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Sample records for 6-keto prostaglandin f1

  1. Production of prostaglandins by the pseudopregnant rat uterus, in vitro, and the effect of tamoxifen with the identification of 6-keto-prostaglandin F1alpha as a major product.

    PubMed Central

    Fenwick, L; Jones, R L; Naylor, B; Poyser, N L; Wilson, N H

    1977-01-01

    1 Prostaglandin production by rat uterus homogenates has been studied, in vitro, on days 2 to 13 of pseudopregnancy. 2 The highest production of prostaglandins occurred on day 5. 3 The amounts of prostaglandins F and D formed were higher than the amounts of prostaglandin E on every day studied. 4 The ratios of prostglandins F and D to prostaglandin E produced steadily decreased up to day 6. It then increased with the highest values occurring between days 10 and 13, 5 Progesterone levels in peripheral plasma increased rapidly from days 2 to 5, remained high up to day 9, then steadily decreased between days 10 and 13. 6 The anti-oestrogenic drug, tamoxifen administered on day 2, significantly inhibited the increase of prostaglandin production which occurred on day 5. Prostaglandin E production was inhibited more than the production of prostaglandins F and D. 7 Analysis of the uterine extracts by gas chromatography and mass spectrometry showed prostaglandin F2alpha, F1alpha (in trace amounts), E2 and D2 to be present. 8 The major product detected was 6-keto-prostaglandin F1alpha. Its identification forms an addendum to the paper. 9 Also present as a major product was 6(9)-oxy-11,15-dihydroxyprosta-7,13-dienoic acid. PMID:836998

  2. Concentrations of prostaglandins E2, F2 alpha and 6-keto-prostaglandin F1 alpha in the utero-ovarian venous plasma of nonpregnant and early pregnant ewes.

    PubMed

    Silvia, W J; Ottobre, J S; Inskeep, E K

    1984-05-01

    The effect of pregnancy on concentrations of prostaglandins E2, F2 alpha and 6-keto-prostaglandin F1 alpha (PGE2, PGF2 alpha and 6-keto-PGF1 alpha) in utero-ovarian venous plasma was examined in ewes on Days 10 through 14 after estrus, an interval which includes the critical period for maternal recognition of pregnancy. The utero-ovarian vein ipsilateral to a corpus luteum was catheterized on Day 9 or 10 in 6 pregnant and 8 nonpregnant ewes. Five blood samples were collected at 30-min intervals for 2 h beginning at 0500 and 1700 h daily. Sampling began at 0500 h on the day after catheterization. The mean and variance within each 2-h collection period were calculated for each ewe. The natural logarithm of the variance in each collection period (ln variance) was used as an estimate of the fluctuations in secretory activity by the endometrial-conceptus complex. Patterns of the mean concentrations of PGE2 were different between pregnant and nonpregnant ewes (P less than 0.01); PGE2 being higher in the pregnant ewes beginning on Day 13. There was a trend for the patterns of ln variance in PGE2 to differ (P less than 0.1) with pregnancy status over the entire period; ln variance was greater in pregnant ewes beginning on Day 13. The patterns of the mean concentrations and ln variances for PGF2 alpha and 6-keto-PGF1 alpha did not differ between pregnant and nonpregnant ewes. There were significant increases in both of these prostaglandins over time, independent of pregnancy status (P less than 0.01). The association of higher concentrations of PGE2 in utero-ovarian venous plasma with early pregnancy is consistent with the hypothesis that PGE2, originating from the uterus and/or conceptus, is one factor involved in maintenance of the corpus luteum of pregnancy.

  3. Major urinary metabolites of 6-keto-prostaglandin F2α in mice.

    PubMed

    Kuklev, Dmitry V; Hankin, Joseph A; Uhlson, Charis L; Hong, Yu H; Murphy, Robert C; Smith, William L

    2013-07-01

    Western diets are enriched in omega-6 vs. omega-3 fatty acids, and a shift in this balance toward omega-3 fatty acids may have health benefits. There is limited information about the catabolism of 3-series prostaglandins (PG) formed from eicosapentaenoic acid (EPA), a fish oil omega-3 fatty acid that becomes elevated in tissues following fish oil consumption. Quantification of appropriate urinary 3-series PG metabolites could be used for noninvasive measurement of omega-3 fatty acid tone. Here we describe the preparation of tritium- and deuterium-labeled 6-keto-PGF2α and their use in identifying urinary metabolites in mice using LC-MS/MS. The major 6-keto-PGF2α urinary metabolites included dinor-6-keto-PGF2α (~10%) and dinor-13,14-dihydro-6,15-diketo-PGF1α (~10%). These metabolites can arise only from the enzymatic conversion of EPA to the 3-series PGH endoperoxide by cyclooxygenases, then PGI3 by prostacyclin synthase and, finally, nonenzymatic hydrolysis to 6-keto-PGF2α. The 6-keto-PGF derivatives are not formed by free radical mechanisms that generate isoprostanes, and thus, these metabolites provide an unbiased marker for utilization of EPA by cyclooxygenases.

  4. Stimulation of the synthesis of 15-hydroxyeicosatetraenoic acid (15-HETE) and 6-keto-prostaglandin F/sub 1. cap alpha. / (6-keto-PGF/sub 1. cap alpha. /) by cultured human umbilical veins

    SciTech Connect

    Ibe, B.O.; Johnson, A.R.; Falck, J.R.; Campbell, W.B.

    1986-03-05

    These studies were designed to investigate the synthesis of 6-keto-PGF/sub 1..cap alpha../ and 15-HETE in cultured human endothelial cells. The identification of the 15-HETE in these cells was made by UV absorption and gas chromatography/mass spectrometry. Specific radioimmunoassays were developed to quantify the synthesized 6-keto-PGF/sub 1..cap alpha../ and 15-HETE. The release of 15-HETE and 6-keto-PGF/sub 1..cap alpha../ was stimulated by arachidonic acid, histamine or the calcium ionophore A23187. The release of 15-HETE paralleled the release of 6-keto-PGF/sub 1..cap alpha../ and was both concentration-related and time-dependent. Aspirin, ibuprofen and indomethacin inhibited both the formation of 6-keto-PGF/sub 1..cap alpha../ and 15-HETE in similar concentrations. These data indicate that agents which stimulate PGI/sub 2/ synthesis also stimulate the synthesis of 15-HETE. Also, they implicate the cyclooxygenase pathway in the synthesis of 6-keto PGF/sub 1..cap alpha../ and 15-HETE in human endothelial cells.

  5. Increased concentrations of arachidonic acid, prostaglandins E2, D2, and 6-oxo-F1 alpha, and histamine in human skin following UVA irradiation

    SciTech Connect

    Hawk, J.L.; Black, A.K.; Jaenicke, K.F.; Barr, R.M.; Soter, N.A.; Mallett, A.I.; Gilchrest, B.A.; Hensby, C.N.; Parrish, J.A.; Greaves, M.W.

    1983-06-01

    The buttock skin of clinically normal human subjects was subjected to approximately 2.5 minimal erythema doses of ultraviolet A irradiation. Deep red erythema developed during irradiation, faded slightly within the next few hours, increased to maximum intensity between 9-15 h, and decreased gradually thereafter although still persisting strongly at 48 h. Suction blister exudates were obtained at 0, 5, 9, 15, 24, and 48 h after irradiation as well as suction blister exudates from a contralateral control site and assayed for arachidonic acid, prostaglandins D2 and E2, and the prostacyclin breakdown product 6-oxo-prostaglandin F1 alpha by gas chromatography-mass spectrometry, and for histamine by radioenzyme assay. Increased concentrations of arachidonic acid and prostaglandins D2, E2, and 6-oxo-prostaglandin F1 alpha were found maximally between 5-9 h after irradiation, preceding the phase of maximal erythema. Elevations of histamine concentration occurred 9-15 h after irradiation, preceding and coinciding with the phase of maximal erythema. At 24 h, still at the height of the erythemal response, all values had returned to near control levels. Hence increased concentrations of arachidonic acid and its products from the cyclooxygenase pathway, and of histamine, accompany the early stages up to 24 h. A causal role in production of the erythema seems likely for these substances although other mediators are almost certainly involved.

  6. Prostacyclin: its pathogenic role in essential hypertension and the class effect of ACE inhibitors on prostaglandin metabolism.

    PubMed

    Rodríguez-García, J L; Villa, E; Serrano, M; Gallardo, J; García-Robles, R

    1999-01-01

    Angiotensin-converting enzyme inhibitors (ACEI) block degradation of bradykinin, and bradykinin stimulates prostacyclin synthesis. Therefore, we set out to determine whether the effects of ACE inhibitors on prostaglandin production in essential hypertensive patients are class effects or are dependent on ACE inhibitor structure. In addition, we studied whether hypertensives show an impaired capacity to synthesize vasodilator prostaglandins. To address these questions, we compared the effects of captopril (sulfhydryl-containing inhibitor), enalapril and ramipril (carboxyl-containing inhibitors) and fosinopril (phosphoryl-containing inhibitor) on blood pressure and urinary excretion of 6-keto-prostaglandin (PG) F1-alpha (the breakdown product of prostacyclin) in 44 mild-to-moderate essential hypertensive subjects before and 8 weeks after administration of an ACEI. We also studied prostacyclin excretion in 15 normotensive healthy controls. Levels of urinary 6-keto-PGF1-alpha (pg/ml) were measured by specific radioimmunoassay. Hypertensive subjects showed a lower excretion of 6-keto-PGF1-alpha than normotensive controls (212+/-147 vs 353+/-98 pg/ml, p < 0.001). All ACEI induced a significant decrease in MAP and increased the rate of excretion of the prostacyclin metabolite: C, 211+/-200 to 338+/-250 pg/ml, p < 0.05; E, 202+/-133 to 296+/-207 pg/ml, p < 0.05; R, 205+/-127 to 342+/-211 pg/ml, p < 0.05; F, 235+/-128 to 347+/-241 pg/ml, p < 0.05. In hypertensives (n = 44) the decrease in blood pressure correlated negatively with the rise in 6-keto-PGF1-alpha excretion (r = -0.51, p < 0.001). These data suggest that impaired prostacyclin biosynthesis in hypertensive patients could account for haemodynamic changes leading to the hypertensive state. Moreover, the hypotensive mechanisms of ACEI may be mediated by an increase in prostacyclin production; this effect seems to be class-dependent.

  7. The 5-lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophages

    PubMed Central

    Rossi, A; Pergola, C; Koeberle, A; Hoffmann, M; Dehm, F; Bramanti, P; Cuzzocrea, S; Werz, O; Sautebin, L

    2010-01-01

    BACKGROUND AND PURPOSE Zileuton is the only 5-lipoxygenase (5-LOX) inhibitor marketed as a treatment for asthma, and is often utilized as a selective tool to evaluate the role of 5-LOX and leukotrienes. The aim of this study was to investigate the effect of zileuton on prostaglandin (PG) production in vitro and in vivo. EXPERIMENTAL APPROACH Peritoneal macrophages activated with lipopolysaccharide (LPS)/interferon γ (LPS/IFNγ), J774 macrophages and human whole blood stimulated with LPS were used as in vitro models and rat carrageenan-induced pleurisy as an in vivo model. KEY RESULTS Zileuton suppressed PG biosynthesis by interference with arachidonic acid (AA) release in macrophages. We found that zileuton significantly reduced PGE2 and 6-keto prostaglandin F1α (PGF1α) levels in activated mouse peritoneal macrophages and in J774 macrophages. This effect was not related to 5-LOX inhibition, because it was also observed in macrophages from 5-LOX knockout mice. Notably, zileuton inhibited PGE2 production in LPS-stimulated human whole blood and suppressed PGE2 and 6-keto PGF1α pleural levels in rat carrageenan-induced pleurisy. Interestingly, zileuton failed to inhibit the activity of microsomal PGE2 synthase1 and of cyclooxygenase (COX)-2 and did not affect COX-2 expression. However, zileuton significantly decreased AA release in macrophages accompanied by inhibition of phospholipase A2 translocation to cellular membranes. CONCLUSIONS AND IMPLICATION Zileuton inhibited PG production by interfering at the level of AA release. Its mechanism of action, as well as its use as a pharmacological tool, in experimental models of inflammation should be reassessed. PMID:20880396

  8. Prostaglandin content of tissue lining vascular prostheses

    SciTech Connect

    Greisler, H.P.; Kim, D.U.; Nussbaum, M.; Ellinger, J.; Schwarcz, T.H.

    1986-03-01

    This laboratory previously demonstrated arterial regeneration with a confluent endothelial-like flow surface 3-4 weeks after interposition of absorbable prostheses but not of dacron prostheses into the rabbit aorta. This study evaluates prostaglandin contents of inner capsular tissues within arterial prostheses. 6-keto-PGF/sub 1..cap alpha../ and TxB/sub 2/ were assayed (/sup 3/H-RIA) in supernatants of sonicated homogenates of tissues on the inner aspect of (a) absorbable polydioxanone (PDS), (b) absorbable polyglactin 910 (PG910), or (c) compound dacron-PG910 prostheses 3 or 6 months following implantation into rabbit aortas. Normal aortic controls from each rabbit were similarly treated. The 6-keto-PGF/sub 1..cap alpha../ values for all groups were lower than normal controls (p < .05). The ratio 6-keto-PGF/sub 1..cap alpha..//TxB/sub 2/ for PDS was nearly identical to normal aorta (1.69 +/- .54). This study shows that the quantity and ratio of eicosanoids in the inner capsular tissues is modified by the composition of the implanted arterial prosthesis.

  9. Effect of Diethylcarbamazine (DEC) on prostaglandin levels in Wuchereria bancrofti infected microfilaraemics.

    PubMed

    Sankari, T; Hoti, S L; Das, L K; Govindaraj, V; Das, P K

    2013-06-01

    Diethylcarbamazine (DEC) interferes with arachidonic acid metabolism for the clearance of microfilariae in Wuchereria bancrofti infected individuals. In this study, we have quantified the plasma concentrations of prostaglandin E2 (PGE2) and 6-keto-PGF1α, the end products of arachidonic acid metabolic pathway in microfilaraemics (DEC treated and untreated), and normal healthy individuals at pre- and 3,9,12,36, and 72 h of post-DEC treatment. We have also determined the microfilariae counts at pre and post day 2 (36 h) and day 3 (72 h) of DEC treatment by membrane filtration technique. Significant reduction in PGE2 and 6-keto-PGF1α concentrations was found at 12 h of DEC treatment. Rapid reduction in microfilarial counts was observed at 36 h of post-DEC treatment. Higher levels of prostaglandins were found at pre-treatment hours in microfilaraemics compared to normal healthy individuals (P < 0.05). Our findings indicate that DEC inhibits prostaglandins for the clearance of microfilariae, and increased levels of prostaglandins in microfilaraemics may be contributed by the parasite or host upon stimulation.

  10. Stretch-induced prostaglandins and protein turnover in cultured skeletal muscle

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman H.; Hatfaludy, Sophia; Sohar, Istvan; Shansky, Janet

    1990-01-01

    The purpose of the study is to determine whether mechanical stimulation of cultured muscle cells influences prostaglandin efflux rates and whether they are related to stretch-induced alterations in protein turnover rates. The materials and methods of the experiment, including cell cultures, mechanical stimulation, protein synthesis, and degradation assays are outlined, and emphasis is placed on the effect of short-term mechanical stimulation in basal medium prostaglandin efflux from cultured skeletal muscle and stretch-induced alterations in prostaglandins efflux in complete medium. The major finding of the study is that mechanical stimulation of tissue-cultured skeletal-muscle cells under conditions inducing skeletal-muscle hypertropy increases the efflux of PGE(2) and PGE(2-alpha) but not 6-keto-PGF(1-alpha), the prostacyclin product.

  11. Prostaglandins in the perilymph of guinea pig with type II collagen induced ear diseases

    SciTech Connect

    Takeda, T.; Chiang, T.; Kitano, H.; Sudo, N.; Kim, S.Y.; Ha, S.; Woo, V.; Wolf, B.; Floyd, R.; Yoo, T.J.

    1986-03-01

    The authors have studied the prostaglandins (PGs) in the perilymph from guinea pig with type II collagen induced autoimmune ear disease. Hartly guinea pigs were immunized with type II collagen in CFA and auditory brain stem responses (ABR) were measured at 2, 3, 4, and 6 months after initial immunization perilymph was obtained and the levels of PGE2 and 6 keto-PGFl..cap alpha.. were measured by radioimmunoassays. Temporal bones were examined for the histopathologic changes. Immunized guinea pigs showed the evidence of hearing loss by ABR. The temporal bones showed the following changes: spiral ganglia degeneration, mild to moderate degree of degeneration in organ of Corti, infrequent very mild endolymphatic hydrops and labrynthitis. The perilymph from immunized animals contained about 5 times more PGE2 and about 3 times more 6 keto-PGFl..cap alpha.. than control animals. However, between these two groups, there was no difference in the CSF and sera levels of PGE2 and 6 keto-PGFl..cap alpha... Thus, this study suggests that these inflammatory mediators might be involved in the pathogenesis of collagen induced autoimmune inner ear disease.

  12. Biosynthesis of prostaglandins in gingiva of patients with chronic periodontitis

    SciTech Connect

    Mendieta, C.F.; Reeve, C.M.; Romero, J.C.

    1985-01-01

    This study was undertaken to determine the ability of inflamed and normal gingival tissues to synthesize prostaglandins (PGs) from the precursor arachidonic acid. Thirteen samples of inflamed human gingival tissue and six samples of normal human gingival tissue were studied. The inflammation was characterized histologically. After incubation of the tissue with (/sup 14/C)arachidonate, PG metabolites were separated by thin-layer chromatography and identified by comparison with co-chromatographed standards. Inflamed gingival tissue synthesized significantly larger amounts, compared to normal tissue, of 6-keto-PGF1 alpha (P less than 0.05), thromboxane B2, PGD2, and PGA2. Some unidentified metabolites, possibly lipoxygenase products were detected in significantly larger amounts in inflamed than in normal tissue.

  13. Double blind controlled study on the effect of sucralfate on gastric prostaglandin formation and microbleeding in normal and aspirin treated man.

    PubMed Central

    Konturek, S J; Kwiecień, N; Obtułowicz, W; Kopp, B; Oleksy, J

    1986-01-01

    Two groups A and B each comprising 12 healthy young male subjects were used in a double blind, placebo controlled trial to assess the effects of 1.0 g sucralfate qid on prostaglandin (PG) generation and mucosal integrity in the intact and aspirin-treated stomach. Mucosal formation and luminal release of PGE2, 6-keto-PGE1 alpha and thromboxane B2, gastric microbleeding and DNA loss (integrity indicators) and basal and pentagastrin induced acid secretion were measured after placebo and sucralfate treatment in subjects without (group A) and with administration of 2.5 g aspirin (group B). Sucralfate significantly reduced spontaneous gastric microbleeding and DNA loss in group A and prevented blood loss but not DNA loss caused by aspirin in group B. The protective effects of sucralfate on spontaneous gastric microbleeding were accompanied by increased mucosal biosynthesis and luminal release of PGE2 and 6-keto-PGF1 alpha with a reduction in release of thromboxane B2. In aspirin treated subjects both mucosal generation and luminal release of prostaglandins and thromboxane B2 were greatly suppressed although sucralfate treatment did not influence these prostaglandins in spite of the reduction in mucosal damage. It is concluded that sucralfate has a potent protective action on spontaneous and aspirin treated gastric microbleeding in man and that this protection may be partly because of the increased mucosal biosynthesis of prostaglandins. PMID:3492413

  14. Unidirectional transfer of prostaglandin endoperoxides between platelets and endothelial cells.

    PubMed Central

    Schafer, A I; Crawford, D D; Gimbrone, M A

    1984-01-01

    An important determinant of platelet-vessel wall interactions is the local balance of production of endothelial prostacyclin (PGI2) and platelet thromboxane (TX) A2, labile eicosanoids with opposing effects on hemostasis. Disputed evidence suggests that platelet-derived prostaglandin endoperoxide intermediates may be utilized as substrates for vascular PGI2 synthesis. Using several different approaches, we have found that platelets can transfer endoperoxides to cultured endothelial cells for efficient conversion to PGI2, but a reciprocal transfer of endothelial endoperoxides for utilization by platelet thromboxane synthetase does not occur under the same experimental conditions. However, platelets can utilize arachidonic acid released by endothelial cells for lipoxygenase metabolism. We have directly demonstrated the production of [3H]6-keto-PGF1 alpha (the breakdown product of [3H]PGI2) by aspirin-treated endothelial cells in the presence of platelets stimulated with [3H]arachidonic acid. In coincubation experiments using either arachidonate or ionophore A23187 as a stimulus, radioimmunoassay of the net production of arachidonic acid metabolites showed that 6-keto-PGF1 alpha generation by aspirin-treated endothelial cells in the presence of platelets may actually exceed its generation by uninhibited endothelial cells alone. In functional assays, platelet aggregation was inhibited in the presence of aspirin-treated endothelial cells after stimulation with either arachidonate or ionophore A23187. In contrast, the inverse experiments, using aspirin-treated platelets and uninhibited endothelial cells, failed to demonstrate platelet utilization of endothelial endoperoxides for TXA2 production by any of the above methods. These studies thus provide evidence that efficient unidirectional transfer and utilization of platelet-derived endoperoxides for endothelial PGI2 production can occur. This process may serve to amplify PGI2 generation adjacent to areas of vascular

  15. Prostaglandins in reproductive physiology*

    PubMed Central

    Craig, Gillian M.

    1975-01-01

    The role of prostaglandins in reproductive physiology is reviewed with particular emphasis on their possible importance in ovulation in humans. A possible interaction between gonadal steroids, biogenic amines and prostaglandins at hypothalamic-pituitary level, in relation to the release of luteinizing hormone releasing factor, and LH, is discussed. Anomalies regarding the role of oestrogens in LH release are noted, and it is suggested that high oestrogen levels may release prostaglandins from the uterus and/or centrally in humans, in connection with the mid-cycle LH surge and ovulation. A hypothetical role for prostaglandins in sexual behaviour and premenstrual changes is discussed. The hypotheses open up new areas for clinical research to establish the role of prostaglandins in human endocrinology. The need for measurement of prostaglandin metabolites in blood and urine is emphasized. PMID:1089972

  16. Prostaglandins and Inflammation

    PubMed Central

    Ricciotti, Emanuela; FitzGerald, Garret A.

    2011-01-01

    Prostaglandins are lipid autacoids derived from arachidonic acid. They both sustain homeostatic functions and mediate pathogenic mechanisms, including the inflammatory response. They are generated from arachidonate by the action of cyclooxygenase (COX) isoenzymes and their biosynthesis is blocked by nonsteroidal anti-inflammatory drugs (NSAIDs), including those selective for inhibition of COX-2. Despite the clinical efficacy of NSAIDs, prostaglandins may function in both the promotion and resolution of inflammation. This review summarizes insights into the mechanisms of prostaglandin generation and the roles of individual mediators and their receptors in modulating the inflammatory response. Prostaglandin biology has potential clinical relevance for atherosclerosis, the response to vascular injury and aortic aneurysm. PMID:21508345

  17. Angiotensin II and renal prostaglandin release in the dog. Interactions in controlling renal blood flow and glomerular filtration rate.

    PubMed

    Bugge, J F; Stokke, E S

    1994-04-01

    The relationship between angiotensin II and renal prostaglandins, and their interactions in controlling renal blood flow (RBF) and glomerular filtration rate (GFR) were investigated in 18 anaesthetized dogs with acutely denervated kidneys. Intrarenal angiotensin II infusion increased renal PGE2 release (veno-arterial concentration difference times renal plasma flow) from 1.7 +/- 0.9 to 9.1 +/- 0.4 and 6-keto-PGF1 alpha release from 0.1 +/- 0.1 to 5.3 +/- 2.1 pmol min-1. An angiotensin II induced reduction in RBF of 20% did not measurably change GFR whereas a 30% reduction reduced GFR by 18 +/- 8%. Blockade of prostaglandin synthesis approximately doubled the vasoconstrictory action of angiotensin II, and all reductions in RBF were accompanied by parallel reductions in GFR. When prostaglandin release was stimulated by infusion of arachidonic acid (46.8 +/- 13.3 and 15.9 +/- 5.4 pmol min-1 for PGE2, and 6-keto-PGF1 alpha, respectively), angiotensin II did not change prostaglandin release, but had similar effects on the relationship between RBF and GFR as during control. In an ureteral occlusion model with stopped glomerular filtration measurements of ureteral pressure and intrarenal venous pressure permitted calculations of afferent and efferent vascular resistances. Until RBF was reduced by 25-30% angiotensin II increased both afferent and efferent resistances almost equally, keeping the ureteral pressure constant. At greater reductions in RBF, afferent resistance increased more than the efferent leading to reductions in ureteral pressure. This pattern was not changed by blockade of prostaglandin synthesis indicating no influence of prostaglandins on the distribution of afferent and efferent vascular resistances during angiotensin II infusion. In this ureteral occlusion model glomerular effects of angiotensin II will not be detected, and it might well be that the shift from an effect predominantly on RBF to a combined effect on both RBF and GFR induced by inhibition

  18. M2-F1 cockpit

    NASA Technical Reports Server (NTRS)

    1963-01-01

    This photo shows the cockpit configuration of the M2-F1 wingless lifting body. With a top speed of about 120 knots, the M2-F1 had a simple instrument panel. Besides the panel itself, the ribs of the wooden shell (left) and the control stick (center) are also visible. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne to prove it could fly safely and to train pilots before they were towed behind a C-47

  19. Prostaglandin F{sub 2{alpha}} regulates cytokine responses of mast cells through the receptors for prostaglandin E

    SciTech Connect

    Kaneko, Izumi; Hishinuma, Takanori; Suzuki, Kaori; Owada, Yuji; Kitanaka, Noriko; Kondo, Hisatake; Goto, Junichi; Furukawa, Hiroshi; Ono, Masao

    2008-03-14

    There is an increasing body of evidence that prostanoids modulate mast cell functions and contribute to the development of allergic inflammation. The present study aimed to identify an undetermined function of prostaglandin (PG) F{sub 2{alpha}} in mast cell activation and the signaling mechanism involved in it. Simultaneous quantification of prostanoids by liquid chromatography/tandem mass spectrometry revealed the constitutive release of PGF{sub 2{alpha}}, thromboxane B{sub 2}, and 6-keto-PGF{sub 1{alpha}} from bone marrow-derived mast cells (BMMCs). Upon activation of BMMCs by lipopolysaccharide, the cytokine production in BMMCs was enhanced when the culture was supplemented with PGF{sub 2{alpha}}. However, F prostanoid receptor-a selective receptor for PGF{sub 2{alpha}}-was not detected in BMMCs. Further investigations performed using prostanoid receptor antagonists revealed an alternative mechanism wherein the receptors for PGE species-E prostanoid receptors-mediated the PGF{sub 2{alpha}} signal in BMMCs. The present study provides an insight into a novel function of PGF{sub 2{alpha}}, i.e., an autocrine accelerator for mast cell activation.

  20. Regulation of prostaglandin production by nitric oxide; an in vivo analysis.

    PubMed Central

    Salvemini, D; Settle, S L; Masferrer, J L; Seibert, K; Currie, M G; Needleman, P

    1995-01-01

    1. Endotoxin E. Coli lipopolysaccharide (LPS)-treatment in conscious, restrained rats increased plasma and urinary prostaglandin (PG) and nitric oxide (NO) production. Inducible cyclo-oxygenase (COX-2) and nitric oxide synthase (iNOS) expression accounted for the LPS-induced PG and NO release since the glucocorticoid, dexamethasone inhibited both effects. Thus, LPS (4 mg kg-1) increased the plasma levels of nitrite/nitrate from 14 +/- 1 to 84 +/- 7 microM within 3 h and this rise was inhibited to 35 +/- 1 microM by dexamethasone. Levels of 6-keto PGF1 alpha in the plasma were below the detection limit of the assay (< 0.2 ng ml-1). However, 3 h after the injection of LPS these levels rose to 2.6 +/- 0.2 ng ml-1 and to 0.7 +/- 0.01 ng ml-1 after LPS in rats that received dexamethasone. 2. The induced enzymes were inhibited in vivo with selective COX and NOS inhibitors. Furthermore, NOS inhibitors, that did not affect COX activity in vitro markedly suppressed PG production in the LPS-treated animals. For instance, the LPS-induced increased in plasma nitrite/nitrate and 6-keto PGF1 alpha at 3 h was decreased to 18 +/- 2 microM and 0.5 +/- 0.02 ng ml-1, 23 +/- 1 microM and 0.7 +/- 0.01 ng ml-1, 29 +/- 2 microM and 1 +/- 0.01 ng ml-1 in rats treated with LPS in the presence of the NOS inhibitors NG-monomethyl-L-arginine, NG-nitro arginine methyl ester and aminoguanidine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7542531

  1. Assessment of oxidative stress markers and prostaglandins after chronic training of triathletes.

    PubMed

    Medina, Sonia; Domínguez-Perles, Raul; Cejuela-Anta, Roberto; Villaño, Débora; Martínez-Sanz, José M; Gil, Pilar; García-Viguera, Cristina; Ferreres, Federico; Gil, José I; Gil-Izquierdo, Angel

    2012-12-01

    The present study established the pattern of isoprostanes (IsoPs) and prostaglandins metabolites (PGMs) in urine after triathlon training. Fifteen Caucasian triathletes - 5 women and 10 men - performed 793 and 1603 Objective Load Scales, respectively. The optimization of urine hydrolysis conditions, concerning to the type of buffer, the units of hydrolytic enzyme added, and the pH, allowed precise quantification of these metabolites by UPLC-MS/MS, avoiding the under-estimation of their concentrations that occurred in previous studies. Their rate of conjugation ranged between 36% and 100%. This implies significant importance since it supposes non-detection of some IsoPs and PGMs totally conjugated with glucuronic acid developed by other previous methodologies. Among the 13 compounds analyzed, this assay detected and characterized 4 IsoPs and 3 PGMs in the triathletes' urine. The PGMs tetranor-PGEM and 11β-PGF(2α) and the IsoP 8-iso-PGF(2α), showed lower concentrations after the training program, whereas the PGMs 6-keto-PGF(1α) increased (vascular PGI(2) metabolite). In fact, their pattern in the triathletes' urine indicated that their variation may have been related with the physical activity. Due to its high variation, 6-keto PGF(1α) stood out as a useful marker of the vasodilation and inhibition of the platelet aggregation of the PGI(2) linked to the physical exercise. The data obtained provided a global picture of changes in lipid peroxidation and vascular events as a consequence of chronic exercise.

  2. Role of prostaglandins in the renal response to calcium infusion.

    PubMed

    Lahera, V; Fiksen-Olsen, M J; Romero, J C

    1990-04-01

    The effects of intrarenal infusions of calcium gluconate (10 and 100 micrograms Ca.kg-1.min-1) on renal hemodynamics and on renal excretory function were studied in anesthetized mongrel dogs. In one group, the two doses of calcium were infused for 30 min each (1 ml/min). In a second group, the same doses were administered 30 min after the start of an infusion of prostaglandin (PG) inhibitors (intrarenal indomethacin, 10 micrograms.kg-1.min-1, or intravenous bolus injection of meclofenamate, 5 mg/kg). No change with physiological significance was observed during the infusion of 10 micrograms Ca.kg-1.min-1. However, the infusion of 100 micrograms Ca.kg-1.min-1 induced increases (P less than 0.05) in glomerular filtration rate (50%), sodium excretion rate (180%), and fractional excretion of sodium (160%), with respect to control precalcium values. All these changes were prevented by the concurrent administration of PG synthesis inhibitors. Urinary PGE2 and 6-keto-PGF1 alpha increased 220 and 85%, respectively, during the infusion of 100 micrograms Ca.kg-1.min-1, but both decreased (P less than 0.05) below basal levels during the concurrent administration of PG synthesis inhibitors. The infusion of 100 micrograms Ca.kg-1.min-1 decreased (P less than 0.05) renal blood flow by 16% during the administration of PG synthesis inhibitors. These results suggest that PGs are mediating the increase in hemodynamic and excretory factors induced by the intrarenal infusion of 100 micrograms Ca.kg-1.min-1.

  3. F-1 Engine Gas Generator Testing

    NASA Video Gallery

    The gas generator from an F-1 engine is test-fired at the Marshall Space Flight Center in Huntsville, Ala., on Jan. 24, 2013. Data from the 30 second test will be used in the development of advance...

  4. Inhibition of microsomal prostaglandin E synthase-1 by aminothiazoles decreases prostaglandin E2 synthesis in vitro and ameliorates experimental periodontitis in vivo

    PubMed Central

    Kats, Anna; Båge, Tove; Georgsson, Pierre; Jönsson, Jörgen; Quezada, Hernán Concha; Gustafsson, Anders; Jansson, Leif; Lindberg, Claes; Näsström, Karin; Yucel-Lindberg, Tülay

    2013-01-01

    The potent inflammatory mediator prostaglandin E2 (PGE2) is implicated in the pathogenesis of several chronic inflammatory conditions, including periodontitis. The inducible enzyme microsomal prostaglandin E synthase-1 (mPGES-1), catalyzing the terminal step of PGE2 biosynthesis, is an attractive target for selective PGE2 inhibition. To identify mPGES-1 inhibitors, we investigated the effect of aminothiazoles on inflammation-induced PGE2 synthesis in vitro, using human gingival fibroblasts stimulated with the cytokine IL-1β and a cell-free mPGES-1 activity assay, as well as on inflammation-induced bone resorption in vivo, using ligature-induced experimental periodontitis in Sprague-Dawley rats. Aminothiazoles 4-([4-(2-naphthyl)-1,3-thiazol-2-yl]amino)phenol (TH-848) and 4-(3-fluoro-4-methoxyphenyl)-N-(4-phenoxyphenyl)-1,3-thiazol-2-amine (TH-644) reduced IL-1β-induced PGE2 production in fibroblasts (IC50 1.1 and 1.5 μM, respectively) as well as recombinant mPGES-1 activity, without affecting activity or expression of the upstream enzyme cyclooxygenase-2. In ligature-induced experimental periodontitis, alveolar bone loss, assessed by X-ray imaging, was reduced by 46% by local treatment with TH-848, compared to vehicle, without any systemic effects on PGE2, 6-keto PGF1α, LTB4 or cytokine levels. In summary, these results demonstrate that the aminothiazoles represent novel mPGES-1 inhibitors for inhibition of PGE2 production and reduction of bone resorption in experimental periodontitis, and may be used as potential anti-inflammatory drugs for treatment of chronic inflammatory diseases, including periodontitis.—Kats, A., Båge, T., Georgsson, P., Jönsson, J., Quezada, H. C., Gustafsson, A., Jansson, L., Lindberg, C., Näsström, K., Yucel-Lindberg, T. Inhibition of microsomal prostaglandin E synthase-1 by aminothiazoles decreases prostaglandin E2 synthesis in vitro and ameliorates experimental periodontitis in vivo. PMID:23447581

  5. Activation of Ftz-F1-Responsive Genes through Ftz/Ftz-F1 Dependent Enhancers

    PubMed Central

    Field, Amanda; Xiang, Jie; Anderson, W. Ray; Graham, Patricia; Pick, Leslie

    2016-01-01

    The orphan nuclear receptor Ftz-F1 is expressed in all somatic nuclei in Drosophila embryos, but mutations result in a pair-rule phenotype. This was explained by the interaction of Ftz-F1 with the homeodomain protein Ftz that is expressed in stripes in the primordia of segments missing in either ftz-f1 or ftz mutants. Ftz-F1 and Ftz were shown to physically interact and coordinately activate the expression of ftz itself and engrailed by synergistic binding to composite Ftz-F1/Ftz binding sites. However, attempts to identify additional target genes on the basis of Ftz-F1/ Ftz binding alone has met with only limited success. To discern rules for Ftz-F1 target site selection in vivo and to identify additional target genes, a microarray analysis was performed comparing wildtype and ftz-f1 mutant embryos. Ftz-F1-responsive genes most highly regulated included engrailed and nine additional genes expressed in patterns dependent on both ftz and ftz-f1. Candidate enhancers for these genes were identified by combining BDTNP Ftz ChIP-chip data with a computational search for Ftz-F1 binding sites. Of eight enhancer reporter genes tested in transgenic embryos, six generated expression patterns similar to the corresponding endogenous gene and expression was lost in ftz mutants. These studies identified a new set of Ftz-F1 targets, all of which are co-regulated by Ftz. Comparative analysis of enhancers containing Ftz/Ftz-F1 binding sites that were or were not bona fide targets in vivo suggested that GAF negatively regulates enhancers that contain Ftz/Ftz-F1 binding sites but are not actually utilized. These targets include other regulatory factors as well as genes involved directly in morphogenesis, providing insight into how pair-rule genes establish the body pattern. PMID:27723822

  6. Revising the f1(1420 ) resonance

    NASA Astrophysics Data System (ADS)

    Debastiani, V. R.; Aceti, F.; Liang, Wei-Hong; Oset, E.

    2017-02-01

    We have studied the production and decay of the f1(1285 ) into π a0(980 ) and K*K ¯ as a function of the mass of the resonance and find a shoulder around 1400 MeV, tied to a triangle singularity, for the π a0(980 ) mode, and a peak around 1420 MeV with about 60 MeV width for the K*K ¯ mode. Both of these features agree with the experimental information on which the f1(1420 ) resonance is based. In addition, we find that if the f1(1420 ) is a genuine resonance, coupling mostly to K*K ¯ as seen experimentally, one finds unavoidably about a 20% fraction for π a0(980 ) decay of this resonance, in drastic contradiction with all experiments. Altogether, we conclude that the f1(1420 ) is not a genuine resonance, but the manifestation of the π a0(980 ) and K*K ¯ decay modes of the f1(1285 ) at higher energies than the nominal one.

  7. Histamine stimulation of prostaglandin and HETE synthesis in human endothelial cells

    SciTech Connect

    Revtyak, G.E.; Hughes, M.J.; Johnson, A.R.; Campbell, W.B.

    1988-08-01

    Endothelial cells (EC) cultured from human umbilical artery (UA) and vein (UV) metabolized (/sup 14/C)arachidonic acid to prostaglandins (PGs), monohydroxyeicosatetraenoic acids (HETEs), and epoxyeicosatrienoic acids (EETs). Major radioactive products were identified as 6-keto-PGF1 alpha, PGE2, PGF2 alpha, 12-hydroxy heptadecatrienoic acid, 15-HETE, and 11-HETE. In addition, extracts from UV ECs contained 12-HETE, 5-HETE, 14,15-EET, and 5,6-EET as minor products, whereas extracts from UA ECs contained only 12-HETE as a minor product. UA ECs also produced metabolites comigrating with 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET. Histamine increased the release of (/sup 14/C)PGs and (/sup 14/C)HETEs from (/sup 14/C)arachidonic acid-labeled ECs. Indomethacin, aspirin, and nordihydroguauretic acid completely inhibited synthesis of both (/sup 14/C)PGs and (/sup 14/C)HETEs from exogenous (/sup 14/C)arachidonic acid in these cells. Microsomes metabolized (/sup 14/C)arachidonic acid to the same (/sup 14/C)PGs and (/sup 14/C)HETEs as intact cells. Pretreatment of microsomes with indomethacin completely inhibited formation of these products. These data indicate that UA ECs and UV ECs metabolize endogenous and exogenous arachidonic acid to both PGs and HETEs. Also 15-HETE and 11-HETE appear to be synthesized by a microsomal enzyme with the properties of cyclooxygenase.

  8. The role of cyclooxygenase-1 and cyclooxygenase-2 in lipopolysaccharide and interleukin-1 stimulated enterocyte prostanoid formation.

    PubMed

    Longo, W E; Damore, L J; Mazuski, J E; Smith, G S; Panesar, N; Kaminski, D L

    1998-01-01

    Lipopolysaccharide is an inflammatory agent and interleukin-1 is a cytokine. Their pro-inflammatory effects may be mediated by prostanoids produced by inducible cyclooxygenase-2. The aim of this study was to determine the prostanoids produced by lipopolysaccharide and interleukin-1 stimulated enterocytes through the cyclooxygenase-1 and 2 pathways. Cultured enterocytes were stimulated with lipopolysaccharide or interleukin-1beta with and without cyclooxygenase inhibitors. Low concentrations of indomethacin and valerylsalicylic acid (VSA) were evaluated as cyclooxygenase-1 inhibitors and their effects compared with the effects of a specific cyclooxygenase-2 inhibitor, SC-58125. Prostaglandin E2, 6-keto prostaglandin F1alpha, prostaglandin D2 and leukotriene B4 levels were determined by radioimmunoassay. Immunoblot analysis using isoform-specific antibodies showed that the inducible cyclooxygenase enzyme (COX-2) was expressed by 4 h in LPS and IL-1beta treated cells while the constitutive COX-1 remained unaltered in its expression. Interleukin-1beta and lipopolysaccharide stimulated the formation of all prostanoids compared with untreated cells, but failed to stimulate leukotriene B4. Indomethacin at 20 microM concentration, and VSA inhibited lipopolysaccharide and interleukin 1beta stimulated prostaglandin E2, but not 6-keto prostaglandin F1alpha formation. SC-58125 inhibited lipopolysaccharide and interleukin-1beta stimulated 6-keto prostaglandin F1alpha but not prostaglandin E2 release. The specific cyclooxygenase-2 inhibitor also inhibited lipopolysaccharide produced prostaglandin D2 but not interleukin-1beta stimulated prostaglandin D2. While SC-58125 inhibited basal 6-keto prostaglandin-F1alpha formation it significantly increased basal prostaglandin E2 and prostaglandin D2 formation. As SC-58125 inhibited lipopolysaccharide and interleukin-1beta induced 6-keto prostaglandin F1alpha production but not prostaglandin E2 production, it suggests that these agents

  9. M2-F1 in flight

    NASA Technical Reports Server (NTRS)

    1965-01-01

    The M2-F1 Lifting Body is seen here under tow, high above Rogers Dry Lake near the Flight Research Center (later redesignated the Dryden Flight Research Center), Edwards, California. R. Dale Reed effectively advocated the project with the support of NASA research pilot Milt Thompson. Together, they gained the support of Flight Research Center Director Paul Bikle. After a six-month feasibility study, Bikle gave approval in the fall of 1962 for the M2-F1 to be built. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Flight Research Center management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. These initial tests produced enough flight data about the M2-F1 to proceed with flights behind a NASA C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to l20 mph. More than 400 ground tows and 77 aircraft tow flights were carried out with the M2-F1. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at NASA's Ames and Langley research centers--the M2-F2 and the HL

  10. M2-F1 simulator cockpit

    NASA Technical Reports Server (NTRS)

    1963-01-01

    This early simulator of the M2-F1 lifting body was used for pilot training, to test landing techniques before the first ground tow attempts, and to test new control configurations after the first tow attempts and wind-tunnel tests. The M2-F1 simulator was limited in some ways by its analog simulator. It had only limited visual display for the pilot, as well. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne

  11. M2-F1 in flight

    NASA Technical Reports Server (NTRS)

    1964-01-01

    The M2-F1 Lifting Body is seen here under tow by an unseen C-47 at the NASA Flight Research Center (later redesignated the Dryden Flight Research Center), Edwards, California. The low-cost vehicle was the first piloted lifting body to be test flown. The lifting-body concept originated in the mid-1950s at the National Advisory Committee for Aeronautics' Ames Aeronautical Laboratory, Mountain View California. By February 1962, a series of possible shapes had been developed, and R. Dale Reed was working to gain support for a research vehicle. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. These initial tests produced enough flight data about the M2-F1 to proceed with flights behind a NASA C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to l20 mph. More than 400 ground tows and 77 aircraft tow flights were carried out with the M2-F1. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at

  12. Changes in endogenous prostacyclin in the rat brain during clinical death and after resuscitation.

    PubMed

    Kapuściński, A

    1992-01-01

    By means of the radioimmunologic method changes of concentration of 6-keto-prostaglandin F1 alpha (PGF1 alpha)--the stable metabolite of prostacyclin in the rat brain have been evaluated during 5-min clinical death and up to 2 hrs after resuscitation. Ischemia did not produce significant changes of 6-keto-PGF1 alpha concentration in the brain. In the early postresuscitation period the concentration of 6-keto-PGF1 in the and 7-fold control values. Later the concentration of 6-keto-PGF1 alpha in the brain decreased reaching in 30 min a 3-fold the control level, and in 60 and 120 min after resuscitation control values. The reasons of unsuccessful therapy of ischemic stroke with prostacyclin are discussed.

  13. Effect of lactate-buffered peritoneal dialysis fluids on human peritoneal mesothelial cell interleukin-6 and prostaglandin synthesis.

    PubMed

    Witowski, J; Topley, N; Jörres, A; Liberek, T; Coles, G A; Williams, J D

    1995-01-01

    The present study focused on the evaluation of constitutive and cytokine-stimulated human peritoneal mesothelial cell (HPMC) IL-6 and 6-keto-PGF1 alpha release following pre-exposure to peritoneal dialysis fluid (PDF). Exposure of HPMC to PDF pH 5.2 resulted in a time-dependent increase in cell cytotoxicity [as assessed by lactate dehydrogenase (LDH) release] and concomitant inhibition of constitutive and IL-1 beta stimulated IL-6 and 6-keto-PGF1 alpha synthesis. After 15 minutes of exposure to PDF constitutive and IL-1 beta stimulated IL-6 release were reduced by 32.0 +/- 9.7% and 76.0 +/- 7.4% (N = 6, P < 0.046 and P < 0.027, respectively). PCR amplification of reverse transcribed mRNA from HPMC pre-exposed to PDF pH 5.2 demonstrated suppression of IL-1 beta stimulated IL-6 and cyclooxygenase (Cox-1 and Cox-2) transcripts. In order to mimic the dialysis cycle in vivo, an in vitro dialysis system was established. HPMC were exposed first to control medium, PDF pH 5.2 or PDF 7.3 for 15 minutes and then sequentially to pooled spent peritoneal dialysis effluent for up to four hours. The cells were subsequently allowed to recover in control medium for 12 hours in the presence or absence of IL-1 beta or TNF-alpha (both at 1000 pg/ml). There was no evidence of significant cell toxicity as assessed by LDH release during either the 'in vitro dialysis' or 'recovery' phases. Under these conditions short term exposure to PDF pH 5.2 followed by 'in vitro dialysis' resulted in significant inhibition of cytokine stimulated IL-6 (69.6 +/- 18.2 vs. 96.7 +/- 27.9 pg/microgram, N = 13; P < 0.020 for IL-1 beta) and 6-keto-PGF1 alpha (197.5 +/- 89.2 vs. 289.6 +/- 114.5 pg/microgram, N = 13; P < 0.020 for IL-1 beta) and 6-keto-PGF1 alpha (197.5 +/- 89.2 vs. 289.6 +/- 114.5 pg/microgram, N = 13; P < 0.003) release when compared to cells incubated in control medium. Adjustment of the pH of PDF to 7.3 reversed its inhibitory effects. We conclude that short-term exposure to PDF pH 5

  14. Hyperforin, an Anti-Inflammatory Constituent from St. John's Wort, Inhibits Microsomal Prostaglandin E(2) Synthase-1 and Suppresses Prostaglandin E(2) Formation in vivo.

    PubMed

    Koeberle, Andreas; Rossi, Antonietta; Bauer, Julia; Dehm, Friederike; Verotta, Luisella; Northoff, Hinnak; Sautebin, Lidia; Werz, Oliver

    2011-01-01

    The acylphloroglucinol hyperforin (Hyp) from St. John's wort possesses anti-inflammatory and anti-carcinogenic properties which were ascribed among others to the inhibition of 5-lipoxygenase. Here, we investigated whether Hyp also interferes with prostanoid generation in biological systems, particularly with key enzymes participating in prostaglandin (PG)E(2) biosynthesis, i.e., cyclooxygenases (COX)-1/2 and microsomal PGE(2) synthase (mPGES)-1 which play key roles in inflammation and tumorigenesis. Similar to the mPGES-1 inhibitors MK-886 and MD-52, Hyp significantly suppressed PGE(2) formation in whole blood assays starting at 0.03-1 μM, whereas the concomitant generation of COX-derived 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid, thromboxane B(2), and 6-keto PGF(1α) was not significantly suppressed up to 30 μM. In cell-free assays, Hyp efficiently blocked the conversion of PGH(2) to PGE(2) mediated by mPGES-1 (IC(50) = 1 μM), and isolated COX enzymes were not (COX-2) or hardly (COX-1) suppressed. Intraperitoneal (i.p.) administration of Hyp (4 mg kg(-1)) to rats impaired exudate volume and leukocyte numbers in carrageenan-induced pleurisy associated with reduced PGE(2) levels, and Hyp (given i.p.) inhibited carrageenan-induced mouse paw edema formation (ED(50) = 1 mg kg(-1)) being superior over indomethacin (ED(50) = 5 mg kg(-1)). We conclude that the suppression of PGE(2) biosynthesis in vitro and in vivo by acting on mPGES-1 critically contributes to the anti-inflammatory efficiency of Hyp.

  15. Production of prostaglandins, isoprostanes and thromboxane by Aspergillus fumigatus: identification by gas chromatography-tandem mass spectrometry and quantification by enzyme immunoassay.

    PubMed

    Kupfahl, Claudio; Tsikas, Dimitrios; Niemann, Jonas; Geginat, Gernot; Hof, Herbert

    2012-01-01

    Aspergillus fumigatus has been reported to produce prostaglandin (PG)-like substances. The molecular structure of these fungal eicosanoids is however still unknown. By using the gas chromatography-tandem mass spectrometry (GC-MS/MS) methodology we identified a number of eicosanoids that were formed upon incubation of the precursor arachidonic acid ethyl ester (AAE, 10 μM) with three strains of A. fumigatus. The eicosanoids identified include the prostaglandins (PG) PGE(2), 6-keto-PGF(1α) (the stable hydrolysis product of prostacyclin PGI(2)) and PGF(2α), the isoprostanes 15(S)-8-iso-PGF(2α) and 15(S)-8-iso-PGE(2), and thromboxane B(2) (TxB(2), the stable hydrolysis product of TxA(2)). These eicosanoids are identical with those produced by cyclooxygenases (COX) in humans. The biosynthesis of all of these eicosanoids could not be inhibited by the human COX inhibitors indomethacin (100 μM), acetylsalicylic acid (100 μM) or the non-selective human lipoxygenase (LOX) inhibitor nordihydroguaiaretic acid (100 μM). By contrast, the selen-containing antioxidant ebselen (100 μM) was found to inhibit their synthesis. Our results suggest that mammals and fungi employ different eicosanoid biosynthesis pathways. As some of the detected eicosanoids are potent immunomodulators and bronchoconstrictors, they could play a possible role in pulmonary diseases associated with A. fumigatus infection.

  16. Anatomy of F1-ATPase powered rotation

    PubMed Central

    Martin, James L.; Ishmukhametov, Robert; Hornung, Tassilo; Ahmad, Zulfiqar; Frasch, Wayne D.

    2014-01-01

    F1-ATPase, the catalytic complex of the ATP synthase, is a molecular motor that can consume ATP to drive rotation of the γ-subunit inside the ring of three αβ-subunit heterodimers in 120° power strokes. To elucidate the mechanism of ATPase-powered rotation, we determined the angular velocity as a function of rotational position from single-molecule data collected at 200,000 frames per second with unprecedented signal-to-noise. Power stroke rotation is more complex than previously understood. This paper reports the unexpected discovery that a series of angular accelerations and decelerations occur during the power stroke. The decreases in angular velocity that occurred with the lower-affinity substrate ITP, which could not be explained by an increase in substrate-binding dwells, provides direct evidence that rotation depends on substrate binding affinity. The presence of elevated ADP concentrations not only increased dwells at 35° from the catalytic dwell consistent with competitive product inhibition but also decreased the angular velocity from 85° to 120°, indicating that ADP can remain bound to the catalytic site where product release occurs for the duration of the power stroke. The angular velocity profile also supports a model in which rotation is powered by Van der Waals repulsive forces during the final 85° of rotation, consistent with a transition from F1 structures 2HLD1 and 1H8E (Protein Data Bank). PMID:24567403

  17. M2-F1 in flight

    NASA Technical Reports Server (NTRS)

    1963-01-01

    This 25-second clip shows Milt Thompson being towed in the M2-F1 behind a C-47 aircraft. The M2-F1 lifting body, dubbed the 'flying bathtub' by the media, was the precursor of a remarkable series of wingless flying vehicles that contributed data used in the Space Shuttles, the X-33 Advanced Technology Demonstrator for the next century's Reusable Launch Vehicle, and the X-38 Technology Demonstrator for crew return from the International Space Station. Based on the ideas and basic design of Alfred J. Eggers and others at the Ames Aeronautical Laboratory (now the Ames Research Center), Mountain View, California, in the mid-1950's, the M2-F1 was built in 1962-63 over a four-month period for a cost of only about $30,000, plus an additional $8,000-$10,000 for an ejection seat. Engineers and technicians at the NASA Flight Research Center (now NASA Dryden) kept costs low by designing and fabricating it partly in-house, with the plywood shell constructed by a local sailplane builder. Someone at the time estimated that it would have cost a major aircraft company $150,000 to build the same vehicle. Unlike the later lifting bodies, the M2-F1 was unpowered and was initially towed by a souped-up Pontiac convertible until it was airborne. Later a C-47 took over the towing duties. Flown by such famous research pilots as Milt Thompson, Bruce Peterson, Chuck Yeager, and Bill Dana, the lightweight flying bathtub demonstrated that a wingless vehicle shaped for reentry into the Earth's atmosphere from space could be flown and landed safely. Flown from 1963 to 1966, the lightweight M2-F1 paved the way for the heavyweight M2-F2, M2-F3, HL-10, X-24A, and X-24B lifting bodies that flew under rocket power after launch from a B-52 mothership. The heavyweights flew from 1966 to 1975, demonstrating the viability and versatility of the wingless configuration and the ability of a vehicle with low lift-over-drag characteristics to fly to high altitudes and then to land precisely with their rocket

  18. Role of prostaglandins in hypertension.

    PubMed

    Colina-Chourio, J A; Godoy-Godoy, N; Avila-Hernández, R M

    2000-04-01

    The role of prostaglandins (PGs) in hypertension (HT) is reviewed, emphasising their biochemical characteristics, physiological effects and functions, especially in the cardiovascular area, and the current evidence of their participation in the antihypertensive activity of a balanced mechanism to maintain normal blood pressure. Also, the clinical use of PGs and the future of such autacoids in the treatment of HT and other diseases or conditions is mentioned.

  19. Carnosol and carnosic acids from Salvia officinalis inhibit microsomal prostaglandin E2 synthase-1.

    PubMed

    Bauer, Julia; Kuehnl, Susanne; Rollinger, Judith M; Scherer, Olga; Northoff, Hinnak; Stuppner, Hermann; Werz, Oliver; Koeberle, Andreas

    2012-07-01

    Prostaglandin E(2) (PGE(2)), the most relevant eicosanoid promoting inflammation and tumorigenesis, is formed by cyclooxygenases (COXs) and PGE(2) synthases from free arachidonic acid. Preparations of the leaves of Salvia officinalis are commonly used in folk medicine as an effective antiseptic and anti-inflammatory remedy and possess anticancer activity. Here, we demonstrate that a standard ethyl acetate extract of S. officinalis efficiently suppresses the formation of PGE(2) in a cell-free assay by direct interference with microsomal PGE(2) synthase (mPGES)-1. Bioactivity-guided fractionation of the extract yielded closely related fractions that potently suppressed mPGES-1 with IC(50) values between 1.9 and 3.5 μg/ml. Component analysis of these fractions revealed the diterpenes carnosol and carnosic acid as potential bioactive principles inhibiting mPGES-1 activity with IC(50) values of 5.0 μM. Using a human whole-blood assay as a robust cell-based model, carnosic acid, but not carnosol, blocked PGE(2) generation upon stimulation with lipopolysaccharide (IC(50) = 9.3 μM). Carnosic acid neither inhibited the concomitant biosynthesis of other prostanoids [6-keto PGF(1α), 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid, and thromboxane B(2)] in human whole blood nor affected the activities of COX-1/2 in a cell-free assay. Together, S. officinalis extracts and its ingredients carnosol and carnosic acid inhibit PGE(2) formation by selectively targeting mPGES-1. We conclude that the inhibitory effect of carnosic acid on PGE(2) formation, observed in the physiologically relevant whole-blood model, may critically contribute to the anti-inflammatory and anticarcinogenic properties of S. officinalis.

  20. Recovery of Prostaglandins in Human Cutaneous Inflammation*

    PubMed Central

    Greaves, Malcolm W.; Søndergaard, Jørgen; McDonald-Gibson, Wendy

    1971-01-01

    An in-vivo skin perfusion technique has been used to study the pharmacological activity in inflamed skin of patients with allergic contact eczema. Perfusates from 35 out of 45 patients contained a smooth-muscle-contracting agent with prostaglandin-like properties. Solvent partition followed by thinlayer chromatography revealed this activity to be due to a mixture of prostaglandins E and F. This direct evidence supports the view that prostaglandins mediate inflammation in man. PMID:5572386

  1. Equatorial F1 characteristics and the international reference ionosphere model

    NASA Astrophysics Data System (ADS)

    Adeniyi, J. O.

    1996-07-01

    Average values of the F1 critical frequency (f0F1) and the height of the F1 ledge (hmF1) for Ibadan (Latitude 7.4°N, Longitude 3.9°E) were used for this study. Well-defined F1 characteristics are observed during winter at low solar activity. International reference ionosphere (IRI) does not predict F1 parameters during this season. Deviation of predicted F1 electron density (NF1) by the IRI model from observed values are less than 10% for all seasons of low solar activity, when IRI predicts NF1. Higher percentage deviations are observed during summers of high solar activity. IRI overestimates hmF1. Deviations from experimental values vary from 4 to 35%.

  2. Prostaglandin E, pessaries for induction of labour.

    PubMed

    Pearce, J M; Shepherd, J H; Sims, C D

    1979-03-17

    Vaginal pessaries containing 3 mg of prostaglandin E2 were used to induce labour in 200 patients with variable induction features. Prostaglandin-induced labour was augmented where necessary by synthetic oxytocin. There was on failed induction. Only 23% of patients with favourable induction features and 53% of patients with unfavourable features needed oxytocin. There were no adverse fetal or maternal effects. The prostaglandin E2 pessary was as effective in inducing labour as 350 microgram extra-amniotic prostaglandin E2 in tylose in a comparable group of 200 patients in which there were 4 failed inductions.

  3. 26 CFR 1.415(f)-1 - Aggregating plans.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Aggregating plans. 1.415(f)-1 Section 1.415(f)-1...) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.415(f)-1 Aggregating plans. (a) In general. Except as provided in paragraph (g) of this section (regarding multiemployer plans), and...

  4. 26 CFR 1.415(f)-1 - Aggregating plans.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 5 2012-04-01 2011-04-01 true Aggregating plans. 1.415(f)-1 Section 1.415(f)-1...) INCOME TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.415(f)-1 Aggregating plans. (a) In general. Except as provided in paragraph (g) of this section (regarding multiemployer...

  5. 26 CFR 1.415(f)-1 - Aggregating plans.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 5 2011-04-01 2011-04-01 false Aggregating plans. 1.415(f)-1 Section 1.415(f)-1...) INCOME TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.415(f)-1 Aggregating plans. (a) In general. Except as provided in paragraph (g) of this section (regarding multiemployer...

  6. Nonleptonic decays of B →(f1(1285 ),f1(1420 ))V in the perturbative QCD approach

    NASA Astrophysics Data System (ADS)

    Liu, Xin; Xiao, Zhen-Jun; Zou, Zhi-Tian

    2016-12-01

    We investigate the branching ratios, the polarization fractions, the direct C P -violating asymmetries, and the relative phases in 20 nonleptonic decay modes of B →f1V within the framework of the perturbative QCD approach at leading order with f1 including two 3P1-axial-vector states f1(1285 ) and f1(1420 ) . Here, B denotes B+, B0, and Bs0 mesons and V stands for the lightest vector mesons ρ , K*, ω , and ϕ , respectively. The Bs0→f1V decays are studied theoretically for the first time in the literature. Together with the angle ϕf1≈(24-2.7+3.2)∘ extracted from the measurement through Bd /s→J /ψ f1(1285 ) modes for the f1(1285 )-f1(1420 ) mixing system, it is of great interest to find phenomenologically some modes such as the tree-dominated B+→f1ρ+ and the penguin-dominated B+,0→f1K*+,0 , Bs0→f1ϕ with large branching ratios around O (10-6) or even O (10-5), which are expected to be measurable at the LHCb and/or the Belle-II experiments in the near future. The good agreement (sharp contrast) of branching ratios and decay pattern for B+→f1ρ+ , B+,0→f1(1285 )K*+,0[B+,0→f1(1420 )K*+,0] decays between QCD factorization and perturbative QCD factorization predictions can help us to distinguish these two rather different factorization approaches via precision measurements, which would also be helpful for us in exploring the annihilation decay mechanism through its important roles for the considered B →f1V decays.

  7. Single molecule thermodynamics of ATP synthesis by F1-ATPase

    NASA Astrophysics Data System (ADS)

    Toyabe, Shoichi; Muneyuki, Eiro

    2015-01-01

    FoF1-ATP synthase is a factory for synthesizing ATP in virtually all cells. Its core machinery is the subcomplex F1-motor (F1-ATPase) and performs the reversible mechanochemical coupling. The isolated F1-motor hydrolyzes ATP, which is accompanied by unidirectional rotation of its central γ -shaft. When a strong opposing torque is imposed, the γ -shaft rotates in the opposite direction and drives the F1-motor to synthesize ATP. This mechanical-to-chemical free-energy transduction is the final and central step of the multistep cellular ATP-synthetic pathway. Here, we determined the amount of mechanical work exploited by the F1-motor to synthesize an ATP molecule during forced rotations using a methodology combining a nonequilibrium theory and single molecule measurements of responses to external torque. We found that the internal dissipation of the motor is negligible even during rotations far from a quasistatic process.

  8. Enhancement of scleral macromolecular permeability with prostaglandins.

    PubMed Central

    Weinreb, R N

    2001-01-01

    PURPOSE: It is proposed that the sclera is a metabolically active and pharmacologically responsive tissue. These studies were undertaken to determine whether prostaglandin exposure can enhance scleral permeability to high-molecular-weight substances. METHODS: Topical prostaglandin F2 alpha (PGF2 alpha) was administered to monkeys to determine if this altered the amount of scleral matrix metalloproteinases (MMPs). Experiments also were performed to determine whether the prostaglandin F (FP) receptor and gene transcripts are expressed in normal human sclera. Permeability of organ-cultured human sclera following prostaglandin exposure then was studied and the amount of MMP released into the medium measured. Finally, the permeability of human sclera to basic fibroblast growth factor (FGF-2) was determined following prostaglandin exposure. RESULTS: Topical prostaglandin administration that reduced scleral collagen also increased scleral MMP-1, MMP-2, and MMP-3 by 63 +/- 35%, 267 +/- 210%, and 729 +/- 500%, respectively. FP receptor protein was localized in scleral fibroblasts, and FP receptor gene transcript was identified in sclera. Exposure to prostaglandin F2 alpha, 17-phenyltrinor, PGF2 alpha, or latanoprost acid increased scleral permeability by up to 124%, 183%, or 213%, respectively. In these cultures, MMP-1, MMP-2, and MMP-3 were increased by up to 37%, 267%, and 96%, respectively. Finally, transscleral absorption of FGF-2 was increased by up to 126% with scleral exposure to latanoprost. CONCLUSIONS: These studies demonstrate that the sclera is metabolically active and pharmacologically responsive to prostaglandins. Further, they demonstrate the feasibility of cotreatment with prostaglandin to enhance transscleral delivery of peptides, such as growth factors and high-molecular-weight substances, to the posterior segment of the eye. PMID:11797317

  9. 26 CFR 53.4941(f)-1 - Effective dates.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Effective dates. 53.4941(f)-1 Section 53.4941(f)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS... Effective dates. (a) In general. Except as provided in paragraph (b) of this section, §§...

  10. 26 CFR 48.6416(f)-1 - Credit on returns.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 16 2012-04-01 2012-04-01 false Credit on returns. 48.6416(f)-1 Section 48.6416... Special Application to Retailers and Manufacturers Taxes § 48.6416(f)-1 Credit on returns. Any person..., in lieu of claiming refund of the overpayment, claim credit for the overpayment on any return of...

  11. 26 CFR 48.6416(f)-1 - Credit on returns.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 16 2011-04-01 2011-04-01 false Credit on returns. 48.6416(f)-1 Section 48.6416... Special Application to Retailers and Manufacturers Taxes § 48.6416(f)-1 Credit on returns. Any person..., in lieu of claiming refund of the overpayment, claim credit for the overpayment on any return of...

  12. 26 CFR 48.6416(f)-1 - Credit on returns.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 16 2013-04-01 2013-04-01 false Credit on returns. 48.6416(f)-1 Section 48.6416... Special Application to Retailers and Manufacturers Taxes § 48.6416(f)-1 Credit on returns. Any person..., in lieu of claiming refund of the overpayment, claim credit for the overpayment on any return of...

  13. 26 CFR 48.6416(f)-1 - Credit on returns.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Credit on returns. 48.6416(f)-1 Section 48.6416... Special Application to Retailers and Manufacturers Taxes § 48.6416(f)-1 Credit on returns. Any person..., in lieu of claiming refund of the overpayment, claim credit for the overpayment on any return of...

  14. Charmless hadronic B →(f1(1285 ),f1(1420 ))P decays in the perturbative QCD approach

    NASA Astrophysics Data System (ADS)

    Liu, Xin; Xiao, Zhen-Jun; Li, Jing-Wu; Zou, Zhi-Tian

    2015-01-01

    We study 20 charmless hadronic B →f1P decays in the perturbative QCD (pQCD) formalism with B denoting Bu, Bd, and Bs mesons; P standing for the light pseudoscalar mesons; and f1 representing axial-vector mesons f1(1285 ) and f1(1420 ) that result from a mixing of quark-flavor f1 q[u/u ¯ +d d ¯ √{2 } ] and f1 s[s s ¯ ] states with the angle ϕf1.The estimations of C P -averaged branching ratios and C P asymmetries of the considered B →f1P decays, in which the Bs→f1P modes are investigated for the first time, are presented in the pQCD approach with ϕf 1˜24 ° from recently measured Bd /s→J /ψ f1(1285 ) decays. It is found that (a) the tree (penguin) dominant B+→f1π+(K+) decays with large branching ratios [O (10-6) ] and large direct C P violations (around 14%-28% in magnitude) simultaneously are believed to be clearly measurable at the LHCb and Belle II experiments; (b) the Bd→f1KS0 and Bs→f1(η ,η') decays with nearly pure penguin contributions and safely negligible tree pollution also have large decay rates in the order of 10-6- 10-5 , which can be confronted with the experimental measurements in the near future; (c) as the alternative channels, the B+→f1(π+,K+) and Bd→f1KS0 decays have the supplementary power in providing more effective constraints on the Cabibbo-Kobayashi-Maskawa weak phases α , γ , and β , correspondingly, which are explicitly analyzed through the large decay rates and the direct and mixing-induced C P asymmetries in the pQCD approach and are expected to be stringently examined by the measurements with high precision; (d) the weak annihilation amplitudes play important roles in the B+→f1(1420 )K+ , Bd→f1(1420 )KS0 , Bs→f1(1420 )η' decays, and so on, which would offer more evidence, once they are confirmed by the experiments, to identify the soft-collinear effective theory and the pQCD approach on the evaluations of annihilation diagrams and to help further understand the annihilation mechanism in the heavy

  15. A comparison of intraamniotic prostaglandin and extraamniotic prostaglandin gel for midtrimester termination of pregnancy.

    PubMed

    Smith, D H; Dalrymple, J C

    1983-02-01

    A comparison between midtrimester abortion induced by the intraamniotic injection of prostaglandin F2 alpha and abortion induced by prostaglandin F2 alpha in Tylose gel administered extraamniotically was made in a group of 40 patients. The induction-abortion interval in the extraamniotic group was 12.1 hours which was significantly shorter (P less than 0.001) than the intraamniotic group (27.6 hours). The placenta was expelled completely more often and there were no cervical lacerations using the extraamniotic method whereas 2 patients required repair of cervical lacerations after intraamniotic prostaglandin. Extraamniotic administration of prostaglandin F2 alpha in Tylose gel is recommended as a safe and more effective method for inducing midtrimester abortion than intraamniotic prostaglandin.

  16. Torsional elasticity and energetics of F1-ATPase.

    PubMed

    Czub, Jacek; Grubmüller, Helmut

    2011-05-03

    F(o)F(1)-ATPase is a rotary motor protein synthesizing ATP from ADP driven by a cross-membrane proton gradient. The proton flow through the membrane-embedded F(o) generates the rotary torque that drives the rotation of the asymmetric shaft of F(1). Mechanical energy of the rotating shaft is used by the F(1) catalytic subunit to synthesize ATP. It was suggested that elastic power transmission with transient storage of energy in some compliant part of the shaft is required for the observed high turnover rate. We used atomistic simulations to study the spatial distribution and structural determinants of the F(1) torsional elasticity at the molecular level and to comprehensively characterize the elastic properties of F(1)-ATPase. Our fluctuation analysis revealed an unexpected heterogeneity of the F(1) shaft elasticity. Further, we found that the measured overall torsional moduli of the shaft arise from two distinct contributions, the intrinsic elasticity and the effective potential imposed on the shaft by the catalytic subunit. Separation of these two contributions provided a quantitative description of the coupling between the rotor and the catalytic subunit. This description enabled us to propose a minimal quantitative model of the F(1) energetics along the rotary degrees of freedom near the resting state observed in the crystal structures. As opposed to the usually employed models where the motor mechanical progression is described by a single angular variable, our multidimensional treatment incorporates the spatially inhomogeneous nature of the shaft and its interactions with the stator and offers new insight into the mechanoenzymatics of F(1)-ATPase.

  17. Survey of the Asp f 1 allergen in office environments.

    PubMed

    Ryan, T J; Whitehead, L W; Connor, T H; Burau, K D

    2001-06-01

    Sick Building Syndrome remains a prevalent problem with patient complaints similar to typical allergy symptoms. Unlike household allergens typically found in domestic reservoirs, the allergen from a common fungus like Aspergillus fumigatus (i.e., Asp f 1) is conceivably widespread in the work environment. This project surveyed airborne levels of the Asp f 1 allergen in office and non-industrial occupational environments, as well as the dust reservoirs of A. fumigatus believed to be responsible for those levels. Airborne and bulk dust samples were collected, extracted, and assayed for Asp f 1. Concurrently, bulk dusts collected from the same locations were selectively cultured for A. fumigatus, and mesophilic fungi and bacteria. Samples were collected during both wet and dry climatological conditions from paired wet and dry building locations to examine the possibility of Asp f 1 increases due to fungal growth blooms. Very low levels of Asp f 1 were detected but only in the airborne samples (2/120 positive samples, with 3.6 ng/m3 and 1.8 ng/m3; LOD < 1.2 ng/m3). No dust samples showed even detectable traces of the allergen (LOD = 5 ng/g dust). Although A. fumigatus counts from dusts fluctuated significantly with exterior moisture events, analysis of wet versus dry period samples showed no differences in Asp f 1 levels. These results indicate that even in the presence of measurable fungal concentrations, background levels of Asp f 1 are low. Nonindustrial office buildings devoid of indoor air quality issues were not observed to have significant levels of the Asp f 1 allergen in the geographical region studied.

  18. Separation, identification, and estimation of prostaglandins.

    PubMed

    Shaw, J E; Ramwell, P W

    1969-01-01

    The procedures which may be and are being used to provide a basis for the analysis of submicrogram quantitities of prostaglandins are surveyed. Discussion is focused on the following: 1) sources of standards; 2) properties (effect of different pH values, effect of blood, metabolism, solubility); 3) extraction; 4) detection; 5) estimation (ultraviolet, optical rotatory dispersion, densitometry, radioimmunoassay, enzymatic assay, isotopic methods, bioassay); 6) separation of prostaglandins (separation of PGE, PGF, and PGA with PGB compounds, separation of PGA and PGB compounds, and separation of individual prostaglandins); and 6) structural identification. Methods of prostaglandin analysis, with the required sensitivity for application to individual tissue and fluid specimens, are still in the developmental state. Although prostaglandins may be ubiquitous throughout the animal kingdom, no systematic study of their distribution has been made to date. Recent work has shown that PGE1 has a potent effect on the formation of 3',5' cyclic adenosine monophosphate (cyclic AMP) which is widely believed to be an intracellular intermediate in hormone action.

