Preorchiectomy Leydig Cell Dysfunction in Patients With Testicular Cancer.

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Bandak, Mikkel; Jørgensen, Niels; Juul, Anders; Lauritsen, Jakob; Gundgaard Kier, Maria Gry; Mortensen, Mette Saksø; Daugaard, Gedske

2017-02-01

Little is known about preorchiectomy Leydig cell function in patients with testicular germ cell cancer (TGCC). The aim was to estimate the prevalence of preorchiectomy Leydig cell dysfunction and evaluate factors associated with this condition in a cohort of patients with TGCC. We evaluated luteinizing hormone (LH), total testosterone (TT), calculated free T (cFT), estradiol, and sex hormone-binding globulin (SHBG) preorchiectomy in 561 patients with TGCC and compared with 561 healthy controls. We calculated TT/LH and cFT/LH ratios and constructed bivariate charts of TT/LH and cFT/LH from the controls. Logistic regression analysis with an abnormal cFT/LH ratio as outcome and clinical stage, tumor size, age, histology, presence of contralateral germ cell neoplasia in situ (GCNIS), and bilateral tumors as covariates was performed. In patients who were negative for human chorionic gonadotropin (hCG) (n = 374), TT (P = .004), cFT (P < .001), TT/LH ratio (P = .003), and cFT/LH ratio (P = .002) were lower than in controls. A total of 95 (25%) and 91 (24%) of hCG-negative patients had abnormal values when using combined evaluation of TT/LH and cFT/LH, respectively. Increasing tumor size, contralateral GCNIS, and increasing age were associated with Leydig cell dysfunction. In patients positive for hCG (n = 187), all reproductive hormones except SHBG were different from controls (P < .001). Patients with TGCC are at increased risk of Leydig cell dysfunction before orchiectomy. Contralateral GCNIS, increasing age, and increasing tumor size are associated with Leydig cell dysfunction. We hypothesize that patients with preexisting Leydig cell dysfunction are at increased risk of testosterone deficiency following treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Leydig cell dysfunction, systemic inflammation and metabolic syndrome in long-term testicular cancer survivors.

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Bandak, M; Jørgensen, N; Juul, A; Lauritsen, J; Oturai, P S; Mortensen, J; Hojman, P; Helge, J W; Daugaard, G

2017-10-01

Twenty to thirty percent of testicular cancer (TC) survivors have elevated serum levels of luteinising hormone (LH) with or without corresponding low testosterone levels (Leydig cell dysfunction) during clinical follow-up for TC. However, it remains to be clarified if this subgroup of TC survivors has an increased long-term risk of systemic inflammation and metabolic syndrome (MetS) when compared with TC survivors with normal Leydig cell function during follow-up. TC survivors with Leydig cell dysfunction and a control group of TC survivors with normal Leydig cell function during follow-up were eligible for participation in the study. Markers of systemic inflammation and prevalence of MetS were compared between TC survivors with Leydig cell dysfunction and the control group. Of 158 included TC survivors, 28 (18%) had uncompensated Leydig cell dysfunction, 59 (37%) had compensated Leydig cell dysfunction and 71 (45%) had normal Leydig cell function during follow-up. MetS and markers of systemic inflammation were evaluated at a median follow-up of 9.7 years (interquartile range 4.1-17.1) after TC treatment. The prevalence of MetS was significantly lower among patients with compensated Leydig cell dysfunction during follow-up (12% versus 27%, p = 0.04), whereas there was no difference between TC survivors with uncompensated Leydig cell dysfunction and controls (33% versus 27%, p = 0.5). Apart from high-sensitivity C-reactive protein which was higher in TC survivors with uncompensated Leydig cell dysfunction during follow-up, there was no evidence of increased systemic inflammation in patients with Leydig cell dysfunction during clinical follow-up. Total testosterone at follow-up was significantly associated with MetS, whereas there was no association between LH and MetS. We did not find evidence that TC survivors with Leydig cell dysfunction during clinical follow-up had increased long-term risk of MetS. Total testosterone at follow-up was significantly associated

Androgen-Forming Stem Leydig cells: Identification, Function and Therapeutic Potential

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Yunhui Zhang

2008-01-01

Full Text Available Leydig cells are the primary source of testosterone in the male, and differentiation of Leydig cells in the testes is one of the primary events in the development of the male body and fertility. Stem Leydig cells (SLCs exist in the testis throughout postnatal life, but a lack of cell surface markers previously hindered attempts to obtain purified SLC fractions. Once isolated, the properties of SLCs provide interesting clues for the ontogeny of these cells within the embryo. Moreover, the clinical potential of SLCs might be used to reverse age-related declines in testosterone levels in aging men, and stimulate reproductive function in hypogonadal males. This review focuses on the source, identification and outlook for therapeutic applications of SLCs. Separate pools of SLCs may give rise to fetal and adult generations of Leydig cell, which may account for their observed functional differences. These differences should in turn be taken into account when assessing the consequences of environmental pollutants such as the phthalate ester, diethylhexylphthalate (DEHP.

TGF-β1 regulation of estrogen production in mature rat Leydig cells.

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Man-Li Liu

Full Text Available BACKGROUND: Besides androgens, estrogens produced in Leydig cells are also crucial for mammalian germ cell differentiation. Transforming growth factor-β1 (TGF-β1 is now known to have multiple effects on regulation of Leydig cell function. The objective of the present study is to determine whether TGF-β1 regulates estradiol (E2 synthesis in adult rat Leydig cells and then to assess the impact of TGF-β1 on Cx43-based gap junctional intercellular communication (GJIC between Leydig cells. METHODOLOGY/PRINCIPAL FINDINGS: Primary cultured Leydig cells were incubated in the presence of recombinant TGF-β1 and the production of E2 as well as testosterone (T were measured by RIA. The activity of P450arom was addressed by the tritiated water release assay and the expression of Cyp19 gene was evaluated by Western blotting and real time RT-PCR. The expression of Cx43 and GJIC were investigated with immunofluorescence and fluorescence recovery after photo-bleaching (FRAP, respectively. Results from this study show that TGF-β1 down-regulates the level of E2 secretion and the activity of P450arom in a dose-dependent manner in adult Leydig cells. In addition, the expression of Cx43 and GJIC was closely related to the regulation of E2 and TGF-β1, and E2 treatment in turn restored the inhibition of TGF-β1 on GJIC. CONCLUSIONS: Our results indicate, for the first time in adult rat Leydig cells, that TGF-β1 suppresses P450arom activity, as well as the expression of the Cyp19 gene, and that depression of E2 secretion leads to down-regulation of Cx43-based GJIC between Leydig cells.

Cellular Microenvironment Dictates Androgen Production by Murine Fetal Leydig Cells in Primary Culture1

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Carney, Colleen M.; Muszynski, Jessica L.; Strotman, Lindsay N.; Lewis, Samantha R.; O'Connell, Rachel L.; Beebe, David J.; Theberge, Ashleigh B.; Jorgensen, Joan S.

2014-01-01

ABSTRACT Despite the fact that fetal Leydig cells are recognized as the primary source of androgens in male embryos, the mechanisms by which steroidogenesis occurs within the developing testis remain unclear. A genetic approach was used to visualize and isolate fetal Leydig cells from remaining cells within developing mouse testes. Cyp11a1-Cre mice were bred to mT/mG dual reporter mice to target membrane-tagged enhanced green fluorescent protein (GFP) within steroidogenic cells, whereas other cells expressed membrane-tagged tandem-dimer tomato red. Fetal Leydig cell identity was validated using double-labeled immunohistochemistry against GFP and the steroidogenic enzyme 3beta-HSD, and cells were successfully isolated as indicated by qPCR results from sorted cell populations. Because fetal Leydig cells must collaborate with neighboring cells to synthesize testosterone, we hypothesized that the fetal Leydig cell microenvironment defined their capacity for androgen production. Microfluidic culture devices were used to measure androstenedione and testosterone production of fetal Leydig cells that were cultured in cell-cell contact within a mixed population, were isolated but remained in medium contact via compartmentalized co-culture with other testicular cells, or were isolated and cultured alone. Results showed that fetal Leydig cells maintained their identity and steroidogenic activity for 3–5 days in primary culture. Microenvironment dictated proficiency of testosterone production. As expected, fetal Leydig cells produced androstenedione but not testosterone when cultured in isolation. More testosterone accumulated in medium from mixed cultures than from compartmentalized co-cultures initially; however, co-cultures maintained testosterone synthesis for a longer time. These data suggest that a combination of cell-cell contact and soluble factors constitute the ideal microenvironment for fetal Leydig cell activity in primary culture. PMID:25143354

Essential roles of COUP-TFII in Leydig cell differentiation and male fertility.

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Jun Qin

2008-09-01

Full Text Available Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII; also known as NR2F2, is an orphan nuclear receptor of the steroid/thyroid hormone receptor superfamily. COUP-TFII-null mice die during the early embryonic development due to angiogenesis and cardiovascular defects. To circumvent the early embryonic lethality and investigate the physiological function of COUP-TFII, we knocked out COUP-TFII gene in a time-specific manner by using a tamoxifen inducible Cre recombinase. The ablation of COUP-TFII during pre-pubertal stages of male development results in infertility, hypogonadism and spermatogenetic arrest. Homozygous adult male mutants are defective in testosterone synthesis, and administration of testosterone could largely rescue the mutant defects. Notably, the rescued results also provide the evidence that the major function of adult Leydig cell is to synthesize testosterone. Further phenotypic analysis reveals that Leydig cell differentiation is arrested at the progenitor cell stage in the testes of null mice. The failure of testosterone to resumption of Leydig cell maturation in the null mice indicates that COUP-TFII itself is essential for this process. In addition, we identify that COUP-TFII plays roles in progenitor Leydig cell formation and early testis organogenesis, as demonstrated by the ablation of COUP-TFII at E18.5. On the other hand, when COUP-TFII is deleted in the adult stage after Leydig cells are well differentiated, there are no obvious defects in reproduction and Leydig cell function. Taken together, these results indicate that COUP-TFII plays a major role in differentiation, but not the maintenance of Leydig cells.

[Effects of tributyltin chloride (TBT) and triphenyltin chloride (TPT) on rat testicular Leydig cells].

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Wang, Bao-an; Li, Ming; Mu, Yi-ming; Lu, Zhao-hui; Li, Jiang-yuan

2006-06-01

To investigate the effects of tributyltin chloride (TBT) and triphenyltin chloride (TPT) on rat testicular Leydig cells. The rat Leydig cells (LC-540) were incubated with 0 to 80 nmol/L TBT and TPT for 24 to approximately 96 h, and then the cell viability was determined by MTT. DNA fragmentation ladder formation of cell apoptosis was examined by agarose electrophoresis. Effects of chelator of intracellular Ca2+ (BAPTA) and the inhibitors of PKA, PKC and TPK on cell apoptosis induced by TBT were observed. Effects of TBT on testosterone production in primary cultured rat Leydig cells treated with or without hCG were detected. TBT and TPT suppressed Leydig cell survival in a time- and dose-dependent manner. The suppressive effects of TBT and TPT on the cell survival was caused by apoptosis which was determined by DNA ladder formation. The apoptotic effect of TBT was possibly mediated by the rise in intracellular Ca2+ because it could be blocked by BAPTA, the chelator of intracellular Ca2+; PKA, PKC and TPK inhibitors did not prevent the apoptotic effects induced by TBT. TBT markedly suppressed testosterone production of primary cultured rat Leydig cells with or without hCG stimulation. TBT and TPT induced apoptosis in rat testicular Leydig cells possibly through increasing intracellular Ca2+. TBT reduced the testosterone production of rat Leydig cells.

Endocrine Disruptors and Leydig Cell Function

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K. Svechnikov

2010-01-01

Full Text Available During the past decades, a large body of information concerning the effects of endocrine disrupting compounds (EDCs on animals and humans has been accumulated. EDCs are of synthetic or natural origin and certain groups are known to disrupt the action of androgens and to impair the development of the male reproductive tract and external genitalia. The present overview describes the effects of the different classes of EDCs, such as pesticides, phthalates, dioxins, and phytoestrogens, including newly synthesized resveratrol analogs on steroidogenesis in Leydig cells. The potential impact of these compounds on androgen production by Leydig cells during fetal development and in the adult age is discussed. In addition, the possible role of EDCs in connection with the increasing frequency of abnormalities in reproductive development in animals and humans is discussed.

Turnover time of Leydig cells and other interstitial cells in testes of adult rats

NARCIS (Netherlands)

Teerds, K. J.; de rooij, D. G.; Rommerts, F. F.; van der Tweel, I.; Wensing, C. J.

1989-01-01

The aim of this study was to investigate the turnover of Leydig cells and other interstitial cells in the adult rat testis. Normal adult rats received injections of [3H]thymidine at 9:00 and 21:00 for 2, 5, or 8 days. The percentage of labeled Leydig cells, which was initially low (0.8% +/- 0.2%),

Arginine-vasopressin stimulates the formation of phosphatidic acid in rat Leydig cells

DEFF Research Database (Denmark)

Nielsen, J.R.; Hansen, Harald S.; Jensen, B.

1987-01-01

Arginine-vasopressin (AVP) stimulated the formation of labelled phosphatidic acid (PA) in [C]arachidonic acid-prelabelled rat Leydig cells. After addition of 10 M AVP [C]arachidonoylphosphatidic acid reached a maximum within 2 min. The increase was dose-dependent (10-10 M). No change in labelling...

Preorchiectomy Leydig Cell Dysfunction in Patients With Testicular Cancer

DEFF Research Database (Denmark)

Bandak, Mikkel; Jørgensen, Niels; Juul, Anders

2017-01-01

BACKGROUND: Little is known about preorchiectomy Leydig cell function in patients with testicular germ cell cancer (TGCC). The aim was to estimate the prevalence of preorchiectomy Leydig cell dysfunction and evaluate factors associated with this condition in a cohort of patients with TGCC. PATIENTS...... AND METHODS: We evaluated luteinizing hormone (LH), total testosterone (TT), calculated free T (cFT), estradiol, and sex hormone-binding globulin (SHBG) preorchiectomy in 561 patients with TGCC and compared with 561 healthy controls. We calculated TT/LH and cFT/LH ratios and constructed bivariate charts of TT...

The pituitary-Leydig cell axis before and after orchiectomy in patients with stage I testicular cancer

DEFF Research Database (Denmark)

Bandak, Mikkel; Aksglaede, Lise; Juul, Anders

2011-01-01

This study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy.......This study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy....

