous activity commonly elevated in most tumor cells, to activate the cancer selective apoptotic action of Par-4. PMID:15657440

Gurumurthy, Sushma; Goswami, Anindya; Vasudevan, Krishna Murthi; Rangnekar, Vivek M



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

PubMed Central

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.

Antoniak, Silvio; Owens, A. Phillip; Baunacke, Martin; Williams, Julie C.; Lee, Rebecca D.; Weithauser, 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



Use of a GnRH agonist to prevent the endogenous LH surge and injection of exogenous LH to induce ovulation in heifers superstimulated with FSH: A new model for superovulation  

Microsoft Academic Search

A new protocol for superovulating cattle which allows for control of the timing of ovulation after superstimulation with FSH was developed. The preovulatory LH surge was blocked with the GnRH agonist deslorelin, and ovulation was induced by injection of LH. In Experiment 1, heifers (3-yr-old) were assigned to a control group (Group 1A, n = 4) or a group with

M. J. D'Occhio; G. Sudha; D. Jillella; T. Whyte; L. J. Maclellan; J. Walsh; T. E. Trigg; D. Miller



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  

Microsoft Academic Search

stimulation. methods: In this large, double-blind, randomized, non-inferiority trial the ongoing pregnancy rates were assessed after one injection of 150 mg 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

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



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


Taking two rice cultivars (Liangyoupeijiu and Wuxiangjing 14) with different plant types as test materials, a 2-year field experiment was conducted to study the relationships of rice canopy photosynthetically active radiation (PAR) interception and light use efficiency to grain yield under three planting densities and five nitrogen (N) application rates. From tillering to maturing stage, the average PAR reflectance in all treatments was 3.45%. The ratio of reflected PAR to the total loss of PAR from tillering to heading stage was 10.90%, which was significantly lower than that (22.06%) from heading to maturiting stage. The PAR conversion efficiency from tillering to maturing stage decreased with increasing planting density but increased with increasing nitrogen rate, and the conversion efficiency was significantly higher from tillering to heading than from heading to maturing stage. The PAR use efficiency from tillering to maturing stage increased with the increase of planting density and nitrogen application rate, and the average PAR use efficiency of Liangyoupeijiu (1.83 g x MJ(-1)) was significantly higher than that of Wuxiangjing 14 (1.42 g x MJ(-1)). Due to the longer growth period of Wuxiangjing 14, its incident PAR and intercepted PAR under midium and high planting densities were higher, as compared with Liangyoupeijiu. The grain yield was significantly positively correlated with the canopy PAR interceptance and use efficiency at different growth stages, but less correlated with the PAR conversion efficiency. To increase the canopy PAR use efficiency and conversion efficiency on the basis of maintaining higher PAR interception rate could be an effective way to increase rice yield. PMID:22919837

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



Paracrine apoptotic effect of p53 mediated by tumor suppressor Par-4.  


The guardian of the genome, p53, is often mutated in cancer and may contribute to therapeutic resistance. Given that p53 is intact and functional in normal tissues, we harnessed its potential to inhibit the growth of p53-deficient cancer cells. Specific activation of p53 in normal fibroblasts selectively induced apoptosis in p53-deficient cancer cells. This paracrine effect was mediated by p53-dependent secretion of the tumor suppressor Par-4. Accordingly, the activation of p53 in normal mice, but not p53(-)/(-) or Par-4(-)/(-) mice, caused systemic elevation of Par-4, which induced apoptosis of p53-deficient tumor cells. Mechanistically, p53 induced Par-4 secretion by suppressing the expression of its binding partner, UACA, which sequesters Par-4. Thus, normal cells can be empowered by p53 activation to induce Par-4 secretion for the inhibition of therapy-resistant tumors. PMID:24412360

Burikhanov, Ravshan; Shrestha-Bhattarai, Tripti; Hebbar, Nikhil; Qiu, Shirley; Zhao, Yanming; Zambetti, Gerard P; Rangnekar, Vivek M



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



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

NASA Astrophysics Data System (ADS)

Le projet de la these est defini par rapport a la recente exploitation commerciale du brut lourd de Doba, une region du Tchad, pays enclave d'ou le brut ainsi produit doit etre achemine par pipeline. Le but dans ce travail est de caracteriser ce brut et de determiner une strategie thermique de transformation en vue de reduire de la facon la plus economique, la viscosite du brut pour permettre son transport par pipeline. Concernant la partie caracterisation, nous avons utilise entre autres, un rheometre rotatif et des analyseurs (LECO CHN-2000 & LECO S-144DR Elemental Analyzers) pour evaluer respectivement la viscosite et les elements tels que C, H, N, O, S. Sur la base des methodes de transformation disponibles, nous avons determine une strategie simple de transformation thermique par hydroviscoreduction , strategie dans laquelle, la fraction legere du brut comme le naphta (80--180°C), pourrait constituer la source d'hydrogene a utiliser. Le brut de Doba, a une faible teneur en soufre (0.14%) et sa densite specifique de 0.940 a 15.6°C, soit 18.8° API, le classe parmi les bruts lourds. Outre le point initial se situant a 85°C, la distillation du brut a revele que la fraction distillant avant 250°C ne represente que 10% (v/v) et que le craquage thermique du substrat debute a 300°C. Par ailleurs, outre son caractere Newtonien, les densites specifiques de la fraction lourde de l'essence (100--200°C) et de la fraction distillant au-dessus 350°C, etant respectivement de 0.813 (0.813 > 0.800) et de 0.951 (0.930 < 0.951 < 0.975), le brut de Doba est donc de type aromatique. Les viscosites du brut et du brut desasphalte, sont respectivement de 184.4 cSt et 152.4 cSt a 50°C, suggerant que le desasphaltage ne constitue pas une methode efficace pouvant aider au pompage du brut par pipeline, d'ou la necessite de transformation. Les resultats des travaux en autoclave montrent que, si le brut doit etre traite entierement, la viscosite de 25cSt 50°C, recommandee pour le transport par pipeline, peut-etre atteinte a une severite de traitement log(R0) = 6.3. Pour des raisons economiques, si le brut traite, devrait etre melange avec 50% en poids du brut non-traite, un traitement a une severite de 6.4 s'impose. De plus, La viscosite du brut traite a une severite de 6.4 ne souffre d'aucun effet de vieillissement meme apres deux mois, ce qui correspond au temps de sejour du brut dans le pipeline. L'etude montre aussi que les asphaltenes du brut traite en absence d'un catalyseur sont moins aromatiques que ceux du brut non-traite.

Dehkissia, Soumaine


Decreased expression of the pro-apoptotic protein Par4 in renal cell carcinoma  

Microsoft Academic Search

Par-4 is a widely expressed leucine zipper protein that confers sensitization to apoptosis induced by exogenous insults. Because the expression of genes that promote apoptosis may be down-regulated during tumorigenesis, we sought to examine the expression of Par-4 in human tumors. We present here evidence that Par-4 protein levels were severely decreased in human renal cell carcinoma specimens relative to

Jason Cook; Sumathi Krishnan; Subbian Ananth; Stephen F Sells; Yang Shi; McClellan M Walther; W Marston Linehan; Vikas P Sukhatme; Michael H Weinstein; Vivek M Rangnekar



A low-complexity PAR-reduction method for DMT-VDSL  

Microsoft Academic Search

Abstract DMT-VDSL signals have a high peak-to-average power ratio (PAR). In the transmitters, the PAR governs the necessary resolution of the digital-to-analog converter (DAC) and is an important factor for the power consumption of the line-driver. Aiming at implementation in a specific system, we propose a low complexity PAR-reduction method based on the iterative algorithm derived in [5, 20, 24,

Per Ola B Orjesson; Hans G. Feichtinger; Niklas Grip; Mikael Isaksson; Norbert Kaiblinger; Per Odling; Lars-erik Persson


Suppression of Par4 Protects Human Renal Proximal Tubule Cells from Apoptosis Induced by Oxidative Stress  

Microsoft Academic Search

Background: Oxidative stress is an important inducer of cell apoptosis and plays a key role in the development of renal inflammation. The prostate apoptosis response factor-4 (Par-4) gene was originally identified in prostate cells undergoing apoptosis. Subsequently, Par-4 was found to possess potent pro-apoptotic activity in various cellular systems. However, it remains unclear whether Par-4 is involved in oxidant injury

Bin Sun; Chao Lu; Guo-Ping Zhou; Chang-Ying Xing



Bacterial DNA segregation dynamics mediated by the polymerizing protein ParF  

Microsoft Academic Search

Prokaryotic DNA segregation most commonly involves members of the Walker-type ParA superfamily. Here we show that the ParF partition protein specified by the TP228 plasmid is a ParA ATPase that assembles into extensive filaments in vitro. Polymerization is potentiated by ATP binding and does not require nucleotide hydrolysis. Analysis of mutations in conserved residues of the Walker A motif established

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



ScalParC: A New Scalable and Efficient Parallel Classification Algorithm for Mining Large Datasets  

Microsoft Academic Search

In this paper, we present ScalParC ( Scalable Parallel Classifier), a new parallel formulation of a decision tree based classification process. Like other state-of-the-art de- cision tree classifiers such as SPRINT, ScalParC is suited for handling large datasets. We show that existing parallel formulation of SPRINT is unscalable, whereas ScalParC is shown to be scalable in both runtime and memory

Mahesh V. Joshi; George Karypis; Vipin Kumar



Pars intermedia of the pituitary gland and integumentary colour changes in the garden lizard Calotes versicolor  

Microsoft Academic Search

1.The effect of light and of colour of the background on the secretory activity of the pars intermedia of the garden lizard has been investigated.2.Absence of light, as well as black illuminated background, produces increased acticity of the pars intermedia, proportional to the duration of the experiment.3.Pale illuminated background has no effect on the secretory activity of the pars intermedia.4.The

Shanta Nayar; K. R. Pandalai



DmPAR-6 directs epithelial polarity and asymmetric cell division of  

Microsoft Academic Search

The Drosophila protein Bazooka is required for both apical-basal polarity in epithelial cells and directing asymmetric cell division in neuroblasts. Here we show that the PDZ-domain protein DmPAR-6 cooperates with Bazooka for both of these functions. DmPAR-6 colocalizes with Bazooka at the apical cell cortex of epithelial cells and neuroblasts, and binds to Bazooka in vitro. DmPAR-6 localization requires Bazooka,

Mark Petronczki; Juergen A. Knoblich; Bohr Gasse


DmPAR-6 directs epithelial polarity and asymmetric cell division of neuroblasts in Drosophila  

Microsoft Academic Search

The Drosophila protein Bazooka is required for both apical–basal polarity in epithelial cells and directing asymmetric cell division in neuroblasts. Here we show that the PDZ-domain protein DmPAR-6 cooperates with Bazooka for both of these functions. DmPAR-6 colocalizes with Bazooka at the apical cell cortex of epithelial cells and neuroblasts, and binds to Bazooka in vitro . DmPAR-6 localization requires

Mark Petronczki; Juergen A. Knoblich



Pharmacodynamics of a single low dose of long-acting recombinant follicle-stimulating hormone (FSH-carboxy terminal peptide, corifollitropin alfa) in women with World Health Organization group II anovulatory infertility.  