  19. Effects of sulglycotide on endogenous prostaglandin synthesis in human antral mucosa.

    PubMed

    Calabrò, A; Orsini, B; Milani, S; Psilogenis, M; Surrenti, C

    1992-12-01

    The effect of sulglycotide, a polysulphated glycopeptide isolated from pig duodenum, on PGE2, 6-ketoPGF1 alpha and TxB2 production from isolated biopsy specimens of human antral mucosa was investigated in vitro, in comparison with carbenoxolone. In addition to a tendency toward increased PGE2 production just short of statistical significance, both sulglycotide and carbenoxolone significantly increased 6-ketoPGF1 alpha accumulation in the incubation medium. TxB2 levels were not significantly modified by the two drugs. Therefore, changes in the prostanoid production by human antral mucosa could, at least partially account for the cytoprotective effects of sulglycotide in man.

  20. The evolution of F1 postzygotic incompatibilities in birds.

    PubMed

    Price, Trevor D; Bouvier, Michelle M

    2002-10-01

    We analyzed the rate at which postzygotic incompatibilities accumulate in birds. Our purposes were to assess the role of intrinsic F1 hybrid infertility and inviability in the speciation process, and to compare rates of loss of fertility and viability between the sexes. Among our sample more than half the crosses between species in the same genus produce fertile hybrids. Complete loss of F1 hybrid fertility takes on the order of millions of years. Loss of F1 hybrid viability occurs over longer timescales than fertility: some viable hybrids have been produced between taxa that appear to have been separated for more than 55 my. There is strong support for Haldane's rule, with very few examples where the male has lower fitness than the female. However, in contrast to Drosophila, fertility of the homogametic sex in the F1 appears to be lost before viability of the heterogametic sex in the F1. We conclude that the time span of loss of intrinsic hybrid fertility and viability is often, but not always, longer than the time to speciation. Premating isolation is an important mechanism maintaining reproductive isolation in birds. In addition, other factors causing postzygotic reproductive isolation such as ecological causes of hybrid unfitness, reduced mating success of hybrids, and genetic incompatibilities in the F2s and backcrosses may often be involved in the speciation process.

  1. E2F1 — EDRN Public Portal

    Cancer.gov

    The E2F1 protein belongs to the E2F/DP family of transcription factors. E2F1 binds DNA cooperatively with dp (differentiation regulated transcription factor proteins)proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. E2F1 can mediate both cell proliferation and p53-dependent/independent apoptosis.

  2. Improvements on foF1 estimation at polar regions

    NASA Astrophysics Data System (ADS)

    Sabbagh, Dario; Scotto, Carlo; Sgrigna, Vittorio

    2016-04-01

    The analysis of a sample of polar ionograms reveals that the DuCharme and Petrie empirical formula often fails in the foF1 estimation at polar regions. A study of the discrepancies between modeled and observed foF1 values is presented, using a data set of Antarctic ionograms from different stations. Such discrepancies have been quantitatively evaluated. Based on this study a correction to the DuCharme and Petrie formula is proposed. This correction is performed to be implemented in an improved version of Autoscala software for a particular ionospheric station, in the frame of AUSPICIO (Automatic Interpretation of Polar Ionograms and Cooperative Ionospheric Observations) project.

  3. M2-F1 in flight on tow line

    NASA Technical Reports Server (NTRS)

    1964-01-01

    The M2-F1 Lifting Body is seen here under tow at the Flight Research Center (later redesignated the Dryden Flight Research Center), Edwards, California. The wingless, lifting-body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Flight Research Center management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The M2-F1 project had limited goals. They were to show that a piloted lifting body could be built, that it could not only fly but be controlled in flight, and that it could make a successful landing. While the M2-F1 did prove the concept, with a wooden fuselage and fixed landing gear, it was far from an operational spacecraft. The next step in the lifting-body development was to build a heavyweight, rocket-powered vehicle that was more like an operational lifting body, albeit one without the thermal protection system that would be needed for reentry into the atmosphere from space at near-orbital speeds. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. These initial tests produced enough flight data about the M2-F1 to proceed with flights behind a NASA C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to

  4. Prostaglandin-induced iridial pigmentation in primates.

    PubMed

    Selén, G; Stjernschantz, J; Resul, B

    1997-02-01

    Latanoprost, a new ocular hypotensive prostaglandin F2 alpha analogue prodrug, was found to induce increased pigmentation of monkey irides in chronic toxicity studies. This prompted us to investigate the effect of naturally occurring prostaglandins on the monkey iris to determine whether this pigmentary effect is unique for latanoprost or whether it is a class effect of prostaglandins. PGF2 alpha-isopropyl ester (IE), PGE2-IE and latanoprost were applied topically to cynomolgus monkey eyes for 18-44 weeks. One eye of each animal was treated, while the other served as control. In addition, latanoprost was applied to sympathectomized monkey eyes. PGF2 alpha-IE, PGE2-IE, as well as latanoprost, induced increased pigmentation in the monkey eye. The first signs of this effect were seen after about two months of treatment. Latanoprost also induced increased pigmentation in sympathectomized eyes. It is concluded that both naturally occurring prostaglandins and their synthetic analogues can induce increased iridial pigmentation in cynomolgus monkeys, and that the effect does not require the presence of sympathetic nerves.

  5. Prostaglandins and their receptors in insect biology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We treat the biological significance of prostaglandins (PGs) and their known receptors in insect biology. PGs and related eicosanoids are oxygenated derivatives of arachidonic acid (AA) and two other C20 polyunsaturated fatty acids. PGs are mostly appreciated in the context of biomedicine, but a gr...

  6. M2-F1 on lakebed with pilot Milt Thompson

    NASA Technical Reports Server (NTRS)

    1963-01-01

    NASA Flight Research Pilot Milt Thompson, shown here on the lakebed with the M2-F1 lifting body, was an early backer of R. Dale Reed's lifting-body proposal. He urged Flight Research Center director Paul Bikle to approve the M2-F1's construction. Thompson also made the first glide flights in both the M2-F1 and its successor, the heavyweight M2-F2. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, NASA Flight Research Center (later Dryden Flight Research Center, Edwards, CA) management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved

  7. M2-F1 ejection seat test at South Edwards

    NASA Technical Reports Server (NTRS)

    1963-01-01

    The M2-F1 was fitted with an ejection seat before the airtow flights began. The project selected the seat used in the T-37 as modified by the Weber Company to use a rocket rather than a ballistic charge for ejection. To test the ejection seat, the Flight Research Center's Dick Klein constructed a plywood mockup of the M2-F1's top deck and canopy. On the first firings, the test was unsuccessful, but on the final test the dummy in the seat landed safely. The M2-F1 ejection seat was later used in the two Lunar Landing Research Vehicles and the three Lunar Landing Training Vehicles. Three of them crashed, but in each case the pilot ejected from the vehicle successfully. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with

  8. Robustness of the rotary catalysis mechanism of F1-ATPase.

    PubMed

    Watanabe, Rikiya; Matsukage, Yuki; Yukawa, Ayako; Tabata, Kazuhito V; Noji, Hiroyuki

    2014-07-11

    F1-ATPase (F1) is the rotary motor protein fueled by ATP hydrolysis. Previous studies have suggested that three charged residues are indispensable for catalysis of F1 as follows: the P-loop lysine in the phosphate-binding loop, GXXXXGK(T/S); a glutamic acid that activates water molecules for nucleophilic attack on the γ-phosphate of ATP (general base); and an arginine directly contacting the γ-phosphate (arginine finger). These residues are well conserved among P-loop NTPases. In this study, we investigated the role of these charged residues in catalysis and torque generation by analyzing alanine-substituted mutants in the single-molecule rotation assay. Surprisingly, all mutants continuously drove rotary motion, even though the rotational velocity was at least 100,000 times slower than that of wild type. Thus, although these charged residues contribute to highly efficient catalysis, they are not indispensable to chemo-mechanical energy coupling, and the rotary catalysis mechanism of F1 is far more robust than previously thought.

  9. Robustness of the Rotary Catalysis Mechanism of F1-ATPase*

    PubMed Central

    Watanabe, Rikiya; Matsukage, Yuki; Yukawa, Ayako; Tabata, Kazuhito V.; Noji, Hiroyuki

    2014-01-01

    F1-ATPase (F1) is the rotary motor protein fueled by ATP hydrolysis. Previous studies have suggested that three charged residues are indispensable for catalysis of F1 as follows: the P-loop lysine in the phosphate-binding loop, GXXXXGK(T/S); a glutamic acid that activates water molecules for nucleophilic attack on the γ-phosphate of ATP (general base); and an arginine directly contacting the γ-phosphate (arginine finger). These residues are well conserved among P-loop NTPases. In this study, we investigated the role of these charged residues in catalysis and torque generation by analyzing alanine-substituted mutants in the single-molecule rotation assay. Surprisingly, all mutants continuously drove rotary motion, even though the rotational velocity was at least 100,000 times slower than that of wild type. Thus, although these charged residues contribute to highly efficient catalysis, they are not indispensable to chemo-mechanical energy coupling, and the rotary catalysis mechanism of F1 is far more robust than previously thought. PMID:24876384

  10. Stiffness of γ subunit of F(1)-ATPase.

    PubMed

    Okuno, Daichi; Iino, Ryota; Noji, Hiroyuki

    2010-11-01

    F(1)-ATPase is a molecular motor in which the γ subunit rotates inside the α(3)β(3) ring upon adenosine triphosphate (ATP) hydrolysis. Recent works on single-molecule manipulation of F(1)-ATPase have shown that kinetic parameters such as the on-rate of ATP and the off-rate of adenosine diphosphate (ADP) strongly depend on the rotary angle of the γ subunit (Hirono-Hara et al. 2005; Iko et al. 2009). These findings provide important insight into how individual reaction steps release energy to power F(1) and also have implications regarding ATP synthesis and how reaction steps are reversed upon reverse rotation. An important issue regarding the angular dependence of kinetic parameters is that the angular position of a magnetic bead rotation probe could be larger than the actual position of the γ subunit due to the torsional elasticity of the system. In the present study, we assessed the stiffness of two different portions of F(1) from thermophilic Bacillus PS3: the internal part of the γ subunit embedded in the α(3)β(3) ring, and the complex of the external part of the γ subunit and the α(3)β(3) ring (and streptavidin and magnetic bead), by comparing rotational fluctuations before and after crosslinkage between the rotor and stator. The torsional stiffnesses of the internal and remaining parts were determined to be around 223 and 73 pNnm/radian, respectively. Based on these values, it was estimated that the actual angular position of the internal part of the γ subunit is one-fourth of the magnetic bead position upon stalling using an external magnetic field. The estimated elasticity also partially explains the accommodation of the intrinsic step size mismatch between F(o) and F(1)-ATPase.

  11. M2-F1 in hangar with Pontiac tow vehicle

    NASA Technical Reports Server (NTRS)

    1963-01-01

    The M2-F1 Lifting Body is seen here in a hangar with its hotrod Pontiac convertible tow vehicle at the Flight Research Center (later the Dryden Flight Research Center), Edwards, California. The car was a 1963 Pontiac Catalina convertible, fitted with a 421-cubic-inch tripower engine like those being run at the Daytona 500 auto race. The vehicle also had a four-speed transmission and a heavy-duty suspension and cooling system. A roll bar was also added and the passenger seat turned around so an observer could watch the M2-F1 while it was being towed. The rear seat was removed and a second, side-facing seat installed. The lifting-body team used the Pontiac for all the ground-tow flights over the next three years. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey

  12. Internal steel structure of M2-F1

    NASA Technical Reports Server (NTRS)

    1963-01-01

    The internal steel structure for the M2-F1 was built at the Flight Research Center (predecessor of the Dryden Flight Research Center, Edwards, CA) in a section of the calibration hangar dubbed 'Wright Bicycle Shop.' Visible are the stick, rudder pedals, and ejection seat. The external wooden shell was attached to the steel structure. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne to prove it could fly

  13. Effects of prostaglandins and prostaglandin synthesis inhibitors on sexual behavior in boars.

    PubMed

    Estienne, Mark J; Harper, Allen F; Beal, Wilfred E; Crawford, Russell J

    2007-07-01

    Experiments were conducted investigating the effects of prostaglandins and prostaglandin synthesis inhibitors on libido in boars. In Experiment 1, two prostaglandin products were compared with regard to expediting the training of boars for semen collection. On each of five consecutive days, boars received i.m. treatment with saline, dinoprost tromethamine or cloprostenol sodium (n=12/group). On each of day 1 (p=0.06), day 2 (p<0.05), and day 3 (p<0.05), but not on day 4 or 5 (p>0.1), the percentage of boars collected after dinoprost tromethamine, but not cloprostenol sodium, was greater than controls. In Experiments 2 and 3, libido in boars that were trained previously for semen collection was assessed after treatment with prostaglandin synthesis inhibitors, testing the hypothesis that endogenous release of prostaglandin is necessary for expression of sexual behaviors. In Experiment 2, boars treated with flunixin meglumine (n=12) had suppressed (p<0.01) levels of 15-ketodihydro-prostaglandin-F(2) (PGFM) in serum but characteristics of libido were similar (p>0.1) to controls (n=12). In Experiment 3, boars were administered indomethacin orally (n=12) or served as untreated controls (n=12). Indomethacin decreased (p<0.01) serum levels of PGFM, increased (p<0.05) the number of false mounts (mounting artificial sow but dismounting before an ejaculate was collected), and tended (p=0.09) to lengthen the interval between entering the collection pen and the start of ejaculation. These results suggest that prostaglandin synthesis and release is necessary for the complete display of normal sexual behaviors in boars.

  14. Construction Progress of the F-1 Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the stand itself, related facilities were constructed during this time. North of the massive S-IC test stand, the F-1 Engine test stand was built. Designed to assist in the development of the F-1 Engine, the F-1 test stand is a vertical engine firing test stand, 239 feet in elevation and 4,600 square feet in area at the base. Capability was provided for static firing of 1.5 million pounds of thrust using liquid oxygen and kerosene. Like the S-IC stand, the foundation of the F

  15. Construction Progress of the F-1 Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. North of the massive S-IC test stand, the F-1 Engine test stand was built. Designed to assist in the development of the F-1 Engine, the F-1 test stand is a vertical engine firing test stand, 239 feet in elevation and 4,600 square feet in area at the base. Capability was provided for static firing of 1.5 million pounds of thrust using liquid oxygen and kerosene. Like the S-IC stand, the foundation of the F-1 stand is keyed into the bedrock approximately 40 feet below grade. This photo, taken

  16. Construction Progress of the F-1 Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the stand itself, related facilities were constructed during this time. North of the massive S-IC test stand, the F-1 Engine test stand was built. Designed to assist in the development of the F-1 Engine, the F-1 test stand is a vertical engine firing test stand, 239 feet in elevation and 4,600 square feet in area at the base. Capability was provided for static firing of 1.5 million pounds of thrust using liquid oxygen and kerosene. Like the S-IC stand, the foundation of the F

  17. Construction Progress of the F-1 Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. North of the massive S-IC test stand, the F-1 Engine test stand was built. Designed to assist in the development of the F-1 Engine, the F-1 test stand is a vertical engine firing test stand, 239 feet in elevation and 4,600 square feet in area at the base. Capability was provided for static firing of 1.5 million pounds of thrust using liquid oxygen and kerosene. Like the S-IC stand, the foundation of the F-1 stand is keyed into the bedrock approximately 40 feet below grade. This photo depicts

  18. Construction Progress of the F-1 Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. North of the massive S-IC test stand, the F-1 Engine test stand was built. Designed to assist in the development of the F-1 Engine, the F-1 test stand is a vertical engine firing test stand, 239 feet in elevation and 4,600 square feet in area at the base. Capability was provided for static firing of 1.5 million pounds of thrust using liquid oxygen and kerosene. Like the S-IC stand, the foundation of the F-1 stand is keyed into the bedrock approximately 40 feet below grade. This photo, taken

  19. Construction Progress of the F-1 Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the stand itself, related facilities were constructed during this time. North of the massive S-IC test stand, the F-1 Engine test stand was built. Designed to assist in the development of the F-1 Engine, the F-1 test stand is a vertical engine firing test stand, 239 feet in elevation and 4,600 square feet in area at the base. Capability was provided for static firing of 1.5 million pounds of thrust using liquid oxygen and kerosene. Like the S-IC stand, the foundation of the F

  20. Construction Progress of the F-1 Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the stand itself, related facilities were constructed during this time. Northeast of the massive S-IC test stand, the F-1 Engine test stand was built. The F-1 test stand is a vertical engine firing test stand, 239 feet in elevation and 4,600 square feet in area at the base, and was designed to assist in the development of the F-1 Engine. Capability was provided for static firing of 1.5 million pounds of thrust using liquid oxygen and kerosene. Like the S-IC stand, the

  1. Construction Progress of the F-1 Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. North of the massive S-IC test stand, the F-1 Engine test stand was built. Designed to assist in the development of the F-1 Engine, the F-1 test stand is a vertical engine firing test stand, 239 feet in elevation and 4,600 square feet in area at the base. Capability was provided for static firing of 1.5 million pounds of thrust using liquid oxygen and kerosene. Like the S-IC stand, the foundation of the F-1 stand is keyed into the bedrock approximately 40 feet below grade. This photo shows

  2. Construction Progress of the F-1 Test Stand

    NASA Technical Reports Server (NTRS)

    1962-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the stand itself, related facilities were constructed during this time. North of the massive S-IC test stand, the F-1 Engine test stand was built. Designed to assist in the development of the F-1 Engine, the F-1 test stand is a vertical engine firing test stand, 239 feet in elevation and 4,600 square feet in area at the base. Capability was provided for static firing of 1.5 million pounds of thrust using liquid oxygen and kerosene. Like the S-IC stand, the foundation of the F

  3. Construction Progress of the F-1 Engine Test Stand

    NASA Technical Reports Server (NTRS)

    1962-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the S-IC test stand, related facilities were built during this time. Built to the north of the massive S-IC test stand, was the F-1 Engine test stand. The F-1 test stand, a vertical engine firing test stand, 239 feet in elevation and 4,600 square feet in area at the base, was designed to assist in the development of the F-1 Engine. Capability was provided for static firing of 1.5 million pounds of thrust using liquid oxygen and kerosene. Like the S-IC stand, the foundation of

  4. Construction Progress of the F-1 Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the S-IC test stand, related facilities were constructed during this time frame. Built just north of the massive S-IC test stand was the F-1 Engine test stand. The F-1 test stand is a vertical engine firing test stand, 239 feet in elevation and 4,600 square feet in area at the base, and was designed to assist in the development of the F-1 Engine. Capability was provided for static firing of 1.5 million pounds of thrust using liquid oxygen and kerosene. Like the S-IC stand, the

  5. Dysregulation of FURIN by prostaglandin-endoperoxide synthase 2 in lung epithelial NCI-H292 cells.

    PubMed

    Brant, Kelly A; Leikauf, George D

    2014-03-01

    Because proprotein convertases (PCSKs) activate growth factors and matrix metalloproteinase, these enzymes have been implicated in non-small cell lung cancer tumor progression and aggressiveness. Previous studies indicate that one PCSK member, FURIN is overexpressed in NSCLC, but little is known regarding the mechanisms driving PCSKs expression during malignant change. We sought to determine whether prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (PTGS2) (aka COX2), whose expression is also frequently increased in NSCLC, differentially regulates PCSK expression and activity between normal (NHBE) and NSCLC epithelial cells (NCI-H292, NCI-H441, A549). NSCLC cells exhibit significantly greater cell-associated and secreted PCSK activity as compared with NHBE. The heightened activity is consistent with increased FURIN, PCSK4, and PCSK6 protein in the NCSLC cells. Inhibition of PTGS2 activity using NS-398 and siRNA decreased FURIN mRNA, protein, activity along with cell proliferation in NCI-H292 cells but not NHBE cells. NSCLC also expressed elevated levels of the transcription factor E2F1. When NCI-H292 cells were transfected with E2F1 siRNA, both PTGS2 expression and PCSK activity were attenuated, arguing a pivotal role for E2F1 in the differential regulation of PCSKs by PTGS2. Our results highlight a novel role for PTGS2 in NSCLC and may provide a mechanism, whereby PTGS2 inhibitors suppress lung cancer cell growth.

  6. Regulation of the thermoalkaliphilic F1-ATPase from Caldalkalibacillus thermarum

    PubMed Central

    Ferguson, Scott A.; Cook, Gregory M.; Montgomery, Martin G.; Leslie, Andrew G. W.

    2016-01-01

    The crystal structure has been determined of the F1-catalytic domain of the F-ATPase from Caldalkalibacillus thermarum, which hydrolyzes adenosine triphosphate (ATP) poorly. It is very similar to those of active mitochondrial and bacterial F1-ATPases. In the F-ATPase from Geobacillus stearothermophilus, conformational changes in the ε-subunit are influenced by intracellular ATP concentration and membrane potential. When ATP is plentiful, the ε-subunit assumes a “down” state, with an ATP molecule bound to its two C-terminal α-helices; when ATP is scarce, the α-helices are proposed to inhibit ATP hydrolysis by assuming an “up” state, where the α-helices, devoid of ATP, enter the α3β3-catalytic region. However, in the Escherichia coli enzyme, there is no evidence that such ATP binding to the ε-subunit is mechanistically important for modulating the enzyme’s hydrolytic activity. In the structure of the F1-ATPase from C. thermarum, ATP and a magnesium ion are bound to the α-helices in the down state. In a form with a mutated ε-subunit unable to bind ATP, the enzyme remains inactive and the ε-subunit is down. Therefore, neither the γ-subunit nor the regulatory ATP bound to the ε-subunit is involved in the inhibitory mechanism of this particular enzyme. The structure of the α3β3-catalytic domain is likewise closely similar to those of active F1-ATPases. However, although the βE-catalytic site is in the usual “open” conformation, it is occupied by the unique combination of an ADP molecule with no magnesium ion and a phosphate ion. These bound hydrolytic products are likely to be the basis of inhibition of ATP hydrolysis. PMID:27621435

  7. Mechanically driven ATP synthesis by F1-ATPase

    NASA Astrophysics Data System (ADS)

    Itoh, Hiroyasu; Takahashi, Akira; Adachi, Kengo; Noji, Hiroyuki; Yasuda, Ryohei; Yoshida, Masasuke; Kinosita, Kazuhiko

    2004-01-01

    ATP, the main biological energy currency, is synthesized from ADP and inorganic phosphate by ATP synthase in an energy-requiring reaction. The F1 portion of ATP synthase, also known as F1-ATPase, functions as a rotary molecular motor: in vitro its γ-subunit rotates against the surrounding α3β3 subunits, hydrolysing ATP in three separate catalytic sites on the β-subunits. It is widely believed that reverse rotation of the γ-subunit, driven by proton flow through the associated Fo portion of ATP synthase, leads to ATP synthesis in biological systems. Here we present direct evidence for the chemical synthesis of ATP driven by mechanical energy. We attached a magnetic bead to the γ-subunit of isolated F1 on a glass surface, and rotated the bead using electrical magnets. Rotation in the appropriate direction resulted in the appearance of ATP in the medium as detected by the luciferase-luciferin reaction. This shows that a vectorial force (torque) working at one particular point on a protein machine can influence a chemical reaction occurring in physically remote catalytic sites, driving the reaction far from equilibrium.

  8. Modulation of macrophage activation by prostaglandins

    PubMed Central

    Carnuccio, R.; D'Acquisto, F.; Rosa, M. Di

    1996-01-01

    The effect of prostaglandtn E2, iloprost and cAMP on both nitric oxide and tumour necrosis factor-α release in J774 macrophages has been studied. Both prostaglandin E2 and iloprost inhibited, in a concentration-dependent fashion, the lipopolysaccharide-induced generation of nitric oxide and tumour necrosis factor-α. The inhibitory effect of these prostanoids seems to be mediated by an increase of the second messenger cAMP since it was mimicked by dibutyryl cAMP and potentiated by the selective type IV phosphodiesterase inhibitor RO-20-1724. Our results suggest that the inhibition of nitric oxide release by prostaglandin E2 and iloprost in lipopolysaccharide-activated J774 macrophages may be secondary to the inhibition of tumour necrosis factor-α generation, which in turn is likely to be mediated by cAMP. PMID:18475691

  9. Animal-like prostaglandins in marine microalgae.

    PubMed

    Di Dato, Valeria; Orefice, Ida; Amato, Alberto; Fontanarosa, Carolina; Amoresano, Angela; Cutignano, Adele; Ianora, Adrianna; Romano, Giovanna

    2017-03-28

    Diatoms are among the most successful primary producers in ocean and freshwater environments. Deriving from a secondary endosymbiotic event, diatoms have a mixed genome containing bacterial, animal and plant genes encoding for metabolic pathways that may account for their evolutionary success. Studying the transcriptomes of two strains of the diatom Skeletonema marinoi, we report, for the first time in microalgae, an active animal-like prostaglandin pathway that is differentially expressed in the two strains. Prostaglandins are hormone-like mediators in many physiological and pathological processes in mammals, playing a pivotal role in inflammatory responses. They are also present in macroalgae and invertebrates, where they act as defense and communication mediators. The occurrence of animal-like prostaglandins in unicellular photosynthetic eukaryotes opens up new intriguing perspectives on the evolution and role of these molecules in the marine environment as possible mediators in cell-to-cell signaling, eventually influencing population dynamics in the plankton.The ISME Journal advance online publication, 28 March 2017; doi:10.1038/ismej.2017.27.

  10. Prostaglandin synthesis inhibition and postprandial intestinal hyperemia.

    PubMed

    Gallavan, R H; Chou, C C

    1982-02-01

    The effect of prostaglandin synthesis inhibition on the postprandial intestinal hyperemia was examined in the jejunum of anesthetized dogs. Both intravenous and intra-arterial infusion of the cyclooxygenase inhibitors indomethacin and mefenamic acid reduced resting jejunal blood flow and markedly enhanced the food-induced jejunal hyperemia. The jejunal vascular response to food did not change after either intravenous or intra-arterial infusion of the carrier solutions or intra-arterial infusion of angiotensin II. The enhancement of the jejunal hyperemia was associated with an increase in the food-induced increase in jejunal oxygen consumption. Infusion of the cyclooxygenase inhibitors increased the mean amplitude of the monophasic intestinal contractions; however, this did not appear to play a role in the enhancement of the food-induced hyperemia. The study indicates that inhibition of prostaglandin synthesis has a marked effect on the postprandial intestinal hyperemia and that this may be due to its enhancement of the jejunal metabolic response to food. The prostaglandins involved and their mechanism of action are unknown.

  11. Prostaglandin synthesis in human T cells: its partial inhibition by lectins and anti-CD3 antibodies as a possible step in T cell activation.

    PubMed

    Aussel, C; Mary, D; Fehlmann, M

    1987-05-15

    The human leukemic T cell line Jurkat was used to study arachidonic acid (AA) metabolism. We demonstrated that Jurkat cells are able to convert AA into prostaglandins (PG) and thromboxanes. The presence of tritiated 6-keto-PGF1 alpha, PGE2, PGA2 (B2), and thromboxane B2 in the culture medium was shown either by thin-layer chromatography after a 4-hr incubation period of [3H]AA-prelabeled Jurkat cells or by using specific radioimmuno assays. PG synthesis was inhibited by both indomethacin and niflumic acid, two cyclooxygenase inhibitors. AA metabolism through the cyclooxygenase pathway was followed during T cell activation. T cells were activated by lectins or anti-CD3 monoclonal antibodies (mAb) to trigger the T3-Ti complex and by 12-0-tetradecanoylphorbol 13-acetate (TPA) to mimic IL 1-dependent pathways. Our results show that lectins and anti-CD3 mAb both reduce the amount of PG released by the cells, whereas TPA did not. We confirmed that a combination of TPA and lectins or TPA and anti-CD3 mAb is necessary to obtain full activation of Jurkat cells if this event is monitored by using measurement of IL 2 synthesis. In addition, lectins and anti-CD3 mAb can be replaced by the cyclooxygenase inhibitors indomethacin or niflumic acid. Indeed, a combination of TPA and one of these two drugs induced maximal IL 2 synthesis. These results thus suggest that a reduction in PG synthesis might be a prerequisite to allow the cascade of events involved in T cell activation.

  12. Effects of a novel Hungarian antacid containing Al and Mg (Tisacid) on mucosal prostaglandin generation and oxygen free radicals in normal rats.

    PubMed

    Nagy, L; Mózsik, G; Vincze, A; Süto G; Hunyady, B; Rinfel, J; Past, T; Jávor, T

    1990-01-01

    A new patented chemical agent (Al-Mg-hydroxy-carbonate; acid-binding capacity greater than 30 mmol/g) was produced by our work-team. After our preliminary pharmacological and some prospective, randomized, multicentre, controlled clinical studies, this antacid was registered (Tisacid tablet and suspension; Alkaloida, Hungary). A cumulative ulcer healing rate of 80-85% was proved by Tisacid monotherapy applied in low doses (from 80 to 160 mmol/day) in patients with duodenal ulcer. The aims of this study were: (i) to determine the role of different antacids on the genesis of mucosal prostaglandins (PGs) (PGE2 and 6-keto-PGF1 alpha) in normal rats; (ii) to evaluate the effects of indomethacin pre-treatment (20 mg/kg b.w.,s.c.) on the Tisacid-induced alterations of gastric mucosal PG-contents; (iii) to analyse the generation of oxygen free radicals and lipid peroxidation in the rat oxyntic mucosa by the application of different doses of Tisacid (activities of CAT, GSH-px and SOD, contents of MDA and red. GSH). It was found that: Tisacid has a potent gastroproprotective effect in gastric mucosa, via (a) an increase in the mucosal levels of PGs, and (b) a scavenging-like effect in normal rat gastric mucosa. It is concluded that the gastroprotective effect of Tisacid appears because of the following: (i) excellent acid-neutralizing capacity; (ii) mucosal generation of PGs (PGE2 and PGI2); (iii) free radical scavenging; (iv) its possible activity as a Ca-antagonist (Mg-containing compound).

  13. Prostaglandin E2 Regulation of Chondrocyte Proliferation and Differentiation

    DTIC Science & Technology

    1994-05-01

    increases bone prostaglandin E. Effect of acetylsalicylic acid on disuse osteoporosis studied in dogs. Acta Orthopaedica Scandinavica, 62:238-243. 121...bovine serum, 1% antibiotics, and 50 pg/ml ascorbic acid in 100% humidity at 37oC. Prostaglandin E2 was added to confluent, fourth passage cultures... acid from membrane phospholipids. This, in turn, may lead to the formation of prostaglandins, thromboxanes and prostacyclins through the metabolism of

  14. Cyclooxygenase-2 induced β1-integrin expression in NSCLC and promoted cell invasion via the EP1/MAPK/E2F-1/FoxC2 signal pathway

    PubMed Central

    Pan, Jinshun; Yang, Qinyi; Shao, Jiaofang; Zhang, Li; Ma, Juan; Wang, Yipin; Jiang, Bing-Hua; Leng, Jing; Bai, Xiaoming

    2016-01-01

    Cyclooxygenase-2 (COX-2) has been implicated in cell invasion in non-small-cell lung cancer (NSCLC). However, the mechanism is unclear. The present study investigated the effect of COX-2 on β1-integrin expression and cell invasion in NSCLC. COX-2 and β1-integrin were co-expressed in NSCLC tissues. COX-2 overexpression or Prostaglandin E2 (PGE2) treatment increased β1-integrin expression in NSCLC cell lines. β1-integrin silencing suppressed COX-2-mediated tumour growth and cancer cell invasion in vivo and in vitro. Prostaglandin E Receptor EP1 transfection or treatment with EP1 agonist mimicked the effect of PGE2 treatment. EP1 siRNA blocked PGE2-mediated β1-integrin expression. EP1 agonist treatment promoted Erk1/2, p38 phosphorylation and E2F-1 expression. MEK1/2 and p38 inhibitors suppressed EP1-mediated β1-integrin expression. E2F-1 silencing suppressed EP1-mediated FoxC2 and β1-integrin upregulation. ChIP and Luciferase Reporter assays identified that EP1 agonist treatment induced E2F-1 binding to FoxC2 promotor directly and improved FoxC2 transcription. FoxC2 siRNA suppressed β1-integrin expression and EP1-mediated cell invasion. Immunohistochemistry showed E2F-1, FoxC2, and EP1R were all highly expressed in the NSCLC cases. This study suggested that COX-2 upregulates β1-integrin expression and cell invasion in NSCLC by activating the MAPK/E2F-1 signalling pathway. Targeting the COX-2/EP1/PKC/MAPK/E2F-1/FoxC2/β1-integrin pathway might represent a new therapeutic strategy for the prevention and treatment of this cancer. PMID:27654511

  15. Extra-amniotic prostaglandin E2 and the unfavourable cervix.

    PubMed

    Shepherd, J; Sims, C; Craft, I

    1976-10-02

    A small dose of prostaglandin E2 suspended in a viscous medium was instilled as a single application into the extra-amniotic space of patients with unfavourable induction features the day before planned induction in an attempt to improve the condition of the cervix. Two groups of 15 patients were studied, one receiving prostaglandin E2 250 mug suspended in methyl ethyl cellulose ('Tylose') 6% solution, and the other tylose alone. Cervical status did not change in those receiving tylose alone, whereas a significant improvement occurred in 14 out of 15 patients receiving the prostaglandin. Labour began before formal induction in 1 patient receiving tylose and in 8 receiving prostaglandin.

  16. Photoproduction of the f1(1285 ) meson

    NASA Astrophysics Data System (ADS)

    Dickson, R.; Schumacher, R. A.; Adhikari, K. P.; Akbar, Z.; Amaryan, M. J.; Anefalos Pereira, S.; Badui, R. A.; Ball, J.; Battaglieri, M.; Batourine, V.; Bedlinskiy, I.; Biselli, A.; Boiarinov, S.; Briscoe, W. J.; Burkert, V. D.; Cao, T.; Carman, D. S.; Celentano, A.; Chandavar, S.; Charles, G.; Chetry, T.; Ciullo, G.; Colaneri, L.; Cole, P. L.; Compton, N.; Contalbrigo, M.; Cortes, O.; Crede, V.; D'Angelo, A.; Dashyan, N.; De Vita, R.; De Sanctis, E.; Deur, A.; Djalali, C.; Dugger, M.; Dupre, R.; El Alaoui, A.; El Fassi, L.; Eugenio, P.; Fanchini, E.; Fedotov, G.; Filippi, A.; Fleming, J. A.; Gevorgyan, N.; Ghandilyan, Y.; Gilfoyle, G. P.; Giovanetti, K. L.; Girod, F. X.; Gothe, R. W.; Griffioen, K. A.; Guo, L.; Hafidi, K.; Hakobyan, H.; Hanretty, C.; Harrison, N.; Hattawy, M.; Holtrop, M.; Hicks, K.; Hughes, S. M.; Ilieva, Y.; Ireland, D. G.; Ishkhanov, B. S.; Isupov, E. L.; Jiang, H.; Jo, H. S.; Joosten, S.; Keller, D.; Khachatryan, G.; Khandaker, M.; Kim, A.; Kim, W.; Klein, F. J.; Kubarovsky, V.; Kuleshov, S. V.; Lanza, L.; Lenisa, P.; Livingston, K.; Lu, H. Y.; MacGregor, I. J. D.; Mattione, P.; McKinnon, B.; Meyer, C. A.; Mirazita, M.; Markov, N.; Mokeev, V.; Moriya, K.; Munevar, E.; Murdoch, G.; Nadel-Turonski, P.; Net, L. A.; Ni, A.; Osipenko, M.; Ostrovidov, A. I.; Park, K.; Pasyuk, E.; Phelps, W.; Pisano, S.; Pogorelko, O.; Price, J. W.; Prok, Y.; Puckett, A. J. R.; Raue, B. A.; Ripani, M.; Rizzo, A.; Rosner, G.; Roy, P.; Salgado, C.; Seder, E.; Sharabian, Y. G.; Skorodumina, Iu.; Smith, E. S.; Smith, G. D.; Sober, D.; Sokhan, D.; Sparveris, N.; Stepanyan, S.; Strakovsky, I. I.; Stankovic, I.; Strauch, S.; Sytnik, V.; Taiuti, M.; Ungaro, M.; Voskanyan, H.; Voutier, E.; Walford, N. K.; Watts, D. P.; Weygand, D.; Wood, M. H.; Zachariou, N.; Zana, L.; Zhang, J.; Zonta, I.; CLAS Collaboration

    2016-06-01

    The f1(1285 ) meson with mass 1281.0 ±0.8 MeV/c2 and width 18.4 ±1.4 MeV (full width at half maximum) was measured for the first time in photoproduction from a proton target using CLAS at Jefferson Lab. Differential cross sections were obtained via the η π+π-,K+K¯0π- , and K-K0π+ decay channels from threshold up to a center-of-mass energy of 2.8 GeV. The mass, width, and an amplitude analysis of the η π+π- final-state Dalitz distribution are consistent with the axial-vector JP=1+ f1(1285 ) identity, rather than the pseudoscalar 0- η (1295 ) . The production mechanism is more consistent with s -channel decay of a high-mass N* state and not with t -channel meson exchange. Decays to η π π go dominantly via the intermediate a0±(980 ) π∓ states, with the branching ratio Γ [a0π (noK ¯K )] /Γ [η π π (all)] =0.74 ±0.09 . The branching ratios Γ (K K ¯π ) /Γ (η π π ) =0.216 ±0.033 and Γ (γ ρ0) /Γ (η π π ) =0.047 ±0.018 were also obtained. The first is in agreement with previous data for the f1(1285 ) , while the latter is lower than the world average.

  17. Cleanup Verification Package for the 118-F-1 Burial Ground

    SciTech Connect

    E. J. Farris and H. M. Sulloway

    2008-01-10

    This cleanup verification package documents completion of remedial action for the 118-F-1 Burial Ground on the Hanford Site. This burial ground is a combination of two locations formerly called Minor Construction Burial Ground No. 2 and Solid Waste Burial Ground No. 2. This waste site received radioactive equipment and other miscellaneous waste from 105-F Reactor operations, including dummy elements and irradiated process tubing; gun barrel tips, steel sleeves, and metal chips removed from the reactor; filter boxes containing reactor graphite chips; and miscellaneous construction solid waste.

  18. 16 CFR Appendix F1 to Part 305 - Standard Clothes Washers

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Standard Clothes Washers F1 Appendix F1 to... LABELING RULEâ) Pt. 305, App. F1 Appendix F1 to Part 305—Standard Clothes Washers Range Information “Standard” includes all household clothes washers with a tub capacity of 1.6 cu. ft. or more. Capacity...

  19. M2-F1 under tow across lakebed by car

    NASA Technical Reports Server (NTRS)

    1963-01-01

    This 20-second clip shows the M2-F1 being towed by the Pontiac across Rogers Dry Lakebed. The M2-F1 lifting body, dubbed the 'flying bathtub' by the media, was the precursor of a remarkable series of wingless flying vehicles that contributed data used in the Space Shuttles, the X-33 Advanced Technology Demonstrator for the next century's Reusable Launch Vehicle, and the X-38 Technology Demonstrator for crew return from the International Space Station. Based on the ideas and basic design of Alfred J. Eggers and others at the Ames Aeronautical Laboratory (now the Ames Research Center), Mountain View, California, in the mid-1950's, the M2-F1 was built in 1962-63 over a four-month period for a cost of only about $30,000, plus an additional $8,000-$10,000 for an ejection seat. Engineers and technicians at the NASA Flight Research Center (now NASA Dryden) kept costs low by designing and fabricating it partly in-house, with the plywood shell constructed by a local sailplane builder. Someone at the time estimated that it would have cost a major aircraft company $150,000 to build the same vehicle. Unlike the later lifting bodies, the M2-F1 was unpowered and was initially towed by a souped-up Pontiac convertible until it was airborne. Later a C-47 took over the towing duties. Flown by such famous research pilots as Milt Thompson, Bruce Peterson, Chuck Yeager, and Bill Dana, the lightweight flying bathtub demonstrated that a wingless vehicle shaped for reentry into the Earth's atmosphere from space could be flown and landed safely. Flown from 1963 to 1966, the lightweight M2-F1 paved the way for the heavyweight M2-F2, M2`F3, HL-10, X-24A, and X-24B lifting bodies that flew under rocket power after launch from a B-52 mothership. The heavyweights flew from 1966 to 1975, demonstrating the viability and versatility of the wingless configuration and the ability of a vehicle with low lift-over-drag characteristics to fly to high altitudes and then to land precisely with their

  20. UVB light upregulates prostaglandin synthases and prostaglandin receptors in mouse keratinocytes

    SciTech Connect

    Black, Adrienne T.; Gray, Joshua P.; Shakarjian, Michael P.; Mishin, Vladimir; Laskin, Debra L.; Heck, Diane E.; Laskin, Jeffrey D.

    2008-10-01

    Prostaglandins belong to a class of cyclic lipid-derived mediators synthesized from arachidonic acid via COX-1, COX-2 and various prostaglandin synthases. Members of this family include prostaglandins such as PGE{sub 2}, PGF{sub 2{alpha}}, PGD{sub 2} and PGI{sub 2} (prostacyclin) as well as thromboxane. In the present studies we analyzed the effects of UVB on prostaglandin production and prostaglandin synthase expression in primary cultures of undifferentiated and calcium-differentiated mouse keratinocytes. Both cell types were found to constitutively synthesize PGE{sub 2}, PGD{sub 2} and the PGD{sub 2} metabolite PGJ{sub 2}. Twenty-four hours after treatment with UVB (25 mJ/cm{sup 2}), production of PGE{sub 2} and PGJ{sub 2} increased, while PGD{sub 2} production decreased. This was associated with increased expression of COX-2 mRNA and protein. UVB (2.5-25 mJ/cm{sup 2}) also caused marked increases in mRNA expression for the prostanoid synthases PGDS, mPGES-1, mPGES-2, PGFS and PGIS, as well as expression of receptors for PGE{sub 2} (EP1 and EP2), PGD{sub 2} (DP and CRTH2) and prostacyclin (IP). UVB was more effective in inducing COX-2 and DP in differentiated cells and EP1 and IP in undifferentiated cells. UVB readily activated keratinocyte PI-3-kinase (PI3K)/Akt, JNK and p38 MAP signaling pathways which are known to regulate COX-2 expression. While inhibition of PI3K suppressed UVB-induced mPGES-1 and CRTH2 expression, JNK inhibition suppressed mPGES-1, PGIS, EP2 and CRTH2, and p38 kinase inhibition only suppressed EP1 and EP2. These data indicate that UVB modulates expression of prostaglandin synthases and receptors by distinct mechanisms. Moreover, both the capacity of keratinocytes to generate prostaglandins and their ability to respond to these lipid mediators are stimulated by exposure to UVB.

  1. Adenylate cyclase of human articular chondrocytes. Responsiveness to prostaglandins and other hormones.

    PubMed Central

    Houston, J P; McGuire, M K; Meats, J E; Ebsworth, N M; Russell, R G; Crawford, A; Mac Neil, S

    1982-01-01

    Adenylate cyclase [ATP pyrophosphate lyase (cyclizing), EC 4.6.1.1] was shown to be present in cultured human articular chondrocytes. Optimal conditions of incubation time, protein and substrate concentrations and pH were determined in whole cell lysates. Maximal activity occurred at pH 8.5 with no decrease in activity up to pH 10.0. Adenylate cyclase activity of particulate membrane preparations was enhanced by the addition of crude cytosol preparations. The prostaglandins E1, E2, F1 alpha, F2 alpha, D2, B1, B2, A1 and A2, as well as adrenaline and isoprenaline, stimulated adenylate cyclase derived from either adult or foetal chondrocytes. No significant stimulation was observed in the presence of human calcitonin or glucagon. Bovine parathyroid hormone always significantly stimulated the adenylate cyclase derived from foetal chondrocytes, but not from adult chondrocytes. Preincubation of the chondrocytes in culture with indomethacin and with or without supernatant medium from cultured mononuclear cells increased the responsiveness of the adenylate cyclase to prostaglandin E1. PMID:7159397

  2. 16,16-Dimethyl prostaglandin E2 increases survival in mice following irradiation

    SciTech Connect

    Walden, T.L.; Patchen, M.; Snyder, S.L.

    1987-01-01

    16,16-Dimethyl prostaglandin E2(DiPGE2), a stable analog of PGE2, increases the LD 50/30 survival in CD2F1 male mice when given prior to ionizing radiation. Subcutaneous administration of 40 microgram of DiPGE2 30 min prior to /sup 60/Co gamma irradiation extends the LD 50/30 from 9.39 Gy in the control animals to 16.14 Gy in DiPGE2 treated, with a dose-reduction factor of 1.72p95% confidence limits: 1.62, 1.82. The degree of protection is dependent on both the time of administration and the dose of the prostaglandin. Ten micrograms administered 5 min prior to receiving a lethal dose of 10 Gy provides 90% survival but only 10% survival if administered 30 min prior to irradiation. Experiments to determine the in vivo concentration of DiPGE2 in organs post injection show increased levels over time, but these are not correlated with protection. At 30 min after injection, as much as 80% of the DiPGE2 present in the spleen and plasma is unmetabolized. These results suggest that the protection results from the physiologic action of DiPGE2 rather than direct in vivo detoxification of radicals.

  3. Interplay between the prostaglandin transporter OATP2A1 and prostaglandin E2-mediated cellular effects.

    PubMed

    Bujok, Krystyna; Glaeser, Hartmut; Schuh, Wolfgang; Rau, Tilman T; Schmidt, Ingrid; Fromm, Martin F; Mandery, Kathrin

    2015-03-01

    Prostaglandins such as prostaglandin E2 (PGE2) play a pivotal role in physiological and pathophysiological pathways in gastric mucosa. Little is known about the interrelation of the prostaglandin E (EP) receptors with the prostaglandin transporter OATP2A1 in the gastric mucosa and gastric carcinoma. Therefore, we first investigated the expression of OATP2A1 and EP4 in normal and carcinoma gastric mucosa. Different PGE2-mediated cellular pathways and mechanisms were investigated using human embryonic kidney cells (HEK293) and the human gastric carcinoma cell line AGS stably transfected with OATP2A1. Colocalization and expression of OATP2A1 and EP4 were detected in mucosa of normal gastric tissue and of gastric carcinomas. OATP2A1 reduced the PGE2-mediated cAMP production in HEK293 and AGS cells overexpressing EP4 and OATP2A1. The expression of OATP2A1 in AGS cells resulted in a reduction of [(3)H]-thymidine incorporation which was in line with a higher accumulation of AGS-OATP2A1 cells in S-phase of the cell cycle compared to control cells. In contrast, the expression of OATP2A1 in HEK293 cells had no influence on the distribution in the S-phase compared to control cells. OATP2A1 also diminished the PGE2-mediated expression of interleukin-8 mRNA (IL-8) and hypoxia-inducible-factor 1α (HIF1α) protein in AGS-OATP2A1 cells. The expression of OATP2A1 increased the sensitivity of AGS cells against irinotecan which led to reduced cell viability. Taken together, these data show that OATP2A1 influences PGE2-mediated cellular pathways. Therefore, OATP2A1 needs to be considered as a key determinant for the understanding of the physiology and pathophysiology of prostaglandins in healthy and tumorous gastric mucosa.

  4. Measurement of inclusive f1(1285) and f1(1420) production in Z decays with the DELPHI detector

    NASA Astrophysics Data System (ADS)

    Abdallah, J.; Abreu, P.; Adam, W.; Adzic, P.; Albrecht, T.; Alderweireld, T.; Alemany-Fernandez, R.; Allmendinger, T.; Allport, P. P.; Amaldi, U.; Amapane, N.; Amato, S.; Anashkin, E.; Andreazza, A.; Andringa, S.; Anjos, N.; Antilogus, P.; Apel, W.-D.; Arnoud, Y.; Ask, S.; Asman, B.; Augustin, J. E.; Augustinus, A.; Baillon, P.; Ballestrero, A.; Bambade, P.; Barbier, R.; Bardin, D.; Barker, G.; Baroncelli, A.; Battaglia, M.; Baubillier, M.; Becks, K.-H.; Begalli, M.; Behrmann, A.; Ben-Haim, E.; Benekos, N.; Benvenuti, A.; Berat, C.; Berggren, M.; Berntzon, L.; Bertrand, D.; Besancon, M.; Besson, N.; Bloch, D.; Blom, M.; Bluj, M.; Bonesini, M.; Boonekamp, M.; Booth, P. S. L.; Borisov, G.; Botner, O.; Bouquet, B.; Bowcock, T. J. V.; Boyko, I.; Bracko, M.; Brenner, R.; Brodet, E.; Bruckman, P.; Brunet, J. M.; Bugge, L.; Buschmann, P.; Calvi, M.; Camporesi, T.; Canale, V.; Carena, F.; Castro, N.; Cavallo, F.; Chapkin, M.; Charpentier, Ph.; Checchia, P.; Chierici, R.; Chliapnikov, P.; Chudoba, J.; Chung, S. U.; Cieslik, K.; Collins, P.; Contri, R.; Cosme, G.; Cossutti, F.; Costa, M. J.; Crawley, B.; Crennell, D.; Cuevas, J.; D'Hondt, J.; Dalmau, J.; da Silva, T.; da Silva, W.; Della Ricca, G.; de Angelis, A.; de Boer, W.; de Clercq, C.; de Lotto, B.; de Maria, N.; de Min, A.; de Paula, L.; di Ciaccio, L.; di Simone, A.; Doroba, K.; Drees, J.; Dris, M.; Eigen, G.; Ekelof, T.; Ellert, M.; Elsing, M.; Espirito Santo, M. C.; Fanourakis, G.; Fassouliotis, D.; Feindt, M.; Fernandez, J.; Ferrer, A.; Ferro, F.; Flagmeyer, U.; Foeth, H.; Fokitis, E.; Fulda-Quenzer, F.; Fuster, J.; Gandelman, M.; Garcia, C.; Gavillet, Ph.; Gazis, E.; Gokieli, R.; Golob, B.; Gomez-Ceballos, G.; Goncalves, P.; Graziani, E.; Grosdidier, G.; Grzelak, K.; Guy, J.; Haag, C.; Hallgren, A.; Hamacher, K.; Hamilton, K.; Hansen, J.; Haug, S.; Hauler, F.; Hedberg, V.; Hennecke, M.; Herr, H.; Hoffman, J.; Holmgren, S.-O.; Holt, P. J.; Houlden, M. A.; Hultqvist, K.; Jackson, J. N.; Jarlskog, G.; Jarry, P.; Jeans, D.; Johansson, E. K.; Johansson, P. D.; Jonsson, P.; Joram, C.; Jungermann, L.; Kapusta, F.; Katsanevas, S.; Katsoufis, E.; Kernel, G.; Kersevan, B. P.; Kiiskinen, A.; King, B. T.; Kjaer, N. J.; Kluit, P.; Kokkinias, P.; Kourkoumelis, C.; Kouznetsov, O.; Krumstein, Z.; Kucharczyk, M.; Lamsa, J.; Leder, G.; Ledroit, F.; Leinonen, L.; Leitner, R.; Lemonne, J.; Lepeltier, V.; Lesiak, T.; Liebig, W.; Liko, D.; Lipniacka, A.; Lopes, J. H.; Lopez, J. M.; Loukas, D.; Lutz, P.; Lyons, L.; MacNaughton, J.; Malek, A.; Maltezos, S.; Mandl, F.; Marco, J.; Marco, R.; Marechal, B.; Margoni, M.; Marin, J.-C.; Mariotti, C.; Markou, A.; Martinez-Rivero, C.; Masik, J.; Mastroyiannopoulos, N.; Matorras, F.; Matteuzzi, C.; Mazzucato, F.; Mazzucato, M.; Mc Nulty, R.; Meroni, C.; Meyer, W. T.; Migliore, E.; Mitaroff, W.; Mjoernmark, U.; Moa, T.; Moch, M.; Moenig, K.; Monge, R.; Montenegro, J.; Moraes, D.; Moreno, S.; Morettini, P.; Mueller, U.; Muenich, K.; Mulders, M.; Mundim, L.; Murray, W.; Muryn, B.; Myatt, G.; Myklebust, T.; Nassiakou, M.; Navarria, F.; Nawrocki, K.; Nicolaidou, R.; Nikolenko, M.; Oblakowska-Mucha, A.; Obraztsov, V.; Olshevski, A.; Onofre, A.; Orava, R.; Osterberg, K.; Ouraou, A.; Oyanguren, A.; Paganoni, M.; Paiano, S.; Palacios, J. P.; Palka, H.; Papadopoulou, Th. D.; Pape, L.; Parkes, C.; Parodi, F.; Parzefall, U.; Passeri, A.; Passon, O.; Peralta, L.; Perepelitsa, V.; Perrotta, A.; Petrolini, A.; Piedra, J.; Pieri, L.; Pierre, F.; Pimenta, M.; Piotto, E.; Podobnik, T.; Poireau, V.; Pol, M. E.; Polok, G.; Poropat, P.; Pozdniakov, V.; Pukhaeva, N.; Pullia, A.; Rames, J.; Ramler, L.; Read, A.; Rebecchi, P.; Rehn, J.; Reid, D.; Reinhardt, R.; Renton, P.; Richard, F.; Ridky, J.; Rivero, M.; Rodriguez, D.; Romero, A.; Ronchese, P.; Rosenberg, E.; Roudeau, P.; Rovelli, T.; Ruhlmann-Kleider, V.; Ryabtchikov, D.; Sadovsky, A.; Salmi, L.; Salt, J.; Savoy-Navarro, A.; Schwickerath, U.; Segar, A.; Sekulin, R.; Siebel, M.; Sisakian, A.; Smadja, G.; Smirnova, O.; Sokolov, A.; Sopczak, A.; Sosnowski, R.; Spassov, T.; Stanitzki, M.; Stocchi, A.; Strauss, J.; Stugu, B.; Szczekowski, M.; Szeptycka, M.; Szumlak, T.; Tabarelli, T.; Taffard, A. C.; Tegenfeldt, F.; Timmermans, J.; Tkatchev, L.; Tobin, M.; Todorovova, S.; Tome, B.; Tonazzo, A.; Tortosa, P.; Travnicek, P.; Treille, D.; Tristram, G.; Trochimczuk, M.; Troncon, C.; Turluer, M.-L.; Tyapkin, I. A.; Tyapkin, P.; Tzamarias, S.; Uvarov, V.; Valenti, G.; van Dam, P.; van Eldik, J.; van Lysebetten, A.; van Remortel, N.; van Vulpen, I.; Vegni, G.; Veloso, F.; Venus, W.; Verbeure, F.; Verdier, P.; Verzi, V.; Vilanova, D.; Vitale, L.; Vrba, V.; Wahlen, H.; Washbrook, A. J.; Weiser, C.; Wicke, D.; Wickens, J.; Wilkinson, G.; Winter, M.; Witek, M.; Yushchenko, O.; Zalewska, A.; Zalewski, P.; Zavrtanik, D.; Zhuravlov, V.; Zimin, N. I.; Zintchenko, A.; Zupan, M.; Delphi Collaboration

    2003-09-01

    DELPHI results are presented on the inclusive production of two (KoverlineKπ)0 states in the mass region 1.2-1.6 GeV/c2 in hadronic Z decays at LEP I. The measured masses (widths) are 1274±6 MeV/c2 (29±12 MeV/c2) and 1426±6 MeV/c2 (51±14 MeV/c2), respectively. A partial-wave analysis of the (KoverlineKπ)0 system shows that the first peak is consistent with the IG(JPC)=0+(1++)/(0-+)a0(980)π and the second with the IG(JPC)=0+(1++)K∗(892)overlineK+c.c. assignments. The total hadronic production rates per hadronic Z decay are (0.165±0.051) and (0.056±0.012), respectively. These measurements are consistent with the two states being the f1(1285) and f1(1420) mesons.

  5. Measurement of inclusive f1(1285) and f1(1420) production in /Z decays with the DELPHI detector

    NASA Astrophysics Data System (ADS)

    DELPHI Collaboration; Abdallah, J.; Abreu, P.; Adam, W.; Adzic, P.; Albrecht, T.; Alderweireld, T.; Alemany-Fernandez, R.; Allmendinger, T.; Allport, P. P.; Amaldi, U.; Amapane, N.; Amato, S.; Anashkin, E.; Andreazza, A.; Andringa, S.; Anjos, N.; Antilogus, P.; Apel, W.-D.; Arnoud, Y.; Ask, S.; Asman, B.; Augustin, J. E.; Augustinus, A.; Baillon, P.; Ballestrero, A.; Bambade, P.; Barbier, R.; Bardin, D.; Barker, G.; Baroncelli, A.; Battaglia, M.; Baubillier, M.; Becks, K.-H.; Begalli, M.; Behrmann, A.; Ben-Haim, E.; Benekos, N.; Benvenuti, A.; Berat, C.; Berggren, M.; Berntzon, L.; Bertrand, D.; Besancon, M.; Besson, N.; Bloch, D.; Blom, M.; Bluj, M.; Bonesini, M.; Boonekamp, M.; Booth, P. S. L.; Borisov, G.; Botner, O.; Bouquet, B.; Bowcock, T. J. V.; Boyko, I.; Bracko, M.; Brenner, R.; Brodet, E.; Bruckman, P.; Brunet, J. M.; Bugge, L.; Buschmann, P.; Calvi, M.; Camporesi, T.; Canale, V.; Carena, F.; Castro, N.; Cavallo, F.; Chapkin, M.; Charpentier, Ph.; Checchia, P.; Chierici, R.; Chliapnikov, P.; Chudoba, J.; Chung, S. U.; Cieslik, K.; Collins, P.; Contri, R.; Cosme, G.; Cossutti, F.; Costa, M. J.; Crawley, B.; Crennell, D.; Cuevas, J.; D'Hondt, J.; Dalmau, J.; da Silva, T.; da Silva, W.; della Ricca, G.; de Angelis, A.; de Boer, W.; de Clercq, C.; de Lotto, B.; de Maria, N.; de Min, A.; de Paula, L.; di Ciaccio, L.; di Simone, A.; Doroba, K.; Drees, J.; Dris, M.; Eigen, G.; Ekelof, T.; Ellert, M.; Elsing, M.; Espirito Santo, M. C.; Fanourakis, G.; Fassouliotis, D.; Feindt, M.; Fernandez, J.; Ferrer, A.; Ferro, F.; Flagmeyer, U.; Foeth, H.; Fokitis, E.; Fulda-Quenzer, F.; Fuster, J.; Gandelman, M.; Garcia, C.; Gavillet, Ph.; Gazis, E.; Gokieli, R.; Golob, B.; Gomez-Ceballos, G.; Goncalves, P.; Graziani, E.; Grosdidier, G.; Grzelak, K.; Guy, J.; Haag, C.; Hallgren, A.; Hamacher, K.; Hamilton, K.; Hansen, J.; Haug, S.; Hauler, F.; Hedberg, V.; Hennecke, M.; Herr, H.; Hoffman, J.; Holmgren, S.-O.; Holt, P. J.; Houlden, M. A.; Hultqvist, K.; Jackson, J. N.; Jarlskog, G.; Jarry, P.; Jeans, D.; Johansson, E. K.; Johansson, P. D.; Jonsson, P.; Joram, C.; Jungermann, L.; Kapusta, F.; Katsanevas, S.; Katsoufis, E.; Kernel, G.; Kersevan, B. P.; Kiiskinen, A.; King, B. T.; Kjaer, N. J.; Kluit, P.; Kokkinias, P.; Kourkoumelis, C.; Kouznetsov, O.; Krumstein, Z.; Kucharczyk, M.; Lamsa, J.; Leder, G.; Ledroit, F.; Leinonen, L.; Leitner, R.; Lemonne, J.; Lepeltier, V.; Lesiak, T.; Liebig, W.; Liko, D.; Lipniacka, A.; Lopes, J. H.; Lopez, J. M.; Loukas, D.; Lutz, P.; Lyons, L.; MacNaughton, J.; Malek, A.; Maltezos, S.; Mandl, F.; Marco, J.; Marco, R.; Marechal, B.; Margoni, M.; Marin, J.-C.; Mariotti, C.; Markou, A.; Martinez-Rivero, C.; Masik, J.; Mastroyiannopoulos, N.; Matorras, F.; Matteuzzi, C.; Mazzucato, F.; Mazzucato, M.; Mc Nulty, R.; Meroni, C.; Meyer, W. T.; Migliore, E.; Mitaroff, W.; Mjoernmark, U.; Moa, T.; Moch, M.; Moenig, K.; Monge, R.; Montenegro, J.; Moraes, D.; Moreno, S.; Morettini, P.; Mueller, U.; Muenich, K.; Mulders, M.; Mundim, L.; Murray, W.; Muryn, B.; Myatt, G.; Myklebust, T.; Nassiakou, M.; Navarria, F.; Nawrocki, K.; Nicolaidou, R.; Nikolenko, M.; Oblakowska-Mucha, A.; Obraztsov, V.; Olshevski, A.; Onofre, A.; Orava, R.; Osterberg, K.; Ouraou, A.; Oyanguren, A.; Paganoni, M.; Paiano, S.; Palacios, J. P.; Palka, H.; Papadopoulou, Th. D.; Pape, L.; Parkes, C.; Parodi, F.; Parzefall, U.; Passeri, A.; Passon, O.; Peralta, L.; Perepelitsa, V.; Perrotta, A.; Petrolini, A.; Piedra, J.; Pieri, L.; Pierre, F.; Pimenta, M.; Piotto, E.; Podobnik, T.; Poireau, V.; Pol, M. E.; Polok, G.; Poropat, P.; Pozdniakov, V.; Pukhaeva, N.; Pullia, A.; Rames, J.; Ramler, L.; Read, A.; Rebecchi, P.; Rehn, J.; Reid, D.; Reinhardt, R.; Renton, P.; Richard, F.; Ridky, J.; Rivero, M.; Rodriguez, D.; Romero, A.; Ronchese, P.; Rosenberg, E.; Roudeau, P.; Rovelli, T.; Ruhlmann-Kleider, V.; Ryabtchikov, D.; Sadovsky, A.; Salmi, L.; Salt, J.; Savoy-Navarro, A.; Schwickerath, U.; Segar, A.; Sekulin, R.; Siebel, M.; Sisakian, A.; Smadja, G.; Smirnova, O.; Sokolov, A.; Sopczak, A.; Sosnowski, R.; Spassov, T.; Stanitzki, M.; Stocchi, A.; Strauss, J.; Stugu, B.; Szczekowski, M.; Szeptycka, M.; Szumlak, T.; Tabarelli, T.; Taffard, A. C.; Tegenfeldt, F.; Timmermans, J.; Tkatchev, L.; Tobin, M.; Todorovova, S.; Tome, B.; Tonazzo, A.; Tortosa, P.; Travnicek, P.; Treille, D.; Tristram, G.; Trochimczuk, M.; Troncon, C.; Turluer, M.-L.; Tyapkin, I. A.; Tyapkin, P.; Tzamarias, S.; Uvarov, V.; Valenti, G.; van Dam, P.; van Eldik, J.; van Lysebetten, A.; van Remortel, N.; van Vulpen, I.; Vegni, G.; Veloso, F.; Venus, W.; Verbeure, F.; Verdier, P.; Verzi, V.; Vilanova, D.; Vitale, L.; Vrba, V.; Wahlen, H.; Washbrook, A. J.; Weiser, C.; Wicke, D.; Wickens, J.; Wilkinson, G.; Winter, M.; Witek, M.; Yushchenko, O.; Zalewska, A.; Zalewski, P.; Zavrtanik, D.; Zhuravlov, V.; Zimin, N. I.; Zintchenko, A.; Zupan, M.

    2003-09-01

    DELPHI results are presented on the inclusive production of two (KKπ)0 states in the mass region 1.2-1.6 GeV/c2 in hadronic /Z decays at LEP I. The measured masses (widths) are /1274+/-6 MeV/c2 (/29+/-12 MeV/c2) and /1426+/-6 MeV/c2 (/51+/-14 MeV/c2), respectively. A partial-wave analysis of the (KKπ)0 system shows that the first peak is consistent with the IG(JPC)=0+(1++)/(0-+)a0(980)π and the second with the IG(JPC)=0+(1++)K*(892)K+c.c. assignments. The total hadronic production rates per hadronic /Z decay are /(0.165+/-0.051) and /(0.056+/-0.012), respectively. These measurements are consistent with the two states being the f1(1285) and f1(1420) mesons.

  6. Inherent conformational flexibility of F1-ATPase α-subunit.

    PubMed

    Hahn-Herrera, Otto; Salcedo, Guillermo; Barril, Xavier; García-Hernández, Enrique

    2016-09-01

    The core of F1-ATPase consists of three catalytic (β) and three noncatalytic (α) subunits, forming a hexameric ring in alternating positions. A wealth of experimental and theoretical data has provided a detailed picture of the complex role played by catalytic subunits. Although major conformational changes have only been seen in β-subunits, it is clear that α-subunits have to respond to these changes in order to be able to transmit information during the rotary mechanism. However, the conformational behavior of α-subunits has not been explored in detail. Here, we have combined unbiased molecular dynamics (MD) simulations and calorimetrically measured thermodynamic signatures to investigate the conformational flexibility of isolated α-subunits, as a step toward deepening our understanding of its function inside the α3β3 ring. The simulations indicate that the open-to-closed conformational transition of the α-subunit is essentially barrierless, which is ideal to accompany and transmit the movement of the catalytic subunits. Calorimetric measurements of the recombinant α-subunit from Geobacillus kaustophilus indicate that the isolated subunit undergoes no significant conformational changes upon nucleotide binding. Simulations confirm that the nucleotide-free and nucleotide-bound subunits show average conformations similar to that observed in the F1 crystal structure, but they reveal an increased conformational flexibility of the isolated α-subunit upon MgATP binding, which might explain the evolutionary conserved capacity of α-subunits to recognize nucleotides with considerable strength. Furthermore, we elucidate the different dependencies that α- and β-subunits show on Mg(II) for recognizing ATP.

  7. Acetylation of prostaglandin synthase by aspirin.

    PubMed Central

    Roth, G J; Stanford, N; Majerus, P W

    1975-01-01

    When microsomes of sheep or bovine seminal vesicles are incubated with [acetyl-3H]aspirin (acetyl salicylic acid), 200 Ci/mol, we observe acetylation of a single protein, as measured by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The protein has a molecular weight of 85,000 and corresponds to a similar acetylated protein found in the particulate fraction of aspirin-treated human platelets. The aspirin-mediated acetylation reaction proceeds with the same time course and at the same concentration as does the inhibition of prostaglandin synthase (cyclo-oxygenase) (EC 1.14.99.1; 8,11,14-eicosatrienoate, hydrogen-donor:oxygen oxidoreductase) by the drug. At 100 muM aspirin, 50% inhibition of prostaglandin synthase and 50% of maximal acetylation are observed after 15 min at 37 degrees. Furthermore, the substrate for cyclo-oxygenase, arachidonic acid, inhibits protein acetylation by aspirin at concentrations (50% inhibition at 10-30 muM) which correlate with the Michaelis constant of arachidonic acid as a substrate for cyclooxygenase. Arachidonic acid analogues and indomethacin inhibit the acetylation reaction in proportion to their effectiveness as cyclo-oxygenase inhibitors. The results suggest that aspirin acts as an active-site acetylating agent for the enzyme cyclo-oxygenase. This action of aspirin may account for its anti-inflammatory and anti-platelet action. PMID:810797

  8. Prostaglandins, renin, aldosterone, and catecholamines in preeclampsia.

    PubMed

    Pedersen, E B; Christensen, N J; Christensen, P; Johannesen, P; Kornerup, H J; Kristensen, S; Lauritsen, J G; Leyssac, P P; Rasmussen, A B; Wohlert, M

    1983-01-01

    Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin (PRC), aldosterone (PAC), noradrenaline (PNA) and adrenaline (PA) were determined in the third trimester of pregnancy, 5 days and 3 months after delivery in preeclampsia and normotensive pregnant and non-pregnant control subjects. PGE2 was higher in pregnant control subjects than in non-pregnant subjects, but reduced to non-pregnant level in preeclampsia. PGF2 alpha was the same in preeclampsia and normotensive pregnancy but higher than in the non-pregnant group. PRC and PAC were increased during pregnancy, but considerably lesser in preeclampsia than during normotensive pregnancy. PNA and PA were the same in all three groups. All parameters were normal 3 months after delivery. There were no correlations between any of the hormones and blood pressure in any of the groups. PGE2 was positively correlated to PRC. The lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion, and the changes in PRC and PAC are supposed to be secondary to changes in PGE2. It is hypothesised that preeclampsia is a state of prostaglandin deficiency.

  9. Immunosuppression and human cancer: role of prostaglandins.

    PubMed

    Harvey, H A; Allegra, J C; Demers, L M; Luderer, J R; Brenner, D E; Trautlein, J J; White, D S; Gillin, M A; Lipton, A

    1977-06-01

    Prostaglandins, unsaturated fatty acid derivatives with diversified pharmacologic activity, have been implicated in the pathophysiology of many diseases. Prostaglandin E (PGE) levels were measured by radioimmunoassay in the plasma of 41 normocalcemic patients with various stages of malignancies. Delayed hypersensitivity was assessed by a battery of six recall skin test antigens (ST) and by Dinitrochlorobenzene (DNCB) sensitization and challenge. Twenty-five patients with one or more positive skin tests had a mean PGE level of 87+/-8 pg/ml, whereas 16 patients with negative ST had a mean PGE level of 96+/-12 pg/ml. Twenty-one DNCB negative patients had a mean PGE level of 98+/-12 pg/ml and eight totally anergic patients had a mean PGE of 96+/-12 pg/ml. All PGE values were within the normal range and there was no statistical difference between the four groups. (p less than 0.1). We concluded that circulating PGE does not correlate with the non-specific immunosuppression seen in cancer patients.

  10. [Prostaglandins, insulin secretion and diabetes mellitus].

    PubMed

    Giugliano, D; Torella, R; Scheen, A J; Lefebvre, P J; D'Onofrio, F

    1988-12-01

    The islets of Langerhans have the enzymatic equipment permitting the synthesis of the metabolites of arachidonic acid: cyclo-oxygenase and lipo-oxygenase. Numerous studies have shown that cyclo-oxygenase derivatives, mainly PGE2, reduce the insulin response to glucose whereas lipo-oxygenase derivatives, mainly 15-HPETE, stimulate insulin secretion. So, for instance, drugs that increase prostaglandins synthesis as colchicine or furosemide inhibit insulin secretion while non steroid anti-inflammator drugs, mainly salicylates, which inhibit cyclo-oxygenase, enhance the insulin response to various stimuli. In type-2 (non insulin-dependent) diabetes, an increased sensitivity to endogenous prostaglandins has been proposed as a possible cause for the insulin secretion defect which characterizes this disease. Play in favor of this hypothesis the fact that the administration of PGE inhibits the insulin response to arginine in type-2 diabetics but not in normal subject and the fact that the administration of salicylates could improve the insulin response to glucose in some of these patients.

  11. Suppression of newborn natural killer cell activity by prostaglandin E2

    SciTech Connect

    Milch, P.O.; Salvatore, W.; Luft, B.; Baker, D.A.

    1988-10-01

    The effect of prostaglandin E2 on natural killer cell activity of cord blood was examined. Natural killer cell activity, determined by chromium 51 release, was significantly reduced after prostaglandin E2 (1 microgram/ml) treatment. Prostaglandin E2 has been found to enhance the cellular spread of herpesvirus. Thus prostaglandins may enhance viral infections indirectly by suppressing natural killer cell activity.