Conazole fungicides inhibit Leydig cell testosterone secretion and androgen receptor activation in vitro

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Maarke J.E. Roelofs

2014-01-01

Full Text Available Conazole fungicides are widely used in agriculture despite their suspected endocrine disrupting properties. In this study, the potential (anti-androgenic effects of ten conazoles were assessed and mutually compared with existing data. Effects of cyproconazole (CYPRO, fluconazole (FLUC, flusilazole (FLUS, hexaconazole (HEXA, myconazole (MYC, penconazole (PEN, prochloraz (PRO, tebuconazole (TEBU, triadimefon (TRIA, and triticonazole (TRIT were examined using murine Leydig (MA-10 cells and human T47D-ARE cells stably transfected with an androgen responsive element and a firefly luciferase reporter gene. Six conazoles caused a decrease in basal testosterone (T secretion by MA-10 cells varying from 61% up to 12% compared to vehicle-treated control. T secretion was concentration-dependently inhibited after exposure of MA-10 cells to several concentrations of FLUS (IC50 = 12.4 μM or TEBU (IC50 = 2.4 μM in combination with LH. The expression of steroidogenic and cholesterol biosynthesis genes was not changed by conazole exposure. Also, there were no changes in reactive oxygen species (ROS formation that could explain the altered T secretion after exposure to conazoles. Nine conazoles decreased T-induced AR activation (IC50s ranging from 10.7 to 71.5 μM and effect potencies (REPs were calculated relative to the known AR antagonist flutamide (FLUT. FLUC had no effect on AR activation by T. FLUS was the most potent (REP = 3.61 and MYC the least potent (REP = 0.03 AR antagonist. All other conazoles had a comparable REP from 0.12 to 0.38. Our results show distinct in vitro anti-androgenic effects of several conazole fungicides arising from two mechanisms: inhibition of T secretion and AR antagonism, suggesting potential testicular toxic effects. These effects warrant further mechanistic investigation and clearly show the need for accurate exposure data in order to perform proper (human risk assessment of this class of compounds.

Leydig cell dysfunction, systemic inflammation and metabolic syndrome in long-term testicular cancer survivors

DEFF Research Database (Denmark)

Bandak, M; Jørgensen, N; Juul, A

2017-01-01

of TC survivors has an increased long-term risk of systemic inflammation and metabolic syndrome (MetS) when compared with TC survivors with normal Leydig cell function during follow-up. PATIENTS AND METHODS: TC survivors with Leydig cell dysfunction and a control group of TC survivors with normal Leydig...

Imatinib mesylate inhibits Leydig cell tumor growth: evidence for in vitro and in vivo activity.

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Basciani, Sabrina; Brama, Marina; Mariani, Stefania; De Luca, Gabriele; Arizzi, Mario; Vesci, Loredana; Pisano, Claudio; Dolci, Susanna; Spera, Giovanni; Gnessi, Lucio

2005-03-01

Leydig cell tumors are usually benign tumors of the male gonad. However, if the tumor is malignant, no effective treatments are currently available. Leydig cell tumors express platelet-derived growth factor (PDGF), kit ligand and their respective receptors, PDGFR and c-kit. We therefore evaluated the effects of imatinib mesylate (imatinib), a selective inhibitor of the c-kit and PDGFR tyrosine kinases, on the growth of rodent Leydig tumor cell lines in vivo and in vitro, and examined, in human Leydig cell tumor samples, the expression of activated PDGFR and c-kit and the mutations in exons of the c-kit gene commonly associated with solid tumors. Imatinib caused concentration-dependent decreases in the viability of Leydig tumor cell lines, which coincided with apoptosis and inhibition of proliferation and ligand-stimulated phosphorylation of c-kit and PDGFRs. Mice bearing s.c. allografts of a Leydig tumor cell line treated with imatinib p.o., had an almost complete inhibition of tumor growth, less tumor cell proliferation, increased apoptosis, and a lesser amount of tumor-associated mean vessel density compared with controls. No drug-resistant tumors appeared during imatinib treatment but tumors regrew after drug withdrawal. Human Leydig cell tumors showed an intense expression of the phosphorylated form of c-kit and a less intense expression of phosphorylated PDGFRs. No activating mutations in common regions of mutation of the c-kit gene were found. Our studies suggest that Leydig cell tumors might be a potential target for imatinib therapy.

Paradoxical sleep deprivation decreases serum testosterone and Leydig cells in male rats

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Fitranto Arjadi

2014-04-01

Full Text Available Background Chronic stress increases glucocorticoid levels and accelerates reduction in Leydig cells functions and numbers. Chronic stress models in the working place comprise sleep deprivation, sedentary stress, and physical stress. The aim of this study was to evaluate the effect of various work stress models, such as stress from paradoxical sleep deprivation (PSD, immobilization, and footshock, on serum testosterone levels and number of Leydig cells in male albino rats. Methods This study was of experimental randomized post-test only with control group design using 24 male Wistar albino rats (Rattus norvegicus. The sample was divided into 4 groups: K1 (control, K2 (PSD, K3 (immobilization and K4 (footshock, receiving treatment for 25 days. Measured parameters were serum testosterone level and Leydig cell number. Analysis of variance (ANOVA was used for statistical analysis, followed by post hoc LSD. Results Mean serum testosterone levels (0.07 ± 0.08 ng/mL and Leydig cell numbers (4.22 ± l0.96 were lowest in the PSD stress model. Serum testosterone levels differed significantly between controls and PSD group (p=0.014, while there was a significant difference in numbers of Leydig cells between footshock stress and PSD (p=0.011 and between the three stress groups and controls (p=0.006. Conclusion This study demonstrated that PSD, immobilization and footshock stress significantly decreased serum testosterone levels and number of Leydig cells in male albino rats (Rattus norvegicus. The mechanism by which PSD affects serum testosterone is still unclear.

Genetics Home Reference: Leydig cell hypoplasia

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... normal male sexual development before birth and during puberty. In Leydig cell hypoplasia , affected individuals with a typical male chromosomal pattern (46,XY) may have a range of genital abnormalities. Affected males may have a small penis (micropenis), the opening of the urethra on the ...

The Effects of Imatinib Mesylate on Cellular Viability, Platelet Derived Growth Factor and Stem Cell Factor in Mouse Testicular Normal Leydig Cells.

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Kheradmand, Fatemeh; Hashemnia, Seyyed Mohammad Reza; Valizadeh, Nasim; Roshan-Milani, Shiva

2016-01-01

Growth factors play an essential role in the development of tumor and normal cells like testicular leydig cells. Treatment of cancer with anti-cancer agents like imatinib mesylate may interfere with normal leydig cell activity, growth and fertility through failure in growth factors' production or their signaling pathways. The purpose of the study was to determine cellular viability and the levels of, platelet derived growth factor (PDGF) and stem cell factor (SCF) in normal mouse leydig cells exposed to imatinib, and addressing the effect of imatinib on fertility potential. The mouse TM3 leydig cells were treated with 0 (control), 2.5, 5, 10 and 20 μM imatinib for 2, 4 and 6 days. Each experiment was repeated three times (15 experiments in each day).The cellular viability and growth factors levels were assessed by MTT and ELISA methods, respectively. For statistical analysis, one-way ANOVA with Tukey's post hoc and Kruskal-Wallis test were performed. A p-value less than 0.05 was considered statistically significant. With increasing drug concentration, cellular viability decreased significantly (pcellular viability, PDGF and SCF levels. Imatinib may reduce fertility potential especially at higher concentrations in patients treated with this drug by decreasing cellular viability. The effect of imatinib on leydig cells is associated with PDGF stimulation. Of course future studies can be helpful in exploring the long term effects of this drug.

Phthalate-induced testicular dysgenesis syndrome: Leydig cell influence.

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Hu, Guo-Xin; Lian, Qing-Quan; Ge, Ren-Shan; Hardy, Dianne O; Li, Xiao-Kun

2009-04-01

Phthalates, the most abundantly produced plasticizers, leach out from polyvinyl chloride plastics and disrupt androgen action. Male rats that are exposed to phthalates in utero develop symptoms characteristic of the human condition referred to as testicular dysgenesis syndrome (TDS). Environmental influences have been suspected to contribute to the increasing incidence of TDS in humans (i.e. cryptorchidism and hypospadias in newborn boys and testicular cancer and reduced sperm quality in adult males). In this review, we discuss the recent findings that prenatal exposure to phthalates affects Leydig cell function in the postnatal testis. This review also focuses on the recent progress in our understanding of how Leydig cell factors contribute to phthalate-mediated TDS.

Effect of gonadotrophin inhibiting material isolated from human urine on action of prolactin at rat Leydig cell

Energy Technology Data Exchange (ETDEWEB)

Bagli, N P; Rajendran, K G; Shah, P N [Cancer Research Inst., Bombay (India). Div. of Endocrinology

1980-05-01

To study the effect of gonadotropin inhibiting material (GIM) on the binding of prolactin to Leydig cell receptors isolated Leydig cells were incubated with sup(125)I-prolactin. Presence of GIM in the incubation mixture did not inhibit the binding of sup(125)I-prolactin to Leydig cells whereas unlabelled prolactin significantly reduced the binding. In another experiment, testicular cells were incubated with FITC-tagged GIM. Binding of GIM to Leydig cells was seen by the presence of fluorescence on these cells. This binding could be inhibited by untagged GIM but not by prolactin. The results suggest the presence of separate receptors for GIM and prolactin on the Leydig cells and indicate that termination of pregnancy by GIM is not due to any interference with prolactin binding to its receptors.

Fine structure of the epidermal Leydig cells in the axolotl Ambystoma mexicanum in relation to their function.

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Jarial, M S

1989-01-01

The fine structure of the Leydig cells in the epidermis of the strictly aquatic adult axolotl Ambystoma mexicanum resembles that of similar cells in larval salamanders. The major finding of this study is that the mucous secretion of the Leydig cells is released into the intercellular spaces from which it is discharged through pores onto the surface of the epidermis where it forms a mucous layer to protect the skin. Images Figs. 1-2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Figs. 11-13 PMID:2630544

Arginine vasopressin stimulates phosphoinositide turnover in an enriched rat Leydig cell preparation

DEFF Research Database (Denmark)

Nielsen, J.R.; Hansen, Harald S.; Jensen, B.

1989-01-01

An enriched rat Leydig cell preparation was preincubated with [C]arachidonic acid. Stimulation of the cells with arginine vasopressin (AVP) (1 µM) for 2 min caused a significant increase in labelled phosphatidic acid and a significant fall in radioactivity in phosphatidylinositol and phosphatidyl......An enriched rat Leydig cell preparation was preincubated with [C]arachidonic acid. Stimulation of the cells with arginine vasopressin (AVP) (1 µM) for 2 min caused a significant increase in labelled phosphatidic acid and a significant fall in radioactivity in phosphatidylinositol...

Nicotine affects rat Leydig cell function in vivo and vitro via down-regulating some key steroidogenic enzyme expressions.

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Guo, Xiaoling; Wang, Huang; Wu, Xiaolong; Chen, Xianwu; Chen, Yong; Guo, Jingjing; Li, Xiaoheng; Lian, Qingquan; Ge, Ren-Shan

2017-12-01

Nicotine is consumed largely as a component of cigarettes and has a potential effect on pubertal development of Leydig cells in males. To investigate its effects, 49-day-old male Sprague Dawley rats received intraperitoneal injections of nicotine (0.5 or 1 mg/kg/day) for 2 weeks and immature Leydig cells were isolated from the testes of 35-day-old rats and treated with nicotine (0.05-50 μM). Serum hormones, Leydig cell number and related gene expression levels after in vivo treatment were determined and medium androgen levels were measured and cell cycle, apoptosis, mitochondrial membrane potential (△Ψm), and reactive oxygen species (ROS) of Leydig cells after in vitro treatment were measured. In vivo exposure to nicotine lowered serum luteinizing hormone, follicle stimulating hormone, and testosterone levels and reduced Leydig cell number and gene expression levels. Nicotine in vitro inhibited androgen production in Leydig cells by downregulating the expression levels of P450 cholesterol side cleavage enzyme, 3β-hydroxysteroid dehydrogenase 1, and steroidogenic factor 1 at different concentration ranges. In conclusion, nicotine disrupts Leydig cell steroidogenesis during puberty possibly via down-regulating some key steroidogenic enzyme expressions. Copyright © 2017. Published by Elsevier Ltd.

RODENT LEYDIG CELL TUMORIGENESIS: A REVIEW OF THE PHYSIOLOGY, PATHOLOGY, MECHANISMS, AND RELEVANCE TO HUMANS

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Leydig cells (LCs) are the cells of the testis that have as their primary function the production of testosterone. LCs are a common target of compounds tested in rodent carcinogenicity bioassays. The number of reviews on Leydig cell tumors (LCTs) has increased in recent years bec...

Circadian rhythm of the Leydig cells endocrine function is attenuated during aging.

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Baburski, Aleksandar Z; Sokanovic, Srdjan J; Bjelic, Maja M; Radovic, Sava M; Andric, Silvana A; Kostic, Tatjana S

2016-01-01

Although age-related hypofunction of Leydig cells is well illustrated across species, its circadian nature has not been analyzed. Here we describe changes in circadian behavior in Leydig cells isolated from adult (3-month) and aged (18- and 24-month) rats. The results showed reduced circadian pattern of testosterone secretion in both groups of aged rats despite unchanged LH circadian secretion. Although arrhythmic, the expression of Insl3, another secretory product of Leydig cells, was decreased in both groups. Intracellular cAMP and most important steroidogenic genes (Star, Cyp11a1 and Cyp17a1), together with positive steroidogenic regulator (Nur77), showed preserved circadian rhythm in aging although rhythm robustness and expression level were attenuated in both aged groups. Aging compromised cholesterol mobilization and uptake by Leydig cells: the oscillatory transcription pattern of genes encoding HDL-receptor (Scarb1), hormone sensitive lipase (Lipe, enzyme that converts cholesterol esters from lipid droplets into free cholesterol) and protein responsible for forming the cholesterol esters (Soat2) were flattened in 24-month group. The majority of examined clock genes displayed circadian behavior in expression but only a few of them (Bmal1, Per1, Per2, Per3 and Rev-Erba) were reduced in 24-month-old group. Furthermore, aging reduced oscillatory expression pattern of Sirt1 and Nampt, genes encoding key enzymes that connect cellular metabolism and circadian network. Altogether circadian amplitude of Leydig cell's endocrine function decreased during aging. The results suggest that clock genes are more resistant to aging than genes involved in steroidogenesis supporting the hypothesis about peripheral clock involvement in rhythm maintenance during aging. Copyright © 2015 Elsevier Inc. All rights reserved.

Specific dose-dependent effects of ethane 1,2-dimethanesulfonate in rat and mouse Leydig cells and non-steroidogenic cells on programmed cell death

NARCIS (Netherlands)

F.F.G. Rommerts (Focko); L. Kuhne; W.A. van Cappellen (Gert); D.M. Stocco; S.R. King (Steven); A. Jankowska

2004-01-01

textabstractThe mechanism by which ethane 1,2-dimethanesulfonate (EDS) selectively kills Leydig cells is poorly understood. To characterize further the cell-specific actions of EDS, we studied biochemical and morphological changes during apoptosis in different Leydig cell and

Modulation of mouse Leydig cell steroidogenesis through a specific arginine-vasopressin receptor

International Nuclear Information System (INIS)

Tahri-Joutei, A.; Pointis, G.

1988-01-01

Characterization of specific vasopressin binding sites was investigated in purified mouse Leydig cells using tritiated arginine-vasopressin. Binding of radioligand was saturable, time- and temperature-dependent and reversible. ( 3 H)-AVP was found to bind to a single class of sites with high affinity and low capacity. Binding displacements with specific selection analogs of AVP indicated the presence of V 1 subtype receptors on Leydig cells. The ability of AVP to displace ( 3 H)-AVP binding was greater than LVP and oxytocin. The unrelated peptides, somatostatin and substance P, were less potent, while neurotensin and LHRH did not displace ( 3 H)-AVP binding. The time-course effects of AVP-pretreatment on basal and hCG-stimulated testosterone and cAMP accumulations were studied in primary culture of Leydig cells. Basal testosterone accumulation was significantly increased by a 24 h AVP-pretreatment of Leydig cells. This effect was potentiated by the phosphodiesterase inhibitor (MIX) and was concomitantly accompanied by a slight but significant increase in cAMP accumulation. AVP-pretreatment of the cells for 72 h had no effect on basal testosterone accumulation, but exerted a marked inhibitory effect on the hCG-stimulated testosterone accumulation. This reduction of testosterone accumulation occurred even in the presence of MIX and was not accompanied by any significant change of cAMP levels

Fluoride-Induced Autophagy via the Regulation of Phosphorylation of Mammalian Targets of Rapamycin in Mice Leydig Cells.