In a double-blind, placebo-controlled, randomized study, 55 anovulatory subjects received a single s.c. injection of placebo (n = 10) or recombinant long-acting FSH [FSH-carboxy terminal peptide (CTP), ORG 36286, corifollitropin alfa; NV Organon, The Netherlands] in doses of 7.5 (n = 13), 15 (n = 10), 30 (n = 11), or 60 microg (n = 11). The injection was given 2 or 3 d after the onset of a spontaneous or progestagen-induced withdrawal bleed. After drug administration, the induced follicular response varied widely among subjects in each dose group. The percentage of subjects with a follicular response (at least one follicle > or = 10.0 mm) increased with the dose (P < 0.01) and was 10, 31, 70, 73, and 82% in the placebo and 7.5-, 15-, 30-, and 60-microg treatment groups, respectively. In responding subjects, the average maximum number of follicles was 4.0, 7.6, 13.4, and 20.0, respectively, which was reached at 6.5, 6.9, 6.6, and 8.2 d after a single dose of 7.5, 15, 30, and 60 microg FSH-CTP, respectively. The dose-response for the number of follicles was statistically significant within the dose range tested (P < 0.01). Peak serum inhibin-B levels were significantly correlated with serum estradiol (E2) levels (r = 0.84, P < 0.01), and peak concentrations of inhibin-B and E2 correlated with the number of follicles observed at the same time point (for both hormones; r = 0.47, P < 0.01). Overall per treatment group, serum E2 and inhibin B concentrations significantly increased only in the two highest FSH-CTP dose groups, reaching peak concentrations at d 3 in the 30-microg group and at d 5 in the 60-microg group. Thereafter these hormone values declined rapidly, returning to baseline within 1 wk after FSH-CTP administration. In total, nine of the 55 treated subjects (16.4%) ovulated after drug administration: one subject in the placebo group, two subjects in the 7.5-microg group, three subjects in the 15-microg group, two in the 30-microg group, and one in the 60-microg group. Three subjects had monofollicular ovulation after placebo (n = 1) and a single dose of 15 microg FSH-CTP (n = 2). In two subjects with too many preovulatory follicles, (multiple) ovulation was prevented by GnRH antagonist administration. Thus, a single low dose of long-acting FSH-CTP was able to induce one or more follicles to grow up to ovulatory sizes, but the anovulatory status was not reversed because the incidence of subsequent (mono)ovulations was low. PMID:15579793

Balen, A H; Mulders, A G; Fauser, B C; Schoot, B C; Renier, M A; Devroey, P; Struijs, M J; Mannaerts, B M



Immunohistochemical analysis of the proapoptotic protein Par-4 in normal rat tissues.  


Prostate apoptosis response 4 (par-4) is a recently identified gene that encodes a transcription factor, Par-4, with a leucine zipper domain. Par-4 protein is constitutively expressed in various cell lines and is functionally required but not sufficient for apoptosis. Induction of Par-4 in cultured cells is found exclusively during apoptosis, and ectopic overexpression of Par-4 enhances the potency of apoptotic stimuli. Western or Northern blot analysis on mRNA or protein extracts, respectively, from rat organs revealed that the expression of Par-4 was ubiquitous and was not restricted to any specific organ(s). To further identify specific cell types that expressed Par-4, we performed an immunohistochemical analysis of the protein in paraffin-embedded sections of various organs from rats. Our findings indicated that consistent with its proapoptotic role, Par-4 is expressed in apoptotic granulosa cells of atretic ovarian follicles and in terminally differentiated cells, such as the cardiomyocytes, cerebellar Purkinje cells, and pyramidal cells of the hypothalamus. Moreover, testosterone ablation by castration of rats caused an early and transient induction of Par-4 in the ductal cells of the prostate that undergo apoptosis. By contrast, in tissues in which the cells could be visually differentiated from their mature counterparts, Par-4 expression was lowest in the mature cells. This was the case for epithelia of the mammary and the prostate gland in which the basal cells maintained higher protein levels of Par-4 than did the terminally differentiated ductal cells. Similarly, cells of the stratum corneum of the skin and cells on top of the duodenal villi stained less intensely for Par-4 as compared to the stem cells in the stratum basale and at the bottom of the crypts of Lieberkühn, respectively. It is possible that Par-4 has to be down-regulated for successful differentiation in these tissues. Taken together, the widespread expression of Par-4 in various adult cell types underscores the physiological importance of the protein. The observation of constitutive Par-4 expression in the stem cell compartments is inconsistent with the probability of apoptosis per se and can be extended to determine whether Par-4 plays a role in other cellular processes. PMID:9269897

Boghaert, E R; Sells, S F; Walid, A J; Malone, P; Williams, N M; Weinstein, M H; Strange, R; Rangnekar, V M



Cancer-selective apoptotic effects of extracellular and intracellular Par-4.  


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

Shrestha-Bhattarai, T; Rangnekar, V M



ParA ATPases can move and position DNA and subcellular structures.  


Prokaryotic chromosomes and plasmids can be actively segregated by partitioning (par) loci. The common ParA-encoding par loci segregate plasmids by arranging them in regular arrays over the nucleoid by an unknown mechanism. Recent observations indicate that ParA moves plasmids and chromosomes by a pulling mechanism. Even though ParAs form filaments in vitro it is not known whether similar structures are present in vivo. ParA of P1 forms filaments in vitro at very high concentrations only and filament-like structures have not been observed in vivo. Consequently, a 'diffusion-ratchet' mechanism was suggested to explain plasmid movement by ParA of P1. We compare this mechanism with our previously proposed filament model for plasmid movement by ParA. Remarkably, ParA homologues have been discovered to arrange subcellular structures such as carboxysomes and chemotaxis sensory receptors in a regular manner very similar to those of the plasmid arrays. PMID:21963112

Szardenings, Florian; Guymer, David; Gerdes, Kenn



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


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



Key to the cladocera of Par Pond on the Savannah River Plant  

SciTech Connect

A key is provided for the identification of the cladocerans of Par Pond, a thermally enriched impoundment on the grounds of the Savannah River Plant near Aiken, South Carolina. Extensive use was made of existing data on cladoceran species and their distribution in Par Pond. Information is presented under the following section headings: species found in Par Pond: their abundance, temporal, and spatial distribution; methods for collection, preservation, and identification; key to the cladocerans of Par Pond (including, major divisions of the order cladocera and genera and species within the families). A glossary is included. (JGB)

Berner, D.B.



Isolation and characterization of par1(+) and par2(+): two Schizosaccharomyces pombe genes encoding B' subunits of protein phosphatase 2A.  

PubMed Central

Protein phosphatase 2A (PP2A) is one of the major serine/threonine phosphatases found in eukaryotic cells. We cloned two genes, par1(+) and par2(+), encoding distinct B' subunits of PP2A in fission yeast. They share 52% identity at the amino acid sequence level. Neither gene is essential but together they are required for normal septum positioning and cytokinesis, for growth at both high and low temperature, and for growth under a number of stressful conditions. Immunofluorescence microscopy revealed that Par2p has a cell-cycle-related localization pattern, being localized at cell ends during interphase and forming a medial ring in cells that are undergoing septation and cytokinesis. Our analyses also indicate that Par1p is more abundant than Par2p in the cell. Cross-organism studies showed that both par1(+) and par2(+) could complement the rts1Delta allele in Saccharomyces cerevisiae, albeit to different extents, in spite of the fact that neither contains a serine/threonine-rich N-terminal domain like that found in the S. cerevisiae homolog Rts1p. Thus, while Schizosaccharomyces pombe is more similar to higher eukaryotes with respect to its complement of B'-encoding genes, the function of those proteins is conserved relative to that of Rts1p.

Jiang, W; Hallberg, R L



The Two Cis-Acting Sites, parS1 and oriC1, Contribute to the Longitudinal Organisation of Vibrio cholerae Chromosome I  

PubMed Central

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.