  12. Identification and purification of a Bombyx mori homologue of FTZ-F1.

    PubMed Central

    Ueda, H; Hirose, S

    1990-01-01

    Extracts from embryos and from posterior and middle silk glands of the silkworm, Bombyx mori contain a sequence specific DNA binding factor termed BmFTZ-F1. The factor binds to the recognition site of FTZ-F1, a positive regulator of the fushi tarazu gene in Drosophila melanogaster. BmFTZ-F1 and FTZ-F1 share the same methylation interference patterns, the same chromatographic behaviors and similar protease digestion profiles. Anti-FTZ-F1 cross reacts with BmFTZ-F1. These results indicate that BmFTZ-F1 is a B. mori homologue of FTZ-F1. The mobility of the factor-DNA complex formed in the silk gland extract changes depending on the developmental stages. Purification of BmFTZF1 to an almost homogeneous state reveals that the factor is a 73 kd protein. Images PMID:2124348

  13. Changes in F2-F1 as a voicing cue

    NASA Astrophysics Data System (ADS)

    Warren, Willis J.; Coren, Amy E.

    2003-10-01

    The interaction between formant transitions and vowel length was measured with respect to syllable final voicing distinctions. A synthesized ad VC token of 360 ms was edited in 5-ms intervals from either side, onset or offset, so that 260 ms were preserved. Ten subjects were asked to make final voicing judgments for the words ``odd'' and ``ought'' ([ad] vs [at]) when hearing the 20 edited tokens. Each token was presented five times, randomly, for a total of 1000 judgements. Results showed an overwhelming number of voiced responses when the entire offset was preserved and symmetrical voiceless results with the deletion of offset. A follow-up experiment utilized a similarly synthesized token of 460 ms. The results when adding 100 ms onto the vowel were insignificantly different than the results acquired for formant transitions, suggesting the latter are a more important cue for syllable final voicing distinctions. These findings contradict previous vowel length conclusions [L. J. Raphael, J. Acoust. Soc. Am. 51, 1296-1303 (1972)] and further suggest that in addition to F1 [V. Summers, J. Acoust. Soc. Am. 84, 485-492 (1988)], F2 transitions are also an important cue to final voicing distinctions in low vowel contexts.

  14. Theoretical Analysis of the F1-ATPase Experimental Data

    PubMed Central

    Perez-Carrasco, Ruben; Sancho, J.M.

    2010-01-01

    Abstract F1-ATPase is a rotatory molecular motor fueled by ATP nucleotides. Different loads can be attached to the motor axis to show that it rotates in main discrete steps of 120° with substeps of ∼80° and 40°. Experimental data show the dependence on the mean rotational velocity ω with respect to the external control parameters: the nucleotide concentration [ATP] and the friction of the load γL. In this work we present a theoretical analysis of the experimental data whose main results are: 1), A derivation of a simple analytical formula for ω([ATP], γL) that compares favorably with experiments; 2), The introduction of a two-state flashing ratchet model that exhibits experimental phenomenology of a greater specificity than has been, to our knowledge, previously available; 3), The derivation of an argument to obtain the values of the substep sizes; 4), An analysis of the energy constraints of the model; and 5), The theoretical analysis of the coupling ratio between the ATP consumed and the success of a forward step. We also discuss the compatibility of our approach with recent experimental observations. PMID:20513403

  15. Close phylogenetic relationship between Angolan and Romanian HIV-1 subtype F1 isolates

    PubMed Central

    Guimarães, Monick L; Vicente, Ana Carolina P; Otsuki, Koko; da Silva, Rosa Ferreira FC; Francisco, Moises; da Silva, Filomena Gomes; Serrano, Ducelina; Morgado, Mariza G; Bello, Gonzalo

    2009-01-01

    Background Here, we investigated the phylogenetic relationships of the HIV-1 subtype F1 circulating in Angola with subtype F1 strains sampled worldwide and reconstructed the evolutionary history of this subtype in Central Africa. Methods Forty-six HIV-1-positive samples were collected in Angola in 2006 and subtyped at the env-gp41 region. Partial env-gp120 and pol-RT sequences and near full-length genomes from those env-gp41 subtype F1 samples were further generated. Phylogenetic analyses of partial and full-length subtype F1 strains isolated worldwide were carried out. The onset date of the subtype F1 epidemic in Central Africa was estimated using a Bayesian Markov chain Monte Carlo approach. Results Nine Angolan samples were classified as subtype F1 based on the analysis of the env-gp41 region. All nine Angolan sequences were also classified as subtype F1 in both env-gp120 and pol-RT genomic regions, and near full-length genome analysis of four of these samples confirmed their classification as "pure" subtype F1. Phylogenetic analyses of subtype F1 strains isolated worldwide revealed that isolates from the Democratic Republic of Congo (DRC) were the earliest branching lineages within the subtype F1 phylogeny. Most strains from Angola segregated in a monophyletic group together with Romanian sequences; whereas South American F1 sequences emerged as an independent cluster. The origin of the subtype F1 epidemic in Central African was estimated at 1958 (1934–1971). Conclusion "Pure" subtype F1 strains are common in Angola and seem to be the result of a single founder event. Subtype F1 sequences from Angola are closely related to those described in Romania, and only distantly related to the subtype F1 lineage circulating in South America. Original diversification of subtype F1 probably occurred within the DRC around the late 1950s. PMID:19386115

  16. The calculation of the height of the characteristic point in the F1 layer

    NASA Astrophysics Data System (ADS)

    Radicella, S. M.; Mosert de Gonzalez, M.

    The paper describes a method for computing the height of the F1 characteristic point by utilizing the electron density and the local magnetic dip. The characteristic points in the F1 layers for several locations are used to develop a linear relation between hF1 and NF1 with the local magnetic dip as a parameter. The equation given agrees with the data in question and can be used to determine the F1 point with similar sets of data.

  17. Biologic interaction of prostaglandin, thromboxane and prostacyclin: potential clinical applications.

    PubMed

    Bell, T G; Smith, W L; Oxender, W D

    1986-01-01

    Prostaglandins are vasoactive agents which have potent and varied effects depending on the species, conditions and organs tested. The clinician wishing to gain a significant overview of the field from current research literature has a demanding task for himself. A review of biologic interactions is exactly what is needed in a consideration of possible clinical applications of prostaglandins. Thus, it is necessary first to recount the last five years' advances in prostaglandin research. Only then will the listing and discussion of some diseases soon to benefit from the application of research be meaningful.

  18. Role of renal prostaglandins in the action of ramipril (HOE-498) in normotensive rats.

    PubMed

    Lahera, V; Durán, F; Cachofeiro, V; Cañizo, F J; Cantón, J J; Rodriguez, F J; Tresguerres, J A

    1989-01-01

    Changes in blood pressure, plasma renin activity, urine volume, urinary PGE2, 6-keto-PGF1 alpha and kinins, were studied after the administration of the angiotensin converting enzyme inhibitor ramipril (100 mu/kg/day), for one week in concomitantly indomethacin (1 mg/kg/day) treated and untreated rats. Measurements were made basally, before Ramipril administration and on days 1 and 7 during the treatment. Ramipril given alone induced a decrease in urinary PGE2 (NS) and 6-keto-PGF1 alpha (p less than 0.05) on day 1, together with an increase in urinary kinins on day 7 (p less than 0.01) and in urine volume on days 1 and 7 (p less than 0.05). Increased urinary PGE2 (NS) and 6-keto-PGF1 alpha (p less than 0.05) were observed in indomethacin pretreated rats after ramipril administration. No modifications in BP levels were observed either with indomethacin or with ramipril given alone or with ramipril plus indomethacin. Ramipril increased plasma renin activity levels both in indomethacin treated and untreated rats on days 1 (p less than 0.01) and 7 (p less than 0.05). The diuretic effect of ramipril and the stimulation of kinins were blunted when concomitant indomethacin was administered. Although a stimulatory effect of ramipril on urinary PGS was only observed during indomethacin administration, the present results would suggest that a non-inhibited PGS synthesis would be required for the renal actions of Ramipril.

  19. 16 CFR Appendix F1 to Part 305 - Standard Clothes Washers

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Standard Clothes Washers F1 Appendix F1 to... Appendix F1 to Part 305—Standard Clothes Washers Range Information “Standard” includes all household clothes washers with a tub capacity of 1.6 cu. ft. or more. Capacity Range of Estimated Annual...

  20. 16 CFR Appendix F1 to Part 305 - Standard Clothes Washers

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Standard Clothes Washers F1 Appendix F1 to... Appendix F1 to Part 305—Standard Clothes Washers Range Information “Standard” includes all household clothes washers with a tub capacity of 1.6 cu. ft. or more. Capacity Range of Estimated Annual...

  1. 16 CFR Appendix F1 to Part 305 - Standard Clothes Washers

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Standard Clothes Washers F1 Appendix F1 to... Appendix F1 to Part 305—Standard Clothes Washers Range Information “Standard” includes all household clothes washers with a tub capacity of 1.6 cu. ft. or more. Capacity Range of Estimated Annual...

  2. 26 CFR 1.430(f)-1 - Effect of prefunding balance and funding standard carryover balance.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 5 2012-04-01 2011-04-01 true Effect of prefunding balance and funding standard carryover balance. 1.430(f)-1 Section 1.430(f)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF...(f)-1 Effect of prefunding balance and funding standard carryover balance. (a) In...

  3. 26 CFR 1.430(f)-1 - Effect of prefunding balance and funding standard carryover balance.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 5 2013-04-01 2013-04-01 false Effect of prefunding balance and funding standard carryover balance. 1.430(f)-1 Section 1.430(f)-1 Internal Revenue INTERNAL REVENUE SERVICE... § 1.430(f)-1 Effect of prefunding balance and funding standard carryover balance. (a) In...

  4. 26 CFR 1.430(f)-1 - Effect of prefunding balance and funding standard carryover balance.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 5 2014-04-01 2014-04-01 false Effect of prefunding balance and funding standard carryover balance. 1.430(f)-1 Section 1.430(f)-1 Internal Revenue INTERNAL REVENUE SERVICE... § 1.430(f)-1 Effect of prefunding balance and funding standard carryover balance. (a) In...

  5. 26 CFR 1.430(f)-1 - Effect of prefunding balance and funding standard carryover balance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 5 2011-04-01 2011-04-01 false Effect of prefunding balance and funding standard carryover balance. 1.430(f)-1 Section 1.430(f)-1 Internal Revenue INTERNAL REVENUE SERVICE... § 1.430(f)-1 Effect of prefunding balance and funding standard carryover balance. (a) In...

  6. 17 CFR 270.17f-1 - Custody of securities with members of national securities exchanges.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... members of national securities exchanges. 270.17f-1 Section 270.17f-1 Commodity and Securities Exchanges....17f-1 Custody of securities with members of national securities exchanges. (a) No registered... custody of a company which is a member of a national securities exchange as defined in the...

  7. 17 CFR 270.17f-1 - Custody of securities with members of national securities exchanges.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... members of national securities exchanges. 270.17f-1 Section 270.17f-1 Commodity and Securities Exchanges....17f-1 Custody of securities with members of national securities exchanges. (a) No registered... custody of a company which is a member of a national securities exchange as defined in the...

  8. 17 CFR 270.17f-1 - Custody of securities with members of national securities exchanges.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... members of national securities exchanges. 270.17f-1 Section 270.17f-1 Commodity and Securities Exchanges....17f-1 Custody of securities with members of national securities exchanges. (a) No registered... custody of a company which is a member of a national securities exchange as defined in the...

  9. 17 CFR 270.17f-1 - Custody of securities with members of national securities exchanges.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... members of national securities exchanges. 270.17f-1 Section 270.17f-1 Commodity and Securities Exchanges....17f-1 Custody of securities with members of national securities exchanges. (a) No registered... custody of a company which is a member of a national securities exchange as defined in the...

  10. 17 CFR 270.17f-1 - Custody of securities with members of national securities exchanges.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... members of national securities exchanges. 270.17f-1 Section 270.17f-1 Commodity and Securities Exchanges....17f-1 Custody of securities with members of national securities exchanges. (a) No registered... custody of a company which is a member of a national securities exchange as defined in the...

  11. Use of vaginal prostaglandin gel before induction of labour.

    PubMed

    Murphy, A J; Jalland, M; Pepperell, R J; Quinn, M A

    1980-05-01

    Tylose gel containing either 1.5 mg, 3.0 mg or 10.0 mg of prostaglandin F2 alpha was inserted into the posterior vaginal fornix of 165 patients on the evening before induction of labour. A control group of 100 patients received the gel alone. There was a significant reduction in the induction-delivery interval in nulliparae receiving at least 3.0 mg of prostaglandin, whereas, in multiparae all doses achieved this effect. There was also a significant reduction in the incidence of forceps delivery in nulliparae who received 3.0 mg or more of the prostaglandin gel; however, there was no difference in the incidence of spontneous labour, epidural anaesthesia or Caesarean section between the patients who received prostaglandin or those receiving gel alone.

  12. Reduction in urinary prostaglandin excretion in the premenstrual syndrome.

    PubMed

    Piccoli, A; Modena, F; Calò, L; Cantaro, S; Avogadro, A; Nardo, G; Cerutti, R

    1993-12-01

    The purpose of the present work was to study some factors involved in renal handling of salt and water in the premenstrual syndrome (PMS), in which salt and water retention is frequently observed. In 18 women with PMS and in 18 healthy women we studied the levels of cyclic adenosine monophosphate, aldosterone, prostaglandin E2, prostaglandin F2 alpha and kallikrein in urinary samples collected during the luteal phase. There was no difference between the two groups regarding sodium, aldosterone and kallikrein urinary excretion. In the PMS group there was a significant reduction in urinary excretion of cyclic adenosine monophosphate, prostaglandin E2 and prostaglandin F2 alpha with respect to the control group. At multivariate analysis sodium urinary excretion proved not to be the same as the model validated in healthy women. There may be different renal handling of water and electrolytes during the luteal phase of the menstrual cycle in women with PMS.

  13. The nonlinear chemo-mechanic coupled dynamics of the F 1 -ATPase molecular motor.

    PubMed

    Xu, Lizhong; Liu, Fang

    2012-03-01

    The ATP synthase consists of two opposing rotary motors, F0 and F1, coupled to each other. When the F1 motor is not coupled to the F0 motor, it can work in the direction hydrolyzing ATP, as a nanomotor called F1-ATPase. It has been reported that the stiffness of the protein varies nonlinearly with increasing load. The nonlinearity has an important effect on the rotating rate of the F1-ATPase. Here, considering the nonlinearity of the γ shaft stiffness for the F1-ATPase, a nonlinear chemo-mechanical coupled dynamic model of F1 motor is proposed. Nonlinear vibration frequencies of the γ shaft and their changes along with the system parameters are investigated. The nonlinear stochastic response of the elastic γ shaft to thermal excitation is analyzed. The results show that the stiffness nonlinearity of the γ shaft causes an increase of the vibration frequency for the F1 motor, which increases the motor's rotation rate. When the concentration of ATP is relatively high and the load torque is small, the effects of the stiffness nonlinearity on the rotating rates of the F1 motor are obvious and should be considered. These results are useful for improving calculation of the rotating rate for the F1 motor and provide insight about the stochastic wave mechanics of F1-ATPase.

  14. Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasis

    PubMed Central

    Lacroix, Matthieu; Caramel, Julie; Goguet-Rubio, Perrine; Linares, Laetitia K.; Estrach, Soline; Hatchi, Elodie; Rodier, Geneviève; Lledo, Gwendaline; de Bettignies, Carine; Thépot, Amélie; Deraison, Céline; Chébli, Karim; Hainaut, Pierre; Dubus, Pierre; Sardet, Claude; Le Cam, Laurent

    2010-01-01

    A growing body of evidence suggests that the multifunctional protein E4F1 is involved in signaling pathways that play essential roles during normal development and tumorigenesis. We generated E4F1 conditional knockout mice to address E4F1 functions in vivo in newborn and adult skin. E4F1 inactivation in the entire skin or in the basal compartment of the epidermis induces skin homeostasis defects, as evidenced by transient hyperplasia in the interfollicular epithelium and alteration of keratinocyte differentiation, followed by loss of cellularity in the epidermis and severe skin ulcerations. E4F1 depletion alters clonogenic activity of epidermal stem cells (ESCs) ex vivo and ends in exhaustion of the ESC pool in vivo, indicating that the lesions observed in the E4F1 mutant skin result, at least in part, from cell-autonomous alterations in ESC maintenance. The clonogenic potential of E4F1 KO ESCs is rescued by Bmi1 overexpression or by Ink4a/Arf or p53 depletion. Skin phenotype of E4F1 KO mice is also delayed in animals with Ink4a/Arf and E4F1 compound gene deficiencies. Our data identify a regulatory axis essential for ESC-dependent skin homeostasis implicating E4F1 and the Bmi1–Arf–p53 pathway. PMID:21088222

  15. E4F1 deficiency results in oxidative stress–mediated cell death of leukemic cells

    PubMed Central

    Hatchi, Elodie; Rodier, Genevieve; Lacroix, Matthieu; Caramel, Julie; Kirsh, Olivier; Jacquet, Chantal; Schrepfer, Emilie; Lagarrigue, Sylviane; Linares, Laetitia Karine; Lledo, Gwendaline; Tondeur, Sylvie; Dubus, Pierre

    2011-01-01

    The multifunctional E4F1 protein was originally discovered as a target of the E1A viral oncoprotein. Growing evidence indicates that E4F1 is involved in key signaling pathways commonly deregulated during cell transformation. In this study, we investigate the influence of E4F1 on tumorigenesis. Wild-type mice injected with fetal liver cells from mice lacking CDKN2A, the gene encoding Ink4a/Arf, developed histiocytic sarcomas (HSs), a tumor originating from the monocytic/macrophagic lineage. Cre-mediated deletion of E4F1 resulted in the death of HS cells and tumor regression in vivo and extended the lifespan of recipient animals. In murine and human HS cell lines, E4F1 inactivation resulted in mitochondrial defects and increased production of reactive oxygen species (ROS) that triggered massive cell death. Notably, these defects of E4F1 depletion were observed in HS cells but not healthy primary macrophages. Short hairpin RNA–mediated depletion of E4F1 induced mitochondrial defects and ROS-mediated death in several human myeloid leukemia cell lines. E4F1 protein is overexpressed in a large subset of human acute myeloid leukemia samples. Together, these data reveal a role for E4F1 in the survival of myeloid leukemic cells and support the notion that targeting E4F1 activities might have therapeutic interest. PMID:21708927

  16. Pharmacogenomics of Prostaglandin and Leukotriene Receptors

    PubMed Central

    Cornejo-García, José A.; Perkins, James R.; Jurado-Escobar, Raquel; García-Martín, Elena; Agúndez, José A.; Viguera, Enrique; Pérez-Sánchez, Natalia; Blanca-López, Natalia

    2016-01-01

    Individual genetic background together with environmental effects are thought to be behind many human complex diseases. A number of genetic variants, mainly single nucleotide polymorphisms (SNPs), have been shown to be associated with various pathological and inflammatory conditions, representing potential therapeutic targets. Prostaglandins (PTGs) and leukotrienes (LTs) are eicosanoids derived from arachidonic acid and related polyunsaturated fatty acids that participate in both normal homeostasis and inflammatory conditions. These bioactive lipid mediators are synthesized through two major multistep enzymatic pathways: PTGs by cyclooxygenase and LTs by 5-lipoxygenase. The main physiological effects of PTGs include vasodilation and vascular leakage (PTGE2); mast cell maturation, eosinophil recruitment, and allergic responses (PTGD2); vascular and respiratory smooth muscle contraction (PTGF2), and inhibition of platelet aggregation (PTGI2). LTB4 is mainly involved in neutrophil recruitment, vascular leakage, and epithelial barrier function, whereas cysteinyl LTs (CysLTs) (LTC4, LTD4, and LTE4) induce bronchoconstriction and neutrophil extravasation, and also participate in vascular leakage. PTGs and LTs exert their biological functions by binding to cognate receptors, which belong to the seven transmembrane, G protein-coupled receptor superfamily. SNPs in genes encoding these receptors may influence their functionality and have a role in disease susceptibility and drug treatment response. In this review we summarize SNPs in PTGs and LTs receptors and their relevance in human diseases. We also provide information on gene expression. Finally, we speculate on future directions for this topic. PMID:27708579

  17. Subcutaneous fat necrosis, hypercalcemia, and prostaglandin E.

    PubMed

    Sharata, H; Postellon, D C; Hashimoto, K

    1995-03-01

    We present two patients with subcutaneous fat necroses (SCFN) in whom endocrinologic studies revealed an association with elevated prostaglandin E (PGE) levels. A boy born after prolonged labor complicated by meconium aspiration developed erythematous, indurated plaques over the back, arms, buttocks, and cheeks at 4 days of age. A biopsy specimen of involved skin showed panniculitis with foci of necrotic adipocytes containing radially arranged, needle-shaped clefts and a granulomatous infiltrate in the septae. Laboratory studies revealed hypercalcemia of 13.6 mg/dl (normal 8.8-10.1 mg/dl), elevated 1.25-1.25(OH)2D3, and increased urinary excretion of PGE2. The child was hospitalized and treated with systemic steroids and diuretics, with resolution of SCFN and hypercalcemia. The second patient was a girl born with cyanotic heart disease. A diagnosis of Ebstein anomaly was made, and intravenous PGE1 was started to keep patent the ductus arteriosus. Four days later erythematous, indurated plaques were noted on the knee, back, and anterior chest. A skin biopsy specimen revealed SCFN. There was no associated laboratory abnormality. On discontinuing PGE1, no new lesions formed and the existing panniculitis resolved. These two cases demonstrate the association between SCFN and elevated PGE levels (endogenous in patient 1, exogenous in patient 2). No previous reports of SCFN after the administration of PGE1 have appeared in the literature.

  18. Prostaglandins as PPARγ Modulators in Adipogenesis

    PubMed Central

    Fujimori, Ko

    2012-01-01

    Adipocytes and fat cells play critical roles in the regulation of energy homeostasis. Adipogenesis (adipocyte differentiation) is regulated via a complex process including coordinated changes in hormone sensitivity and gene expression. PPARγ is a ligand-dependent transcription factor and important in adipogenesis, as it enhances the expression of numerous adipogenic and lipogenic genes in adipocytes. Prostaglandins (PGs), which are lipid mediators, are associated with the regulation of PPARγ function in adipocytes. Prostacyclin promotes the differentiation of adipocyte-precursor cells to adipose cells via activation of the expression of C/EBPβ and δ. These proteins are important transcription factors in the activation of the early phase of adipogenesis, and they activate the expression of PPARγ, which event precedes the maturation of adipocytes. PGE2 and PGF2α strongly suppress the early phase of adipocyte differentiation by enhancing their own production via receptor-mediated elevation of the expression of cycloxygenase-2, and they also suppress the function of PPARγ. In contrast, PGD2 and its non-enzymatic metabolite, Δ12-PGJ2, activate the middle-late phase of adipocyte differentiation through both DP2 receptors and PPARγ. This paper focuses on potential roles of PGs as PPARγ modulators in adipogenesis and regulators of obesity. PMID:23319937

  19. Simulated microgravity upregulates an endothelial vasoconstrictor prostaglandin

    NASA Technical Reports Server (NTRS)

    Sangha, D. S.; Han, S.; Purdy, R. E.

    2001-01-01

    Endothelial nitric oxide contributes to the vascular hyporesponsiveness to norepinephrine (NE) observed in carotid arteries from rats exposed to simulated microgravity. The goal of the present study was to determine whether a cyclooxygenase product of arachidonic acid also influences vascular responsiveness in this setting. Microgravity was simulated in rats by hindlimb unweighting (HU). After 20 days of HU, carotid arteries were isolated from control and HU-treated rats, and vascular rings were mounted in tissue baths for the measurement of isometric contraction. Two cyclooxygenase inhibitors, indomethacin and ibuprofen, and the selective thromboxane A(2) prostanoid-receptor antagonist, SQ-29548, had no effect on the contraction to NE in control vessels but markedly reduced contraction to NE in HU vessels. When the endothelium was removed, indomethacin no longer had any effect on the NE-induced contraction in HU vessels. In endothelium-intact vessels in the presence of indomethacin, the addition of the nitric oxide synthase inhibitor, N(G)-L-nitro-arginine methyl ester, to the medium bathing HU vessels increased the contraction to NE to the level of that of the control vessels. These results indicate that HU treatment induced two endothelial changes in carotid artery that opposed each other. Nitric oxide activity was increased and was responsible for the vascular hyporesponsiveness to NE. The activity of a vasoconstrictor prostaglandin was also increased, and attenuated the vasodilating effect of nitric oxide.

  20. Sulforaphane Inhibits Prostaglandin E2 Synthesis by Suppressing Microsomal Prostaglandin E Synthase 1

    PubMed Central

    Zhou, Jiping; Joplin, Denise G.; Cross, Janet V.; Templeton, Dennis J.

    2012-01-01

    Sulforaphane (SFN) is a dietary cancer preventive with incompletely characterized mechanism(s) of cancer prevention. Since prostaglandin E2 (PGE2) promotes cancer progression, we hypothesized that SFN may block PGE2 synthesis in cancer cells. We found that SFN indeed blocked PGE2 production in human A549 cancer cells not by inhibiting COX-2, but rather by suppressing the expression of microsomal prostaglandin E synthase (mPGES-1), the enzyme that directly synthesizes PGE2. We identified the Hypoxia Inducible Factor 1 alpha (HIF-1α) as the target of SFN-mediated mPGES-1 suppression. SFN suppressed HIF-1α protein expression and the presence of HIF-1α at the mPGES-1 promoter, resulting in reduced transcription of mPGES-1. Finally, SFN also reduced expression of mPGES-1 and PGE2 production in A549 xenograft tumors in mice. Together, these results point to the HIF-1α, mPGES-1 and PGE2 axis as a potential mediator of the anti-cancer effects of SFN, and illustrate the potential of SFN for therapeutic control of cancer and inflammation. Harmful side effects in patients taking agents that target the more upstream COX-2 enzyme render the downstream target mPGES-1 a significant target for anti-inflammatory therapy. Thus, SFN could prove to be an important therapeutic approach to both cancer and inflammation. PMID:23166763

  1. Parameters to Maximize 2f2-f1 Distortion Product Otoacoustic Emission Levels

    ERIC Educational Resources Information Center

    Horn, Jennifer H.; Pratt, Shiela R.; Durrant, John D.

    2008-01-01

    Purpose: Past research has established parameters for the 2f1-f2 distortion product otoacoustic emissions (DPOAEs) that enhance response levels (e.g., L1 - L2 = 10 dB; f2/f1 = 1.22; L1, L2 = 65, 55 dB SPL). These same parameters do not optimize 2f2-f1 DPOAEs. Therefore, this study was conducted to evaluate more completely those parameters that…

  2. Alimentary Tract Absorption (f1 Values) for Radionuclides in Local and Regional Fallout from Nuclear Tests

    PubMed Central

    Ibrahim, Shawki; Simon, Steven L; Bouville, André; Melo, Dunstana; Beck, Harold

    2009-01-01

    This paper presents gastrointestinal absorption fractions (f1 values) for estimating internal doses from local and regional fallout radionuclides due to nuclear tests. The choice of f1 values are based on specific circumstances of weapons test conditions and a review of reported f1 values for elements in different physical and chemical states. Special attention is given to fallout from nuclear tests conducted at the Marshall Islands. We make a distinction between the f1 values for intakes of radioactive materials immediately after deposition (acute intakes) and intakes that occur in the course of months and years after deposition, following incorporation into terrestrial and aquatic foodstuffs (chronic intakes). Multiple f1 values for different circumstances where persons are exposed to radioactive fallout (e.g. local vs. regional fallout and coral vs. continental tests) are presented when supportive information is available. In some cases, our selected f1 values are similar to those adopted by the ICRP (e.g. iodine and most actinides). However, f1 values for cesium and strontium derived from urine bioassay data of the Marshallese population are notably lower than the generic f1 values recommended by ICRP, particularly for acute intakes from local fallout (0.4 and 0.05 for Cs and Sr, respectively. The f1 values presented here form the first complete set of values relevant to realistic dose assessments for exposure to local or regional radioactive fallout. PMID:20622554

  3. Characteristics Analysis of F1 Hybrids between Genetically Modified Brassica napus and B. rapa.

    PubMed

    Sohn, Soo-In; Oh, Young-Ju; Lee, Kyeong-Ryeol; Ko, Ho-Cheol; Cho, Hyun-Suk; Lee, Yeon-Hee; Chang, Ancheol

    2016-01-01

    A number of studies have been conducted on hybridization between transgenic Brassica napus and B. rapa or backcross of F1 hybrid to their parents. However, trait changes must be analyzed to evaluate hybrid sustainability in nature. In the present study, B. rapa and transgenic (BrAGL20) B. napus were hybridized to verify the early flowering phenomenon of F1 hybrids, and F1 hybrid traits were analyzed to predict their impact on sustainability. Flowering of F1 hybrid has been induced slightly later than that of the transgenic B. napus, but flowering was available in the greenhouse without low temperature treatment to young plant, similar to the transgenic B. napus. It is because the BrAGL20 gene has been transferred from transgenic B. napus to F1 hybrid. The size of F1 hybrid seeds was intermediate between those of B. rapa and transgenic B. napus, and ~40% of F1 pollen exhibited abnormal size and morphology. The form of the F1 stomata was also intermediate between that of B. rapa and transgenic B. napus, and the number of stomata was close to the parental mean. Among various fatty acids, the content of erucic acid exhibited the greatest change, owing to the polymorphism of parental FATTY ACID ELONGASE 1 alleles. Furthermore, F2 hybrids could not be obtained. However, BC1 progeny were obtained by hand pollination of B. rapa with F1 hybrid pollen, with an outcrossing rate of 50%.

  4. Alimentary tract absorption (f1 values) for radionuclides in local and regional fallout from nuclear tests.

    PubMed

    Ibrahim, Shawki A; Simon, Steven L; Bouville, André; Melo, Dunstana; Beck, Harold L

    2010-08-01

    This paper presents gastrointestinal absorption fractions (f1 values) for estimating internal doses from local and regional fallout radionuclides due to nuclear tests. The choice of f1 values are based on specific circumstances of weapons test conditions and a review of reported f1 values for elements in different physical and chemical states. Special attention is given to fallout from nuclear tests conducted at the Marshall Islands. We make a distinction between the f1 values for intakes of radioactive materials immediately after deposition (acute intakes) and intakes that occur in the course of months and years after deposition, following incorporation into terrestrial and aquatic foodstuffs (chronic intakes). Multiple f1 values for different circumstances where persons are exposed to radioactive fallout (e.g., local vs. regional fallout and coral vs. continental tests) are presented when supportive information is available. In some cases, our selected f1 values are similar to those adopted by the International Commission on Radiological Protection (ICRP) (e.g., iodine and most actinides). However, f1 values for cesium and strontium derived from urine bioassay data of the Marshallese population are notably lower than the generic f1 values recommended by ICRP, particularly for acute intakes from local fallout (0.4 and 0.05 for Cs and Sr, respectively). The f1 values presented here form the first complete set of values relevant to realistic dose assessments for exposure to local or regional radioactive fallout.

  5. Arginine methylation-dependent reader-writer interplay governs growth control by E2F-1.

    PubMed

    Zheng, Shunsheng; Moehlenbrink, Jutta; Lu, Yi-Chien; Zalmas, Lykourgos-Panagiotis; Sagum, Cari A; Carr, Simon; McGouran, Joanna F; Alexander, Leila; Fedorov, Oleg; Munro, Shonagh; Kessler, Benedikt; Bedford, Mark T; Yu, Qiang; La Thangue, Nicholas B

    2013-10-10

    The mechanisms that underlie and dictate the different biological outcomes of E2F-1 activity have yet to be elucidated. We describe the residue-specific methylation of E2F-1 by the asymmetric dimethylating protein arginine methyltransferase 1 (PRMT1) and symmetric dimethylating PRMT5 and relate the marks to different functional consequences of E2F-1 activity. Methylation by PRMT1 hinders methylation by PRMT5, which augments E2F-1-dependent apoptosis, whereas PRMT5-dependent methylation favors proliferation by antagonizing methylation by PRMT1. The ability of E2F-1 to prompt apoptosis in DNA damaged cells coincides with enhanced PRMT1 methylation. In contrast, cyclin A binding to E2F-1 impedes PRMT1 methylation and augments PRMT5 methylation, thus ensuring that E2F-1 is locked into its cell-cycle progression mode. The Tudor domain protein p100-TSN reads the symmetric methylation mark, and binding of p100-TSN downregulates E2F-1 apoptotic activity. Our results define an exquisite level of precision in the reader-writer interplay that governs the biological outcome of E2F-1 activity.

  6. Arginine methylation-dependent reader-writer interplay governs growth control by E2F-1

    PubMed Central

    Zheng, Shunsheng; Moehlenbrink, Jutta; Lu, Yi-Chien; Zalmas, Lykourgos-Panagiotis; Sagum, Cari A.; Carr, Simon; McGouran, Joanna F.; Alexander, Leila; Fedorov, Oleg; Munro, Shonagh; Kessler, Benedikt; Bedford, Mark T.; Yu, Qiang; La Thangue, Nicholas B.

    2014-01-01

    Summary The mechanisms that underlie and dictate the different biological outcomes of E2F-1 activity have yet to be elucidated. We describe the residue-specific methylation of E2F-1 by the asymmetric dimethylating protein arginine methyltransferase (PRMT) 1 and symmetric dimethylating PRMT5, and relate the marks to different functional consequences of E2F-1 activity. Methylation by PRMT1 hinders methylation by PRMT5, which augments E2F-1-dependent apoptosis, whereas PRMT5-dependent methylation favours proliferation by antagonising methylation by PRMT1. The ability of E2F-1 to prompt apoptosis in DNA damaged cells coincides with enhanced PRMT1 methylation. In contrast, cyclin A binding to E2F-1 impedes PRMT1 methylation and augments PRMT5 methylation, thus ensuring that E2F-1 is locked into its cell cycle progression mode. The Tudor domain protein p100-TSN reads the symmetric methylation mark, and binding of p100-TSN down-regulates E2F-1 apoptotic activity. Our results define an exquisite level of precision in the reader-writer interplay that governs the biological outcome of E2F-1 activity. PMID:24076217

  7. Characteristics Analysis of F1 Hybrids between Genetically Modified Brassica napus and B. rapa

    PubMed Central

    Sohn, Soo-In; Oh, Young-Ju; Lee, Kyeong-Ryeol; Ko, Ho-Cheol; Cho, Hyun-Suk; Lee, Yeon-Hee; Chang, Ancheol

    2016-01-01

    A number of studies have been conducted on hybridization between transgenic Brassica napus and B. rapa or backcross of F1 hybrid to their parents. However, trait changes must be analyzed to evaluate hybrid sustainability in nature. In the present study, B. rapa and transgenic (BrAGL20) B. napus were hybridized to verify the early flowering phenomenon of F1 hybrids, and F1 hybrid traits were analyzed to predict their impact on sustainability. Flowering of F1 hybrid has been induced slightly later than that of the transgenic B. napus, but flowering was available in the greenhouse without low temperature treatment to young plant, similar to the transgenic B. napus. It is because the BrAGL20 gene has been transferred from transgenic B. napus to F1 hybrid. The size of F1 hybrid seeds was intermediate between those of B. rapa and transgenic B. napus, and ~40% of F1 pollen exhibited abnormal size and morphology. The form of the F1 stomata was also intermediate between that of B. rapa and transgenic B. napus, and the number of stomata was close to the parental mean. Among various fatty acids, the content of erucic acid exhibited the greatest change, owing to the polymorphism of parental FATTY ACID ELONGASE 1 alleles. Furthermore, F2 hybrids could not be obtained. However, BC1 progeny were obtained by hand pollination of B. rapa with F1 hybrid pollen, with an outcrossing rate of 50%. PMID:27632286

  8. E2F1 transcription factor and its impact on growth factor and cytokine signaling.

    PubMed

    Ertosun, Mustafa Gokhan; Hapil, Fatma Zehra; Osman Nidai, Ozes

    2016-10-01

    E2F1 is a transcription factor involved in cell cycle regulation and apoptosis. The transactivation capacity of E2F1 is regulated by pRb. In its hypophosphorylated form, pRb binds and inactivates DNA binding and transactivating functions of E2F1. The growth factor stimulation of cells leads to activation of CDKs (cyclin dependent kinases), which in turn phosphorylate Rb and hyperphosphorylated Rb is released from E2F1 or E2F1/DP complex, and free E2F1 can induce transcription of several genes involved in cell cycle entry, induction or inhibition of apoptosis. Thus, growth factors and cytokines generally utilize E2F1 to direct cells to either fate. Furthermore, E2F1 regulates expressions of various cytokines and growth factor receptors, establishing positive or negative feedback mechanisms. This review focuses on the relationship between E2F1 transcription factor and cytokines (IL-1, IL-2, IL-3, IL-6, TGF-beta, G-CSF, LIF), growth factors (EGF, KGF, VEGF, IGF, FGF, PDGF, HGF, NGF), and interferons (IFN-α, IFN-β and IFN-γ).

  9. Impotence evaluated by the use of prostaglandin E1

    SciTech Connect

    Hwang, T.I.; Yang, C.R.; Wang, S.J.; Chang, C.L.; Tzai, T.S.; Chang, C.H.; Wu, H.C.

    1989-06-01

    We screened 80 patients at our hospital for the differential diagnosis of impotence using intracavernous injection of prostaglandin E1 (20 micrograms). The rate of positive response was 78.8 per cent (63 patients). Neither systemic reactions nor priapism occurred. However, a considerable incidence (23.8 per cent, 19 of 80 patients) of tolerable injection pain was encountered. The 133-xenon penile washout study was conducted routinely in impotent men for hemodynamic evaluation of penile vascularity. In 80 patients a positive correlation between the response of intracavernous prostaglandin E1 injection and the result of the washout study was found (r equals 0.381, p less than 0.0002). We selected 14 subjects randomly to receive additional intravenous infusions of prostaglandin E1 (6 ampules, 120 micrograms total) for 3 days, after which another 133-xenon washout study was done. The washout studies before and after intravenous prostaglandin E1 infusion were compared, and 10 patients (71.4 per cent) appeared to obtain improvement in half-time clearance and penile blood flow. However, only 3 patients noticed improvement subjectively. We suggest that prostaglandin E1 could be a desirable alternative for the diagnosis and treatment of impotence.

  10. Prostaglandins and Their Receptors in Insect Biology

    PubMed Central

    Stanley, David; Kim, Yonggyun

    2011-01-01

    We treat the biological significance of prostaglandins (PGs) and their known receptors in insect biology. PGs and related eicosanoids are oxygenated derivatives of arachidonic acid (AA) and two other C20 polyunsaturated fatty acids. PGs are mostly appreciated in the context of biomedicine, but a growing body of literature indicates the biological significance of these compounds extends throughout the animal kingdom, and possibly beyond. The actions of most PGs are mediated by specific receptors. Biomedical research has discovered a great deal of knowledge about PG receptors in mammals, including their structures, pharmacology, molecular biology and cellular locations. Studies of PG receptors in insects lag behind the biomedical background, however, recent results hold the promise of accelerated research in this area. A PG receptor has been identified in a class of lepidopteran hemocytes and experimentally linked to the release of prophenoloxidase. PGs act in several crucial areas of insect biology. In reproduction, a specific PG, PGE2, releases oviposition behavior in most crickets and a few other insect species; PGs also mediate events in egg development in some species, which may represent all insects. PGs play major roles in modulating fluid secretion in Malpighian tubules, rectum and salivary glands, although, again, this has been studied in only a few insect species that may represent the Class. Insect immunity is a very complex defense system. PGs and other eicosanoids mediate a large number of immune reactions to infection and invasion. We conclude that research into PGs and their receptors in insects will lead to important advances in our understanding of insect biology. PMID:22654840

  11. Prostaglandins and their receptors in insect biology.

    PubMed

    Stanley, David; Kim, Yonggyun

    2011-01-01

    We treat the biological significance of prostaglandins (PGs) and their known receptors in insect biology. PGs and related eicosanoids are oxygenated derivatives of arachidonic acid (AA) and two other C20 polyunsaturated fatty acids. PGs are mostly appreciated in the context of biomedicine, but a growing body of literature indicates the biological significance of these compounds extends throughout the animal kingdom, and possibly beyond. The actions of most PGs are mediated by specific receptors. Biomedical research has discovered a great deal of knowledge about PG receptors in mammals, including their structures, pharmacology, molecular biology and cellular locations. Studies of PG receptors in insects lag behind the biomedical background, however, recent results hold the promise of accelerated research in this area. A PG receptor has been identified in a class of lepidopteran hemocytes and experimentally linked to the release of prophenoloxidase. PGs act in several crucial areas of insect biology. In reproduction, a specific PG, PGE(2), releases oviposition behavior in most crickets and a few other insect species; PGs also mediate events in egg development in some species, which may represent all insects. PGs play major roles in modulating fluid secretion in Malpighian tubules, rectum and salivary glands, although, again, this has been studied in only a few insect species that may represent the Class. Insect immunity is a very complex defense system. PGs and other eicosanoids mediate a large number of immune reactions to infection and invasion. We conclude that research into PGs and their receptors in insects will lead to important advances in our understanding of insect biology.

  12. E2F1 enhances glycolysis through suppressing Sirt6 transcription in cancer cells.

    PubMed

    Wu, Minghui; Seto, Edward; Zhang, Jingsong

    2015-05-10

    The fast proliferation of cancer cells requires reprogramming of its energy metabolism with aerobic glycolysis as a major energy source. Sirt6, a class III histone deacetylase, has been shown to down regulate glycolysis by inhibiting the expression of several key glycolytic genes. Based on the published study on the metabolic phenotype of E2F1 -/- mice and SIRT6 -/- mice, we hypothesize that E2F1 enhances glycolysis and inhibits the expression of Sirt6. Indeed, over-expressing of E2F1, but not its DNA binding deficient mutant, significantly enhanced glucose uptake and lactate production in bladder and prostate cancer cell lines. E2F1 over-expression also suppressed Sirt6 expression and function. Moreover, E2F1 directly bound to Sirt6 promoter and suppressed Sirt6 promoter activity under both normoxic and hypoxic culture conditions. E2F1 siRNA blocked the up-regulation of E2F1 under hypoxia, increased Sirt6 expression and decreased glycolysis compared to those of scrambled siRNA transected cells. Furthermore, HDAC1 deacetylated E2F1 and diminished its transcription suppression of Sirt6 promoter. Treatment with the HDAC inhibitor, trichostatin A (TSA), suppressed Sirt6 promoter activity with increased binding of acetylated E2F1 to Sirt6 promoter. Mutating the E2F1 binding site on the proximal Sirt6 promoter abolished the suppression of Sirt6 transcription by TSA. These data indicate a novel oncogenic role of E2F1, i.e. enhancing glycolysis by suppressing Sirt6 transcription.

  13. Contrasting feature in the repopulation of host-type T cells in the spleens of F1----P and P----F1 radiation bone marrow chimeras

    SciTech Connect

    Hirokawa, K.; Sado, T.; Kubo, S.; Kamisaku, H.; Utsuyama, M.

    1986-11-01

    The regeneration and persistence of host- and donor-derived T cells were examined in the thymus as well as the spleen of mouse radiation bone marrow chimeras of two semiallogeneic combinations (F1----P, P----F1) with different Thy-1 markers on T cells of donor and host origins. An unexpectedly large number of host-type T cells were recovered from the spleens of F1----P chimeras, amounting to as high as 45 and 25% of total T cells at 6 and 14 weeks after bone marrow transplantation (BMT), respectively. To the contrary, the residual host-type T cells in the spleens of P----F1 chimeras disappeared quickly, resulting in less than 0.1% of total T cells at 6 weeks after BMT. It was also revealed that the number of host-type T cells in the spleens of F1----P chimeras decreased in proportion to increase of radiation dose given to the recipients.

  14. 26 CFR 5c.44F-1 - Leases and qualified research expenses.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 14 2014-04-01 2013-04-01 true Leases and qualified research expenses. 5c.44F-1 Section 5c.44F-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) TEMPORARY INCOME TAX REGULATIONS UNDER THE ECONOMIC RECOVERY TAX ACT OF 1981 §...

  15. 26 CFR 5c.44F-1 - Leases and qualified research expenses.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 14 2013-04-01 2013-04-01 false Leases and qualified research expenses. 5c.44F-1 Section 5c.44F-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) TEMPORARY INCOME TAX REGULATIONS UNDER THE ECONOMIC RECOVERY TAX ACT OF 1981 §...

  16. 26 CFR 5c.44F-1 - Leases and qualified research expenses.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 14 2011-04-01 2010-04-01 true Leases and qualified research expenses. 5c.44F-1 Section 5c.44F-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) TEMPORARY INCOME TAX REGULATIONS UNDER THE ECONOMIC RECOVERY TAX ACT OF 1981 §...

  17. 26 CFR 5c.44F-1 - Leases and qualified research expenses.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 14 2012-04-01 2012-04-01 false Leases and qualified research expenses. 5c.44F-1 Section 5c.44F-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) TEMPORARY INCOME TAX REGULATIONS UNDER THE ECONOMIC RECOVERY TAX ACT OF 1981 §...

  18. Sterile Insect Technique and F1 Sterility in the European Grapevine Moth, Lobesia botrana

    PubMed Central

    Saour, George

    2014-01-01

    Newly emerged adults of the European grapevine moth, Lobesia botrana (Denis and Schiffermuller) (Lepidoptera: Tortricidae), were irradiated with various doses of gamma radiation and crossed to unirradiated counterparts of the opposite sex. Fecundity was decreased when unirradiated females were mated with either 300- or 350-Gy-irradiated males. Adult males that were irradiated with 400 Gy and mated with unirradiated females retained a residual fertility of 2.7%. The radiation dose at which irradiated females were found to be 100% sterile when mated with unirradiated males was 150 Gy. The inherited effects in the F1 progeny of irradiated male parents were examined at 100, 150, and 200 Gy. Fecundity and fertility of the F1 progeny of males irradiated with 150 Gy and inbred or crossed with irradiated and unirradiated moths were also recorded. A significant reduction in fertility was observed when F1 males mated with either F1 or unirradiated females. According to sterility index, F1 females who mated with F1 males had greater sterility than when F1 females were crossed to 150-Gy-irradiated males. Based upon the results of this study, 150 Gy of gamma radiation would be the optimal dose to use in a sterile insect technique and F1 sterility program against L. botrana. PMID:25373155

  19. 26 CFR 1.514(f)-1 - Definition of business lease.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Definition of business lease. 1.514(f)-1 Section... § 1.514(f)-1 Definition of business lease. (a) In general. The term business lease means any lease...) if at the close of the organization's taxable year there is a business lease indebtedness as...

  20. 26 CFR 1.430(f)-1 - Effect of prefunding balance and funding standard carryover balance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Effect of prefunding balance and funding standard carryover balance. 1.430(f)-1 Section 1.430(f)-1 Internal Revenue INTERNAL REVENUE SERVICE... Effect of prefunding balance and funding standard carryover balance. (a) In general—(1) Overview....

  1. Bmal1 is a direct transcriptional target of the orphan nuclear receptor, NR2F1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Orphan nuclear receptor NR2F1 (also known as COUP-TFI, Chicken Ovalbumin Upstream Promoter Transcription Factor I) is a highly conserved member of the nuclear receptor superfamily. NR2F1 plays a critical role during embryonic development, particularly in the central and peripheral nervous systems a...

  2. 16 CFR Appendix F1 to Part 305 - Standard Clothes Washers

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Standard Clothes Washers F1 Appendix F1 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULE CONCERNING DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER PRODUCTS REQUIRED UNDER THE ENERGY...

  3. 26 CFR 5c.44F-1 - Leases and qualified research expenses.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Leases and qualified research expenses. 5c.44F-1 Section 5c.44F-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) TEMPORARY INCOME TAX REGULATIONS UNDER THE ECONOMIC RECOVERY TAX ACT OF 1981 §...

  4. E4F1 dysfunction results in autophagic cell death in myeloid leukemic cells

    PubMed Central

    Hatchi, Elodie; Rodier, Geneviève; Sardet, Claude

    2011-01-01

    The multifunctional E4F1 protein was originally identified as a cellular target of the E1A adenoviral oncoprotein. Although E4F1 is implicated in several key oncogenic pathways, its roles in tumorigenesis remain unclear. Using a genetically engineered mouse model of myeloid leukemia (histiocytic sarcomas, HS) based on the genetic inactivation of the tumor suppressor Ink4a/Arf locus, we have recently unraveled an unsuspected function of E4F1 in the survival of leukemic cells. In vivo, genetic ablation of E4F1 in established myeloid tumors results in tumor regression. E4F1 inactivation results in a cascade of alterations originating from dysfunctional mitochondria that induce increased reactive oxygen species (ROS) levels and ends in massive autophagic cell death in HS transformed, but not normal myeloid cells. E4F1 depletion also induces cell death in various human myeloid leukemic cell lines, including acute myeloid leukemic (AML) cell lines. Interestingly, the E4F1 protein is overexpressed in a large proportion of human AML samples. These data provide new insights into E4F1-associated survival functions implicated in tumorigenesis and could open the path for new therapeutic strategies. PMID:22024746

  5. 26 CFR 1.514(f)-1 - Definition of business lease.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 7 2011-04-01 2009-04-01 true Definition of business lease. 1.514(f)-1 Section... TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxation of Business Income of Certain Exempt Organizations § 1.514(f)-1 Definition of business lease. (a) In general. The term business lease means any...

  6. 26 CFR 1.514(f)-1 - Definition of business lease.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 7 2013-04-01 2013-04-01 false Definition of business lease. 1.514(f)-1 Section... TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxation of Business Income of Certain Exempt Organizations § 1.514(f)-1 Definition of business lease. (a) In general. The term business lease means any...

  7. 26 CFR 301.6501(f)-1 - Personal holding company tax.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Personal holding company tax. 301.6501(f)-1... Collection § 301.6501(f)-1 Personal holding company tax. If a corporation which is a personal holding company... capital stock of the corporation, the personal holding company tax for such year may be assessed, or...

  8. 26 CFR 301.6501(f)-1 - Personal holding company tax.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 18 2013-04-01 2013-04-01 false Personal holding company tax. 301.6501(f)-1... Collection § 301.6501(f)-1 Personal holding company tax. If a corporation which is a personal holding company... capital stock of the corporation, the personal holding company tax for such year may be assessed, or...

  9. 26 CFR 301.6501(f)-1 - Personal holding company tax.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 18 2012-04-01 2012-04-01 false Personal holding company tax. 301.6501(f)-1... Collection § 301.6501(f)-1 Personal holding company tax. If a corporation which is a personal holding company... capital stock of the corporation, the personal holding company tax for such year may be assessed, or...

  10. 26 CFR 301.6501(f)-1 - Personal holding company tax.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 18 2014-04-01 2014-04-01 false Personal holding company tax. 301.6501(f)-1... Collection § 301.6501(f)-1 Personal holding company tax. If a corporation which is a personal holding company... capital stock of the corporation, the personal holding company tax for such year may be assessed, or...

  11. 26 CFR 301.6501(f)-1 - Personal holding company tax.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 18 2011-04-01 2011-04-01 false Personal holding company tax. 301.6501(f)-1... Collection § 301.6501(f)-1 Personal holding company tax. If a corporation which is a personal holding company... capital stock of the corporation, the personal holding company tax for such year may be assessed, or...

  12. 78 FR 69538 - Attestation Process for Employers Using F-1 Students in Off-Campus Work

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-20

    ... F-1 Students in Off- Campus Work AGENCY: Employment and Training Administration, Department of Labor... employers seeking to hire F-1 foreign students as part-time workers off-campus. These subparts became...), supplemented sections 101(a)(15)(F) of the Immigration and Nationality Act (8 U.S.C 1101(a)(15)(F)) by...

  13. E2F-1 gene therapy induces apoptosis and increases chemosensitivity in human pancreatic carcinoma cells.

    PubMed

    Elliott, Mary Jane; Farmer, Michael R; Atienza, Cesar; Stilwell, Ariel; Dong, Yan Bin; Yang, Hai Liang; Wong, Sandra L; McMasters, Kelly M

    2002-01-01

    Pancreatic cancer is often resistant to conventional chemotherapy. In this study, we examined the role of adenovirus-mediated overexpression of E2F-1 in inducing apoptosis and increasing the sensitivity of pancreatic cancer cells to chemotherapeutic agents. MIA PaCa-2 pancreatic head exocrine adenocarcinoma cells (mutant p53) were treated by mock infection or adenoviruses expressing beta-galactosidase or E2F-1 (Ad-E2F-1) alone or in combination with sublethal concentrations of each chemotherapeutic drug. Cell growth and viability were assessed at selected time points. Apoptosis was evaluated by flow cytometry, characteristic changes in cell morphology and poly (ADP-ribose) polymerase (PARP) cleavage. Western blot analysis was used to examine the expression of E2F-1 and Bcl-2 family member proteins and PARP cleavage. Western blot analysis revealed marked overexpression of E2F-1 at a multiplicity of infection (MOI) of 20 and 70. By 3 days after infection, Ad-E2F-1 treatment at an MOI of 70 resulted in approximately a 20-fold reduction in cell growth and 60% reduction in cell viability as compared to mock-infected cells. Cell cycle analysis, PARP cleavage and changes in cell morphology supported apoptosis as the mechanism of cell death in response to E2F-1. In order to test the efficacy of treatment with a combination of gene therapy and chemotherapy, we utilized concentrations of Ad-E2F-1 which reduced viability to 50% in combination with each chemotherapeutic agent. Cotreatment of the cells with E2F-1 virus and roscovitine (ROS) or etoposide resulted in an additive effect on cell growth inhibition and induction of apoptosis. Interestingly, 5-fluorouracil did not cooperate with Ad-E2F-1 in the mediation of tumor death or inhibition of cell growth. Immunoblotting for Bcl-2 family members revealed no significant changes in the expression levels of Bcl-2, Bcl X(L), Bax or Bak following gene or 'chemogene' therapy with E2F-1. However, a Bax cleavage product was noted

  14. Suppression of Alzheimer-Associated Inflammation by Microglial Prostaglandin-E2 EP4 Receptor Signaling

    PubMed Central

    Woodling, Nathaniel S.; Wang, Qian; Priyam, Prachi G.; Larkin, Paul; Shi, Ju; Johansson, Jenny U.; Zagol-Ikapitte, Irene; Boutaud, Olivier

    2014-01-01

    A persistent and nonresolving inflammatory response to accumulating Aβ peptide species is a cardinal feature in the development of Alzheimer's disease (AD). In response to accumulating Aβ peptide species, microglia, the innate immune cells of the brain, generate a toxic inflammatory response that accelerates synaptic and neuronal injury. Many proinflammatory signaling pathways are linked to progression of neurodegeneration. However, endogenous anti-inflammatory pathways capable of suppressing Aβ-induced inflammation represent a relatively unexplored area. Here we report that signaling through the prostaglandin-E2 (PGE2) EP4 receptor potently suppresses microglial inflammatory responses to Aβ42 peptides. In cultured microglial cells, EP4 stimulation attenuated levels of Aβ42-induced inflammatory factors and potentiated phagocytosis of Aβ42. Microarray analysis demonstrated that EP4 stimulation broadly opposed Aβ42-driven gene expression changes in microglia, with enrichment for targets of IRF1, IRF7, and NF-κB transcription factors. In vivo, conditional deletion of microglial EP4 in APPSwe-PS1ΔE9 (APP-PS1) mice conversely increased inflammatory gene expression, oxidative protein modification, and Aβ deposition in brain at early stages of pathology, but not at later stages, suggesting an early anti-inflammatory function of microglial EP4 signaling in the APP-PS1 model. Finally, EP4 receptor levels decreased significantly in human cortex with progression from normal to AD states, suggesting that early loss of this beneficial signaling system in preclinical AD development may contribute to subsequent progression of pathology. PMID:24760848

  15. Observation of B(s)(0) → J/ψ f1(1285) decays and measurement of the f1(1285) mixing angle.

    PubMed

    Aaij, R; Adeva, B; Adinolfi, M; Adrover, C; Affolder, A; Ajaltouni, Z; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amerio, S; Amhis, Y; Anderlini, L; Anderson, J; Andreassen, R; Andreotti, M; Andrews, J E; Appleby, R B; Aquines Gutierrez, O; Archilli, F; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Bachmann, S; Back, J J; Badalov, A; Baesso, C; Balagura, V; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Batozskaya, V; Bauer, Th; Bay, A; Beddow, J; Bedeschi, F; Bediaga, I; Belogurov, S; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Benton, J; Berezhnoy, A; Bernet, R; Bettler, M-O; van Beuzekom, M; Bien, A; Bifani, S; Bird, T; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Bowcock, T J V; Bowen, E; Bozzi, C; Brambach, T; van den Brand, J; Bressieux, J; Brett, D; Britsch, M; Britton, T; Brook, N H; Brown, H; Bursche, A; Busetto, G; Buytaert, J; Cadeddu, S; Calabrese, R; Callot, O; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Campora Perez, D; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carranza-Mejia, H; Carson, L; Carvalho Akiba, K; Casse, G; Castillo Garcia, L; Cattaneo, M; Cauet, Ch; Cenci, R; Charles, M; Charpentier, Ph; Cheung, S-F; Chiapolini, N; Chrzaszcz, M; Ciba, K; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coca, C; Coco, V; Cogan, J; Cogneras, E; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Coquereau, S; Corti, G; Couturier, B; Cowan, G A; Craik, D C; Cruz Torres, M; Cunliffe, S; Currie, R; D'Ambrosio, C; David, P; David, P N Y; Davis, A; De Bonis, I; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Silva, W; De Simone, P; Decamp, D; Deckenhoff, M; Del Buono, L; Déléage, N; Derkach, D; Deschamps, O; Dettori, F; Di Canto, A; Dijkstra, H; Dogaru, M; Donleavy, S; Dordei, F; Dosil Suárez, A; Dossett, D; Dovbnya, A; Dupertuis, F; Durante, P; Dzhelyadin, R; Dziurda, A; Dzyuba, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; van Eijk, D; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; El Rifai, I; Elsasser, Ch; Falabella, A; Färber, C; Farinelli, C; Farry, S; Ferguson, D; Fernandez Albor, V; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fiore, M; Fiorini, M; Fitzpatrick, C; Fontana, M; Fontanelli, F; Forty, R; Francisco, O; Frank, M; Frei, C; Frosini, M; Furfaro, E; Gallas Torreira, A; Galli, D; Gandelman, M; Gandini, P; Gao, Y; Garofoli, J; Garosi, P; Garra Tico, J; Garrido, L; Gaspar, C; Gauld, R; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gibson, V; Giubega, L; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gorbounov, P; Gordon, H; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graziani, G; Grecu, A; Greening, E; Gregson, S; Griffith, P; Grillo, L; Grünberg, O; Gui, B; Gushchin, E; Guz, Yu; Gys, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Hafkenscheid, T W; Haines, S C; Hall, S; Hamilton, B; Hampson, T; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; Hartmann, T; He, J; Head, T; Heijne, V; Hennessy, K; Henrard, P; Hernando Morata, J A; van Herwijnen, E; Heß, M; Hicheur, A; Hicks, E; Hill, D; Hoballah, M; Hombach, C; Hulsbergen, W; Hunt, P; Huse, T; Hussain, N; Hutchcroft, D; Hynds, D; Iakovenko, V; Idzik, M; Ilten, P; Jacobsson, R; Jaeger, A; Jans, E; Jaton, P; Jawahery, A; Jing, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Kaballo, M; Kandybei, S; Kanso, W; Karacson, M; Karbach, T M; Kenyon, I R; Ketel, T; Khanji, B; Kochebina, O; Komarov, I; Koopman, R F; Koppenburg, P; Korolev, M; Kozlinskiy, A; Kravchuk, L; Kreplin, K; Kreps, M; Krocker, G; Krokovny, P; Kruse, F; Kucharczyk, M; Kudryavtsev, V; Kurek, K; Kvaratskheliya, T; La Thi, V N; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lambert, R W; Lanciotti, E; Lanfranchi, G; Langenbruch, C; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J-P; Lefèvre, R; Leflat, A; Lefrançois, J; Leo, S; Leroy, O; Lesiak, T; Leverington, B; Li, Y; Li Gioi, L; Liles, M; Lindner, R; Linn, C; Liu, B; Liu, G; Lohn, S; Longstaff, I; Lopes, J H; Lopez-March, N; Lu, H; Lucchesi, D; Luisier, J; Luo, H; Luppi, E; Lupton, O; Machefert, F; Machikhiliyan, I V; Maciuc, F; Maev, O; Malde, S; Manca, G; Mancinelli, G; Maratas, J; Marconi, U; Marino, P; Märki, R; Marks, J; Martellotti, G; Martens, A; Martín Sánchez, A; Martinelli, M; Martinez Santos, D; Martins Tostes, D; Martynov, A; Massafferri, A; Matev, R; Mathe, Z; Matteuzzi, C; Maurice, E; Mazurov, A; McCann, M; McCarthy, J; McNab, A; McNulty, R; McSkelly, B; Meadows, B; Meier, F; Meissner, M; Merk, M; Milanes, D A; Minard, M-N; Molina Rodriguez, J; Monteil, S; Moran, D; Morawski, P; Mordà, A; Morello, M J; Mountain, R; Mous, I; Muheim, F; Müller, K; Muresan, R; Muryn, B; Muster, B; Naik, P; Nakada, T; Nandakumar, R; Nasteva, I; Needham, M; Neubert, S; Neufeld, N; Nguyen, A D; Nguyen, T D; Nguyen-Mau, C; Nicol, M; Niess, V; Niet, R; Nikitin, N; Nikodem, T; Nomerotski, A; Novoselov, A; Oblakowska-Mucha, A; Obraztsov, V; Oggero, S; Ogilvy, S; Okhrimenko, O; Oldeman, R; Onderwater, G; Orlandea, M; Otalora Goicochea, J M; Owen, P; Oyanguren, A; Pal, B K; Palano, A; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Parkes, C; Parkinson, C J; Passaleva, G; Patel, G D; Patel, M; Patrick, G N; Patrignani, C; Pavel-Nicorescu, C; Pazos Alvarez, A; Pearce, A; Pellegrino, A; Penso, G; Pepe Altarelli, M; Perazzini, S; Perez Trigo, E; Pérez-Calero Yzquierdo, A; Perret, P; Perrin-Terrin, M; Pescatore, L; Pesen, E; Pessina, G; Petridis, K; Petrolini, A; Phan, A; Picatoste Olloqui, E; Pietrzyk, B; Pilař, T; Pinci, D; Playfer, S; Plo Casasus, M; Polci, F; Polok, G; Poluektov, A; Polycarpo, E; Popov, A; Popov, D; Popovici, B; Potterat, C; Powell, A; Prisciandaro, J; Pritchard, A; Prouve, C; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, W; Rachwal, B; Rademacker, J H; Rakotomiaramanana, B; Rangel, M S; Raniuk, I; Rauschmayr, N; Raven, G; Redford, S; Reichert, S; Reid, M M; Dos Reis, A C; Ricciardi, S; Richards, A; Rinnert, K; Rives Molina, V; Roa Romero, D A; Robbe, P; Roberts, D A; Rodrigues, A B; Rodrigues, E; Rodriguez Perez, P; Roiser, S; Romanovsky, V; Romero Vidal, A; Rotondo, M; Rouvinet, J; Ruf, T; Ruffini, F; Ruiz, H; Ruiz Valls, P; Sabatino, G; Saborido Silva, J J; Sagidova, N; Sail, P; Saitta, B; Salustino Guimaraes, V; Sanmartin Sedes, B; Santacesaria, R; Santamarina Rios, C; Santovetti, E; Sapunov, M; Sarti, A; Satriano, C; Satta, A; Savrie, M; Savrina, D; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmidt, B; Schneider, O; Schopper, A; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Seco, M; Semennikov, A; Senderowska, K; Sepp, I; Serra, N; Serrano, J; Seyfert, P; Shapkin, M; Shapoval, I; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, O; Shevchenko, V; Shires, A; Silva Coutinho, R; Sirendi, M; Skidmore, N; Skwarnicki, T; Smith, N A; Smith, E; Smith, E; Smith, J; Smith, M; Sokoloff, M D; Soler, F J P; Soomro, F; Souza, D; Souza De Paula, B; Spaan, B; Sparkes, A; Spradlin, P; Stagni, F; Stahl, S; Steinkamp, O; Stevenson, S; Stoica, S; Stone, S; Storaci, B; Straticiuc, M; Straumann, U; Subbiah, V K; Sun, L; Sutcliffe, W; Swientek, S; Syropoulos, V; Szczekowski, M; Szczypka, P; Szilard, D; Szumlak, T; T'jampens, S; Teklishyn, M; Tellarini, G; Teodorescu, E; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Tolk, S; Tomassetti, L; Tonelli, D; Topp-Joergensen, S; Torr, N; Tournefier, E; Tourneur, S; Tran, M T; Tresch, M; Tsaregorodtsev, A; Tsopelas, P; Tuning, N; Ubeda Garcia, M; Ukleja, A; Ustyuzhanin, A; Uwer, U; Vagnoni, V; Valenti, G; Vallier, A; Vazquez Gomez, R; Vazquez Regueiro, P; Vázquez Sierra, C; Vecchi, S; Velthuis, J J; Veltri, M; Veneziano, G; Vesterinen, M; Viaud, B; Vieira, D; Vilasis-Cardona, X; Vollhardt, A; Volyanskyy, D; Voong, D; Vorobyev, A; Vorobyev, V; Voß, C; Voss, H; Waldi, R; Wallace, C; Wallace, R; Wandernoth, S; Wang, J; Ward, D R; Watson, N K; Webber, A D; Websdale, D; Whitehead, M; Wicht, J; Wiechczynski, J; Wiedner, D; Wiggers, L; Wilkinson, G; Williams, M P; Williams, M; Wilson, F F; Wimberley, J; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wright, S; Wu, S; Wyllie, K; Xie, Y; Xing, Z; Yang, Z; Yuan, X; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, F; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhokhov, A; Zhong, L; Zvyagin, A

    2014-03-07

    Decays of B(s)(0) and B(0) mesons into J/ψ π+π-π+π- final states, produced in pp collisions at the LHC, are investigated using data corresponding to an integrated luminosity of 3 fb-1 collected with the LHCb detector. B(s)(0) → J/ψ f1(1285) decays are seen for the first time, and the branching fractions are measured. Using these rates, the f1(1285) mixing angle between strange and nonstrange components of its wave function in the qq structure model is determined to be ±(24.0-2.6-0.8+3.1+0.6)°. Implications on the possible tetraquark nature of the f1(1285) are discussed.

  16. Fo-driven Rotation in the ATP Synthase Direction against the Force of F1 ATPase in the FoF1 ATP Synthase*

    PubMed Central

    Martin, James; Hudson, Jennifer; Hornung, Tassilo; Frasch, Wayne D.

    2015-01-01

    Living organisms rely on the FoF1 ATP synthase to maintain the non-equilibrium chemical gradient of ATP to ADP and phosphate that provides the primary energy source for cellular processes. How the Fo motor uses a transmembrane electrochemical ion gradient to create clockwise torque that overcomes F1 ATPase-driven counterclockwise torque at high ATP is a major unresolved question. Using single FoF1 molecules embedded in lipid bilayer nanodiscs, we now report the observation of Fo-dependent rotation of the c10 ring in the ATP synthase (clockwise) direction against the counterclockwise force of ATPase-driven rotation that occurs upon formation of a leash with Fo stator subunit a. Mutational studies indicate that the leash is important for ATP synthase activity and support a mechanism in which residues aGlu-196 and cArg-50 participate in the cytoplasmic proton half-channel to promote leash formation. PMID:25713065

  17. Suppression of F1 Male-Specific Lethality in Caenorhabditis Hybrids by cbr-him-8

    PubMed Central

    Ragavapuram, Vaishnavi; Hill, Emily Elaine; Baird, Scott Everet

    2015-01-01

    Haldane’s Rule and Darwin’s Corollary to Haldane’s Rule are the observations that heterogametic F1 hybrids are frequently less fit than their homogametic siblings, and that asymmetric results are often obtained from reciprocal hybrid crosses. In Caenorhabditis, Haldane’s Rule and Darwin’s Corollary have been observed in several hybrid crosses, including crosses of Caenorhabditis briggsae and C. nigoni. Fertile F1 females are obtained from reciprocal crosses. However, F1 males obtained from C. nigoni mothers are sterile and F1 males obtained from C. briggsae die during embryogenesis. We have identified cbr-him-8 as a recessive maternal-effect suppressor of F1 hybrid male-specific lethality in this combination of species. This result implicates epigenetic meiotic silencing in the suppression of F1 male-specific lethality. It is also shown that F1 males bearing a C. briggsae X chromosome are fertile. When crossed to C. briggsae hermaphrodites or F1 females derived from C. briggsae hermaphrodites, viable F2 and backcross (B2) progeny were obtained. Sibling males that possessed a C. nigoni X chromosome were sterile. Therefore, the sterility of F1 males bearing a C. nigoni X chromosome must result from dysgenic interactions between the X chromosome of C. nigoni and the autosomes of C. briggsae. The fertility of F1 males bearing a C. briggsae X chromosome provides an opportunity to identify C. nigoni loci that prevent spermatogenesis, and hence hermaphroditic reproduction, in diplo-X hybrids. PMID:26721896

  18. Alterations in locomotor activity induced by radioprotective doses of 16,16-dimethyl prostaglandin E2

    SciTech Connect

    Landauer, M.R.; Walden, T.L.; Davis, H.D.; Dominitz, J.A.

    1987-01-01

    16,16-Dimethyl prostaglandin E2 (DiPGE2) is an effective radioprotectant when administered before irradiation. A notable side effect of this compound is sedation. In separate experiments, the dose-response determinations of the time course of locomotor activity and 30-day survival after 10 Gy gamma irradiation (LD100) were made. Adult male CD2F1 mice were injected subcutaneously with vehicle or DiPGE2 in doses ranging from 0.01 to 40 micrograms per mouse. A dose of 0.01 micrograms did not result in alterations in locomotor behaviour or enhance survival. Doses greater than 1 microgram produced ataxia and enhanced radiation survival in a dose-dependent fashion. Full recovery of locomotor activity did not occur until 6 and 30 hr after injection for the 10 microgram and 40 microgram groups, respectively. Radioprotection was observed when DiPGE2 was administered preirradiation but not postirradiation. Doses of 1 and 10 micrograms were maximally effective as a radioprotectant if injected 5 min prior to irradiation (80%-90% survival). A dose of 40 micrograms resulted in 100% survival when injected 5-30 min before irradiation. Therefore, increasing doses of DiPGE2 resulted in an enhanced effectiveness as a radioprotectant. However, the doses that were the most radioprotective were also the most debilitating to the animal.

  19. Function of the nuclear receptor FTZ-F1 during the pupal stage in Drosophila melanogaster.

    PubMed

    Sultan, Abdel-Rahman S; Oish, Yasuhiro; Ueda, Hitoshi

    2014-04-01

    The nuclear receptor βFTZ-F1 is expressed in most cells in a temporally specific manner, and its expression is induced immediately after decline in ecdysteroid levels. This factor plays important roles during embryogenesis, larval ecdysis, and early metamorphic stages. However, little is known about the expression pattern, regulation and function of this receptor during the pupal stage. We analyzed the expression pattern and regulation of ftz-f1 during the pupal period, as well as the phenotypes of RNAi knockdown or mutant animals, to elucidate its function during this stage. Western blotting revealed that βFTZ-F1 is expressed at a high level during the late pupal stage, and this expression is dependent on decreasing ecdysteroid levels. By immunohistological analysis of the late pupal stage, FTZ-F1 was detected in the nuclei of most cells, but cytoplasmic localization was observed only in the oogonia and follicle cells of the ovary. Both the ftz-f1 genetic mutant and temporally specific ftz-f1 knockdown using RNAi during the pupal stage showed defects in eclosion and in the eye, the antennal segment, the wing and the leg, including bristle color and sclerosis. These results suggest that βFTZ-F1 is expressed in most cells at the late pupal stage, under the control of ecdysteroids and plays important roles during pupal development.