Science.gov (United States)

Zhang, Jianhai; Zhu, Yuchen; Shi, Yan; Han, Yongli; Liang, Chen; Feng, Zhiyuan; Zheng, Heping; Eng, Michelle; Wang, Jundong

2017-10-11

Fluoride is known to impair testicular function and decrease testosterone levels, yet the underlying mechanisms remain inconclusive. The objective of this study is to investigate the roles of autophagy in fluoride-induced male reproductive toxicity using both in vivo and in vitro Leydig cell models. Using transmission electron microscopy and monodansylcadaverine staining, we observed increasing numbers of autophagosomes in testicular tissue, especially in Leydig cells of fluoride-exposed mice. Further study revealed that fluoride increased the levels of mRNA and protein expression of autophagy markers LC3, Beclin1, and Atg 5 in primary Leydig cells. Furthermore, fluoride inhibited the phosphorylation of mammalian targets of rapamycin and 4EBP1, which in turn resulted in a decrease in the levels of AKT and PI3K mRNA expression, as well as an elevation of the level of AMPK expression in both testes and primary Leydig cells. Additionally, fluoride exposure significantly changed the mRNA expression of the PDK1, TSC, and Atg13 regulator genes in primary Leydig cells but not in testicular cells. Taken together, our findings highlight the roles of autophagy in fluoride-induced testicular and Leydig cell damage and contribute to the elucidation of the underlying mechanisms of fluoride-induced male reproductive toxicity.

Compensated reduction in Leydig cell function is associated with lower semen quality variables

DEFF Research Database (Denmark)

Jørgensen, N.; Joensen, U. N.; Toppari, J.

2016-01-01

STUDY QUESTION: Is the Leydig cell function of young European men associated with semen quality? SUMMARY ANSWER: Compensated reduction in Leydig cell function, defined as increased LH concentration combined with adequate testosterone production is associated with lower semen quality. WHAT...... IS ALREADY KNOWN: Semen quality of young European men shows a heterogeneous pattern. Many have sperm counts below and in the lower WHO reference where there nevertheless is a significant risk of subfecundity. Little is known about differences in Leydig cell function between men with semen quality below......, Lithuania, and Spain. The men originated from the general populations, all were young, almost all were unaware of their fecundity and each provided a semen and blood sample. Associations between semen parameters and serum levels of testosterone and luteinising hormone (LH), calculated free testosterone...

Bilateral sertoli-leydig cell tumor of the ovary: A rare case report

OpenAIRE

Alam Kiran; Maheshwari Veena; Rashid Seema; Bhargava Shruti

2009-01-01

Sertoli leydig cell tumors also known as arrhenoblastoma, are a rare member of the sex cord-stromal tumor group of ovarian and testicular cancers, comprising less than 1% of all ovarian tumors, which occur in young adults and are almost always unilateral. We hereby report a case of a 17-year-old female presenting with a short history of irregular menses and an abdominal lump, which was histologically proven to be a bilateral sertoli leydig cell tumor of the ovary, an exceptionally rare...

RITA--Registry of Industrial Toxicology Animal data: the application of historical control data for Leydig cell tumors in rats.

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Nolte, Thomas; Rittinghausen, Susanne; Kellner, Rupert; Karbe, Eberhard; Kittel, Birgit; Rinke, Matthias; Deschl, Ulrich

2011-11-01

Historical data for Leydig cell tumors from untreated or vehicle treated rats from carcinogenicity studies collected in the RITA database are presented. Examples are given for analyses of these data for dependency on variables considered to be of possible influence on the spontaneous incidence of Leydig cell tumors. In the 7453 male rats available for analysis, only one case of a Leydig cell carcinoma was identified. The incidence of Leydig cell adenomas differed markedly between strains. High incidences of close to 100% have been found in F344 rats, while the mean incidence was 4.2% in Sprague-Dawley rats and 13.7% in Wistar rats. Incidences in Wistar rats were highly variable, primarily caused by different sources of animals. Mean incidences per breeder varied from 2.8 to 39.9%. Analyses for the dependency on further parameters have been performed in Wistar rats. In breeders G and I, the Leydig cell tumor incidence decreased over the observation period and with increasing mean terminal body weight. The incidence of Leydig cell tumors increased with mean age at necropsy and was higher in studies with dietary admixture compared to gavage studies. These parameters had no effect on Leydig cell tumor incidence in breeders A and B. Animals from almost all breeders had a considerably higher mean age at necropsy when bearing a Leydig cell adenoma than animals without a Leydig cell adenoma. Studies with longitudinal trimming of the testes had a higher incidence than studies with transverse trimming. The observed dependencies and breeder differences are discussed and explanations are given. Consequences for the use of historical control data are outlined. With the retrospective analyses presented here we were able to confirm the published features of Leydig cell adenomas and carcinomas. This indicates that the RITA database is a valuable tool for analyses of tumors for their biological features. Furthermore, it demonstrates that the RITA database is highly beneficial for

Effects of polybrominated diphenyl ethers on steroidogenesis in rat Leydig cells.

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Wang, Kai-Lee; Hsia, Shih-Min; Mao, I-Fang; Chen, Mei-Lien; Wang, Shyi-Wu; Wang, Paulus S

2011-08-01

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants that have been defined as major environmental pollutants. While previous studies have found that PBDEs may enhance the levels of sex-steroid hormones, their effects on testosterone secretion from rat Leydig cells are unclear. This study investigated the effects and mechanisms of PBDE-710, a mixture of tetra- and penta-PBDEs, on testosterone biosynthesis in rat Leydig cells. Leydig cells from adult male rats were challenged with different concentrations of PBDE-710 (0.5-15 ng/ml) to evaluate the effects on testosterone steroidogenesis. Concentrations of testosterone and of cAMP and pregnenolone in medium were measured by radioimmunoassay (RIA) and by enzyme-linked immunosorbent assay, respectively. Nuclear translocation of protein kinase A α (PKAα) was determined by immunofluorence assay and western blot assay, and the mRNA expression of steroidogenic acute regulatory protein (StAR) was analyzed by quantitative real-time polymerase chain reaction. In this in vitro study, PBDE-710 (5 or 15 ng/ml) increased basal testosterone secretion and cAMP production by 3- and 2-fold, respectively. The stimulatory effect was abolished by adenylyl cyclase inhibitor. Enzyme activity of CYP11A1, as determined by the pregnenolone concentration, was stimulated by PBDE-710 treatment. Furthermore, nuclear translocation of PKAα was increased by 20% and StAR gene expression was elevated by 4-fold after PBDE-710 treatment. These results suggest that low concentrations of PBDE-710 could stimulate testosterone secretion by acting directly on Leydig cells to activate the cAMP pathway and increase expression of StAR.

Steroid metabolism by purified adult rat Leydig cells in primary culture

International Nuclear Information System (INIS)

Browning, J.Y.; Tcholakian, R.K.; Kessler, M.J.; Grotjan, H.E. Jr.

1982-01-01

To characterize Leydig cell steroidogensis, we examined the metabolism of [3H]pregnenolone (3 beta-hydroxy-5-pregnen-20-one) to androgens in the presence and absence of human chorionic gonadotropin (hCG) as a function of culture duration. Approximately 20-30% of the (3H)pregnenolone was converted to testosterone (17 beta-hydroxy-4-androsten-3-one) by purified Leydig cells at 0, 3 and 5 days (d) of culture. Androstenedione (4-androstene-3,17-dione) and dihydrotestosterone (17 beta-hydroxy-5 alpha-androstan-3-one) were also produced while on day 5 of culture, significant amounts of progesterone (4-pregnene-3,20-dione) were isolated. The delta 5 intermediates, 17-hydroxypregnenolone (3 beta, 17-dihydroxy-5-pregnen-20-one) and dehydroepiandrosterone (3 beta-hydroxy-5-androsten-17-one), accounted for less than 1% of substrate conversion, indicating a clear preference for Leydig cells to metabolize (3H)pregnenolone via the delta 4 pathway. On day 0 of culture, unidentified metabolites considered of predominately polar steroids while on day 5 of culture, the unidentified metabolites consisted of predominately nonpolar steroids. In the presence of hCG, (3H-pregnenolone metabolism did not differ from basal on day 0 or 3 of culture. HCG increased the conversion of pregnenolone to progesterone and 17-hydroxyprogesterone (17-hydroxy-4-pregnene-3,20-dione) on 5d. This suggests that Leydig cells cultured for 5d have decreased C17-20 desmolase activity or that hCG acutely stimulates 3 beta-hydroxysteroid dehydrogenase and delta 5-delta 5 isomerase activities

Estrogenic compounds inhibit gap junctional intercellular communication in mouse Leydig TM3 cells

International Nuclear Information System (INIS)

Iwase, Yumiko; Fukata, Hideki; Mori, Chisato

2006-01-01

Some estrogenic compounds are reported to cause testicular disorders in humans and/or experimental animals by direct action on Leydig cells. In carcinogenesis and normal development, gap junctional intercellular communication (GJIC) plays an essential role in maintaining homeostasis. In this study, we examine the effects of diethylstilbestrol (DES, a synthetic estrogen), 17β-estradiol (E 2 , a natural estrogen), and genistein (GEN, a phytoestrogen) on GJIC between mouse Leydig TM3 cells using Lucifer yellow microinjection. The three compounds tested produced GJIC inhibition in the TM3 cells after 24 h. Gradually, 10 μM DES began to inhibit GJIC for 24 h and this effect was observed until 72 h. On the other hand, both 20 μM E 2 and 25 μM GEN rapidly inhibited GJIC in 6 h and 2 h, respectively. The effects continued until 24 h, but weakened by 72 h. Furthermore, a combined effect at μM level between DES and E 2 on GJIC inhibition was observed, but not between GEN and E 2 . DES and E 2 showed GJIC inhibition at low dose levels (nearly physiological estrogen levels) after 72 h, but GEN did not. DES-induced GJIC inhibition at 10 pM and 10 μM was completely counteracted by ICI 182,780 (ICl), an estrogen receptor antagonist. On the other hand, the inhibitory effects on GJIC with E 2 (10 pM and 20 μM) and GEN (25 μM) were partially blocked by ICI or calphostin C, a protein kinase C (PKC) inhibitor, and were completely blocked by the combination of ICI and calphostin C. These results demonstrate that DES inhibits GJIC between Leydig cells via the estrogen receptor (ER), and that E 2 and GEN inhibit GJIC via ER and PKC. These estrogenic compounds may have different individual nongenotoxic mechanism including PKC pathway on testicular carcinogenesis or development

Bilateral sertoli-leydig cell tumor of the ovary: A rare case report

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Alam Kiran

2009-01-01

Full Text Available Sertoli leydig cell tumors also known as arrhenoblastoma, are a rare member of the sex cord-stromal tumor group of ovarian and testicular cancers, comprising less than 1% of all ovarian tumors, which occur in young adults and are almost always unilateral. We hereby report a case of a 17-year-old female presenting with a short history of irregular menses and an abdominal lump, which was histologically proven to be a bilateral sertoli leydig cell tumor of the ovary, an exceptionally rare entity in itself.

STEREOLOGICAL QUANTITATION OF LEYDIG AND SERTOLI CELLS IN THE TESTIS FROM YOUNG AND OLD MEN

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Peter M Petersen

2011-05-01

Full Text Available One of the newer stereological methods, the optical fractionator, was applied to the study of the effects of ageing on the human testis. The estimated total number of Sertoli and Leydig cells per testis in men younger than 30 years were 430×106 (CV = SD/mean = 0.35 and 117×106 (CV = 0.53, respectively, while in men older than 50 years the estimated total Sertoli cell number was 266×106 (CV = 0.46 and the mean Leydig cell number 83×106 (CV = 0.53. The difference between the number of Sertoli cells in men younger than 30 years compared with men older than 50 years was close to statistical significance (p = 0.052 while no differences was found in total Leydig cell number (p = 0.22.

Leydig cell damage after testicular irradiation for lymphoblastic leukemia

International Nuclear Information System (INIS)

Shalet, S.M.; Horner, A.; Ahmed, S.R.; Morris-Jones, P.H.

1985-01-01

The effect of testicular irradiation on Leydig cell function has been studied in a group of boys irradiated between 1 and 5 years earlier for a testicular relapse of acute lymphoblastic leukemia. Six of the seven boys irradiated during prepubertal life had an absent testosterone response to HCG stimulation. Two of the four boys irradiated during puberty had an appropriate basal testosterone level, but the testosterone response to HCG stimulation was subnormal in three of the four. Abnormalities in gonadotropin secretion consistent with testicular damage were noted in nine of the 11 boys. Evidence of severe Leydig cell damage was present irrespective of whether the boys were studied within 1 year or between 3 and 5 years after irradiation, suggesting that recovery is unlikely. Androgen replacement therapy has been started in four boys and will be required by the majority of the remainder to undergo normal pubertal development

The changes of stage distribution of seminiferous epithelium cycle and its correlations with Leydig cell stereological parameters in aging men.

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Huang, Rui; Zhu, Wei-Jie; Li, Jing; Gu, Yi-Qun

2014-12-01

To evaluate the changes of stage distribution of seminiferous epithelium cycle and its correlations with Leydig cell stereological parameters in aging men. Point counting method was used to analyze the stereological parameters of Leydig cells. The stage number of seminiferous epithelium cycle was calculated in the same testicular tissue samples which were used for Leydig cell stereological analysis. The aging group had shown more severe pathological changes as well as higher pathologic scores than the young group. Compared with the control group, the volume density (VV) and surface density (NA) of Leydig cells in the aging group were increased significantly. The stage number of seminiferous epithelium cycle in the aging group was decreased coincidently compared to the young group. Leydig cell Vv in the young group has a positive relationship with stages I, II, III, V and VI of seminiferous epithelium cycle, and Leydig cell NA and numerical density (NV) were positively related to stage IV. However, only the correlation between NV and stage II was found in the aging group. The stage number of seminiferous epithelium cycle was decreased in aging testes. Changes in the stage distribution in aging testes were related to the Leydig cell stereological parameters which presented as a sign of morphological changes. Copyright © 2014 Elsevier GmbH. All rights reserved.

True precocious puberty following treatment of a Leydig cell tumour: two case reports and literature review

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Alberto eVerrotti

2015-11-01

Full Text Available Leydig cell testicular tumours are a rare cause of precocious pseudopuberty in boys. Surgery is the main therapy and shows good overall prognosis. The physical signs of precocious puberty are expected to disappear shortly after surgical removal of the mass. We report two children, 7.5 and 7.7 year-old boys, who underwent testis-sparing surgery for a Leydig cell testicular tumour causing precocious pseudopuberty. During follow-up, after an immediate clinical and laboratory regression, both boys presented signs of precocious puberty and ultimately developed central precocious puberty. They were successfully treated with gonadotropin releasing hormone analogues. Only 6 other cases have been described regarding the development of central precocious puberty after successful treatment of a Leydig cell tumour causing precocious pseudo puberty. Gonadotropin-dependent precocious puberty should be considered in children treated for a Leydig cell tumour presenting persistent or recurrent physical signs of puberty activation. In such cases, therapy with gonadotropin releasing hormone analogues appears to be the most effective medical treatment.