David, Ariane; Demarre, Gaelle; Muresan, Leila; Paly, Evelyne; Barre, Francois-Xavier; Possoz, Christophe



Emerging Roles of PAR-1 and PAFR in Melanoma Metastasis  

PubMed Central

Melanoma growth, angiogenesis and metastatic progression are strongly promoted by the inflammatory tumor microenvironment due to high levels of cytokine and chemokine secretion by the recruited inflammatory and stromal cells. In addition, platelets and molecular components of procoagulant pathways have been recently emerging as critical players of tumor growth and metastasis. In particular, thrombin, through the activity of its receptor protease-activated receptor-1 (PAR-1), regulates tumor cell adhesion to platelets and endothelial cells, stimulates tumor angiogenesis, and promotes tumor growth and metastasis. Notably, in many tumor types including melanoma, PAR-1 expression directly correlates with their metastatic phenotype and is directly responsible for the expression of interleukin-8, matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor, platelet-derived growth factor, and integrins. Another proinflammatory receptor–ligand pair, platelet-activating factor (PAF) and its receptor (PAFR), have been shown to act as important modulators of tumor cell adhesion to endothelial cells, angiogenesis, tumor growth and metastasis. PAF is a bioactive lipid produced by a variety of cells from membrane glycerophospholipids in the same reaction that releases arachidonic acid, and can be secreted by platelets, inflammatory cells, keratinocytes and endothelial cells. We have demonstrated that in metastatic melanoma cells, PAF stimulates the phosphorylation of cyclic adenosine monophosphate response element-binding protein (CREB) and activating transcription factor 1 (ATF-1), which results in overexpression of MMP-2 and membrane type 1-MMP (membrane type 1-MMP). Since only metastatic melanoma cells overexpress CREB/ATF-1, we propose that metastatic melanoma cells are better equipped than their non-metastatic counterparts to respond to PAF within the tumor microenvironment. The evidence supporting the hypothesis that the two G-protein coupled receptors, PAR-1 and PAFR, contribute to the acquisition of the metastatic phenotype of melanoma is presented and discussed.

Melnikova, Vladislava O.; Villares, Gabriel J.



Diffraction d’ondes électromagnétiques impulsionnelles par des obstacles métalliques  

Microsoft Academic Search

\\u000a Analyse  \\u000a La diffraction en régime transitoire est traitée directement dans le domaine temporel par une méthode originale utilisant\\u000a la théorie des distributions. Pour les obstacles métalliques parfaitement conducteurs, cette approche généralise les solutions\\u000a existantes dans la littérature, mais permet aussi d’établir de nouvelles équations intégrales donnant la solution des problèmes\\u000a de diffraction à deux dimensions (l’onde et l’obstacle présentent une

Bernard Jecko



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.



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



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.

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



Co-culture of spermatogonial stem cells with sertoli cells in the presence of testosterone and FSH improved differentiation via up-regulation of post meiotic genes.  


Spermatogonial stem cells (SSCs) maintain spermatogenesis throughout life in the male. Maintenance of SSCs and induction of spermiogenesis in vitro may provide a therapeutic strategy to treat male infertility. This study investigated in vitro differentiation of mouse SSCs in presence or absence of Sertoli cells, hormones and vitamins. Spermatogonial populations were enriched from testes of 4-6 week old males by magnetic activated cell sorting and anti-Thy-1 antibody. Sertoli cells isolated from 6-8 week old testes were enriched using lectin-DSA-coated plates. Isolated SSCs were cultured in the presence of Leukemia inhibitory factor (LIF) for 7 days in gelatin-coated dishes, then dissociated and cultured for 7 days in media lacking LIF in the presence or absence of Sertoli cells, with or without FSH, testosterone and vitamins. After one week, the effects of Sertoli cells ± supplementary media on SSC differentiation was evaluated by microscopy and expression of meiotic and postmeiotic transcripts using RT-PCR. SSC colonies had limited development after LIF removal alone, exhibiting low expression of meiotic (Scp3, Th2b) but not postmeiotic transcript, and loss of Stra8 and Dazl expression. SSCs co-cultured with Sertoli cells, hormones and vitamins developed spermatid-like cells expressing postmeiotic markers (TP1, TP2, Prm1) at levels over 2-fold higher than Sertoli cells or hormone/vitamins alone. Our present SSC-Sertoli co-culture provides conditions that may allow efficient in vitro differentiation of SSCs for the treatment of male infertility. PMID:23456578

Minaee Zanganeh, Bagher; Rastegar, Tayebeh; Habibi Roudkenar, Mehryar; Ragerdi Kashani, Iraj; Amidi, Fardin; Abolhasani, Farid; Barbarestani, Mohammad



The polarity protein Par6 is coupled to the microtubule network during molluscan early embryogenesis  

SciTech Connect

Research highlights: {yields} The cDNAs encoding Par6 and aPKC homologues were cloned from the snail Lymnaea stagnalis. {yields} L. stagnalis Par6 directly interacts with tubulin and microtubules and localizes to the microtubule cytoskeleton during the early embryogenesis. {yields} Identical sequence and localization of LsPar6 for the dextral and the sinistral snails exclude the possibility of the gene being the primary determinant of body handedness. -- Abstract: Cell polarity, which directs the orientation of asymmetric cell division and segregation of fate determinants, is a fundamental feature of development and differentiation. Regulators of polarity have been extensively studied, and the critical importance of the Par (partitioning-defective) complex as the polarity machinery is now recognized in a wide range of eukaryotic systems. The Par polarity module is evolutionarily conserved, but its mechanism and cooperating factors vary among different systems. Here we describe the cloning and characterization of a pond snail Lymnaea stagnalis homologue of partitioning-defective 6 (Lspar6). The protein product LsPar6 shows high affinity for microtubules and localizes to the mitotic apparatus during embryonic cell division. In vitro assays revealed direct binding of LsPar6 to tubulin and microtubules, which is the first evidence of the direct interaction between the two proteins. The interaction is mediated by two distinct regions of LsPar6 both located in the N-terminal half. Atypical PKC, a functional partner of Par6, was also found to localize to the mitotic spindle. These results suggest that the L. stagnalis Par complex employs the microtubule network in cell polarity processes during the early embryogenesis. Identical sequence and localization of LsPar6 for the dextral and the sinistral snails exclude the possibility of the gene being the primary determinant of handedness.

Homma, Taihei [Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)] [Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Shimizu, Miho [Kuroda Chiromorphology Team, ERATO-SORST, JST, Komaba, Meguro-ku, Tokyo 153-8902 (Japan)] [Kuroda Chiromorphology Team, ERATO-SORST, JST, Komaba, Meguro-ku, Tokyo 153-8902 (Japan); Kuroda, Reiko, E-mail: [Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan) [Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Kuroda Chiromorphology Team, ERATO-SORST, JST, Komaba, Meguro-ku, Tokyo 153-8902 (Japan); Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro-ku, Tokyo 153-8902 (Japan)



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

PubMed Central

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 analysis approach to generate hypotheses about differences between PARS and other cases of schizophrenia. Methods We studied PARS (operationally defined as not having any family history of schizophrenia among first and second-degree relatives and fathers’ age at birth ?35 years) in a series of schizophrenia cases recruited from a research unit. Data were available on demographic variables, symptoms (Positive and Negative Syndrome Scale; PANSS), cognitive tests (Wechsler Adult Intelligence Scale—Revised; WAIS-R) and olfaction (University of Pennsylvania Smell Identification Test; UPSIT). We conducted a series of k-means clustering analyses to identify clusters of cases containing high concentrations of PARS. Results Two analyses generated clusters with high concentrations of PARS cases. The first analysis (N=136; PARS=34) revealed a cluster containing 83% PARS cases, in which the patients showed a significant discrepancy between verbal and performance intelligence. The mean paternal and maternal ages were 41 and 33, respectively. The second analysis (N=123; PARS=30) revealed a cluster containing 71% PARS cases, of which 93% were females; the mean age of onset of psychosis, at 17.2, was significantly early. Conclusions These results strengthen the evidence that PARS cases differ from other patients with schizophrenia. Hypothesis-generating findings suggest that features of PARS may include a discrepancy between verbal and performance intelligence, and in females, an early age of onset. These findings provide a rationale for separating these phenotypes from others in future clinical, genetic and pathophysiologic studies of schizophrenia and in considering responses to treatment.

Lee, Hyejoo; Malaspina, Dolores; Ahn, Hongshik; Perrin, Mary; Opler, Mark G.; Kleinhaus, Karine; Harlap, Susan; Goetz, Raymond; Antonius, Daniel



Brulure par Foudre. A Propos d'une Observation  

PubMed Central

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

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



Comparison and influence of two newly produced Iranian oil dispersants (Pars1 &Pars2) with the Gamlen OD4000 on rainbow trout.  


Dispersants are the group of chemicals, designed to be sprayed on to the oil slicks to accelerate the process of natural dispersion. In this study, the acute toxicity of two newly produced Iranian oil dispersants (Pars1 &Pars2) was evaluated and compared to the Gamlen OD 4000 in different concentrations on 28-32 g of rainbow trout (Oncorhynchus mykiss). The 50% of lethal concentration (LC50) of 96-h acute toxicity of exposed fish were determined by means of Probit value and ANOVA test. Relative effectiveness toxicity (RET) of all oil dispersants according to their LC50 has been measured. Pars1 has the lowest RET (12.56) in contrast to Pars2 (RET = 47.51) and Gamlen OD4000 (RET = 21.34) proved to have the highest efficiency and to be the best one under the laboratory conditions used in this study. PMID:18988096

Bordbar, Leila; Emtyazjoo, Mozhgan; Farkhani, Daroush



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.

Khazaei, Mohammad R.; Puschel, Andreas W.



Negative regulation of Par4 by oncogenic Ras is essential for cellular transformation  

Microsoft Academic Search

Oncogenic variants of the cellular Ras protein are often associated with different types of human cancers. However, the mechanisms by which oncogenic Ras induces transformation are not fully established. Expression of the transcriptional repressor Par-4 was down-regulated by oncogenic Ras via the Raf – MEK – ERK pathway. Restoration of Par-4 levels by abrogation of the Raf – MEK –

Shirley Guofang Qiu; Sumathi Krishnan; Nadia El-Guendy; Vivek M Rangnekar



The tumor suppressor Par-4 activates an extrinsic pathway for apoptosis.  