  20. Structure and partial genomic sequence of the human E2F1 gene.

    PubMed

    Neuman, E; Sellers, W R; McNeil, J A; Lawrence, J B; Kaelin, W G

    1996-09-16

    The E2F family of transcription factors appears to play a critical role in the transcription of certain genes required for cell cycle progression. E2F1, the first cloned member of this family, is regulated during the cell cycle at the mRNA level by changes in transcription of the E2F1 gene and at the protein level by complex formation with proteins such as the retinoblastoma gene product (pRB), cyclin A and DP1. E2F1 can override a pRB-induced G1/S block and can behave as an oncogene in certain cells. E2F1 was cloned and was found to contain seven exons. The dinucleotides at the 5' and 3' splice sites of intron 4 do not agree with consensus splice site sequences. Fluorescence in situ hybridization localized E2F1 to chromosome 20q11. Knowledge of the organization of E2F1 may facilitate identification of additional E2F family members, as well as detection of E2F1 abnormalities in human tumors.

  1. E4F1-mediated control of pyruvate dehydrogenase activity is essential for skin homeostasis.

    PubMed

    Goguet-Rubio, Perrine; Seyran, Berfin; Gayte, Laurie; Bernex, Florence; Sutter, Anne; Delpech, Hélène; Linares, Laetitia Karine; Riscal, Romain; Repond, Cendrine; Rodier, Geneviève; Kirsh, Olivier; Touhami, Jawida; Noel, Jean; Vincent, Charles; Pirot, Nelly; Pavlovic, Guillaume; Herault, Yann; Sitbon, Marc; Pellerin, Luc; Sardet, Claude; Lacroix, Matthieu; Le Cam, Laurent

    2016-09-27

    The multifunctional protein E4 transcription factor 1 (E4F1) is an essential regulator of epidermal stem cell (ESC) maintenance. Here, we found that E4F1 transcriptionally regulates a metabolic program involved in pyruvate metabolism that is required to maintain skin homeostasis. E4F1 deficiency in basal keratinocytes resulted in deregulated expression of dihydrolipoamide acetyltransferase (Dlat), a gene encoding the E2 subunit of the mitochondrial pyruvate dehydrogenase (PDH) complex. Accordingly, E4f1 knock-out (KO) keratinocytes exhibited impaired PDH activity and a redirection of the glycolytic flux toward lactate production. The metabolic reprogramming of E4f1 KO keratinocytes associated with remodeling of their microenvironment and alterations of the basement membrane, led to ESC mislocalization and exhaustion of the ESC pool. ShRNA-mediated depletion of Dlat in primary keratinocytes recapitulated defects observed upon E4f1 inactivation, including increased lactate secretion, enhanced activity of extracellular matrix remodeling enzymes, and impaired clonogenic potential. Altogether, our data reveal a central role for Dlat in the metabolic program regulated by E4F1 in basal keratinocytes and illustrate the importance of PDH activity in skin homeostasis.

  2. Genomic and Genetic Variation in E2F1 in Men with Non-Obstructive Azoospermia

    PubMed Central

    Jorgez, Carolina J.; Wilken, Nathan; Addai, Josephine B.; Newberg, Justin; Vangapandu, Hima V.; Pastuszak, Alexander W.; Mukherjee, Sarmistha; Rosenfeld, Jill A.; Lipshultz, Larry I.; Lamb, Dolores J.

    2014-01-01

    Objective To identify gene dosage changes associated with non-obstructive azoospermia (NOA) using array comparative genomic hybridization (aCGH). Design Prospective study. Patients 110 men with NOA and 78 fertile controls. Settings Medical School Interventions None Main Outcome Measure The study has four distinct analytic components: aCGH, a molecular karyotype that detects copy-number-variations (CNV), Taqman-CNV assays to validate CNVs, mutation identification by Sanger sequencing and histologic analyses of testicular tissues. Results A microduplication at 20q11.22 encompassing E2F1 was identified in one of eight men with NOA analyzed using aCGH. CNVs were confirmed and an additional 102 men with NOA screened using Taqman CNV assays for a total of 110 NOA men analyzed for CNVs in E2F1. Eight of 110 (7.3%) NOA men had microduplications or microdeletions of E2F1 that were absent in fertile controls. Conclusions E2F1 microduplications or microdeletions are present in NOA men (7.3%). Duplications or deletions of E2F1 occur very rarely in the general population (0.011%), but E2F1 gene dosage changes, previously reported only in cancers, are present in a subset of NOA men. These results recapitulate the infertility phenotype seen in mice lacking or over-expressing E2f1. PMID:25439843

  3. E4F1-mediated control of pyruvate dehydrogenase activity is essential for skin homeostasis

    PubMed Central

    Goguet-Rubio, Perrine; Seyran, Berfin; Gayte, Laurie; Sutter, Anne; Delpech, Hélène; Linares, Laetitia Karine; Riscal, Romain; Repond, Cendrine; Rodier, Geneviève; Touhami, Jawida; Noel, Jean; Vincent, Charles; Pirot, Nelly; Herault, Yann; Pellerin, Luc; Sardet, Claude; Lacroix, Matthieu; Le Cam, Laurent

    2016-01-01

    The multifunctional protein E4 transcription factor 1 (E4F1) is an essential regulator of epidermal stem cell (ESC) maintenance. Here, we found that E4F1 transcriptionally regulates a metabolic program involved in pyruvate metabolism that is required to maintain skin homeostasis. E4F1 deficiency in basal keratinocytes resulted in deregulated expression of dihydrolipoamide acetyltransferase (Dlat), a gene encoding the E2 subunit of the mitochondrial pyruvate dehydrogenase (PDH) complex. Accordingly, E4f1 knock-out (KO) keratinocytes exhibited impaired PDH activity and a redirection of the glycolytic flux toward lactate production. The metabolic reprogramming of E4f1 KO keratinocytes associated with remodeling of their microenvironment and alterations of the basement membrane, led to ESC mislocalization and exhaustion of the ESC pool. ShRNA-mediated depletion of Dlat in primary keratinocytes recapitulated defects observed upon E4f1 inactivation, including increased lactate secretion, enhanced activity of extracellular matrix remodeling enzymes, and impaired clonogenic potential. Altogether, our data reveal a central role for Dlat in the metabolic program regulated by E4F1 in basal keratinocytes and illustrate the importance of PDH activity in skin homeostasis. PMID:27621431

  4. A Coregulatory Network of NR2F1 and microRNA-140

    PubMed Central

    Ruiz, Fernanda R.; Li, Na; Pereira, Fred A.

    2013-01-01

    Background Both nuclear receptor subfamily 2 group F member 1 (NR2F1) and microRNAs (miRNAs) have been shown to play critical roles in the developing and functional inner ear. Based on previous studies suggesting interplay between NR2F1 and miRNAs, we investigated the coregulation between NR2F1 and miRNAs to better understand the regulatory mechanisms of inner ear development and functional maturation. Results Using a bioinformatic approach, we identified 11 potential miRNAs that might coregulate target genes with NR2F1 and analyzed their targets and potential roles in physiology and disease. We selected 6 miRNAs to analyze using quantitative real-time (qRT) -PCR and found that miR-140 is significantly down-regulated by 4.5-fold (P=0.004) in the inner ear of NR2F1 knockout (Nr2f1–/–) mice compared to wild-type littermates but is unchanged in the brain. Based on this, we performed chromatin-immunoprecipitation followed by qRT-PCR and confirmed that NR2F1 directly binds and regulates both miR-140 and Klf9 in vivo. Furthermore, we performed luciferase reporter assay and showed that miR-140 mimic directly regulates KLF9-3’UTR, thereby establishing and validating an example coregulatory network involving NR2F1, miR-140, and Klf9. Conclusions We have described and experimentally validated a novel tissue-dependent coregulatory network for NR2F1, miR-140, and Klf9 in the inner ear and we propose the existence of many such coregulatory networks important for both inner ear development and function. PMID:24349493

  5. Inhibition of Prostaglandin D Synthase Suppresses Muscular Necrosis

    PubMed Central

    Mohri, Ikuko; Aritake, Kosuke; Taniguchi, Hidetoshi; Sato, Yo; Kamauchi, Shinya; Nagata, Nanae; Maruyama, Toshihiko; Taniike, Masako; Urade, Yoshihiro

    2009-01-01

    Duchenne muscular dystrophy is a fatal muscle wasting disease that is characterized by a deficiency in the protein dystrophin. Previously, we reported that the expression of hematopoietic prostaglandin D synthase (HPGDS) appeared in necrotic muscle fibers from patients with either Duchenne muscular dystrophy or polymyositis. HPGDS is responsible for the production of the inflammatory mediator, prostaglandin D2. In this paper, we validated the hypothesis that HPGDS has a role in the etiology of muscular necrosis. We investigated the expression of HPGDS/ prostaglandin D2 signaling using two different mouse models of muscle necrosis, that is, bupivacaine-induced muscle necrosis and the mdx mouse, which has a genetic muscular dystrophy. We treated each mouse model with the HPGDS-specific inhibitor, HQL-79, and measured both necrotic muscle volume and selected cytokine mRNA levels. We confirmed that HPGDS expression was induced in necrotic muscle fibers in both bupivacaine-injected muscle and mdx mice. After administration of HQL-79, necrotic muscle volume was significantly decreased in both mouse models. Additionally, mRNA levels of both CD11b and transforming growth factor β1 were significantly lower in HQL-79-treated mdx mice than in vehicle-treated animals. We also demonstrated that HQL-79 suppressed prostaglandin D2 production and improved muscle strength in the mdx mouse. Our results show that HPGDS augments inflammation, which is followed by muscle injury. Furthermore, the inhibition of HPGDS ameliorates muscle necrosis even in cases of genetic muscular dystrophy. PMID:19359520

  6. Remaining Sites Verification Package for the 1607-F1 Sanitary Sewer System (124-F-1) and the 100-F-26:8 (1607-F1) Sanitary Sewer Pipelines Waste Sites, Waste Site Reclassification Form 2004-130

    SciTech Connect

    L. M. Dittmer

    2008-03-14

    The 1607-F1 Sanitary Sewer System (124-F-1), consisted of a septic tank, drain field, and associated pipelines that received sanitary waste water from the 1701-F Gatehouse, 1709-F Fire Station, and the 1720-F Administrative Office via the 100-F-26:8 pipelines. The septic tank required remedial action based on confirmatory sampling. In accordance with this evaluation, the verification sampling results support a reclassification of this site to Interim Closed Out. The results of verification sampling show that residual contaminant concentrations do not preclude any future uses and allow for unrestricted use of shallow zone soils. The results also demonstrate that residual contaminant concentrations are protective of groundwater and the Columbia River.

  7. [Process of meiosis in interspecific hybrid F1 Lycopersicon esculentum Mill. x Lycopersicon chilense Dun].

    PubMed

    Montvid, P Iu; Samovol, O P; Miroshnychenko, V P

    2011-01-01

    The investigation concerns meiosis behaviour in embryo-culture-obtained Lycopersicon esculentum Mill. (mutant seedline Mo 638) x L. chilense Dun. F1 hybrid and its parental forms. It was determined that chiasma frequency decreased while univalent and meiotic disorder frequencies increased in F1 plants in comparison with parents forms. Univalent number and the percent of main disorders lowered with bud tier increasing. The conclusion was made about meiosis regularity connection with the influence of environment factors and heterozygous genotype of F1 plants Lycopersicon esculentum x L. chilense.

  8. Synthetic pathways of gallbladder mucosal prostanoids: the role of cyclooxygenase-1 and 2.

    PubMed

    Longo, W E; Panesar, N; Mazuski, J E; Kaminski, D

    1999-02-01

    Acute cholecystitis is associated with increased gallbladder prostanoid formation and the inflammatory changes and prostanoid increases can be inhibited by nonsteroidal anti-inflammatory agents. Recent information indicates that prostanoids are produced by two cyclooxygenase (COX) enzymes, COX-1 and COX-2. The purpose of this study was to determine the COX enzymatic pathway in gallbladder mucosal cells involved in the production of prostanoids stimulated by inflammatory agents. Human gallbladder mucosal cells were isolated from cholecystectomy specimens and maintained in cell culture and studied in comparison with cells from a well differentiated gallbladder mucosal carcinoma cell line. COX enzymes were evaluated by Western immunoblotting and prostanoids were measured by ELISA. Unstimulated and stimulated cells were exposed to specific COX-1 and COX-2 inhibitors. In both normal and transformed cells constitutive COX-1 was evident and in gallbladder cancer cells lysophosphatidyl choline (LPC) induced the formation of constitutive COX-1 enzyme. While not detected in unstimulated normal mucosal cells and cancer cells, COX-2 protein was induced by both lipopolysaccharide (LPS) and LPC. Unstimulated gallbladder mucosal cells and cancer cells produced prostaglandin E2 (PGE2) and prostacyclin (6-keto prostaglandin F1alpha, 6-keto PGF1alpha) continuously. In freshly isolated normal gallbladder mucosal cells, continuously produced 6 keto PGF1alpha was inhibited by both COX-1 and COX-2 inhibitors while PGE2 levels were not affected. Both LPS and LPC stimulated PGE2 and 6 keto PGF1alpha formation were blocked by COX-2 inhibitors in freshly isolated, normal human gallbladder mucosal cells and in the gallbladder cancer cells. The prostanoid response of gallbladder cells stimulated by proinflammatory agents is inhibited by COX-2 inhibitors suggesting that these agents may be effective in treating the pain and inflammation of gallbladder disease.

  9. Long-term assessment of prostaglandin analogs and timolol fixed combinations vs prostaglandin analogs monotherapy

    PubMed Central

    Liu, Ai-Wei; Gan, Lin-Yang; Yao, Xiang; Zhou, Jian

    2016-01-01

    AIM To draw a Meta-analysis over the comparison of the intraocular pressure (IOP)-lowering efficacy and safety between the commonly used fixed-combinations of prostaglandin analogs and 0.5% timolol with prostaglandin analogs (PGAs) monotherapy. METHODS After searching the published reports from MEDLINE, EMBASE, the Cochrane Library, all randomized controlled clinical trials (RCTs) comparing the fixed combination of PGAs/timolol therapy (FCs) and PGAs monotherapy with treatment duration at least 6mo were included. The efficacy outcomes were mean diurnal IOP, percentage of participants whose IOP were lower than 18 mm Hg, incidence of visual field change, while the safety outcomes included corneal side effects, hyperemia and eye irritation. The analysis was carried out in RevMan version 5.3 software. RESULTS After six-month medical intervention, the mean diurnal IOP of FCs was lower than PGAs (MD -1.14, 95% CI -1.82 to -0.46, P=0.001); the percentage of target IOP achieving between FCs and PGAs showed no significant difference (RR 1.18, 95% CI 0.97 to 1.43, P=0.10). No statistically significant differences of the incidence of hyperemia (RR 0.67, 95% CI 0.45 to 1.01, P=0.06) and eye irritation (RR 1.20, 95% CI 0.95 to 1.51, P=0.12) between the FCs and PGAs monotherapy were detected. Only one research involved in corneal events, result of this trial revealed no difference between two intervention groups regarding corneal effects (central endothelial cell density, MD -0.20, 95% CI -0.72 to 0.32, P=0.45; central corneal thickness, MD -0.01, 95% CI -0.02 to 0.00, P=0.23). The evaluation of visual field change was not performed due to the limited duration of the trials included in this Meta-analysis. CONCLUSION The long-term efficacy of the FCs overweighed the PGAs monotherapy in lowering IOP, but in the incidence of hyperemia and eye irritation syndromes, the differences are not statically significant. More RCTs with detailed and authentic data over the assessments of

  10. Metabolic fate of radiolabeled prostaglandin D2 in a normal human male volunteer

    SciTech Connect

    Liston, T.E.; Roberts, L.J. 2d.

    1985-10-25

    50 microCi of (TH)prostaglandin D2 tracer (100 Ci/mmol) was infused intravenously into a normal human male volunteer. 75% of the infused radioactivity was excreted into the urine within 5 h. This urine was added to urine obtained from two mastocytosis patients with marked overproduction of prostaglandin D2. Radiolabeled prostaglandin D2 urinary metabolites were chromatographically isolated and purified and subsequently identified by gas chromatography-mass spectrometry. 25 metabolites were identified. 23 of these compounds comprising 37% of the recovered radioactivity had prostaglandin F-ring structures, and only two metabolites comprising 2.7% of the recovered radioactivity retained the prostaglandin D-ring structure. The single most abundant metabolite identified was 9,11-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-ene-1,20-dioic acid which was isolated in a tricyclic form as a result of formation of a lower side chain hemiketal followed by lactonization of the terminal carboxyl and the hemiketal hydroxyl. Different isomeric forms of several prostaglandin F-ring metabolites were identified. An isomer of prostaglandin F2 alpha was also excreted intact into the urine as a metabolite of prostaglandin D2. 15 PGF-ring compounds were treated with n-butylboronic acid and 13 failed to form a boronate derivative, suggesting that the orientation of the hydroxyl group at C-11 in these 13 metabolites is beta. This study documents that prostaglandin D2 is metabolized to prostaglandin F-ring metabolites in vivo in humans. These results also bring into question the accuracy of quantifying prostaglandin F2 alpha metabolites as a specific index of endogenous prostaglandin F2 alpha biosynthesis, as well as quantifying urinary prostaglandin F2 alpha as an accurate index of renal production of prostaglandin F2 alpha.

  11. Interactions between inducible isoforms of nitric oxide synthase and cyclo-oxygenase in vivo: investigations using the selective inhibitors, 1400W and celecoxib

    PubMed Central

    Hamilton, Lorna C; Warner, Timothy D

    1998-01-01

    Exposure of tissues to endotoxin (LPS) and/or cytokines leads to the induction of both inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2). It has previously been reported that there is `cross-talk' between these two systems. However, such previous studies have been limited by the availability of highly selective inhibitors. Here we have investigated the interactions between iNOS and COX-2 in vivo using 1400W, an iNOS-selective inhibitor, and celecoxib, a COX-2-selective inhibitor.Infusion of LPS to rats for 6 h caused a time-dependent increase in the plasma concentrations of 6 keto-prostaglandin F1α (6 keto-PGF1α) and nitrite/nitrate (NO2/NO3), consistent with the induction of iNOS and COX-2. Bolus injection of arachidonic acid (AA) at t=6 h resulted in a further increase of circulating levels of 6 keto-PGF1α in LPS-treated animals.Treatment of rats with 1400W or the non-selective NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) inhibited the increase in plasma NO2/NO3 but were both without effect on the plasma concentration of 6 keto-PGF1α before or after AA.Treatment with the non-steroidal anti-inflammatory drugs (NSAIDs), A771726 or diclofenac, or with celecoxib significantly reduced the increase in circulating 6 keto-PGF1α caused by LPS, and the large increase in 6 keto-PGF1α following injection of AA. None of the COX inhibitors affected the increase in plasma NO2/NO3. Dexamethasone, however, significantly inhibited both the increase in 6 keto-PGF1α and the increase in NO2/NO3.In conclusion, the use of selective inhibitors does not support the concept of cross talk in vivo between iNOS and COX-2. PMID:9786506

  12. Recovered Apollo-Era Saturn V F-1 Engines Arrive at Cape Canaveral

    NASA Video Gallery

    Two F-1 engines that powered the first stage of the Saturn V rockets that lifted NASA’s Apollo missions to the moon were recovered from the Atlantic Ocean March 20, 2013 by Jeff Bezos, the founde...

  13. Giant Acceleration of Diffusion Observed in a Single-Molecule Experiment on F1-ATPase

    NASA Astrophysics Data System (ADS)

    Hayashi, Ryunosuke; Sasaki, Kazuo; Nakamura, Shuichi; Kudo, Seishi; Inoue, Yuichi; Noji, Hiroyuki; Hayashi, Kumiko

    2015-06-01

    The giant acceleration (GA) of diffusion is a universal phenomenon predicted by the theoretical analysis given by Reimann et al. [Phys. Rev. Lett. 87, 010602 (2001)]. Here we apply the theory of the GA of diffusion to a single-molecule experiment on a rotary motor protein, F1 , which is a component of Fo F1 adenosine triphosphate synthase. We discuss the energetic properties of F1 and identify a high energy barrier of the rotary potential to be 20 kBT , with the condition that the adenosine diphosphates are tightly bound to the F1 catalytic sites. To conclude, the GA of diffusion is useful for measuring energy barriers in nonequilibrium and single-molecule experiments.

  14. 24. CLOSEUP OF MOUNT FOR F1 ENGINE ON STATIC TEST ...

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

    24. CLOSE-UP OF MOUNT FOR F-1 ENGINE ON STATIC TEST TOWER WITH STRUCTURAL DYNAMICS TEST STAND IN DISTANCE. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

  15. 22. STATIC TEST TOWER VIEW OF TEST CELLS AND F1 ...

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

    22. STATIC TEST TOWER VIEW OF TEST CELLS AND F-1 TEST LOCK DOWN FOR ENGINE. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

  16. Arabidopsis RabF1 (ARA6) Is Involved in Salt Stress and Dark-Induced Senescence (DIS)

    PubMed Central

    Yin, Congfei; Karim, Sazzad; Zhang, Hongsheng; Aronsson, Henrik

    2017-01-01

    Arabidopsis small GTPase RabF1 (ARA6) functions in endosomal vesicle transport and may play a crucial role in recycling and degradation of molecules, thus involved in stress responses. Here we have reported that complementary overexpression lines RabF1OE (overexpression), GTPase mutants RabF1Q93L (constitutively active) and RabF1S47N (dominant negative) lines show longer root growth than wild-type, rabF1 knockout and N-myristoylation deletion (Δ1−29, N-terminus) complementary overexpression mutant plants under salt induced stress, which indicates that N-myristoylation of RabF1 is indispensable for salt tolerance. Moreover, RabF1 is highly expressed during senescence and RabF1OE lines were more tolerant of dark-induced senescence (DIS) than wild-type and rabF1. PMID:28157156

  17. Evaluation of IRI predicted characteristics of ionospheric F1 layer by ionosonde observations in Nicosia, Cyprus

    NASA Astrophysics Data System (ADS)

    Mostafa, Md Golam; Haralambous, Haris; Oikonomou, Christina

    2017-03-01

    This paper presents an investigation of F1 layer characteristics derived from manually scaled digital ionosonde measurements at the low-middle latitude European station in Nicosia, Cyprus (geographical coordinates: 35°N, 33°E, geomagnetic lat. 29.38°N, I = 51.7°) from low to high solar activity conditions (2009-2014) and their comparison with IRI-2012 predictions. It assesses the predictability of occurrence probability by employing all three options included in IRI-2012: IRI-95, Scotto-97 no L, and Scotto-97 with L. Results show that Scotto-97 no L option slightly overestimates the occurrence probability but predicts better than IRI-95 option, whereas IRI-95 option closely reflects the time range for F1 layer appearance. The Scotto-97 with L option slightly underestimates the occurrence probability of foF1 + ledge type. A seasonal variation marked with higher occurrence probability in the equinoctial months than in winter is observed, both at low and high solar activity. IRI predictions match reasonably well observed values of foF1 with maximum 0.3 MHz over/under estimation at low solar activity. At high solar activity, IRI slightly overestimates the values of foF1 throughout the year with a varying degree from 0.3 to 1.3 MHz, except for the months of August and September, when the values are underestimated by 0.3 MHz. A seasonal variation with higher foF1 values during equinoctial months than that of summer and winter is noticed in the observations at high solar activity in 2014. Long-term solar variation in the observed foF1 values were evident. Deviation of IRI-2012 predictions from observed foF1 values increases at high solar activity. Observed values of hmF1 demonstrate no distinct diurnal variation. However, these are lower in winter than those of summer and equinoctial months. No significant long-term solar variation in hmF1 was detected during the entire period under consideration. Throughout 2009-2014, with a few exceptions, IRI generally

  18. Complete genome sequence of Staphylothermus marinus Stetter and Fiala 1986 type strain F1

    SciTech Connect

    Anderson, Iain; Sun, Hui; Lapidus, Alla L.; Copeland, A; Glavina Del Rio, Tijana; Tice, Hope; Dalin, Eileen; Lucas, Susan; Barry, Kerrie; Land, Miriam L; Richardson, P M; Huber, Harald; Kyrpides, Nikos C

    2009-01-01

    Staphylothermus marinus Fiala and Stetter 1986 belongs to the order Desulfurococcales within the archaeal phylum Crenarchaeota. S. marinus is a hyperthermophilic, sulfur-dependent, anaerobic heterotroph. Strain F1 was isolated from geothermally heated sediments at Vulcano, Italy, but S. marinus has also been isolated from a hydrothermal vent on the East Pacific Rise. We report the complete genome of S. marinus strain F1, the type strain of the species. This is the fifth reported complete genome sequence from the order Desulfurococcales.

  19. Maternal Vitamin D Deficiency Delays Glomerular Maturity in F1 and F2 Offspring

    PubMed Central

    Nascimento, Fernanda A. M.; Ceciliano, Thais C.; Aguila, Marcia B.; Mandarim-de-Lacerda, Carlos A.

    2012-01-01

    Background There is a high prevalence of vitamin D insufficiency in women of reproductive age. Methods This work studied the first two generations of offspring (F1 and F2) of Swiss mice from mothers fed one of two diets: SC (standard chow) or VitD- (vitamin D-deficient). Functional and developmental kidney measurements were taken. Results The first two generations of the VitD- group had higher blood pressure at 6 months of age than the offspring of the SC group as well as an increase in renin and AT1r expression. However, at all ages, both F1 and F2 VitD- mice had shorter glomerular diameters, and diet played a significant role in the total variation. Both the F1 and F2 generations of the VitD- group had more immature glomeruli than offspring from the SC group. Immature glomeruli begin to disappear at 10 days, but at this age, F1-VitD- mice had more immature and mature glomeruli than F1-SC mice. At 6 months of age, F1-VitD- mice exhibited more glomeruli, while F2-VitD- mice exhibited the same number of glomeruli as F2-SC mice, but fewer glomeruli compared to the F1-VitD group. Both diet and generation account for the total variation in the number of glomeruli. Decreases in urine output and podocin expression and increases in urea and creatinine in the urine were observed in F1 offspring. Conclusion These findings demonstrate that maternal vitamin D deficiency accompanies changes in the renal expression of important factors that may retard the maturation of glomeruli by extending the period of nephrogenesis. PMID:22927914

  20. 26 CFR 31.3121(f)-1 - American vessel and aircraft.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 15 2013-04-01 2013-04-01 false American vessel and aircraft. 31.3121(f)-1... § 31.3121(f)-1 American vessel and aircraft. (a) The term “American vessel” means any vessel which is...”, see § 31.3121 (e)-1.) (b) The term “American aircraft” means any aircraft registered under the laws...

  1. 26 CFR 31.3121(f)-1 - American vessel and aircraft.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false American vessel and aircraft. 31.3121(f)-1... § 31.3121(f)-1 American vessel and aircraft. (a) The term “American vessel” means any vessel which is...”, see § 31.3121 (e)-1.) (b) The term “American aircraft” means any aircraft registered under the laws...

  2. 26 CFR 31.3121(f)-1 - American vessel and aircraft.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 15 2011-04-01 2011-04-01 false American vessel and aircraft. 31.3121(f)-1... § 31.3121(f)-1 American vessel and aircraft. (a) The term “American vessel” means any vessel which is...”, see § 31.3121 (e)-1.) (b) The term “American aircraft” means any aircraft registered under the laws...

  3. 26 CFR 31.3121(f)-1 - American vessel and aircraft.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 15 2014-04-01 2014-04-01 false American vessel and aircraft. 31.3121(f)-1... § 31.3121(f)-1 American vessel and aircraft. (a) The term “American vessel” means any vessel which is...”, see § 31.3121 (e)-1.) (b) The term “American aircraft” means any aircraft registered under the laws...

  4. 26 CFR 31.3121(f)-1 - American vessel and aircraft.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 15 2012-04-01 2012-04-01 false American vessel and aircraft. 31.3121(f)-1... § 31.3121(f)-1 American vessel and aircraft. (a) The term “American vessel” means any vessel which is...”, see § 31.3121 (e)-1.) (b) The term “American aircraft” means any aircraft registered under the laws...

  5. Cezanne regulates E2F1-dependent HIF2α expression

    PubMed Central

    Moniz, Sonia; Bandarra, Daniel; Biddlestone, John; Campbell, Kirsteen J.; Komander, David; Bremm, Anja; Rocha, Sonia

    2015-01-01

    ABSTRACT Mechanisms regulating protein degradation ensure the correct and timely expression of transcription factors such as hypoxia inducible factor (HIF). Under normal O2 tension, HIFα subunits are targeted for proteasomal degradation, mainly through vHL-dependent ubiquitylation. Deubiquitylases are responsible for reversing this process. Although the mechanism and regulation of HIFα by ubiquitin-dependent proteasomal degradation has been the object of many studies, little is known about the role of deubiquitylases. Here, we show that expression of HIF2α (encoded by EPAS1) is regulated by the deubiquitylase Cezanne (also known as OTUD7B) in an E2F1-dependent manner. Knockdown of Cezanne downregulates HIF2α mRNA, protein and activity independently of hypoxia and proteasomal degradation. Mechanistically, expression of the HIF2α gene is controlled directly by E2F1, and Cezanne regulates the stability of E2F1. Exogenous E2F1 can rescue HIF2α transcript and protein expression when Cezanne is depleted. Taken together, these data reveal a novel mechanism for the regulation of the expression of HIF2α, demonstrating that the HIF2α promoter is regulated by E2F1 directly and that Cezanne regulates HIF2α expression through control of E2F1 levels. Our results thus suggest that HIF2α is controlled transcriptionally in a cell-cycle-dependent manner and in response to oncogenic signalling. PMID:26148512

  6. Rb inactivation leads to E2F1-mediated DNA double-strand break accumulation.

    PubMed

    Pickering, M T; Kowalik, T F

    2006-02-02

    Although it is unclear which cellular factor(s) is responsible for the genetic instability associated with initiating and sustaining cell transformation, it is known that many cancers have mutations that inactivate the Rb-mediated proliferation pathway. We show here that pRb inactivation and the resultant deregulation of one E2F family member, E2F1, leads to DNA double-strand break (DSB) accumulation in normal diploid human cells. These DSBs occur independent of Atm, p53, caspases, reactive oxygen species, and apoptosis. Moreover, E2F1 does not contribute to c-Myc-associated DSBs, indicating that the DSBs associated with these oncoproteins arise through distinct pathways. We also find E2F1-associated DSBs in an Rb mutated cancer cell line in the absence of an exogenous DSB stimulus. These basal, E2F1-associated DSBs are not observed in a p16(ink4a) inactivated cancer cell line that retains functional pRb, unless pRb is depleted. Thus, Rb status is key to regulating both the proliferation promoting functions associated with E2F and for preventing DNA damage accumulation if E2F1 becomes deregulated. Taken together, these data suggest that loss of Rb creates strong selective pressure, via DSB accumulation, for inactivating p53 mutations and that E2F1 contributes to the genetic instability associated with transformation and tumorigenesis.

  7. MEF/ELF4 transactivation by E2F1 is inhibited by p53.

    PubMed

    Taura, Manabu; Suico, Mary Ann; Fukuda, Ryosuke; Koga, Tomoaki; Shuto, Tsuyoshi; Sato, Takashi; Morino-Koga, Saori; Okada, Seiji; Kai, Hirofumi

    2011-01-01

    Myeloid elf-1-like factor (MEF) or Elf4 is an E-twenty-six (ETS)-related transcription factor with strong transcriptional activity that influences cellular senescence by affecting tumor suppressor p53. MEF downregulates p53 expression and inhibits p53-mediated cellular senescence by transcriptionally activating MDM2. However, whether p53 reciprocally opposes MEF remains unexplored. Here, we show that MEF is modulated by p53 in human cells and mice tissues. MEF expression and promoter activity were suppressed by p53. While we found that MEF promoter does not contain p53 response elements, intriguingly, it contains E2F consensus sites. Subsequently, we determined that E2F1 specifically binds to MEF promoter and transactivates MEF. Nevertheless, E2F1 DNA binding and transactivation of MEF promoter was inhibited by p53 through the association between p53 and E2F1. Furthermore, we showed that activation of p53 in doxorubicin-induced senescent cells increased E2F1 and p53 interaction, diminished E2F1 recruitment to MEF promoter and reduced MEF expression. These observations suggest that p53 downregulates MEF by associating with and inhibiting the binding activity of E2F1, a novel transcriptional activator of MEF. Together with previous findings, our present results indicate that a negative regulatory mechanism exists between p53 and MEF.

  8. Comparison between single-molecule and X-ray crystallography data on yeast F1-ATPase.

    PubMed

    Steel, Bradley C; Nord, Ashley L; Wang, Yamin; Pagadala, Vijayakanth; Mueller, David M; Berry, Richard M

    2015-03-10

    Single molecule studies in recent decades have elucidated the full chemo-mechanical cycle of F1-ATPase, mostly based on F1 from thermophilic bacteria. In contrast, high-resolution crystal structures are only available for mitochondrial F1. Here we present high resolution single molecule rotational data on F1 from Saccharomyces cerevisiae, obtained using new high throughput detection and analysis tools. Rotational data are presented for the wild type mitochondrial enzyme, a "liver" isoform, and six mutant forms of yeast F1 that have previously been demonstrated to be less efficient or partially uncoupled. The wild-type and "liver" isoforms show the same qualitative features as F1 from Escherichia coli and thermophilic bacteria. The analysis of the mutant forms revealed a delay at the catalytic dwell and associated decrease in Vmax, with magnitudes consistent with the level of disruption seen in the crystal structures. At least one of the mutant forms shows a previously un-observed dwell at the ATP binding angle, potentially attributable to slowed release of ADP. We discuss the correlation between crystal structures and single molecule results.

  9. NR2F1 controls tumor cell dormancy via SOX9 and RARβ driven quiescence programs

    PubMed Central

    Sosa, Maria Soledad; Parikh, Falguni; Maia, Alexandre Gaspar; Estrada, Yeriel; Bosch, Almudena; Bragado, Paloma; Ekpin, Esther; George, Ajish; Zheng, Yang; Lam, Hung-Ming; Morrissey, Colm; Chung, Chi-Yeh; Farias, Eduardo F.; Bernstein, Emily; Aguirre-Ghiso, Julio A.

    2014-01-01

    Metastases can originate from disseminated tumor cells (DTCs), which may be dormant for years before reactivation. Here we find that the orphan nuclear receptor NR2F1 is epigenetically upregulated in experimental HNSCC dormancy models and in DTCs from prostate cancer patients carrying dormant disease for 7–18 years. NR2F1-dependent dormancy is recapitulated by a co-treatment with the DNA demethylating agent 5-Aza-C and retinoic acid across various cancer types. NR2F1-induced quiescence is dependent on SOX9, RARβ and CDK inhibitors. Intriguingly, NR2F1 induces global chromatin repression and the pluripotency gene NANOG, which contributes to dormancy of DTCs in the bone marrow. When NR2F1 is blocked in vivo, growth arrest or survival of dormant DTCs is interrupted in different organs. We conclude that NR2F1 is a critical node in dormancy induction and maintenance by integrating epigenetic programs of quiescence and survival in DTCs. PMID:25636082

  10. Transcriptional regulation of human RANK ligand gene expression by E2F1

    SciTech Connect

    Hu Yan; Sun Meng; Nadiminty, Nagalakshmi; Lou Wei; Pinder, Elaine; Gao, Allen C.

    2008-06-06

    Receptor activator of nuclear factor kappa B ligand (RANKL) is a critical osteoclastogenic factor involved in the regulation of bone resorption, immune function, the development of mammary gland and cardiovascular system. To understand the transcriptional regulation of RANKL, we amplified and characterized a 1890 bp 5'-flanking sequence of human RANKL gene (-1782 bp to +108 bp relative to the transcription start site). Using a series of deletion mutations of the 1890 bp RANKL promoter, we identified a 72 bp region (-172 to -100 bp) mediating RANKL basal transcriptional activity. Sequence analysis revealed a putative E2F binding site within this 72 bp region in the human RANKL promoter. Overexpression of E2F1 increased RANKL promoter activity, while down-regulation of E2F1 expression by small interfering RNA decreased RANKL promoter activity. RT-PCR and enzyme linked immunosorbent assays (ELISA) further demonstrated that E2F1 induced the expression of RANKL. Electrophoretic gel mobility shift assays (EMSA) and antibody competition assays confirmed that E2F1 proteins bind to the consensus E2F binding site in the RANKL promoter. Mutation of the E2F consensus binding site in the RANKL promoter profoundly reduced the basal promoter activity and abolished the transcriptional modulation of RANKL by E2F1. These results suggest that E2F1 plays an important role in regulating RANKL transcription through binding to the E2F consensus binding site.

  11. Phylodynamics of HIV-1 subtype F1 in Angola, Brazil and Romania.

    PubMed

    Bello, Gonzalo; Afonso, Joana Morais; Morgado, Mariza G

    2012-07-01

    The HIV-1 subtype F1 is exceptionally prevalent in Angola, Brazil and Romania. The epidemiological context in which the spread of HIV occurred was highly variable from one country to another, mainly due to the existence of a long-term civil war in Angola and the contamination of a large number of children in Romania. Here we apply phylogenetic and Bayesian coalescent-based methods to reconstruct the phylodynamic patterns of HIV-1 subtype F1 in such different epidemiological settings. The phylogenetic analyses of HIV-1 subtype F1 pol sequences sampled worldwide confirmed that most sequences from Angola, Brazil and Romania segregated in country-specific monophyletic groups, while most subtype F1 sequences from Romanian children branched as a monophyletic sub-cluster (Romania-CH) nested within sequences from adults. The inferred time of the most recent common ancestor of the different subtype F1 clades were as follow: Angola=1983 (1978-1989), Brazil=1977 (1972-1981), Romania adults=1980 (1973-1987), and Romania-CH=1985 (1978-1989). All subtype F1 clades showed a demographic history best explained by a model of logistic population growth. Although the expansion phase of subtype F1 epidemic in Angola (mid 1980s to early 2000s) overlaps with the civil war period (1975-2002), the mean estimated growth rate of the Angolan F1 clade (0.49 year(-1)) was not exceptionally high, but quite similar to that estimated for the Brazilian (0.69 year(-1)) and Romanian adult (0.36 year(-1)) subtype F1 clades. The Romania-CH subtype F1 lineage, by contrast, displayed a short and explosive dissemination phase, with a median growth rate (2.47 year(-1)) much higher than that estimated for adult populations. This result supports the idea that the AIDS epidemic that affected the Romanian children was mainly caused by the spread of the HIV through highly efficient parenteral transmission networks, unlike adult populations where HIV is predominantly transmitted through sexual route.

  12. Studies on the metabolism of prostaglandin D/sub 2/ in humans

    SciTech Connect

    Liston, T.E.

    1985-01-01

    Fifty ..mu..Ci of (/sup 3/H)-prostaglandin D/sub 2/ tracer (100 Ci/mMole) was infused intravenously into a normal human male volunteer. Seventy-five percent of the infused radioactivity was excreted into the urine within 5 hours. This urine was added to urine obtained from two mastocytosis patients with marked overproduction of prostaglandin D/sub 2/. Twenty-five radiolabelled prostaglandin D/sub 2/ urinary metabolites were chromatographically isolated and purified and subsequently identified by gas chromatography-mass spectrometry. Twenty-three of these metabolites, comprising 37% of the recovered radioactivity, had prostaglandin F-ring structures, and only 2 metabolites, comprising 2.7% of the recovered radioactivity retained the prostaglandin D-ring structure. The single most abundant metabolite identified was 9,11-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-energy-1,20-dioic acid which was isolated in a tricyclic form. Different isomeric forms of several prostaglandin F-ring metabolites were identified. To further investigate the metabolism of prostaglandin D/sub 2/, in vitro studies examining the metabolic transformation of prostaglandin D/sub 2/ by human liver were conducted. This study documents that prostaglandin D/sub 2/ is metabolized to PGF-ring metabolites in vivo in humans, and is converted to a structurally new prostaglandin, 9/sub ..cap alpha../, 11/sub ..beta../-PGF/sub 2/ in vitro by a cytosolic NADPH-dependent 11-Ketoreductase in the human liver.

  13. Effects of centrally administered prostaglandin E(3) and thromboxane A(3) on plasma noradrenaline and adrenaline in rats: comparison with prostaglandin E(2) and thromboxane A(2).

    PubMed

    Shimizu, Takahiro; Yokotani, Kunihiko

    2009-06-02

    Previously, we reported the involvement of brain omega-6 prostanoids, especially prostaglandin E(2) and thromboxane A(2), in the activation of central sympatho-adrenomedullary outflow in rats. omega-3 Prostanoids, including prostaglandin E(3) and thromboxane A(3), are believed to be less bioactive than omega-6 prostanoids, although studies on the functions of omega-3 prostanoids in the central nervous system have not been reported. In the present study, therefore, we compared the effects of centrally administered omega-3 prostanoids, prostaglandin E(3) and thromboxane A(3), with those of omega-6 prostanoids, prostaglandin E(2) and thromboxane A(2), on the plasma catecholamines in anesthetized rats. Intracerebroventricularly (i.c.v.) administered prostaglandin E(2) (0.15, 0.3 and 1.5 nmol/animal) and prostaglandin E(3) (0.3 and 3 nmol/animal) predominantly elevated plasma noradrenaline but not adrenaline, but the latter was less efficient than the former. On the other hand, U-46619 (an analog of thromboxane A(2)) (30, 100 and 300 nmol/animal, i.c.v.) and Delta(17)-U-46619 (an analog of thromboxane A(3)) (100 and 300 nmol/animal, i.c.v.) both elevated plasma catecholamines (adrenaline>noradrenaline) to the same degree. These results suggest that centrally administered prostaglandin E(3) is less effective than prostaglandin E(2) to elevate plasma noradrenaline, and that thromboxane A(3) is almost as equipotent as thromboxane A(2) to elevate plasma catecholamines in rats.

  14. Metabolism of prostaglandin F2 alpha in Zellweger syndrome. Peroxisomal beta-oxidation is a major importance for in vivo degradation of prostaglandins in humans.

    PubMed Central

    Diczfalusy, U; Kase, B F; Alexson, S E; Björkhem, I

    1991-01-01

    We have recently shown in vitro that the peroxisomal fraction of a rat liver homogenate has the highest capacity to beta-oxidize prostaglandins. In order to evaluate the relative importance of peroxisomes for this conversion also in vivo, we administered [3H]prostaglandin F2 alpha to an infant suffering from Zellweger syndrome, a congenital disorder characterized by the absence of intact peroxisomes. As a control, labeled compound was administered to two healthy volunteers. Urine was collected, fractionated on a SEP-PAK C18 cartridge, and subjected to reversed-phase high-performance liquid chromatography. The Zellweger patient was found to excrete prostaglandin metabolites considerably less polar than those of the control subjects. The major urinary metabolite in the control subjects was practically absent in the urine from the Zellweger patient. The major urinary prostaglandin F2 alpha metabolite from the Zellweger patient was identified as an omega-oxidized C20-prostaglandin, 9,11-dihydroxy-15-oxoprost-5-ene-1,20-dioic acid. The major urinary prostaglandin F2 alpha metabolite from the control subjects had chromatographic properties of a tetranor (C16) prostaglandin, in accordance with earlier published data. The present results, in combination with our previous in vitro data, indicate that peroxisomal beta-oxidation is of major importance for in vivo chain shortening of prostaglandins. PMID:1885782

  15. Remaining Sites Verification Package for the 1607-F1 Sanitary Sewer System (124-F-1) and the 100-F-26:8 (1607-F1) Sanitary Sewer Pipelines Waste Sites, Waste Site Reclassification Form 2005-004

    SciTech Connect

    L. M. Dittmer

    2008-03-14

    The 100-F-26:8 waste site consisted of the underground pipelines that conveyed sanitary waste water from the 1701-F Gatehouse, 1709-F Fire Station, and the 1720-F Administrative Office to the 1607-F1 septic tank. The site has been remediated and presently exists as an open excavation. In accordance with this evaluation, the verification sampling results support a reclassification of this site to Interim Closed Out. The results of verification sampling demonstrated that residual contaminant concentrations do not preclude any future uses and allow for unrestricted use of shallow zone soils. The results also showed that residual contaminant concentrations are protective of groundwater and the Columbia River.

  16. Prostaglandin E receptors as inflammatory therapeutic targets for atherosclerosis.

    PubMed

    Yang, Cui; Liu, Xiuxia; Cao, Qing; Liang, Qian; Qiu, Xiaohua

    2011-01-31

    Prostaglandin E receptors (EPs) are the G-protein-coupled receptors (GPCRs) that respond to type E(2) prostaglandin (PGE(2)). Data has shown that PGE(2) may function as an endogenous anti-inflammatory mediator by suppressing the production of cytokines. However, other studies have demonstrated that PGE(2), a pro-inflammatory mediator produced by various cell types within the wounded vascular wall, plays a crucial role in early atherosclerotic development. These contradictory results may be due to the versatility of EPs. Experimental data suggest an individual role for each PGE(2) receptor, such as EP(1), EP(2), EP(3) and EP(4), in atherosclerosis. In this review, the roles of EPs in atherosclerosis are summarized, and the value of EPs as new therapeutic targets for atherosclerosis is explored.

  17. Sex, drugs and sports: prostaglandins, epitestosterone and sexual development.

    PubMed

    Sanders, Bryan K

    2007-01-01

    Amateau and McCarthy's findings published in Nature Neuroscience (June 2004) are noteworthy for suggesting a role for prostaglandins in sexual development. However, evidence suggests that in manipulating PGE2, they unknowingly implicated 3alpha-hydroxysteroid dehydrogenase [E.C. 1.1.1.50], 3(or 17)alpha-hydroxysteroid dehydrogenase [E.C. 1.1.1.209] and their respective products, androsterone (ADT) and epitestosterone (EpiT), in the developmental masculinization of sex behavior. EpiT is generally regarded as a hormonally inactive 17alpha-epimer of testosterone (T). In rats, the kidney is the primary site of EpiT formation, whereas in humans it originates from the gonads, with only a small contribution secreted by the adrenals. Because the ratio of T to EpiT is nearly constant, it is presently used for assessing steroid abuse in competitive sports, where the World Anti-Doping Agency (WADA) considers a T/EpiT ratio >4 evidence of T doping. Despite its central role in the detection of illict anabolic steroid use, our knowledge of factors effecting EpiT production is poor. Clues in the literature, however, reveal that prostaglandin-mediated processes, such as LHRH release, may influence its production. Antimycotics, NSAIDs, and opioid analgesics used in sports medicine are all known to effect prostaglandin E2 synthesis. Primary PGs are potent inhibitors of ADT oxidation, while indomethacin, a prostaglandin blocker, powerfully inhibits 3alpha-HSD reduction and ADT oxidation. This is significant because ADT inhibits the oxidation of EpiT, and may modulate its antiandrogenic and neuroprotective effects. It is hypothesized that the T/EpiT ratio is increased by COX-2 inhibitors and opiod analgesics, and decreased by antimycotics that do not impair testosterone biosynthesis. Given the devastating personal and career consequences that may result from false positive drug tests, substantive research on the effects of PGE2 manipulations on EpiT is warranted.

  18. Phosphoprotein F1: purification and characterization of a brain kinase C substrate related to plasticity.

    PubMed

    Chan, S Y; Murakami, K; Routtenberg, A

    1986-12-01

    To study the role of protein kinase C (PKC) and its substrates in neuronal function, we have investigated the in vitro endogenous phosphorylation of the neuronal phosphoprotein F1 after induction of synaptic plasticity by long-term potentiation (LTP). The protein F1 phosphorylation was found to increase 5 min (Routtenberg et al., 1985), 1 hr (Lovinger et al., 1986) and 3 d (Lovinger et al., 1985) after LTP. The characteristics of this protein bear close similarities to a number of proteins characterized in various neuronal systems, such as B50 (brain specific, synaptosome-enriched protein), pp46 (a growth cone protein), and GAP 43 (nerve growth and regeneration-associated protein). A positive identification of the purified protein F1 with these proteins would link protein F1 to the developmental growth of axons, nerve regeneration, and polyphosphoinositide metabolism, as well as adult plasticity. We have therefore purified and partially characterized native protein F1 so that a meaningful comparison among the properties of these proteins can be made. Using synaptosomal plasma membrane (P2') as starting material, subsequent purification involved pH extraction, 40-80% ammonium sulfate precipitation, hydroxylapatite, and phenyl-Sepharose column chromatography. This procedure achieved greater than 800-fold purification and about 45% yield relative to P2'. Purified protein F1 (Mr = 47,000, pI = 4.5) was found to be a hydrophilic molecule and was phosphorylated by 1000-fold purified PKC in the presence of phosphatidylserine (PS) and Ca2+. The Ka of PS activation is about 15 micrograms/ml (approximately 20 microM), and that of Ca2+ is about 25 microM. Diolein and DiC:8 (a synthetic diacylglycerol) lowered the requirement of Ca2+ for maximal stimulation from 100 to 5 microM. Ca2+-calmodulin kinases type I and II did not phosphorylate protein F1. The phosphoamino acid analysis showed that 97% of the total incorporated 32P-phosphate was on the serine residue. Phosphopeptide

  19. Expression of ADAM12 is regulated by E2F1 in small cell lung cancer.

    PubMed

    Li, Zunling; Wang, Yaopeng; Kong, Lijun; Yue, Zhen; Ma, Ying; Chen, Xufang

    2015-12-01

    Our previous study reported that ADAM12 was highly expressed in small cell lung cancer (SCLC) and could be an effective marker for diagnosis and prognosis. Yet, the reason for the high expression of ADAM12 in SCLC requires further elucidation. Transcription factor E2F1 has been receiving increasing attention due to the complexity and diversity of its function in cancer. In the present study, the expression of ADAM12 was significantly decreased following silencing of E2F1 expression by siRNA, thus indicating that E2F1 may regulate the expression of ADAM12 at the level of transcription. Chromatin immunoprecipitation-to-sequence analysis identified three binding sites for E2F1 in the locus for ADAM12. They were Chr10: 128010444-128011026, located in the intron of ADAM12, named seq0; Chr10: 128076927‑128078127, located in the promoter of ADAM12, named seq1; and Chr10: 128086195‑128086876, located in the upstream 20 kb from the transcription start site of ADAM12, named: seq2. Dual‑luciferase reporter experiments revealed that seq1 not seq0 and seq2 was able to promote the expression of luciferase. Notably, co-transfection of E2F1 significantly increased the activity of seq1 not seq0 and seq2, but quantitative polymerase chain reaction results showed that seq0, seq1 and seq2 could recruit E2F1, indicating that the influence of E2F1 in regulating the expression of ADAM12 was complex. Sequence analysis clarified that seq1 was a part of the ADAM12 promoter, yet the functions of seq0 and seq2 were unknown. Fusion fragments containing seq0-seq1 or seq2-seq1 were analyzed in luciferase constructs. Compared with seq1 alone, the activities of these fusion fragments were non-significantly reduced. The activities of fusion fragments were significantly decreased following co-transfection with E2F1. Thus, the present findings support the conclusion that the E2F1 transcription factor regulates the expression of ADAM12 by binding differential cis-acting elements.

  20. E4F1 controls a transcriptional program essential for pyruvate dehydrogenase activity

    PubMed Central

    Lacroix, Matthieu; Rodier, Geneviève; Houles, Thibault; Delpech, Hélène; Seyran, Berfin; Gayte, Laurie; Casas, Francois; Pessemesse, Laurence; Heuillet, Maud; Bellvert, Floriant; Portais, Jean-Charles; Berthet, Charlene; Brivet, Michele; Boutron, Audrey; Le Cam, Laurent; Sardet, Claude

    2016-01-01

    The mitochondrial pyruvate dehydrogenase (PDH) complex (PDC) acts as a central metabolic node that mediates pyruvate oxidation and fuels the tricarboxylic acid cycle to meet energy demand. Here, we reveal another level of regulation of the pyruvate oxidation pathway in mammals implicating the E4 transcription factor 1 (E4F1). E4F1 controls a set of four genes [dihydrolipoamide acetlytransferase (Dlat), dihydrolipoyl dehydrogenase (Dld), mitochondrial pyruvate carrier 1 (Mpc1), and solute carrier family 25 member 19 (Slc25a19)] involved in pyruvate oxidation and reported to be individually mutated in human metabolic syndromes. E4F1 dysfunction results in 80% decrease of PDH activity and alterations of pyruvate metabolism. Genetic inactivation of murine E4f1 in striated muscles results in viable animals that show low muscle PDH activity, severe endurance defects, and chronic lactic acidemia, recapitulating some clinical symptoms described in PDC-deficient patients. These phenotypes were attenuated by pharmacological stimulation of PDH or by a ketogenic diet, two treatments used for PDH deficiencies. Taken together, these data identify E4F1 as a master regulator of the PDC. PMID:27621446

  1. Synergistic cooperation of MDM2 and E2F1 contributes to TAp73 transcriptional activity

    SciTech Connect

    Kasim, Vivi; Huang, Can; Zhang, Jing; Jia, Huizhen; Wang, Yunxia; Yang, Li; Miyagishi, Makoto; Wu, Shourong

    2014-07-04

    Highlights: • MDM2 is a novel positive regulator of TAp73 transcriptional activity. • MDM2 colocalizes together and physically interacts with E2F1. • Synergistic cooperation of MDM2 and E2F1 is crucial for TAp73 transcription. • MDM2 regulates TAp73 transcriptional activity in a p53-independent manner. - Abstract: TAp73, a structural homologue of p53, plays an important role in tumorigenesis. E2F1 had been reported as a transcriptional regulator of TAp73, however, the detailed mechanism remains to be elucidated. Here we reported that MDM2-silencing reduced the activities of the TAp73 promoters and the endogenous TAp73 expression level significantly; while MDM2 overexpression upregulated them. We further revealed that the regulation of TAp73 transcriptional activity occurs as a synergistic effect of MDM2 and E2F1, most probably through their physical interaction in the nuclei. Furthermore, we also suggested that MDM2 might be involved in DNA damage-induced TAp73 transcriptional activity. Finally, we elucidated that MDM2-silencing reduced the proliferation rate of colon carcinoma cells regardless of the p53 status. Our data show a synergistic effect of MDM2 and E2F1 on TAp73 transcriptional activity, suggesting a novel regulation pathway of TAp73.

  2. Spatial reference memory in normal aging Fischer 344 × Brown Norway F1 hybrid rats.

    PubMed

    McQuail, Joseph A; Nicolle, Michelle M

    2015-01-01

    Fischer 344 × Brown Norway F1 (F344 × BN-F1) hybrid rats express greater longevity with improved health relative to aging rodents of other strains; however, few behavioral reports have thoroughly evaluated cognition across the F344 × BN-F1 lifespan. Consequently, this study evaluated spatial reference memory in F344 × BN-F1 rats at 6, 18, 24, or 28 months of age in the Morris water maze. Reference memory decrements were observed between 6 and 18 months and 18 and 24 months. At 28 months, spatial learning was not worse than 24 months, but swim speed was significantly slower. Reliable individual differences revealed that ∼50% of 24- to 28-month-old rats performed similarly to 6 months, whereas others were spatial learning impaired. Aged rats were impaired at learning within daily training sessions but not impaired at retaining information between days of training. Aged rats were also slower to learn to escape onto the platform, regardless of strategy. In summary, these data clarify the trajectory of cognitive decline in aging F344 × BN-F1 rats and elucidate relevant behavioral parameters.

  3. E4F1 controls a transcriptional program essential for pyruvate dehydrogenase activity.

    PubMed

    Lacroix, Matthieu; Rodier, Geneviève; Kirsh, Olivier; Houles, Thibault; Delpech, Hélène; Seyran, Berfin; Gayte, Laurie; Casas, Francois; Pessemesse, Laurence; Heuillet, Maud; Bellvert, Floriant; Portais, Jean-Charles; Berthet, Charlene; Bernex, Florence; Brivet, Michele; Boutron, Audrey; Le Cam, Laurent; Sardet, Claude

    2016-09-27

    The mitochondrial pyruvate dehydrogenase (PDH) complex (PDC) acts as a central metabolic node that mediates pyruvate oxidation and fuels the tricarboxylic acid cycle to meet energy demand. Here, we reveal another level of regulation of the pyruvate oxidation pathway in mammals implicating the E4 transcription factor 1 (E4F1). E4F1 controls a set of four genes [dihydrolipoamide acetlytransferase (Dlat), dihydrolipoyl dehydrogenase (Dld), mitochondrial pyruvate carrier 1 (Mpc1), and solute carrier family 25 member 19 (Slc25a19)] involved in pyruvate oxidation and reported to be individually mutated in human metabolic syndromes. E4F1 dysfunction results in 80% decrease of PDH activity and alterations of pyruvate metabolism. Genetic inactivation of murine E4f1 in striated muscles results in viable animals that show low muscle PDH activity, severe endurance defects, and chronic lactic acidemia, recapitulating some clinical symptoms described in PDC-deficient patients. These phenotypes were attenuated by pharmacological stimulation of PDH or by a ketogenic diet, two treatments used for PDH deficiencies. Taken together, these data identify E4F1 as a master regulator of the PDC.

  4. F1-ATPase conformational cycle from simultaneous single-molecule FRET and rotation measurements

    PubMed Central

    Sugawa, Mitsuhiro; Okazaki, Kei-ichi; Kobayashi, Masaru; Matsui, Takashi; Hummer, Gerhard; Masaike, Tomoko; Nishizaka, Takayuki

    2016-01-01

    Despite extensive studies, the structural basis for the mechanochemical coupling in the rotary molecular motor F1-ATPase (F1) is still incomplete. We performed single-molecule FRET measurements to monitor conformational changes in the stator ring-α3β3, while simultaneously monitoring rotations of the central shaft-γ. In the ATP waiting dwell, two of three β-subunits simultaneously adopt low FRET nonclosed forms. By contrast, in the catalytic intermediate dwell, two β-subunits are simultaneously in a high FRET closed form. These differences allow us to assign crystal structures directly to both major dwell states, thus resolving a long-standing issue and establishing a firm connection between F1 structure and the rotation angle of the motor. Remarkably, a structure of F1 in an ε-inhibited state is consistent with the unique FRET signature of the ATP waiting dwell, while most crystal structures capture the structure in the catalytic dwell. Principal component analysis of the available crystal structures further clarifies the five-step conformational transitions of the αβ-dimer in the ATPase cycle, highlighting the two dominant modes: the opening/closing motions of β and the loosening/tightening motions at the αβ-interface. These results provide a new view of tripartite coupling among chemical reactions, stator conformations, and rotary angles in F1-ATPase. PMID:27166420

  5. Identification of E2F1 as a positive transcriptional regulator for {delta}-catenin

    SciTech Connect

    Kim, Kwonseop; Oh, Minsoo; Ki, Hyunkyoung; Wang Tao; Bareiss, Sonja; Fini, M. Elizabeth.; Li Dawei; Lu Qun

    2008-05-02

    {delta}-Catenin is upregulated in human carcinomas. However, little is known about the potential transcriptional factors that regulate {delta}-catenin expression in cancer. Using a human {delta}-catenin reporter system, we have screened several nuclear signaling modulators to test whether they can affect {delta}-catenin transcription. Among {beta}-catenin/LEF-1, Notch1, and E2F1, E2F1 dramatically increased {delta}-catenin-luciferase activities while {beta}-catenin/LEF-1 induced only a marginal increase. Rb suppressed the upregulation of {delta}-catenin-luciferase activities induced by E2F1 but did not interact with {delta}-catenin. RT-PCR and Western blot analyses in 4 different prostate cancer cell lines revealed that regulation of {delta}-catenin expression is controlled mainly at the transcriptional level. Interestingly, the effects of E2F1 on {delta}-catenin expression were observed only in human cancer cells expressing abundant endogenous {delta}-catenin. These studies identify E2F1 as a positive transcriptional regulator for {delta}-catenin, but further suggest the presence of strong negative regulator(s) for {delta}-catenin in prostate cancer cells with minimal endogenous {delta}-catenin expression.

  6. Independent Review of the Failure Modes of F-1 Engine and Propellants System

    NASA Technical Reports Server (NTRS)

    Ray, Paul

    2003-01-01

    The F-1 is the powerful engine, that hurdled the Saturn V launch vehicle from the Earth to the moon on July 16,1969. The force that lifted the rocket overcoming the gravitational force during the first stage of the flight was provided by a cluster of five F-1 rocket engines, each of them developing over 1.5 million pounds of thrust (MSFC-MAN-507). The F-1 Rocket engine used RP-1 (Rocket Propellant-1, commercially known as Kerosene), as fuel with lox (liquid Oxygen) as oxidizer. NASA terminated Saturn V activity and has focused on Space Shuttle since 1972. The interest in rocket system has been revived to meet the National Launch System (NLS) program and a directive from the President to return to the Moon and exploration of the space including Mars. The new program Space Launch Initiative (SLI) is directed to drastically reduce the cost of flight for payloads, and adopt a reusable launch vehicle (RLV). To achieve this goal it is essential to have the ability of lifting huge payloads into low earth orbit. Probably requiring powerful boosters as strap-ons to a core vehicle, as was done for the Saturn launch vehicle. The logic in favor of adopting Saturn system, a proven technology, to meet the SLI challenge is very strong. The F-1 engine was the largest and most powerful liquid rocket engine ever built, and had exceptional performance. This study reviews the failure modes of the F-1 engine and propellant system.

  7. Mechanism and clinical significance of prostaglandin-induced iris pigmentation.

    PubMed

    Stjernschantz, Johan W; Albert, Daniel M; Hu, Dan-Ning; Drago, Filippo; Wistrand, Per J

    2002-08-01

    The new glaucoma drugs latanoprost, isopropyl unoprostone, travoprost, and bimatoprost cause increased pigmentation of the iris in some patients. The purpose of the present article is to survey the available preclinical and clinical data on prostaglandin-induced iris pigmentation and to assess the phenomenon from a clinical perspective. Most of the data have been obtained with latanoprost, and it appears that there is a predisposition to latanoprost-induced iris pigmentation in individuals with hazel or heterochromic eye color. As latanoprost and travoprost are selective agonists for the prostaglandin F(2alpha) receptor, it is likely that the phenomenon is mediated by this receptor. Several studies indicate that latanoprost stimulates melanogenesis in iridial melanocytes, and transcription of the tyrosinase gene is upregulated. The safety aspects of latanoprost-induced iris pigmentation have been addressed in histopathologic studies, and no evidence of harmful consequences of the side effect has been found. Although a final assessment of the clinical significance of prostaglandin-induced iris pigmentation currently is impossible to make, it appears that the only clear-cut disadvantage is a potential heterochromia between the eyes in unilaterally treated patients because the heterochromia is likely to be permanent, or very slowly reversible.

  8. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis

    PubMed Central

    North, Trista E.; Goessling, Wolfram; Walkley, Carl R.; Lengerke, Claudia; Kopani, Kamden R.; Lord, Allegra M.; Weber, Gerhard J.; Bowman, Teresa V.; Jang, Il-Ho; Grosser, Tilo; FitzGerald, Garret A.; Daley, George Q.; Orkin, Stuart H.; Zon, Leonard I.

    2009-01-01

    Haematopoietic stem cell (HSC) homeostasis is tightly controlled by growth factors, signalling molecules and transcription factors. Definitive HSCs derived during embryogenesis in the aorta-gonad-mesonephros region subsequently colonize fetal and adult haematopoietic organs1,2. To identify new modulators of HSC formation and homeostasis, a panel of biologically active compounds was screened for effects on stem cell induction in the zebrafish aorta-gonad-mesonephros region. Here, we show that chemicals that enhance prostaglandin (PG) E2 synthesis increased HSC numbers, and those that block prostaglandin synthesis decreased stem cell numbers. The cyclooxygenases responsible for PGE2 synthesis were required for HSC formation. A stable derivative of PGE2 improved kidney marrow recovery following irradiation injury in the adult zebrafish. In murine embryonic stem cell differentiation assays, PGE2 caused amplification of multipotent progenitors. Furthermore, ex vivo exposure to stabilized PGE2 enhanced spleen colony forming units at day 12 post transplant and increased the frequency of long-term repopulating HSCs present in murine bone marrow after limiting dilution competitive transplantation. The conserved role for PGE2 in the regulation of vertebrate HSC homeostasis indicates that modulation of the prostaglandin pathway may facilitate expansion of HSC number for therapeutic purposes. PMID:17581586

  9. Effects of nonhypotensive endotoxemia in conscious rats: Role of prostaglandins

    SciTech Connect

    Burnier, M.; Waeber, B.; Aubert, J.F.; Nussberger, J.; Brunner, H.R. )

    1988-03-01

    A nonhypotensive dose of endotoxin was administered to normal conscious rats to evaluate the vascular and humoral effects of endotoxemia per se. Mean blood pressure and heart rate remained stable during the 45 min infusion of Escherichia coli endotoxin. However, a marked increase in plasma renin activity plasma epinephrine and plasma norepinephrine was observed during infusion in endotoxin-treated rats when compared with the vehicle-treated animals. In addition, the blood pressure response to exogenous norepinephrine was significantly reduced during nonhypotensive endotoxemia. Significant changes in regional blood flow distribution, as assessed by radiolabeled microspheres, were observed in endotoxemic rats; in particular a decrease in renal blood flow, and an increase in coronary blood flow were found. The role of prostaglandins in the vascular and humoral alterations induced by nonhypotensive endotoxemia was also examined. Pretreatment with indomethacin (5 mg) prevent the increase in plasma renin activity as well as plasma catecholamine levels. On the contrary, the decreased vascular reactivity and the reduction in renal blood flow observed during endotoxemia were not affected by prostaglandin synthesis inhibition. Thus significant vascular and humoral changes have been found during endotoxemia even in absence of hypotension. The humoral but not the vascular effects of endotoxemia were abolished when prostaglandin synthesis was inhibited.

  10. Mid trimester abortion by one shot administration of prostaglandin.

    PubMed

    Ganguli, A C; Krishna, U R; Mhatre, V S; Purandare, V N

    1977-10-01

    268 cases in which mid trimester abortion in the 2nd trimester of pregnancy was performed by injecting prostaglandins by intra-amniotic route were studied. Details are presented of 1 study in which 100 cases had prostaglandin injected intraamniotically in 1 shot. 50 cases received 50 mg of PGF2a and 40 received 2.5 mg of 15 Methyl PGF2a, an analogue more potent and longer acting. The majority of the patients were primigravida, most of these being unmarried mothers. The average gestation period in both groups was between 17-18 weeks. The average induction onset interval was considerably shorter in PGF2a group, but its abortion time was just about 1 hour less than that of the methyl analogue. The average incidence of vomiting is about 2-folds and that of loose motionsis almost 5 times in the 15 Methyl group. 81% of the patients were followed up, and 86% of this group stopped bleeding within 10 days and the remaining within 20 days. There has not been a single incidence of post abortal infection. The disadvantages associated with the original intravenous administration of prostaglandin have been overcome by using the intra-amniotic routes. 1 of the greatest advantages of 1 shot intra-amniotic PGF2a 50 mg was a low incidence of incomplete abortion. Only 12% of cases in this group had retained placenta compared to 40-50% in the other groups.

  11. 26 CFR 1.167(f)-1 - Reduction of salvage value taken into account for certain personal property.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Reduction of salvage value taken into account for certain personal property. 1.167(f)-1 Section 1.167(f)-1 Internal Revenue INTERNAL REVENUE SERVICE... for Individuals and Corporations § 1.167(f)-1 Reduction of salvage value taken into account...

  12. 26 CFR 54.4980F-1 - Notice requirements for certain pension plan amendments significantly reducing the rate of future...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... whether an amendment is a section 204(h) amendment. Thus, for example, provisions relating to the right to... amendments significantly reducing the rate of future benefit accrual. 54.4980F-1 Section 54.4980F-1 Internal... (CONTINUED) PENSION EXCISE TAXES § 54.4980F-1 Notice requirements for certain pension plan...

  13. 26 CFR 54.4980F-1 - Notice requirements for certain pension plan amendments significantly reducing the rate of future...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... whether an amendment is a section 204(h) amendment. Thus, for example, provisions relating to the right to... amendments significantly reducing the rate of future benefit accrual. 54.4980F-1 Section 54.4980F-1 Internal... (CONTINUED) PENSION EXCISE TAXES § 54.4980F-1 Notice requirements for certain pension plan...

  14. 40 CFR Table F-1 to Subpart F of... - Performance Specifications for PM2.5 Class II Equivalent Samplers

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Performance Specifications for PM2.5 Class II Equivalent Samplers F Table F-1 to Subpart F of Part 53 Protection of Environment ENVIRONMENTAL..., Subpt. F, Table F-1 Table F-1 to Subpart F of Part 53—Performance Specifications for PM2.5 Class...

  15. 40 CFR Table F-1 to Subpart F of... - Performance Specifications for PM2.5 Class II Equivalent Samplers

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 5 2011-07-01 2011-07-01 false Performance Specifications for PM2.5 Class II Equivalent Samplers F Table F-1 to Subpart F of Part 53 Protection of Environment ENVIRONMENTAL..., Subpt. F, Table F-1 Table F-1 to Subpart F of Part 53—Performance Specifications for PM2.5 Class...

  16. Influence of ShuJinHuoXue tablets on ischemia reperfusion injury of animals' skeletal muscle.

    PubMed

    Tong, Zhihong; Yu, Fang; Liu, Zhonghua; Liang, Haidong

    2012-07-16

    Ischemia-reperfusion (IR) can lead to serious tissue oxidative injury in animals. ShuJinHuoXue tablet (SJHXT) is a Chinese Traditional Medicine which can relax the muscles and stimulate the blood circulation and has been used as a clinical medicine. In the present study, we investigated the effects of SJHXT pretreatment on oxidative injury using an animal model of acute limb IR. Results showed that SJHXT pre-treatment (200, 300 and 400 mg/kg/day) markedly reduced serum endothelin-1 (ET-1), thromboxane B2 (TXB₂) levels and thromboxane B2/6-keto- prostaglandin F1α (TXB₂/6-Keto-PGF(1α)), wet weight/dried weight (W/D) ratio, myeloperoxidase (MPO), creatine kinase (CK), lactate dehydrogenase (LDH) activities, and increased serum nitric oxide (NO), 6-Keto-PGF(1α) levels and NO/ET-1 ratio in the IR+SJHXT groups. In addition, the SJHXT pre-treatment (200, 300 and 400 mg/kg/day) markedly reduced skeletal muscle Ca²⁺, malondialdehyde (MDA) levels, increased Na⁺-K⁺-ATPase, Ca²⁺-Mg²⁺-ATPase, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. Our results suggest that SJHXT pre-treatment may improve skeletal muscle blood vessel microcirculation, decrease skeletal muscle oxidative injury and enhance antioxidant enzymes activities in IR animals.