Aging has the opposite effect on cAMP and cGMP circadian variations in rat Leydig cells.

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Baburski, Aleksandar Z; Sokanovic, Srdjan J; Andric, Silvana A; Kostic, Tatjana S

2017-05-01

The Leydig cell physiology displays a circadian rhythm driven by a complex interaction of the reproductive axis hormones and circadian system. The final output of this regulatory process is circadian pattern of steroidogenic genes expression and testosterone production. Aging gradually decreases robustness of rhythmic testosterone secretion without change in pattern of LH secretion. Here, we analyzed effect of aging on circadian variation of cAMP and cGMP signaling in Leydig cells. Results showed opposite effect of aging on cAMP and cGMP daily variation. Reduced amplitude of cAMP circadian oscillation was probably associated with changed expression of genes involved in cAMP production (increased circadian pattern of Adcy7, Adcy9, Adcy10 and decreased Adcy3); cAMP degradation (increased Pde4a, decreased Pde8b, canceled rhythm of Pde4d, completely reversed circadian pattern of Pde7b and Pde8a); and circadian expression of protein kinase A subunits (Prkac/PRKAC and Prkar2a). Aging stimulates expression of genes responsible for cGMP production (Nos2, Gucy1a3 and Gucy1b3/GUCYB3) and degradation (Pde5a, Pde6a and Pde6h) but the overall net effect is elevation of cGMP circadian oscillations in Leydig cells. In addition, the expression of cGMP-dependent kinase, Prkg1/PRKG1 is up-regulated. It seems that aging potentiate cGMP- and reduce cAMP-signaling in Leydig cells. Since both signaling pathways affect testosterone production and clockwork in the cells, further insights into these signaling pathways will help to unravel disorders linked to the circadian timing system, aging and reproduction.

HBCDD-induced sustained reduction in mitochondrial membrane potential, ATP and steroidogenesis in peripubertal rat Leydig cells

Energy Technology Data Exchange (ETDEWEB)

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

2015-01-01

Hexabromocyclododecane (HBCDD), a brominated flame retardant added to various consumer products, is a ubiquitous environmental contaminant. We have previously shown that 6-hour exposure to HBCDD disturbs basal and human chorionic gonadotropin (hCG)-induced steroidogenesis in rat Leydig cells. Reduction in mitochondrial membrane potential (ΔΨm) and cAMP production was also observed. Here, we further expanded research on the effect of HBCDD on Leydig cells by using a prolonged exposure scenario. Cells were incubated in the presence of HBCDD during 24 h and then treated with HBCDD + hCG for additional 2 h. Results showed that HBCDD caused a sustained reduction in ATP level after 24 h of exposure, which persisted after additional 2-hour treatment with HBCDD + hCG. cAMP and androgen accumulations measured after 2 h of HBCDD + hCG treatment were also inhibited. Real-time PCR analysis showed significant inhibition in the expression of genes for steroidogenic enzymes, luteinizing hormone receptor, regulatory and transport proteins, and several transcription factors under both treatment conditions. Western blot analysis revealed a decreased level of 30 kDa steroidogenic acute regulatory protein (StAR) after HBCDD + hCG treatment. In addition, HBCDD decreased the conversion of 22-OH cholesterol to pregnenolone and androstenedione to testosterone, indicating loss of the activity of cytochrome P450C11A1 (CYP11A1) and 17β-hydroxysteroid dehydrogenase (HSD17β). Cell survival was not affected, as confirmed by cytotoxicity and trypan blue tests or DNA fragmentation analysis. In summary, our data showed that HBCDD inhibits ATP supply, most likely through a decrease in ΔΨm, and targets multiple sites in the steroidogenic pathway in Leydig cells. - Highlights: • HBCDD causes a sustained reduction in ΔΨm and ATP level in Leydig cells. • Prolonged HBCDD exposure decreases hCG-supported steroidogenesis in Leydig cells. • HBCDD targets StAR, HSD17β and CYP11A1 in Leydig

HBCDD-induced sustained reduction in mitochondrial membrane potential, ATP and steroidogenesis in peripubertal rat Leydig cells

International Nuclear Information System (INIS)

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

2015-01-01

Hexabromocyclododecane (HBCDD), a brominated flame retardant added to various consumer products, is a ubiquitous environmental contaminant. We have previously shown that 6-hour exposure to HBCDD disturbs basal and human chorionic gonadotropin (hCG)-induced steroidogenesis in rat Leydig cells. Reduction in mitochondrial membrane potential (ΔΨm) and cAMP production was also observed. Here, we further expanded research on the effect of HBCDD on Leydig cells by using a prolonged exposure scenario. Cells were incubated in the presence of HBCDD during 24 h and then treated with HBCDD + hCG for additional 2 h. Results showed that HBCDD caused a sustained reduction in ATP level after 24 h of exposure, which persisted after additional 2-hour treatment with HBCDD + hCG. cAMP and androgen accumulations measured after 2 h of HBCDD + hCG treatment were also inhibited. Real-time PCR analysis showed significant inhibition in the expression of genes for steroidogenic enzymes, luteinizing hormone receptor, regulatory and transport proteins, and several transcription factors under both treatment conditions. Western blot analysis revealed a decreased level of 30 kDa steroidogenic acute regulatory protein (StAR) after HBCDD + hCG treatment. In addition, HBCDD decreased the conversion of 22-OH cholesterol to pregnenolone and androstenedione to testosterone, indicating loss of the activity of cytochrome P450C11A1 (CYP11A1) and 17β-hydroxysteroid dehydrogenase (HSD17β). Cell survival was not affected, as confirmed by cytotoxicity and trypan blue tests or DNA fragmentation analysis. In summary, our data showed that HBCDD inhibits ATP supply, most likely through a decrease in ΔΨm, and targets multiple sites in the steroidogenic pathway in Leydig cells. - Highlights: • HBCDD causes a sustained reduction in ΔΨm and ATP level in Leydig cells. • Prolonged HBCDD exposure decreases hCG-supported steroidogenesis in Leydig cells. • HBCDD targets StAR, HSD17β and CYP11A1 in Leydig

Ovarian Leydig Cell Hyperplasia: An Unusual Case of Virilization in a Postmenopausal Woman

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Jaya M. Mehta

2014-01-01

Full Text Available Objective. To report an unusual case of ovarian Leydig cell hyperplasia resulting in virilization in a postmenopausal woman. Methods. Patient’s medical history and pertinent literature were reviewed. Results. A 64-year-old woman presented with virilization with worsening hirsutism, deepening of her voice, male musculature, and male pattern alopecia. Her pertinent past medical history included type 1 diabetes, hyperlipidemia, and hypertension. Her pertinent past surgical history included hysterectomy due to fibroids. On further work-up, her serum total testosterone was 506 ng/dL (nl range: 2–45 and free testosterone was 40 pg/mL (nl range: 0.1–6.4. After ruling out adrenal causes, the patient underwent an empiric bilateral oophorectomy that showed Leydig cell hyperplasia on pathology. Six weeks postoperatively, serum testosterone was undetectable with significant clinical improvement. Conclusion. Postmenopausal hyperandrogenism can be the result of numerous etiologies ranging from normal physiologic changes to ovarian or rarely adrenal tumors. Our patient was found to have Leydig cell hyperplasia of her ovaries, a rarely reported cause of virilization.

Does signaling of estrogen-related receptors affect structure and function of bank vole Leydig cells?

Science.gov (United States)

Pawlicki, P; Milon, A; Zarzycka, M; Galas, J; Tworzydlo, W; Kaminska, A; Pardyak, L; Lesniak, K; Pacwa, A; Bilinska, B; Gorowska-Wojtowicz, E; Kotula-Balak, M

2017-06-01

To get a deeper insight into the function of estrogen-related receptors (ERRs) and dissect underlying mechanism in Leydig cells, ERRs (type α, β and γ) were blocked or activated in testes of adult bank voles (Myodes glareolus) which show seasonal changes in the intratesticular sex hormones level. Both actively reproducing animals (long day conditions; LD) and those with regression of the reproductive system (short day conditions; SD) received intraperitoneal injections of selective ERRα antagonist 3-[4-(2,4-Bis-trifluoromethylbenzyloxy)-3-methoxyphenyl]-2-cyano-N-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)acrylamide (XCT 790) or selective ERRβ/ERRγ agonist N-(4-(Diethylaminobenzylidenyl)-N'-(4-hydroxybenzoyl)-hydrazine (DY131) (50 μ/kg bw; six doses every other day). Markedly more, XCT 790 (P endogenous estrogen level in treated males. Notably, immunolocalization of ERRs and above proteins, exclusively in Leydig cells, indicated their involvement in Leydig cell function control based on interactions with endogenous estrogen level and/or estrogen signaling via ERRs. Treatment with XCT 790 or DY131 significantly decreased (P endogenous estrogen status in the testis. Further understanding of mechanism(s) by which individual types of ERRs can control Leydig cell function is relevant for predicting and preventing steroidogenic and spermatogenic disorders.

Impact of methoxyacetic acid on mouse Leydig cell gene expression

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Waxman David J

2010-06-01

Full Text Available Abstract Background Methoxyacetic acid (MAA is the active metabolite of the widely used industrial chemical ethylene glycol monomethyl ether, which is associated with various developmental and reproductive toxicities, including neural toxicity, blood and immune disorders, limb degeneration and testicular toxicity. Testicular toxicity is caused by degeneration of germ cells in association with changes in gene expression in both germ cells and Sertoli cells of the testis. This study investigates the impact of MAA on gene expression in testicular Leydig cells, which play a critical role in germ cell survival and male reproductive function. Methods Cultured mouse TM3 Leydig cells were treated with MAA for 3, 8, and 24 h and changes in gene expression were monitored by genome-wide transcriptional profiling. Results A total of 3,912 MAA-responsive genes were identified. Ingenuity Pathway analysis identified reproductive system disease, inflammatory disease and connective tissue disorder as the top biological functions affected by MAA. The MAA-responsive genes were classified into 1,366 early responders, 1,387 mid-responders, and 1,138 late responders, based on the time required for MAA to elicit a response. Analysis of enriched functional clusters for each subgroup identified 106 MAA early response genes involved in transcription regulation, including 32 genes associated with developmental processes. 60 DNA-binding proteins responded to MAA rapidly but transiently, and may contribute to the downstream effects of MAA seen for many mid and late response genes. Genes within the phosphatidylinositol/phospholipase C/calcium signaling pathway, whose activity is required for potentiation of nuclear receptor signaling by MAA, were also enriched in the set of early MAA response genes. In contrast, many of the genes responding to MAA at later time points encode membrane proteins that contribute to cell adhesion and membrane signaling. Conclusions These findings

ROS generation and MAPKs activation contribute to the Ni-induced testosterone synthesis disturbance in rat Leydig cells.

Science.gov (United States)

Han, Aijie; Zou, Lingyue; Gan, Xiaoqin; Li, Yu; Liu, Fangfang; Chang, Xuhong; Zhang, Xiaotian; Tian, Minmin; Li, Sheng; Su, Li; Sun, Yingbiao

2018-06-15

Nickel (Ni) can disorder testosterone synthesis in rat Leydig cells, whereas the mechanisms remain unclear. The aim of this study was to investigate the role of reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) in Ni-induced disturbance of testosterone synthesis in rat Leydig cells. The testosterone production and ROS levels were detected in Leydig cells. The mRNA and protein levels of testosterone synthetase, including StAR, CYP11A1, 3β-HSD, CYP17A1 and 17β-HSD, were determined. Effects of Ni on the ERK1/2, p38 and JNK MAPKs were also investigated. The results showed that Ni triggered ROS generation, consequently resulted in the decrease of testosterone synthetase expression and testosterone production in Leydig cells, which were then attenuated by ROS scavengers of N-acetylcysteine (NAC) and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), indicating that ROS are involved in the Ni-induced testosterone biosynthesis disturbance. Meanwhile Ni activated the ERK1/2, p38 and JNK MAPKs. Furthermore, Ni-inhibited testosterone synthetase expression levels and testosterone secretion were all alleviated by co-treatment with MAPK specific inhibitors (U0126 and SB203580, respectively), implying that Ni inhibited testosterone synthesis through activating ERK1/2 and p38 MAPK signal pathways in Leydig cells. In conclusion, these findings suggest that Ni causes testosterone synthesis disorder, partly, via ROS and MAPK signal pathways. Copyright © 2018 Elsevier B.V. All rights reserved.

Implications of progesterone metabolism in MA-10 cells for accurate measurement of the rate of steroidogenesis

NARCIS (Netherlands)

F.F.G. Rommerts (Focko); S.R. King (Steven); P.N. Span (Paul)

2001-01-01

textabstractIn virtually all studies with MA-10 cells, progesterone RIAs have been used to measure steroid synthesis. To test whether progesterone is a stable end product, we investigated the metabolism of added tritiated progesterone and pregnenolone in MA-10 cells over a period

Leydig cell micronodules are a common finding in testicular biopsies from men with impaired spermatogenesis and are associated with decreased testosterone/LH ratio

DEFF Research Database (Denmark)

Holm, Mette; Rajpert-De Meyts, Ewa; Andersson, Anna-Maria

2003-01-01

To assess the biological significance of Leydig cell 'hyperplasia' in man, Leydig cell distribution, volume, and function were studied in patients with infertility or testicular cancer and in suddenly deceased controls. A total of 156 biopsies from 95 patients and 18 necropsies from 13 controls......), and were rare in testes from controls (median = 0, p = 0.02). The proportion of testicular tissue occupied by Leydig cells increased with decreasing spermatogenic capacity. In contrast, the total volume of Leydig cells per testis was roughly comparable irrespective of the histological pattern...... in the hyperstimulated testes, as reflected by an increased LH/testosterone ratio. In conclusion, Leydig cell micronodules were more frequent in biopsies with impaired spermatogenesis and associated with decreased ratios of testicular hormones to gonadotrophins. The presence of micronodules thus seems...

Sertoli cells maintain Leydig cell number and peritubular myoid cell activity in the adult mouse testis.

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Diane Rebourcet

Full Text Available The Sertoli cells are critical regulators of testis differentiation and development. In the adult, however, their known function is restricted largely to maintenance of spermatogenesis. To determine whether the Sertoli cells regulate other aspects of adult testis biology we have used a novel transgenic mouse model in which Amh-Cre induces expression of the receptor for Diphtheria toxin (iDTR specifically within Sertoli cells. This causes controlled, cell-specific and acute ablation of the Sertoli cell population in the adult animal following Diphtheria toxin injection. Results show that Sertoli cell ablation leads to rapid loss of all germ cell populations. In addition, adult Leydig cell numbers decline by 75% with the remaining cells concentrated around the rete and in the sub-capsular region. In the absence of Sertoli cells, peritubular myoid cell activity is reduced but the cells retain an ability to exclude immune cells from the seminiferous tubules. These data demonstrate that, in addition to support of spermatogenesis, Sertoli cells are required in the adult testis both for retention of the normal adult Leydig cell population and for support of normal peritubular myoid cell function. This has implications for our understanding of male reproductive disorders and wider androgen-related conditions affecting male health.