Prostate apoptosis response-4 (Par-4) is a proapoptotic protein with intracellular functions in the cytoplasm and nucleus. Unexpectedly, we noted Par-4 protein is spontaneously secreted by normal and cancer cells in culture, and by Par-4 transgenic mice that are resistant to spontaneous tumors. Short exposure to endoplasmic reticulum (ER) stress-inducing agents further increased cellular secretion of Par-4 by a brefeldin A-sensitive pathway. Secretion occurred independently of caspase activation and apoptosis. Interestingly, extracellular Par-4 induced apoptosis by binding to the stress response protein, glucose-regulated protein-78 (GRP78), expressed at the surface of cancer cells. The interaction of extracellular Par-4 and cell surface GRP78 led to apoptosis via ER stress and activation of the FADD/caspase-8/caspase-3 pathway. Moreover, apoptosis inducible by TRAIL, which also exerts cancer cell-specific effects, is dependent on extracellular Par-4 signaling via cell surface GRP78. Thus, Par-4 activates an extrinsic pathway involving cell surface GRP78 receptor for induction of apoptosis. PMID:19632185

Burikhanov, Ravshan; Zhao, Yanming; Goswami, Anindya; Qiu, Shirley; Schwarze, Steven R; Rangnekar, Vivek M



Par6 regulates skeletogenesis and gut differentiation in sea urchin larvae.  


Partitioning-defective (par) genes were originally identified as genes that are essential for the asymmetric division of the Caenorhabditis elegans zygote. Studies have since revealed that the gene products are part of an evolutionarily conserved PAR-atypical protein kinase C system involved in cell polarity in various biological contexts. In this study, we analyzed the function of par6 during sea urchin morphogenesis by morpholino-mediated knockdown and by manipulation swapping of the primary mesenchyme cells (PMCs). Loss of Par6 resulted in defects in skeletogenesis and gut differentiation in larvae. Phenotypic analyses of chimeras constructed by PMC swapping showed that Par6 in non-PMCs is required for differentiation of archenteron into functional gut. In contrast, Par6 in both PMCs and ectodermal cells cooperatively regulates skeletogenesis. We suggest that Par6 in PMCs plays an immediate role in the deposition of biomineral in the syncytial cable, whereas Par6 in ectoderm may stabilize skeletal rods via an unknown signal(s). PMID:22903233

Shiomi, Kosuke; Yamazaki, Atsuko; Kagawa, Mitsuyoshi; Kiyomoto, Masato; Yamaguchi, Masaaki



PAR-4: a possible new target for age-related disease.  


Introduction: Apoptosis plays an important role in age-related disease, and prostate apoptosis response-4 (PAR-4) is a novel apoptosis-inducing factor that regulates apoptosis in most cells. Recent studies suggest that PAR-4 plays an important role in the progression of many age-related diseases. This review highlights the significance of PAR-4 and builds a strong case supporting its role as a possible therapeutic target in age-related disease. Areas covered: This review covers the advancements over the last 15 years with respect to PAR-4 and its significance in age-related disease. Additionally, it provides knowledge regarding the significance of PAR-4 in age-related disease as well as its role in apoptotic signaling pathways, endoplasmic reticulum (ER) stress, and other mechanisms that may induce age-related disease. Expert Opinion: PAR-4 may be a potential therapeutic target that can trigger selective apoptosis in cancer cells. It is induced by ER stress and increased ER stress, and it is involved in the activity of the dopamine D2 receptor. Abnormal expression of PAR-4 may be associated with cardiovascular disease and diabetes. PAR-4 agonists and inhibitors must be identified before gene therapy can commence. PMID:24890982

Qinan, Wu; Ling, Zhang; Bing, Chen




Microsoft Academic Search

Les petits exploitants agricoles, les artisans ruraux et en général les plus pauvres opérateurs des zones rurales des P.V.D., dont la production est caractérisée par de nombreuses contraintes et par des risques élevés, sont restés en marge du développement économique de leur pays. La mécanisation, les innovations technologiques, les « révolutions vertes » et de façon générale l'ensemble des politiques

K. P. Padmanbhan



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.

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



Visual Results and Complications after Trans Pars Plana Vitrectomy and Lensectomy for Lens Dislocation  

Microsoft Academic Search

Background: The aim of this study is to determine the relationship between the cause of lens dislocation and visual outcomes with complications in patients undergo- ing trans pars plana vitrectomy (TPPV) and trans pars plana lensectomy (TPPL) for lens dislocation. Methods: This retrospective study was carried out from July 1995 through November 2003. After excluding patients with previous retinal detachment

Hsiu-Mei Huang; Min-Lun Kao; Shih-Hao Tsai; Yung-Jen Chen; Chi-Chang Liu


Diffraction de rayons X sur les plaquettes de fer durcies par cyanuration  

NASA Astrophysics Data System (ADS)

Une méthode de cyanuration a été developpée pour les surfaces des plaquettes de fer, basée sur une réaction thermochimique qui conduit à la formation des couches dures sur le métal. Les échantillons ont été analysés, pour de temps différents de traitement, par diffraction de rayons X et par mesures de dureté.

Popescu, M.; Hoyer, W.; Stegarescu, M.; Cornet, A.; Broll, N.



PAR-1 upregulation by trimethyltin and lipopolysaccharide in cultured rat astrocytes.  


We have previously shown that various protease-activated receptor (PAR) isoforms, mainly PAR-1, are upregulated in reactive astrocytes of rat hippocampus following i.p. administration of trimethyltin (TMT), a neurotoxicant which is known to cause neuronal death and reactive gliosis. In the present paper, we demonstrate that this PAR-1 upregulation was also mimicked in primary cultures of neonatal rat cortex astrocytes after exposure (24 and 48 h) to TMT (10-100 microM). This result suggests that the PAR-1 increase we have observed in vivo may represent a direct effect of TMT on astrocytes rather than a consequence of a complex astrocytic reaction following neuronal death. Furthermore, an evident upregulation of PAR-1 in cultured primary astrocytes also occurred following exposure to lipopolysaccharide (LPS) (a well-known inductor of glial cell activation) whereas other neurotoxic agents (such as staurosporine, hydrogen peroxide and sodium azide), which are known to induce cell death, were unable to determine any PAR-1 variation. Similarly to astrocytes, both TMT and LPS induced an upregulation of PAR-1 in the rat astrocytoma cell line, C6, thus indicating that this phenomenon was independent from microglial cells eventually contaminating astrocyte primary cultures. Furthermore, after exposure to TMT and LPS, the levels of tumor necrosis factor-alpha and interleukin-1beta were also increased in astrocyte cultures, suggesting that the PAR-1 upregulation we have detected may be involved in glial inflammatory response rather than in cell death. PMID:16786153

Pompili, Elena; Fabrizi, Cinzia; Fumagalli, Lorenzo



Generating and forecasting monthly flows of the Ganges river with PAR model  

Microsoft Academic Search

Contemporary building techniques and underlying theories of periodic autoregressive (PAR) models are revisited, reviewed, modified and recast. New techniques for generating synthetic data from any PAR model with provision to constrain some parameter values to zero have been proposed. The developed method is applied to the Ganges river for its monthly flow forecasting and generation. The results demonstrate that the

M. Shahjahan Mondal; Saleh A. Wasimi



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.

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



Structural Mechanism of ATP-induced Polymerization of the Partition Factor ParF  

PubMed Central

Segregation of the bacterial multidrug resistance plasmid TP228 requires the centromere-binding protein ParG, the parH centromere, and the Walker box ATPase ParF. The cycling of ParF between ADP- and ATP-bound states drives TP228 partition; ATP binding stimulates ParF polymerization, which is essential for segregation, whereas ADP binding antagonizes polymerization and inhibits DNA partition. The molecular mechanism involved in this adenine nucleotide switch is unclear. Moreover, it is unknown how any Walker box protein polymerizes in an ATP-dependent manner. Here, we describe multiple ParF structures in ADP- and phosphomethylphosphonic acid adenylate ester (AMPPCP)-bound states. ParF-ADP is monomeric but dimerizes when complexed with AMPPCP. Strikingly, in ParF-AMPPCP structures, the dimers interact to create dimer-of-dimer “units” that generate a specific linear filament. Mutation of interface residues prevents both polymerization and DNA segregation in vivo. Thus, these data provide insight into a unique mechanism by which a Walker box protein forms polymers that involves the generation of ATP-induced dimer-of-dimer building blocks.

Schumacher, Maria A.; Ye, Qiaozhen; Barge, Madhuri T.; Zampini, Massimiliano; Barilla, Daniela; Hayes, Finbarr



Vissage percutan? du scapho?de carpien par vis de Herbert - ? propos de 10 cas  

PubMed Central

Les fractures du scaphoïde carpien sont de diagnostic et de traitement difficiles. Les auteurs rapportent les résultats du traitement de ces fractures par le vissage percutané par la vis de Herbert. Les résultats étaient intéressants vu la rapidité de consolidation et la qualité du résultat fonctionnel.

Abbassi, Najib; Abdeljawad, Najib; Erraji, Moncef; Abdelillah, Rachid; Daoudi, Abdelkrim; Yacoubi, Hicham



Relationship between woody biomass and PAR conversion efficiency for estimating net primary production from NDVI  

Microsoft Academic Search

Terrestrial net primary production (NPP) may be determined from remotely-sensed vegetation indices by estimating the amount of photosynthetically active radiation (PAR) absorbed by vegetation. Studies from the literature were used to determine the upper limit of the PAR conversion efficiency (?) as a function of woody biomass for forest vegetation. Without climatic or other limitations, the upper limit was about




Interface between a Biomation 805 and a PAR 4202 signal averager  

Microsoft Academic Search

An easy to build low cost interface between a Biomation 805 waveform recorder and a Princeton Applied Research 4202 Signal Averager is described. This allows averaging of faster signals than is possible with the PAR 4202. A circuit modification of the PAR 4202 Signal Averager permits remote control of the front panel functions CLEAR\\/START\\/STOP and ERASE MEM. The function of

M. Meier



Caspase-8-mediated PAR-4 cleavage is required for TNF?-induced apoptosis  

PubMed Central

The tumor suppressor protein prostate apoptosis response-4 (PAR-4) is silenced in a subset of human cancers and its down-regulation serves as a mechanism for cancer cell survival following chemotherapy. PAR-4 re-expression selectively causes apoptosis in cancer cells but how its pro-apoptotic functions are controlled and executed precisely is currently unknown. We demonstrate here that UV-induced apoptosis results in a rapid caspase-dependent PAR-4 cleavage at EEPD131G, a sequence that was preferentially recognized by caspase-8. To investigate the effect on cell growth for this cleavage event we established stable cell lines that express wild-type-PAR-4 or the caspase cleavage resistant mutant PAR-4 D131G under the control of a doxycycline-inducible promoter. Induction of the wild-type protein but not the mutant interfered with cell proliferation, predominantly through induction of apoptosis. We further demonstrate that TNF?-induced apoptosis leads to caspase-8-dependent PAR-4-cleavage followed by nuclear accumulation of the C-terminal PAR-4 (132-340) fragment, which then induces apoptosis. Taken together, our results indicate that the mechanism by which PAR-4 orchestrates the apoptotic process requires cleavage by caspase-8.