  17. Hypotensive and Angiotensin-Converting Enzyme Inhibitory Activities of Eisenia fetida Extract in Spontaneously Hypertensive Rats

    PubMed Central

    Mao, Shumei; Li, Chengde

    2015-01-01

    Objectives. This study aimed to investigate the antihypertensive effects of an Eisenia fetida extract (EFE) and its possible mechanisms in spontaneously hypertensive rats (SHR rats). Methods. Sixteen-week-old SHR rats and Wistar-Kyoto rats (WKY rats) were used in this study. Rats were, respectively, given EFE (EFE group), captopril (captopril group), or phosphate-buffered saline (PBS) (normal control group and SHR group) for 4 weeks. ACE inhibitory activity of EFE in vitro was determined. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using a Rat Tail-Cuff Blood Pressure System. Levels of angiotensin II (Ang II), aldosterone (Ald), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1α) in plasma were determined by radioimmunoassay, and serum nitric oxide (NO) concentration was measured by Griess reagent systems. Results. EFE had marked ACE inhibitory activity in vitro (IC50 = 2.5 mg/mL). After the 4-week drug management, SHR rats in EFE group and in captopril group had lower SBP and DBP, lower levels of Ang II and Ald, and higher levels of 6-keto-PGF1α and NO than the SHR rats in SHR group. Conclusion. These results indicate that EFE has hypotensive effects in SHR rats and its effects might be associated with its ACE inhibitory activity. PMID:26798397

  18. Hydroxytyrosyl alkyl ether derivatives inhibit platelet activation after oral administration to rats.

    PubMed

    Muñoz-Marín, Javier; De la Cruz, José Pedro; Reyes, José Julio; López-Villodres, Juan Antonio; Guerrero, Ana; López-Leiva, Inmaculada; Espartero, José Luis; Labajos, María Teresa; González-Correa, José Antonio

    2013-08-01

    The low lipophilicity of hydroxytyrosol (HT) has motivated efforts to synthesize homologous series with better lipid solubility, such as the ethers, which are more lipophilic than HT. Because HT inhibits platelet aggregation, the aim of the study was to assess the possible anti-platelet effect of five HT ether derivatives (ethyl, butyl, hexyl, octyl and dodecyl) after oral administration to rats. Whole blood collagen-induced platelet aggregation and calcium-induced thromboxane B2 (TxB2), aortic 6-keto-prostaglandin F1α (6-keto-PGF1α) and nitrites+nitrates, plasma concentration of lipid peroxides (TBARS) and red blood cell content of reduced glutathione (GSH) were measured. The administration of 20 mg/kg/day inhibited platelet aggregation, TxB2 and TBARS in a non-linear manner related to the length of the carbon chain, with a cut-off effect in the hexyl derivative. Aortic nitrite and red blood cell GSH production were also increased. The aortic production of 6-keto-PGF1α was unaltered except in the group treated with the dodecyl derivative. The administration of 50 mg/kg/day showed a similar pharmacodynamic profile but without the non-linear effect. In conclusion, HT ethers, especially the hexyl derivative, are a potential alternative to hydroxytyrosol, and their effect merits additional research to determine their role in the prophylaxis of vascular disease.

  19. Eicosanoid synthesis in cardiomyocytes: influence of hypoxia, reoxygenation, and polyunsaturated fatty acids.

    PubMed

    Oudot, F; Grynberg, A; Sergiel, J P

    1995-01-01

    The synthesis of eicosanoids was investigated in cultured rat ventricular myocytes. Under normoxia, the cardiomyocytes released 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and prostaglandin (PG) E2 and smaller amounts of PGF2 alpha and thromboxane B2. Hypoxia enhanced the production of PGE2 and PGF2 alpha, whereas the synthesis of 6-keto-PGF1 alpha was not affected. Conversely, posthypoxic reoxygenation greatly increased the synthesis of 6-keto-PGF1 alpha, whereas the synthesis of PGF2 alpha, was not affected and that of PGE2 was reduced. The cardiomyocyte polyunsaturated fatty acid (PUFA) profile was altered by arachidonic acid or eicosapentaenoic acid and docosahexaenoic acid. Under normoxia, the eicosanoid production appeared to be roughly related to the cell phospholipid arachidonic acid content. Conversely, during posthypoxic reoxygenation, the production of eicosanoids was related to the cell phospholipid n-3 PUFA content, with the n-3-rich cells displaying a marked inhibition of the synthesis. This inhibition was mainly attributed to eicosapentaenoic acid and/or docosapentaenoic acid. Whether this inhibition occurs in vivo during postischemic reperfusion, it may contribute to the beneficial effect of n-3 PUFA on the heart.

  20. Microbial ketonization of ginsenosides F1 and C-K by Lactobacillus brevis.

    PubMed

    Jin, Yan; Jung, Sun Young; Kim, Yeon-Ju; Lee, Dae-Young; Min, Jin-Woo; Wang, Chao; Yang, Deok-Chun

    2014-12-01

    Ginsenosides are the major pharmacological components in ginseng. We isolated lactic acid bacteria from Kimchi to identify microbial modifications of ginsenosides. Phylogenetic analysis of 16S rRNA gene sequences indicated that the strain DCY65-1 belongs to the genus Lactobacillus and is most closely related to Lactobacillus brevis. On the basis of TLC and HPLC analysis, we found two metabolic pathways: F1 → 6α,12β-dihydroxydammar-3-one-20(S)-O-β-D-glucopyranoside and C-K → 12β-hydroxydammar-3-one-20(S)-O-β-D-glucopyranoside. These results suggest that strain DCY65-1 is capable of potent ketonic decarboxylation, ketonizing the hydroxyl group at C-3. The F1 metabolite had a more potent inhibitory effect on mushroom tyrosinase than did the substrate. Therefore, the F1 and C-K derivatives may be more pharmacologically active compounds, which should be further characterized.

  1. Optical pumping effect in absorption imaging of F =1 atomic gases

    NASA Astrophysics Data System (ADS)

    Kim, Sooshin; Seo, Sang Won; Noh, Heung-Ryoul; Shin, Y.

    2016-08-01

    We report our study of the optical pumping effect in absorption imaging of 23Na atoms in the F =1 hyperfine spin states. Solving a set of rate equations for the spin populations in the presence of a probe beam, we obtain an analytic expression for the optical signal of the F =1 absorption imaging. Furthermore, we verify the result by measuring the absorption spectra of 23Na Bose-Einstein condensates prepared in various spin states with different probe-beam pulse durations. The analytic result can be used in the quantitative analysis of F =1 spinor condensate imaging and readily applied to other alkali-metal atoms with I =3 /2 nuclear spin such as 87Rb.

  2. Prostaglandin E2 Receptor Expression by Osteoblasts is Modulated by Implant Surface Roughness and Prostaglandin E2

    DTIC Science & Technology

    2006-05-01

    al. 1996; Trancik et al. 1989). Thus, it is of vital importance to the field of dental implantology to investigate how prostaglandins mediate their...of Texas Graduate School of Biomedical Sciences at San Antonio Supervising Professor: David D. Dean, Ph.D. While the predictability of dental implants...control media lacking PGE2. Cells were incubated for an additional 3, 6, or 120 hrs to simulate the early response after dental implant placement, after

  3. Mechanical stimulation of skeletal muscle cells mitigates glucocorticoid-induced decreases in prostaglandin production and prostaglandin synthase activity

    NASA Technical Reports Server (NTRS)

    Chromiak, J. A.; Vandenburgh, H. H.

    1994-01-01

    The glucocorticoid dexamethasone (Dex) induces a decline in protein synthesis and protein content in tissue cultured, avian skeletal muscle cells, and this atrophy is attenuated by repetitive mechanical stretch. Since the prostaglandin synthesis inhibitor indomethacin mitigated this stretch attenuation of muscle atrophy, the effects of Dex and mechanical stretch on prostaglandin production and prostaglandin H synthase (PGHS) activity were examined. In static cultures, 10(-8) M Dex reduced PGF2 alpha production 55-65% and PGE2 production 84-90% after 24-72 h of incubation. Repetitive 10% stretch-relaxations of non-Dex-treated cultures increased PGF2 alpha efflux 41% at 24 h and 276% at 72 h, and increased PGE2 production 51% at 24 h and 236% at 72 h. Mechanical stimulation of Dex-treated cultures increased PGF2 alpha production 162% after 24 h, returning PGF2 alpha efflux to the level of non-Dex-treated cultures. At 72 h, stretch increased PGF2 alpha efflux 65% in Dex-treated cultures. Mechanical stimulation of Dex-treated cultures also increased PGE2 production at 24 h, but not at 72 h. Dex reduced PGHS activity in the muscle cultures by 70% after 8-24 h of incubation, and mechanical stimulation of the Dex-treated cultures increased PGHS activity by 98% after 24 h. Repetitive mechanical stimulation attenuates the catabolic effects of Dex on cultured skeletal muscle cells in part by mitigating the Dex-induced declines in PGHS activity and prostaglandin production.

  4. Role of endogenous prostaglandins in protection of rat gastric mucosa by tripotassium dicitrate bismuthate.

    PubMed

    Malandrino, S; Bestetti, A; Fumagalli, G; Borsa, M; Viganó, T; Tonon, G

    1987-10-01

    Gross and microscopic examination of rat gastric mucosa demonstrated that intragastric administration to rats of tripotassium dicitrate bismuthate (TDB), a colloidal bismuth compound, protects against gastric lesions induced by 85% ethanol. Indomethacin, a prostaglandin synthetase inhibitor, significantly blocked the gastric mucosal protective effect of TDB. The release of gastric mucosal prostaglandins was greater in animals treated with TDB than in control animals, both time- and dose-dependently. These results seem to indicate involvement of prostaglandins in the action of TDB.

  5. Cat (Fel d 1) and dog (Can f 1) allergen levels in cars, dwellings and schools.

    PubMed

    Niesler, A; Ścigała, G; Łudzeń-Izbińska, B

    Pets are an important source of indoor allergens. The aim of the study was to compare cat and dog allergen levels in cars, schools and homes. The study was carried out in 17 cars, 14 classrooms and 19 dwellings located in the highly industrialized and urbanized region of Poland. Dust and air samples were analyzed for Fel d 1 and Can f 1 using a double monoclonal ELISA assay. The highest amounts of cat and dog allergens (Fel d 1: 1169 μg/g; Can f 1: 277 μg/g) were found in dwellings with pets. Allergen concentrations were correlated with the number of animals kept at home. Although concentrations on automobile seats were lower, Fel d 1 levels exceeded 8 μg/g in 23.5 % of cars and high levels of Can f 1 (>10 μg/g) were found in 17.6 % of cars. The study revealed that cars of pet owners may be reservoirs of cat and dog allergens even when animals are not transported in them. In schools, concentrations of pet allergens did not reach high levels, but the moderate levels of Fel d 1 (≥1-8 μg/g) and Can f 1 (≥2-10 μg/g) were detected in 42.9 and 7.1 % of the investigated classrooms. Concentrations of cat and dog allergen in schools were higher than in homes without pets. While airborne Fel d 1 and Can f 1 levels were found low, residential allergen concentrations in settled dust and air were correlated. The study results suggest that classrooms and cars of pet owners may be important sites of exposure to cat and dog allergens, though the highest concentrations of Fel d 1 and Can f 1 are found in homes of pet owners.

  6. How release of phosphate from mammalian F1-ATPase generates a rotary substep

    PubMed Central

    Bason, John V.; Montgomery, Martin G.; Leslie, Andrew G. W.; Walker, John E.

    2015-01-01

    The rotation of the central stalk of F1-ATPase is driven by energy derived from the sequential binding of an ATP molecule to its three catalytic sites and the release of the products of hydrolysis. In human F1-ATPase, each 360° rotation consists of three 120° steps composed of substeps of about 65°, 25°, and 30°, with intervening ATP binding, phosphate release, and catalytic dwells, respectively. The F1-ATPase inhibitor protein, IF1, halts the rotary cycle at the catalytic dwell. The human and bovine enzymes are essentially identical, and the structure of bovine F1-ATPase inhibited by IF1 represents the catalytic dwell state. Another structure, described here, of bovine F1-ATPase inhibited by an ATP analog and the phosphate analog, thiophosphate, represents the phosphate binding dwell. Thiophosphate is bound to a site in the αEβE-catalytic interface, whereas in F1-ATPase inhibited with IF1, the equivalent site is changed subtly and the enzyme is incapable of binding thiophosphate. These two structures provide a molecular mechanism of how phosphate release generates a rotary substep as follows. In the active enzyme, phosphate release from the βE-subunit is accompanied by a rearrangement of the structure of its binding site that prevents released phosphate from rebinding. The associated extrusion of a loop in the βE-subunit disrupts interactions in the αEβE-catalytic interface and opens it to its fullest extent. Other rearrangements disrupt interactions between the γ-subunit and the C-terminal domain of the αE-subunit. To restore most of these interactions, and to make compensatory new ones, the γ-subunit rotates through 25°–30°. PMID:25918412

  7. Preeclampsia -- a state of prostaglandin deficiency? Urinary prostaglandin excretion, the renin-aldosterone system, and circulating catecholamines in preeclampsia.

    PubMed

    Pedersen, E B; Christensen, N J; Christensen, P; Johannesen, P; Kornerup, H J; Kristensen, S; Lauritsen, J G; Leyssac, P P; Rasmussen, A; Wohlert, M

    1983-01-01

    Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin, aldosterone, norepinephrine (NE) and epinephrine (E) were determined during pregnancy, 5 days, 3, and 6 months after delivery in preeclampsia, normotensive pregnant, and nonpregnant control subjects. The PGE2 was higher in normotensive pregnant control subjects than in nonpregnant subjects. In preeclampsia, PGE2 was reduced to nonpregnant level. PGF2 alpha was the same in preeclampsia and in normotensive pregnancy, but elevated when compared to the normotensive nonpregnant control group. Plasma concentrations of renin and aldosterone were increased during pregnancy, but considerably less in preeclampsia than during normotensive pregnancy. NE and E were the same as in nonpregnant subjects during both hypertensive and normotensive pregnancy. All parameters were normal 3 months after delivery. There were no correlations between PGE2, PGF2 alpha, plasma concentrations of renin, aldosterone, NE, or E and blood pressure level in third trimester either in preeclampsia or in normotensive pregnancy. PGE2 was positively correlated to plasma concentrations of renin. It is suggested that the lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion. It is hypothesized that preeclampsia is a state of prostaglandin deficiency. The changes in the renin-aldosterone system may be secondary to changes in prostaglandin concentration both in preeclampsia and normotensive pregnancy.

  8. Inflammation-induced anorexia and fever are elicited by distinct prostaglandin dependent mechanisms, whereas conditioned taste aversion is prostaglandin independent.

    PubMed

    Nilsson, Anna; Wilhelms, Daniel Björk; Mirrasekhian, Elahe; Jaarola, Maarit; Blomqvist, Anders; Engblom, David

    2017-03-01

    Systemic inflammation evokes an array of brain-mediated responses including fever, anorexia and taste aversion. Both fever and anorexia are prostaglandin dependent but it has been unclear if the cell-type that synthesizes the critical prostaglandins is the same. Here we show that pharmacological inhibition or genetic deletion of cyclooxygenase (COX)-2, but not of COX-1, attenuates inflammation-induced anorexia. Mice with deletions of COX-2 selectively in brain endothelial cells displayed attenuated fever, as demonstrated previously, but intact anorexia in response to peripherally injected lipopolysaccharide (10μg/kg). Whereas intracerebroventricular injection of a cyclooxygenase inhibitor markedly reduced anorexia, deletion of COX-2 selectively in neural cells, in myeloid cells or in both brain endothelial and neural cells had no effect on LPS-induced anorexia. In addition, COX-2 in myeloid and neural cells was dispensable for the fever response. Inflammation-induced conditioned taste aversion did not involve prostaglandin signaling at all. These findings collectively show that anorexia, fever and taste aversion are triggered by distinct routes of immune-to-brain signaling.

  9. Operating principles of rotary molecular motors: differences between F1 and V1 motors.

    PubMed

    Yamato, Ichiro; Kakinuma, Yoshimi; Murata, Takeshi

    2016-01-01

    Among the many types of bioenergy-transducing machineries, F- and V-ATPases are unique bio- and nano-molecular rotary motors. The rotational catalysis of F1-ATPase has been investigated in detail, and molecular mechanisms have been proposed based on the crystal structures of the complex and on extensive single-molecule rotational observations. Recently, we obtained crystal structures of bacterial V1-ATPase (A3B3 and A3B3DF complexes) in the presence and absence of nucleotides. Based on these new structures, we present a novel model for the rotational catalysis mechanism of V1-ATPase, which is different from that of F1-ATPases.

  10. [Meiosis passing age dependence in Solanum linnaeum L. x solanum incanum L. F1 interspecific hybrid].

    PubMed

    Montvid, P Iu

    2011-01-01

    Meiosis passing in the first- and second-year-plants of F1 interspecific hybrid Solanum linnaeum L. x Solanum incanum L. has been carried out. Fruit with seeds were formed during a second year of vegetation. The quantities of uni- and tetravalents and main disorders frequency lowered with plant age. Meiosis in parental forms was normal. The conclusion was drawn about F1 Solanum linnaeum L. x Solanum incanum L. meiosis regularity connection with heterozygous genotype, influence of environmental factors and plant age.

  11. Torque generation and elastic power transmission in the rotary F(O)F(1)-ATPase.

    PubMed

    Junge, Wolfgang; Sielaff, Hendrik; Engelbrecht, Siegfried

    2009-05-21

    Adenosine triphosphate (ATP), the universal fuel of the cell, is synthesized from adenosine diphosphate (ADP) and inorganic phosphate (P(i)) by 'ATP synthase' (F(O)F(1)-ATPase). During respiration or photosynthesis, an electrochemical potential difference of protons is set up across the respective membranes. This powers the enzyme's electrical rotary nanomotor (F(O)), which drives the chemical nanomotor (F(1)) by elastic mechanical-power transmission, producing ATP with high kinetic efficiency. Attempts to understand in detail the mechanisms of torque generation in this simple and robust system have been both aided and complicated by a wealth of sometimes conflicting data.

  12. Endogenous biosynthesis of thromboxane and prostacyclin in 2 distinct murine models of atherosclerosis.

    PubMed

    Praticò, D; Cyrus, T; Li, H; FitzGerald, G A

    2000-12-01

    Thromboxane A(2) is a potent vasoconstrictor and platelet agonist; prostacyclin is a potent platelet inhibitor and vasodilator. Altered biosynthesis of these eicosanoids is a feature of human hypercholesterolemia and atherosclerosis. This study examined whether in 2 murine models of atherosclerosis their levels are increased and correlated with the evolution of the disease. Urinary 2,3-dinor thromboxane B(2) and 2,3-dinor-6-keto prostaglandin F(1 alpha), metabolites of thromboxane and prostacyclin, respectively, were assayed in apoliprotein E (apoE)-deficient mice on chow and low-density lipoprotein receptor (LDLR)-deficient mice on chow and a Western-type diet. Atherosclerosis lesion area was measured by en face method. Both eicosanoids increased in apoE-deficient mice on chow and in LDLR-deficient mice on a high-fat diet, but not in LDLR-deficient mice on chow by the end of the study. Aspirin suppressed ex vivo platelet aggregation, serum thromboxane B(2), and 2,3-dinor thromboxane B(2), and significantly reduced the excretion of 2,3-dinor-6-keto prostaglandin F(1 alpha) in these animals. This study demonstrates that thromboxane as well as prostacyclin biosynthesis is increased in 2 murine models of atherogenesis and is secondary to increased in vivo platelet activation. Assessment of their generation in these models may afford the basis for future studies on the functional role of these eicosanoids in the evolution and progression of atherosclerosis. (Blood. 2000;96:3823-3826)

  13. M2-F1 in flight being towed by a C-47

    NASA Technical Reports Server (NTRS)

    1964-01-01

    The M2-F1 Lifting Body is seen here being towed behind a C-47 at the Flight Research Center (later redesignated the Dryden Flight Research Center), Edwards, California. In this rear view, the M2-F1 is flying above and to one side of the C-47. This was done to avoid wake turbulence from the towplane. Lacking wings, the M2-F1 used an unusual configuration for its control surfaces. It had two rudders on the fins, two elevons (called 'elephant ears') mounted on the outsides of the fins, and two body flaps on the upper rear fuselage. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. These initial tests produced enough flight data about the M2-F1 to proceed with flights behind the C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to l20 mph. More than 400 ground tows and 77 aircraft tow flights were carried out with the M2-F1. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at NASA's Ames and

  14. POU5F1 isoforms show different expression patterns in human embryonic stem cells and preimplantation embryos.

    PubMed

    Cauffman, Greet; Liebaers, Inge; Van Steirteghem, André; Van de Velde, Hilde

    2006-12-01

    The contribution of the POU domain, class 5, transcription factor-1 (POU5F1) in maintaining totipotency in human embryonic stem cells (hESCs) has been repeatedly proven. In humans, two isoforms are encoded: POU5F1_iA and POU5F1_iB. So far, no discrimination has been made between the isoforms in POU5F1 studies, and it is unknown which isoform contributes to the undifferentiated phenotype. Using immunocytochemistry, expression of POU5F1_iA and POU5F1_iB was examined in hESCs and all stages of human preimplantation development to look for differences in expression, biological activity, and relation to totipotency. POU5F1_iA and POU5F1_iB displayed different temporal and spatial expression patterns. During human preimplantation development, a significant POU5F1_iA expression was seen in all nuclei of compacted embryos and blastocysts and a clear POU5F1_iB expression was detected from the four-cell stage onwards in the cytoplasm of all cells. The cytoplasmic localization might imply no or other biological functions beyond transcription activation for POU5F1_iB. The stemness properties of POU5F1 can be assigned to POU5F1_iA because hESCs expressed POU5F1_iA but not POU5F1_iB. However, POU5F1_iA is not the appropriate marker to identify totipotent cells, because POU5F1_iA was also expressed in the nontotipotent trophectoderm and was not expressed in zygotes and early cleavage stage embryos, which are assumed to be totipotent. The expression pattern of POU5F1_iA may suggest that POU5F1_iA alone cannot sustain totipotency and that coexpression with other stemness factors might be the key to totipotency.

  15. F1 rotary motor of ATP synthase is driven by the torsionally-asymmetric drive shaft

    NASA Astrophysics Data System (ADS)

    Kulish, O.; Wright, A. D.; Terentjev, E. M.

    2016-06-01

    F1F0 ATP synthase (ATPase) either facilitates the synthesis of ATP in a process driven by the proton moving force (pmf), or uses the energy from ATP hydrolysis to pump protons against the concentration gradient across the membrane. ATPase is composed of two rotary motors, F0 and F1, which compete for control of their shared γ -shaft. We present a self-consistent physical model of F1 motor as a simplified two-state Brownian ratchet using the asymmetry of torsional elastic energy of the coiled-coil γ -shaft. This stochastic model unifies the physical concepts of linear and rotary motors, and explains the stepped unidirectional rotary motion. Substituting the model parameters, all independently known from recent experiments, our model quantitatively reproduces the ATPase operation, e.g. the ‘no-load’ angular velocity is ca. 400 rad/s anticlockwise at 4 mM ATP. Increasing the pmf torque exerted by F0 can slow, stop and overcome the torque generated by F1, switching from ATP hydrolysis to synthesis at a very low value of ‘stall torque’. We discuss the motor efficiency, which is very low if calculated from the useful mechanical work it produces - but is quite high when the ‘useful outcome’ is measured in the number of H+ pushed against the chemical gradient.

  16. Short communication: hair cortisol concentrations in Holstein-Friesian and crossbreed F1 heifers.

    PubMed

    Peric, T; Comin, A; Corazzin, M; Montillo, M; Cappa, A; Campanile, G; Prandi, A

    2013-05-01

    The aim of this study was to evaluate the hypothalamic-pituitary-adrenal (HPA) axis activity of Holstein-Friesian and crossbreed F1 heifers by analysis of the cortisol concentrations in hair samples. Cortisol, the primary hormone of the HPA axis, is the biological endpoint for the investigation of the HPA response. The study was conducted on 290 prepubertal heifers; 142 heifers were pure Holstein-Friesian and 148 were crossbreed F1 heifers obtained from the 3-way rotational system with Swedish Red and Montbéliarde breeds. Extraction was performed on the hair using methanol, and cortisol concentrations were determined by a radioimmunoassay method. Cortisol concentrations measured in regrown hair of crossbreed F1 heifers were significantly lower than those in hair of Holstein-Friesian heifers. This result helps us to better understand the differences in HPA activity and allostatic load between Holstein-Friesian and crossbreed F1 heifers and allows us to better assess the adaptability of these animals to the environment and the importance of crossbreed traits for profitability in dairy farming.

  17. F1 rotary motor of ATP synthase is driven by the torsionally-asymmetric drive shaft

    PubMed Central

    Kulish, O.; Wright, A. D.; Terentjev, E. M.

    2016-01-01

    F1F0 ATP synthase (ATPase) either facilitates the synthesis of ATP in a process driven by the proton moving force (pmf), or uses the energy from ATP hydrolysis to pump protons against the concentration gradient across the membrane. ATPase is composed of two rotary motors, F0 and F1, which compete for control of their shared γ -shaft. We present a self-consistent physical model of F1 motor as a simplified two-state Brownian ratchet using the asymmetry of torsional elastic energy of the coiled-coil γ -shaft. This stochastic model unifies the physical concepts of linear and rotary motors, and explains the stepped unidirectional rotary motion. Substituting the model parameters, all independently known from recent experiments, our model quantitatively reproduces the ATPase operation, e.g. the ‘no-load’ angular velocity is ca. 400 rad/s anticlockwise at 4 mM ATP. Increasing the pmf torque exerted by F0 can slow, stop and overcome the torque generated by F1, switching from ATP hydrolysis to synthesis at a very low value of ‘stall torque’. We discuss the motor efficiency, which is very low if calculated from the useful mechanical work it produces - but is quite high when the ‘useful outcome’ is measured in the number of H+ pushed against the chemical gradient. PMID:27321713

  18. 26 CFR 301.6229(f)-1 - Special rule for partial settlement agreements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... Pursuant to section 6226(c), a partner is a party to a partnership-level judicial proceeding with respect... additional amounts. When a partner settles partnership items, the settled partnership items convert to....6229(f)-1 Special rule for partial settlement agreements. (a) In general. If a partner enters into...

  19. Irradiation of adult Epiphyas postvittana (Lepidoptera: Tortricidae): egg sterility in parental and F1 generations.

    PubMed

    Jang, Eric B; McInnis, Donald O; Kurashima, Rick; Woods, Bill; Suckling, David M

    2012-02-01

    Adult Epiphyas postvittana Walker were irradiated using a Cobalt 60 source to determine the dose needed to achieve complete egg sterility of mated female moths, and egg sterility of female moths mated to F1 generation males. Adult male and female E. postvittana were irradiated at 100, 200, 250, and 300 Gy and their fertility (when crossed with normal moths) was compared with nonirradiated moths. Viable progeny (determined by egg hatch) were found at doses of 100 and 200 Gy, but very little at 250 and 300 Gy. In particular, there was no survival of female progeny into the F1 generation. Males irradiated at 250 and 300 Gy had very low egg eclosion rates (2.25 and 1.86% at 250 and 300 Gy, respectively) when mated with normal females. The F2 generation from those male progeny had a mean percent hatched of < 1.02%. Based on our results, a dose of 250-300 Gy is recommended for irradiation of E. postvittana adults used for sterile insect technique (SIT) if sterility of parental moths is the desired outcome. Our data also suggests that inclusion of F1 hybrid sterility rather than parental generation sterility into programs using the SIT may allow for doses lower than what we have reported, especially during initial phases of an eradication program where increase fitness of moths might be desirable. Further research is needed to verify the use of F1 hybrid sterility in light brown apple moth SIT programs.

  20. Initial Report for the Radiation Effects Research Foundation F1 Mail Survey.

    PubMed

    Milder, Cm; Sakata, R; Sugiyama, H; Sadakane, A; Utada, M; Cordova, Ka; Hida, A; Ohishi, W; Ozasa, K; Grant, Ej

    2016-01-01

    To study the full health effects of parental radiation exposure on the children of the atomic bomb survivors, the Radiation Effects Research Foundation developed a cohort of 76,814 children born to atomic bomb survivors (F1 generation) to assess cancer incidence and mortality from common adult diseases. In analyzing radiationassociated health information, it is important to be able to adjust for sociodemographic and lifestyle variations that may affect health. In order to gain this and other background information on the F1 cohort and to determine willingness to participate in a related clinical study, the F1 Mail Survey Questionnaire was designed with questions corresponding to relevant health, sociodemographic, and lifestyle indicators. Between the years 2000 and 2006, the survey was sent to a subset of the F1 Mortality Cohort. A total of 16,183 surveys were completed and returned: 10,980 surveys from Hiroshima residents and 5,203 from Nagasaki residents. The response rate was 65.6%, varying somewhat across parental exposure category, city, gender, and year of birth. Differences in health and lifestyle were noted in several variables on comparison across city and gender. No major differences in health, lifestyle, sociodemographics, or disease were seen across parental exposure categories, though statistically significant tests for heterogeneity and linear trend revealed some possible changes with dose. The data described herein provide a foundation for studies in the future.

  1. Linkage analysis and map construction in genetic populations of clonal F1 and double cross.

    PubMed

    Zhang, Luyan; Li, Huihui; Wang, Jiankang

    2015-01-15

    In this study, we considered four categories of molecular markers based on the number of distinguishable alleles at the marker locus and the number of distinguishable genotypes in clonal F1 progenies. For two marker loci, there are nine scenarios that allow the estimation of female, male, and/or combined recombination frequencies. In a double cross population derived from four inbred lines, five categories of markers are classified and another five scenarios are present for recombination frequency estimation. Theoretical frequencies of identifiable genotypes were given for each scenario, from which the maximum likelihood estimates of one or more of the three recombination frequencies could be estimated. If there was no analytic solution, then Newton-Raphson method was used to acquire a numerical solution. We then proposed to use an algorithm in Traveling Salesman Problem to determine the marker order. Finally, we proposed a procedure to build the two haploids of the female parent and the two haploids of the male parent in clonal F1. Once the four haploids were built, clonal F1 hybrids could be exactly regarded as a double cross population. Efficiency of the proposed methods was demonstrated in simulated clonal F1 populations and one actual maize double cross. Extensive comparisons with software JoinMap4.1, OneMap, and R/qtl show that the methodology proposed in this article can build more accurate linkage maps in less time.

  2. 26 CFR 1.904(f)-1 - Overall foreign loss and the overall foreign loss account.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... States § 1.904(f)-1 Overall foreign loss and the overall foreign loss account. (a)(1) Overview of...)(3) when the taxpayer disposes of property used predominantly outside the United States in a trade or... to recapture when the taxpayer disposes of certain properties under section 904(f)(3)); and §...

  3. Whole-Genome Sequences of Four Corynebacterium CDC Group F-1 Strains Isolated from Urine

    PubMed Central

    Bernier, Anne-Marie; Peters, Geoffrey A.

    2017-01-01

    ABSTRACT Three draft and one complete genome sequence from strains isolated from urine and consistent with Corynebacterium CDC group F-1 were assembled and studied. Genome sizes ranged between 2.3 and 2.44 Mb, with G+C content between 60.4% and 60.7%. PMID:28153894

  4. M2-F1 in flight over lakebed on tow line

    NASA Technical Reports Server (NTRS)

    1963-01-01

    Following the first M2-F1 airtow flight on 16 August 1963, the Flight Research Center used the vehicle for both research flights and to check out new lifting-body pilots. These included Bruce Peterson, Don Mallick, Fred Haise, and Bill Dana from NASA. Air Force pilots who flew the M2-F1 included Chuck Yeager, Jerry Gentry, Joe Engle, Jim Wood, and Don Sorlie, although Wood, Haise, and Engle only flew on car tows. In the three years between the first and last flights of the M2-F1, it made about 400 car tows and 77 air tows. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and

  5. M2-F1 lifting body aircraft on a flatbed truck

    NASA Technical Reports Server (NTRS)

    1997-01-01

    After the grounding of the M2-F1 in 1966, it was kept in outside storage on the Dryden complex. After several years, its fabric and plywood structure was damaged by the sun and weather. Restoration of the vehicle began in February 1994 under the leadership of NASA retiree Dick Fischer, with other retirees who had originally worked on the M2-F1's construction and flight research three decades before also participating. The photo shows the now-restored M2-F1 returning to the site of its flight research, now called the Dryden Flight Research Center, on 22 August 1997. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, NASA Flight Research Center (later Dryden Flight Research Center, Edwards, CA) management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available

  6. 26 CFR 301.6223(f)-1 - Duplicate copy of final partnership administrative adjustment.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 18 2011-04-01 2011-04-01 false Duplicate copy of final partnership... In General § 301.6223(f)-1 Duplicate copy of final partnership administrative adjustment. (a) In... the notice of final partnership administrative adjustment (for example, in the event the...

  7. 26 CFR 301.6223(f)-1 - Duplicate copy of final partnership administrative adjustment.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 18 2014-04-01 2014-04-01 false Duplicate copy of final partnership... In General § 301.6223(f)-1 Duplicate copy of final partnership administrative adjustment. (a) In... the notice of final partnership administrative adjustment (for example, in the event the...

  8. 26 CFR 301.6223(f)-1 - Duplicate copy of final partnership administrative adjustment.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 18 2013-04-01 2013-04-01 false Duplicate copy of final partnership... In General § 301.6223(f)-1 Duplicate copy of final partnership administrative adjustment. (a) In... the notice of final partnership administrative adjustment (for example, in the event the...

  9. 26 CFR 301.6223(f)-1 - Duplicate copy of final partnership administrative adjustment.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Duplicate copy of final partnership... In General § 301.6223(f)-1 Duplicate copy of final partnership administrative adjustment. (a) In... the notice of final partnership administrative adjustment (for example, in the event the...

  10. 26 CFR 301.6223(f)-1 - Duplicate copy of final partnership administrative adjustment.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 18 2012-04-01 2012-04-01 false Duplicate copy of final partnership... In General § 301.6223(f)-1 Duplicate copy of final partnership administrative adjustment. (a) In... the notice of final partnership administrative adjustment (for example, in the event the...

  11. Chromosomal rearrangements directly cause underdominant F1 pollen sterility in Mimulus lewisii-Mimulus cardinalis hybrids.

    PubMed

    Stathos, Angela; Fishman, Lila

    2014-11-01

    Chromosomal rearrangements can contribute to the evolution of postzygotic reproductive isolation directly, by disrupting meiosis in F1 hybrids, or indirectly, by suppressing recombination among genic incompatibilities. Because direct effects of rearrangements on fertility imply fitness costs during their spread, understanding the mechanism of F1 hybrid sterility is integral to reconstructing the role(s) of rearrangements in speciation. In hybrids between monkeyflowers Mimulus cardinalis and Mimulus lewisii, rearrangements contain all quantitative trait loci (QTLs) for both premating barriers and pollen sterility, suggesting that they may have facilitated speciation in this model system. We used artificial chromosome doubling and comparative mapping to test whether heterozygous rearrangements directly cause underdominant male sterility in M. lewisii-M. cardinalis hybrids. Consistent with a direct chromosomal basis for hybrid sterility, synthetic tetraploid F1 s showed highly restored fertility (83.4% pollen fertility) relative to diploids F1 s (36.0%). Additional mapping with Mimulus parishii-M. cardinalis and M. parishii-M. lewisii hybrids demonstrated that underdominant male sterility is caused by one M. lewisii specific and one M. cardinalis specific reciprocal translocation, but that inversions had no direct effects on fertility. We discuss the importance of translocations as causes of reproductive isolation, and consider models for how underdominant rearrangements spread and fix despite intrinsic fitness costs.

  12. Fluorographane (C1H(x)F(1-x-δ))n: synthesis and properties.

    PubMed

    Sofer, Zdeněk; Šimek, Petr; Mazánek, Vlastimil; Šembera, Filip; Janoušek, Zbyněk; Pumera, Martin

    2015-04-04

    Fluorographane (C1HxF1-x-δ)n was obtained from graphene by hydrogenation via the Birch reaction with consequent fluorination of the resulting graphane. Fluorographane exhibits fast heterogeneous electron transfer rates and hydrophobicity, which increase with increasing fluorination.

  13. In Utero Nutritional Manipulation Provokes Dysregulated Adipocytokines Production in F1 Offspring in Rats

    PubMed Central

    Hanafi, Mervat Y.; Saleh, Moustafa M.; Kamel, Maher A.

    2016-01-01

    Background. Intrauterine environment plays a pivotal role in the origin of fatal diseases such as diabetes. Diabetes and obesity are associated with low-grade inflammatory state and dysregulated adipokines production. This study aims to investigate the effect of maternal obesity and malnutrition on adipokines production (adiponectin, leptin, and TNF-α) in F1 offspring in rats. Materials and Methods. Wistar rats were allocated in groups: F1 offspring of control mothers under control diet (CF1-CD) and under high-fat diet (CF1-HCD), F1 offspring of obese mothers under CD (OF1-CD) and under HCD (OF1-HCD), and F1 offspring of malnourished mothers under CD (MF1-CD) and under HCD (MF1-HCD). Every 5 weeks postnatally, blood samples were obtained for biochemical analysis. Results. At the end of the 30-week follow-up, OF1-HCD and MF1-HCD exhibited hyperinsulinemia, moderate dyslipidemia, insulin resistance, and impaired glucose homeostasis compared to CF1-CD and CF1-HCD. OF1-HCD and MF1-HCD demonstrated low serum levels of adiponectin and high levels of leptin compared to CF1-CD and CF1-HCD. OF1-CD, OF1-HCD, and MF1-HCD had elevated serum levels of TNF-α compared to CF1-CD and CF1-HCD (p < 0.05). Conclusion. Maternal nutritional manipulation predisposes the offspring to development of insulin resistance in their adult life, probably via instigating dysregulated adipokines production. PMID:27200209

  14. Saturn V F-1 Engine Gas Generator Blazes Back To Life

    NASA Video Gallery

    On Jan. 10, 2013, a resurrected gas generator from a Saturn V F-1 engine completed two hot-fire tests that are part of a series of tests at Test Stand 116 located in the East Test Area at NASA's Ma...

  15. Cleanup Verification Package for the 126-F-1, 184-F Powerhouse Ash Pit

    SciTech Connect

    S. W. Clark and H. M. Sulloway

    2007-09-26

    This cleanup verification package documents completion of remedial action for the 126-F-1, 184-F Powerhouse Ash Pit. This waste site received coal ash from the 100-F Area coal-fired steam plant. Leakage of process effluent from the 116-F-14 , 107-F Retention Basins flowed south into the ash pit, contaminating the northern portion.

  16. Cleanup Verification Package for the 126-F-1, 184-F Powerhouse Ash Pit

    SciTech Connect

    S. W. Clark and H. M Sulloway

    2007-10-31

    This cleanup verification package documents completion of remedial action for the 126-F-1, 184-F Powerhouse Ash Pit. This waste site received coal ash from the 100-F Area coal-fired steam plant. Leakage of process effluent from the 116-F-14 , 107-F Retention Basins flowed south into the ash pit, contaminating the northern portion.

  17. The transcription factor E4F1 coordinates CHK1-dependent checkpoint and mitochondrial functions.

    PubMed

    Rodier, Geneviève; Kirsh, Olivier; Baraibar, Martín; Houlès, Thibault; Lacroix, Matthieu; Delpech, Hélène; Hatchi, Elodie; Arnould, Stéphanie; Severac, Dany; Dubois, Emeric; Caramel, Julie; Julien, Eric; Friguet, Bertrand; Le Cam, Laurent; Sardet, Claude

    2015-04-14

    Recent data support the notion that a group of key transcriptional regulators involved in tumorigenesis, including MYC, p53, E2F1, and BMI1, share an intriguing capacity to simultaneously regulate metabolism and cell cycle. Here, we show that another factor, the multifunctional protein E4F1, directly controls genes involved in mitochondria functions and cell-cycle checkpoints, including Chek1, a major component of the DNA damage response. Coordination of these cellular functions by E4F1 appears essential for the survival of p53-deficient transformed cells. Acute inactivation of E4F1 in these cells results in CHK1-dependent checkpoint deficiency and multiple mitochondrial dysfunctions that lead to increased ROS production, energy stress, and inhibition of de novo pyrimidine synthesis. This deadly cocktail leads to the accumulation of uncompensated oxidative damage to proteins and extensive DNA damage, ending in cell death. This supports the rationale of therapeutic strategies simultaneously targeting mitochondria and CHK1 for selective killing of p53-deficient cancer cells.

  18. Rocketdyne - F-1 Saturn V First Stage Engine. Chapter 1, Appendix C

    NASA Technical Reports Server (NTRS)

    Biggs, Robert

    2009-01-01

    Before I go into the history of F-1, I want to discuss the F-1 engine s role in putting man on the moon. The F-1 engine was used in a cluster of five on the first stage, and that was the only power during the first stage. It took the Apollo launch vehicle, which was 363 feet tall and weighed six million pounds, and threw it downrange fifty miles, threw it up to forty miles of altitude, at Mach 7. It took two and one-half minutes to do that and, in the process, burned four and one-half million pounds of propellant, a pretty sizable task. (See Slide 2, Appendix C) My history goes back to the same year I started working at Rocketdyne. That s where the F-1 had its beginning, back early in 1957. In 1957, there was no space program. Rocketdyne was busy working overtime and extra days designing, developing, and producing rocket engines for weapons of mass destruction, not for scientific reasons. The Air Force contracted Rocketdyne to study how to make a rocket engine that had a million pounds of thrust. The highest thing going at the time had 150,000 pounds of thrust. Rocketdyne s thought was the new engine might be needed for a ballistic missile, not that it was going to go on a moon shot.

  19. Less is more: reduced catechol production permits Pseudomonas putida F1 to grow on styrene.

    PubMed

    George, Kevin W; Hay, Anthony

    2012-11-01

    Pseudomonas putida F1 is unable to grow on styrene due to the accumulation of 3-vinylcatechol, a toxic metabolite that is produced through the toluene degradation (tod) pathway and causes catechol-2,3-dioxygenase (C23O) inactivation. In this study, we characterized a spontaneous F1 mutant, designated SF1, which acquired the ability to grow on styrene and did not accumulate 3-vinylcatechol. Whereas adaptation to new aromatic substrates has typically been shown to involve increased C23O activity or the acquisition of resistance to C23O inactivation, SF1 retained wild-type C23O activity. Surprisingly, SF1 grew more slowly on toluene, its native substrate, and exhibited reduced toluene dioxygenase (TDO) activity (approximately 50 % of that of F1), the enzyme responsible for ring hydroxylation and subsequent production of 3-vinylcatechol. DNA sequence analysis of the tod operon of SF1 revealed a single base pair mutation in todA (C479T), a gene encoding the reductase component of TDO. Replacement of the wild-type todA allele in F1 with todA(C479T) reduced TDO activity to SF1 levels, obviated vinylcatechol accumulation, and conferred the ability to grow on styrene. This novel 'less is more' strategy - reduced catechol production as a means to expand growth substrate range - sheds light on an alternative approach for managing catechol toxicity during the metabolism of aromatic compounds.

  20. 40 CFR Figure F-1 to Subpart F of... - Designation Testing Checklist

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Designation Testing Checklist F Figure F-1 to Subpart F of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Testing Performance Characteristics of Class II Equivalent Methods for PM2.5 Pt. 53, Subpt. F, Fig....

  1. 40 CFR Figure F-1 to Subpart F of... - Designation Testing Checklist

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 5 2011-07-01 2011-07-01 false Designation Testing Checklist F Figure F-1 to Subpart F of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Testing Performance Characteristics of Class II Equivalent Methods for PM2.5 Pt. 53, Subpt. F, Fig....

  2. Correlations between measures of feed efficiency and feedlot return for F1 lambs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective estimates of feedlot return for progeny of terminal-sire breeds of sheep are needed to improve lamb profitability. Thus, we used recent economic data to determine the effects of terminal-sire breed on returns of F1 lambs. Annually for 3 yr, Columbia, USMARC Composite, Suffolk, and Texel ra...

  3. M2-F1 on lakebed with Pontiac convertible tow vehicle

    NASA Technical Reports Server (NTRS)

    1963-01-01

    The M2-F1 lifting body, dubbed the 'flying bathtub' by the media, was the precursor of a remarkable series of wingless flying vehicles that contributed data used in the space shuttle and the X-38 Technology Demonstrator for crew return from the International Space Station. The early tow tests were done using the 1963 Pontiac Catalina convertible modified for the purpose. The first flight attempt occurred on 1 March 1963 but was unsuccessful due to control-system problems. It was not until 5 April 1963, after tests in the Ames Research Center wind tunnel, that Milt Thompson made the first M2-F1 tow flight. Based on the ideas and basic design of Alfred J. Eggers and others at the Ames Aeronautical Laboratory (now the Ames Research Center), Mountain View, Calif., in the mid-1950s, the M2-F1 came to be built over a four-month period in 1962-63 for a cost of only about $30,000 plus perhaps an additional $8,000-$10,000 for an ejection seat and $10,000 for solid-propellant rockets to add time to the landing flare. Engineers and technicians at the NASA Flight Research Center (now NASA Dryden) kept costs low by designing and fabricating it partly in-house, with the plywood shell constructed by a local sailplane builder. Someone at the time estimated that it would have cost a major aircraft company $150,000 to build the same vehicle. Unlike the later lifting bodies, the M2-F1 was unpowered and was initially towed until it was airborne by a souped-up Pontiac convertible. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina

  4. Cloning and expression of Aca f 1: a new allergen of Acacia farnesiana pollen

    PubMed Central

    Khosravi, Gholam Reza; Morakabati, Payam; Akbari, Bahareh; Dousti, Fatemeh

    2016-01-01

    Acacia farnesiana is the main source of allergenic pollen and one of the most important causes of respiratory allergic disease in tropical and subtropical regions of the world. The purpose of this study was to produce a recombinant variety of allergenic Ole e 1-like protein from the pollen of this tree. To predict its allergenic cross-reactivity with other members of the Ole e 1-like protein family of common allergenic plants, the nucleotide sequence homology of the Acacia Ole e 1-like protein was evaluated. Amplification of cDNA strands encoding Acacia Ole e 1-like protein was performed by polymerase chain reaction (PCR) and sequenced. Following expression in Escherichia coli using the pET-21b(+) vector, the recombinant protein was purified using metal-affinity chromatography. IgE-binding competence of purified recombinant Ole e 1- like protein (rAca f 1) was analysed by immunoassay using 25 sera collected from Acacia pollen-sensitised patients. Nucleotide sequencing revealed an open reading frame of 453 bp encoding 150 amino acid residues that belonged to the Ole e 1-like protein family, and 11 patients (44%) had considerable specific IgE levels for the rAca f 1. Immunodetection and inhibition assays indicated that the purified rAca f 1 may be the same as that in the crude extract. Aca f 1, the second allergen from Acacia pollen, was identified as a member of the family of Ole e 1-like protein. A high degree of homology was found among amino acid sequences of Aca f 1 and several allergenic members of Ole e 1-like protein family. PMID:27833445

  5. Polymorphisms and expression of the chicken POU1F1 gene associated with carcass traits.

    PubMed

    Xu, Heng-Yong; Wang, Yan; Liu, Yi-Ping; Wang, Ji-Wen; Zhu, Qing

    2012-08-01

    POU1F1 is an essential factor that regulates the development and reproduction of animal. The objective of the current research was to screen for polymorphism, expression of POU1F1 and their association with carcass quality traits. A total of 126 Erlang mountainous chickens from two strains (SD02 and SD03) were employed for testing. Seventeen single nucleotide polymorphisms (SNPs) were detected, but only two SNPs (g.96217999 T > C and g.96219442 C > T) were associated with carcass quality traits. In SD03 chicken, g.96217999 T > C genotypes were significantly associated with body weight (BW), carcass weight (CW), eviscerated weight (EW), and semi-eviscerated weight (SEW; P < 0.05), and was highly significantly associated with breast muscle weight (BMW) and abdominal fat weight (AW; P < 0.01). g.96219442 C > T was significantly associated with BW, EW, SEW (P < 0.05). However, these two SNPs were not significantly associated with any carcass traits in SD02 chicken. Diplotypes showed that in SD03 chicken, the haplotype [C: C] was the most favorable haplotype because it was associated with higher BW, CW, SEW, EW, BMW, and AW (P < 0.05). On the contrary, haplotype [T: T] was associated with lower carcass quality traits (P < 0.01). In addition, qRT-PCR revealed that at 13 weeks, the POU1F1 mRNA expression was significantly higher in breast muscle of cock compared to that of hens (P < 0.05), whereas there was no significant correlation between POU1F1 expression and carcass traits. These results suggested that POU1F1 could be a potential candidate gene for carcass traits in chicken.

  6. Cloning and expression of Aca f 1: a new allergen of Acacia farnesiana pollen.

    PubMed

    Khosravi, Gholam Reza; Assarehzadegan, Mohammad-Ali; Morakabati, Payam; Akbari, Bahareh; Dousti, Fatemeh

    2016-01-01

    Acacia farnesiana is the main source of allergenic pollen and one of the most important causes of respiratory allergic disease in tropical and subtropical regions of the world. The purpose of this study was to produce a recombinant variety of allergenic Ole e 1-like protein from the pollen of this tree. To predict its allergenic cross-reactivity with other members of the Ole e 1-like protein family of common allergenic plants, the nucleotide sequence homology of the Acacia Ole e 1-like protein was evaluated. Amplification of cDNA strands encoding Acacia Ole e 1-like protein was performed by polymerase chain reaction (PCR) and sequenced. Following expression in Escherichia coli using the pET-21b(+) vector, the recombinant protein was purified using metal-affinity chromatography. IgE-binding competence of purified recombinant Ole e 1- like protein (rAca f 1) was analysed by immunoassay using 25 sera collected from Acacia pollen-sensitised patients. Nucleotide sequencing revealed an open reading frame of 453 bp encoding 150 amino acid residues that belonged to the Ole e 1-like protein family, and 11 patients (44%) had considerable specific IgE levels for the rAca f 1. Immunodetection and inhibition assays indicated that the purified rAca f 1 may be the same as that in the crude extract. Aca f 1, the second allergen from Acacia pollen, was identified as a member of the family of Ole e 1-like protein. A high degree of homology was found among amino acid sequences of Aca f 1 and several allergenic members of Ole e 1-like protein family.

  7. Inheritance of Trans Chromosomal Methylation patterns from Arabidopsis F1 hybrids.

    PubMed

    Greaves, Ian K; Groszmann, Michael; Wang, Aihua; Peacock, W James; Dennis, Elizabeth S

    2014-02-04

    Hybridization in plants leads to transinteractions between the parental genomes and epigenomes that can result in changes to both 24 nt siRNA and cytosine methylation ((m)C) levels in the hybrid. In Arabidopsis the principle processes altering the hybrid methylome are Trans Chromosomal Methylation (TCM) and Trans Chromosomal deMethylation (TCdM) in which the (m)C pattern of a genomic segment attains the same (m)C pattern of the corresponding segment on the other parental chromosome. We examined two loci that undergo TCM/TCdM in the Arabidopsis C24/Landsberg erecta (Ler) F1 hybrids, which show patterns of inheritance dependent on the properties of the particular donor and recipient chromosomal segments. At At1g64790 the TCM- and TCdM-derived (m)C patterns are maintained in the F2 generation but are transmitted in outcrosses or backcrosses only by the C24 genomic segment. At a region between and adjacent to At3g43340 and At3g43350, the originally unmethylated Ler genomic segment receives the C24 (m)C pattern in the F1, which is then maintained in backcross plants independent of the presence of the parental C24 segment. In backcrosses to an unmethylated Ler allele, the newly methylated F1 Ler segment may act as a TCM source in a process comparable to paramutation in maize. TCM-derived (m)C patterns are associated with reduced expression of both At3g43340 and At3g43350 in F1 and F2 plants, providing support for such events influencing the transcriptome. The inheritance of the F1 (m)C patterns and the segregation of other genetic and epigenetic determinants may contribute to the reduced hybrid vigor in the F2 and subsequent generations.

  8. Thermodynamic analysis of F1-ATPase rotary catalysis using high-speed imaging

    PubMed Central

    Watanabe, Rikiya; Minagawa, Yoshihiro; Noji, Hiroyuki

    2014-01-01

    F1-ATPase (F1) is a rotary motor protein fueled by ATP hydrolysis. Although the mechanism for coupling rotation and catalysis has been well studied, the molecular details of individual reaction steps remain elusive. In this study, we performed high-speed imaging of F1 rotation at various temperatures using the total internal reflection dark-field (TIRDF) illumination system, which allows resolution of the F1 catalytic reaction into elementary reaction steps with a high temporal resolution of 72 µs. At a high concentration of ATP, F1 rotation comprised distinct 80° and 40° substeps. The 80° substep, which exhibited significant temperature dependence, is triggered by the temperature-sensitive reaction, whereas the 40° substep is triggered by ATP hydrolysis and the release of inorganic phosphate (Pi). Then, we conducted Arrhenius analysis of the reaction rates to obtain the thermodynamic parameters for individual reaction steps, that is, ATP binding, ATP hydrolysis, Pi release, and TS reaction. Although all reaction steps exhibited similar activation free energy values, ΔG‡ = 53–56 kJ mol−1, the contributions of the enthalpy (ΔH‡), and entropy (ΔS‡) terms were significantly different; the reaction steps that induce tight subunit packing, for example, ATP binding and TS reaction, showed high positive values of both ΔH‡ and ΔS‡. The results may reflect modulation of the excluded volume as a function of subunit packing tightness at individual reaction steps, leading to a gain or loss in water entropy. PMID:25262814

  9. M2-F1 lifting body and Paresev 1B on ramp

    NASA Technical Reports Server (NTRS)

    1963-01-01

    In this photo of the M2-F1 lifting body and the Paresev 1B on the ramp, the viewer sees two vehicles representing different approaches to building a research craft to simulate a spacecraft able to land on the ground instead of splashing down in the ocean as the Mercury capsules did. The M2-F1 was a lifting body, a shape able to re-enter from orbit and land. The Paresev (Paraglider Research Vehicle) used a Rogallo wing that could be (but never was) used to replace a conventional parachute for landing a capsule-type spacecraft, allowing it to make a controlled landing on the ground. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop

  10. M2-F1 mounted in NASA Ames Research Center 40x80 foot wind tunnel

    NASA Technical Reports Server (NTRS)

    1962-01-01

    After the first attempted ground-tow tests of the M2-F1 in March 1963, the vehicle was taken to the Ames Research Center, Mountain View, CA, for wind-tunnel testing. During these tests, Milt Thompson and others were in the M2-F1 to position the control surfaces for each test. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne to prove it could fly safely and to train pilots before they were towed behind a C

  11. Wooden shell of M2-F1 being assembled at El Mirage

    NASA Technical Reports Server (NTRS)

    1962-01-01

    Wooden shell of the M2-F1 being assembled at El Mirage, CA. While Flight Research Center technicians built the internal steel structure of the M2-F1, sailplane builder Gus Briegleb built the vehicle's outer wooden shell. Its skin was 3/32-inch mahogany plywood, with 1/8-inch mahogany rib sections reinforced with spruce. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne to prove it could fly safely and to

  12. Proposed Ames M2-F1, M1-L half-cone, and Langley lenticular bodies.

    NASA Technical Reports Server (NTRS)

    1962-01-01

    Dale Reed, who inaugurated the lifting-body flight research at NASA's Flight Research Center (later, Dryden Flight Research Center, Edwards, CA), originally proposed that three wooden outer shells be built. These would then be attached to the single internal steel structure. The three shapes were (viewer's left to right) the M2-F1, the M1-L, and a lenticular shape. Milt Thompson, who supported Reed's advocacy for a lifting-body research project, recommended that only the M2-F1 shell be built, believing that the M1-L shape was 'too radical,' while the lenticular one was 'too exotic.' Although the lenticular shape was often likened to that of a flying saucer, Reed's wife Donna called it the 'powder puff.' The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey

  13. M2-F1 in flight over lakebed on tow line

    NASA Technical Reports Server (NTRS)

    1963-01-01

    After initial ground-tow flights of the M2-F1 using the Pontiac as a tow vehicle, the way was clear to make air tows behind a C-47. The first air tow took place on 16 August 1963. Pilot Milt Thompson found that the M2-F1 flew well, with good control. This first flight lasted less than two minutes from tow-line release to touchdown. The descent rate was 4,000 feet per minute. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got

  14. E2F1 promote the aggressiveness of human colorectal cancer by activating the ribonucleotide reductase small subunit M2

    SciTech Connect

    Fang, Zejun; Gong, Chaoju; Liu, Hong; Zhang, Xiaomin; Mei, Lingming; Song, Mintao; Qiu, Lanlan; Luo, Shuchai; Zhu, Zhihua; Zhang, Ronghui; Gu, Hongqian; Chen, Xiang

    2015-08-21

    As the ribonucleotide reductase small subunit, the high expression of ribonucleotide reductase small subunit M2 (RRM2) induces cancer and contributes to tumor growth and invasion. In several colorectal cancer (CRC) cell lines, we found that the expression levels of RRM2 were closely related to the transcription factor E2F1. Mechanistic studies were conducted to determine the molecular basis. Ectopic overexpression of E2F1 promoted RRM2 transactivation while knockdown of E2F1 reduced the levels of RRM2 mRNA and protein. To further investigate the roles of RRM2 which was activated by E2F1 in CRC, CCK-8 assay and EdU incorporation assay were performed. Overexpression of E2F1 promoted cell proliferation in CRC cells, which was blocked by RRM2 knockdown attenuation. In the migration and invasion tests, overexpression of E2F1 enhanced the migration and invasion of CRC cells which was abrogated by silencing RRM2. Besides, overexpression of RRM2 reversed the effects of E2F1 knockdown partially in CRC cells. Examination of clinical CRC specimens demonstrated that both RRM2 and E2F1 were elevated in most cancer tissues compared to the paired normal tissues. Further analysis showed that the protein expression levels of E2F1 and RRM2 were parallel with each other and positively correlated with lymph node metastasis (LNM), TNM stage and distant metastasis. Consistently, the patients with low E2F1 and RRM2 levels have a better prognosis than those with high levels. Therefore, we suggest that E2F1 can promote CRC proliferation, migration, invasion and metastasis by regulating RRM2 transactivation. Understanding the role of E2F1 in activating RRM2 transcription will help to explain the relationship between E2F1 and RRM2 in CRC and provide a novel predictive marker for diagnosis and prognosis of the disease. - Highlights: • E2F1 promotes RRM2 transactivation in CRC cells. • E2F1 promotes the proliferation of CRC cells by activating RRM2. • E2F1 promotes the migration and

  15. Role of prostaglandins in development of porcine blastocysts.

    PubMed

    Geisert, R D; Rasby, R J; Minton, J E; Wetteman, R P

    1986-02-01

    Rapid elongation of porcine blastocysts between Days 11 to 12 of pregnancy coincides with an increase in uterine luminal content of prostaglandins. The present study evaluated the effect of two prostaglandin synthesis inhibitors (indomethacin and flunixin meglumine) on elongation of porcine blastocysts from spherical to filamentous forms between Day 11 to 12 of pregnancy. Gilts were hemi-hysterectomized on Day 11 of pregnancy. The excised uterine horn was flushed with 0.9% saline and diameter of blastocysts recovered were measured. Immediately following surgery, pregnant gilts were assigned to receive either: 1) vehicle every 4 h, 2) flunixin meglumine (banamine) every 4 h, or 3) indomethacin every 12 h. The remaining uterine horn was removed and flushed after the time of blastocyst elongation estimated for each gilt on basis of blastocyst development in the first horn. Uterine flushings were analyzed for total calcium, protein, acid phosphatase activity, estrone, estradiol-17 beta and prostaglandin F. Pretreatment blastocyst diameter was similar for all groups and ranged from 1 mm to 20 mm. Treatment of gilts with either banamine or indomethacin effectively inhibited (P less than 0.001) the increase in uterine luminal content of PGF. Total calcium, estrone and estradiol-17 beta were not influenced by treatment. Total uterine luminal protein and acid phosphatase activity were reduced (P less than 0.05) in banamine treated gilts compared to those receiving vehicle or indomethacin treatments. Although total PGF recovered in uterine flushings was reduced during the period of blastocyst elongation, treatment with PGF synthetase inhibitors failed to block rapid elongation of blastocysts from the spherical to filamentous forms.

  16. Genotype-specific environmental impact on the variance of blood values in inbred and F1 hybrid mice.

    PubMed

    Klempt, Martina; Rathkolb, Birgit; Fuchs, Edith; de Angelis, Martin Hrabé; Wolf, Eckhard; Aigner, Bernhard

    2006-02-01

    Mice are important models for biomedical research because of the possibility of standardizing genetic background and environmental conditions, which both affect phenotypic variability. Inbred mouse strains as well as F1 hybrid mice are routinely used as genetically defined animal models; however, only a few studies investigated the variance of phenotypic parameters in inbred versus F1 hybrid mice and the potential interference of the genetic background with different housing conditions. Thus, we analyzed the ranges of clinical chemical and hematologic parameters in C3H and C57BL/6 inbred mice and their reciprocal F1 hybrids (B6C3F1, C3B6F1) in two different mouse facilities. Two thirds of the blood parameters examined in the same strain differed between the facilities for both the inbred strains and the F1 hybrid lines. The relation of the values between inbred and F1 hybrid mice was also affected by the facility. The variance of blood parameters in F1 hybrid mice compared with their parental inbred strains was inconsistent in one facility but generally smaller in the other facility. A subsequent study of F1 hybrid animals derived from the parental strains C3H and BALB/c, which was done in the latter housing unit, detected no general difference in the variance of blood parameters between F1 hybrid and inbred mice. Our study clearly demonstrates the possibility of major interactions between genotype and environment regarding the variance of clinical chemical and hematologic parameters.

  17. Screening of Zulu medicinal plants for prostaglandin-synthesis inhibitors.

    PubMed

    Jäger, A K; Hutchings, A; van Staden, J

    1996-06-01

    Aqueous and ethanolic extracts of 39 plants used in traditional Zulu medicine to treat headache or inflammatory diseases were screened for prostaglandin-synthesis inhibitors. Extracts were tested in an in vitro assay for cyclooxygenase inhibitors. In general, ethanolic extracts caused higher inhibition than aqueous extracts. Two-thirds of the plants screened had high inhibitory activity. The highest inhibition was obtained with ethanolic extracts of Bidens pilosa, Eucomis autumnalis, Harpephyllum caffrum, Helichrysum nudifolium, Leonotis intermedia, L. leonorus, Ocotea bullata, Rumex saggitatus, Solanum mauritianum, Synadenium cupulare and Trichilia dregeana.

  18. Effective Protective Immunity to Yersinia pestis Infection Conferred by DNA Vaccine Coding for Derivatives of the F1 Capsular Antigen

    PubMed Central

    Grosfeld, Haim; Cohen, Sara; Bino, Tamar; Flashner, Yehuda; Ber, Raphael; Mamroud, Emanuelle; Kronman, Chanoch; Shafferman, Avigdor; Velan, Baruch

    2003-01-01

    Three plasmids expressing derivatives of the Yersinia pestis capsular F1 antigen were evaluated for their potential as DNA vaccines. These included plasmids expressing the full-length F1, F1 devoid of its putative signal peptide (deF1), and F1 fused to the signal-bearing E3 polypeptide of Semliki Forest virus (E3/F1). Expression of these derivatives in transfected HEK293 cells revealed that deF1 is expressed in the cytosol, E3/F1 is targeted to the secretory cisternae, and the nonmodified F1 is rapidly eliminated from the cell. Intramuscular vaccination of mice with these plasmids revealed that the vector expressing deF1 was the most effective in eliciting anti-F1 antibodies. This response was not limited to specific mouse strains or to the mode of DNA administration, though gene gun-mediated vaccination was by far more effective than intramuscular needle injection. Vaccination of mice with deF1 DNA conferred protection against subcutaneous infection with the virulent Y. pestis Kimberley53 strain, even at challenge amounts as high as 4,000 50% lethal doses. Antibodies appear to play a major role in mediating this protection, as demonstrated by passive transfer of anti-deF1 DNA antiserum. Taken together, these observations indicate that a tailored genetic vaccine based on a bacterial protein can be used to confer protection against plague in mice without resorting to regimens involving the use of purified proteins. PMID:12496187

  19. M2-F1 in flight during low-speed car tow

    NASA Technical Reports Server (NTRS)

    1963-01-01

    The M2-F1 shown in flight during a low-speed car tow runs across the lakebed. Such tests allowed about two minutes to test the vehicle's handling in flight. NASA Flight Research Center (later redesignated the Dryden Flight Research Center) personnel conducted as many as 8 to 14 ground-tow flights in a single day either to test the vehicle in preparation for air tows or to train pilots to fly the vehicle before they undertook air tows. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30

  20. M2-F1 fabrication by Grierson Hamilton, Bob Green, and Ed Browne

    NASA Technical Reports Server (NTRS)

    1962-01-01

    Flight Research Center discretionary funds paid for the M2-F-1's construction. NASA mechanics, sheet-metal smiths, and technicians did much of the work in a curtained-off area of a hangar called the 'Wright Bicycle Shop.' The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne to prove it could fly safely and to train pilots before they were towed behind a C-47 aircraft and released. These initial car-tow tests

  1. The effect of prostaglandin E1 analog misoprostol on chronic cyclosporin nephrotoxicity.

    PubMed

    John, E G; Fornell, L C; Radhakrishnan, J; Anutrakulchai, S; Jonasson, O

    1993-11-01

    Cyclosporin A has markedly improved graft survival in transplant patients but its side effects, such as renal toxicity and hypertension, pose management problems in transplant recipients. This toxicity has been attributed to prostaglandin inhibition. Concurrent administration of misoprostol (a prostaglandin E1 analog) prevents chronic cyclosporin A-induced nephrotoxicity but not hypertension in rats.

  2. Enteral feeding in prostaglandin-dependent neonates: is it a safe practice?

    PubMed

    Willis, Lisa; Thureen, Patti; Kaufman, Jonathan; Wymore, Erica; Skillman, Heather; da Cruz, Eduardo

    2008-12-01

    In many centers presurgical term neonates with prostaglandin-dependent cardiac lesions experience nutritional deficiency because of postponed enteral feeds. We recently adopted early enteral feeding in these infants. This retrospective study demonstrates feeding tolerance in 33 of 34 neonates fed enterally while receiving prostaglandin, suggesting the safety of this practice.

  3. Construction Progress of the S-IC and F-1 Test Stands

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the stand itself, related facilities were constructed during this time. North of the massive S-IC test stand, the F-1 Engine test stand was built. Designed to assist in the development of the F-1 Engine, the F-1 test stand is a vertical engine firing test stand, 239 feet in elevation and 4,600 square feet in area at the base. Capability was provided for static firing of 1.5 million pounds of thrust using liquid oxygen and kerosene. Like the S-IC stand, the foundation of the F

  4. Construction Progress of the S-IC and F-1 Test Stands

    NASA Technical Reports Server (NTRS)

    1962-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the S-IC test stand, related facilities were built during this time. Built to the north of the massive S-IC test stand, was the F-1 Engine test stand. The F-1 test stand, a vertical engine firing test stand, 239 feet in elevation and 4,600 square feet in area at the base, was designed to assist in the development of the F-1 Engine. Capability was provided for static firing of 1.5 million pounds of thrust using liquid oxygen and kerosene. Like the S-IC stand, the foundation of

  5. Influence of different prostaglandin applications on cervical rheology.

    PubMed

    Spätling, L; Neuman, M R; Huch, R; Huch, A

    1985-10-01

    The softening effect of prostaglandin (PG) on cervical tissue prior to elective pregnancy termination is quantified by a new technique for the measurement of the elastance and relaxation of the cervix. The method is based on the pressure-volume relation of a compliant balloon placed in the cervical canal. These properties have been measured before and after different applications of prostaglandins in 58 patients electively terminating pregnancy. Application techniques used included high pressure jet application of PGE2 into the tissue of the portio uteri and the internal cervical os (120 micrograms), PGE2 and PGF2 alpha in Tylose gel (100 micrograms/0.5 ml); PGE2 as an intracervical tablet (150 micrograms) and PGE2 oral tablets placed into the posterior fornix of the vagina. Significant changes in cervical elastance were seen with the intracervically applied PGE2 in Tylose gel and the vaginally applied PGE2 tablets. The intracervically applied PGE2 gel also gave significant changes in cervical relaxation. No side effects other than mild cramping (2 patients) were seen with any of the applications in this study.

  6. Prostaglandins, catecholamines, renin and aldosterone during hypertensive and normotensive pregnancy.

    PubMed

    Pedersen, E B; Christensen, N J; Christensen, P; Johannesen, P; Kornerup, H J; Kristensen, S; Lauritsen, J G; Leyssac, P P; Rasmussen, A B; Wohlert, M

    1982-01-01

    Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin (PRC), aldosterone (PAC), noradrenaline (PNA) and adrenaline (PA) were determined in the third trimester of pregnancy, 5 days and 3 months after delivery in preeclampsia and normotensive pregnant and non-pregnant control subjects. PGE2 was higher in pregnant control subjects than in non-pregnant subjects, but reduced to non-pregnant level in preeclampsia. PGF2 alpha was the same in preeclampsia and normotensive pregnancy but higher than in the non-pregnant group. PRC and PAC were increased during pregnancy, but considerably lesser in preeclampsia than during normotensive pregnancy. PNA and PA were the same in all three groups. All parameters were normal 3 months after delivery. There were no correlations between any of the hormones and blood pressure in any of the groups. PGE2 was positively correlated to PRC. The lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion, and the changes in PRC and PAC are supposed to be secondary to changes in PGE2. It is hypothesised that preeclampsia is a state of prostaglandin deficiency.

  7. Role of prostaglandins in marihuana-induced bronchodilation.

    PubMed

    Laviolette, M; Bélanger, J

    1986-01-01

    In vitro evidence suggests that physiological effects of marihuana may be mediated by prostaglandins via the stimulation of phospholipase A2. To verify if marihuana could act by this route in vivo, we tested the effects of acetylsalicylic and mefenamic acids, inhibitors of cyclooxygenase, on marihuana-induced bronchodilation and tachycardia. In 11 healthy volunteers, marihuana smoking (7 mg/kg, 1.7% delta 9-tetrahydrocannabinol) produced a significant increase in specific airway conductance (from 0.262 +/- 0.033 to 0.360 +/- 0.050 s-1 X cm H2O-1, mean +/- SE, p less than 0.01), forced expiratory volume in 1 s (4.02 +/- 0.22-4.27 +/- 0.25 liter, p less than 0.05) and heart rate (73.2 +/- 2.0-108.5 +/- 5.2 beats/min, p less than 0.001). In a second session, acetylsalicylic or mefenamic acid was taken for 30 h before marihuana smoking. No inhibition of marihuana-induced increase of specific airway conductance, forced expiratory volume in 1 s and heart rate was found. These findings suggest that the bronchodilation and the tachycardia induced by marihuana smoking in humans are not mediated by prostaglandins.

  8. Canine gastric mucosal vasodilation with prostaglandins and histamine analogs

    SciTech Connect

    Gerber, J.G.; Nies, A.S.

    1982-10-01

    The effect of direct intragastric artery infusion of prostaglandins E2 and I2, arachidonic acid, dimaprit (histamine H2 agonist), and 2',2'-pyridylethylamine (histamine H1 agonist) on gastric mucosal blood flow was examined in dogs to elucidate the relationship between gastric secretory state and mucosal blood flow in dogs. These compounds were chosen because of their diverse effect on gastric acid secretion. Gastric fundus blood flow was measured both electromagnetically with a flow probe around the left gastric artery which supplies the fundus almost exclusively, and by the radioactive microsphere technique. Intraarterial infusion of all the compounds resulted in gastric mucosal vasodilation even though PGE2, PGI2, and arachidonic acid inhibit gastric acid secretion, dimaprit stimulated gastric acid secretion, and 2',2'-pyridylethylamine does not affect gastric acid secretion. There was total agreement in the blood flow measurements by the two different techniques. Our data suggest that gastric acid secretion and gastric vasodilation are independently regulated. In addition, the validity of the studies in which the aminopyrine clearance indicates that prostaglandins are mucosal vasoconstrictors needs to be questioned because of the reliance of those measurements on the secretory state of the stomach.