The natural history of Leydig cell testicular tumours: an analysis of the National Cancer Registry.

Science.gov (United States)

Nason, G J; Redmond, E J; Considine, S W; Omer, S I; Power, D; Sweeney, P

2018-05-01

Leydig cell tumour (LCT) of the testis is a rare histological subtype of stromal tumours, accounting for 1 to 3% of testicular neoplasms. The natural history of LCT is poorly understood. The aim of this study was to assess the incidence and natural history of Leydig cell tumours (LCT) of the testes. A search of the National Cancer Registry of Ireland database was performed regarding Leydig cell testicular tumours. Recurrence free survival (RFS) and disease-specific survival (DSS) were analysed. Between 1994 and 2013, 2755 new cases of testicular cancer were diagnosed in Ireland. Of these, 22 (0.79%) were Leydig cell tumours. Nineteen were invasive (stage T1) and three were in situ (stage Tis). One patient developed a local recurrence following an organ preserving procedure and underwent a completion orchidectomy 107 days after initial diagnosis. No further treatment was required. There have been no disease-specific deaths. The 1-, 3- and 5-year overall survival (OS) rates were 95.5, 88.2 and 73.3%, respectively. The 5-year disease-specific survival (DSS) was 100% and the 5-year recurrence free survival (RFS) was 93.3%. From the National Cancer Registry, LCT has been shown to be a rare subtype of testicular tumour. Due to the relatively favourable natural history, it may be possible to tailor less aggressive surveillance regimens in these patients.

Implications of progesterone metabolism in MA-10 cells for accurate measurement of the rate of steroidogenesis.

NARCIS (Netherlands)

Rommerts, F.F.; King, S.R.; Span, P.N.

2001-01-01

In virtually all studies with MA-10 cells, progesterone RIAs have been used to measure steroid synthesis. To test whether progesterone is a stable end product, we investigated the metabolism of added tritiated progesterone and pregnenolone in MA-10 cells over a period of 3 h. Steroids were then

SERTOLI-LEYDIG CELL TUMOR; A RARE CASE IN A POSTMENOPAUSAL PATIENT – CASE REPORT

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Petra Krajnc

2018-02-01

Full Text Available Background. Sertoli-Leydig cell tumors belong to the group of sex cord stromal tumors of the ovary. They account for less than 0.5 % of all ovarian tumors and occur primarily in young women between 20 and 30 years of age. This type of tumors can secrete androgens, causing virilisation, and are extremely rarely presented in postmenopausis. Methods. A 73-year old multiparous woman was presented to our institution with complaints of abdominal distention and abdominal pain in her lower abdomen. On physical examination, she had a large, fixed palpable abdominal mass, approximately 20 cm in diameter, arising from the pelvis. The laboratoric tests revealed an elevated level of CA125 of 221.3 U/ml of serum. The ultrasound showed a complex cystic and solid pelvic tumor. There was no sign of ascites. Her hormonal status was within normal range and she also showed no signs of virilisation. On laparotomy a complex left ovarian mass, measuring 30 × 27 × 15 cm was found and sent to frozen section. The result of frozen section was a malignant tumor of unknown origin, therefore a radical surgical procedure was performed. The histopathological examination established the diagnosis of a malignant Sertoli-Leydig cell tumor of the left ovary, of intermediate differentiation. Other removed tissue was free of malignant cells. The early postoperative course was uneventful and the patient was released from hospital 10 days after surgery. However, she returned to our institution 16 days after surgery due to a proximal thrombosis of v. saphena magna. The patient was treated with low-molecularweight heparin and later warfarin for 6 weeks post operation. 16 months after the operation she was symptomatically treated for severe microcytic anemia. She showed no signs of a relapse. 27 months after primary surgery she was operated for the second time due to acute bowel obstruction. She had large masses of necrotic tumor removed from abdomen and transversostomia was performed

Covalent affinity labeling, radioautography, and immunocytochemistry localize the glucocorticoid receptor in rat testicular Leydig cells

International Nuclear Information System (INIS)

Stalker, A.; Hermo, L.; Antakly, T.

1989-01-01

The presence and distribution of glucocorticoid receptors in the rat testis were examined by using 2 approaches: in vivo quantitative radioautography and immunocytochemistry. Radioautographic localization was made possible through the availability of a glucocorticoid receptor affinity label, dexamethasone 21-mesylate, which binds covalently to the glucocorticoid receptor, thereby preventing dissociation of the steroid-receptor complex. Adrenalectomized adult rats were injected with a tritiated (3H) form of this steroid into the testis and the tissue was processed for light-microscope radioautography. Silver grains were observed primarily over the Leydig cells of the interstitial space and to a lesser extent, over the cellular layers which make up the seminiferous epithelium, with no one cell type showing preferential labeling. To determine the specificity of the labeling, a 25- or 50-fold excess of unlabeled dexamethasone was injected simultaneously with the same dose of (3H)-dexamethasone 21-mesylate. In these control experiments, a marked reduction in label intensity was noted over the Leydig as well as tubular cells. Endocytic macrophages of the interstitium were non-specifically labeled, indicating uptake of the ligand possibly by fluid-phase endocytosis. A quantitative analysis of the label confirmed the presence of statistically significant numbers of specific binding sites for glucocorticoids in both Leydig cells and the cellular layers of the seminiferous epithelium; 86% of the label was found over Leydig cells, and only 14% over the cells of the seminiferous epithelium. These binding data were confirmed by light-microscope immunocytochemistry using a monoclonal antibody to the glucocorticoid receptor

Retiform Sertoli-Leydig Cell Tumor in a 38-Year-Old Woman: A Case Report, Retrospective Review, and Review of Current Literature

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Laura C. Nwogu

2017-01-01

Full Text Available Ovarian sex cord-stromal tumors arise from the stromal cells that surround and support the oocytes. Sertoli-Leydig cell tumors belong to this category of ovarian neoplasms. We present the case of a 38-year-old woman who was found to have a right ovarian mass. The mass was resected and diagnosed as Stage I Sertoli-Leydig cell tumor, retiform variant, following histopathologic and immunohistochemical examination. This case is unusual given the rarity of the retiform variant of Sertoli-Leydig cell tumor and the atypically older age of 38 years at presentation.

Feeding hydroalcoholic extract powder of Lepidium meyenii (maca) increases serum testosterone concentration and enhances steroidogenic ability of Leydig cells in male rats.

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Ohta, Y; Yoshida, K; Kamiya, S; Kawate, N; Takahashi, M; Inaba, T; Hatoya, S; Morii, H; Takahashi, K; Ito, M; Ogawa, H; Tamada, H

2016-04-01

Although Lepidium meyenii (maca), a plant growing in Peru's central Andes, has been traditionally used for enhancing fertility and reproductive performance in domestic animals and human beings, effects of maca on reproductive organs are still unclear. This study examined whether feeding the hydroalcoholic extract powder of maca for 6 weeks affects weight of the reproductive organs, serum concentrations of testosterone and luteinising hormone (LH), number and cytoplasmic area of immunohistochemically stained Leydig cells, and steroidogenesis of cultured Leydig cells in 8-week-old male rats. Feeding the extract powder increased weight of seminal vesicles, serum testosterone level and cytoplasmic area of Leydig cells when compared with controls. Weight of prostate gland, serum LH concentration and number of Leydig cells were not affected by the maca treatment. The testosterone production by Leydig cells significantly increased when cultured with 22R-hydroxycholesterol or pregnenolone and tended to increase when cultured with hCG by feeding the extract powder. The results show that feeding the hydroalcoholic extract powder of maca for 6 weeks increases serum testosterone concentration associated with seminal vesicle stimulation in male rats, and this increase in testosterone level may be related to the enhanced ability of testosterone production by Leydig cells especially in the metabolic process following cholesterol. © 2015 Blackwell Verlag GmbH.

Mechanism of nuclear factor of activated T-cells mediated FasL expression in corticosterone -treated mouse Leydig tumor cells

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Wang Qian

2008-06-01

Full Text Available Abstract Background Fas and FasL is important mediators of apoptosis. We have previously reported that the stress levels of corticosterone (CORT, glucocorticoid in rat increase expression of Fas/FasL and activate Fas/FasL signal pathway in rat Leydig cells, which consequently leads to apoptosis. Moreover, our another study showed that nuclear factor of activated T-cells (NFAT may play a potential role in up-regulation of FasL during CORT-treated rat Leydig cell. It is not clear yet how NFAT is involved in CORT-induced up-regulation of FasL. The aim of the present study is to investigate the molecular mechanisms of NFAT-mediated FasL expression in CORT-treated Leydig cells. Results Western blot analysis showed that NFAT2 expression is present in mouse Leydig tumor cell (mLTC-1. CORT-induced increase in FasL expression in mLTC-1 was ascertained by Western Blot analysis and CORT-induced increase in apoptotic frequency of mLTC-1 cells was detected by FACS with annexin-V labeling. Confocal imaging of NFAT2-GFP in mLTC-1 showed that high level of CORT stimulated NFAT translocation from the cytoplasm to the nucleus. RNA interference-mediated knockdown of NFAT2 significantly attenuated CORT-induced up-regulation of FasL expression in mLTC. These results corroborated our previous finding that NFAT2 is involved in CORT-induced FasL expression in rat Leydig cells and showed that mLTC-1 is a suitable model for investigating the mechanism of CORT-induced FasL expression. The analysis of reporter constructs revealed that the sequence between -201 and +71 of mouse FasL gene is essential for CORT-induced FasL expression. The mutation analysis demonstrated that CORT-induced FasL expression is mediated via an NFAT binding element located in the -201 to +71 region. Co-transfection studies with an NFAT2 expression vector and reporter construct containing -201 to +71 region of FasL gene showed that NFAT2 confer a strong inducible activity to the FasL promoter at its

Molecular Mechanisms Elicited by d-Aspartate in Leydig Cells and Spermatogonia

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Maria Maddalena Di Fiore

2016-07-01

Full Text Available A bulk of evidence suggests that d-aspartate (d-Asp regulates steroidogenesis and spermatogenesis in vertebrate testes. This review article focuses on intracellular signaling mechanisms elicited by d-Asp possibly via binding to the N-methyl-d-aspartate receptor (NMDAR in both Leydig cells, and spermatogonia. In Leydig cells, the amino acid upregulates androgen production by eliciting the adenylate cyclase-cAMP and/or mitogen-activated protein kinase (MAPK pathways. d-Asp treatment enhances gene and protein expression of enzymes involved in the steroidogenic cascade. d-Asp also directly affects spermatogonial mitotic activity. In spermatogonial GC-1 cells, d-Asp induces phosphorylation of MAPK and AKT serine-threonine kinase proteins, and stimulates expression of proliferating cell nuclear antigen (PCNA and aurora kinase B (AURKB. Further stimulation of spermatogonial GC-1 cell proliferation might come from estradiol/estrogen receptor β (ESR2 interaction. d-Asp modulates androgen and estrogen levels as well as the expression of their receptors in the rat epididymis by acting on mRNA levels of Srd5a1 and Cyp19a1 enzymes, hence suggesting involvement in spermatozoa maturation.

A rare ovarian tumor, leydig stromal cell tumor, presenting with virilization: a case report

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Soheila Aminimoghaddam

2012-11-01

Full Text Available  Abstract Leydig stromal cell tumor is a rare ovarian tumor that belongs to the group of sex-cord stromal tumors. They produce testosterone leading to hyperandrogenism. We present a 41yr old woman with symptoms of virilization and a mass of right adenex via ultra Sonography, and a rise of total and free serum testosterone. An ovarian source of androgen was suspected and a surgery performed. A diagnosis of leydig-stromal cell tumor was confirmed. Our report is a reminder that although idiopathic hirsutism and other benign androgen excess disorder like Polycystic Ovarian Syndrome (PCOs are common, ovarian mass should be considered in differential diagnosis. 

An in vitro prototype of a porcine biomimetic testis-like cell culture system: a novel tool for the study of reassembled Sertoli and Leydig cells

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Iva Arato

2018-01-01

Full Text Available At present, there is no reliable in vitro assembled prepubertal testis-like biomimetic organ culture system designed to assess the functional effects of human gonadotropins on Sertoli and Leydig cells. Spermatogenesis is regulated by endocrine, paracrine, and juxtacrine factors (testicular cross-talk, mainly orchestrated by gonadotropins such as luteinizing hormone (LH and follicle-stimulating hormone (FSH that play a pivotal role by stimulating Leydig and Sertoli cells, respectively. The aim of our study was to set up an in vitro prepubertal porcine bioengineered construct as a new model for experimental studies on reassembled Sertoli and Leydig cells. We have evaluated Sertoli and Leydig cells obtained from 15- to 20-day-old neonatal pig testes in terms of purity and function. Subsequently, purified Sertoli and enriched Leydig cells were subjected to coincubation to obtain an in vitro prepubertal porcine testis-like culture system. We performed enzyme-linked immunosorbent assay (ELISA for anti-Müllerian hormone (AMH, inhibin B, and testosterone secretion in the medium, and Real-Time PCR analysis of AMH, inhibin B, FSH-r, aromatase, LHr, and 3β-HSD mRNA expression levels. This in vitro testis-like system was highly responsive to the effects of human gonadotropins and testosterone. AMH mRNA expression and secretion declined, and inhibin-B increased, while FSH-receptor expression was downregulated upon FSH/LH exposure/treatment. Finally, the production of testosterone was increased selectively upon LH treatment. In summary, our proposed model could help to better determine the action of human gonadotropins on Sertoli and Leydig cells. The potential usefulness of the system for shedding light into male infertility-related issues is evident.

Ovarian Sertoli-Leydig cell tumor with heterologous elements of gastrointestinal type associated with elevated serum alpha-fetoprotein level: an unusual case and literature review.

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Horta, Mariana; Cunha, Teresa Margarida; Marques, Rita Canas; Félix, Ana

2014-11-01

Here we describe the case of a 19-year-old woman with a poorly differentiated ovarian Sertoli-Leydig cell tumor and an elevated serum alpha-fetoprotein level. The patient presented with diffuse abdominal pain and bloating. Physical examination, ultrasound, and magnetic resonance imaging revealed a right ovarian tumor that was histopathologically diagnosed as a poorly differentiated Sertoli-Leydig cell tumor with heterologous elements. Her alpha-fetoprotein serum level was undetectable after tumor resection. Sertoli-Leydig cell tumors are rare sex cord-stromal tumors that account for 0.5% of all ovarian neoplasms. Sertoli-Leydig cell tumors tend to be unilateral and occur in women under 30 years of age. Although they are the most common virilizing tumor of the ovary, about 60% are endocrine-inactive tumors. Elevated serum levels of alpha-fetoprotein are rarely associated with Sertoli-Leydig cell tumors, with only approximately 30 such cases previously reported in the literature. The differential diagnosis should include common alpha-fetoprotein-producing ovarian entities such as germ cell tumors, as well as other non-germ cell tumors that have been rarely reported to produce this tumor marker.

Glycidamide inhibits progesterone production through reactive oxygen species-induced apoptosis in R2C Rat Leydig Cells.