Treude, Fabian; Kappes, Ferdinand; Fahrenkamp, Dirk; Muller-Newen, Gerhard; Dajas-Bailador, Federico; Kramer, Oliver H.; Luscher, Bernhard; Hartkamp, Jorg



Activation of protease-activated receptor (PAR) 1 by frog trefoil factor (TFF) 2 and PAR4 by human TFF2  

Microsoft Academic Search

Trefoil factors (TFFs) promote epithelial cell migration to reseal superficial wounds after mucosal injury, but their receptors\\u000a and the molecular mechanisms underlying this process are poorly understood. In this study, we showed that frog TFF2 activates\\u000a protease-activated receptor (PAR) 1 to induce human platelet aggregation. Based on this result, we further tested the involvement\\u000a of PARs in human TFF2 (hTFF2)-promoted

Yong Zhang; Guoyu Yu; Yanjie Wang; Yang Xiang; Qian Gao; Ping Jiang; Jie Zhang; Wenhui Lee; Yun Zhang


L'influence du système neurovégétatif sur l'hyperglycémie par la glucagone et sur l'hypoglycémie par N-(4-méthyl-benzosulfonyl)-N'-butylurée  

Microsoft Academic Search

Résumé Les Auteurs, ayant déterminé chez le lapin de modifications de la glycémie après administration intraveineuse de substances douées d'action pharmacodynamique sur le système neuro-végétatif central (chloropromazine) ou périphérique (ergotamine et atropine), étudient les effets des mêmes substances sur l'hyperglycémie par la glucagone et sur l'hypoglycémie par la N-(4-méthyl-benzosulfonyl)-N'-butylurée (D 860). La chloropromazine à la dose de mg 5\\/kg et

C. Cavallero; B. Malandra



Developmental Role of Zebrafish Protease-Activated Receptor 1 (PAR1) in the Cardio-Vascular System  

PubMed Central

Thrombin receptor, F2R or PAR1 is a G-protein coupled receptor, located in the membrane of endothelial cells. It has been initially found to transduce signals in hemostasis, but recently also known to act in cancer and in vascular development. Mouse embryos lacking PAR1 function die from hemorrhages with varying frequency at midgestation. We have performed a survey of potential PAR1 homologs in the zebrafish genome and identified a teleost ortholog of mammalian PAR1. Knockdown of par1 function in zebrafish embryos demonstrates a requirement for Par1 in cardio-vascular development. Furthermore, we show that function of Par1 requires the presence of a phylogenetically conserved proteolytic cleavage site and a second intracellular domain. Altogether our results demonstrate a high degree of conservation of PAR1 proteins in the vertebrate lineage in respect to amino acid sequence as well as protein function.

Bouzaffour, Mohamed; Dufourcq, Pascale; Trayer, Vincent; Gauron, Carole; Vriz, Sophie; Affolter, Markus; Rampon, Christine



Par-4 is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer disease.  


Prostate apoptosis response-4 (Par-4) is a protein containing both a leucine zipper and a death domain that was isolated by differential screening for genes upregulated in prostate cancer cells undergoing apoptosis. Par-4 is expressed in the nervous system, where its function is unknown. In Alzheimer disease (AD), neurons may die by apoptosis, and amyloid beta-protein (A beta) may play a role in this. We report here that Par-4 expression is increased in vulnerable neurons in AD brain and is induced in cultured neurons undergoing apoptosis. Blockade of Par-4 expression or function prevented neuronal apoptosis induced by Ab and trophic factor withdrawal. Par-4 expression was enhanced, and mitochondrial dysfunction and apoptosis exacerbated, in cells expressing presenilin-1 mutations associated with early-onset inherited AD. PMID:9701251

Guo, Q; Fu, W; Xie, J; Luo, H; Sells, S F; Geddes, J W; Bondada, V; Rangnekar, V M; Mattson, M P



The ParA/MinD family puts things in their place  

PubMed Central

Bacteria must segregate their DNA and position a septum to grow and divide. In many bacteria MinD is involved in spatial regulation of the cytokinetic Z ring and ParAs are involved in chromosome and plasmid segregation. The use of the MinD/ParA family to provide positional information for spatial organization continues to expand with the recognition that orphan ParAs are required for segregating cytoplasmic protein clusters and the polar localization of chemotaxis proteins, conjugative transfer machinery, type IV pili and cellulose synthesis. Also, some bacteria lacking MinD use orphan ParAs to regulate cell division. Positioning of MinD/ParA proteins is either due to self-organization on a surface or reliance on a landmark protein which functions as a molecular beacon.

Lutkenhaus, Joe



ParA-like protein uses nonspecific chromosomal DNA binding to partition protein complexes  

PubMed Central

Recent data have shown that plasmid partitioning Par-like systems are used by some bacterial cells to control localization of protein complexes. Here we demonstrate that one of these homologs, PpfA, uses nonspecific chromosome binding to separate cytoplasmic clusters of chemotaxis proteins upon division. Using fluorescent microscopy and point mutations, we show dynamic chromosome binding and Walker-type ATPase activity are essential for cluster segregation. The N-terminal domain of a cytoplasmic chemoreceptor encoded next to ppfA is also required for segregation, probably functioning as a ParB analog to control PpfA ATPase activity. An orphan ParA involved in segregating protein clusters therefore uses a similar mechanism to plasmid-segregating ParA/B systems and requires a partner protein for function. Given the large number of genomes that encode orphan ParAs, this may be a common mechanism regulating segregation of proteins and protein complexes.

Roberts, Mark A. J.; Wadhams, George H.; Hadfield, Katie A.; Tickner, Susan; Armitage, Judith P.



Patterns of axonal branching of neurons of the substantia nigra pars reticulata and pars lateralis in the rat.  


Axons from neurons of the rat substantia nigra pars reticulata (SNr) and pars lateralis (SNl) were traced after injecting their cell body with biotinylated dextran amine. Thirty-two single axons were reconstructed from serial sagittal sections with a camera lucida, whereas four other SNr axons were reconstructed in the coronal plane to determine whether they innervate the contralateral hemisphere. Four distinct types of SNr projection neurons were identified based on their main axonal targets: type I neurons that project to the thalamus; type II neurons that target the thalamus, the superior colliculus (SC), and the pedunculopontine tegmental nucleus (PPTg); type III neurons that project to the periaqueductal gray matter and the thalamus; and type IV neurons that target the deep mesencephalic nucleus (DpMe) and the SC. The axons of the SNl showed the same branching patterns as SNr axons of types I, II, and IV. The coronal reconstructions demonstrated that SNr neurons innervate the thalamus, the SC, and the DpMe bilaterally. At the thalamic level, SNr and SNl axons targeted preferentially the ventral medial, ventral lateral, paracentral, parafascicular, and mediodorsal nuclei. Axons reaching the SC arborized selectively within the deep layers of this structure. Our results reveal that the SNr and SNl harbor several subtypes of projection neurons endowed with a highly patterned set of axon collaterals. This organization allows single neurons of these output structures of the basal ganglia to exert a multifaceted influence on a wide variety of diencephalic and midbrain structures. PMID:16217789

Cebrián, Carolina; Parent, André; Prensa, Lucía



Pituitary expression of LHbeta- and FSHbeta-subunit mRNA, cellular distribution of LHbeta-subunit mRNA and LH and FSH synthesis during and after treatment with a gonadotrophin-releasing hormone agonist in heifers.  


The aim was to examine transcriptional and post-transcriptional regulation of LH and FSH biosynthesis. Female cattle were allocated to three groups: (i) Group 1, control (n = 6), synchronized to be at around Day 11 of the oestrous cycle on Day 31; (ii) Group 2 (n = 6), treated with gonadotrophin-releasing hormone (GnRH) agonist (deslorelin) for 31 days; and (iii) Group 3 (n = 6), treated with deslorelin for 28 days. All animals were slaughtered on Day 31. For animals in Group 2, pituitary content of LHbeta-subunit mRNA was suppressed 60% (P < 0.001) and LH 95% (P < 0.001), whereas FSHbeta-subunit mRNA was suppressed 25% (P > 0.05) and FSH 90% (P < 0.001). Three days after treatment with deslorelin (Group 3) LHbeta-subunit mRNA and LH remained suppressed (50% and 95%, respectively; P < 0.001). At the same time, FSHbeta-subunit mRNA did not differ from controls (P > 0.05) whereas FSH remained reduced by 80% (P < 0.001). The ratio of LHbeta-subunit mRNA present in the nucleus versus cytoplasm of gonadotroph cells was reduced (P < 0.05) in heifers during treatment with deslorelin (0.59 +/- 0.05) compared with the ratio in control heifers (1.31 +/- 0.22) and heifers 3 days after discontinuation of treatment (1.01 +/- 0.05). The findings indicated that treatment with GnRH agonist can suppress LHbeta-subunit mRNA expression without any significant effect on FSHbeta-subunit mRNA. As LH and FSH contents were suppressed to a greater degree than their beta-subunit mRNAs, it would appear that treatment with a GnRH agonist might influence gonadotrophin biosynthesis by a post-transcriptional mechanism(s). For LHbeta-subunit mRNA, this would appear not to be reduced export of message from the nucleus. PMID:12921701

Aspden, W J; Jackson, A; Trigg, T E; D'Occhio, M J



Protease-activated receptors (PAR)-1 and -3 drive epithelial-mesenchymal transition of alveolar epithelial cells - potential role in lung fibrosis.  