  9. Optimising daytime deliveries when inducing labour using prostaglandin vaginal inserts

    PubMed Central

    Miller, Hugh; Goetzl, Laura; Wing, Deborah A.; Powers, Barbara; Rugarn, Olof

    2016-01-01

    Abstract Objective: To determine induction start time(s) that would maximise daytime deliveries when using prostaglandin vaginal inserts. Methods: Women enrolled into the Phase III trial, EXPEDITE (clinical trial registration: NCT01127581), had labour induced with either a misoprostol or dinoprostone vaginal insert (MVI or DVI). A secondary analysis was conducted to determine the optimal start times for induction by identifying the 12-h period with the highest proportion of deliveries by parity and treatment. Results: Optimal start times for achieving daytime deliveries when using MVI appear to be 19:00 in nulliparae and 23:00 in multiparae. Applying these start times, the median time of onset of active labour would be approximately 08:30 for both parities and the median time of delivery would be the following day at approximately 16:30 for nulliparae and 12:00 (midday) for multiparae. Optimal start times when using DVI appear to be 07:00 for nulliparae and 23:00 for multiparae. Using these start times, the median time of onset of active labour would be the following day at approximately 04:00 and 11:50, and the median time of delivery would be approximately 13:40 and 16:10, respectively. Conclusions: When optimising daytime deliveries, different times to initiate induction of labour may be appropriate depending on parity and the type of retrievable prostaglandin vaginal insert used. PMID:25758619

  10. Role of prostaglandins in intrauterine migration of the equine conceptus.

    PubMed

    Stout, T A; Allen, W R

    2001-05-01

    Between at least day 9 and day 16 after ovulation the spherical equine conceptus migrates continuously throughout the uterine lumen, propelled by peristaltic myometrial contractions. This unusually long period of intrauterine movement ensures that the conceptus delivers its anti-luteolytic signal to the entire endometrium to achieve luteostasis. The present experiment tested the hypothesis that prostaglandins stimulate the myometrial contractions that result in the migration of the conceptus. Serial ultrasonographic examinations of the uteri of eight mares performed during 2 h periods between day 10 and day 18 of gestation recorded the pattern of conceptus migration before and after treatment with the cyclo-oxygenase inhibitor flunixin meglumine. Conceptus mobility was high between day 10 and day 14 after ovulation (4.3 +/- 0.8, 4.7 +/- 0.8 and 4.3 +/- 0.9 changes of location per h on day 10, day 12 and day 14, respectively), but was reduced immediately and markedly by an i.v. injection of flunixin meglumine (3.8 +/- 1.5, 1.8 +/- 0.8 and 0.7 +/- 0.2 location changes per h), thereby implicating prostaglandins as the primary stimulus for the myometrial contractions that drive migration of the conceptus.

  11. Prevotella intermedia induces prostaglandin E2 via multiple signaling pathways.

    PubMed

    Guan, S-M; Fu, S-M; He, J-J; Zhang, M

    2011-01-01

    Prostaglandin E(2) (PGE(2)) plays important roles in the bone resorption of inflammatory diseases such as rheumatoid arthritis and periodontitis via specific prostaglandin receptors (i.e., EP1-EP4). In this study, the authors examined whether Prevotella intermedia regulates PGE(2) production and EP expression in human periodontal ligament fibroblasts (hPDLs); they also explored the potential signaling pathways involved in PGE(2) production. P. intermedia induced PGE(2) production and cyclooxygenase-2 (COX-2) expression in a dose- and time-dependent manner. Indomethacin and NS-398 completely abrogated the P. intermedia-induced PGE(2) production without modulating COX-2 expression. Specific inhibitors of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, phosphatidylinositol 3-kinase, and protein kinase C--but not c-AMP and protein kinase A--significantly attenuated the P. intermedia-induced COX-2 and PGE(2) expression. P. intermedia reduced EP1 expression in a concentration- and time-dependent manner. The results indicate that the COX-2-dependent induction of PGE(2) by P. intermedia in hPDLs is mediated by multiple signaling pathways.

  12. Enhancement of neural and thermal vasoconstriction by prostaglandin B1.

    PubMed

    Engelbrecht, J A; Greenberg, S; Wilson, W R

    1975-03-01

    The vascular effects of prostaglandin B1 (PGB1) were studied during constant-flow perfusion of the canine hindpaw. The effects of PGB1 (50-200 ng/kg/min ia) on systemic and hindpaw perfusion pressures and on responses to local cooling (4 degrees C for 90 sec) and local heating (45 degrees C for 60 sec) were measured in 15 dogs. PGB1 (50-100 ng/kg/min) decreased perfusion pressure without any significant effect on systemic arterial pressure. Higher concentrations of PGB1 (200 ng/kg/min) elevated perfusion pressure to control values. The pressor responses to local cooling were increased from 11 to 32 mmHg while the dilator responses to local heating and nitroglycerin were reduced during infusions of PGB1. PGB1 also enhanced the pressor responses to norepinephrine or tyramine. These findings support the conclusions that (1) low concentrations of prostaglandin B1 enhance neurotransmitter release with minimal effects on vascular smooth muscle cells and (2) these effects are not secondary to increased perfusion pressures or vascular wall stresses since infusions of PGB1 resulted in vasodilation.

  13. Prostaglandins are important in thermoregulation of a reptile (Pogona vitticeps).

    PubMed

    Seebacher, Frank; Franklin, Craig E

    2003-08-07

    The effectiveness of behavioural thermoregulation in reptiles is amplified by cardiovascular responses, particularly by differential rates of heart beat in response to heating and cooling (heart-rate hysteresis). Heart-rate hysteresis is ecologically important in most lineages of ectothermic reptile, and we demonstrate that heart-rate hysteresis in the lizard Pogona vitticeps is mediated by prostaglandins. In a control treatment (administration of saline), heart rates during heating were significantly faster than during cooling at any given body temperature. When cyclooxygenase 1 and 2 enzymes were inhibited, heart rates during heating were not significantly different from those during cooling. Administration of agonists showed that thromboxane B(2) did not have a significant effect on heart rate, but prostacyclin and prostaglandin F(2alpha) caused a significant increase (3.5 and 13.6 beats min(-1), respectively) in heart rate compared with control treatments. We speculate that heart-rate hysteresis evolved as a thermoregulatory mechanism that may ultimately be controlled by neurally induced stimulation of nitric oxide production, or maybe via photolytically induced production of vitamin D.

  14. Trichloroethylene degradation by Escherichia coli containing the cloned Pseudomonas putida F1 toluene dioxygenase genes

    SciTech Connect

    Zylstra, G.J.; Gibson, D.T. ); Wackett, L.P. )

    1989-12-01

    Toluene dioxygenase from Pseudomonas putida F1 has been implicated as an enzyme capable of degrading trichloroethylene. This has now been confirmed with Escherichia coli JM109(pDTG601) that contains the structural genes (todC1C2BA) of toluene dioxygenase under the control of the tac promoter. The extent of trichloroethylene degradation by the recombinant organism depended on the cell concentration and the concentration of trichloroethylene. A linear rate of trichloroethylene degradation was observed with the E. coli recombinant strain. In contrast, P. putida F39/D, a mutant strain of P. putida F1 that does not contain cis-toluene dihydrodiol dehydrogenase, showed a much faster initial rate of trichloroethylene degradation which decreased over time.

  15. Development of High Speed Digital Camera: EXILIM EX-F1

    NASA Astrophysics Data System (ADS)

    Nojima, Osamu

    The EX-F1 is a high speed digital camera featuring a revolutionary improvement in burst shooting speed that is expected to create entirely new markets. This model incorporates a high speed CMOS sensor and a high speed LSI processor. With this model, CASIO has achieved an ultra-high speed 60 frames per second (fps) burst rate for still images, together with 1,200 fps high speed movie that captures movements which cannot even be seen by human eyes. Moreover, this model can record movies at full High-Definition. After launching it into the market, it was able to get a lot of high appraisals as an innovation camera. We will introduce the concept, features and technologies about the EX-F1.

  16. The alpha subunit of a plant mitochondrial F1-ATPase is translated in mitochondria.

    PubMed

    Boutry, M; Briquet, M; Goffeau, A

    1983-07-25

    The mitochondrial F1-ATPase from bean (Vicia faba L.) was solubilized by a chloroform treatment of mitochondrial membranes and purified by centrifugation on a glycerol gradient. The active fraction contained 5 subunits: alpha (Mr = 52,000), beta (Mr = 51,000), gamma (Mr = 34,000), delta (Mr = 23,800), and epsilon (Mr = 22,900). Purified coupled mitochondria were incubated in the presence of [ 35S ]methionine and malate to allow mitochondrial translation to occur. The largest labeled polypeptide (Mr = 52,000) was present in the chloroform extract, co-sedimented with the F1-ATPase on glycerol gradient and co-migrated with the alpha subunit upon two-dimensional electrophoresis. The results indicate that the alpha subunit of bean mitochondrial ATPase is translated on mitoribosomes, in contrast to the situation in other organisms.

  17. V gene analysis of anti-cardiolipin antibodies from (NZW x BXSB) F1 mice.

    PubMed Central

    Kita, Y; Sumida, T; Iwamoto, I; Yoshida, S; Koike, T

    1994-01-01

    In (NZW x BXSB) F1 (W/B F1) male mice, systemic lupus-like disease, thrombocytopenia and coronary vascular disease with myocardial infarction occur, due to the presence of platelet-associated antibodies, anti-platelet antibodies and anti-cardiolipin antibodies (aCL). We developed monoclonal aCL and analysed the specificity of aCL. In the W/B F1 mice, there are aCL with pathogenic properties, which have an IgG isotype and reveal a cofactor-dependent binding to CL, binding activity to platelets, and lupus anti-coagulant (LA) activity. Here, we analysed the usage of VH and V kappa genes of six aCL, including two pathogenic aCL, from W/B F1 mice, in an attempt to address the question of whether or not aCL with pathogenic properties use restricted Ig V genes. Sequence analysis of VH and V kappa genes of aCL showed that the pathogenic aCL had VHJ558 and V kappa 21 or V kappa 23 genes, whereas the other aCL without pathogenic features used mainly the 7183 VH family and the random V kappa gene group. However, two pathogenic aCL showed a 86.6% homology with the IgV region, each other, indicating that they were not closely related clones. Thus, these findings suggest the possibility that usage of Ig VH genes in pathogenic aCL is not random, but that there may exist a few epitopes of antigen recognized by the pathogenic aCL. PMID:7959886

  18. Carryover of cigarette smoke effects on hematopoietic cytokines to F1 mouse litters.

    PubMed

    Shukla, Mamta; Kumar, Pradeep; Mishra, Vani; Chaudhari, Bhushan Pradosh; Munjal, Ashok Kumar; Tripathi, Shambhoo Sharan; Raisuddin, Seikh; Paul, Bhola Nath

    2011-09-01

    Neutrophils have been implicated in the pathogenesis of COPD, being recruited into the lung in response to cigarette smoke (CS) inhalation and responsible for the release of proteases and oxidant-producing enzymes, resulting in bronchitis and emphysema. Several hematopoietic cytokines are involved in neutrophil growth and recruitment; however, little is known about the effects of CS on hematopoietic cytokines are transmitted between generations. In the present investigation we evaluate the expression of hematopoietic and proinflammatory cytokines in different organs of female F(0) mice subjected to sub-chronic CS exposure, and in F(1) litters. Virgin female Balb/c mice inhaled either air or air containing CS for 90 days. The specific resistance of the airways (sRaw) was evaluated and, thereafter, the mice were mated with unexposed adult males. The levels of granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF), interleukin-6 (IL-6), IL-1β and TNF-α mRNA and protein were evaluated in the bone marrow, amniotic fluid and bronchoalveolar lavage fluid (BALF) of F(0) dams at gestation day(14) (gd(14)) and the bone marrow, BALF and lungs of F(0) dams and F(1) littermates at post natal day(21) (pnd(21)). At gd(14), overexpression of GM-CSF, G-CSF and IL-6 mRNA and protein was observed in the bone marrow, amniotic fluid and BALF of F(0) dams. These hematopoietic cytokines were also overexpressed in the lungs of F(1) littermates compared with the control F(1) litters at pnd(21). Lineage-specific hematopoietic growth factors may play an important role in the transmission of neutrophil-associated disease susceptibility across generations.

  19. How the regulatory protein, IF1, inhibits F1-ATPase from bovine mitochondria

    PubMed Central

    Gledhill, Jonathan R.; Montgomery, Martin G.; Leslie, Andrew G. W.; Walker, John E.

    2007-01-01

    The structure of bovine F1-ATPase inhibited by a monomeric form of the inhibitor protein, IF1, known as I1–60His, lacking most of the dimerization region, has been determined at 2.1-Å resolution. The resolved region of the inhibitor from residues 8–50 consists of an extended structure from residues 8–13, followed by two α-helices from residues 14–18 and residues 21–50 linked by a turn. The binding site in the βDP-αDP catalytic interface is complex with contributions from five different subunits of F1-ATPase. The longer helix extends from the external surface of F1 via a deep groove made from helices and loops in the C-terminal domains of subunits βDP, αDP, βTP, and αTP to the internal cavity surrounding the central stalk. The linker and shorter helix interact with the γ-subunit in the central stalk, and the N-terminal region extends across the central cavity to interact with the nucleotide binding domain of the αE subunit. To form these complex interactions and penetrate into the core of the enzyme, it is likely that the initial interaction of the inhibitor with F1 forms via the open conformation of the βE subunit. Then, as two ATP molecules are hydrolyzed, the βE-αE interface converts to the βDP-αDP interface via the βTP-αTP interface, trapping the inhibitor progressively in its binding site and a nucleotide in the catalytic site of subunit βDP. The inhibition probably arises by IF1 imposing the structure and properties of the βTP-αTP interface on the βDP-αDP interface, thereby preventing it from hydrolyzing the bound ATP. PMID:17895376

  20. VIIRS F1 "best" relative spectral response characterization by the government team

    NASA Astrophysics Data System (ADS)

    Moeller, Chris; McIntire, Jeff; Schwarting, Tom; Moyer, Dave

    2011-10-01

    The VIIRS Flight 1 (F1) instrument completed sensor level testing, including relative spectral response (RSR) characterization in 2009 and is moving forward towards a launch on the NPP platform late in 2011. As part of its mandate to produce analyses of F1 performance essentials, the VIIRS Government Team, consisting of NASA, Aerospace Corp., and MIT/Lincoln Lab elements, has produced an independent (from that of industry) analysis of F1 RSR. The test data used to derive RSR for all VIIRS spectral bands was collected in the TVAC environment using the Spectral Measurement Assembly (SpMA), a dual monochromator system with tungsten and ceramic glow bar sources. These spectrally contiguous measurements were analyzed by the Government Team to produce a complete in-band + out-of-band RSR for 21 of the 22 VIIRS bands (exception of the Day-Night Band). The analysis shows that VIIRS RSR was well measured in the pre-launch test program for all bands, although the measurement noise floor is high on the thermal imager band I5. The RSR contain expected detector to detector variation resulting from the VIIRS non-telecentric optical design, and out-of-band features are present in some bands; non-compliances on the integrated out-of-band spectral performance metric are noted in M15 and M16A,B bands and also for several VisNIR bands, though the VisNIR non-compliances were expected due to known scattering in the VisNIR integrated filter assembly. The Government Team "best" RSR have been released into the public domain for use by the science community in preparation for the post-launch era of VIIRS F1.

  1. Bioleaching of heavy metals from a contaminated soil using indigenous Penicillium chrysogenum strain F1.

    PubMed

    Deng, Xinhui; Chai, Liyuan; Yang, Zhihui; Tang, Chongjian; Tong, Haixia; Yuan, Pingfu

    2012-09-30

    Bioleaching of heavy metals from contaminated soil using Penicillium chrysogenum strain F1 was investigated. Batch experiments were performed to compare leaching efficiencies of heavy metals between one-step and two-step processes and to determine the transformation of heavy metal fractions before and after bioleaching. The results showed that two-step process had higher leaching efficiencies of heavy metals than one-step process. When the mass ratio of soil to culture medium containing P. chrysogenum strain F1 was 5% (w/v), 50%, 35%, 9% and 40% of Cd, Cu, Pb and Zn were removed in one-step process, respectively. The two-step process had higher removals of 63% Cd, 56% Cu, 14% Pb and 54% Zn as compared with one-step process. The results of the sequential extraction showed that the metals remaining in the soil were mainly bonded in stable fractions after bioleaching. The results of TEM and SEM showed that during bioleaching process, although the mycelium of P. chrysogenum was broken into fragments, no damage was obviously observed on the surface of the living cell except for thinner cell wall, smaller vacuoles and concentrated cytoplasm. The result implied that P. chrysogenum strain F1 can be used to remove heavy metals from polluted soil.

  2. Simultaneous F 0-F 1 modifications of Arabic for the improvement of natural-sounding

    NASA Astrophysics Data System (ADS)

    Ykhlef, F.; Bensebti, M.

    2013-03-01

    Pitch (F 0) modification is one of the most important problems in the area of speech synthesis. Several techniques have been developed in the literature to achieve this goal. The main restrictions of these techniques are in the modification range and the synthesised speech quality, intelligibility and naturalness. The control of formants in a spoken language can significantly improve the naturalness of the synthesised speech. This improvement is mainly dependent on the control of the first formant (F 1). Inspired by this observation, this article proposes a new approach that modifies both F 0 and F 1 of Arabic voiced sounds in order to improve the naturalness of the pitch shifted speech. The developed strategy takes a parallel processing approach, in which the analysis segments are decomposed into sub-bands in the wavelet domain, modified in the desired sub-band by using a resampling technique and reconstructed without affecting the remained sub-bands. Pitch marking and voicing detection are performed in the frequency decomposition step based on the comparison of the multi-level approximation and detail signals. The performance of the proposed technique is evaluated by listening tests and compared to the pitch synchronous overlap and add (PSOLA) technique in the third approximation level. Experimental results have shown that the manipulation in the wavelet domain of F 0 in conjunction with F 1 guarantees natural-sounding of the synthesised speech compared to the classical pitch modification technique. This improvement was appropriate for high pitch modifications.

  3. Polycomb recruitment attenuates retinoic acid-induced transcription of the bivalent NR2F1 gene.

    PubMed

    Laursen, Kristian B; Mongan, Nigel P; Zhuang, Yong; Ng, Mary M; Benoit, Yannick D; Gudas, Lorraine J

    2013-07-01

    Polycomb proteins play key roles in mediating epigenetic modifications that occur during cell differentiation. The Polycomb repressive complex 2 (PRC2) mediates the tri-methylation of histone H3 lysine 27 (H3K27me3). In this study, we identify a distinguishing feature of two classes of PRC2 target genes, represented by the Nr2F1 (Coup-TF1) and the Hoxa5 gene, respectively. Both genes are transcriptionally activated by all-trans retinoic acid (RA) and display increased levels of the permissive H3K9/K14ac and tri-methylated histone H3 lysine 4 epigenetic marks in response to RA. However, while in response to RA the PRC2 and H3K27me3 marks are greatly decreased at the Hoxa5 promoter, these marks are initially increased at the Nr2F1 promoter. Functional depletion of the essential PRC2 protein Suz12 by short hairpin RNA (shRNA) technology enhanced the RA-associated transcription of Nr2F1, Nr2F2, Meis1, Sox9 and BMP2, but had no effect on the Hoxa5, Hoxa1, Cyp26a1, Cyp26b1 and RARβ2 transcript levels in wild-type embryonic stem cells. We propose that PRC2 recruitment attenuates the RA-associated transcriptional activation of a subset of genes. Such a mechanism would permit the fine-tuning of transcriptional networks during differentiation.

  4. Genome reorganization in F1 hybrids uncovers the role of retrotransposons in reproductive isolation

    PubMed Central

    Senerchia, Natacha; Felber, François; Parisod, Christian

    2015-01-01

    Interspecific hybridization leads to new interactions among divergent genomes, revealing the nature of genetic incompatibilities having accumulated during and after the origin of species. Conflicts associated with misregulation of transposable elements (TEs) in hybrids expectedly result in their activation and genome-wide changes that may be key to species boundaries. Repetitive genomes of wild wheats have diverged under differential dynamics of specific long terminal repeat retrotransposons (LTR-RTs), offering unparalleled opportunities to address the underpinnings of plant genome reorganization by selfish sequences. Using reciprocal F1 hybrids between three Aegilops species, restructuring and epigenetic repatterning was assessed at random and LTR-RT sequences with amplified fragment length polymorphism and sequence-specific amplified polymorphisms as well as their methylation-sensitive counterparts, respectively. Asymmetrical reorganization of LTR-RT families predicted to cause conflicting interactions matched differential survival of F1 hybrids. Consistent with the genome shock model, increasing divergence of merged LTR-RTs yielded higher levels of changes in corresponding genome fractions and lead to repeated reorganization of LTR-RT sequences in F1 hybrids. Such non-random reorganization of hybrid genomes is coherent with the necessary repression of incompatible TE loci in support of hybrid viability and indicates that TE-driven genomic conflicts may represent an overlooked factor supporting reproductive isolation. PMID:25716787

  5. 16Oxygen irradiation enhances cued fear memory in B6D2F1 mice

    NASA Astrophysics Data System (ADS)

    Raber, Jacob; Marzulla, Tessa; Kronenberg, Amy; Turker, Mitchell S.

    2015-11-01

    The space radiation environment includes energetic charged particles that may impact cognitive performance. We assessed the effects of 16O ion irradiation on cognitive performance of C57BL/6J × DBA/2J F1 (B6D2F1) mice at OHSU (Portland, OR) one month following irradiation at Brookhaven National Laboratory (BNL, Upton, NY). Hippocampus-dependent contextual fear memory and hippocampus-independent cued fear memory of B6D2F1 mice were tested. 16O ion exposure enhanced cued fear memory. This effect showed a bell-shaped dose response curve. Cued fear memory was significantly stronger in mice irradiated with 16O ions at a dose of 0.4 or 0.8 Gy than in sham-irradiated mice or following irradiation at 1.6 Gy. In contrast to cued fear memory, contextual fear memory was not affected following 16O ion irradiation at the doses used in this study. These data indicate that the amygdala might be particularly susceptible to effects of 16O ion exposure.

  6. Bovine F1Fo ATP synthase monomers bend the lipid bilayer in 2D membrane crystals

    PubMed Central

    Jiko, Chimari; Davies, Karen M; Shinzawa-Itoh, Kyoko; Tani, Kazutoshi; Maeda, Shintaro; Mills, Deryck J; Tsukihara, Tomitake; Fujiyoshi, Yoshinori; Kühlbrandt, Werner; Gerle, Christoph

    2015-01-01

    We have used a combination of electron cryo-tomography, subtomogram averaging, and electron crystallographic image processing to analyse the structure of intact bovine F1Fo ATP synthase in 2D membrane crystals. ATPase assays and mass spectrometry analysis of the 2D crystals confirmed that the enzyme complex was complete and active. The structure of the matrix-exposed region was determined at 24 Å resolution by subtomogram averaging and repositioned into the tomographic volume to reveal the crystal packing. F1Fo ATP synthase complexes are inclined by 16° relative to the crystal plane, resulting in a zigzag topology of the membrane and indicating that monomeric bovine heart F1Fo ATP synthase by itself is sufficient to deform lipid bilayers. This local membrane curvature is likely to be instrumental in the formation of ATP synthase dimers and dimer rows, and thus for the shaping of mitochondrial cristae. DOI: http://dx.doi.org/10.7554/eLife.06119.001 PMID:25815585

  7. Effects of shikonin isolated from zicao on lupus nephritis in NZB/W F1 mice.

    PubMed

    Wang, Xin Chang; Feng, Jian; Huang, Feng; Fan, Yong Sheng; Wang, Yan Yan; Cao, Ling Yong; Wen, Cheng Pin

    2009-09-01

    The present study was performed to evaluate the potential protective effects of Shikonin extracted from Zicao on lupus nephritis (LN) using NZB/W F1 mice. Oral administration of Shikonin (24, 40 mg/kg body weight/d) or vehicle was applied to sixty female NZB/W F1 mice of 28-week-old with LN. Treatment with Shikonin for 14 weeks suppressed proteinuria dose-dependently with the mean proteinuria of 274.0 mg/dl and 160.3 mg/dl for low-dose and high-dose Shikonin groups, respectively, compared to 499.2 mg/dl for the vehicle. Also, Shikonin was observed to reduce circulating adhesion molecules significantly and down-regulate intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) mRNA expression in kidney. However, anti-double stranded (ds)DNA antibody in mice with low or high Shikonin dose administration both exhibited no significant elevation, differing from vehicle group. Kidney histological examination showed that renal glomerular lesions were alleviated after Shikonin application. These results suggest that Shikonin has therapeutic effects on LN in NZB/W F1 mice, to which inhibition of anti-dsDNA may be potential contribution, and its part mechanism is related to suppression of mRNA expression of cell adhesion molecules (CAMs) in the kidney.

  8. Properties of kojic acid and curcumin: Assay on cell B16-F1

    NASA Astrophysics Data System (ADS)

    Sugiharto, Ariff, Arbakariya; Ahmad, Syahida; Hamid, Muhajir

    2016-03-01

    Ultra violet (UV) exposure and oxidative stress are casually linked to skin disorders. They can increase melanin synthesis, proliferation of melanocytes, and hyperpigmentation. It is possible that antioxidants or inhibitors may have a beneficial effect on skin health to reduce hyperpigmentation. In the last few years, a huge number of natural herbal extracts have been tested to reduce hyperpigmentation. The objective of this study was to determine and to compare of kojic acid and curcumin properties to viability cell B16-F1. In this study, our data showed that the viability of cell B16-F1 was 63.91% for kojic acid and 64.12% for curcumin at concentration 100 µg/ml. Further investigation assay of antioxidant activities, indicated that IC50 for kojic acid is 63.8 µg/ml and curcumin is 16.05 µg/ml. Based on the data, kojic acid and curcumin have potential antioxidant properties to reduce hyperpigmentation with low toxicity effect in cell B16-F1.

  9. A Bacterial Virulence Protein Promotes Pathogenicity by Inhibiting the Bacterium's Own F1Fo ATP Synthase

    PubMed Central

    Lee, Eun-Jin; Pontes, Mauricio H.; Groisman, Eduardo A.

    2013-01-01

    SUMMARY Several intracellular pathogens including Salmonella enterica and Mycobacterium tuberculosis require the virulence protein MgtC to survive within macrophages and to cause a lethal infection in mice. We now report that, unlike secreted virulence factors that target the host vacuolar ATPase to withstand phagosomal acidity, the MgtC protein acts on Salmonella's own F1Fo ATP synthase. This complex couples proton translocation to ATP synthesis/ hydrolysis and is required for virulence. We establish that MgtC interacts with the a subunit of the F1Fo ATP synthase, hindering ATP-driven proton translocation and NADH-driven ATP synthesis in inverted vesicles. An mgtC null mutant displays heightened ATP levels and an acidic cytoplasm whereas mgtC overexpression decreases ATP levels. A single amino acid substitution in MgtC that prevents binding to the F1Fo ATP synthase abolishes control of ATP levels and attenuates pathogenicity. MgtC provides a singular example of a virulence protein that promotes pathogenicity by interfering with another virulence protein. PMID:23827679

  10. Long-Term Prostaglandin E1 Infusion for Newborns with Critical Congenital Heart Disease.

    PubMed

    Aykanat, Alper; Yavuz, Taner; Özalkaya, Elif; Topçuoğlu, Sevilay; Ovalı, Fahri; Karatekin, Güner

    2016-01-01

    Prostaglandin E1 is crucial for keeping the patent ductus arteriosus in critical congenital heart disease for the survival and palliation of particularly prematurely born babies until a cardiosurgical intervention is available. In this study, the side effects of prostaglandin E1 in newborns with critical congenital heart disease and clinical outcomes were evaluated. Thirty-five newborns diagnosed with critical congenital heart disease were treated with prostaglandin E1 between January 2012 and September 2014 at our hospital. Patient charts were examined for prostaglandin E1 side effects (metabolic, gastric outlet obstruction, apnea), clinical status, and prognosis. Acquired data were analyzed in the SPSS 20.0 program. Patients with birth weight under 2500 g needed more days of prostaglandin E1 infusion than ones with birthweight over 2500 g (P = 0.016). The ratio of patients with birth weight under 2500 g who received prostaglandin E1 longer than 7 days was higher than the patients with birth weight over 2500 g (P = 0.02). Eighteen side effects were encountered in 11 of 35 patients (31%). Of these side effects, 1 patient had 4, 4 patients had 2, and 6 patients had only 1 side effect. Discontinuation of the therapy was never needed. Prostaglandin E1 is an accepted therapy modality for survival and outcome in critical congenital heart disease in particularly low-birth-weight babies until a surgical intervention is available. Side effects are not less encountered but are almost always manageable, and discontinuation is not needed.

  11. Regional distribution of prostaglandin endoperoxide synthase studied by enzyme-linked immunoassay using monoclonal antibodies.

    PubMed

    Yoshimoto, T; Magata, K; Ehara, H; Mizuno, K; Yamamoto, S

    1986-06-11

    Prostaglandin endoperoxide synthase transforms arachidonic acid to prostaglandin H2 via prostaglandin G2. The enzyme purified from bovine vesicular gland was given to mice as antigen, and monoclonal antibodies were raised by the hybridoma technique. Two species of the monoclonal antibody recognizing different sites of the enzyme were utilized to establish a peroxidase-linked immunoassay of prostaglandin endoperoxide synthase. Fab' fragment of one of the antibodies was prepared and conjugated to horseradish peroxidase. The conjugate was then bound to prostaglandin endoperoxide synthase, and the labeled enzyme was precipitated by the addition of the other antibody. The peroxidase activity of the immunoprecipitate correlated linearly with the amount of prostaglandin endoperoxide synthase. This sensitive and convenient method to determine the enzyme amount rather than the enzyme activity was utilized to extensively screen the amount of prostaglandin endoperoxide synthase in various bovine tissues. In addition to vesicular gland, platelets and kidney medulla previously known as rich enzyme sources, the immunoenzymometric assay demonstrated a high content of the enzyme in various parts of alimentary tract and a low but significant amount of enzyme in some parts of brain.

  12. Forkhead transcription factor FoxF1 interacts with Fanconi anemia protein complexes to promote DNA damage response.

    PubMed

    Pradhan, Arun; Ustiyan, Vladimir; Zhang, Yufang; Kalin, Tanya V; Kalinichenko, Vladimir V

    2016-01-12

    Forkhead box F1 (Foxf1) transcription factor is an important regulator of embryonic development but its role in tumor cells remains incompletely understood. While 16 proteins were characterized in Fanconi anemia (FA) core complex, its interactions with cellular transcriptional machinery remain poorly characterized. Here, we identified FoxF1 protein as a novel interacting partner of the FA complex proteins. Using multiple human and mouse tumor cell lines and Foxf1+/- mice we demonstrated that FoxF1 physically binds to and increases stability of FA proteins. FoxF1 co-localizes with FANCD2 in DNA repair foci in cultured cells and tumor tissues obtained from cisplatin-treated mice. In response to DNA damage, FoxF1-deficient tumor cells showed significantly reduced FANCD2 monoubiquitination and FANCM phosphorylation, resulting in impaired formation of DNA repair foci. FoxF1 knockdown caused chromosomal instability, nuclear abnormalities, and increased tumor cell death in response to DNA-damaging agents. Overexpression of FoxF1 in DNA-damaged cells improved stability of FA proteins, decreased chromosomal and nuclear aberrations, restored formation of DNA repair foci and prevented cell death after DNA damage. These findings demonstrate that FoxF1 is a key component of FA complexes and a critical mediator of DNA damage response in tumor cells.

  13. 17 CFR 249.1200 - Form X-17F-1A-Report for missing, lost, stolen or counterfeit securities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Form X-17F-1A-Report for... Reporting and Inquiry With Respect to Missing, Lost, Stolen, or Counterfeit Securities § 249.1200 Form X-17F... Register citations affecting Form X-17F-1A, see the List of CFR Sections Affected, which appears in...

  14. 26 CFR 54.4980F-1 - Notice requirements for certain pension plan amendments significantly reducing the rate of future...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... amendments significantly reducing the rate of future benefit accrual. 54.4980F-1 Section 54.4980F-1 Internal... significantly reducing the rate of future benefit accrual. The following questions and answers concern the... a plan amendment of an applicable pension plan that significantly reduces the rate of future...

  15. Role of the transcription factor E2F1 in CXCR4-mediated neurotoxicity and HIV neuropathology

    PubMed Central

    Shimizu, Saori; Khan, Muhammad Z.; Hippensteel, Randi L; Parkar, Anjum; Raghupathi, Ramesh; Meucci, Olimpia

    2006-01-01

    This study sought to determine the role of the transcription factor E2F1 in CXCR4-mediated neurotoxicity and HIV neuropathology. We studied the effect of the HIV envelope protein gp120 on the expression of E2F1-dependent apoptotic proteins in human and rodent neurons and examined the expression pattern of E2F1 in the brain of HIV-infected individuals. Our findings suggest that in cultured neurons gp120 increased E2F1 levels in the nucleus, stimulated its transcriptional activity, and enhanced the expression of the E2F1 target proteins Cdc2 and Puma. Studies with neuronal cultures from E2F1 deficient mice demonstrated that the transcription factor is required for gp120-induced neurotoxicity and up-regulation of Cdc2 and Puma. Levels of E2F1 protein were greater in the nucleus of neurons in brains of HIV-infected patients exhibiting dementia when compared to HIV-negative subjects or HIV-positive neurologically normal patients. Overall, these studies indicate that E2F1 is primarily involved in CXCR4-mediated neurotoxicity and HIV neuropathogenesis. PMID:17011204

  16. 26 CFR 48.4216(f)-1 - Value of used components excluded from price of certain trucks.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Value of used components excluded from price of certain trucks. 48.4216(f)-1 Section 48.4216(f)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... of the finished article. For example, where a manufacturer builds a truck for a customer who...

  17. Forkhead transcription factor FoxF1 interacts with Fanconi anemia protein complexes to promote DNA damage response

    PubMed Central

    Pradhan, Arun; Ustiyan, Vladimir; Zhang, Yufang; Kalin, Tanya V.; Kalinichenko, Vladimir V.

    2016-01-01

    Forkhead box F1 (Foxf1) transcription factor is an important regulator of embryonic development but its role in tumor cells remains incompletely understood. While 16 proteins were characterized in Fanconi anemia (FA) core complex, its interactions with cellular transcriptional machinery remain poorly characterized. Here, we identified FoxF1 protein as a novel interacting partner of the FA complex proteins. Using multiple human and mouse tumor cell lines and Foxf1+/− mice we demonstrated that FoxF1 physically binds to and increases stability of FA proteins. FoxF1 co-localizes with FANCD2 in DNA repair foci in cultured cells and tumor tissues obtained from cisplatin-treated mice. In response to DNA damage, FoxF1-deficient tumor cells showed significantly reduced FANCD2 monoubiquitination and FANCM phosphorylation, resulting in impaired formation of DNA repair foci. FoxF1 knockdown caused chromosomal instability, nuclear abnormalities, and increased tumor cell death in response to DNA-damaging agents. Overexpression of FoxF1 in DNA-damaged cells improved stability of FA proteins, decreased chromosomal and nuclear aberrations, restored formation of DNA repair foci and prevented cell death after DNA damage. These findings demonstrate that FoxF1 is a key component of FA complexes and a critical mediator of DNA damage response in tumor cells. PMID:26625197

  18. ‘Caro-Tex 312’, a high yielding, orange-fruited, Habanero-type, F1 hybrid pepper

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Agricultural Research Service of the U. S. Department of Agriculture and the College of Agriculture and Life Sciences of Texas A&M University have released the high yielding, orange-fruited, Habanero-type, F1 hybrid pepper cultivar CaroTex-312. CaroTex-312 is the result of an F1 cross made at C...

  19. F1 and Tbilisi Are Closely Related Brucellaphages Exhibiting Some Distinct Nucleotide Variations Which Determine the Host Specificity

    PubMed Central

    Al Dahouk, Sascha; Nöckler, Karsten; Göllner, Cornelia; Appel, Bernd; Hertwig, Stefan

    2014-01-01

    We report on the 41,143-bp genome of brucellaphage F1, a podovirus that infects several Brucella species. The F1 genome is almost identical to the genome of brucellaphage Tb. However, some structural proteins of the phages exhibit extensive polymorphisms and might be responsible for their different host ranges. PMID:24482520

  20. 17 CFR 249.1200 - Form X-17F-1A-Report for missing, lost, stolen or counterfeit securities.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Form X-17F-1A-Report for... Reporting and Inquiry With Respect to Missing, Lost, Stolen, or Counterfeit Securities § 249.1200 Form X-17F... Register citations affecting Form X-17F-1A, see the List of CFR Sections Affected, which appears in...

  1. 17 CFR 249.1200 - Form X-17F-1A-Report for missing, lost, stolen or counterfeit securities.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Form X-17F-1A-Report for... Reporting and Inquiry With Respect to Missing, Lost, Stolen, or Counterfeit Securities § 249.1200 Form X-17F... Register citations affecting Form X-17F-1A, see the List of CFR Sections Affected, which appears in...

  2. 17 CFR 249.1200 - Form X-17F-1A-Report for missing, lost, stolen or counterfeit securities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Form X-17F-1A-Report for... Reporting and Inquiry With Respect to Missing, Lost, Stolen, or Counterfeit Securities § 249.1200 Form X-17F... Register citations affecting Form X-17F-1A, see the List of CFR Sections Affected, which appears in...

  3. 17 CFR 249.1200 - Form X-17F-1A-Report for missing, lost, stolen or counterfeit securities.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Form X-17F-1A-Report for... Reporting and Inquiry With Respect to Missing, Lost, Stolen, or Counterfeit Securities § 249.1200 Form X-17F... Register citations affecting Form X-17F-1A, see the List of CFR Sections Affected, which appears in...

  4. Intestine-specific homeobox (ISX) upregulates E2F1 expression and related oncogenic activities in HCC

    PubMed Central

    Chai, Chee-Yin; Hsi, Edward; Kuo, Hsing-Tao; Yokoyama, Kazunari K.; Hsu, Shih-Hsien

    2016-01-01

    Intestine-specific homeobox (ISX), a newly identified proto-oncogene, is involved in cell proliferation and progression of hepatocellular carcinoma (HCC). However, the underlying mechanisms linking gene expression and tumor formation remain unclear. In this study, we found that ISX transcriptionally activated E2F transcription factor 1 (E2F1) and associated oncogenic activity by directly binding to the E2 site of its promoter. Forced expression of ISX increased the expression of and phosphorylated the serine residue at position 332 of E2F1, which may be translocated into the nucleus to form the E2F1–DP-1 complex, suggesting that the promotion of oncogenic activities of the ISX–E2F1 axis plays a critical role in hepatoma cells. Coexpression of ISX and E2F1 significantly promoted p53 and RB-mediated cell proliferation and anti-apoptosis, and repressed apoptosis and autophagy. In contrast, short hairpin RNAi-mediated attenuation of ISX and E2F1 decreased cell proliferation and malignant transformation, respectively, in hepatoma cells in vitro and in vivo. The mRNA expression of E2F1 and ISX in 238 paired specimens from human HCC patients, and the adjacent, normal tissues exhibited a tumor-specific expression pattern which was highly correlated with disease pathogenesis, patient survival time, progression stage, and poor prognosis. Therefore, our results indicate that E2F1 is an important downstream gene of ISX in hepatoma progression. PMID:27175585

  5. [COX-2 regulation of prostaglandins in synaptic signaling].

    PubMed

    Yang, Hong-Wei

    2009-10-01

    Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme converting arachidonic acid to prostaglandins (PGs), which is a key messenger in traumatic brain injury- and ischemia-induced neuronal damage and in neuroinflammation. COX-2 is implicated in the pathogeneses of neurodegenerative diseases. Growing evidence implies that the contribution of COX-2 to neuropathology is associated with its involvement in synaptic alteration. Elevation or inhibition of COX-2 has been shown to enhance or suppress excitatory glutamatergic neurotransmission and long-term potentiation (LTP). These events are mainly mediated via PGE2, the predominant reaction product of COX-2, and the PGE2 subtype 2 receptor (EP2). Thus, elucidation of COX-2 in synaptic signaling may provide a mechanistic basis for designing new drugs aimed at preventing, treating or alleviating neuroinflammation-associated neurological disorders.

  6. Local prostaglandin administration for mid trimester abortion: a retrospective analysis.

    PubMed

    Cameron, I T; Baird, D T

    1987-01-01

    The hospital records of 548 consecutive patients undergoing midtrimester pregnancy termination by the local administration of prostaglandins (PGs) have been reviewed. Most women (352 or 64%) were single and 322 (59%) were pregnant for the 1st time. 2/3 of the patients (361 or 66%) were between 12-16 weeks pregnant, whereas 7 (1%) were considered to be more than 20 weeks pregnant. In 401 cases (92%), abortion was performed under Item 2 of the 1967 Abortion Act, although Item 4 was cited in 34 (81%) of those individuals with a pregnancy of greater than 17 weeks duration. Apart from 10 women (2%) in whom severe hemorrhage was documented, the major complication rate was less than 1%. The use of local PGs provides a safe, effective treatment method for therapeutic abortion in the 2nd trimester.

  7. Prostaglandin Pathway Gene Therapy for Sustained Reduction of Intraocular Pressure

    PubMed Central

    Barraza, Román A; McLaren, Jay W; Poeschla, Eric M

    2009-01-01

    Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in prostaglandin (PG) biosynthesis. In the eye, loss of COX-2 expression in aqueous humor–secreting cells has been associated with primary open-angle glaucoma (POAG). Reduction of intraocular pressure (IOP) is the main treatment goal in this disease. We used lentiviral vectors to stably express COX-2 and other PG biosynthesis and response transgenes in the ciliary body epithelium and trabecular meshwork (TM), the ocular suborgans that produce aqueous humor and regulate its outflow, respectively. We show that robust ectopic COX-2 expression and PG production require COX-2 complementary DNA (cDNA) sequence optimization. When COX-2 expression was coupled with a similarly optimized synthetic PGF2α receptor transgene to enable downstream signaling, gene therapy produced substantial and sustained reductions in IOP in a large animal model, the domestic cat. This study provides the first gene therapy for correcting the main cause of glaucoma. PMID:19953083

  8. High performance liquid chromotography of prostaglandins: biological applications.

    PubMed

    Carr, K; Sweetman, B J; Frölich, J C

    1976-01-01

    Two procedures are described for separation and purification of prostaglandins by high performance liquid chromatography. Both systems show excellent resolution of PGA2, PGE2 and PGF2a. Peak definition on the micro-particle silicic acid system is particularly good with the PGs appearing in 2-3 ml of organs effluent. Studies on reproducibility showed that PGE2 and PGE2a could be recovered with a retention volume of 54.2+/-0.76 ml and 64+/-0.6 ml, respectively (n=7, mean +/-50) with good recovery. The column can be run in about one hour and can be regenerated indefinitely (greater than 200 times). The degree of purification is compatible with analysis by gas chromatography-mass spectrometry. Examples showing the application of this chromatographic method to human seminal fluid, human renal tissue, platelet rich plasma and human urine samples indicate that it makes possible analysis of these samples even at low levels.

  9. Effect of flunixin meglumine on prostaglandin F2 alpha synthesis and metabolism in the pig.

    PubMed

    Odensvik, K; Cort, N; Basu, S; Kindahl, H

    1989-09-01

    The effect of flunixin meglumine on prostaglandin synthesis and metabolism was evaluated in the pig in vivo. It was found that the prostaglandin metabolite, 15-ketodihydro-PGF2 alpha, was decreased in the peripheral circulation within 20 min of injection of the drug. In therapeutic doses in the pig the drug had no effect on the metabolism of PGF2 alpha. Flunixin was compared with some other non-steroidal anti-inflammatory drugs in an in vitro test system utilizing sheep vesicular gland microsomes. It was concluded that this drug is a potent inhibitor of prostaglandin synthesis.

  10. [Image and quantity analysis of prostaglandin in rats' blood plasma and Na(+)-K(+)-ATPase in their cerebellum during the prevention of motion sickness by cinnarizine].

    PubMed

    Dong, W; Tian, D; Zhang, M

    1998-06-01

    To study the mechanism of cinnarizine in preventing motion sickness, TXB2, 6-Keto-PGF1 alpha in rats' blood plasma and Na(+)-K(+)-ATPase activity in the endothelial cells of their cerebellar capillary were measured and analysed by a radioactive immunity analyser and a computer image system. The results showed that TXB2 and 6-Keto-PGF1 alpha in rats' blood plasma in the cinnarizine preventing group (CPG) decreased remarkably, compared with those in the motion sickness group(MSG) (p < 0.05). The activity of Na(+)-K(+)-ATPase in the endothelial cells of rats' cerebellar capillary in CPG was higher than that in MSG (p < 0.01). The authors suggest that the lower concentration of TXB2 and 6-Keto-PGF1 alpha in rats' blood plasma in CPG is closely related to cinnarizine which prevents Ca2+ from entering into the platelets and into the endothelial cells of blood vessels. The higher activity of Na(+)-K(+)-ATPase in the cerebellum may be caused by cinnarizene which dilates the blood vessels in the brain, increases the blood flow therein, and hinders Ca2+ from getting into the cerebellum cells. These change are believed to be the important mechanism of how cinnarizine prevents motion sickness.

  11. Prostaglandin endoperoxide H synthases: peroxidase hydroperoxide specificity and cyclooxygenase activation.

    PubMed

    Liu, Jiayan; Seibold, Steve A; Rieke, Caroline J; Song, Inseok; Cukier, Robert I; Smith, William L

    2007-06-22

    The cyclooxygenase (COX) activity of prostaglandin endoperoxide H synthases (PGHSs) converts arachidonic acid and O2 to prostaglandin G2 (PGG2). PGHS peroxidase (POX) activity reduces PGG2 to PGH2. The first step in POX catalysis is formation of an oxyferryl heme radical cation (Compound I), which undergoes intramolecular electron transfer forming Intermediate II having an oxyferryl heme and a Tyr-385 radical required for COX catalysis. PGHS POX catalyzes heterolytic cleavage of primary and secondary hydroperoxides much more readily than H2O2, but the basis for this specificity has been unresolved. Several large amino acids form a hydrophobic "dome" over part of the heme, but when these residues were mutated to alanines there was little effect on Compound I formation from H2O2 or 15-hydroperoxyeicosatetraenoic acid, a surrogate substrate for PGG2. Ab initio calculations of heterolytic bond dissociation energies of the peroxyl groups of small peroxides indicated that they are almost the same. Molecular Dynamics simulations suggest that PGG2 binds the POX site through a peroxyl-iron bond, a hydrogen bond with His-207 and van der Waals interactions involving methylene groups adjoining the carbon bearing the peroxyl group and the protoporphyrin IX. We speculate that these latter interactions, which are not possible with H2O2, are major contributors to PGHS POX specificity. The distal Gln-203 four residues removed from His-207 have been thought to be essential for Compound I formation. However, Q203V PGHS-1 and PGHS-2 mutants catalyzed heterolytic cleavage of peroxides and exhibited native COX activity. PGHSs are homodimers with each monomer having a POX site and COX site. Cross-talk occurs between the COX sites of adjoining monomers. However, no cross-talk between the POX and COX sites of monomers was detected in a PGHS-2 heterodimer comprised of a Q203R monomer having an inactive POX site and a G533A monomer with an inactive COX site.

  12. Fetal placental prostaglandin metabolism in the peripartum cow

    SciTech Connect

    Gross, T.S.; Williams, W.F.; Lewis, G.S.

    1986-03-05

    Previous results demonstrate that fetal placental tissue synthesizes prostaglandin E (PGE) prior to parturition. When placental membranes do not separate postpartum, PGE synthesis is maintained, while prostaglandin F (PGF) synthesis predominates when the membranes separate. Concurrent with separation is a decline in fetal placental binucleate cell (BNC) numbers. These data suggest a fetal placental conversion of PGE to PGF. For this experiment, placentomes were collected at ten days prepartum (PRE, n=12) and within 1 hr postpartum. Nine of the postpartum animals had fetal membrane separation within 12 hr postpartum (S) and eight did not exhibit membrane separation (NS). For each placentome, fetal (villi) components were manually isolated and examined for the ability to interconvert /sup 3/H labeled PGE/sub 2/ and PGF/sub 2/. All villi were unable to convert PGE/sub 2/ to PGF/sub 2/ (P > .05). The PRE and NS villi were able to convert PGF/sub 2/ to PGE/sub 2/ (P < .05) while S villi could not. When the BNC decline in numbers, as in the S villi, the ability to convert PGF/sub 2/ to PGE/sub 2/ (P < .05) while S villi could not. When the BNC decline in numbers, as in the S villi, the ability to convert PGF/sub 2/ to PGE/sub 2/ also declines (P < .05). These data suggest that peripartum fetal placental tissue might synthesize PGF which is then converted to PGE. It is possible that the BNC are directly converting PGF to PGE or that they are modulating this conversion. Therefore, with a decline in BNC numbers, PGF synthesis would predominate.

  13. Classifying genotype F of hepatitis B virus into F1 and F2 subtypes

    PubMed Central

    Kato, Hideaki; Fujiwara, Kei; Gish, Robert G.; Sakugawa, Hiroshi; Yoshizawa, Hiroshi; Sugauchi, Fuminaka; Orito, Etsuro; Ueda, Ryuzo; Tanaka, Yasuhito; Kato, Takanobu; Miyakawa, Yuzo; Mizokami, Masashi

    2005-01-01

    AIM: To explore the propriety of providing hepatitis B virus (HBV) genotypes F and H with two distinct genotypes. METHODS: Eleven HBV isolates of genotype F (HBV/F) were recovered from patients living in San Francisco, Japan, Panama, and Venezuela, and their full-length sequences were determined. Phylogenetic analysis was carried out among them along with HBV isolates previously reported. RESULTS: Seven of them clustered with reported HBV/F isolates in the phylogenetic tree constructed on the entire genomic sequence. The remaining four flocked on another branch along with three HBV isolates formerly reported as genotype H. These seven HBV isolates, including the four in this study and the three reported, had a sequence divergence of 7.3-9.5% from the other HBV/F isolates, and differed by >13.7% from HBV isolates of the other six genotypes (A-E and G). Based on a marked genomic divergence, falling just short of >8% separating the seven genotypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences among the 7 HBV/F2 isolates and against 47 HBV/F1 isolates as well as 136 representing the other six genotypes (A-E and G), two clusters separated by distinct genetic distances emerged. CONCLUSION: Based on these analyses, classifying HBV/F isolates into two subtypes (F1 and F2) would be more appropriate than providing them with two distinct genotypes (F and H). PMID:16419158

  14. None of the rotor residues of F1-ATPase are essential for torque generation.

    PubMed

    Chiwata, Ryohei; Kohori, Ayako; Kawakami, Tomonari; Shiroguchi, Katsuyuki; Furuike, Shou; Adachi, Kengo; Sutoh, Kazuo; Yoshida, Masasuke; Kinosita, Kazuhiko

    2014-05-20

    F1-ATPase is a powerful rotary molecular motor that can rotate an object several hundred times as large as the motor itself against the viscous friction of water. Forced reverse rotation has been shown to lead to ATP synthesis, implying that the mechanical work against the motor's high torque can be converted into the chemical energy of ATP. The minimal composition of the motor protein is α3β3γ subunits, where the central rotor subunit γ turns inside a stator cylinder made of alternately arranged α3β3 subunits using the energy derived from ATP hydrolysis. The rotor consists of an axle, a coiled coil of the amino- and carboxyl-terminal α-helices of γ, which deeply penetrates the stator cylinder, and a globular protrusion that juts out from the stator. Previous work has shown that, for a thermophilic F1, significant portions of the axle can be truncated and the motor still rotates a submicron sized bead duplex, indicating generation of up to half the wild-type (WT) torque. Here, we inquire if any specific interactions between the stator and the rest of the rotor are needed for the generation of a sizable torque. We truncated the protruding portion of the rotor and replaced part of the remaining axle residues such that every residue of the rotor has been deleted or replaced in this or previous truncation mutants. This protrusionless construct showed an unloaded rotary speed about a quarter of the WT, and generated one-third to one-half of the WT torque. No residue-specific interactions are needed for this much performance. F1 is so designed that the basic rotor-stator interactions for torque generation and control of catalysis rely solely upon the shape and size of the rotor at very low resolution. Additional tailored interactions augment the torque to allow ATP synthesis under physiological conditions.

  15. Trends in the E and F1 Regions of the Earth's Ionosphere

    NASA Astrophysics Data System (ADS)

    Bremer, J.

    2007-05-01

    Ground based ionosonde measurements are a very important source for investigations of long-term variations in the ionospheric E and F1 regions. Data of such observations are available at many different ionospheric stations all over the world since partly more than 50 years. Here mainly standard parameters foE, h'E, and foF1 are used for trend analyses. Two main problems have to be taken into consideration in these analyses. Firstly, the data series have to be homogeneous, i. e. the observations should not be disturbed by artificial steps due to changes in the used technical equipment or in the evaluation algorithm. Secondly, the strong solar and geomagnetic influences upon the ionospheric data have carefully to be removed by an appropriate regression analysis. Otherwise it is impossible to detect the small trends in the different ionospheric parameters. The trends derived at individual stations differ markedly. Nevertheless, the mean global trends estimated from the trends at the different stations are statistically significant different from zero (positive trends in foE and foF1, negative trend in h'E). These mean trends can at least qualitatively be explained by an increasing atmospheric greenhouse effect (increase of CO2 content or of other greenhouse gases) and decreasing ozone values. The positive foE trend is also in qualitative agreement with rocket mass spectrometer observations of ion densities in the E region. Furthermore first indications could be found that the changing ozone trend (before about 1979, between 1979 until 1995, and after about 1995) can modify the estimated long-term variations at least in foE.

  16. Temperature Dependence of the Rotation and Hydrolysis Activities of F1-ATPase

    PubMed Central

    Furuike, Shou; Adachi, Kengo; Sakaki, Naoyoshi; Shimo-Kon, Rieko; Itoh, Hiroyasu; Muneyuki, Eiro; Yoshida, Masasuke; Kinosita, Kazuhiko

    2008-01-01

    F1-ATPase, a water-soluble portion of the enzyme ATP synthase, is a rotary molecular motor driven by ATP hydrolysis. To learn how the kinetics of rotation are regulated, we have investigated the rotational characteristics of a thermophilic F1-ATPase over the temperature range 4–50°C by attaching a polystyrene bead (or bead duplex) to the rotor subunit and observing its rotation under a microscope. The apparent rate of ATP binding estimated at low ATP concentrations increased from 1.2 × 106 M−1 s−1 at 4°C to 4.3 × 107 M−1 s−1 at 40°C, whereas the torque estimated at 2 mM ATP remained around 40 pN·nm over 4–50°C. The rotation was stepwise at 4°C, even at the saturating ATP concentration of 2 mM, indicating the presence of a hitherto unresolved rate-limiting reaction that occurs at ATP-waiting angles. We also measured the ATP hydrolysis activity in bulk solution at 4–65°C. F1-ATPase tends to be inactivated by binding ADP tightly. Both the inactivation and reactivation rates were found to rise sharply with temperature, and above 30°C, equilibrium between the active and inactive forms was reached within 2 s, the majority being inactive. Rapid inactivation at high temperatures is consistent with the physiological role of this enzyme, ATP synthesis, in the thermophile. PMID:18375515

  17. RAPD linkage mapping in a longleaf pine x slash pine F1 family.

    PubMed

    Kubisiak, T L; Nelson, C D; Nance, W L; Stine, M

    1995-06-01

    Random amplified polymorphic DNAs (RAPDs) were used to construct linkage maps of the parent of a longleaf pine (Pinus palustris Mill.) slash pine (Pinus elliottii Englm.) F1 family. A total of 247 segregating loci [233 (1∶1), 14 (3∶1)] and 87 polymorphic (between parents), but non-segregating, loci were identified. The 233 loci segregating 1∶1 (testcross configuration) were used to construct parent-specific linkage maps, 132 for the longleaf-pine parent and 101 for the slash-pine parent. The resulting linkage maps consisted of 122 marker loci in 18 groups (three or more loci) and three pairs (1367.5 cM) for longleaf pine, and 91 marker loci in 13 groups and six pairs for slash pine (952.9 cM). Genome size estimates based on two-point linkage data ranged from 2348 to 2392 cM for longleaf pine, and from 2292 to 2372 cM for slash pine. Linkage of 3∶1 loci to testcross loci in each of the parental maps was used to infer further linkages within maps, as well as potentially homologous counterparts between maps. Three of the longleaf-pine linkage groups appear to be potentially homologous counterparts to four different slash-pine linkage groups. The number of heterozygous loci (previously testcross in parents) per F1 individual, ranged from 96 to 130. With the 87 polymorphic, but non-segregating, loci that should also be heterozygous in the F1 progeny, a maximum of 183-217 heterozygous loci could be available for mapping early height growth (EHG) loci and for applying genomic selection in backcross populations.

  18. Dale Reed with model in front of M2-F1

    NASA Technical Reports Server (NTRS)

    1967-01-01

    Dale Reed with a model of the M2-F1 in front of the actual lifting body. Reed used the model to show the potential of the lifting bodies. He first flew it into tall grass to test stability and trim, then hand-launched it from buildings for longer flights. Finally, he towed the lifting-body model aloft using a powered model airplane known as the 'Mothership.' A timer released the model and it glided to a landing. Dale's wife Donna used a 9 mm. camera to film the flights of the model. Its stability as it glided--despite its lack of wings--convinced Milt Thompson and some Flight Research Center engineers including the center director, Paul Bikle, that a piloted lifting body was possible. The lifting body concept evolved in the mid-1950s as researchers considered alternatives to ballistic reentries of piloted space capsules. The designs for hypersonic, wingless vehicles were on the boards at NASA Ames and NASA Langley facilities, while the US Air Force was gearing up for its Dyna-Soar program, which defined the need for a spacecraft that would land like an airplane. Despite favorable research on lifting bodies, there was little support for a flight program. Dryden engineer R. Dale Reed was intrigued with the lifting body concept, and reasoned that some sort of flight demonstration was needed before wingless aircraft could be taken seriously. In February 1962, he built a model lifting body based upon the Ames M2 design, and air-launched it from a radio controlled 'mothership.' Home movies of these flights, plus the support of research pilot Milt Thompson, helped pursuade the facilities director, Paul Bikle, to give the go-ahead for the construction of a full-scale version, to be used as a wind-tunnel model and possibly flown as a glider. Comparing lifting bodies to space capsules, an unofficial motto of the project was, 'Don't be Rescued from Outer Space--Fly Back in Style.' The construction of the M2-F1 was a joint effort by Dryden and a local glider manufacturer, the

  19. Surface Plasmon Resonance Analysis of Histidine-Tagged F1-ATPase Surface Adsorption

    NASA Astrophysics Data System (ADS)

    Tucker, Jenifer K.; Richter, Mark L.; Berrie, Cindy L.

    2015-11-01

    Studies of the rotational activity of the enzymatic core (α3β3γ) of the F1-ATPase motor protein have relied on binding the enzyme to NTA-coated glass surfaces via polyhistidine tags engineered into the C-termini of each of the three α or β subunits. Those studies revealed the rotational motion of the central γ subunit by monitoring the motion of attached micron-long actin filaments or spherical nanoparticles. However, only a small percentage of the attached filaments or particles were observed to rotate, likely due, at least in part, to non-uniform surface attachment of the motor proteins. In this study, we have applied surface plasmon resonance to monitor the kinetics and affinity of binding of the His-tagged motor protein to NTA-coated gold sensor surfaces. The binding data, when fit to a heterogeneous binding model, exhibit two sets of adsorption-desorption rate constants with two dissociation constants of 4.0 × 10-9 M and 8.6 × 10-11 M for 6His-α3β3γ binding to the nickel ion-activated NTA surface. The data are consistent with mixed attachment of the protein via two (bimodal) and three (trimodal) NTA/Ni2+-His-tag interactions, respectively, with the less stable bimodal interaction dominating. The results provide a partial explanation for the low number of surface-attached F1 motors previously observed in rotation studies and suggest alternative approaches to uniform F1 motor surface attachment for future fabrication of motor-based nanobiodevices and materials.

  20. None of the Rotor Residues of F1-ATPase Are Essential for Torque Generation

    PubMed Central

    Chiwata, Ryohei; Kohori, Ayako; Kawakami, Tomonari; Shiroguchi, Katsuyuki; Furuike, Shou; Adachi, Kengo; Sutoh, Kazuo; Yoshida, Masasuke; Kinosita, Kazuhiko

    2014-01-01

    F1-ATPase is a powerful rotary molecular motor that can rotate an object several hundred times as large as the motor itself against the viscous friction of water. Forced reverse rotation has been shown to lead to ATP synthesis, implying that the mechanical work against the motor’s high torque can be converted into the chemical energy of ATP. The minimal composition of the motor protein is α3β3γ subunits, where the central rotor subunit γ turns inside a stator cylinder made of alternately arranged α3β3 subunits using the energy derived from ATP hydrolysis. The rotor consists of an axle, a coiled coil of the amino- and carboxyl-terminal α-helices of γ, which deeply penetrates the stator cylinder, and a globular protrusion that juts out from the stator. Previous work has shown that, for a thermophilic F1, significant portions of the axle can be truncated and the motor still rotates a submicron sized bead duplex, indicating generation of up to half the wild-type (WT) torque. Here, we inquire if any specific interactions between the stator and the rest of the rotor are needed for the generation of a sizable torque. We truncated the protruding portion of the rotor and replaced part of the remaining axle residues such that every residue of the rotor has been deleted or replaced in this or previous truncation mutants. This protrusionless construct showed an unloaded rotary speed about a quarter of the WT, and generated one-third to one-half of the WT torque. No residue-specific interactions are needed for this much performance. F1 is so designed that the basic rotor-stator interactions for torque generation and control of catalysis rely solely upon the shape and size of the rotor at very low resolution. Additional tailored interactions augment the torque to allow ATP synthesis under physiological conditions. PMID:24853745

  1. New orbit recalculations of comet C/1890 F1 Brooks and its dynamical evolution

    NASA Astrophysics Data System (ADS)

    Królikowska, Małgorzata; Dybczyński, Piotr A.

    2016-08-01

    C/1890 F1 Brooks belongs to a group of 19 comets used by Jan Oort to support his famous hypothesis on the existence of a spherical cloud containing hundreds of billions of comets with orbits of semi-major axes between 50 000 and 150 000 au. Comet Brooks stands out from this group because of a long series of astrometric observations as well as a nearly 2-yr-long observational arc. Rich observational material makes this comet an ideal target for testing the rationality of an effort to recalculate astrometric positions on the basis of original (comet-star) measurements using modern star catalogues. This paper presents the results of such a new analysis based on two different methods: (i) automatic re-reduction based on cometary positions and the (comet-star) measurements and (ii) partially automatic re-reduction based on the contemporary data for the reference stars originally used. We show that both methods offer a significant reduction in the uncertainty of orbital elements. Based on the most preferred orbital solution, the dynamical evolution of comet Brooks during three consecutive perihelion passages is discussed. We conclude that C/1890 F1 is a dynamically old comet that passed the Sun at a distance below 5 au during its previous perihelion passage. Furthermore, its next perihelion passage will be a little closer than during the 1890-1892 apparition. C/1890 F1 is interesting also because it suffered extremely small planetary perturbations when it travelled through the planetary zone. Therefore, in the next passage through perihelion, it will once again be a comet from the Oort spike.

  2. Enhanced inhibitory effects of TBT chloride on the development of F1 rats.

    PubMed

    Asakawa, H; Tsunoda, M; Kaido, T; Hosokawa, M; Sugaya, C; Inoue, Y; Kudo, Y; Satoh, T; Katagiri, H; Akita, H; Saji, M; Wakasa, M; Negishi, T; Tashiro, T; Aizawa, Y

    2010-05-01

    Neurotoxicity is one of the major effects of tributyltin (TBT). The effects on the next generation of F(1) rats exposed to TBT via the placenta and their dams' milk may be stronger than those on adults. Pregnant Wister rats were exposed to TBT at 0 and 125 ppm in their food. Half of the female F(1) rats in both groups were exposed to TBT at 125 ppm in their food from 9 to 15 weeks of age. Female F(1) rats were divided into the following groups: the control-control (CC) group, with no exposure; the TBT-control (TC) group, exposed to TBT via the placenta and their dams' milk; the control-TBT (CT) group, exposed to TBT via their food from 9 to 15 weeks of age; and the TBT-TBT (TT) group, exposed to TBT via the placenta, their dams' milk, and their food (n = 10/group). After administration, an open-field test and prepulse inhibition (PPI) test were performed at 15 weeks of age. The mean body weights of the TC and TT groups were significantly lower than that of the CC group from 9 to 15 weeks of age. The mean relative thymus weight of the TC and TT groups was significantly lower than that of the CC group. In the open-field test, a marked decrease in the total locomotion distance was observed in the TT group. The mean values in the TT and TC groups were significantly lower than that in the CC group. For the locomotion distance between 15 and 20 min, the mean values in the CT, TC, and TT groups were significantly lower than that in the CC group. The mean locomotor distance between 25 and 30 min in the TT group was significantly lower than that in the CC and TC groups. The mean values of instances of wall rearing in the TC, CT, and TT groups were significantly lower than that in the CC group. The mean value of face washing or body washing in the TT group was significantly lower than that in the CT group. There were no significant differences in indexes of the PPI test. Exposure to TBT via the placenta and their dams' milk inhibited the development of F(1) rats, which

  3. Mineral requirements for growth and maintenance of F1 Boer × Saanen male kids.

    PubMed

    Teixeira, I A M A; Härter, C J; Pereira Filho, J M; Sobrinho, A G da Silva; Resende, K T

    2015-05-01

    The objective of this study was to determine the net requirements of minerals for the growth and maintenance of intact male F1 Boer × Saanen goat kids in the initial phase of growth. The following 2 experiments were performed: Exp. 1 was performed to determine the net growth requirements for Ca, P, Mg, Na, and K by F1 Boer × Saanen goat kids from 5 to 25 kg of BW and Exp. 2 was performed to determine the maintenance requirements of F1 Boer × Saanen goats from 15 to 25 kg BW. In Exp. 1, 32 intact male goat kids were distributed in a completely randomized design and mineral body composition was fit to an allometric equation in the form of a nonlinear model. To determine the mineral requirements for maintenance in Exp. 2, 21 intact male goat kids were distributed in a randomized block design, where the goat kids were subjected to 3 levels of feed restriction (0, 30, and 60% feed restriction). At the onset of Exp. 2, 7 goat kids were harvested and used to estimate the initial body composition (15 kg BW). Initial body composition was used to calculate the retention of minerals. The maintenance requirements were estimated by regressions obtained from the retention of minerals in the empty body and the intake of the mineral. The concentration of Ca, P, Na, and K in the empty BW decreased by 11, 13, 26, and 23% with the increase in BW from 5 to 25 kg (P < 0.01). As a consequence, our results showed that net requirements of Ca, P, Mg, Na, and K for weight gain decreased by 27.5, 27.8, 4.25, 43.2, and 39.7%, respectively, with the increase in BW from 5 to 25 kg (P < 0.01). The net requirements (g/kg of ADG) decreased from 9.7 to 7.0 for Ca, 6.5 to 4.7 for P, 0.38 to 0.36 for Mg, 0.88 to 0.50 for Na, and 1.9 to 1.2 for K when BW increased from 5 to 25 kg. The daily net requirements for maintenance per kilogram of BW were 38 mg of Ca, 42 mg of P, 1.6 mg of Mg, 5.0 mg of Na, and 19 mg of K. These results for the nutritional requirements of minerals may help to formulate more

  4. Peroxidative oxidation of leuco-dichlorofluorescein by prostaglandin H synthase in prostaglandin biosynthesis from polyunsaturated fatty acids.

    PubMed

    Larsen, L N; Dahl, E; Bremer, J

    1996-01-05

    Prostaglandin H synthase can oxidize arachidonic acid with leuco-dichlorofluorescein as reducing cosubstrate. Addition of 0.5 mM phenol increases the oxidation of leuco-dichlorofluorescein to dichlorofluorescein 5-fold, probably by acting as a cyclic intermediate in the oxidation. Tetramethyl-p-phenylenediamine is also oxidized as cosubstrate. Its oxidation is not influenced by phenol. A stoichiometry of close to one mole of tetramethyl-p-phenylenediamine or leuco-dichlorofluorescein consumed per mole of arachidonic acid was found in the initial phase of the reaction. In the presence of phenol + leuco-dichlorofluorescein, the oxidation rate of arachidonic acid is about 40% lower than with phenol alone as cosubstrate. Since dichlorofluorescein has a molar extinction coefficient of 91 . 10(3) at 502 nm, the oxidation of less than 1 microM leuco-dichlorofluorescein can be detected spectrophotometrically. The rate of extinction change with leuco-dichlorofluorescein (at 502 nm) is about 4-fold more rapid than with tetramethyl-p-phenylenediamine (at 611 nm). With this spectrophotometric assay we have confirmed that arachidonic acid, linolenic acid, adrenic acid, gamma-linolenic acid, eicosapentaenoic acid, are substrates for prostaglandin H synthase with decreasing reaction rates in the mentioned order. The same order of reaction rates were found when oxygen consumption was measured. The assay also shows that docosahexaenoic acid is substrate for the enzyme. The reaction rate of the enzyme evidently is decreased both by a n-3 double bond and by deviation from a 20 carbon chain length of the fatty acid substrate.

  5. Testosterone induction of prostaglandin-endoperoxide synthase 2 expression and prostaglandin F(2alpha) production in hamster Leydig cells.

    PubMed

    Matzkin, María E; Gonzalez-Calvar, Silvia I; Mayerhofer, Artur; Calandra, Ricardo S; Frungieri, Mónica B

    2009-07-01

    We have previously observed expression of prostaglandin-endoperoxide synthase 2 (PTGS2), the key enzyme in the biosynthesis of prostaglandins (PGs), in reproductively active Syrian hamster Leydig cells, and reported an inhibitory role of PGF(2alpha) on hamster testicular steroidogenesis. In this study, we further investigated PTGS2 expression in hamster Leydig cells during sexual development and photoperiodic gonadal regression. Since PTGS2 is mostly expressed in pubertal and reproductively active adult hamsters with high circulating levels of LH and androgens, we studied the role of these hormones in the regulation/maintenance of testicular PTGS2/PGF(2alpha). In active hamster Leydig cells, LH/hCG and testosterone induced PTGS2 and PGF(2alpha) production, and their actions were abolished by the antiandrogen bicalutamide (Bi). These results indicate that LH does not exert a direct effect on PG synthesis. Testosterone also stimulated phosphorylation of the mitogen-activated protein kinase isoforms 3/1 (MAPK3/1) within minutes and hours, but the testosterone metabolite dihydrotestosterone had no effect on PTGS2 and MAPK3/1. Because Bi and U0126, an inhibitor of the MAP kinase kinases 1 and 2 (MAP2K1/2), abolished testosterone actions on MAPK3/1 and PTGS2, our studies suggest that testosterone directly induces PTGS2/PGF(2alpha) in hamster Leydig cells via androgen receptors and a non-classical mechanism that involves MAPK3/1 activation. Since PGF(2alpha) inhibits testosterone production, it might imply the existence of a regulatory loop that is setting a brake on steroidogenesis. Thus, the androgen environment might be crucial for the regulation of testicular PG production at least during sexual development and photoperiodic variations in hamsters.

  6. Extensive allelic variation in gene expression in populus F1 hybrids.

    PubMed

    Zhuang, Yan; Adams, Keith L

    2007-12-01

    Hybridization between plant species can induce speciation as well as phenotypic novelty and heterosis. Hybrids also can show genome rearrangements and gene expression changes compared with their parents. Here we determined the allelic variation in gene expression in Populus trichocarpa x Populus deltoides F(1) hybrids. Among 30 genes analyzed in four independently formed hybrids, 17 showed >1.5-fold expression biases for one of the two alleles, and there was monoallelic expression of one gene. Expression ratios of the alleles differed between leaves and stems for 10 genes. The results suggest differential regulation of the two parental alleles in the hybrids. To determine if the allelic expression biases were caused by hybridization we compared the ratios of species-specific transcripts between an F(1) hybrid and its parents. Thirteen of 19 genes showed allelic expression ratios in the hybrid that were significantly different from the ratios of the parental species. The P. deltoides allele of one gene was silenced in the hybrid. Modes of gene regulation were inferred from the hybrid-parent comparisons. Cis-regulation was inferred for 6 genes, trans-regulation for 1 gene, and combined cis- and trans-regulation for 9 genes. The results from this study indicate that hybridization between plant species can have extensive effects on allelic expression patterns, some of which might lead to phenotypic changes.