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Li, Mingwei; Sun, Jianxia; Zou, Feiyan; Bai, Shun; Jiang, Xinwei; Jiao, Rui; Ou, Shiyi; Zhang, Hui; Su, Zhijian; Huang, Yadong; Bai, Weibin

2017-10-01

The food contaminant acrylamide (AA) is usually recognized as a probable human carcinogen. In addition, AA has also been found able to induce male infertility in animals. Interestingly, resent research work revealed that the toxic effect of AA on the ability of male reproduction in vivo may due to glycidamide (GA) which is the metabolite of AA. In this study, R2C Leydig cells was used to investigate the toxic effects of GA on progesterone production. GA caused dose-dependent inhibition on the cell growth, with IC 25 , IC 50, and IC 75 values found at 0.635, 0.872, and 1.198 mM, respectively. The results of single cell gel/Comet assay showed that GA significantly induced early-phase cell apoptosis, reduced progesterone production, as well as decreasing the protein expression of steroidogenic acute regulatory (StAR) in R2C cells. Furthermore, GA induced overproduction of intracellular reactive oxygen species (ROS), upregulated Bax expression, decreased mitochondrial membrane potential, and triggered mitochondria-mediated cell apoptosis. Consequently, the downstream effector caspase-3 was activated, resulting in Leydig cells apoptosis. Overall, our results showed that GA could damage R2C Leydig cells by the lesion of the ability of progesterone genesis and inducing cells apoptosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inhibition of acrolein-induced autophagy and apoptosis by a glycosaminoglycan from Sepia esculenta ink in mouse Leydig cells.

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Gu, Yi-Peng; Yang, Xiao-Mei; Luo, Ping; Li, Yan-Qun; Tao, Ye-Xing; Duan, Zhen-Hua; Xiao, Wei; Zhang, Da-Yan; Liu, Hua-Zhong

2017-05-01

In our recent reports, a squid ink polysaccharide (SIP) was found having preventive activity against cyclophosphamide induced damage in mouse testis and ovary. Here we further reveal the regulative mechanism of SIP against chemical toxicity on testis. Leydig cells exposed to acrolein (ACR) underwent apoptosis at 12h and 24h. Before apoptosis, cells occurred autophagy that was confirmed by high autophagic rate and Beclin-1 protein content at 3h. PI3K/Akt and p38 MAPK signal pathways involved in the regulatory mechanisms. These outcomes of ACR were recovered completely by SIP, which was demonstrated by attenuated disruption of redox equilibrium and increased testosterone production, through suppressing ACR-caused autophagy and apoptosis regulated by PI3K/Akt and p38 MAPK signal pathways in Leydig cells. Summarily, autophagy occurred before apoptosis caused by ACR-activated p38 MAPK and PI3K/Akt pathways were blocked by SIP, resulting in survival and functional maintenance of Leydig cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

The total number of Leydig and Sertoli cells in the testes of men across various age groups - a stereological study

DEFF Research Database (Denmark)

Petersen, Peter M; Seierøe, Karina; Pakkenberg, Bente

2015-01-01

is particularly sensitive to methodological problems. Therefore, using the optical fractionator technique and a sampling design specifically optimized for human testes, we estimated the total number of Sertoli and Leydig cells in the testes from 26 post mortem male subjects ranging in age from 16 to 80 years...... of Sertoli cells with age; no such decline was found for Leydig cells. Quantitative stereological analysis of post mortem tissue may help understand the influence of age or disease on the number of human testicular cells....

Androgen receptor signalling in peritubular myoid cells is essential for normal differentiation and function of adult Leydig cells

DEFF Research Database (Denmark)

Welsh, M.; Moffat, L.; Belling, Kirstine Christensen

2012-01-01

Testosterone synthesis depends on normal Leydig cell (LC) development, but the mechanisms controlling this development remain unclear. We recently demonstrated that androgen receptor (AR) ablation from a proportion of testicular peritubular myoid cells (PTM-ARKO) did not affect LC number, but res......Testosterone synthesis depends on normal Leydig cell (LC) development, but the mechanisms controlling this development remain unclear. We recently demonstrated that androgen receptor (AR) ablation from a proportion of testicular peritubular myoid cells (PTM-ARKO) did not affect LC number......’ subpopulation that had arrested development and only weakly expressed INSL3, luteinizing hormone receptor, and several steroidogenic enzymes. Furthermore, unlike ‘normal’ LCs in PTM-ARKOs, the ‘abnormal’ LCs did not involute as expected in response to exogenous testosterone. Differential function of these LC...... sub-populations is likely to mean that the ‘normal’ LCs work harder to compensate for the ‘abnormal’ LCs to maintain normal serum testosterone. These findings reveal new paracrine mechanisms underlying adult LC development, which can be further investigated using PTM-ARKOs....

[The ultrastructure of Leydig cells under the influence of drinking mineral water and electromagnetic radiation under the stress conditions in the rats].

Science.gov (United States)

Geniatulina, M S; Korolev, Yu N; Nikulina, L A

The objective of the present study was elucidate the peculiar features of low-intensity electromagnetic radiation (LI EMR) and mineral water (MW) on the ultrastructure of rat Leydig cells under conditions of immobilization stress. The experiments were carried out on outbred male rats with the use of electron microscopy. It has been demonstrated that the prophylactic consumption of drinking sulfate-containing mineral water and the application low-intensity electromagnetic radiation (with the flow power density of 1 mcW/cm2 and frequency around 1,000 Hz) or the combination of these two modalities under conditions of immobilization stress reduced the degree of ultrastructural derangement in the rat Leydig cells and stimulated the development of regenerative processes. In the cases of the single-factor impact, drinking mineral water exerted more pronounced action than low-intensity electromagnetic radiation on mitochondrial regeneration. In case of the simultaneous application of the two factors their protective action on the Leydig cells was much more conspicuous than that of either of them applied alone. It is concluded that drinking sulfate-containing mineral water in combination with the application of low-intensity electromagnetic radiation enhances resistance of the rat Leydig cells to stress.

Ascorbic acid supplementation enhances recovery from ethanol induced inhibition of Leydig cell steroidogenesis than abstention in male guinea pigs.

Science.gov (United States)

Radhakrishnakartha, Harikrishnan; Appu, Abhilash Puthuvelvippel; Indira, Madambath

2014-01-15

The impact of ascorbic acid supplementation against ethanol induced Leydig cell toxicity was studied in guinea pigs. Male guinea pigs were exposed to ethanol (4g/kgb.wt.) for 90 days. After 90 days, ethanol administration was completely stopped and animals in the ethanol group were divided into abstention group and ascorbic acid supplemented group (25mg/100gb.wt.) and those in control group were maintained as control and control+ascorbic acid group. Ethanol administration reduced the serum testosterone and LH (luteinising hormone) levels and elevated estradiol levels. Cholesterol levels in Leydig cell were increased whereas the mRNA and protein expressions of StAR (steroidogenic acute regulatory) protein, cytochrome P450scc (cytochrome p450side chain cleavage enzyme), 3β-HSD (3β-hydroxysteroid dehydrogenase), 17β-HSD (17β-hydroxysteroid dehydrogenase) and LH receptor were drastically reduced. Administration of ascorbic acid resulted in alteration of all these parameters indicating enhanced recovery from ethanol induced inhibition of Leydig cell steroidogenesis. Although abstention could also reduce the inhibition of steroidogenesis, this was lesser in comparison with ascorbic acid supplemented group. © 2013 Published by Elsevier B.V.

Cytotoxic mechanism related to dihydrolipoamide dehydrogenase in Leydig cells exposed to heavy metals

International Nuclear Information System (INIS)

Ji, Xunmin; Li, Zhiliang; Chen, Hongxia; Li, Junqi; Tian, Huajian; Li, Zengli; Gao, Xuejuan; Xiang, Qi; Su, Zhijian; Huang, Yadong; Zhang, Qihao

2015-01-01

Heavy metals are common environmental toxicants with adverse effects on steroid biosynthesis. The importance of mitochondria has been recognized in cytotoxic mechanism of heavy metals on Leydig cells these years. But it is still poorly known. Our previous study reported that dihydrolipoamide dehydrogenase (DLD) located on the mitochondria was significantly decreased in Leydig cells exposed to cadmium, which suggested that DLD might be involved in the cytotoxic effects. Therefore, the altered expression of DLD was validated in rats and R2C cells exposed to cadmium, manganese and lead, and the role of DLD in the steroid synthesis pathway cAMP/PKA-ERK1/2 was investigated in this study. With a low expression of DLD, heavy metals dramatically reduced the levels of steroid hormone by inhibiting the activation of cAMP/PKA, PKC signaling pathway and the steroidogenic enzymes StAR, CYP11A1 and 3β-HSD. After knockdown of DLD in R2C cells, progesterone synthesis was reduced by 40%, and the intracellular concentration of cAMP, protein expression of StAR, 3β-HSD, PKA, and the phosphorylation of ERK1/2 were also decreased. These results highlight that DLD is down-regulation and related to steroid biosynthesis in Leyig cells exposed to heavy metals; cAMP/PKA act as downstream effector molecules of DLD, which activate phosphorylation of ERK1/2 to initiate the steroidogenesis

Comparison of the Effects of Dibutyl and Monobutyl Phthalates on the Steroidogenesis of Rat Immature Leydig Cells

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Linxi Li

2016-01-01

Full Text Available Dibutyl phthalate (DBP is a widely used synthetic phthalic diester and monobutyl phthalate (MBP is its main metabolite. DBP can be released into the environment and potentially disrupting mammalian male reproductive endocrine system. However, the potencies of DBP and MBP to inhibit Leydig cell steroidogenesis and their possible mechanisms are not clear. Immature Leydig cells isolated from rats were cultured with 0.05–50 μM DBP or MBP for 3 h in combination with testosterone synthesis regulator or intermediate. The concentrations of 5α-androstanediol and testosterone in the media were measured, and the mRNA levels of the androgen biosynthetic genes were detected by qPCR. The direct actions of DBP or MBP on CYP11A1, CYP17A1, SRD5A1, and AKR1C14 activities were measured. MBP inhibited androgen production by the immature Leydig cell at as low as 50 nM, while 50 μM was required for DBP to suppress its androgen production. MBP mainly downregulated Cyp11a1 and Hsd3b1 expression levels at 50 nM. However, 50 μM DBP downregulated Star, Hsd3b1, and Hsd17b3 expression levels and directly inhibited CYP11A1 and CYP17A1 activities. In conclusion, DBP is metabolized to more potent inhibitor MBP that downregulated the expression levels of some androgen biosynthetic enzymes.

Occult Leydig Cell Tumour Presenting as Bilateral Gynaecomastia. Case Report and Literature Review

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A. B. Patel

2005-01-01

Full Text Available Gynaecomastia is the most common benign breast disorder in men. Among the various causes, testicular malignancies are an uncommon, life-threatening condition requiring prompt diagnosis and treatment. The case of a 28-year-old man is discussed, who presented with a 6-month history of painful bilateral gynaecomastia with no abnormality on clinical or biochemical examination. The patient's symptoms spontaneously resolved within 4 weeks. He then represented 10 years later with similar symptoms and an associated secondary hypogonadism. Ultrasound imaging revealed a clinically occult, hypoechoic mass in the left testis (Leydig cell tumour on histology. Clinical and hormonal findings normalized following surgical excision. This report underlines the importance in clinical practice of ultrasonographic evaluation of the testis, in all patients with gynaecomastia, despite unremarkable findings on physical examination.

The effects of treatment with melatonin on the ultrastructure of mouse leydig cells: a quantitative study Efeito do tratamento com melatonina sobre a ultra-estrutura das células de Leydig do camundongo: estudo quantitativo

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C. A. REDINS

2002-08-01

Full Text Available Both the presence of receptors for gonadal steroids in the pineal gland and in vitro observations of direct action of melatonin upon Leydig cells, inhibiting testosterone secretion, indicate a direct connection between pineal gland and gonadal function. In the present study, we used a transmission electron microscope to analyze the morphologic parameters of Leydig cells from adult Swiss outbred white mice treated with daily subcutaneous injections of 100 µg of melatonin (N-acetyl, 5-methoxytryptamine, during 22 consecutive days, compared with sham-control animals which had only received the melatonin vehicle. The melatonin group of mice showed a decrease in nuclear volume and fractional nuclear volume; smooth and rough endoplasmic reticulum; mitochondria; and Golgi complex. Our data also showed an increase in cytoplasmic volume, fractional cytoplasmic volume, and lysosomes in these same animals. The results suggest that melatonin, directly or indirectly, alters the ultrastructure of mouse Leydig cells and possibly influences their secretory activity by inhibiting their capacity to secrete steroids.No presente trabalho, utilizamos a microscopia eletrônica de transmissão para analisar os parâmetros morfológicos das células de Leydig de camundongos adultos, suíços outbred, tratados com uma injeção subcutânea diária de 100 µg de melatonina (5-metoxi-N-acetil-triptamina, durante 22 dias consecutivos, comparando-os com animais sham-controle que receberam apenas o veículo da melatonina. Os animais tratados com melatonina mostraram diminuição do volume nuclear, da fração volumétrica do núcleo, do retículo endoplasmático liso e rugoso, das mitocôndrias e do complexo de Golgi. Nos mesmos animais ocorreu, também, aumento do volume do citoplasma e da fração volumétrica do citoplasma e dos lisossomos. Esses resultados sugerem que a melatonina pode alterar, direta ou indiretamente, a ultra-estrutura das células de Leydig do

A randomized double-blind study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention).

Science.gov (United States)

Bandak, Mikkel; Jørgensen, Niels; Juul, Anders; Lauritsen, Jakob; Kreiberg, Michael; Oturai, Peter Sandor; Helge, Jørn Wulff; Daugaard, Gedske

2017-07-03

Elevated serum levels of luteinizing hormone and slightly decreased serum levels of testosterone (mild Leydig cell insufficiency) is a common hormonal disturbance in testicular cancer (TC) survivors. A number of studies have shown that low serum levels of testosterone is associated with low grade inflammation and increased risk of metabolic syndrome. However, so far, no studies have evaluated whether testosterone substitution improves metabolic dysfunction in TC survivors with mild Leydig cell insufficiency. This is a single-center, randomized, double-blind, placebo-controlled study, designed to evaluate the effect of testosterone replacement therapy in TC survivors with mild Leydig cell insufficiency. Seventy subjects will be randomized to receive either testosterone replacement therapy or placebo. The subjects will be invited for an information meeting where informed consent will be obtained. Afterwards, a 52-weeks treatment period begins in which study participants will receive a daily dose of transdermal testosterone or placebo. Dose adjustment will be made three times during the initial 8 weeks of the study to a maximal daily dose of 40 mg of testosterone in the intervention arm. Evaluation of primary and secondary endpoints will be performed at baseline, 26 weeks post-randomization, at the end of treatment (52 weeks) and 3 months after completion of treatment (week 64). This study is the first to investigate the effect of testosterone substitution in testicular cancer survivors with mild Leydig cell insufficiency. If positive, it may change the clinical handling of testicular cancer survivors with borderline low levels of testosterone. ClinicalTrials.gov : NCT02991209 (November 25, 2016).

Cell context-specific expression of primary cilia in the human testis and ciliary coordination of Hedgehog signalling in mouse Leydig cells

DEFF Research Database (Denmark)

Berg Nygaard, Marie; Almstrup, Kristian; Lindbæk, Louise

2015-01-01

Primary cilia are sensory organelles that coordinate numerous cellular signalling pathways during development and adulthood. Defects in ciliary assembly or function lead to a series of developmental disorders and diseases commonly referred to as ciliopathies. Still, little is known about...... cells of mature seminiferous epithelium, but present in Sertoli cell-only tubules in Klinefelter syndrome testis. Peritubular cells in atrophic testis produce overly long cilia. Furthermore cultures of growth-arrested immature mouse Leydig cells express primary cilia that are enriched in components...