Extravascular activation of the coagulation cascade in the lung is commonly observed in pulmonary fibrosis. Coagulation proteases may exert profibrotic cellular effects via protease-activated receptors (PARs)-1 and -2. Here, we investigated the potential role of two other members of the PAR family, namely PAR-3 and PAR-4, in the pathobiology of lung fibrosis. Elevated expression of PAR-3, but not PAR-4, was detected in the lungs of idiopathic pulmonary fibrosis (IPF) patients and in bleomycin-induced lung fibrosis in mice. Increased PAR-3 expression in fibrotic lungs was mainly attributable to alveolar type II (ATII) cells. Stimulation of primary mouse ATII, MLE15 and A549 cells with thrombin (FIIa) - that may activate PAR-1, PAR-3 and PAR-4 - induced epithelial-mesenchymal transition (EMT), a process that has been suggested to be a possible mechanism underlying the expanded (myo)fibroblast pool in lung fibrosis. EMT was evidenced by morphological alterations, expression changes of epithelial and mesenchymal phenotype markers, and functional changes. Single knockdown of FIIa receptors, PAR-1, PAR-3, or PAR-4, had no major impact on FIIa-induced EMT. Simultaneous depletion of PAR-1 and PAR-3, however, almost completely inhibited this process, whereas only a partial effect on FIIa-mediated EMT was observed when PAR-1 and PAR-4, or PAR-3 and PAR-4 were knocked down. PAR-1 and PAR-3 co-localise within ATII cells with both being predominantely plasma membrane associated. In conclusion, our study indicates that PARs synergise to mediate FIIa-induced EMT and provides first evidence that PAR-3 via its ability to potentiate FIIa-triggered EMT could potentially contribute to the pathogenesis of pulmonary fibrosis. PMID:23739922

Wygrecka, Malgorzata; Didiasova, Miroslava; Berscheid, Sebastian; Piskulak, Katarzyna; Taborski, Brigitte; Zakrzewicz, Dariusz; Kwapiszewska, Grazyna; Preissner, Klaus T; Markart, Philipp



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.



Over-expression of PAR3 suppresses contact-mediated inhibition of cell migration in MDCK cells  

Microsoft Academic Search

Background: PAR-3 is one of the PAR proteins, previously named ASIP, which are indispensable for the establishment of cell polarity in the embryo as well as differentiated epithelial cells. In mammalian epithelial cells, it forms a ternary complex with aPKC and PAR-6, and is localized to the tight junction that has been suggested as being important for creating cell polarity.

Aki Mishima; Atsushi Suzuki; Makiko Enaka; Tomonori Hirose; Keiko Mizuno; Tetsuo Ohnishi; Hiroshi Mohri; Yoshiaki Ishigatsubo; Shigeo Ohno



Gene expression of ACTH, glucocorticoid receptors, 11?HSD enzymes, LH-, FSH-, GH receptors and aromatase in equine epididymal and testicular tissue.  


Glucocorticoids (GCs) are important mediators of the stress response and have been implicated in the function and regulation of testicular functions in different species. In many tissues, intracellular glucocorticoid activity is controlled by either or both of the two known isoforms of 11?-hydroxysteroid dehydrogenase (11?HSD) type 1 and 2, which interconvert active and inactive GCs. Little is known about the effects of stress on fertility in the equine species. The main objective of the present study was to investigate the expression of receptors for GCs and adrenocorticotropic hormone [ACTH, melanocortin 2 receptor (MC2R)] as well 11?HSD1 and 11?HSD2 in male equine epididymal and testicular tissue. In addition, expression of aromatase P-450 and receptors for luteinizing hormone (LHR), follicle stimulating hormone (FSHR) and growth hormone (GHR) was studied. Reverse transcriptase PCR and quantitative real-time PCR were performed in tissue from the epididymis (caput and cauda) and testes collected from nine healthy mature stallions (age 4-10 years). mRNA for ACTH and GC receptors as well as 11?HSD1 and -2 were found in epididymal and testicular tissue. Expression of the genes studied was always positive in testicular tissue, while it was inconsistent in epididymal tissue. Quantitative gene expression in relation to ?-actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was significantly correlated (R = 0.403, p < 0.001). Quantitative PCR in relation to ?-actin revealed significant differences in the gene expression of 11?HSD1, 11?HSD2, LHR, FSHR, MC2R and aromatase between tissue collected from caput epididymidis, cauda epididymidis and testicular parenchyma (p < 0.05). With GAPDH, differences between tissues were significant for 11?HSD1, 11?HSD2 and MC2R (p < 0.05) In addition, high concentrations of mRNA of aromatase and receptors of LH and FSH were found in testicular tissue, while a pronounced expression of GH receptor was present in epididymal tissue. The results support the hypothesis of an interaction between the pituitary-adrenal axis and testicular function in the stallion. PMID:22335522

Herrera-Luna, C V; Budik, S; Aurich, C



Estimation of aerosol direct radiative effects on surface PAR radiation at Xianghe, Northern China  

NASA Astrophysics Data System (ADS)

In northern China, anthropogenic activities cause emissions of large amount of aerosol particles to the atmosphere. Such particles could alter the radiation balance directly by scattering and absorbing incident solar radiation, thus decrease the amount of light reaching the surface and increase the fraction of diffuse radiation. By using the aerosol data obtained from both the Aerosol Robotic Network (AERONET) and Moderate Resolution Imaging Spectroradiometer (MODIS), aerosol effects on surface photosynthetically active radiation (PAR) are explored in this study. PAR is quantitatively estimated using the NCAR Tropospheric Ultraviolet-Visible (TUV) radiation transfer model, with the influence of clouds taken into account through sunshine-duration data and the diffuse PAR calculated with diffuse radiation empirical models. This method is examined against the observations of PAR under all-sky conditions at Xianghe, northern China, and a significant linear correlation between the measured and estimated PAR is obtained with R of 0.96 and relative error of 8.47%. Aerosol effects on PAR are thus evaluated with this method. Compared with the background aerosol loading (defined as aerosol optical depth = 0.05), the monthly average PAR under present aerosol level for May, June, July and August decreases 20.65, 26.17, 17.38 and 17.84 W/m2 respectively, while the diffuse PAR for the four months increases 14.03, 21.39, 7.29, and 5.44 W/m2 respectively. The mean ratios of global and diffuse PAR under present aerosol level to that under background aerosol loading for this period are 82.9% and 130% respectively. It is found that the diffuse PAR is determined predominantly by clouds and to a lesser extent by aerosol loading. For days with high cloud transmittance, aerosols could significantly increase the diffuse PAR. In contrast, clouds with very low transmittance causes high ratio of diffuse to global PAR, and aerosols could even decrease both global and diffuse PAR. The effects of such changes induced by aerosols on plant productivity would be further studied.

Shao, Siya; Zhang, Jing



Magnétomètre à ^3He pompé par diode laser  

NASA Astrophysics Data System (ADS)

We describe the realization of a ^3He magnetometer based on the free precession of nuclear spins oriented by optical pumping with a laser. The use of a laser diode, directly tuned to 1.083 ?m, and the increase of the ^3He nuclear orientation relaxation time with cesium coated cells, allow us to elaborate a new original magnetometer, which operates sequentially and opens several possibilities of use. Nous décrivons une réalisation d'un magnétomètre à ^3He mettant en oeuvre la précession libre des spins nucléaires orientés par pompage optique laser. L'utilisation d'une diode laser directement accordée à 1,083 ?m ainsi que l'allongement du temps de relaxation de l'orientation nucléaire de ^3He à l'aide d'une cellule avec enduit de césium nous a permis de réaliser un nouveau magnétomètre à fonctionnement séquentiel original et aux possiblités d'utilisation multiples.

Moreau, O.; Chéron, B.; Gilles, H.; Hamel, J.; Noël, E.



Par-4 for molecular therapy of prostate cancer.  


Prostate cancer is the most frequently diagnosed malignancy and the second leading cause of cancer deaths in American men. Although many treatment measures such as androgen deprivation, radiation therapy, and cryoablation exist for primary prostate cancer, there is currently no effective treatment for patients presenting advanced or metastatic stages of the disease. Molecular therapy offers an attractive approach to the treatment of primary prostate cancer because the prostate is not a life-sustaining organ, and a number of tissue specific promoters can be used for prostatic gene expression following relatively straightforward delivery routes. This review discusses the general molecular therapy applications in the context of prostate cancer, and most importantly, identifies the prostate apoptosis response-4 (Par-4) gene, which exclusively induces apoptosis in cancer cells and not normal cells, as a prospective molecule for therapy of the disease. PMID:12643472

Butler, James; Rangnekar, Vivek M



Mécanismes d'éjection de particules par laser impulsionnel  

NASA Astrophysics Data System (ADS)

L'enlèvement de particules de dimensions nanométriques est l'un des principaux challenges à relever pour atteindre les futurs objectifs de l'industrie microélectronique. Les procédés laser présentent, dans certains cas, des performances très intéressantes, mais les mécanismes d'éjection des particules polluant la surface restent cependant fort mal connus. L'étude de la dynamique d'éjection des particules, par une technique optique, a mis en évidence l'existence de deux mécanismes dont l'importance relative dépend de la fluence d'irradiation. A forte fluence l'ablation locale du substrat sous la particule prédomine, alors que pour les fluences plus faibles le mécanisme semble être lié à l'enlèvement de l'humidité résiduelle à l'interface particule substrat. Contrairement aux modèles précédemment proposés, la contribution de la force d'inertie s'exerçant sur la particule lors de l'expansion thermique rapide des matériaux est négligeable.

Grojo, D.; Cros, A.; Delaporte, Ph.; Sentis, M.; Dubus, H.; Mionetto, R.