  7. Little qualitative RNA misexpression in sterile male F1 hybrids of Drosophila pseudoobscura and D. persimilis

    PubMed Central

    Reiland, Jane; Noor, Mohamed AF

    2002-01-01

    Background Although the genetics of hybrid sterility has been the subject of evolutionary studies for over sixty years, no one has shown the reason(s) why alleles that operate normally within species fail to function in another genetic background. Several lines of evidence suggest that failures in normal gene transcription contribute to hybrid dysfunctions, but genome-wide studies of gene expression in pure-species and hybrids have not been undertaken. Here, we study genome-wide patterns of expression in Drosophila pseudoobscura, D. persimilis, and their sterile F1 hybrid males using differential display. Results Over five thousand amplifications were analyzed, and 3312 were present in amplifications from both of the pure species. Of these, 28 (0.5%) were not present in amplifications from adult F1 hybrid males. Using product-specific primers, we were able to confirm one of nine of the transcripts putatively misexpressed in hybrids. This transcript was shown to be male-specific, but without detectable homology to D. melanogaster sequence. Conclusion We tentatively conclude that hybrid sterility can evolve without widespread, qualitative misexpression of transcripts in species hybrids. We suggest that, if more misexpression exists in sterile hybrids, it is likely to be quantitative, tissue-specific, and/ or limited to earlier developmental stages. Although several caveats apply, this study was a first attempt to determine the mechanistic basis of hybrid sterility, and one potential candidate gene has been identified for further study. PMID:12223116

  8. What Causes Partial F1 Hybrid Viability? Incomplete Penetrance versus Genetic Variation

    PubMed Central

    López-Fernández, Hernán; Bolnick, Daniel I.

    2007-01-01

    Background Interspecific hybrid crosses often produce offspring with reduced but non-zero survivorship. In this paper we ask why such partial inviability occurs. This partial inviability could arise from incomplete penetrance of lethal Dobzhansky-Muller incompatibilities (DMIs) shared by all members of a hybrid cross. Alternatively, siblings may differ with respect to the presence or number of DMIs, leading to genotype-dependent variation in viability and hence non-Mendelian segregation of parental alleles in surviving F1 hybrids. Methodology/Principal Findings We used amplified fragment length polymorphisms (AFLPs) to test for segregation distortion in one hybrid cross between green and longear sunfish (Lepomis cyanellus and L. megalotis). Hybrids showed partial viability, and twice as much segregation distortion (36.8%) of AFLPs as an intraspecific control cross (18.8%). Incomplete penetrance of DMIs, which should cause genotype-independent mortality, is insufficient to explain the observed segregation distortion. Conclusions/Significance We conclude that F1 hybrid sunfish are polymorphic for DMIs, either due to sex-linked DMI loci (causing Haldane's Rule), or polymorphic autosomal DMI loci. Because few AFLP markers were sex-linked (2%), the most parsimonious conclusion is that parents may have been heterozygous for loci causing hybrid inviability. PMID:18074018

  9. Variability in the amount of homoeologous pairing among F1 hybrids

    PubMed Central

    Poggio, Lidia; Greizerstein, Eduardo; Ferrari, María

    2016-01-01

    Genes involved in the exclusive pairing of homologous chromosomes have been described in several polyploid species but little is known about the activity of these genes in diploids (which have only one dose of each homoeologous genome). Analysis of the meiotic behaviour of species, natural and artificial hybrids and polyploids of Glandularia suggests that, in allopolyploids where homoeologous genomes are in two doses, regulator genes prevent homoeologous pairing. The different meiotic phenotypes in diploid F1 hybrids between Glandularia pulchella and Glandularia incisa strongly suggest that these pairing regulator genes possess an incomplete penetrance when homoeologous genomes are in only one dose. Moreover, the meiotic analysis of natural and artificial F1 hybrids suggests that the genetic constitution of parental species influences the activity of pairing regulator genes and is mainly responsible for variability in the amount of homoeologous pairing observed in diploid hybrids. In Glandularia, the pairing regulator genes originated in South American diploid species. The cytogenetic characteristics of this genus make it a good model to analyse and explore in greater depth the activity of pairing regulator genes at different ploidy levels. PMID:27255515

  10. Replication of a chronic hepatitis B virus genotype F1b construct.

    PubMed

    Hernández, Sergio; Jiménez, Gustavo; Alarcón, Valentina; Prieto, Cristian; Muñoz, Francisca; Riquelme, Constanza; Venegas, Mauricio; Brahm, Javier; Loyola, Alejandra; Villanueva, Rodrigo A

    2016-03-01

    Genotype F is one of the less-studied genotypes of human hepatitis B virus, although it is widely distributed in regions of Central and South American. Our previous studies have shown that HBV genotype F is prevalent in Chile, and phylogenetic analysis of its full-length sequence amplified from the sera of chronically infected patients identified it as HBV subgenotype F1b. We have previously reported the full-length sequence of a HBV molecular clone obtained from a patient chronically infected with genotype F1b. In this report, we established a system to study HBV replication based on hepatoma cell lines transfected with full-length monomers of the HBV genome. Culture supernatants were analyzed after transfection and found to contain both HBsAg and HBeAg viral antigens. Consistently, fractionated cell extracts revealed the presence of viral replication, with both cytoplasmic and nuclear DNA intermediates. Analysis of HBV-transfected cells by indirect immunofluorescence or immunoelectron microscopy revealed the expression of viral antigens and cytoplasmic viral particles, respectively. To test the functionality of the ongoing viral replication further at the level of chromatinized cccDNA, transfected cells were treated with a histone deacetylase inhibitor, and this resulted in increased viral replication. This correlated with changes posttranslational modifications of histones at viral promoters. Thus, the development of this viral replication system for HBV genotype F will facilitate studies on the regulation of viral replication and the identification of new antiviral drugs.

  11. Risk reduction activities for an F-1-based advanced booster for NASA's Space Launch System

    NASA Astrophysics Data System (ADS)

    Crocker, A. M.; Doering, K. B.; Cook, S. A.; Meadows, R. G.; Lariviere, B. W.; Bachtel, F. D.

    For NASA's Space Launch System (SLS) Advanced Booster Engineering Demonstration and/or Risk Reduction (ABEDRR) procurement, Dynetics, Inc. and Pratt & Whitney Rocketdyne (PWR) formed a team to offer a wide-ranging set of risk reduction activities and full-scale, system-level demonstrations that support NASA's goal of enabling competition on an affordable booster that meets the evolved capabilities of the SLS. During the ABEDRR effort, the Dynetics Team will apply state-of-the-art manufacturing and processing techniques to the heritage F-1, resulting in a low recurring cost engine while retaining the benefits of Apollo-era experience. ABEDRR will use NASA test facilities to perform full-scale F-1 gas generator and powerpack hot-fire test campaigns for engine risk reduction. Dynetics will also fabricate and test a tank assembly to verify the structural design. The Dynetics Team is partnered with NASA through Space Act Agreements (SAAs) to maximize the expertise and capabilities applied to ABEDRR.

  12. Maternal obesity and malnourishment exacerbate perinatal oxidative stress resulting in diabetogenic programming in F1 offspring.

    PubMed

    Saad, M I; Abdelkhalek, T M; Haiba, M M; Saleh, M M; Hanafi, M Y; Tawfik, S H; Kamel, M A

    2016-06-01

    The effect of in-utero environment on fetal health and survival is long-lasting, and this is known as the fetal origin hypothesis. The oxidative stress state during gestation could play a pivotal role in fetal programming and development of diseases such as diabetes. In this study, we investigated the effect of intra-uterine obesity and malnutrition on oxidative stress markers in pancreatic and peripheral tissues of F1 offspring both prenatally and postnatally. Furthermore, the effect of postnatal diet on oxidative stress profile was evaluated. The results indicated that intra-uterine obesity and malnourishment significantly increased oxidative stress in F1 offspring. Moreover, the programming effect of obesity was more pronounced and protracted than malnutrition. The obesity-induced programming of offspring tissues was independent of high-caloric environment that the offspring endured; however, high-caloric diet potentiated its effect. In addition, pancreas and liver were the most affected tissues by fetal reprogramming both prenatally and postnatally. In conclusion, maternal obesity and malnutrition-induced oxidative stress could predispose offspring to insulin resistance and diabetes.

  13. Developmental trajectories and breakdown in F1 interpopulation hybrids of Tribolium castaneum

    PubMed Central

    Drury, Douglas W; Ehmke, Ross C; Jideonwo, Victoria N; Wade, Michael J

    2013-01-01

    When hybrid inviability is an indirect by-product of local adaptation, we expect its degree of severity between pairs of populations to vary and to be sensitive to the environment. While complete reciprocal hybrid inviability is the outcome of the gradual process of local adaptation, it is not representative of the process of accumulation of incompatibility. In the flour beetle, Tribolium castaneum, some pairs of populations exhibit complete, reciprocal F1 hybrid incompatibility while other pairs are fully or partially compatible. We characterize this naturally occurring variation in the degree and timing of expression of the hybrid incompatible phenotype to better understand the number of genes or developmental processes contributing to speciation. We assessed the morphological and developmental variation in four Tribolium castaneum populations and their 12 possible F1 hybrids at each life-history stage from egg to adult. We find that the rate of hybrid larval development is affected in all interpopulation crosses, including those eventually producing viable, fertile adults. Hybrid incompatibility manifests early in development as changes in the duration of instars and diminished success in the transition between instars are relative to the parent populations. Parent populations with similar developmental profiles may produce hybrids with disrupted development. The degree and timing of expression of hybrid inviability depends upon populations crossed, direction of the cross, and environment in which hybrids are raised. Our findings suggest that the coordinated expression of genes involved in transitional periods of development is the underlying cause of hybrid incompatibility in this species. PMID:23919145

  14. Effects of changing jaw height on F1 during babble: a case study at 9 months.

    PubMed

    Steeve, Roger W

    2012-04-01

    An empirical gap exists in our understanding of the extent that mandibular kinematics modulate acoustic changes in natural babble productions of infants. Data were recorded from a normal developing 9-month-old infant. Mandibular position was tracked from the infant during vowel and canonical babble. Linear predictive coding analysis was used to track estimates of formant center-frequency for F1. For each sample, a correlation coefficient was computed between changes in jaw height and formant history for F1. A Mann-Whitney rank sum test reached significance for differences among coefficients for vowel and canonical babble. Coefficients for vowel babble productions were nearest to -1 with a median of r=-0.76, showing the strongest relationship between jaw position and formant history, while the median for canonical babble coefficients was r=-0.54, indicating greater contribution of the tongue and lips. This 9-month-old infant exhibited plasticity for coordinating the jaw, tongue and lips among babble types.

  15. Engineering a light-controlled F1 ATPase using structure-based protein design

    PubMed Central

    2016-01-01

    The F1 sub-complex of ATP synthase is a biological nanomotor that converts the free energy of ATP hydrolysis into mechanical work with an astonishing efficiency of up to 100% (Kinosita et al., 2000). To probe the principal mechanics of the machine, I re-engineered the active site of E.coli F1 ATPase with a structure-based protein design approach: by incorporation of a site-specific, photoswitchable crosslinker, whose end-to-end distance can be modulated by illumination with light of two different wavelengths, a dynamic constraint was imposed on the inter-atomic distances of the α and β subunits. Crosslinking reduced the ATP hydrolysis activity of four designs tested in vitro and in one case created a synthetic ATPase whose activity can be reversibly modulated by subsequent illumination with near UV and blue light. The work is a first step into the direction of the long-term goal to design nanoscaled machines based on biological parts that can be precisely controlled by light. PMID:27547581

  16. Role of mucosal prostaglandins and DNA synthesis in gastric cytoprotection by luminal epidermal growth factor.

    PubMed Central

    Konturek, S J; Brzozowski, T; Piastucki, I; Dembinski, A; Radecki, T; Dembinska-Kiec, A; Zmuda, A; Gregory, H

    1981-01-01

    This study compares the effect of epidermal growth factor and prostaglandins (PGE2 or PGI2), applied topically to gastric mucosa, on gastric secretion and formation of ASA-induced gastric ulcerations in rats. Epidermal growth factor given topically in non-antisecretory doses prevented dose-dependently the formation of ASA-induced ulcers without affecting prostaglandin generation but with a significant rise in DNA synthesis in the oxyntic mucosa. The anti-ulcer effect of topical prostaglandins was also accompanied by an increase in DNA synthesis. This study indicates that topical epidermal growth factor, like PGE2 or PGI2, is cytoprotective and that this cytoprotection is not mediated by the inhibition of gastric secretion or prostaglandin formation but related to the increase in DNA synthesis in oxyntic mucosa. PMID:7030877

  17. Determination of prostaglandin analogs in cosmetic products by high performance liquid chromatography with tandem mass spectrometry.

    PubMed

    Wittenberg, James B; Zhou, Wanlong; Wang, Perry G; Krynitsky, Alexander J

    2014-09-12

    A method was developed and validated for the determination of 16 prostaglandin analogs in cosmetic products. The QuEChERS (Quick, Easy, Cheap, Efficient, Rugged, Safe) liquid-liquid extraction method, typically used for pesticide residue analysis, was utilized as the sample preparation technique. The prostaglandin analogs were chromatographically separated and quantified using high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Thirty-one cosmetic products were surveyed, and 13 products were determined to contain a prostaglandin analog with amounts ranging from 27.4 to 297μg/g. The calculated concentrations for the cosmetic products were in a similar range when compared to the concentrations of three different prostaglandin analog-containing prescription products.

  18. [Prostaglandin E1 in the treatment of chronic ischemia of the extremities].

    PubMed

    Kowal-Gierczak, B; Kurzawska-Mielecka, M; Czarnacki, M

    1990-11-01

    The authors observed the effect of prostaglandin E1 (Prostavasine) on the blood flow in the lower extremities in 25 patients with chronic ischemia caused by thrombo-angitis obliterans and arteriosclerosis obliterans (clinical stage III and IV). The blood flow in the lower extremities and the effects of prostaglandin E1 were assessed by means of rheo-angiographic and Doppler-testing investigations. The parameters A (amplitude), S (area) and WOT (index) of rheo-angiographic curves showed significant increased. No significant changes were found in the determined Doppler's indexes. The observed differences of values the parameters of rheo-angiographic curves suggests that prostaglandin E1 evident improvement the tissue blood flow in patients with critical ischemia of the lower extremities. The authors found that prostaglandin E1 was without any significant effect dilating the great vessels, but an evident improvement was observed in rheo-angiographic records which reflect rather the blood flow values in the small vessels.

  19. RORα Binds to E2F1 To Inhibit Cell Proliferation and Regulate Mammary Gland Branching Morphogenesis

    PubMed Central

    Xiong, Gaofeng

    2014-01-01

    Retinoic acid receptor-related orphan nuclear receptor alpha (RORα) is a potent tumor suppressor that reduces cell proliferation and inhibits tumor growth. However, the molecular mechanism by which it inhibits cell proliferation remains unknown. We demonstrate a noncanonical nuclear receptor pathway in which RORα binds to E2F1 to inhibit cell cycle progression. We showed that RORα bound to the heptad repeat and marked box region of E2F1 and suppressed E2F1-regulated transcription in epithelial cells. Binding of RORα inhibited E2F1 acetylation and its DNA-binding activity by recruiting histone deacetylase 1 (HDAC1) to the protein complexes. Knockdown of HDAC1 or inhibition of HDAC activity at least partially rescued transcription factor activity of E2F1 that was repressed by RORα. Importantly, RORα levels were increased in mammary ducts compared to terminal end buds and inversely correlated with expression of E2F1 target genes and cell proliferation. Silencing RORα in mammary epithelial cells significantly enhanced cell proliferation in the ductal epithelial cells and promoted side branching of the mammary ducts. These results reveal a novel link between RORα and E2F1 in regulating cell cycle progression and mammary tissue morphogenesis. PMID:24891616

  20. A proline-to-histidine mutation in POU1F1 is associated with production traits in dairy cattle.

    PubMed

    Huang, W; Maltecca, C; Khatib, H

    2008-10-01

    POU class 1 homeobox 1 (POU1F1) is a member of the tissue-specific POU-containing transcription factor family. The expression of POU1F1 in mammalian pituitary gland controls the transcription of the genes encoding growth hormone, prolactin (PRL) and the subunits of thyroid-stimulating hormone. In addition, some genes in the JAK/STAT signalling pathway downstream of POU1F1 have been shown to be associated with different production traits in dairy cattle. To investigate whether the POU1F1 gene is associated with economically important traits in dairy cattle, a pooled DNA sequencing approach was used to identify single nucleotide polymorphisms (SNPs) in the gene. An SNP in exon 3 of POU1F1 that changes a proline to a histidine was identified. A total of 2141 individuals from two North American Holstein cattle resource populations were genotyped for this SNP using a modified PCR-RFLP method. Statistical analyses revealed significant association of POU1F1 variants with milk yield and productive life, which makes POU1F1 a possible candidate for marker-assisted selection in dairy cattle breeding programmes.

  1. Spawning and fertility of F1 hybrids of the coral genus Acropora in the Indo-Pacific

    NASA Astrophysics Data System (ADS)

    Isomura, Naoko; Iwao, Kenji; Morita, Masaya; Fukami, Hironobu

    2016-09-01

    The role of hybridization through multi-specific synchronous spawning in the evolution of reef-building corals has been discussed since the 1990s, particularly for the genus Acropora. However, F1 hybrids have been reported as common in only one case in the Caribbean, with no evidence of mechanisms that would allow continuous reproduction of the hybrids. In this study, we report for the first time the fecundity of two F1 hybrid colonies produced experimentally from two Indo-Pacific species, A. intermedia and A. florida. These F1 hybrids spawned at the same time as the parental corals. Backcrossing and F1 hybrid crossing were successful in both directions. Furthermore, more than 90% self-fertilization was achieved in an F1 hybrid, although it was negligible in the parental corals. While it is possible that the F1 hybrid was a chimera, these results suggest that some products of interspecific hybridization may persist as the offspring of self-fertilizing F1 hybrids.

  2. The cat lipocalin Fel d 7 and its cross-reactivity with the dog lipocalin Can f 1.

    PubMed

    Apostolovic, D; Sánchez-Vidaurre, S; Waden, K; Curin, M; Grundström, J; Gafvelin, G; Cirkovic Velickovic, T; Grönlund, H; Thomas, W R; Valenta, R; Hamsten, C; van Hage, M

    2016-10-01

    We investigated the prevalence of sensitization to the cat lipocalin Fel d 7 among 140 cat-sensitized Swedish patients and elucidated its allergenic activity and cross-reactivity with the dog lipocalin Can f 1. Sixty-five of 140 patients had IgE to rFel d 7 whereof 60 also had IgE to rCan f 1. A moderate correlation between IgE levels to rFel d 7 and rCan f 1 was found. rFel d 7 activated basophils in vitro and inhibited IgE binding to rCan f 1 in 4 of 13 patients, whereas rCan f 1 inhibited IgE binding to rFel d 7 in 7 of 13 patients. Fel d 7 and Can f 1 showed high similarities in protein structure and epitopes in common were found using cross-reactive antisera. Fel d 7 is a common allergen in a Swedish cat-sensitized population that cross-reacts with Can f 1, and may contribute to symptoms in cat- but also in dog-allergic patients.

  3. E2F1 interactions with hHR23A inhibit its degradation and promote DNA repair

    PubMed Central

    Singh, Randeep K.; Dagnino, Lina

    2016-01-01

    Nucleotide excision repair (NER) is a major mechanism for removal of DNA lesions induced by exposure to UV radiation in the epidermis. Recognition of damaged DNA sites is the initial step in their repair, and requires multiprotein complexes that contain XPC and hHR23 proteins, or their orthologues. A variety of transcription factors are also involved in NER, including E2F1. In epidermal keratinocytes, UV exposure induces E2F1 phosphorylation, which allows it to recruit various NER factors to sites of DNA damage. However, the relationship between E2F1 and hHR23 proteins vis-à-vis NER has remained unexplored. We now show that E2F1 and hHR23 proteins can interact, and this interaction stabilizes E2F1, inhibiting its proteasomal degradation. Reciprocally, E2F1 regulates hHR23A subcellular localization, recruiting it to sites of DNA photodamage. As a result, E2F1 and hHR23A enhance DNA repair following exposure to UV radiation, contributing to genomic stability in the epidermis. PMID:27028861

  4. Platypus Pou5f1 reveals the first steps in the evolution of trophectoderm differentiation and pluripotency in mammals.

    PubMed

    Niwa, Hitoshi; Sekita, Yoko; Tsend-Ayush, Enkhjargal; Grützner, Frank

    2008-01-01

    Uterine nourishment of embryos by the placenta is a key feature of mammals. Although a variety of placenta types exist, they are all derived from the trophectoderm (TE) cell layer of the developing embryo. Egg-laying mammals (platypus and echidnas) are distinguished by a very short intrauterine embryo development, in which a simple placenta forms from TE-like cells. The Pou5f1 gene encodes a class V POU family transcription factor Oct3/4. In mice, Oct3/4 together with the highly conserved caudal-related homeobox transcription factor Cdx2, determines TE fate in pre-implantation development. In contrast to Cdx2, Pou5f1 has only been identified in eutherian mammals and marsupials, whereas, in other vertebrates, pou2 is considered to be the Pou5f1 ortholog. Here, we show that platypus and opossum genomes contain a Pou5f1 and pou2 homolog, pou2-related, indicating that these two genes are paralogues and arose by gene duplication in early mammalian evolution. In a complementation assay, we found that platypus or human Pou5f1, but not opossum or zebrafish pou2, restores self-renewal in Pou5f1-null mouse ES cells, showing that platypus possess a fully functional Pou5f1 gene. Interestingly, we discovered that parts of one of the conserved regions (CR4) is missing from the platypus Pou5f1 promoter, suggesting that the autoregulation and reciprocal inhibition between Pou5f1 and Cdx2 evolved after the divergence of monotremes and may be linked to the development of more elaborate placental types in marsupial and eutherian mammals.

  5. Protease Omi facilitates neurite outgrowth in mouse neuroblastoma N2a cells by cleaving transcription factor E2F1

    PubMed Central

    Ma, Qi; Hu, Qing-song; Xu, Ran-jie; Zhen, Xue-chu; Wang, Guang-hui

    2015-01-01

    Aim: Omi is an ATP-independent serine protease that is necessary for neuronal function and survival. The aim of this study was to investigate the role of protease Omi in regulating differentiation of mouse neuroblastoma cells and to identify the substrate of Omi involved in this process. Methods: Mouse neuroblastoma N2a cells and Omi protease-deficient mnd2 mice were used in this study. To modulate Omi and E2F1 expression, N2a cells were transfected with expression plasmids, shRNA plasmids or siRNA. Protein levels were detected using immunoblot assays. The interaction between Omi and E2F1 was studied using immunoprecipitation, GST pulldown and in vitro cleavage assays. N2a cells were treated with 20 μmol/L retinoic acid (RA) and 1% fetal bovine serum to induce neurite outgrowth, which was measured using Image J software. Results: E2F1 was significantly increased in Omi knockdown cells and in brain lysates of mnd2 mice, and was decreased in cells overexpressing wild-type Omi, but not inactive Omi S276C. In brain lysates of mnd2 mice, endogenous E2F1 was co-immunoprecipitated with endogenous Omi. In vitro cleavage assay demonstrated that Omi directly cleaved E2F1. Treatment of N2a cells with RA induced marked differentiation and neurite outgrowth accompanied by significantly increased Omi and decreased E2F1 levels, which were suppressed by pretreatment with the specific Omi inhibitor UCF-101. Knockdown of Omi in N2a cells suppressed RA-induced neurite outgrowth, which was partially restored by knockdown of E2F1. Conclusion: Protease Omi facilitates neurite outgrowth by cleaving the transcription factor E2F1 in differentiated neuroblastoma cells; E2F1 is a substrate of Omi. PMID:26238290

  6. Isolation and expression analysis of FTZ-F1 encoding gene of black rock fish ( Sebastes schlegelii)

    NASA Astrophysics Data System (ADS)

    Shafi, Muhammad; Wang, Yanan; Zhou, Xiaosu; Ma, Liman; Muhammad, Faiz; Qi, Jie; Zhang, Quanqi

    2013-03-01

    Sex related FTZ-F1 is a transcriptional factor regulating the expression of fushi tarazu (a member of the orphan nuclear receptors) gene. In this study, FTZ-F1 gene ( FTZ-F1) was isolated from the testis of black rockfish ( Sebastes schlegeli) by homology cloning. The full-length cDNA of S. schlegeli FTZ-F1 ( ssFTZ-F1) contained a 232bp 5' UTR, a 1449bp ORF encoding FTZ-F1 (482 amino acid residules in length) with an estimated molecular weight of 5.4kD and a 105bp 3' UTR. Sequence, tissue distribution and phylogenic analysis showed that ssFTZ-F1 belonged to FTZ group, holding highly conserved regions including I, II and III FTZ-F1 boxes and an AF-2 hexamer. Relatively high expression was observed at different larva stages. In juveniles (105 days old), the transcript of ssFTZ-F1 can be detected in all tissues and the abuncance of the gene transcript in testis, ovary, spleen and brain was higher than that in other tissues. In mature fish, the abundance of gene transcript was higher in testis, ovary, spleen and brain than that in liver (trace amount), and the gene was not transcribed in other tissues. The highest abundance of gene transcript was always observed in gonads of both juvenile and mature fish. In addition, the abundance of gene transcript in male tissues were higher than that in female tissue counterparts ( P<0.05).

  7. Phenotypical and functional evaluation of CD8+/S6F1+ T lymphocytes in haemophiliac individuals with HIV-1 infection.

    PubMed Central

    Cavallin, F; Traldi, A; Zambello, R

    1993-01-01

    In this study we investigated the distribution of the S6F1 antigen, an epitope of the lymphocyte function-associated antigen, on CD8+ T lymphocytes in a series of 15 HIV-1+ and 20 HIV-1- haemophiliac patients. MoAbs recognizing the S6F1 antigen have been claimed to distinguish between killer effectors (brightly S6F1+ stained) and suppressor cells (dimly S6F1+ stained) within the CD8+ lymphoid population. In addition, we tried to find a correlation between the spontaneous in vitro immunoglobulin synthesis from patients' peripheral blood lymphocytes and the pattern of S6F1 expression. Although the total number of double-positive CD8+/S6F1+ cells was similar in both HIV-1+ and HIV-1- haemophiliac patients, a significant increase in the CD8+/S6F1+ population bright versus dim was documented in HIV-1-infected with respect to HIV-1- haemophiliacs (bright/dim ratio 3.97 +/- 0.61 versus 0.75 +/- 0.1, respectively, P < 0.005). This finding was correlated to a significant increase in spontaneous in vitro immunoglobulin production in HIV-1+ subjects compared with control haemophiliacs (P < 0.005). Purified CD8+ lymphocytes from HIV-1+ subjects showed a reduced suppressor activity on mitogen-induced immunoglobulin production. Taken together, these data suggest that HIV-1 infection favours the generation of CD8+/S6F1+ bright cells with putative cytotoxic-associated function, leading to a progressive reduction in the number of CD8+/S6F1+ dim suppressor lymphocytes. This phenomenon may contribute to the polyclonal hypergammaglobulinaemia present in HIV-1+ haemophiliac patients. PMID:8324903

  8. Plasma prostaglandins across the tumor bed of patients with gynecologic malignancy.

    PubMed

    Mortel, R; Allegra, J C; Demers, L M; Harvey, H A; Trautlein, J; Nahhas, W; White, D; Gillin, M A; Lipton, A

    1977-05-01

    Prostaglandin E produced by tumors has recently been implicated as a mechanism by which tumors may subvert the immune system and grow despite their antigenicity. Arterial and venous determinations of prostaglandin E were performed in eleven patients with gynecologic malignancy. No significant difference was found when arterial and venous levels were compared and there was no difference in venous PGE levels when subjects with cancer were compared to patients with benign gynecologic disease.

  9. ROS production is essential for the apoptotic function of E2F1 in pheochromocytoma and neuroblastoma cell lines.

    PubMed

    Espada, Lilia; Meo-Evoli, Nathalie; Sancho, Patricia; Real, Sebastian; Fabregat, Isabel; Ambrosio, Santiago; Tauler, Albert

    2012-01-01

    In this study we demonstrate that accumulation of reactive oxygen species (ROS) is essential for E2F1 mediated apoptosis in ER-E2F1 PC12 pheochromocytoma, and SH-SY5Y and SK-N-JD neuroblastoma stable cell lines. In these cells, the ER-E2F1 fusion protein is expressed in the cytosol; the addition of 4-hydroxytamoxifen (OHT) induces its translocation to the nucleus and activation of E2F1target genes. Previously we demonstrated that, in ER-E2F1 PC12 cells, OHT treatment induced apoptosis through activation of caspase-3. Here we show that caspase-8 activity did not change upon treatment with OHT. Moreover, over-expression of Bcl-xL arrested OHT-induced apoptosis; by contrast, over-expression of c-FLIP, did not have any effect on OHT-induced apoptosis. OHT addition induces BimL expression, its translocation to mitochondria and activation of Bax, which is paralleled by diminished mitochondrial enrichment of Bcl-xL. Treatment with a Bax-inhibitory peptide reduced OHT-induced apoptosis. These results point out the essential role of mitochondria on the apoptotic process driven by E2F1. ROS accumulation followed E2F1 induction and treatment with the antioxidant N-acetylcysteine, inhibited E2F1-induced Bax translocation to mitochondria and subsequent apoptosis. The role of ROS in mediating OHT-induced apoptosis was also studied in two neuroblastoma cell lines, SH-SY5Y and SK-N-JD. In SH-SY5Y cells, activation of E2F1 by the addition of OHT induced ROS production and apoptosis, whereas over-expression of E2F1 in SK-N-JD cells failed to induce either response. Transcriptional profiling revealed that many of the genes responsible for scavenging ROS were down-regulated following E2F1-induction in SH-SY5Y, but not in SK-N-JD cells. Finally, inhibition of GSK3β blocked ROS production, Bax activation and the down regulation of ROS scavenging genes. These findings provide an explanation for the apparent contradictory role of E2F1 as an apoptotic agent versus a cell cycle activator.

  10. Up-regulation of E2F-1 in Down's syndrome brain exhibiting neuropathological features of Alzheimer-type dementia.

    PubMed

    Motonaga, K; Itoh, M; Hirayama, A; Hirano, S; Becker, L E; Goto, Y; Takashima, S

    2001-06-29

    We studied the expression of the apoptosis-related protein, E2F-1, in Down's syndrome (DS) brains. The immunoreactivity for E2F-1 was detected in the pyramidal neurons of the cerebral cortex from DS brains exhibiting the neuropathological features of dementia of Alzheimer type (DAT), in accordance with the amyloid beta protein (A beta) deposition in the neuron. Therefore, the implication is that A beta deposition may trigger E2F-1-mediated neuronal apoptosis in DS brains with DAT.

  11. E2F1 and TFDP1 Regulate PITX1 Expression in Normal and Osteoarthritic Articular Chondrocytes

    PubMed Central

    Wang, DaShen; Lavigne, Patrick; Moreau, Alain

    2016-01-01

    We previously reported a loss-of-PITX1 expression in patients suffering of knee/hip osteoarthritis (OA). Search for the mechanism underlying this event led us to discover that PITX1 repression was triggered by the aberrant nuclear accumulation of Prohibitin (PHB1), an E2F1 co-repressor, in OA articular chondrocytes. In the current study, we assessed in details the involvement of E2F transcription factors in regulating PITX1 expression. We also analyzed other genes that are similarly regulated by E2F in regard to osteoarthritis. The transcriptional regulation of the PITX1 promoter by E2F1 was analyzed with the luciferase reporter assay, and chromatin immunoprecipitation assays, which confirmed direct E2F1-PITX1 interactions. The probable binding sites for E2F1 in the PITX1 promoter were identified by DNA pulldown experiments. In silico and in vitro analyses show that the PITX1 proximal promoter region contains 2 specific sequences that are bound by E2F1. Overexpression of E2F1 enhances PITX1 promoter activity and mRNA transcription. In primary control and osteoarthritis chondrocytes, real time RT-PCR was used to measure the mRNA expression levels of candidate genes under E2F1 transcriptional control. Transcription Factor Dp-1 (TFDP1) knockdown experiments confirmed that the E2F1-TFDP1 complex regulates PITX1. Knockdown of TFDP1, an E2F1 dimerization partner, inhibits the activating effect of E2F1 and reduces both PITX1 promoter activity and mRNA transcription. Real time RT-PCR results reveal reduced expression of TFDP1 and a similar downregulation of their targets PITX1, BRCA1, CDKN1A, and RAD51 in mid-stage OA chondrocytes. Collectively, our data define a previously uncharacterized role for E2F1 and TFDP1 in the transcriptional regulation of PITX1 in articular chondrocytes. Additional E2F1 targets may be affected in OA pathogenesis. PMID:27802335

  12. Signal pathways mediating oxytocin stimulation of prostaglandin synthesis in select target cells.

    PubMed

    Soloff, M S; Jeng, Y J; Copland, J A; Strakova, Z; Hoare, S

    2000-03-01

    A major action of oxytocin is to stimulate prostaglandin production in reproductive tissues. The two major enzyme systems involved are cytosolic phospholipase A2 (cPLA2), which catalyses the formation of arachidonic acid from membrane glycerophospholipids, and prostaglandin endoperoxide-H synthases-1 and -2, which allow conversion of arachidonic acid to prostaglandins. During gestation, the concentrations of all three enzymes rise in the rabbit amnion. Agonists, including oxytocin, increase cPLA2 activity, in part, by elevating intracellular Ca2+ concentration, which causes cPLA2 to be translocated from the cytosol to intracellular membrane binding sites. Cytosolic PLA2 is then activated by a mitogen-activated protein kinase (MAPK)-dependent step. Our studies have elucidated signal pathways involved in oxytocin-stimulated prostaglandin output in both rabbit amnion cells and Chinese hamster ovary cells stably transfected with the rat oxytocin receptor. The two cell types are alike with respect to oxytocin-stimulated intracellular Ca2+ transients, mediation via Gq, and the specific MAPK that catalyses the phosphorylation of cPLA2. However, they differ with respect to the mechanisms of upregulation of key enzymes involved in prostaglandin E2 synthesis. These findings illustrate the tiers of complementary mechanisms involved in oxytocin stimulation of prostaglandin E2, and the extent of the diversity in the cellular signalling pathways involved.

  13. Circadian variations of prostaglandin E2 and F2 alpha release in the golden hamster retina.

    PubMed

    de Zavalía, Nuria; Fernandez, Diego C; Sande, Pablo H; Keller Sarmiento, María I; Golombek, Diego A; Rosenstein, Ruth E; Silberman, Dafne M

    2010-02-01

    Circadian variations of prostaglandin E2 and F2alpha release were examined in the golden hamster retina. Both parameters showed significant diurnal variations with maximal values at midnight. When hamsters were placed under constant darkness for 48 h, the differences in prostaglandin release between subjective mid-day and subjective midnight persisted. Western blot analysis showed that cyclooxygenase (COX)-1 levels were significantly higher at midnight than at mid-day, and at subjective midnight than at subjective mid-day, whereas no changes in COX-2 levels were observed among these time points. Immunohistochemical studies indicated the presence of COX-1 and COX-2 in the inner (but not outer) retina. Circadian variations of retinal prostaglandin release were also assessed in suprachiasmatic nuclei (SCN)-lesioned animals. Significant differences in retinal prostaglandin release between subjective mid-day and subjective midnight were observed in SCN-lesioned animals. These results indicate that hamster retinal prostaglandin release is regulated by a retinal circadian clock independent from the SCN. Thus, the present results suggest that the prostaglandin/COX-1 system could be a retinal clock output or part of the retinal clock mechanism.

  14. 8-Chloro-adenosine-induced E2F1 promotes p14ARF gene activation in H1299 cells through displacing Sp1 from multiple overlapping E2F1/Sp1 sites.

    PubMed

    Zhang, Hai-Jun; Li, Wen-Juan; Yang, Sheng-Yong; Li, Shu-Yan; Ni, Ju-Hua; Jia, Hong-Ti

    2009-02-15

    The regulation of p14ARF gene by E2F transcription factor, which differs from that of classical E2F targets, has recently been attributed to a variant E2F-response element. However, promoter assays suggest multiple elements present in the p14ARF promoter and argue against the idea that the ARF promoter has a unique ability to distinguish between aberrant and physiological levels of E2F1. Therefore, the functional characterization of the promoter still needs to be done. We demonstrate that at least two overlapping E2F1/Sp1 binding sites are present in the p14ARF promoter, and E2F1 activates the promoter through displacing constitutive Sp1 from the overlapping sites. We found that 8-chloro-adenosine (a metabolite of 8-Cl-cAMP) exposure induced the p14ARF gene in human lung cancer H1299 cells, followed by increased expression of E2F1 and constitutive expression of Sp1. The combination of cotransfection and electrophoretic mobility shift assay (EMSA) indicated that constitutive binding of Sp1 to the overlapping sites contributed to a constitutive expression of the ARF gene in unexposed H1299, whereas displacing Sp1 from the overlapping sites by E2F1 promoted the gene activation after exposure. EMSA and chromatin immunoprecipitation revealed increased association of E2F1 with the overlapping sites in the active promoter in 8-Cl-Ado-exposed cells. Together, these data suggest that the overlapping E2F1/Sp1 site, being present in multiple copies in the p14ARF promoter, may serve as the targets for both E2F1 and Sp1, thereby playing a crucial role in response to some oncogenic signals and stimulators, which activate the ARF gene through inducing E2F in the cell.

  15. Cytosine chemoreceptor McpC in Pseudomonas putida F1 also detects nicotinic acid.

    PubMed

    Parales, Rebecca E; Nesteryuk, Vasyl; Hughes, Jonathan G; Luu, Rita A; Ditty, Jayna L

    2014-12-01

    Soil bacteria are generally capable of growth on a wide range of organic chemicals, and pseudomonads are particularly adept at utilizing aromatic compounds. Pseudomonads are motile bacteria that are capable of sensing a wide range of chemicals, using both energy taxis and chemotaxis. Whilst the identification of specific chemicals detected by the ≥26 chemoreceptors encoded in Pseudomonas genomes is ongoing, the functions of only a limited number of Pseudomonas chemoreceptors have been revealed to date. We report here that McpC, a methyl-accepting chemotaxis protein in Pseudomonas putida F1 that was previously shown to function as a receptor for cytosine, was also responsible for the chemotactic response to the carboxylated pyridine nicotinic acid.

  16. Asymmetry in the F1-ATPase and Its Implications for the Rotational Cycle

    PubMed Central

    Sun, Sean X.; Wang, Hongyun; Oster, George

    2004-01-01

    ATP synthase uses a rotary mechanism to carry out its cellular function of manufacturing ATP. The centralγ-shaft rotates inside a hexameric cylinder composed of alternating α- and β-subunits. When operating in the hydrolysis direction under high frictional loads and low ATP concentrations, a coordinated mechanochemical cycle in the three catalytic sites of the β-subunits rotates the γ-shaft in three 120° steps. At low frictional loads, the 120° steps alternate with three ATP-independent substeps separated by ∼30°. We present a quantitative model that accounts for these substeps and show that the observed pauses are due to 1), the asymmetry of the F1 hexamer that produces a propeller-like motion of the power-stroke and 2), the relatively tight binding of ADP to the catalytic sites. PMID:14990467

  17. Control of spinor dynamics in an anti-ferromagnetic F=1 Bose-Einstein condensate

    NASA Astrophysics Data System (ADS)

    Glassman, Zachary; Fahey, Donald; Wilson, Ryan; Tiesinga, Eite; Lett, Paul

    2016-05-01

    Spin-exchange collisions driving coherent population oscillations of the F = 1 ground state magnetic sublevels can be used for precision quantum measurements in a condensed Bose gas. Entanglement generated by these dynamics enables below standard quantum limit phase estimation by way of an SU(1,1) interferometer and antiferromagnetic spin-nematic squeezing. In order to observe these effects, we have simulated the spinor dynamics in the single mode approximation with both fully quantum and semi-classical models. We present a study of microwave pulse sequences, which can be used to control the spinor dynamics via energy level shifts and rotations, and discuss improved methods for future experiments in this field.

  18. Measurement of the Microwave Lensing shift in NIST-F1 and NIST-F2

    NASA Astrophysics Data System (ADS)

    Jefferts, S. R.; Heavner, T. P.; Barlow, S. E.; Ashby, N.

    2016-06-01

    With several Primary Frequency Standards (PFS) across the world demonstrating systematic fractional frequency uncertainties on order of 1 x 10-16, it is crucial to accurately measure or model even small frequency shifts that could affect the ultimate PFS uncertainty, and thus ultimately impact the rate of Coordinated Universal Time (UTC) which relies on precision PFS measurements. Recently there has been controversy about the physical causes and size of PFS frequency shifts due to microwave lensing effects. We present here the first measurements of microwave lensing frequency shifts in the PFS NIST-F1 and NIST-F2. The measured frequency shifts agree well with the recent theory of Ashby et al [1].

  19. Tumor induction by monoenergetic neutrons in B6C3F1 mice.

    PubMed

    Watanabe, Hiromitsu; Kashimoto, Naoki; Kajimura, Junko; Ishikawa, Masayori; Kamiya, Kenji

    2007-05-01

    This study was undertaken to investigate induction of tumors by monoenergetic neutrons in B6C3F1 mice. Individual groups of 6 week-old animals of both sexes (about 30 mice/group) were exposed to 0.5 Gy of various monoenergetic neutrons (dose rate 0.5 cGy/min) and then observed for 13 months. The incidences of tumors (mainly liver neoplasms) in non-irradiated male and female controls were 11% and 0%, respectively. In the irradiated animals, the incidences were 53%, 50%, 60% and 43% in males, and 75%, 81%, 71%, and 85% in females, after 0.18, 0.32, 0.6 and 1.0 MeV neutron exposure, respectively. There were no significant differences in the tumor induction rate among the different energy groups.

  20. Simulation of proton movement in FoF1-ATP synthase by quantum-mechanical approach

    NASA Astrophysics Data System (ADS)

    Ivontsin, L. A.; Mashkovtseva, E. V.; Nartsissov, Ya R.

    2017-01-01

    Quantum-mechanical approach is applied to the description of proton transport through FoF1-ATP synthase which is the crucial process in ATP synthesis. Proton was described as a particle located in potential wells formed by charged centers along the half-channels. Energy spectra of bounded states were calculated using Bohr-Sommerfeld quantization, and the initial population of each quantum level was determined by Boltzman distribution. Water molecules were stochastically distributed in an inlet half-channel taking into account atomic radii. Characteristic time of proton transition between the charged centers (amino acid or water molecule) was estimated and it revealed the critical areas needed to be full with water. All possible pathways were analyzed in Monte-Carlo simulation which allows calculating of a mean time of proton transfer trough the inlet half-channel (23 ms).

  1. [Study of the effects of gamma-irradiation of common wheat F1 seeds using gliadins as genetic markers].

    PubMed

    Kozub, N O; Sozinov, I O; Blium, Ia B; Sozinov, O O

    2013-01-01

    Effects of irradiation of dry F1 seeds with gamma rays in the dose of 200 Gy were studied. Hybrids between near-isogenic lines on the basis of the variety Bezostaya 1 served as the material of investigation. Irradiation markedly reduced productivity traits of F1 plants and did not affect the survival of F1 plants under the given growth conditions. A significant relative increase in the frequency of pollen grains with the 1BL/1RS translocation that formed F2 seeds in comparison with the control was one of the effects of irradiation of F1 seeds. Irradiation with gamma-rays induced mutations at gliadin loci with the frequency of 7,4 % (at 0,5 % in the control).

  2. Gene expression and epigenetic aberrations in F1-placentas fathered by obese males.

    PubMed

    Mitchell, Megan; Strick, Reiner; Strissel, Pamela L; Dittrich, Ralf; McPherson, Nicole O; Lane, Michelle; Pliushch, Galyna; Potabattula, Ramya; Haaf, Thomas; El Hajj, Nady

    2017-02-10

    Gene expression and/or epigenetic deregulation may have consequences for sperm and blastocysts, as well as for the placenta, together potentially contributing to problems observed in offspring. We previously demonstrated specific perturbations of fertilization, blastocyst formation, implantation, as well as aberrant glucose metabolism and adiposity in offspring using a mouse model of paternal obesity. The current investigation analyzed gene expression and methylation of specific CpG residues in F1 placentas of pregnancies fathered by obese and normal-weight male mice, using real-time PCR and bisulfite pyrosequencing. Our aim was to determine if paternal obesity deregulated placental gene expression and DNA methylation when compared to normal-weight males. Gene methylation of sperm DNA was analyzed and compared to placentas to address epigenetic transmission. Of the 10 paternally expressed genes (Pegs), 11 genes important for development and transport of nutrients, and the long-terminal repeat Intracisternal A particle (IAP) elements, derived from a member of the class II endogenous retroviral gene family, we observed a significant effect of paternal diet-induced obesity on deregulated expression of Peg3, Peg9, Peg10, and the nutrient transporter gene Slc38a2, and aberrant DNA methylation of the Peg9 promoter in F1 placental tissue. Epigenetic changes in Peg9 were also found in sperm from obese fathers. We therefore propose that paternal obesity renders changes in gene expression and/or methylation throughout the placental genome, which could contribute to the reproductive problems related to fertility and to the metabolic, long-term health impact on offspring.

  3. Proteomics reveals a core molecular response of Pseudomonas putida F1 to acute chromate challenge

    PubMed Central

    2010-01-01

    Background Pseudomonas putida is a model organism for bioremediation because of its remarkable metabolic versatility, extensive biodegradative functions, and ubiquity in contaminated soil environments. To further the understanding of molecular pathways responding to the heavy metal chromium(VI) [Cr(VI)], the proteome of aerobically grown, Cr(VI)-stressed P. putida strain F1 was characterized within the context of two disparate nutritional environments: rich (LB) media and minimal (M9L) media containing lactate as the sole carbon source. Results Growth studies demonstrated that F1 sensitivity to Cr(VI) was impacted substantially by nutrient conditions, with a carbon-source-dependent hierarchy (lactate > glucose >> acetate) observed in minimal media. Two-dimensional HPLC-MS/MS was employed to identify differential proteome profiles generated in response to 1 mM chromate under LB and M9L growth conditions. The immediate response to Cr(VI) in LB-grown cells was up-regulation of proteins involved in inorganic ion transport, secondary metabolite biosynthesis and catabolism, and amino acid metabolism. By contrast, the chromate-responsive proteome derived under defined minimal growth conditions was characterized predominantly by up-regulated proteins related to cell envelope biogenesis, inorganic ion transport, and motility. TonB-dependent siderophore receptors involved in ferric iron acquisition and amino acid adenylation domains characterized up-regulated systems under LB-Cr(VI) conditions, while DNA repair proteins and systems scavenging sulfur from alternative sources (e.g., aliphatic sulfonates) tended to predominate the up-regulated proteome profile obtained under M9L-Cr(VI) conditions. Conclusions Comparative analysis indicated that the core molecular response to chromate, irrespective of the nutritional conditions tested, comprised seven up-regulated proteins belonging to six different functional categories including transcription, inorganic ion transport

  4. The repression of E2F-1 is critical for the activity of Minerval against cancer.

    PubMed

    Martínez, Jordi; Gutiérrez, Antonio; Casas, Jesús; Lladó, Victoria; López-Bellan, Alicia; Besalduch, Joan; Dopazo, Ana; Escribá, Pablo V

    2005-10-01

    The recently discovered anticancer drug Minerval (2-hydroxy-9-cis-octadecenoic acid) is a synthetic fatty acid that modifies the structure of the membrane. This restructuring facilitates the recruitment of protein kinase C (PKC) alpha to membranes and is associated with the antineoplastic activity of Minerval in cellular and animal models of cancer. Minerval is a derivative of oleic acid (OA) with an enhanced antiproliferative activity in human cancer cells and animal models of cancer, which is associated with PKCalpha activation and p21(CIP) overexpression. However, the signaling cascades involved in its pharmacological activity remain largely unknown. Here, we showed that this drug induced cell cycle arrest before entry into S phase, human lung adenocarcinoma (A549) cells accumulating in the G0/G1 phase. This cell cycle arrest was associated with a marked decrease in the expression of E2F-1. This transcription factor activates several cell cycle-related genes, and, accordingly, the expression of certain cyclins and cyclin-dependent kinases (cdks) was markedly lower upon exposure to Minerval. The reduced availability of these kinase heterodimers was associated with reduced phosphorylation of the retinoblastoma protein (pRb) observed after drug treatment. Significantly, hypophosphorylated pRb remains bound to E2F-1 and maintains this transcription factor inactive. The modulation of these antiproliferative mechanisms by Minerval explains its anticancer potency, through a new therapeutic strategy that can be used to develop new antitumor drugs. On the other hand, apoptosis did not seem to be involved in its pharmacological mechanism. Interestingly, whereas the changes induced by OA were only modest, they may reflect the beneficial effects of high olive oil intake against cancer.

  5. Impaired peripheral glucose sensing in F1 offspring of diabetic pregnancy.

    PubMed

    Kamel, Maher A; Helmy, Madiha H; Hanafi, Mervat Y; Mahmoud, Shimaa A; Abo Elfetooh, Hanan

    2014-09-01

    Maternal diabetes can induce permanent changes in glucose homeostasis that can occur pre- and post-natal and leads to type 2 diabetes in adulthood. This study aimed to investigate the effect of maternal diabetes on the F1 offspring peripheral glucose sensing and mitochondrial biogenesis in an attempt to clarify the mechanism of diabetogenic programming. Two groups of female Wistar rats were used (diabetic and control); diabetes was neonatally induced by STZ injection to 5-day old rats. After the pregnancy and delivery, the offspring were weaned to control diet or high-caloric (HCD) diet and followed up for 30 weeks. Every 5 weeks, OGTT was constructed, and serum and tissues were obtained for the assessment of mTFA, mtDNA, UCP2, insulin receptor (IR), phospho-insulin receptor (phospho-IR), and GLUT4. The result indicated impaired glucose tolerance (IGT) and insulin resistance in the offspring under control diet at the 15th week of age and thereafter while those offspring under HCD showed IGT at 10th week, and diabetes was evidenced at the 25th week of age. This defect in glucose metabolism was preceded by impairment in the phosphorylation of IR and decreased IR and Glut4 that cause impaired glucose sensing together with inhibited mitochondrial biogenesis in muscle and adipose tissues. This study indicated that maternal diabetes caused impaired glucose sensing and insulin resistance in the peripheral tissues and caused change in the expression of genes involved in mitochondrial biogenesis and function. Post-natal feeding with HCD may accelerate these changes. Male F1 offspring appears to be more sensitive than females for fetal programming of T2D.

  6. Immune resistance of semisyngeneic F1 hybrid mice to lymphoma grafts differs from natural hybrid resistance in its genetic pattern

    SciTech Connect

    Klein, G.O.; Klein, G.

    1984-07-01

    Resistance of semisyngeneic F1 hybrid mice immunized three times with irradiated tumor cells was compared to the genetic pattern of natural hybrid resistance to challenge with live tumor cells. Syngeneic mice responded equally well to immunization with all five hemopoietic tumor lines tested as the naturally much more highly resistant F1 hybrids. Natural hybrid resistance was found to be severely reduced by sublethal irradiation with 4 Gy, in contrast to hybrid resistance to parental bone marrow.

  7. The Drosophila nuclear receptors DHR3 and betaFTZ-F1 control overlapping developmental responses in late embryos.

    PubMed

    Ruaud, Anne-Françoise; Lam, Geanette; Thummel, Carl S

    2010-01-01

    Studies of the onset of metamorphosis have identified an ecdysone-triggered transcriptional cascade that consists of the sequential expression of the transcription-factor-encoding genes DHR3, betaFTZ-F1, E74A and E75A. Although the regulatory interactions between these genes have been well characterized by genetic and molecular studies over the past 20 years, their developmental functions have remained more poorly understood. In addition, a transcriptional sequence similar to that observed in prepupae is repeated before each developmental transition in the life cycle, including mid-embryogenesis and the larval molts. Whether the regulatory interactions between DHR3, betaFTZ-F1, E74A and E75A at these earlier stages are similar to those defined at the onset of metamorphosis, however, is unknown. In this study, we turn to embryonic development to address these two issues. We show that mid-embryonic expression of DHR3 and betaFTZ-F1 is part of a 20-hydroxyecdysone (20E)-triggered transcriptional cascade similar to that seen in mid-prepupae, directing maximal expression of E74A and E75A during late embryogenesis. In addition, DHR3 and betaFTZ-F1 exert overlapping developmental functions at the end of embryogenesis. Both genes are required for tracheal air filling, whereas DHR3 is required for ventral nerve cord condensation and betaFTZ-F1 is required for proper maturation of the cuticular denticles. Rescue experiments support these observations, indicating that DHR3 has essential functions independent from those of betaFTZ-F1. DHR3 and betaFTZ-F1 also contribute to overlapping transcriptional responses during embryogenesis. Taken together, these studies define the lethal phenotypes of DHR3 and betaFTZ-F1 mutants, and provide evidence for functional bifurcation in the 20E-responsive transcriptional cascade.

  8. Selective solid-phase extraction of urinary 2,3-dinor-6-ketoprostaglandin F1 alpha for determination with radioimmunoassay.

    PubMed

    Riutta, A; Nurmi, E; Weber, C; Hansson, G; Vapaatalo, H; Mucha, I

    1994-08-01

    This paper describes a method for selective two-step solid-phase extraction of urinary 2,3-dinor-6-ketoprostaglandin F1 alpha for reliable determination with radioimmunoassay. In the immunoreactivity profile of non-selectively extracted urine after HPLC separation, over 90% of the total 2,3-dinor-6-ketoprostaglandin F1 alpha immunoreactivity consisted of interfering material coeluting with 6-ketoprostaglandin F1 alpha and 2,3-dinor-6-ketoprostaglandin F1 alpha. Among the alkyl silica sorbents studied (methyl, butyl, octyl, and octadecyl), an efficient separation of 2,3-dinor-6-ketoprostaglandin F1 alpha from 6-ketoprostaglandin F1 alpha and the lowest immunoreactive concentration of analyte were achieved in extraction on the methyl silica sorbent by elution of 2,3-dinor-6-ketoprostaglandin F1 alpha with chloroform: hexane (85:15, v/v) from the cartridge. The proportion of specific immunoreactivity could be further increased by two-step extraction of sample on methyl silica cartridges, first at pH 3 and then at pH 10 using diethyl ether:hexane (85:15, v/v) and chloroform as eluent, respectively. After this, a high correlation was found with concentrations of samples determined by radioimmunoassay using three different antisera. A significant correlation of values was also observed between samples measured by radioimmunoassay and those measured by GC-MS. The values of 12-h excretion of 2,3-dinor-6-ketoprostaglandin F1 alpha in eight volunteers (268 +/- 204 ng/g creatinine, mean +/- SD) as well as the inhibitory effect of acetylsalicylic acid (74 +/- 12%) are in accordance with those reported in the literature. This selective extraction procedure provides a high validity in radioimmunoassay without requiring subsequent TLC or HPLC purification.

  9. M2-F1 lifting body and Paresev 1B on ramp

    NASA Technical Reports Server (NTRS)

    1963-01-01

    In this photo of the M2-F1 lifting body and the Paresev 1B on the ramp, the viewer sees two vehicles representing different approaches to building a research craft to simulate a spacecraft able to land on the ground instead of splashing down in the ocean as the Mercury capsules did. The M2-F1 was a lifting body, a shape able to re-enter from orbit and land. The Paresev (Paraglider Research Vehicle) used a Rogallo wing that could be (but never was) used to replace a conventional parachute for landing a capsule-type spacecraft, allowing it to make a controlled landing on the ground. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop

  10. Hypoxia promotes cell proliferation by modulating E2F1 in chicken pulmonary arterial smooth muscle cells

    PubMed Central

    2013-01-01

    In this study, we sought to investigate the expression of the transcription factor E2F1 in chicken pulmonary arterial smooth muscle cells upon hypoxia exposure, as well as the role that E2F1 played in the regulation of cell proliferation. Isolated chicken pulmonary arterial smooth muscle cells were subjected to hypoxia or normoxia for indicated time points. Cell viability, DNA synthesis, cell cycle profile, and expression of E2F1 were analyzed. The results showed that hypoxia promoted cell proliferation and DNA synthesis which was accompanied by an increased S phase entry and upregulation of E2F1 at mRNA and protein levels. Using siRNA technology, we demonstrated that gene inactivation of endogenous E2F1 abolished hypoxia-induced cell proliferation, DNA synthesis, and S phase entry compared with negative siRNA transfected cells. These results suggest that hypoxia-induced proliferation is mediated by inducing E2F1 in chicken pulmonary arterial smooth muscle cells. PMID:23902684

  11. Bcl-xL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthase

    PubMed Central

    Alavian, Kambiz N.; Li, Hongmei; Collis, Leon; Bonanni, Laura; Zeng, Lu; Sacchetti, Silvio; Lazrove, Emma; Nabili, Panah; Flaherty, Benjamin; Graham, Morven; Chen, Yingbei; Messerli, Shanta; Mariggio, Maria A.; Rahner, Christoph; McNay, Ewan; Shore, Gordon; Smith, Peter J. S.; Hardwick, J. Marie; Jonas, Elizabeth A.

    2011-01-01

    Anti-apoptotic Bcl2 family proteins such as Bcl-xL protect cells from death by sequestering apoptotic molecules, but also contribute to normal neuronal function. We find in hippocampal neurons that Bcl-xL enhances the efficiency of energy metabolism. Our evidence suggests that Bcl-xL interacts directly with the beta subunit of the F1FO ATP synthase, decreasing an ion leak within the F1FO ATPase complex and thereby increasing net transport of H+ by F1FO during F1FO ATPase activity. By patch clamping submitochondrial vesicles enriched in F1FO ATP synthase complexes, we find that, in the presence of ATP, pharmacological or genetic inhibition of Bcl-xL increases the membrane leak conductance. In addition, recombinant Bcl-xL protein directly increases ATPase activity of purified synthase complexes, while inhibition of endogenous Bcl-xL decreases F1FO enzymatic activity. Our findings suggest that increased mitochondrial efficiency contributes to the enhanced synaptic efficacy found in Bcl-xL expressing neurons. PMID:21926988

  12. Bcl-xL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthase.

    PubMed

    Alavian, Kambiz N; Li, Hongmei; Collis, Leon; Bonanni, Laura; Zeng, Lu; Sacchetti, Silvio; Lazrove, Emma; Nabili, Panah; Flaherty, Benjamin; Graham, Morven; Chen, Yingbei; Messerli, Shanta M; Mariggio, Maria A; Rahner, Christoph; McNay, Ewan; Shore, Gordon C; Smith, Peter J S; Hardwick, J Marie; Jonas, Elizabeth A

    2011-09-18

    Anti-apoptotic Bcl2 family proteins such as Bcl-x(L) protect cells from death by sequestering apoptotic molecules, but also contribute to normal neuronal function. We find in hippocampal neurons that Bcl-x(L) enhances the efficiency of energy metabolism. Our evidence indicates that Bcl-x(L)interacts directly with the β-subunit of the F(1)F(O) ATP synthase, decreasing an ion leak within the F(1)F(O) ATPase complex and thereby increasing net transport of H(+) by F(1)F(O) during F(1)F(O) ATPase activity. By patch clamping submitochondrial vesicles enriched in F(1)F(O) ATP synthase complexes, we find that, in the presence of ATP, pharmacological or genetic inhibition of Bcl-x(L) activity increases the membrane leak conductance. In addition, recombinant Bcl-x(L) protein directly increases the level of ATPase activity of purified synthase complexes, and inhibition of endogenous Bcl-x(L) decreases the level of F(1)F(O) enzymatic activity. Our findings indicate that increased mitochondrial efficiency contributes to the enhanced synaptic efficacy found in Bcl-x(L)-expressing neurons.

  13. The generation mechanisms and repeatability of 2F1-F2 distortion product otoacoustic emissions: study on normally hearing subjects.

    PubMed

    Parazzini, M; Wilson, H K; Bell, S; Tognola, G; Ravazzani, P; Lutman, M E

    2006-01-01

    The 2F1-F2 distortion product otoacoustic emission (DPOAE) is considered to consist of two generation mechanisms, the so-called place-fixed and wave-fixed mechanisms, depending on the frequency ratio F2/F1. The general assumption is that for a small frequency ratio there is a predominantly place-fixed emission mechanism, while with a larger frequency ratio there is a predominantly wave-fixed mechanism. There is also a lack of published data on the repeatability of the two components when separated. One aim of this study was therefore to identify the wave-fixed and place-fixed components of the 2F1-F2 DPOAE using a time-window separation method. The second aim was to quantify the test-retest repeatability of the separated 2F1-F2 DPOAE components in a group of normally hearing subjects. Results confirmed the presence of wave-fixed and place-fixed components for 2F1-F2 and a predominance of place or wave-fixed DPOAE as a function of frequency ratio. This pattern varied somewhat among subjects. Moreover, regardless of which component was stronger for any F2/F1, both components were highly repeatable across time within individual ears.

  14. Prostaglandin E2 As a Modulator of Viral Infections

    PubMed Central

    Sander, Willem J.; O'Neill, Hester G.; Pohl, Carolina H.

    2017-01-01

    Viral infections are a major cause of infectious diseases worldwide. Inflammation and the immune system are the major host defenses against these viral infection. Prostaglandin E2 (PGE2), an eicosanoid generated by cyclooxygenases, has been shown to modulate inflammation and the immune system by regulating the expression/concentration of cytokines. The effect of PGE2 on viral infection and replication is cell type- and virus-family-dependent. The host immune system can be modulated by PGE2, with regards to immunosuppression, inhibition of nitrogen oxide (NO) production, inhibition of interferon (IFN) and apoptotic pathways, and inhibition of viral receptor expression. Furthermore, PGE2 can play a role in viral infection directly by increasing the production and release of virions, inhibiting viral binding and replication, and/or stimulating viral gene expression. PGE2 may also have a regulatory role in the induction of autoimmunity and in signaling via Toll-like receptors. In this review the known effects of PGE2 on the pathogenesis of various infections caused by herpes simplex virus, rotavirus, influenza A virus and human immunodeficiency virus as well the therapeutic potential of PGE2 are discussed. PMID:28261111

  15. Prostaglandin signaling suppresses beneficial microglial function in Alzheimer's disease models.

    PubMed

    Johansson, Jenny U; Woodling, Nathaniel S; Wang, Qian; Panchal, Maharshi; Liang, Xibin; Trueba-Saiz, Angel; Brown, Holden D; Mhatre, Siddhita D; Loui, Taylor; Andreasson, Katrin I

    2015-01-01

    Microglia, the innate immune cells of the CNS, perform critical inflammatory and noninflammatory functions that maintain normal neural function. For example, microglia clear misfolded proteins, elaborate trophic factors, and regulate and terminate toxic inflammation. In Alzheimer's disease (AD), however, beneficial microglial functions become impaired, accelerating synaptic and neuronal loss. Better understanding of the molecular mechanisms that contribute to microglial dysfunction is an important objective for identifying potential strategies to delay progression to AD. The inflammatory cyclooxygenase/prostaglandin E2 (COX/PGE2) pathway has been implicated in preclinical AD development, both in human epidemiology studies and in transgenic rodent models of AD. Here, we evaluated murine models that recapitulate microglial responses to Aβ peptides and determined that microglia-specific deletion of the gene encoding the PGE2 receptor EP2 restores microglial chemotaxis and Aβ clearance, suppresses toxic inflammation, increases cytoprotective insulin-like growth factor 1 (IGF1) signaling, and prevents synaptic injury and memory deficits. Our findings indicate that EP2 signaling suppresses beneficial microglia functions that falter during AD development and suggest that inhibition of the COX/PGE2/EP2 immune pathway has potential as a strategy to restore healthy microglial function and prevent progression to AD.

  16. [Morphologic and biochemical aspects of prostaglandin-induced cervix ripening].

    PubMed

    Rath, W; Adelmann-Grill, B C; Schauer, A; Kuhn, W

    1987-01-01

    For examination by electron microscopy tissue samples were taken from the posterior lip of the cervix of 8 patients having a termination of pregnancy at 9-12th week gestation and 16 patients of comparable gestational age who had an intracervical application of either 2 ml 5% tylose or 50 micrograms sulprostone-tylose gel 8 hours before biopsy. The efficacy of cervical priming was demonstrated objectively by tonometric studies. In addition, collagenase and protease activities were determined in the cervical tissue extracts of the different treatment groups. For identification of typical collagen fragments SDS-polyacrylamide-gel-electrophoresis were carried out on the acetic acid soluble extracts. The local application of sulprostone gel induced a marked multifocal loosening of the collagenous framework; there was no evidence for leucocyte infiltration or necrosis caused by the prostaglandin (PG) pretreatment. In the areas of disorganized collagen fibres cervical fibroblasts seemed to be activated characterized by fine granular loosening of the cytoplasma, dilated cisternae of rough endoplasmatic reticulum, vacuolized enlarged mitochondria and an increased number of cytoplasmatic vesicles close to the cell surface. Collagenase and protease activities were found in all extracts of the different treatment groups, however, PG-application led to no significant increase in enzymatic activities. There was no evidence for the presence of typical collagen cleavage products in the SDS-electrophoresis. Contradictory to the hitherto published literature enzymatic collagen degradation does not play an essential role in PG-induced cervical ripening.

  17. Prostaglandin E2 Mediates Immunosuppression in Acutely Decompensated Cirrhosis

    PubMed Central

    O’Brien, Alastair J.; Fullerton, James N.; Massey, Karen A.; Auld, Grace; Sewell, Gavin; James, Sarah; Newson, Justine; Karra, Effie; Winstanley, Alison; Alazawi, William; Garcia-Marquez, Rita; Cordoba, Juan; Nicolaou, Anna; Gilroy, Derek W.

    2017-01-01

    Patients with advanced cirrhosis experience frequent infections leading to sepsis, which carries high mortality. While innate immune dysfunction underlies this vulnerability, the precise cause remains elusive. We found prostaglandin (PGE2) elevated in acutely decompensated (AD) patients at immunosuppressive levels. Plasma from AD and end-stage liver disease (ESLD) patients suppressed macrophage cytokine secretion and bacteria killing in a PGE2 receptor-dependent manner, effects not seen in stable cirrhosis. Mouse models (bile duct ligation and CCL4-liver injury) also demonstrated elevated PGE2, which when inhibited completely restored immune competence and survival following infection. Importantly, albumin binds/inactivates PGE2 resulting in greater PGE2 bioavailability. This results in enhanced immunosuppressive effects of AD plasma in patients with low albumin levels. Administering albumin to AD patients reversed immunosuppressive properties of their plasma; protective effects recapitulated in rodent survival studies. Thus, elevated PGE2 combined with hypoalbuminemia mediates immunosuppression in AD and ESLD patients, which can be reversed with albumin. PMID:24728410

  18. Prostaglandin concentrations in uterine fluid of cows with pyometra.

    PubMed Central

    Manns, J G; Nkuuhe, J R; Bristol, F

    1985-01-01

    Uterine fluid was obtained from eight clinical cases of pyometra with retained corpus luteum and nine additional samples of fluid were collected from animals slaughtered at an abattoir. These samples, along with uterine flushes from normal cows in their luteal phase were analyzed for prostaglandin of the F (PGF) and E (PGE) groups. Blood samples were also obtained from the clinical cases for analysis of 13,14-dihydro-15-keto PGF (PGFM) the major metabolite of PGF. Pyometrial exudate from clinical cases of abattoir samples had high concentrations of PGF (17.9 ng/mL) and PGE (33.2 ng/mL) and the total amount of PGF and PGE in the uterus was calculated to be several hundred times as great as in normal cows. Furthermore, clinical cases had elevated PGFM in their blood compared to that of controls, which suggests that at least some of the PGF was being absorbed from the uterus. These results are discussed in light of our current understanding of the maternal recognition of pregnancy in cattle. PMID:4075244

  19. Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.

    PubMed

    Cutler, Corey; Multani, Pratik; Robbins, David; Kim, Haesook T; Le, Thuy; Hoggatt, Jonathan; Pelus, Louis M; Desponts, Caroline; Chen, Yi-Bin; Rezner, Betsy; Armand, Philippe; Koreth, John; Glotzbecker, Brett; Ho, Vincent T; Alyea, Edwin; Isom, Marlisa; Kao, Grace; Armant, Myriam; Silberstein, Leslie; Hu, Peirong; Soiffer, Robert J; Scadden, David T; Ritz, Jerome; Goessling, Wolfram; North, Trista E; Mendlein, John; Ballen, Karen; Zon, Leonard I; Antin, Joseph H; Shoemaker, Daniel D

    2013-10-24

    Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates, and early mortality. 16,16-Dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis, and we hypothesized that brief ex vivo modulation with dmPGE2 could improve patient outcomes by increasing the "effective dose" of HSCs. Molecular profiling approaches were used to determine the optimal ex vivo modulation conditions (temperature, time, concentration, and media) for use in the clinical setting. A phase 1 trial was performed to evaluate the safety and therapeutic potential of ex vivo modulation of a single UCB unit using dmPGE2 before reduced-intensity, double UCB transplantation. Results from this study demonstrated clear safety with durable, multilineage engraftment of dmPGE2-treated UCB units. We observed encouraging trends in efficacy, with accelerated neutrophil recovery (17.5 vs 21 days, P = .045), coupled with preferential, long-term engraftment of the dmPGE2-treated UCB unit in 10 of 12 treated participants.

  20. Possible role of prostaglandin F in blastocyst implantation

    SciTech Connect

    Kasamo, M.; Ishikawa, M.; Yamashita, K.; Sengoku, K.; Shimizu, T.

    1986-02-01

    The synthesis and release of Prostaglandin F (PGF) by the rabbit blastocyst and endometrium were investigated on Day 6 and Day 7, using radioimmunoassay, autoradiography and conversion experiments. The following results were obtained: The content of PGF in the blastocyst increased significantly (P less than 0.01) from Day 6 to Day 7. The content of PGF in the endometrium was significantly higher (P less than 0.05) on Day 7 implantation sites compared to the other areas. The in vitro synthesis and release of PGF by Day 6 blastocysts sharply increased after one and two hours of culture, respectively. Thereafter both values declined with time. The in vitro synthesis and release of PGF by Day 6 endometria increased continuously with time. /sup 14/C-arachidonic acid (/sup 14/C-AA) was incorporated into Day 6 blastocysts in vitro and converted to PGF2 alpha. These results suggest that both the endometrium and the blastocyst are the sources of the PGs involved in implantation, and that PGF derived from the blastocysts may act as the trigger of implantation.

  1. Prostaglandins temporally regulate cytoplasmic actin bundle formation during Drosophila oogenesis.

    PubMed

    Spracklen, Andrew J; Kelpsch, Daniel J; Chen, Xiang; Spracklen, Cassandra N; Tootle, Tina L

    2014-02-01

    Prostaglandins (PGs)--lipid signals produced downstream of cyclooxygenase (COX) enzymes--regulate actin dynamics in cell culture and platelets, but their roles during development are largely unknown. Here we define a new role for Pxt, the Drosophila COX-like enzyme, in regulating the actin cytoskeleton--temporal restriction of actin remodeling during oogenesis. PGs are required for actin filament bundle formation during stage 10B (S10B). In addition, loss of Pxt results in extensive early actin remodeling, including actin filaments and aggregates, within the posterior nurse cells of S9 follicles; wild-type follicles exhibit similar structures at a low frequency. Hu li tai shao (Hts-RC) and Villin (Quail), an actin bundler, localize to all early actin structures, whereas Enabled (Ena), an actin elongation factor, preferentially localizes to those in pxt mutants. Reduced Ena levels strongly suppress early actin remodeling in pxt mutants. Furthermore, loss of Pxt results in reduced Ena localization to the sites of bundle formation during S10B. Together these data lead to a model in which PGs temporally regulate actin remodeling during Drosophila oogenesis by controlling Ena localization/activity, such that in S9, PG signaling inhibits, whereas at S10B, it promotes Ena-dependent actin remodeling.