Androgen action via testicular arteriole smooth muscle cells is important for Leydig cell function, vasomotion and testicular fluid dynamics.

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Michelle Welsh

2010-10-01

Full Text Available Regulation of blood flow through the testicular microvasculature by vasomotion is thought to be important for normal testis function as it regulates interstitial fluid (IF dynamics which is an important intra-testicular transport medium. Androgens control vasomotion, but how they exert these effects remains unclear. One possibility is by signalling via androgen receptors (AR expressed in testicular arteriole smooth muscle cells. To investigate this and determine the overall importance of this mechanism in testis function, we generated a blood vessel smooth muscle cell-specific AR knockout mouse (SMARKO. Gross reproductive development was normal in SMARKO mice but testis weight was reduced in adulthood compared to control littermates; this reduction was not due to any changes in germ cell volume or to deficits in testosterone, LH or FSH concentrations and did not cause infertility. However, seminiferous tubule lumen volume was reduced in adult SMARKO males while interstitial volume was increased, perhaps indicating altered fluid dynamics; this was associated with compensated Leydig cell failure. Vasomotion was impaired in adult SMARKO males, though overall testis blood flow was normal and there was an increase in the overall blood vessel volume per testis in adult SMARKOs. In conclusion, these results indicate that ablating arteriole smooth muscle AR does not grossly alter spermatogenesis or affect male fertility but does subtly impair Leydig cell function and testicular fluid exchange, possibly by locally regulating microvascular blood flow within the testis.

Effect of an acute exposure of rat testes to gamma rays on germ cells and on Sertoli and Leydig cell functions

International Nuclear Information System (INIS)

Pinon-Lataillade, G.; Maas, J.; Viguier-Martinez, M.C.; Touzalin, A.M.; Jegou, B.

1991-01-01

Germ cells and Sertoli and Leydig cell functions were studied from 7 to 180 days after an acute exposure of 2-month-old rat testes to 9 Gy of γ rays. Body weight, testis and epididymal weights were recorded. Sertoli cell parameters (androgen-binding protein, ABP, in caput epididymis and plasma follicle stimulating hormone, FSH) and Leydig cell parameters (plasma luteinizing hormone, LH, testosterone and prostate and seminal vesicle weights) were determined together with the number of germ cells and Sertoli cells. Irradiation did not affect body weight but significantly reduced testicular and epididymal weights from day 7 and day 15 post-irradiation respectively. The cells killed by irradiation were mainly spermatogonia and preleptotene spermatocytes engaged in replicating their DNA at the time of exposure, but all spermatocytes seemed damaged as they gave abnormal descendent cells. By day 34, only elongated spermatids remained in a few tubules and thereafter very little regeneration of the seminiferous epithelium occurred, except for one rat which showed a better regeneration. Levels of ABP decreased by day 15 when the germ cell depletion had reached the pachytene spermatocytes, whereas FSH and LH levels rose when the number of elongated spermatids decreased. Levels of testosterone and the weight of the seminal vesicles did not change; occasionally, the prostate weight was slightly reduced. These results support our hypothesis that pachytene spermatocytes and elongated spermatids are involved in influencing some aspects of Sertoli cell function in the adult rat

Retiform Sertoli-Leydig cell tumor of ovary in a 9-year-old girl: case report and review of the literature.

Science.gov (United States)

Lou, Weizhen; Cao, Dongyan; Yang, Jiaxin; Guo, Lina; Shen, Keng

2011-12-01

The management of the retiform variant of Sertoli-Leydig cell tumor remains a challenge for the gynecologist. Surgery is the preferred treatment, but it is still inconclusive whether complete staging or postoperative adjuvant therapy is necessary. A 9-year-old girl was admitted with a well-circumscribed, solid cystic mass in the lower abdomen, of size corresponding to a 20-week gravid uterus, without any androgenic manifestations. Per-operatively, the mass arose from left ovary, which had a smooth outer surface with intact capsule. A cut section was almost multiloculated with cysts ranging from 0.5 to 2.5 cm in diameter and filled with thin yellow or brown serous fluid. Left salpingo-oophorectomy, bilateral lymph node dissection, infracolic omentectomy and appendectomy were performed. The pathological diagnosis was retiform pattern of intermediate to poorly differentiated Sertoli-Leydig cell tumor. The clinical stage was IA. The patient was followed up 3-monthly, and was disease-free at 18-month follow-up after the initial treatment. After review of the literature, we conclude that the retiform variant is a special subtype of Sertoli-Leydig cell tumors. Because of their young age, the uncertain malignant potential and rare bilaterality, patients should be treated conservatively whenever possible. There is at present no good evidence that postoperative adjuvant therapy is effective in preventing recurrence.

Recurrent ovarian Sertoli?Leydig cell tumor in a child with Peutz?Jeghers syndrome

OpenAIRE

Bellfield, Edward J.; Alemzadeh, Ramin

2016-01-01

We present a female child with Peutz?Jeghers syndrome (PJS) with a recurrent ovarian Sertoli?Leydig cell tumor (SLCT). SLCTs are relatively rare sex cord neoplasms that can occur in PJS. The patient was an African-American female who first presented at the age of 3 years with precocious puberty, and then at the age of 17 years with abdominal pain and irregular menses. In each case, she had resection of the mass, which included oophorectomy. To our knowledge, this is the first reported case in...

Leydig cell micronodules are a common finding in testicular biopsies from men with impaired spermatogenesis and are associated with decreased testosterone/LH ratio

DEFF Research Database (Denmark)

Holm, Mette; Rajpert-De Meyts, Ewa; Andersson, Anna-Maria

2003-01-01

were examined using a semi-quantitative stereological method. In patients, serum concentrations of testosterone, sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol and inhibin-B were correlated with the findings on histological examination......, with the exception of testes with bilateral micronodules, which had significantly increased Leydig cell volume compared to those without micronodules. The number of micronodules correlated positively to LH (r = 0.577, p ... in the hyperstimulated testes, as reflected by an increased LH/testosterone ratio. In conclusion, Leydig cell micronodules were more frequent in biopsies with impaired spermatogenesis and associated with decreased ratios of testicular hormones to gonadotrophins. The presence of micronodules thus seems...

Long-term feeding of hydroalcoholic extract powder of Lepidium meyenii (maca) enhances the steroidogenic ability of Leydig cells to alleviate its decline with ageing in male rats.

Science.gov (United States)

Yoshida, K; Ohta, Y; Kawate, N; Takahashi, M; Inaba, T; Hatoya, S; Morii, H; Takahashi, K; Ito, M; Tamada, H

2018-02-01

This study examined whether feeding hydroalcoholic extract of Lepidium meyenii (maca) to 8-week-old (sexually maturing) or 18-week-old (mature) male rats for more than a half year affects serum testosterone concentration and testosterone production by Leydig cells cultured with hCG, 22R-hydroxycholesterol or pregnenolone. Testosterone concentration was determined in the serum samples obtained before and 6, 12, 18 and 24 weeks after the feeding, and it was significantly increased only at the 6 weeks in the group fed with the maca extract to maturing rats when it was compared with controls. Testosterone production by Leydig cells significantly increased when cultured with hCG by feeding the maca extract to maturing rats for 27 weeks (35 weeks of age) and when cultured with 22R-hydroxycholesterol by feeding it to mature rats for 30 weeks (48 weeks of age). Overall testosterone production by cultured Leydig cells decreased to about a half from 35 to 48 weeks of age. These results suggest that feeding the maca extract for a long time to male rats may enhance the steroidogenic ability of Leydig cells to alleviate its decline with ageing, whereas it may cause only a transient increase in blood testosterone concentration in sexually maturing male rats. © 2017 Blackwell Verlag GmbH.

The Oncogenic Roles of DICER1 RNase IIIb Domain Mutations in Ovarian Sertoli-Leydig Cell Tumors

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Yemin Wang

2015-08-01

Full Text Available DICER1, an endoribonuclease required for microRNA (miRNA biogenesis, is essential for embryogenesis and the development of many organs including ovaries. We have recently identified somatic hotspot mutations in RNase IIIb domain of DICER1 in half of ovarian Sertoli-Leydig cell tumors, a rare class of sex-cord stromal cell tumors in young women. These hotspot mutations lost IIIb cleavage activity of DICER1 in vitro and failed to produce 5p-derived miRNAs in mouse Dicer1-null ES cells. However, the oncogenic potential of these hotspot DICER1 mutations has not been studied. Here, we further revealed that the global expression of 5p-derived miRNAs was dramatically reduced in ovarian Sertoli-Leydig cell tumors carrying DICER1 hotspot mutations compared with those without DICER1 hotspot mutation. The miRNA production defect was associated with the deregulation of genes controlling cell proliferation and the cell fate. Using an immortalized human granulosa cell line, SVOG3e, we determined that the D1709N-DICER1 hotspot mutation failed to produce 5p-derived miRNAs, deregulated the expression of several genes that control gonadal differentiation and cell proliferation, and promoted cell growth. Re-expression of let-7 significantly inhibited the growth of D1709N-DICER1 SVOG3e cells, accompanied by the suppression of key regulators of cell cycle control and ovarian gonad differentiation. Taken together, our data revealed that DICER1 hotspot mutations cause systemic loss of 5p-miRNAs that can both drive pseudodifferentiation of testicular elements and cause oncogenic transformation in the ovary.

A novel splice mutation in the TP53 gene associated with Leydig cell tumor and primitive neuroectodermal tumor

DEFF Research Database (Denmark)

Stecher, Chalotte Willemann; Grønbaek, Kirsten; Hasle, Henrik

2008-01-01

A 20-month-old boy presented with precocious puberty due to a Leydig cell tumor, and at the age of 6 years with a primitive neuroectodermal brain-tumor (PNET). A novel splice site mutation of the TP53-gene, likely to be associated with a nonfunctional protein, was found in the proband, his father...

Leydig Cell Tumor Associated with Testicular Adrenal Rest Tumors in a Patient with Congenital Adrenal Hyperplasia due to 11β-Hydroxylase Deficiency

Directory of Open Access Journals (Sweden)

Nadia Charfi

2012-01-01

Full Text Available Congenital adrenal hyperplasia (CAH describes a group of inherited autosomal recessive disorders characterized by enzyme defects in the steroidogenic pathways that lead to the biosynthesis of cortisol, aldosterone, and androgens. Chronic excessive adrenocorticotropic hormone (ACTH stimulation may result in hyperplasia of ACTH-sensitive tissues in adrenal glands and other sites such as the testes, causing testicular masses known as testicular adrenal rest tumors (TARTs. Leydig cell tumors (LCTs are make up a very small number of all testicular tumors and can be difficult to distinguish from TARTs. This distinction is interesting because LCTs and TARTs require different therapeutic approaches. Hereby, we present an unusual case of a 19-year-old patient with CAH due to 11β-hydroxylase deficiency, who presented with TARTs and an epididymal Leydig cell tumor.

A case of hirsutism due to bilateral diffuse ovarian Leydig cell hyperplasia in a post-menopausal woman.

Science.gov (United States)

Ali, F S.M.; Stanaway, S E.R.S.; Zakhour, H D.; Spearing, G; Bowen-Jones, D

2003-11-01

Hyperandrogenism in females usually results from ovarian or adrenal pathology. We present a case of virilizaton due to very rare bilateral ovarian diffuse interstitial proliferation of Leydig cells with no tumour or hilar cell hyperplasia identified. Interestingly, the case was further complicated by the finding of high levels of testosterone in one adrenal vein on selective venous sampling (SVS), resulting in an unnecessary unilateral adrenalectomy. Further sampling found high levels also in the ovarian veins, and the condition was finally cured by bilateral oophorectomy.

The role of calcium-sensing receptor and signalling pathways in the pathophysiology in two in vitro models of malignant hypercalcemia: the rat rice H-500 Leydig testis cancer and prostate cancer (PC-3) cells. Expression and regulation of pituitary tumor transforming gene in Leydig testis cancer

DEFF Research Database (Denmark)

Tfelt-Hansen, J.

2008-01-01

The calcium-sensing receptor (CaR) is a seven transmembrane receptor incorporated into the cell membrane that is sensitive to extracellular calcium and other cations. The finding that the CaR is expressed on cancer cells has opened the door to a new understanding of the role of extracellular...... too many adverse effects on calcium homeostasis. In conclusion, the CaR plays diverse roles in cancer-acting as an inhibitor of cell proliferation in the colon crypt cells giving rise to colon cancer but as a promalignant receptor in most other cancer types, including Leydig cell cancers...... calcium as a promalignant stimulus through the CaR and its signaling apparatus as demonstrated in this thesis. I found, in a model of humoral hypercalcemia of malignancy (HHM), that stimulation of the CaR worsens the promalignant features of the testicular H-500 Leydig cancer cells that were used in my...

A Rare Case of Intra-Endometrial Leiomyoma of Uterus Simulating Degenerated Submucosal Leiomyoma Accompanied by a Large Sertoli-Leydig Cell Tumor.

Science.gov (United States)

Jeong, Kyungah; Lee, Sa Ra; Park, Sanghui

2016-03-01

A 50-year-old peri-menopausal woman presented with hard palpable mass on her lower abdomen and anemia from heavy menstrual bleeding. Ultrasonography showed a 13×12 cm sized hypoechoic solid mass in pelvis and a 2.5×2 cm hypoechoic cystic mass in uterine endometrium. Abdomino-pelvic computed tomography revealed a hypodense pelvic mass without enhancement, suggesting a leiomyoma of intraligamentary type or sex cord tumor of right ovary with submucosal myoma of uterus. Laparoscopy revealed a large Sertoli-Leydig cell tumor of right ovary with a very rare entity of intra-endometrial uterine leiomyoma accompanied by adenomyosis. The final diagnosis of ovarian sex-cord tumor (Sertoli-Leydig cell), stage Ia with intra-endometrial leiomyoma with adenomyosis, was made. Considering the large size of the tumor and poorly differentiated nature, 6 cycles of chemotherapy with Taxol and Carboplatin regimen were administered. There is neither evidence of major complications nor recurrence during 20 months' follow-up.

Circadian rhythm genes mediate fenvalerate-induced inhibition of testosterone synthesis in mouse Leydig cells.

Science.gov (United States)

Guo, Yichen; Shen, Ouxi; Han, Jingjing; Duan, Hongyu; Yang, Siyuan; Zhu, Zhenghong; Tong, Jian; Zhang, Jie

2017-01-01

Fenvalerate (Fen), a widely used pesticide, is known to impair male reproductive functions by mechanisms that remain to be elucidated. Recent studies indicated that circadian clock genes may play an important role in successful male reproduction. The aim of this study was to determine the effects of Fen on circadian clock genes involved in the biosynthesis of testosterone using TM3 cells derived from mouse Leydig cells. Data demonstrated that the circadian rhythm of testosterone synthesis in TM3 cells was disturbed following Fen treatment as evidenced by changes in the circadian rhythmicity of core clock genes (Bmal1, Rev-erbα, Rorα). Further, the observed altered rhythms were accompanied by increased intracellular Ca 2+ levels and modified steroidogenic acute regulatory (StAR) mRNA expression. Thus, data suggested that Fen inhibits testosterone synthesis via pathways involving intracellular Ca 2+ and clock genes (Bmal1, Rev-Erbα, Rorα) as well as StAR mRNA expression in TM3 cells.