La structure des verres étudiée par diffraction des neutrons  

NASA Astrophysics Data System (ADS)

La diffraction des neutrons est une méthode largement utilisée pour déterminer la structure des matériaux amorphes et en particulier des verres. L'utilisation de la méthode de substitution isotopique permet d'extraire les fonctions de distribution de paires partielles centrées autour d'un élément choisi. Nous présentons quelques exemples récents d'études par diffraction des neutrons sur des verres qui ont permis de mieux comprendre à la fois le réseau polymérique de la matrice vitreuse et l'environnement local et à moyenne distance autour des cations. Ces études ont révélées un ordre structural s'étendant au delà des premiers voisins, jusque vers de distances d'environ 10Å. Le couplage avec d'autres méthodes expérimentales (diffraction anormale des rayons X) et des techniques de simulations (dynamique moléculaire, Monte Carlo Inverse ou RMC) sont indispensables pour affiner nos connaissances de la structure des verres.

Cormier, L.



Binding and phosphorylation of par-4 by akt is essential for cancer cell survival.  


Activation of the PI3K-Akt pathway by loss of tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) function, increased growth factor signaling, or oncogene expression renders cancer cells resistant to apoptotic signals and promotes tumor growth. Although Akt acts as a global survival signal, the molecular circuits of this pathway have not been completely established. We report that Akt physically binds to the pro-apoptotic protein Par-4 via the Par-4 leucine zipper domain and phosphorylates Par-4 to inhibit apoptosis. Suppression of Akt activation by the PI3K-inhibitor PTEN or LY294002, Akt expression by RNA-interference, or Akt function by dominant-negative Akt caused apoptosis in cancer cells. Apoptosis induced by inhibiting Akt was blocked by inhibition of Par-4 expression, but not by inhibition of other apoptosis agonists that are Akt substrates, suggesting that inhibition of the PI3K-Akt pathway leads to Par-4-dependent apoptosis. Thus, Par-4 is essential for PTEN-inducible apoptosis, and inactivation of Par-4 by Akt promotes cancer cell survival. PMID:16209943

Goswami, Anindya; Burikhanov, Ravshan; de Thonel, Aurelie; Fujita, Naoya; Goswami, Mamta; Zhao, Yanming; Eriksson, John E; Tsuruo, Takashi; Rangnekar, Vivek M



Cathepsin S Signals via PAR2 and Generates a Novel Tethered Ligand Receptor Agonist  

PubMed Central

Protease-activated receptor-2 is widely expressed in mammalian epithelial, immune and neural tissues. Cleavage of PAR2 by serine proteases leads to self-activation of the receptor by the tethered ligand SLIGRL. The contribution of other classes of proteases to PAR activation has not been studied in detail. Cathepsin S is a widely expressed cysteine protease that is upregulated in inflammatory conditions. It has been suggested that cathepsin S activates PAR2. However, cathepsin S activation of PAR2 has not been demonstrated directly nor has the potential mechanism of activation been identified. We show that cathepsin S cleaves near the N-terminus of PAR2 to expose a novel tethered ligand, KVDGTS. The hexapeptide KVDGTS generates downstream signaling events specific to PAR2 but is weaker than SLIGRL. Mutation of the cathepsin S cleavage site prevents receptor activation by the protease while KVDGTS retains activity. In conclusion, the range of actions previously ascribed to cysteine cathepsins in general, and cathepsin S in particular, should be expanded to include molecular signaling. Such signaling may link together observations that had been attributed previously to PAR2 or cathepsin S individually. These interactions may contribute to inflammation.

Lerner, Ethan A.



Dual role of host par2 in a murine model of spontaneous metastatic b16 melanoma.  


Aim: We investigated differences of metastatic spread of normal proteinase-activated receptor-2 (Par2(+/+)) melanoma B16 in Par2(-/-) (knock-out) animals compared to C57Bl6 mice. Materials and Methods: Nine knock-out mice B6.Cg-F2rl1tm1Mslb/J (Par2(-/-)) and nine C57Bl6/J controls were subcutaneously inoculated with B16 melanoma tissue cells. Twelve days after inoculation, all primary tumors were removed. Survival and metastatic spread was followed for up to 100 days after primary tumor extirpation. Results: Excised primary tumors were on average larger in Par2(-/-) mice (360 mm(3) vs. 221 mm(3) in C57Bl6/J). Distant spontaneous metastases developed in only 3 of 9 of Par2(-/-) mice in comparison to 6 of 9 controls. The average survival time was 84 days in Par2(-/-) animals compared to 63 days in C57Bl6/J mice. Conclusion: Host Par2 melanoma model contributes to the limitation of local cancer progression in one area, while on the other hand is important for enhancing distant metastatic spread. PMID:24982362

Olejar, Tomas; Vetvicka, David; Zadinova, Marie; Pouckova, Pavla; Kukal, Jaromir; Jezek, Petr; Matej, Radoslav



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:

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



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)



The proteinase activated receptor-2 (PAR-2) mediates mitogenic responses in human vascular endothelial cells.  

PubMed Central

Proteolytically cleaved receptors, typified by the functional thrombin receptor (TR), represent a novel class of receptors that mediate signaling events by functional coupling to G proteins. Northern blot analysis completed with a human proteinase activated receptor-2 (PAR-2) cDNA as probe demonstrated the approximately 3.5kb PAR-2 transcript in total cellular RNA from human umbilical vein endothelial cells (HUVEC). Microspectrofluorimetry using Fura2-loaded HUVEC demonstrated a dose-dependent elevation in intracellular calcium transients ([Ca2+]i) to murine PAR39-44 (SLIGRL, putative neoligand after cleavage), with an approximate EC50 of 30 microM, and evidence for homologous desensitization with complete recovery at 45 min. Xenopus oocytes microinjected with TR cRNA failed to respond to 200 microM PAR39-44, and TR-targeted antisense oligonucleotides specifically abrogated thrombin-induced but not PAR39-44-mediated [Ca2+]i, excluding the possibility that TR/PAR-2 cell-surface coexpression was structurally linked. HUVEC incubated with PAR39-44 demonstrated a dose- and time-dependent mitogenic response similar to that seen with thrombin or TR42-47 (TR-activating peptide, SFLLRN). Preactivation of HUVEC with either PAR39-44 or thrombin resulted in heterologous desensitization to the corresponding agonist, an effect that was mediated primarily by TR internalization as evaluated by immunofluorescence and quantitative ELISA. These results ascribe a previously unrecognized function to the PAR-2 receptor, imply that a natural enzyme agonist may circulate in plasma, and suggest the presence of an additional regulatory mechanism controlling receptor activation events in vascular endothelial cells.

Mirza, H; Yatsula, V; Bahou, W F



Generating and forecasting monthly flows of the Ganges river with PAR model  

NASA Astrophysics Data System (ADS)

Contemporary building techniques and underlying theories of periodic autoregressive (PAR) models are revisited, reviewed, modified and recast. New techniques for generating synthetic data from any PAR model with provision to constrain some parameter values to zero have been proposed. The developed method is applied to the Ganges river for its monthly flow forecasting and generation. The results demonstrate that the PAR model can capture the seasonal variability of the Ganges river flow reasonably well preserving both its short- and the long-term important historical statistics.

Mondal, M. Shahjahan; Wasimi, Saleh A.



Radiological findings and healing patterns of incomplete stress fractures of the pars interarticularis  

Microsoft Academic Search

Objective  The objective was to retrospectively record the CT and MRI features and healing patterns of acute, incomplete stress fractures\\u000a of the pars interarticularis.\\u000a \\u000a \\u000a \\u000a Method  The CT scans of 156 adolescents referred with suspected pars interarticularis stress fractures were reviewed. Patients with\\u000a incomplete (grade 2) pars fractures were included in the study. Fractures were assessed on CT according to vertebral level,\\u000a location

Andrew J. Dunn; Robert S. D. Campbell; Peter E. Mayor; Dai Rees



Dynamic interplay of ParA with the polarity protein, Scy, coordinates the growth with chromosome segregation in Streptomyces coelicolor.  


Prior to bacterial cell division, the ATP-dependent polymerization of the cytoskeletal protein, ParA, positions the newly replicated origin-proximal region of the chromosome by interacting with ParB complexes assembled on parS sites located close to the origin. During the formation of unigenomic spores from multi-genomic aerial hyphae compartments of Streptomyces coelicolor, ParA is developmentally triggered to form filaments along the hyphae; this promotes the accurate and synchronized segregation of tens of chromosomes into prespore compartments. Here, we show that in addition to being a segregation protein, ParA also interacts with the polarity protein, Scy, which is a component of the tip-organizing centre that controls tip growth. Scy recruits ParA to the hyphal tips and regulates ParA polymerization. These results are supported by the phenotype of a strain with a mutant form of ParA that uncouples ParA polymerization from Scy. We suggest that the ParA-Scy interaction coordinates the transition from hyphal elongation to sporulation. PMID:23536551

Ditkowski, Bartosz; Holmes, Neil; Rydzak, Joanna; Donczew, Magdalena; Bezulska, Martyna; Ginda, Katarzyna; Kedzierski, Pawel; Zakrzewska-Czerwi?ska, Jolanta; Kelemen, Gabriella H; Jakimowicz, Dagmara



Regulation of the proapoptotic functions of prostate apoptosis response-4 (Par-4) by casein kinase 2 in prostate cancer cells.  