  2. Sequential induction of prostaglandin E and D synthases in inflammation

    SciTech Connect

    Schuligoi, Rufina . E-mail: rufina.schuligoi@meduni-graz.at; Grill, Magdalena; Heinemann, Akos; Peskar, Bernhard A.; Amann, Rainer

    2005-09-30

    Enhanced biosynthesis of prostaglandin (PG)D{sub 2} and subsequent formation of 15-deoxy-{delta}{sup 12,14}-PGJ{sub 2} has been suggested to contribute to resolution of inflammation. The primary aim of the present study in mouse heart was, therefore, to determine at the transcriptional level if there is sequential induction of PGE and PGD synthases (S) during inflammation. Expression of interleukin (IL)-1{beta} in heart was enhanced 4 h after systemic inflammation and declined thereafter within 3-5 days to basal levels. In contrast to cyclooxygenase-2 and membrane-bound (m)-PGES-1, which both peaked 4 h after endotoxin administration, hematopoietic (H)-PGDS expression was enhanced only 48 h after endotoxin. The expression of lipocalin-type (L)-PGDS was not significantly influenced. mRNA encoding the putative target of 15-deoxy-{delta}{sup 12,14}-PGJ{sub 2}, peroxisome proliferator-activated receptor {gamma}, was enhanced between 4 and 24 h after induction of inflammation. Treatment of mice with acetylsalicylic acid or indomethacin at doses effective to cause near-complete inhibition of PGE{sub 2} and PGD{sub 2} biosynthesis in heart ex vivo resulted in enhanced expression of IL-1{beta} 24 h after endotoxin administration. These results provide additional support for the hypothesis of a shift towards PGD{sub 2} biosynthesis during resolution of inflammation.

  3. Discovery of anti-inflammatory role of prostaglandin D2

    PubMed Central

    MURATA, Takahisa; MAEHARA, Toko

    2016-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin are one of the most frequently used classes of drug worldwide and inhibit prostaglandin (PG) production by inhibiting cyclooxygenase activity. Although NSAIDs are broadly used against inflammatory diseases, they have side effects including alimentary canal disorders, kidney damage, infection and cardiovascular disorders. Thus, it is necessary to elucidate the pathophysiological role of each PG in various diseases to develop better therapies with fewer and milder side effects. PGD2 is a PG that was identified in 1973 by Hamberg and is produced by the activities of cyclooxygenase and either hematopoietic or lipocalin-type PGD synthase. PGD2 exerts its physiological effects by stimulating two distinct G protein-coupled receptors, namely D prostanoid receptor (DP) and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). The physiological role of PGD2 remains controversial. Some studies have reported that PGD2 has bronchoconstrictory and pro-inflammatory effects inducing immune cell accumulation. In contrast, other groups have reported that PGD2 has anti-inflammatory effects by inhibiting the recruitment of dendritic cells and neutrophils. We have investigated the pathophysiological role of PGD2 using various disease models and reported on its anti-inflammatory actions. Here, we review the anti-inflammatory roles of PGD2 and the underlying mechanisms. PMID:27498997

  4. Rabbit blastocysts accumulate [3H]prostaglandins in vitro.

    PubMed

    Jones, M A; Harper, M J

    1984-08-01

    Rabbit blastocysts obtained on days 5, 6, and 6.8 of pregnancy were incubated in vitro in Tyrode's buffer with 3H-labeled prostaglandins (PGs). Accumulation of PGs was studied, using Whatman GF/F filters to separate bound and free ligands. The uptake and efflux of [3H]PGs were studied as a function of PG type, incubation time, temperature, and effect of metabolic inhibitors as well as age and number of blastocysts. Blastocysts of the same age accumulated approximately the same amount of [3H]PGE2 and [3H]PGF2 alpha from their environment; however, there was no apparent saturation over a PG concentration range of 1-1000 nM. Both the uptake and efflux of PG were age dependent, with older blastocysts accumulating more PGs. Approximately 90% of the [3H]PGs appear to be transported into the blastocoelic fluid, with little PG remaining in the blastomeres. PG accumulation was relatively insensitive to azide, ouabain, cyanide, or bromcresol green, but was affected by incubation at 0 C or the addition of indomethacin (10 micrograms/ml). No catabolism of the accumulated PGs was observed. The release of PGE2 in general did not differ from that of PGF2 alpha, except on day 6.8 of pregnancy when PGE2 was released more rapidly than on day 6. We conclude that rabbit blastocysts can accumulate PGs from their environment, which may imply a storage potential in the blastocyst and release before implantation.

  5. Anti-inflammatory prostaglandins for the prevention of preterm labour.

    PubMed

    Sykes, Lynne; MacIntyre, David A; Teoh, Tiong Ghee; Bennett, Phillip R

    2014-08-01

    Preterm birth occurs in 10-12% of pregnancies and is the primary cause of neonatal mortality and morbidity. Tocolytic therapies have long been the focus for the prevention of preterm labour, yet they do not significantly improve neonatal outcome. A direct causal link exists between infection-induced inflammation and preterm labour. As inflammation and infection are independent risk factors for poor neonatal outcome, recent research focus has been shifted towards exploring the potential for anti-inflammatory strategies. Nuclear factor kappa B (NFκB) is a transcription factor that controls the expression of many labour-associated genes including PTGS2 (COX2), prostaglandins (PGs) and the oxytocin receptor (OXTR) as well as key inflammatory genes. Targeting the inhibition of NFκB is therefore an attractive therapeutic approach for both the prevention of preterm labour and for reducing neonatal exposure to inflammation. While PGs are considered to be pro-labour and pro-inflammatory, the cyclopentenone PG 15-deoxy-Δ(12,14)PGJ2 (15d-PGJ2) exhibits anti-inflammatory properties via the inhibition of NFκB in human amniocytes, myocytes and peripheral blood mononuclear cells in vitro. 15d-PGJ2 also delays inflammation-induced preterm labour in the mouse and significantly increases pup survival. This review examines the current understanding of inflammation in the context of labour and discusses how anti-inflammatory PGs may hold promise for the prevention of preterm labour and improved neonatal outcome.

  6. Prostaglandin E2 Prevents Disuse-Induced Cortical Bone Loss

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.; Akamine, T.; Ke, Hua Zhu; Li, Xiao Jian; Tang, L. Y.; Zeng, Q. Q.

    1992-01-01

    The object of this study was to determine whether prostaglandin E2 (PGE2) can prevent disuse (underloaded)-induced cortical bone loss as well as add extra bone to underloaded bones. Thirteen-month-old retired female Sprague-Dawley breeders served as controls or were subjected to simultaneous right hindlimb immobilization by bandaging and daily subcutaneous doses of 0, 1, 3, or 6 mg PGE2/kg/d for two and six weeks. Histomorphometric analyses were performed on double-fluorescent labeled undecalcified tibial shaft sections (proximal to the tibiofibular junction). Disuse-induced cortical bone loss occurred by enlarging the marrow cavity and increasing intracortical porosity. PGE2 treatment of disuse shafts further increased intracortical porosity above that in disuse alone controls. This bone loss was counteracted by enhancement of periosteal and corticoendosteal bone formation. Stimulation of periosteal and corticoendosteal bone formation slightly enlarged the total tissue (cross-sectional) area and inhibited marrow cavity enlargement. These PGE2-induced activities netted the same percentage of cortical bone with a different distribution than the beginning and age related controls. These findings indicate the PGE2-induced increase in bone formation compensated for the disuse and PGE2-induced bone loss, and thus prevented immobilization induced bone loss.

  7. Prostaglandin-E2 Mediated Increase in Calcium and Phosphate Excretion in a Mouse Model of Distal Nephron Salt Wasting

    PubMed Central

    Soleimani, Manoocher; Barone, Sharon; Xu, Jie; Alshahrani, Saeed; Brooks, Marybeth; McCormack, Francis X.; Smith, Roger D.; Zahedi, Kamyar

    2016-01-01

    Contribution of salt wasting and volume depletion to the pathogenesis of hypercalciuria and hyperphosphaturia is poorly understood. Pendrin/NCC double KO (pendrin/NCC-dKO) mice display severe salt wasting under basal conditions and develop profound volume depletion, prerenal renal failure, and metabolic alkalosis and are growth retarded. Microscopic examination of the kidneys of pendrin/NCC-dKO mice revealed the presence of calcium phosphate deposits in the medullary collecting ducts, along with increased urinary calcium and phosphate excretion. Confirmatory studies revealed decreases in the expression levels of sodium phosphate transporter-2 isoforms a and c, increases in the expression of cytochrome p450 family 4a isotypes 12 a and b, as well as prostaglandin E synthase 1, and cyclooxygenases 1 and 2. Pendrin/NCC-dKO animals also had a significant increase in urinary prostaglandin E2 (PGE-2) and renal content of 20-hydroxyeicosatetraenoic acid (20-HETE) levels. Pendrin/NCC-dKO animals exhibit reduced expression levels of the sodium/potassium/2chloride co-transporter 2 (NKCC2) in their medullary thick ascending limb. Further assessment of the renal expression of NKCC2 isoforms by quantitative real time PCR (qRT-PCR) reveled that compared to WT mice, the expression of NKCC2 isotype F was significantly reduced in pendrin/NCC-dKO mice. Provision of a high salt diet to rectify volume depletion or inhibition of PGE-2 synthesis by indomethacin, but not inhibition of 20-HETE generation by HET0016, significantly improved hypercalciuria and salt wasting in pendrin/NCC dKO mice. Both high salt diet and indomethacin treatment also corrected the alterations in NKCC2 isotype expression in pendrin/NCC-dKO mice. We propose that severe salt wasting and volume depletion, irrespective of the primary originating nephron segment, can secondarily impair the reabsorption of salt and calcium in the thick ascending limb of Henle and/or proximal tubule, and reabsorption of sodium and

  8. Prostaglandin-E2 Mediated Increase in Calcium and Phosphate Excretion in a Mouse Model of Distal Nephron Salt Wasting.

    PubMed

    Soleimani, Manoocher; Barone, Sharon; Xu, Jie; Alshahrani, Saeed; Brooks, Marybeth; McCormack, Francis X; Smith, Roger D; Zahedi, Kamyar

    2016-01-01

    Contribution of salt wasting and volume depletion to the pathogenesis of hypercalciuria and hyperphosphaturia is poorly understood. Pendrin/NCC double KO (pendrin/NCC-dKO) mice display severe salt wasting under basal conditions and develop profound volume depletion, prerenal renal failure, and metabolic alkalosis and are growth retarded. Microscopic examination of the kidneys of pendrin/NCC-dKO mice revealed the presence of calcium phosphate deposits in the medullary collecting ducts, along with increased urinary calcium and phosphate excretion. Confirmatory studies revealed decreases in the expression levels of sodium phosphate transporter-2 isoforms a and c, increases in the expression of cytochrome p450 family 4a isotypes 12 a and b, as well as prostaglandin E synthase 1, and cyclooxygenases 1 and 2. Pendrin/NCC-dKO animals also had a significant increase in urinary prostaglandin E2 (PGE-2) and renal content of 20-hydroxyeicosatetraenoic acid (20-HETE) levels. Pendrin/NCC-dKO animals exhibit reduced expression levels of the sodium/potassium/2chloride co-transporter 2 (NKCC2) in their medullary thick ascending limb. Further assessment of the renal expression of NKCC2 isoforms by quantitative real time PCR (qRT-PCR) reveled that compared to WT mice, the expression of NKCC2 isotype F was significantly reduced in pendrin/NCC-dKO mice. Provision of a high salt diet to rectify volume depletion or inhibition of PGE-2 synthesis by indomethacin, but not inhibition of 20-HETE generation by HET0016, significantly improved hypercalciuria and salt wasting in pendrin/NCC dKO mice. Both high salt diet and indomethacin treatment also corrected the alterations in NKCC2 isotype expression in pendrin/NCC-dKO mice. We propose that severe salt wasting and volume depletion, irrespective of the primary originating nephron segment, can secondarily impair the reabsorption of salt and calcium in the thick ascending limb of Henle and/or proximal tubule, and reabsorption of sodium and

  9. Stage-dependent reduction in T colony formation in Hodgkin's disease. Coincidence with monocyte synthesis of prostaglandins.

    PubMed Central

    Bockman, R S

    1980-01-01

    Prostaglandin synthesis and T lymphocyte colony formation have been examined in previously untreated patients with Hodgkin's disease. Mononuclear cells have been isolated from peripheral blood and spleens of these patients. Significant augmentation in prostaglandin E levels were noted in the mononuclear cell cutures from Hodgkin's disease patients compared with controls (1.64 +/- 0.29 vs. 0.39 +/- 0.09 ng/10(6) cells, P < 0.005). Measured prostaglandin E levels increased with advancing stage of disease. Virtually all of the prostaglandins were synthesized by the adherent monocyte cell population. Prostaglandin E was the major product. Clonal expansion of a T lymphocyte precursor cell, which gives rise to colonies > 50 cells, was determined by a layered soft agar method. T colony formation was significantly reduced in patients with stage II, III, and IV disease. There were progressively reduced colony numbers seen with advancing stage of disease (609 +/- 209, 416 +/- 158, 207 +/- 58 compared with normals 2,274 +/- 360 colonies/10(6) cells plated; P < 0.005). The addition of inhibitors of endogenous prostaglandin synthesis resulted in significant augmentation of T colony number. However, a consistent relative decrease in T colony number was seen even when endogenous prostaglandin E synthesis was blocked. It would appear that both the prostaglandin-dependent and independent T colony precursor cells are lost with progressive stage of disease. A causative role of augmented prostaglandin synthesis in this stage-dependent reduction of T colony formation could not be established. PMID:6967491

  10. [Plasma hormone concentrations in induced abortion with local prostaglandin administration in the 1st trimester].

    PubMed

    Rath, W; König, A; Ulbrich, R; Hilgers, R; Kuske, R; Kuhn, W

    1983-01-01

    Abortion was performed by curettage on 71 women with pregnancies between the 7th and the 13th week of gestation seven to eight hours after intracervical application of a tylose gel containing 3mg prostaglandin F2 alpha. Prior to the application of the prostaglandin and immediately before the surgical intervention a sonographic examination for determining the vitality of the pregnancy was carried out.--Plasma progesteron, estradiol and HPL levels were determined radioimmunologically prior to the application of prostaglandin, at four-hour intervals on the day of intervention, and 24, 48 and 72 hours after the intervention. In 22 women a complete or an incomplete abortion occurred; in two cases a blighted ovum was observed; 47 pregnancies, according to sonographic examination, remained intact until curettage. After seven to eight hours duration of the effect of the prostaglandin gel, progesterone levels were found to be reduced to 60.5 per cent and 17-beta-estradiol to 31.4 per cent of the initial values, whereas the HPL values fell below the specificity of the testing procedure (12.5 ng/ml). Comparative investigations of the pregnancies which, according to sonographic findings, remained intact until curettage and those which were aborted after the application of prostaglandin did not, in spite of low plasma progesterone and estradiol levels in the abortive group, reveal any statistically significant differences. The abortive effect--even with local application--of the prostaglandins was confirmed. Conclusions regarding the effective mechanism of the prostaglandins upon the fetoplacental unit and the function of the corpus luteum remain subject to speculation.

  11. Prostaglandin E production and hypercalcaemia in rats bearing the Walker carcinosarcoma.

    PubMed

    Seyberth, H W; Bonsch, G; Müller, H; Minne, H W; Erlenmaier, T; Strein, K; Imbeck, H; Mrongovius, R

    1980-09-01

    The hypothesis that there is prostaglandin-mediated hypercalcaemia associated with the Walker carcinosarcoma in the rat was tested by measuring PGE production during the development of the hypercalcaemia, and determining the effects of inhibition of prostaglandin synthesis on serum calcium concentration. Parathyroid hormone (PTH) activity was estimated by the determination of the serum concentration of immunoreactive PTH. There was a 3-fold increase in the urinary excretion of 7α-hydroxy-5,11-diketotetranor-prostane-1,16-dioic acid (PGE-M), a major urinary metabolite of the E prostaglandins from basal levels. Treatment with indomethacin, a potent inhibitor of prostaglandin synthesis, did not lower serum calcium concentrations with two different doses (1·6 mg/kg/day orally and 5 mg/kg/day i.m.); effective inhibition of prostaglandin synthesis was demonstrated by the suppression of PGE-M excretion rates below basal levels. Serum concentrations of immunoreactive PTH were not significantly altered by either tumour growth or indomethacin. Dexamethasone (0·5 mg/kg/day i.m.) attenuated both the increased urinary excretion of PGE-M and the rise in serum calcium concentration, suggesting that one or several lipoxygenase products might be the actual mediators of the hypercalcaemia. We conclude that the hypercalcaemia in the rat with Walker carcinosarcoma is probably not mediated by E-prostaglandins and probably not by any other product of the cyclo-oxygenase pathway. The increased PGE turnover may be considered as a biochemical marker of tumour load, but not as an indicator of a prostaglandin-mediated hypercalcaemia.

  12. Prostaglandin E production and hypercalcaemia in rats bearing the Walker carcinosarcoma

    PubMed Central

    Seyberth, H. W.; Bonsch, G.; Müller, H.; Minne, H. W.; Erlenmaier, T.; Strein, K.; Imbeck, H.; Mrongovius, R.

    1980-01-01

    The hypothesis that there is prostaglandin-mediated hypercalcaemia associated with the Walker carcinosarcoma in the rat was tested by measuring PGE production during the development of the hypercalcaemia, and determining the effects of inhibition of prostaglandin synthesis on serum calcium concentration. Parathyroid hormone (PTH) activity was estimated by the determination of the serum concentration of immunoreactive PTH. There was a 3-fold increase in the urinary excretion of 7α-hydroxy-5,11-diketotetranor-prostane-1,16-dioic acid (PGE-M), a major urinary metabolite of the E prostaglandins from basal levels. Treatment with indomethacin, a potent inhibitor of prostaglandin synthesis, did not lower serum calcium concentrations with two different doses (1·6 mg/kg/day orally and 5 mg/kg/day i.m.); effective inhibition of prostaglandin synthesis was demonstrated by the suppression of PGE-M excretion rates below basal levels. Serum concentrations of immunoreactive PTH were not significantly altered by either tumour growth or indomethacin. Dexamethasone (0·5 mg/kg/day i.m.) attenuated both the increased urinary excretion of PGE-M and the rise in serum calcium concentration, suggesting that one or several lipoxygenase products might be the actual mediators of the hypercalcaemia. We conclude that the hypercalcaemia in the rat with Walker carcinosarcoma is probably not mediated by E-prostaglandins and probably not by any other product of the cyclo-oxygenase pathway. The increased PGE turnover may be considered as a biochemical marker of tumour load, but not as an indicator of a prostaglandin-mediated hypercalcaemia. PMID:7426347

  13. Histamine and prostaglandin interaction in regulation of oxytocin and vasopressin secretion.

    PubMed

    Knigge, U; Kjaer, A; Kristoffersen, U; Madsen, K; Toftegaard, C; Jørgensen, H; Warberg, J

    2003-10-01

    Prostaglandins and histamine in the hypothalamus are involved in the regulation of oxytocin and vasopressin secretion, and appear to be involved in the mediation of pituitary hormone responses to immunochallenges. Therefore, we investigated in conscious male rats: (i) whether blockade of H1 or H2 receptors affected the oxytocin and vasopressin responses to prostaglandins and (ii) whether blockade of prostaglandin synthesis affected the oxytocin and vasopressin responses to histamine or to Escherichia coli lipopolysaccharide (LPS), in order to determine any interaction between prostaglandins and histamine in the hypothalamus. Oxytocin secretion was dose-dependently stimulated by intracerebroventricular infusion of 1 or 5 microg of PGE1, PGE2 or PGF2alpha, with PGE2 being the most potent of the compounds used. Prior central infusion of the H1 receptor antagonist mepyramine or the H2 receptor antagonist cimetidine significantly inhibited the oxytocin response to all three prostaglandins by approximately 50%. Vasopressin secretion was increased by PGE1 but not by PGE2 or PGF2alpha. The stimulatory effect of PGE1 was almost annihilated by prior administration of mepyramine or cimetidine. Central infusion of histamine or immunochallenge with LPS administered intraperitoneally increased oxytocin and vasopressin secretion four- and two-fold, respectively. Pretreatment with systemic injection of the prostaglandin synthesis inhibitor indomethacin dose-dependently reduced the oxytocin response and prevented the vasopressin response to histamine or LPS. We conclude that histamine and PGE1, PGE2 or PGF2alpha interact in the regulation of oxytocin secretion, whereas histamine and only PGE1 interact in the regulation of vasopressin secretion. Furthermore, histamine as well as LPS may affect oxytocin and vasopressin neurones via activation of prostaglandins, probably in the hypothalamic supraoptic nucleus.

  14. Mutated and bacteriophage T4 nanoparticle arrayed F1-V immunogens from Yersinia pestis as next generation plague vaccines.

    PubMed

    Tao, Pan; Mahalingam, Marthandan; Kirtley, Michelle L; van Lier, Christina J; Sha, Jian; Yeager, Linsey A; Chopra, Ashok K; Rao, Venigalla B

    2013-01-01

    Pneumonic plague is a highly virulent infectious disease with 100% mortality rate, and its causative organism Yersinia pestis poses a serious threat for deliberate use as a bioterror agent. Currently, there is no FDA approved vaccine against plague. The polymeric bacterial capsular protein F1, a key component of the currently tested bivalent subunit vaccine consisting, in addition, of low calcium response V antigen, has high propensity to aggregate, thus affecting its purification and vaccine efficacy. We used two basic approaches, structure-based immunogen design and phage T4 nanoparticle delivery, to construct new plague vaccines that provided complete protection against pneumonic plague. The NH₂-terminal β-strand of F1 was transplanted to the COOH-terminus and the sequence flanking the β-strand was duplicated to eliminate polymerization but to retain the T cell epitopes. The mutated F1 was fused to the V antigen, a key virulence factor that forms the tip of the type three secretion system (T3SS). The F1mut-V protein showed a dramatic switch in solubility, producing a completely soluble monomer. The F1mut-V was then arrayed on phage T4 nanoparticle via the small outer capsid protein, Soc. The F1mut-V monomer was robustly immunogenic and the T4-decorated F1mut-V without any adjuvant induced balanced TH1 and TH2 responses in mice. Inclusion of an oligomerization-deficient YscF, another component of the T3SS, showed a slight enhancement in the potency of F1-V vaccine, while deletion of the putative immunomodulatory sequence of the V antigen did not improve the vaccine efficacy. Both the soluble (purified F1mut-V mixed with alhydrogel) and T4 decorated F1mut-V (no adjuvant) provided 100% protection to mice and rats against pneumonic plague evoked by high doses of Y. pestis CO92. These novel platforms might lead to efficacious and easily manufacturable next generation plague vaccines.

  15. Circadian and estral changes in the hypothalamic prostaglandin e content and [h]prostaglandin e binding in female rats.

    PubMed

    Bommelaer-Bayet, M C; Wisner, A; Renard, C A; Levi, F A; Dray, F

    1990-04-01

    Abstract Prostaglandin E(2), (PGE(2)) is involved in the luteinizing hormone-releasing hormone-stimulated luteinizing hormone surge in female rats and may act via specific membrane receptors. The following studies were performed to determine whether there were any changes in the hypothalamic PGE(2) binding and/or PGE(2) content which were specific to proestrus and not to the rest of the estrous cycle. Groups of female Wistar rats were sacrificed at 3-h intervals throughout the estrous cycle to determine both the circadian and circaestral changes in the hypothalamic PGE(2) content and [(3)H]PGE(2) binding. The hypothalamic PGE(2) content was maximal at 1700 h on each of the 4 consecutive days of the estrous cycle but was independent of the stage of the cycle. [(3)H]PGE(2) binding also displayed a circadian rhythm; the lowest binding occurred near the circadian peak of PGE(2), suggesting that the PGE(2) binding sites were occupied by endogenous PGE(2). Since such circadian rhythms were not observed in the hypothalamus of male rats, they may be under the control of ovarian steroids. Also, since PGE(2) binding and the PGE(2) content both exhibit a diurnal pattern independent of the day of the cycle, there may be changes in the PGE(2) receptor-mediated process coupled to an adenylyl cyclase which could explain the luteinizing hormone surge in proestrus.

  16. Long-term anabolic effects of prostaglandin-E2 on tibial diaphyseal bone in male rats

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.; Ke, Hua Zhu; Li, Xiao Jian

    1991-01-01

    The effects of long-term prostaglandin E2 (PGE2) on tibial diaphyseal bone were studied in 7-month-old male Sprague-Dawley rats given daily subcutaneous injections of 0, 1, 3 and 6 mg PGE2/kg/day for 60, 120 and 180 days. The tibial shaft was measured by single photon absorptiometry and dynamic histomorphometric analyses were performed on double-fluorescent labeled undecalcified tibial diaphyseal bone samples. Exogenous PGE2 administration produced the following transient changes in a dose-response manner between zero and 60 days: (1) increased bone width and mineral density; (2) increased total tissue and total bone areas; (3) decreased marrow area; (4) increased periosteal and corticoendosteal lamellar bone formation; (5) activated corticoendosteal lamellar and woven trabecular bone formation; and (6) activated intracortical bone remodeling. A new steady-state of increased tibial diaphyseal bone mass and elevated bone activities were observed from day 60 onward. The elevated bone mass level attained after 60 days of PGE2 treatment was maintained at 120 and 180 days. These observations indicate that the powerful anabolic effects of PGE2 will increase both periosteal and corticoendosteal bone mass and sustain the transient increase in bone mass with continuous daily administration of PGE2.

  17. Prostaglandin protection of human isolated gastric glands against indomethacin and ethanol injury. Evidence for direct cellular action of prostaglandin.

    PubMed Central

    Tarnawski, A; Brzozowski, T; Sarfeh, I J; Krause, W J; Ulich, T R; Gergely, H; Hollander, D

    1988-01-01

    Isolated human gastric glands from surgical specimens were preincubated in an oxygenated medium with placebo or 16,16 dimethyl prostaglandin E2 (dmPGE2) and incubated at 37 degrees C in either medium alone, medium containing 4.43 mM indomethacin or medium containing 8% ethanol. We assessed the viability of gland cells with fast green exclusion, release of lactate dehydrogenase (LDH) into the medium, and ultrastructural damage by scanning and transmission electron microscopy. Both indomethacin and ethanol significantly reduced the viability of placebo-pretreated glands, increased LDH release into the medium, and produced prominent ultrastructural damage. DmPGE2 significantly reduced both indomethacin and ethanol-induced injury, increased the number of viable cells, reduced LDH release, and diminished the extent of ultrastructural damage. These studies indicate that PG protection of gastric mucosal cells has a direct cellular action that is not limited to replacement of depleted endogenous PGs. PG protection in our experiments did not depend on PG's previously described systemic actions, such as protection of the microvessels, preservation of the mucosal blood flow, or stimulation of bicarbonate and mucus secretion. Images PMID:3350966

  18. Asymmetric hybridization in Rhododendron agastum: a hybrid taxon comprising mainly F1s in Yunnan, China

    PubMed Central

    Zha, Hong-Guang; Milne, Richard I.; Sun, Hang

    2010-01-01

    Background and Aims Rhododendron (Ericaceae) is a large woody genus in which hybridization is thought to play an important role in evolution and speciation, particularly in the Sino-Himalaya region where many interfertile species often occur sympatrically. Rhododendron agastum, a putative hybrid species, occurs in China, western Yunnan Province, in mixed populations with R. irroratum and R. delavayi. Methods Material of these taxa from two sites 400 km apart (ZhuJianYuan, ZJY and HuaDianBa, HDB) was examined using cpDNA and internal transcribed spacer (ITS) sequences, and amplified fragment length polymorphism (AFLP) loci, to test the possibility that R. agastum was in fact a hybrid between two of the other species. Chloroplast trnL-F and trnS-trnG sequences together distinguished R. irroratum, R. delavayi and some material of R. decorum, which is also considered a putative parent of R. agastum. Key Results All 14 R. agastum plants from the HDB site had the delavayi cpDNA haplotype, whereas at the ZJY site 17 R. agastum plants had this haplotype and four had the R. irroratum haplotype. R. irroratum and R. delavayi are distinguished by five unequivocal point mutations in their ITS sequences; every R. agastum accession had an additive pattern (double peaks) at each of these sites. Data from AFLP loci were acquired for between ten and 21 plants of each taxon from each site, and were analysed using a Bayesian approach implemented by the program NewHybrids. The program confirmed the identity of all accessions of R. delavayi, and all R. irroratum except one, which was probably a backcross. All R. agastum from HDB and 19 of 21 from ZJY were classified as F1 hybrids; the other two could not be assigned a class. Conclusions Rhododendron agastum represents populations of hybrids between R. irroratum and R. delavayi, which comprise mostly or only F1s, at the two sites examined. The sites differ in that at HDB there was no detected variation in cpDNA type or hybrid class

  19. The carcinogenicity of dichloroacetic acid in the male B6C3F1 mouse

    SciTech Connect

    DeAngelo, A.B.; Daniel, F.B.; Stober, J.A.; Olson, G.R. )

    1991-02-01

    Groups of male B6C3F1 mice (N = 50) were provided drinking water containing 2 g/liter sodium chloride (control) and 0.05, 0.5, and 5 g/liter dichloroacetic acid (DCA). Treatment of 30 animals in each group was carried out to 60 or 75 weeks. In a separate experiment, mice exposed to 3.5 g/liter DCA and the corresponding acetic acid control group were killed at 60 weeks. Groups of 5 mice were killed at 4, 15, 30, and 45 weeks. Time-weighted mean daily doses of 7.6, 77, 410, and 486 mg/kg/day were calculated for 0.05, 0.5, 3.5, and 5 g/liter DCA treatments. Animals exposed to 3.5 and 5 g/liter DCA had final body weights that were 87 and 83%, respectively, of the control value. Relative liver weights of 136, 230, and 351% of the control value were measured for 0.5, 3.5, and 5 g/liter, respectively. At 60 weeks mice receiving 5.0 g/liter DCA had a 90% prevalence of liver neoplasia with a mean multiplicity of 4.50 tumors/animal. Exposure to 3.5 g/liter DCA for 60 weeks resulted in a 100% tumor prevalence with an average of 4.0 tumors/animal. The prevalence of liver neoplasia and tumor multiplicity at 60 and 75 weeks in the 0.05 g/liter DCA (24.1%; 0.31 tumors/animal) and in the 0.5 g/liter group (11.1%; 0.11 tumors/animal) did not differ significantly from the control value (7.1% and 0.07 tumors/animal). No liver tumors were found in the group treated with acetic acid. Hyperplastic nodules were seen in the 3.5 (58%; 0.92/animal) and 5 g/liter DCA groups (83%; 1.27/animal). There was a significant positive dose-related trend in the age-adjusted prevalence of liver tumors. These data confirm the hepatocarcinogenicity of DCA administered in the drinking water to male B6C3F1 mice for 60 weeks.

  20. Carcinogenicity of bisphenol-A in Fischer rats and B6C3F1 mice.

    PubMed

    Huff, J

    2001-11-01

    Bisphenol-A (BP-A; 4,4'-isopropylidenediphenol) is a monomer of plastics commonly used in various consumer products, and is used as an intermediate in the manufacture of epoxy, polycarbonate, and polyester-styrene resins. A National Toxicology Program carcinogenesis bioassay of BP-A (>98% pure) was conducted by feeding diets containing 0, 1000, or 2000 ppm BP-A to groups of 50 male and 50 female Fischer (F)344 rats; 0, 1000, or 5000 ppm to groups of 50 male B6C3F1 mice; and 0, 5000, or 10,000 ppm to groups of 50 female B6C3F1 mice for 103 weeks. The mean body weights of the low- and high-dose rats and of female mice and high-dose male mice were lower than those of the controls throughout much of the study. Lower body weight gains in rats were likely caused by reduced food consumption. Survivals were comparable among groups. Regarding neoplasia, leukemias occurred at increased incidences in BP-A-dosed rats of both sexes: male, 13/50 controls vs 12/50 low-dose and 23/50 high-dose (P < 0.03); in females, the respective findings were 7/50, 13/50, and 12/50. Interstitial-cell tumors of the testes were increased in BP-A-dosed male rats: 35/49 controls vs 48/50 (P < 0.01) and 46/49 (P < 0.01); and an increasing trend was observed for mammary gland fibroadenomas in male rats (P < 0.05, 0/50 controls vs 0/50 and 4/50). In male mice, lymphomas/leukemias were increased: 2/49 controls vs 9/50 (P < 0.05) and 5/50. Multinucleated giant hepatocytes were observed in male mice (1/49 controls vs 41/49 and 41/50), whereas there was no increase of liver tumors. In their BP-A bioassay report, the National Toxicology Program concluded that there was no convincing evidence that BP-A was carcinogenic for rats or mice. However, the marginal increases in leukemias in male and female rats, along with increases in the combined incidence of lymphomas and leukemias in male mice, suggest that BP-A may be associated with increased cancers of the hematopoietic system. Increases in interstitial

  1. Acrylonitrile is a multisite carcinogen in male and female B6C3F1 mice.

    PubMed

    Ghanayem, Burhan I; Nyska, Abraham; Haseman, Joseph K; Bucher, John R

    2002-07-01

    Acrylonitrile is a heavily produced unsaturated nitrile, which is used in the production of synthetic fibers, plastics, resins, and rubber. Acrylonitrile is a multisite carcinogen in rats after exposure via gavage, drinking water, or inhalation. No carcinogenicity studies of acrylonitrile in a second animal species were available. The current studies were designed to assess the carcinogenicity of acrylonitrile in B6C3F1 mice of both sexes. Acrylonitrile was administered by gavage at 0, 2.5, 10, or 20 mg/kg/day, 5 days per week, for 2 years. Urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine were measured as markers of exposure to acrylonitrile. In general, there were dose-related increases in urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine concentrations in all dosed groups of mice and at all time points. Survival was significantly (p < 0.001) reduced in the top dose (20 mg/kg) group of male and female mice relative to controls. The incidence of forestomach papillomas and carcinomas was increased in mice of both sexes in association with an increase in forestomach epithelial hyperplasia. The incidence of Harderian gland adenomas and carcinomas was also markedly increased in the acrylonitrile-dosed groups. In female mice, the incidence of benign or malignant granulosa cell tumors (combined) in the ovary in the 10 mg/kg dose group was greater than that in the vehicle control group, but because of a lack of dose response, this was considered an equivocal finding. In addition, the incidences of atrophy and cysts in the ovary of the 10 and 20 mg/kg dose groups were significantly increased. The incidences of alveolar/bronchiolar adenoma or carcinoma (combined) were significantly increased in female mice treated with acrylonitrile at 10 mg/kg/day for 2 years. This was also considered an equivocal result. In conclusion, these studies demonstrated that acrylonitrile causes multiple carcinogenic effects after gavage administration to male and female B6

  2. Oncogenic evaluation of tetrachlorvinphos in the B6C3F1 mouse.

    PubMed

    Parker, C M; Van Gelder, G A; Chai, E Y; Gellatly, J B; Serota, D G; Voelker, R W; Vesselinovitch, S D

    1985-10-01

    Groups of 80 male and 80 female B6C3F1 mice were fed diets containing 17.5, 64, 320, 1600, 8000, and 16000 ppm tetrachlorvinphos (TCVP) for up to 103 weeks. Another group of 80 male and 80 female mice were fed TCVP (16000 ppm) that was used in a previous bioassay. One hundred-sixty male and 160 female mice served as the control group. Ten treated and 20 control mice/sex/group were killed at 6, 12, and 18 months. It was estimated that the study maximum-tolerated dose was exceeded by three- and sixfold in the 8000- and 16000-ppm dose groups, respectively. Consequently, these exposures produced excessive cytotoxicity and regenerative changes in the liver and kidneys which were associated with sex-hormonal imbalance and metabolic overload in liver. A significant decrease (15-40%) in body weight was observed in mice fed 8000 and 16000 ppm TCVP. These treated mice did not gain weight during the study. Reduced food consumption and caloric intake throughout the study were probably responsible for the increased survival and the decreased incidence of spontaneous neoplasia in mice fed 8000 and 16000 ppm TCVP. Classification of pathologic lesions observed in these high-dose groups differed among study and consulting pathologists. The consultant and Shell pathologists concluded that the liver and kidney changes were causally related to excessive toxicity which was manifest primarily by hepatocellular hyperplasia and renal tubular adenoma. Study pathologist in accordance with his classification found statistically significant increases in hepatocellular carcinoma, hepatocellular adenoma or carcinoma, and renal tubular carcinoma in male mice fed 16000 ppm TCVP. The incidence of hepatic neoplasms as evaluated by the study pathologist in female mice fed 8000 and 16000 ppm TCVP although statistically significant was of questionable biologic significance when compared with historical female controls. The only statistically significant finding observed by the consulting pathologist

  3. Mitochondrial F0F1-ATP synthase is a molecular target of 3-iodothyronamine, an endogenous metabolite of thyroid hormone

    PubMed Central

    Cumero, S; Fogolari, F; Domenis, R; Zucchi, R; Mavelli, I; Contessi, S

    2012-01-01

    BACKGROUND AND PURPOSE 3-iodothyronamine (T1AM) is a metabolite of thyroid hormone acting as a signalling molecule via non-genomic effectors and can reach intracellular targets. Because of the importance of mitochondrial F0F1-ATP synthase as a drug target, here we evaluated interactions of T1AM with this enzyme. EXPERIMENTAL APPROACH Kinetic analyses were performed on F0F1-ATP synthase in sub-mitochondrial particles and soluble F1-ATPase. Activity assays and immunodetection of the inhibitor protein IF1 were used and combined with molecular docking analyses. Effects of T1AM on H9c2 cardiomyocytes were measured by in situ respirometric analysis. KEY RESULTS T1AM was a non-competitive inhibitor of F0F1-ATP synthase whose binding was mutually exclusive with that of the inhibitors IF1 and aurovertin B. Both kinetic and docking analyses were consistent with two different binding sites for T1AM. At low nanomolar concentrations, T1AM bound to a high-affinity region most likely located within the IF1 binding site, causing IF1 release. At higher concentrations, T1AM bound to a low affinity-region probably located within the aurovertin binding cavity and inhibited enzyme activity. Low nanomolar concentrations of T1AM increased ADP-stimulated mitochondrial respiration in cardiomyocytes, indicating activation of F0F1-ATP synthase consistent with displacement of endogenous IF1,, reinforcing the in vitro results. CONCLUSIONS AND IMPLICATIONS Effects of T1AM on F0F1-ATP synthase were twofold: IF1 displacement and enzyme inhibition. By targeting F0F1-ATP synthase within mitochondria, T1AM might affect cell bioenergetics with a positive effect on mitochondrial energy production at low, endogenous, concentrations. T1AM putative binding locations overlapping with IF1 and aurovertin binding sites are described. PMID:22452346

  4. Prostaglandin J2: a potential target for halting inflammation-induced neurodegeneration

    PubMed Central

    Figueiredo-Pereira, Maria E.; Corwin, Chuhyon; Babich, John

    2015-01-01

    Prostaglandins are produced via cyclooxygenases, which are enzymes that play a major role in neuroinflammation. Epidemiological studies show that chronic treatment with low levels of cyclooxygenase inhibitors (NSAIDs) lowers the risk for Alzheimer's (AD) and Parkinson's (PD) diseases by as much as 50%. Unfortunately, inhibiting cyclooxygenases with NSAIDs blocks the synthesis of downstream neuroprotective and neurotoxic prostaglandins, thus producing adverse side effects. We focus on prostaglandin J2 (PGJ2) because it is highly neurotoxic compared to PGA1, D2, and E2. Unlike other prostaglandins, PGJ2 and its metabolites have a cyclopentenone ring with reactive α,β-unsaturated carbonyl groups that form covalent Michael adducts with key cysteines in proteins and GSH. Cysteine-binding electrophiles such as PGJ2 are considered to play an important role in determining whether neurons will live or die. We discuss in vitro and in vivo studies showing that PGJ2 induces pathological processes relevant to neurodegenerative disorders such as AD and PD. Furthermore, we found that increasing intracellular cAMP with the lipophilic peptide PACAP27 counteracts some of the PGJ2-induced detrimental effects. In conclusion, new therapeutic strategies that neutralize the effects of specific neurotoxic prostaglandins downstream from cyclooxygenases could have a significant impact on the treatment of chronic neurodegenerative disorders with fewer adverse side effects. PMID:26748744

  5. Borders and comparative cytoarchitecture of the perirhinal and postrhinal cortices in an F1 hybrid mouse.

    PubMed

    Beaudin, Stephane A; Singh, Teghpal; Agster, Kara L; Burwell, Rebecca D

    2013-02-01

    We examined the cytoarchitectonic and chemoarchitectonic organization of the cortical regions associated with the posterior rhinal fissure in the mouse brain, within the framework of what is known about these regions in the rat. Primary observations were in a first-generation hybrid mouse line, B6129PF/J1. The F1 hybrid was chosen because of the many advantages afforded in the study of the molecular and cellular bases of learning and memory. Comparisons with the parent strains, the C57BL6/J and 129P3/J are also reported. Mouse brain tissue was processed for visualization of Nissl material, myelin, acetyl cholinesterase, parvalbumin, and heavy metals. Tissue stained for heavy metals by the Timm's method was particularly useful in the assignment of borders and in the comparative analyses because the patterns of staining were similar across species and strains. As in the rat, the areas examined were parcellated into 2 regions, the perirhinal and the postrhinal cortices. The perirhinal cortex was divided into areas 35 and 36, and the postrhinal cortex was divided into dorsal (PORd) and ventral (PORv) subregions. In addition to identifying the borders of the perirhinal cortex, we were able to identify a region in the mouse brain that shares signature features with the rat postrhinal cortex.

  6. Sensitivity to foot shock in autoimmune NZB x NZW F1 hybrid mice.

    PubMed

    Schrott, L M; Crnic, L S

    1994-11-01

    Prior studies have demonstrated deficits in active avoidance learning in young (12-week-old) mice that develop lupus-like autoimmunity. Because foot shock is the motivating stimulus in this task, sensitivity to foot shock was assessed in autoimmune NZB x NZW F1 hybrid (B/W) and nonautoimmune NZW female mice. Responses to shock at levels ranging from 0.05 to 1.6 mA were recorded twice during the development of autoimmunity. At 12 weeks of age, B/W mice did not differ from NZW mice in sensitivity to shock. However, at 24 weeks of age, when antibody levels were elevated, sensitivity to foot shock decreased in B/W mice at low shock levels and increased at high shock levels. A neurological battery revealed no deficits that could account for these effects. However, IgM anti-DNA antibody levels were positively correlated with responsiveness to high levels of shock. The change in the pattern of sensitivity at 24 weeks may be due to a combination of disease-related sensory impairment at low shock levels and hyperalgesia at high shock levels. The response to high levels of shock may also be an indication of enhanced emotionality, an interpretation consistent with reports in other lupus-prone strains and affective disorders in humans with lupus.

  7. Composition of the nighttime ionospheric F 1 region near the magnetic equator

    NASA Technical Reports Server (NTRS)

    Anderson, D. N.; Rusch, D. W.

    1980-01-01

    The effects of vertical E x B transport on NO(+), O2(+) and O(+) densities in the nighttime equatorial ionospheric F 1 region are investigated. Ion densities are calculated as functions of altitude, latitude and local time by the numerical solution of coupled, time-dependent ion continuity equations, taking into account production, loss by charge exchange and dissociative recombination and transport by diffusion and E x B drift. The results of the calculations are compared with measurements of NO(+), O2(+) and O(+) ion densities obtained at low altitudes by a mass spectrometer on board the Atmospheric Explorer C satellite, and are found to be consistent with the observations, suggesting that in the equatorial region, vertical transport by E x B drift is primarily responsible for producing the observed NO(+), O2(+) and O(+) density profiles. In addition, the reaction of O2(+) with N(4S) is found to be an important sink for O2(+) and a source of NO(+) ions. Implications of the observed and calculated near constancy of electron and ion densities with altitude when NO(+) is the dominant ion on the growth of large-scale irregularities are also considered

  8. Measurement of the inertial properties of the Helios F-1 spacecraft

    NASA Technical Reports Server (NTRS)

    Gayman, W. H.

    1975-01-01

    A gravity pendulum method of measuring lateral moments of inertia of large structures with an error of less than 1% is outlined. The method is based on the fact that in a physical pendulum with a knife-edge support the distance from the axis of rotation to the system center of gravity determines the minimal period of oscillation and is equal to the system centroidal radius of gyration. The method is applied to results of a test procedure in which the Helios F-1 spacecraft was placed in a roll fixture with crossed flexure pivots as elastic constraints and system oscillation measurements were made with each of a set of added moment-of-inertia increments. Equations of motion are derived with allowance for the effect of the finite pivot radius and an error analysis is carried out to find the criterion for maximum accuracy in determining the square of the centroidal radius of gyration. The test procedure allows all measurements to be made with the specimen in upright position.

  9. Thermodynamics and kinetics of the FoF1-ATPase: application of the probability isotherm.

    PubMed

    Chapman, Brian; Loiselle, Denis

    2016-02-01

    We use the results of recent publications as vehicles with which to discuss the thermodynamics of the proton-driven mitochondrial F o F1-ATP synthase, focusing particularly on the possibility that there may be dissociation between rotatory steps and ATP synthesis/hydrolysis. Such stoichiometric 'slippage' has been invoked in the literature to explain observed non-ideal behaviour. Numerical solution of the Rate Isotherm (the kinetic equivalent of the more fundamental Probability Isotherm) suggests that such 'slippage' is an unlikely explanation; instead, we suggest that the experimental results may be more consistent with damage to the enzyme caused by its isolation from the biomembrane and its experimental fixation, resulting in non-physiological friction within the enzyme's rotary mechanism. We emphasize the unavoidable constraint of the Second Law as instantiated by the obligatory dissipation of Gibbs Free Energy if the synthase is to operate at anything other than thermodynamic equilibrium. We use further numerical solution of the Rate Isotherm to demonstrate that there is no necessary association of low thermodynamic efficiency with high metabolic rates in a bio-world in which the dominating mechanism of metabolic control is multifactorial enzyme activation.

  10. Thermodynamics and kinetics of the FoF1-ATPase: application of the probability isotherm

    PubMed Central

    Chapman, Brian; Loiselle, Denis

    2016-01-01

    We use the results of recent publications as vehicles with which to discuss the thermodynamics of the proton-driven mitochondrial FoF1-ATP synthase, focusing particularly on the possibility that there may be dissociation between rotatory steps and ATP synthesis/hydrolysis. Such stoichiometric ‘slippage’ has been invoked in the literature to explain observed non-ideal behaviour. Numerical solution of the Rate Isotherm (the kinetic equivalent of the more fundamental Probability Isotherm) suggests that such ‘slippage’ is an unlikely explanation; instead, we suggest that the experimental results may be more consistent with damage to the enzyme caused by its isolation from the biomembrane and its experimental fixation, resulting in non-physiological friction within the enzyme's rotary mechanism. We emphasize the unavoidable constraint of the Second Law as instantiated by the obligatory dissipation of Gibbs Free Energy if the synthase is to operate at anything other than thermodynamic equilibrium. We use further numerical solution of the Rate Isotherm to demonstrate that there is no necessary association of low thermodynamic efficiency with high metabolic rates in a bio-world in which the dominating mechanism of metabolic control is multifactorial enzyme activation. PMID:26998316

  11. Subchronic studies of doxylamine in B6C3F1 mice.

    PubMed

    Jackson, C D; Blackwell, B N

    1988-02-01

    Doxylamine succinate, a histamine (H1) antagonist (antihistamine), was administered as an admixture in the feed to male and female B6C3F1 mice for 14 or 90 days. Dose levels of 0, 100, 250, 500, 1000, and 2000 ppm doxylamine were administered to males and females in the 14-day study while dose levels of 0, 80, 162, 325, 750, and 1500 ppm were administered to both sexes in the 90-day study. Little toxicity was seen in the 14-day study. Final body weights in the highest dose group were reduced 4.0 and 7.3% in males and females, respectively. Treatment-related histopathological changes in the 14-day study were limited to a very low incidence of hepatic necrosis in both sexes. There was little toxicity observed in the 90-day study and no clear dose response relative to weight gain was observed. Histologically, the liver was the only organ affected by doxylamine administration. The liver lesions consisted of hepatic cell cytomegaly and/or karyomegaly which varied from mild to severe and a possible dose-related hepatic necrosis.

  12. Hormone-regulated defense and stress response networks contribute to heterosis in Arabidopsis F1 hybrids.

    PubMed

    Groszmann, Michael; Gonzalez-Bayon, Rebeca; Lyons, Rebecca L; Greaves, Ian K; Kazan, Kemal; Peacock, W James; Dennis, Elizabeth S

    2015-11-17

    Plant hybrids are extensively used in agriculture to deliver increases in yields, yet the molecular basis of their superior performance (heterosis) is not well understood. Our transcriptome analysis of a number of Arabidopsis F1 hybrids identified changes to defense and stress response gene expression consistent with a reduction in basal defense levels. Given the reported antagonism between plant immunity and growth, we suggest that these altered patterns of expression contribute to the greater growth of the hybrids. The altered patterns of expression in the hybrids indicate decreases to the salicylic acid (SA) biosynthesis pathway and increases in the auxin [indole-3-acetic acid (IAA)] biosynthesis pathway. SA and IAA are hormones known to control stress and defense responses as well as plant growth. We found that IAA-targeted gene activity is frequently increased in hybrids, correlating with a common heterotic phenotype of greater leaf cell numbers. Reduced SA concentration and target gene responses occur in the larger hybrids and promote increased leaf cell size. We demonstrated the importance of SA action to the hybrid phenotype by manipulating endogenous SA concentrations. Increasing SA diminished heterosis in SA-reduced hybrids, whereas decreasing SA promoted growth in some hybrids and phenocopied aspects of hybrid vigor in parental lines. Pseudomonas syringae infection of hybrids demonstrated that the reductions in basal defense gene activity in these hybrids does not necessarily compromise their ability to mount a defense response comparable to the parents.

  13. [Analysis of POU1F1 gene polymorphisms in Qinchuan cattle and Chinese Holstein cattle].

    PubMed

    Yan, Lin-Jun; Liu, Bo; Fang, Xin-Tang; Chen, Hong; Zhang, Run-Feng; Bao, Bin; Zhang, Hai-Jun

    2006-11-01

    PCR-RFLP was applied to analyze the polymorphisms of POU1F1 gene in 218 Qinchuan cattle (QQ) and Chinese Holstein cattle (HC). Results demonstrated Hinf I polymorphisms in the 451 bp PCR product in the two populations. The frequencies of alleles A/B in QQ and HC populations were 0.232/0.768 and 0.132/0.868, respectively. The frequencies of three genotypes AA, AB and BB were 0.030/0.403/0.567 and 0.007/0.251/0.742, respectively. Qinchuan cattle population was at Hardy-Weinberg equilibrium at this locus, but Chinese Holstein cattle population was not. The gene heterozygosity/effective allele gene number/Shannon information entropy/polymorphism information content of Qinchuan cattle and Chinese Holstein cattle populations were listed for 0.356/1.553/0.541/0.292 and 0.229/1.297/0.390/0.203, respectively. All indices were higher in the Qinchuan cattle population.

  14. Immunomodulation by classical conditioning in NZB/W (F1) mice: Lifespan and diurnal variation

    PubMed Central

    Miguel, Mario André Leocadio; Menna-Barreto, Luiz

    2016-01-01

    Systemic Lupus Eritematosus (SLE) is a systemic inflammatory disease often treated with the agent cyclophosphamide (CY), known by provoking important adverse reactions to the organism. Ader and Cohen have demonstrated an alternative way of administrating this agent based on pavlovian conditioning, in order to reduce the aggression caused by CY. Considering the influence of the temporal organization on learning and memory processes, the purpose of this study was to understand the temporal aspects involved in the conditioned immunomodulation. In a search for circadian modulation, we selected NZB/W (F1) female mice, a strain that spontaneously develop SLE. Divided into two major groups, the animals were submitted, in different phases of day, to a classical conditioning immunomodulation protocol, consisting in weekly parings of saccharin solution and CY injections. The success of the paradigm was evaluated by comparing lifespan among the groups. Simultaneously, it was monitored the water intake behavior, in order to correlate the stability of two rhythmic parameters, amplitude and spectral power density of the 24-h rhythm, with the progression of SLE. Our results indicate that mice could benefit from the conditioning task performed either in the light phase or in the dark phase of the LD cycle, as expressed by an increased lifespan. Concerning the rhythmic parameters, there was evidence of association between the rhythmic stability and the evolution of SLE, demonstrated by the maintenance of healthy levels of amplitude and spectral potency of the 24-h rhythm in animals exposed to the conditioning paradigm. PMID:27226820

  15. Effective Hamiltonian for non-leptonic |Delta F| = 1 decays at NNLO in QCD

    SciTech Connect

    Gorbahn, Martin; Haisch, Ulrich; /Fermilab

    2004-11-01

    The authors compute the effective hamiltonian for non-leptonic |{Delta}F| = 1 decays in the standard model including next-to-next-to-leading order QCD corrections. In particular, they present the complete three-loop anomalous dimension matrix describing the mixing of current-current and QCD penguin operators. The calculation is performed in an operator basis which allows to consistently use fully anticommuting {gamma}{sub 5} in dimensional regularization at an arbitrary number of loops. The renormalization scheme dependences and their cancellation in physical quantities is discussed in detail. Furthermore, they demonstrate how the results are transformed to a different basis of effective operators which is frequently adopted in phenomenological applications. They give all necessary two-loop constant terms which allow to obtain the three-loop anomalous dimensions and the corresponding initial conditions of the two-loop Wilson coefficients in the latter scheme. Finally, they solve the renormalization group equation and given the analytic expressions for the low-energy Wilson coefficients relevant for non-leptonic B meson decays beyond next-to-leading order in both renormalization schemes.

  16. [Field experiment of F1 generation and superior families selection of Dendrobium officinale].

    PubMed

    Zhang, Xiao-Ling; Si, Jin-Ping; Wu, Ling-Shang; Guo, Ying-Ying; Yu, Jie; Wang, Lin-Hua

    2013-11-01

    Based on randomized block design of experiment, agronomic traits and yields of 14 F1 generations of Dendrobium officinale were determined. The results showed that the differences in agronomic traits and yields among families were significant, and the hybrid vigor was obvious. Families of 6b x 2a, 9 x 66 and 78 x 69 were selected with the remarkable superiority of yields, agronomic traits and product customization. Correlation analysis between agronomic traits and yields showed that plant height, stem diameter, leaf number, blade length and blade width were all significantly correlated with biological yields and economic yields. Among which, stem diameter, leaf number and blade length were the most significant, and an optimal linear regression model could be established. When the number of shoots was fewer than 4.5, both biological yields and economic yields increased with the increasing number of shoots, but it could not much affect yields when the number of shoots was larger than 4.5. Shoots number, stem diameter and leaf index were basic stability when compared biennial traits to annual, which could be used for early selection.

  17. Metabolic Trade-offs in Yeast are Caused by F1F0-ATP synthase

    PubMed Central

    Nilsson, Avlant; Nielsen, Jens

    2016-01-01

    Intermediary metabolism provides living cells with free energy and precursor metabolites required for synthesizing proteins, lipids, RNA and other cellular constituents, and it is highly conserved among living species. Only a fraction of cellular protein can, however, be allocated to enzymes of intermediary metabolism and consequently metabolic trade-offs may take place. One such trade-off, aerobic fermentation, occurs in both yeast (the Crabtree effect) and cancer cells (the Warburg effect) and has been a scientific challenge for decades. Here we show, using flux balance analysis combined with in vitro measured enzyme specific activities, that fermentation is more catalytically efficient than respiration, i.e. it produces more ATP per protein mass. And that the switch to fermentation at high growth rates therefore is a consequence of a high ATP production rate, provided by a limited pool of enzymes. The catalytic efficiency is also higher for cells grown on glucose compared to galactose and ethanol, which may explain the observed differences in their growth rates. The enzyme F1F0-ATP synthase (Complex V) was found to have flux control over respiration in the model, and since it is evolutionary conserved, we expect the trade-off to occur in organisms from all kingdoms of life. PMID:26928598

  18. Prostaglandin E2 increases the skeletal response to mechanical loading

    NASA Technical Reports Server (NTRS)

    Tang, L. Y.; Cullen, D. M.; Yee, J. A.; Jee, W. S.; Kimmel, D. B.

    1997-01-01

    The study tested the influence of prostaglandin E2 (PGE2) on the skeletal response to increased in vivo mechanical loading through a four-point bending device. One hundred and twenty Sprague-Dawley female rats (6 months old, 354 +/- 34 g) were divided into 12 groups to accommodate all possible combinations of doses of loads (25, 30, or 35 N) and PGE2 (0, 0.1, 0.3, or 1 mg/kg). Rats received subcutaneous injections of PGE2 daily and in vivo loading of the right tibia every Monday, Wednesday, and Friday for four weeks. Histomorphometric analysis of the periosteal and endocortical surfaces following in vivo dual fluorochrome labeling was performed on both the loaded region of the right tibial diaphysis and a similar region of the left tibial diaphysis. Without PGE2, the threshold for loading to stimulate bone formation was 30 N (peak strain 1360 mu epsilon) at the periosteal surface and 25 N (peak strain 580 mu epsilon) at the endocortical surface. Without loading, the minimum dose of PGE2 to stimulate bone formation at all surfaces was 1 mg/kg/day. When 1 mg/kg/day PGE2 was combined with the minimum effective load, an additive effect of PGE2 and loading on bone formation was observed at the endocortical surface, but a synergistic effect was noted at the periosteal surface. No combined effect of ineffective doses of loading and PGE2 was found. A synergistic effect at peak strains of approximately 1625 mu epsilon on the periosteal surface could suggest either the involvement of locally produced growth factors or autoregulation of endogenous synthesis of PGE2 by exogenously administered PGE2.

  19. Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions.

    PubMed

    Pereira, Priscilla Aparecida Tartari; Bitencourt, Claudia da Silva; dos Santos, Daiane Fernanda; Nicolete, Roberto; Gelfuso, Guilherme Martins; Faccioli, Lúcia Helena

    2015-10-12

    Biodegradable lactic-co-glycolic acid (PLGA) microspheres (MS) improve the stability of biomolecules stability and allow enable their sustained release. Lipid mediators represent a strategy for improving host defense; however, most of these mediators, such as prostaglandin D2 (PGD2), have low water solubility and are unstable. The present study aimed to develop and characterize MS loaded with PGD2 (PGD2-MS) to obtain an innovative tool to activate macrophages. PGD2-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process, and the size, zeta potential, surface morphology and encapsulation efficiency were determined. It was also evaluated in vitro the phagocytic index, NF-κB activation, as well as nitric oxide and cytokine production by alveolar macrophages (AMs) in response to PGD2-MS. PGD2-MS were spherical with a diameter of 5.0±3.3 μm and regular surface, zeta potential of -13.4±5.6 mV, and 36% of encapsulation efficiency, with 16-26% release of entrapped PGD2 at 4 and 48 h, respectively. PGD2-MS were more efficiently internalized by AMs than unloaded-MS, and activated NF-κB more than free PGD2. Moreover, PGD2-MS stimulated the production of nitric oxide, TNF-α, IL-1β, and TGF-β, more than free PGD2, indicating that microencapsulation increased the activating effect of PGD2 on cells. In LPS-pre-treated AMs, PGD2-MS decreased the release of IL-6 but increased the production of nitric oxide and IL-1β. These results show that the morphological characteristics of PGD2-MS facilitated interaction with, and activation of phagocytic cells; moreover, PGD2-MS retained the biological activities of PGD2 to trigger effector mechanisms in AMs. It is suggested that PGD2-MS represent a strategy for therapeutic intervention in the lungs of immunocompromised subjects.

  20. Rabbit blastocysts accumulate (/sup 3/H)prostaglandins in vitro

    SciTech Connect

    Jones, M.A.; Harper, M.J.

    1984-08-01

    Rabbit blastocysts obtained on days 5, 6, and 6.8 of pregnancy were incubated in vitro in Tyrode's buffer with /sup 3/H-labeled prostaglandins (PGs). Accumulation of PGs was studied, using Whatman GF/F filters to separate bound and free ligands. The uptake and efflux of (/sup 3/H)PGs were studied as a function of PG type, incubation time, temperature, and effect of metabolic inhibitors as well as age and number of blastocysts. Blastocysts of the same age accumulated approximately the same amount of (/sup 3/H)PGE2 and (/sup 3/H)PGF2 alpha from their environment; however, there was no apparent saturation over a PG concentration range of 1-1000 nM. Both the uptake and efflux of PG were age dependent, with older blastocysts accumulating more PGs. Approximately 90% of the (/sup 3/H)PGs appear to be transported into the blastocoelic fluid, with little PG remaining in the blastomeres. PG accumulation was relatively insensitive to azide, ouabain, cyanide, or bromcresol green, but was affected by incubation at 0 C or the addition of indomethacin (10 micrograms/ml). No catabolism of the accumulated PGs was observed. The release of PGE2 in general did not differ from that of PGF2 alpha, except on day 6.8 of pregnancy when PGE2 was released more rapidly than on day 6. The authors conclude that rabbit blastocysts can accumulate PGs from their environment, which may imply a storage potential in the blastocyst and release before implantation.

  1. Protease-activated receptors and prostaglandins in inflammatory lung disease

    PubMed Central

    Peters, Terence; Henry, Peter J

    2009-01-01

    Protease-activated receptors (PARs) are a novel family of G protein-coupled receptors. Signalling through PARs typically involves the cleavage of an extracellular region of the receptor by endogenous or exogenous proteases, which reveals a tethered ligand sequence capable of auto-activating the receptor. A considerable body of evidence has emerged over the past 20 years supporting a prominent role for PARs in a variety of human physiological and pathophysiological processes, and thus substantial attention has been directed towards developing drug-like molecules that activate or block PARs via non-proteolytic pathways. PARs are widely expressed within the respiratory tract, and their activation appears to exert significant modulatory influences on the level of bronchomotor tone, as well as on the inflammatory processes associated with a range of respiratory tract disorders. Nevertheless, there is debate as to whether the principal response to PAR activation is an augmentation or attenuation of airways inflammation. In this context, an important action of PAR activators may be to promote the generation and release of prostanoids, such as prostglandin E2, which have well-established anti-inflammatory effects in the lung. In this review, we primarily focus on the relationship between PARs, prostaglandins and inflammatory processes in the lung, and highlight their potential role in selected respiratory tract disorders, including pulmonary fibrosis, asthma and chronic obstructive pulmonary disease. This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 PMID:19845685

  2. Modulation of prostaglandin biosynthesis in murine mammary adenocarcinoma tumor cells

    SciTech Connect

    Shalinsky, D.R.

    1988-01-01

    In efforts to exploit the differential oxygen levels within the subcompartments of solid neoplasms, this project has focused on modulating prostaglandin (PG) biosynthesis under aerobic and hypoxic conditions. Mammary adenocarcinoma tumor cells (Line 4526), either intact or sonicated, were incubated with either 2.0 uM {sup 14}C-arachidonic acid (AA) or 20.0 uM {sup 14}C-PGH{sub 2}, respectively. Following metabolism, products were extracted, separated by thin layer chromatography and analyzed by radiochromatographic scan. PGE{sub 2} was predominantly formed with minimal amounts of PGF{sub 2a} or PGD{sub 2}. Indomethacin and ibuprofen inhibited the PGE{sub 2} formation from AA with an IC{sub 50} value of 6.3 {times} 10{sup {minus}8} and 9.6 {times} 10{sup {minus}5}M, respectively. Suspended cells in glass vials were made hypoxic by flushing with N{sub 2} for varying time intervals to study AA metabolism. A time-dependent inhibition of PG biosynthesis was observed under hypoxia, and by 30 min, the PGE{sub 2} synthesis was reduced by 50% which was further inhibited by indomethacin. Misonidazole, a 2-nitroimidazole analogue, partially reversed the inhibition of PGE{sub 2} synthesis under hypoxia by 49% at 100 uM. However, misonidazole did not affect PG biosynthesis under aerobic conditions. The stimulation of PGE{sub 2} biosynthesis by misonidazole under hypoxia was blocked by indomethacin, suggesting that misonidazole can not act independently of the cyclooxygenase.

  3. Immunolocalization of a microsomal prostaglandin E synthase in rabbit kidney.

    PubMed

    Fuson, Amanda L; Komlosi, Peter; Unlap, Tino M; Bell, P Darwin; Peti-Peterdi, János

    2003-09-01

    PGE2, the major cyclooxygenase (COX) metabolite of arachidonic acid, is an important paracrine regulator of numerous tubular and vascular functions in the kidney. To date, COX activity has been considered the key step in prostaglandin synthesis and is well characterized. However, much less is known about the recently cloned microsomal PGE2 synthase (mPGES), the terminal enzyme of PGE2 synthesis, which converts COX-derived PGH2 to the biologically important PGE2. Present studies provide the detailed localization of mPGES protein in the rabbit kidney using immunohistochemistry. In the cortex, strong mPGES labeling was found in the macula densa (MD) and principal cells of the connecting segment and cortical collecting tubule but not in intercalated cells. The medulla was abundant in mPGES-positive structures, with heavy labeling in the collecting duct system. In descending thin limbs and renal medullary interstitial cells, mPGES expression was less intense, and it was below the limits of detection in the vasa recta. Expression of MD mPGES, similarly to COX-2, was greatly increased in response to low-salt diet and angiotensin I-converting enzyme inhibition by captopril. These findings suggest autocrine regulation of renal salt and water transport by PGE2 in descending thin limb and collecting tubule and a paracrine effect of PGE2 on the glomerular and medullary vasculature. Similar to other organs, mPGES in the kidney is an inducible enzyme and may be similarly regulated and acts in concert with COX-2.

  4. Interleukin-2 deficit in hemodialysis patients. Role of prostaglandins.

    PubMed

    Glez-Gutiérrez, M; de Francisco, A L; Sanz de Castro, S; Ruiz, J C; Prieto, M; García Fuentes, M; Arias, M

    1992-01-01

    Uremic patients suffer from various immunological alterations, whose pathogenesis is still unknown. Here, we studied 37 hemodialysis patients in order to investigate the role of prostaglandins (PGs) in uremic immunological deficiency, specifically in relation to interleukin-2 (IL-2) synthesis. We confirmed previous published data on deficient response to PHA in chronic renal failure patients (cpm, mean +/- SEM: 15,400 +/- 2,100 in uremics vs. 29,500 +/- 3,380 in controls, p < 0.04) and established a correlation between this deficiency and diminished IL-2 synthesis (r = 0.619, p < 0.05). The direct measurement of PGs in lymphocyte cultures showed greatly increased concentrations in the presence of uremic serum (US). We found that PGs synthesis can be inhibited by up to 80% if cultures are supplemented with indomethacin (IND--a cyclooxigenase inhibitor) or by removal of monocytes (producers of PGs). Both methods situated the uremic proliferative response within the normal range in cultures with FCS, and close to the normal range in cultures with US. We observed a deficit of IL-2 in hemodialysis patients (means +/- SD: 8,940 +/- 6,420 in uremics vs. 16,900 +/- 3,890 in controls). Addition of exogenous IL-2 normalized lymphocyte response even in US cultures, with no additive effect between PGs inhibition and exogenous IL-2 except in US cultures. It is suggested that IL-2 deficit of uremics depends, at least in part, on an increase in PGs synthesis induced by US.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Inheritance of steroid-independent male sexual behavior in male offspring of B6D2F1 mice.

    PubMed

    McInnis, Christine M; Bonthuis, Paul J; Rissman, Emilie F; Park, Jin Ho

    2016-04-01

    The importance of gonadal steroids in modulating male sexual behavior is well established. Individual differences in male sexual behavior, independent of gonadal steroids, are prevalent across a wide range of species, including man. However, the genetic mechanisms underlying steroid-independent male sexual behavior are poorly understood. A high proportion of B6D2F1 hybrid male mice demonstrates steroid-independent male sexual behavior (identified as "maters"), providing a mouse model that opens up avenues of investigation into the mechanisms regulating male sexual behavior in the absence of gonadal hormones. Recent studies have revealed several proteins that play a significant factor in regulating steroid-independent male sexual behavior in B6D2F1 male mice, including amyloid precursor protein (APP), tau, and synaptophysin. The specific goals of our study were to determine whether steroid-independent male sexual behavior was a heritable trait by determining if it was dependent upon the behavioral phenotype of the B6D2F1 sire, and whether the differential expression of APP, tau, and synaptophysin in the medial preoptic area found in the B6D2F1 sires that did and did not mate after gonadectomy was similar to those found in their male offspring. After adult B6D2F1 male mice were bred with C57BL/6J female mice, they and their male offspring (BXB1) were orchidectomized and identified as either maters or "non-maters". A significant proportion of the BXB1 maters was sired only from B6D2F1 maters, indicating that the steroid-independent male sexual behavior behavioral phenotype of the B6D2F1 hybrid males, when crossed with C57BL/6J female mice, is inherited by their male offspring. Additionally, APP, tau, and synaptophysin were elevated in in the medial preoptic area in both the B6D2F1 and BXB1 maters relative to the B6D2F1 and BXB1 non-maters, respectively, suggesting a potential genetic mechanism for the inheritance of steroid-independent male sexual behavior.

  6. Prostaglandin E and F2 alpha receptors in human myometrium during the menstrual cycle and in pregnancy and labor

    SciTech Connect

    Giannopoulos, G.; Jackson, K.; Kredentser, J.; Tulchinsky, D.

    1985-12-15

    The binding of prostaglandins E1 and F2 alpha has been studied in the human myometrium and cervix during the menstrual cycle and in the myometrium of pregnant patients at term before and during labor. Tritium-labeled prostaglandin E1 and F2 alpha binding was saturable and reversible. Scatchard analysis of tritium-labeled prostaglandin E1 binding was linear, which suggests a single class of high-affinity binding sites with an estimated apparent equilibrium dissociation constant of 2.5 to 5.4 nmol/L and inhibitor affinities of 0.9, 273, 273, and 217 nmol/L for prostaglandins E2, A1, B1, and F2 alpha, respectively. Scatchard analysis of tritium-labeled prostaglandin F2 alpha, binding was also linear, but the affinity of these binding sites was much lower, with an average dissociation constant of 50 nmol/L and inhibitor affinities of 1.6, 2.2, and 11.2 nmol/L for prostaglandins E1, E2, and A1, respectively. In nonpregnant patients, the concentrations and affinities of tritium-labeled prostaglandin E1 binding sites were similar in the myometrium during the proliferative and secretory phases of the menstrual cycle, but the concentration of these sites was much lower in the cervix. The concentration of the tritium-labeled prostaglandin E1 binding sites was significantly lower in the myometrium of pregnant patients at term than in the myometrium of nonpregnant patients. The concentrations and affinities of tritium-labeled prostaglandin E1 binding sites were not significantly different in the upper and lower myometrium of pregnant patients at term or in the myometrium of such patients before and during labor. The concentrations of the tritium-labeled prostaglandin F2 alpha binding sites during the menstrual cycle and in pregnancy at term were similar to those of tritium-labeled prostaglandin E1 binding sites.

  7. Fish oil induced hyperlipidemia and oxidative stress in BioF1B hamsters is attenuated by elderberry extract.

    PubMed

    Dubey, Pratibha; Jayasooriya, Anura P; Cheema, Sukhinder K

    2012-06-01

    We have previously reported fish oil induced hyperlipidemia in BioF1B hamsters compared with Golden Syrian (GS) hamsters. Elderberry (Sambucus nigra L.) extract is abundant in anthocyanins and is believed to exert cardioprotective effects primarily by virtue of its hypolipidemic and antioxidant potential. In the current study, high-fat fish oil feeding increased oxidative stress in BioF1B hamsters compared with GS hamsters; this increase was associated with increased levels of omega-3 polyunsaturated fatty acids in plasma and liver. We then investigated whether cosupplementation with anthocyanin-rich elderberry extract would reverse fish oil induced hyperlipidemia and reduce lipid peroxidation in BioF1B hamsters. Plasma and hepatic lipids decreased significantly when hamsters were fed diets containing elderberry extract along with fish oil. Both plasma and liver thiobarbituric acid reactive substances showed significant reductions upon cosupplementation with elderberry extract in fish oil fed BioF1B hamsters. Our findings demonstrate that cosupplementation with elderberry extract reverses hyperlipidemia and lipid peroxidation observed with dietary fish oil alone in BioF1B hamsters.

  8. An Escherichia coli system for assay of F1p site-specific recombination on substrate plasmids.

    PubMed

    Snaith, M R; Kilby, N J; Murray, J A

    1996-11-21

    We have developed an Escherichia coli system for testing the behaviour of plasmids carrying target sites for the F1p site-specific recomb