The proapoptotic protein, prostate apoptosis response-4 (Par-4), acts as a tumor suppressor in prostate cancer cells. The serine/threonine kinase casein kinase 2 (CK2) has a well-reported role in prostate cancer resistance to apoptotic agents or anticancer drugs. However, the mechanistic understanding on how CK2 supports survival is far from complete. In this work, we demonstrate both in rat and humans that (i) Par-4 is a new substrate of the survival kinase CK2 and (ii) phosphorylation by CK2 impairs Par-4 proapoptotic functions. We also unravel different levels of CK2-dependent regulation of Par-4 between species. In rats, the phosphorylation by CK2 at the major site, S124, prevents caspase-mediated Par-4 cleavage (D123) and consequently impairs the proapoptotic function of Par-4. In humans, CK2 strongly impairs the apoptotic properties of Par-4, independently of the caspase-mediated cleavage of Par-4 (D131), by triggering the phosphorylation at residue S231. Furthermore, we show that human Par-4 residue S231 is highly phosphorylated in prostate cancer cells as compared with their normal counterparts. Finally, the sensitivity of prostate cancer cells to apoptosis by CK2 knockdown is significantly reversed by parallel knockdown of Par-4. Thus, Par-4 seems a critical target of CK2 that could be exploited for the development of new anticancer drugs. PMID:24457960

de Thonel, A; Hazoumé, A; Kochin, V; Isoniemi, K; Jego, G; Fourmaux, E; Hammann, A; Mjahed, H; Filhol, O; Micheau, O; Rocchi, P; Mezger, V; Eriksson, J E; Rangnekar, V M; Garrido, C



Regulation of the proapoptotic functions of prostate apoptosis response-4 (Par-4) by casein kinase 2 in prostate cancer cells  

PubMed Central

The proapoptotic protein, prostate apoptosis response-4 (Par-4), acts as a tumor suppressor in prostate cancer cells. The serine/threonine kinase casein kinase 2 (CK2) has a well-reported role in prostate cancer resistance to apoptotic agents or anticancer drugs. However, the mechanistic understanding on how CK2 supports survival is far from complete. In this work, we demonstrate both in rat and humans that (i) Par-4 is a new substrate of the survival kinase CK2 and (ii) phosphorylation by CK2 impairs Par-4 proapoptotic functions. We also unravel different levels of CK2-dependent regulation of Par-4 between species. In rats, the phosphorylation by CK2 at the major site, S124, prevents caspase-mediated Par-4 cleavage (D123) and consequently impairs the proapoptotic function of Par-4. In humans, CK2 strongly impairs the apoptotic properties of Par-4, independently of the caspase-mediated cleavage of Par-4 (D131), by triggering the phosphorylation at residue S231. Furthermore, we show that human Par-4 residue S231 is highly phosphorylated in prostate cancer cells as compared with their normal counterparts. Finally, the sensitivity of prostate cancer cells to apoptosis by CK2 knockdown is significantly reversed by parallel knockdown of Par-4. Thus, Par-4 seems a critical target of CK2 that could be exploited for the development of new anticancer drugs.

de Thonel, A; Hazoume, A; Kochin, V; Isoniemi, K; Jego, G; Fourmaux, E; Hammann, A; Mjahed, H; Filhol, O; Micheau, O; Rocchi, P; Mezger, V; Eriksson, J E; Rangnekar, V M; Garrido, C



Dynamic interplay of ParA with the polarity protein, Scy, coordinates the growth with chromosome segregation in Streptomyces coelicolor  

PubMed Central

Prior to bacterial cell division, the ATP-dependent polymerization of the cytoskeletal protein, ParA, positions the newly replicated origin-proximal region of the chromosome by interacting with ParB complexes assembled on parS sites located close to the origin. During the formation of unigenomic spores from multi-genomic aerial hyphae compartments of Streptomyces coelicolor, ParA is developmentally triggered to form filaments along the hyphae; this promotes the accurate and synchronized segregation of tens of chromosomes into prespore compartments. Here, we show that in addition to being a segregation protein, ParA also interacts with the polarity protein, Scy, which is a component of the tip-organizing centre that controls tip growth. Scy recruits ParA to the hyphal tips and regulates ParA polymerization. These results are supported by the phenotype of a strain with a mutant form of ParA that uncouples ParA polymerization from Scy. We suggest that the ParA–Scy interaction coordinates the transition from hyphal elongation to sporulation.

Ditkowski, Bartosz; Holmes, Neil; Rydzak, Joanna; Donczew, Magdalena; Bezulska, Martyna; Ginda, Katarzyna; Kedzierski, Pawel; Zakrzewska-Czerwinska, Jolanta; Kelemen, Gabriella H.; Jakimowicz, Dagmara



Par-complex aPKC and Par3 cross-talk with innate immunity NF-?B pathway in epithelial cells  

PubMed Central

Summary Components of the Par-complex, atypical PKC and Par3, have been found to be downregulated upon activation of NF-?B in intestinal epithelial cells. To determine their possible role in pro-inflammatory responses we transduced Caco-2 human colon carcinoma cells with constitutively active (ca) PKC? or anti-Par3 shRNA-expressing lentiviral particles. Contrary to previous reports in other cell types, ca-PKC? did not activate, but rather decreased, baseline NF-?B activity in a luminiscence reporter assay. An identical observation applied to a PB1 domain deletion PKC?, which fails to localize to the tight-junction. Conversely, as expected, the same ca-PKC? activated NF-?B in non-polarized HEK293 cells. Likewise, knockdown of Par3 increased NF-?B activity and, surprisingly, greatly enhanced its response to TNF?, as shown by transcription of IL-8, GRO-1, GRO-2 and GRO-3. We conclude that aPKC and Par3 are inhibitors of the canonical NF-?B activation pathway, although perhaps acting through independent pathways, and may be involved in pro-inflammatory responses.

Forteza, Radia; Wald, Flavia A.; Mashukova, Anastasia; Kozhekbaeva, Zhanna; Salas, Pedro J.



Seismic analysis of the Par Pond Dam: Study of slope failure and liquefaction. Technical evaluation report.  

National Technical Information Service (NTIS)

Stability concerns of the Par Pond Dam, an embankment structure in the Savannah River Site complex, resulted in a comprehensive evaluation of the state of its integrity. Specifically, excessive seepage through the embankment, slope failure due to an earth...

N. Simos M. Reich



Negative regulation of Par-4 by oncogenic Ras is essential for cellular transformation.  


Oncogenic variants of the cellular Ras protein are often associated with different types of human cancers. However, the mechanisms by which oncogenic Ras induces transformation are not fully established. Expression of the transcriptional repressor Par-4 was down-regulated by oncogenic Ras via the Raf-MEK-ERK pathway. Restoration of Par-4 levels by abrogation of the Raf-MEK-ERK pathway with the MEK-inhibitor PD98059 or by ectopic Par-4, that acted to inhibit ERK expression and activation, was sufficient to suppress oncogenic Ras-induced transformation. These findings identify Par-4 as a novel target that has to be down-modulated by oncogenic Ras for successful transformation. PMID:10597313

Qiu, S G; Krishnan, S; el-Guendy, N; Rangnekar, V M



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

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



Latitudinal UVR-PAR measurements in Argentina: extent of the ‘ozone hole’  

Microsoft Academic Search

The UVR-PAR Argentinean Monitoring Network started its operation in September 1994 recording ultraviolet (UVR) and Photosynthetic Available Radiation (PAR) at a frequency of once per minute, at four sites, throughout the entire year. Four spectroradiometers (GUV-511, Biospherical Instruments, Inc.) were installed at research centers separated by about 8–12 degrees of latitude, extending from the Subantarctic-Fueguian region to the Tropic of

V. Luis Orce; E. Walter Helbling



Relation between the Secretory Cells of the Pars Nervosa of the Hypophysis and Classical Neuroglia  

Microsoft Academic Search

GERSH1 has shown that the glial cells of the pars nervosa-the pituicytes of Bucy2-are responsible for the secretion of the anti-diuretic principle of the posterior lobe. I have presented additional evidence3 which demonstrates that these cells elaborate the pars nervosa hormones. By the use of silver carbonate methods for neuroglia, developed by the Spanish school, Bucy showed that the pituicytes,

Mervyn Griffiths



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



Identification of exosite residues of factor Xa involved in recognition of PAR-2 on endothelial cells  

PubMed Central

Recent results have indicated that factor Xa (FXa) cleaves protease-activated receptor 2 (PAR-2) to elicit protective intracellular signaling responses in endothelial cells. In this study, we investigated the molecular determinants of the specificity of FXa interaction with PAR-2 by monitoring the cleavage of PAR-2 by FXa in endothelial cells transiently transfected with a PAR-2 cleavage reporter construct in which the extracellular domain of the receptor was fused to cDNA encoding for alkaline phosphatase. Comparison of the cleavage efficiency of PAR-2 by a series of FXa mutants containing mutations in different surface loops indicated that the acidic residues of 39-loop (Glu-36, Glu-37 and Glu-39) and the basic residues of 60-loop (Lys-62 and Arg-63), 148-loop (Arg-143, Arg-150 and Arg-154) and 162-helix (Arg-165 and Lys-169) contribute to the specificity of receptor recognition by FXa on endothelial cells. This was evidenced by significantly reduced activity of mutants toward PAR-2 expressed on transfected cells. The extent of loss in the PAR-2 cleavage activity of FXa mutants correlated with the extent of loss in their PAR-2-dependent intracellular signaling activity. Further characterization of FXa mutants indicated that, with the exception of basic residues of 162-helix, which play a role in the recognition specificity of the prothrombinase complex, none of the surface loop residues under study makes a significant contribution to the activity of FXa in the prothrombinase complex. These results provide new insight into mechanisms through which FXa specifically interacts with its macromolecular substrates in the clotting and signaling pathways.

Manithody, Chandrashekhara; Yang, Likui; Rezaie, Alireza R.



ParsCit: an Open-source CRF Reference String Parsing Package  

Microsoft Academic Search

We describe ParsCit, a freely available, open-source implementation of a reference string parsing package. At the core of ParsCit is a trained conditional random field (CRF) model used to label th e token sequences in the reference string. A heuristic model wraps this core with added functionality to identify reference string s from a plain text file, and to retrieve

Isaac G. Councill; C. Lee Giles; Min-Yen Kan



Nd:YAG vitreolysis and pars plana vitrectomy: surgical treatment for vitreous floaters  

Microsoft Academic Search

Purpose of study To determine the efficacy of Nd:YAG vitreolysis and pars plana vitrectomy in the treatment of vitreous floaters.Methods This is a single centre retrospective study of 31 patients (42 eyes) who underwent 54 procedures, Nd:YAG vitreolysis or pars plana vitrectomy, for the treatment of vitreous floaters between January 1992 and December 2000. Main outcome measures were percentage symptomatic

Y M Delaney; A Oyinloye; L Benjamin



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


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