Constitutive luteinizing hormone receptor signaling causes sexual dysfunction and Leydig cell adenomas in male mice.

Science.gov (United States)

Hai, Lan; Hiremath, Deepak S; Paquet, Marilène; Narayan, Prema

2017-05-01

The luteinizing hormone receptor (LHCGR) is necessary for fertility, and genetic mutations cause defects in reproductive development and function. Activating mutations in LHCGR cause familial male-limited precocious puberty (FMPP). We have previously characterized a mouse model (KiLHRD582G) for FMPP that exhibits the same phenotype of precocious puberty, Leydig cell hyperplasia, and elevated testosterone as boys with the disorder. We observed that KiLHRD582G male mice became infertile by 6 months of age, although sperm count and motility were normal. In this study, we sought to determine the reason for the progressive infertility and the long-term consequences of constant LHCGR signaling. Mating with superovulated females showed that infertile KiLHRD582G mice had functional sperm and normal accessory gland function. Sexual behavior studies revealed that KiLHRD582G mice mounted females, but intromission was brief and ejaculation was not achieved. Histological analysis of the reproductive tract showed unique metaplastic changes resulting in pseudostratified columnar epithelial cells with cilia in the ampulla and chondrocytes in the penile body of the KiLHRD582G mice. The infertile KiLHRD582G exhibited enlarged sinusoids and a decrease in smooth muscle content in the corpora cavernosa of the penile body. However, collagen content was unchanged. Leydig cell adenomas and degenerating seminiferous tubules were seen in 1-year-old KiLHRD582G mice. We conclude that progressive infertility in KiLHRD582G mice is due to sexual dysfunction likely due to functional defects in the penis. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com.

Consequences of tributyltin chloride induced stress in Leydig cells: an ex-vivo approach.

Science.gov (United States)

Mitra, Sumonto; Srivastava, Ankit; Khanna, Smita; Khandelwal, Shashi

2014-03-01

Tributyltin (TBT), a member of the organotin family, is a known endocrine disruptor. It persists long in the environment and is widely used in various industrial applications. This study was planned to understand its toxic influence on Leydig cells isolated from 28 day old wistar rats. In-vitro exposure to TBT-Chloride (TBTC) (300-3000 nM) reduced cell viability (DNA fragmentation, nuclear condensation and MTT assay) and affected testosterone production. TBTC induced both apoptotic and necrotic cell death (AnnexinV/PI binding assay). Involvement of calcium (Ca(2+)), redox imbalance (ROS, GSH and TBARS) and mitochondria in TBTC toxicity was evaluated by using Ca(2+) inhibitors (BAPTA-AM, EGTA, Ruthenium Red), free radical scavengers (NAC, C-Phycocyanin) and mitochondrial permeability transition pore inhibitor (Cyclosporine A). Protein expression analysis of phosphorylated MAPKinases (ERK1/2, JNK1/2, & p38), steroidogenic proteins (3β-HSD, StAR & TSPO) and apoptotic proteins (Bax, Bcl2) illustrates the cytotoxic and anti-steroidogenic activity of TBTC. Copyright © 2014 Elsevier B.V. All rights reserved.

Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells.

Science.gov (United States)

Kilcoyne, Karen R; Smith, Lee B; Atanassova, Nina; Macpherson, Sheila; McKinnell, Chris; van den Driesche, Sander; Jobling, Matthew S; Chambers, Thomas J G; De Gendt, Karel; Verhoeven, Guido; O'Hara, Laura; Platts, Sophie; Renato de Franca, Luiz; Lara, Nathália L M; Anderson, Richard A; Sharpe, Richard M

2014-05-06

Fetal growth plays a role in programming of adult cardiometabolic disorders, which in men, are associated with lowered testosterone levels. Fetal growth and fetal androgen exposure can also predetermine testosterone levels in men, although how is unknown, because the adult Leydig cells (ALCs) that produce testosterone do not differentiate until puberty. To explain this conundrum, we hypothesized that stem cells for ALCs must be present in the fetal testis and might be susceptible to programming by fetal androgen exposure during masculinization. To address this hypothesis, we used ALC ablation/regeneration to identify that, in rats, ALCs derive from stem/progenitor cells that express chicken ovalbumin upstream promoter transcription factor II. These stem cells are abundant in the fetal testis of humans and rodents, and lineage tracing in mice shows that they develop into ALCs. The stem cells also express androgen receptors (ARs). Reduction in fetal androgen action through AR KO in mice or dibutyl phthalate (DBP) -induced reduction in intratesticular testosterone in rats reduced ALC stem cell number by ∼40% at birth to adulthood and induced compensated ALC failure (low/normal testosterone and elevated luteinizing hormone). In DBP-exposed males, this failure was probably explained by reduced testicular steroidogenic acute regulatory protein expression, which is associated with increased histone methylation (H3K27me3) in the proximal promoter. Accordingly, ALCs and ALC stem cells immunoexpressed increased H3K27me3, a change that was also evident in ALC stem cells in fetal testes. These studies highlight how a key component of male reproductive development can fundamentally reprogram adult hormone production (through an epigenetic change), which might affect lifetime disease risk.

1950MHz Radio Frequency Electromagnetic Radiation Inhibits Testosterone Secretion of Mouse Leydig Cells.

Science.gov (United States)

Lin, Yan-Yun; Wu, Tao; Liu, Jun-Ye; Gao, Peng; Li, Kang-Chu; Guo, Qi-Yan; Yuan, Meng; Lang, Hai-Yang; Zeng, Li-Hua; Guo, Guo-Zhen

2017-12-23

More studies that are focused on the bioeffects of radio-frequency (RF) electromagnetic radiation that is generated from the communication devices, but there were few reports with confirmed results about the bioeffects of RF radiation on reproductive cells. To explore the effects of 1950 MHz RF electromagnetic radiation (EMR) on mouse Leydig (TM3) cells. TM3 cells were irradiated or sham-irradiated continuously for 24 h by the specific absorption rate (SAR) 3 W/kg radiation. At 0, 1, 2, 3, 4, and 5 days after irradiation, cell proliferation was detected by cell counting kit-8 (CCK-8) method, cell cycle distribution, percentage of apoptosis, and cellular reactive oxygen species (ROS) were examined by flow cytometry, Testosterone level was measured using enzyme-linked immunosorbent assay (ELISA) assay, messenger ribonucleic acid (mRNA) expression level of steroidogenic acute regulatory protein (StAR) and P450scc in TM3 cells was detected by real-time polymerase chain reaction (PCR). After being irradiated for 24 h, cell proliferation obviously decreased and cell cycle distribution, secretion capacity of Testosterone, and P450scc mRNA level were reduced. While cell apoptosis, ROS, and StAR mRNA level did not change significantly. The current results indicated that 24 h of exposure at 1950 MHz 3 W/kg radiation could cause some adverse effects on TM3 cells proliferation and Testosterone secretion, further studies about the biological effects in the reproductive system that are induced by RF radiation are also needed.

Leydig Cell Tumor Associated with Testicular Adrenal Rest Tumors in a Patient with Congenital Adrenal Hyperplasia due to 11β-Hydroxylase Deficiency

OpenAIRE

Charfi, Nadia; Kamoun, Mahdi; Feki Mnif, Mouna; Mseddi, Neila; Mnif, Fatma; Kallel, Nozha; Ben Naceur, Basma; Rekik, Nabila; Fourati, Hela; Daoud, Emna; Mnif, Zainab; Hadj Sliman, Mourad; Sellami-Boudawara, Tahia; Abid, Mohamed

2012-01-01

Congenital adrenal hyperplasia (CAH) describes a group of inherited autosomal recessive disorders characterized by enzyme defects in the steroidogenic pathways that lead to the biosynthesis of cortisol, aldosterone, and androgens. Chronic excessive adrenocorticotropic hormone (ACTH) stimulation may result in hyperplasia of ACTH-sensitive tissues in adrenal glands and other sites such as the testes, causing testicular masses known as testicular adrenal rest tumors (TARTs). Leydig cell tumors (...

Morphological and functional maturation of Leydig cells: from rodent models to primates.

Science.gov (United States)

Teerds, Katja J; Huhtaniemi, Ilpo T

2015-01-01

Leydig cells (LC) are the sites of testicular androgen production. Development of LC occurs in the testes of most mammalian species as two distinct growth phases, i.e. as fetal and pubertal/adult populations. In primates there are indications of a third neonatal growth phase. LC androgen production begins in embryonic life and is crucial for the intrauterine masculinization of the male fetal genital tract and brain, and continues until birth after which it rapidly declines. A short post-natal phase of LC activity in primates (including human) termed 'mini-puberty' precedes the period of juvenile quiescence. The adult population of LC evolves, depending on species, in mid- to late-prepuberty upon reawakening of the hypothalamic-pituitary-testicular axis, and these cells are responsible for testicular androgen production in adult life, which continues with a slight gradual decline until senescence. This review is an updated comparative analysis of the functional and morphological maturation of LC in model species with special reference to rodents and primates. Pubmed, Scopus, Web of Science and Google Scholar databases were searched between December 2012 and October 2014. Studies published in languages other than English or German were excluded, as were data in abstract form only. Studies available on primates were primarily examined and compared with available data from specific animal models with emphasis on rodents. Expression of different marker genes in rodents provides evidence that at least two distinct progenitor lineages give rise to the fetal LC (FLC) population, one arising from the coelomic epithelium and the other from specialized vascular-associated cells along the gonad-mesonephros border. There is general agreement that the formation and functioning of the FLC population in rodents is gonadotrophin-responsive but not gonadotrophin-dependent. In contrast, although there is in primates some controversy on the role of gonadotrophins in the formation of

Leydig cell function in boys following treatment for testicular relapse of acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Blatt, J.; Sherins, R.J.; Niebrugge, D.; Bleyer, W.A.; Poplack, D.G.

1985-01-01

Current practice for achieving local control of testicular relapse in males with acute lymphoblastic leukemia (ALL) includes the use of 2,400-rad testicular radiation. Although this therapy is known to cause germ cell depletion, it has been assumed that it does not alter testicular secretion of testosterone. To test this assumption, the authors measured gonadotropin and testosterone levels in seven boys with ALL who had been treated with radiation for clinically apparent testicular relapse. In four of seven boys, testicular relapse was bilateral with overt involvement of one testicle and microscopic involvement of the other. Three of these four boys demonstrated delayed sexual maturation, and in addition to elevated follicle-stimulating hormone (FSH) concentrations, testosterone levels were low and luteinizing hormone levels were elevated compared with controls. These data indicate that boys with overt testicular leukemia who are treated with 2,400-rad testicular radiation are at risk for Leydig cell dysfunction. However, the relative contributions of radiation, prior chemotherapy, and leukemic infiltration to this dysfunction remain to be clarified

High-fat diet aggravates 2,2′,4,4′-tetrabromodiphenyl ether-inhibited testosterone production via DAX-1 in Leydig cells in rats

International Nuclear Information System (INIS)

Zhang, Zhan; Yu, Yongquan; Xu, Hengsen; Wang, Chao; Ji, Minghui; Gu, Jun; Yang, Lu; Zhu, Jiansheng; Dong, Huibin; Wang, Shou-Lin

2017-01-01

Growing evidence has revealed that a high-fat diet (HFD) could lead to disorders of glycolipid metabolism and insulin-resistant states, and HFDs have been associated with the inhibition of testicular steroidogenesis. Our previous study demonstrated that 2,2′,4,4′-tetrabromodiphenyl ether (BDE47) could increase the risk of diabetes in humans and reduce testosterone production in rats. However, whether the HFD affects BDE47-inhibited testosterone production by elevating insulin levels and inducing related pathways remains unknown. In male rats treated with BDE47 by gavage for 12 weeks, the HFD significantly increased the BDE47 content of the liver and testis and increased the weight of the adipose tissue; increased macrovesicular steatosis in the liver and the levels of triglycerides, fasting glucose and insulin; further aggravated the disruption of the seminiferous epithelium; and lowered the level of testosterone, resulting in fewer sperm in the epididymis. Of note, the HFD enhanced BDE47-induced DAX-1 expression and decreased the expression levels of StAR and 3β-HSD in the testicular interstitial compartments in rats. In isolated primary Leydig cells from rats, BDE47 or insulin increased DAX-1 expression, decreased the expression of StAR and 3β-HSD, and reduced testosterone production, which was nearly reversed by knocking down DAX-1. These results indicated that the HFD aggravates BDE47-inhibited testosterone production through hyperinsulinemia, and the accumulation of testicular BDE47 that induces the up-regulation of DAX-1 and the subsequent down-regulation of steroidogenic proteins, i.e., StAR and 3β-HSD, in Leydig cells. - Highlights: • High-fat diet (HFD) aggravates the accumulation of BDE47 in liver and testis in rats. • HFD aggravates BDE47-inhibited testosterone production via DAX-1 in Leydig cells. • HFD enhances BDE47-induced the disorder of glycolipid metabolism and hyperinsulinemia. • Both hyperinsulinemia and accumulation of BDE47

High-fat diet aggravates 2,2′,4,4′-tetrabromodiphenyl ether-inhibited testosterone production via DAX-1 in Leydig cells in rats

Energy Technology Data Exchange (ETDEWEB)

Zhang, Zhan; Yu, Yongquan [State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Xu, Hengsen [Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Wang, Chao [State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Ji, Minghui; Gu, Jun [Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Yang, Lu; Zhu, Jiansheng [State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Dong, Huibin [Changzhou Center for Disease Control and Prevention, 203 Taishan Road, Changzhou 2013022 (China); Wang, Shou-Lin, E-mail: wangshl@njmu.edu.cn [State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China)

2017-05-15

Growing evidence has revealed that a high-fat diet (HFD) could lead to disorders of glycolipid metabolism and insulin-resistant states, and HFDs have been associated with the inhibition of testicular steroidogenesis. Our previous study demonstrated that 2,2′,4,4′-tetrabromodiphenyl ether (BDE47) could increase the risk of diabetes in humans and reduce testosterone production in rats. However, whether the HFD affects BDE47-inhibited testosterone production by elevating insulin levels and inducing related pathways remains unknown. In male rats treated with BDE47 by gavage for 12 weeks, the HFD significantly increased the BDE47 content of the liver and testis and increased the weight of the adipose tissue; increased macrovesicular steatosis in the liver and the levels of triglycerides, fasting glucose and insulin; further aggravated the disruption of the seminiferous epithelium; and lowered the level of testosterone, resulting in fewer sperm in the epididymis. Of note, the HFD enhanced BDE47-induced DAX-1 expression and decreased the expression levels of StAR and 3β-HSD in the testicular interstitial compartments in rats. In isolated primary Leydig cells from rats, BDE47 or insulin increased DAX-1 expression, decreased the expression of StAR and 3β-HSD, and reduced testosterone production, which was nearly reversed by knocking down DAX-1. These results indicated that the HFD aggravates BDE47-inhibited testosterone production through hyperinsulinemia, and the accumulation of testicular BDE47 that induces the up-regulation of DAX-1 and the subsequent down-regulation of steroidogenic proteins, i.e., StAR and 3β-HSD, in Leydig cells. - Highlights: • High-fat diet (HFD) aggravates the accumulation of BDE47 in liver and testis in rats. • HFD aggravates BDE47-inhibited testosterone production via DAX-1 in Leydig cells. • HFD enhances BDE47-induced the disorder of glycolipid metabolism and hyperinsulinemia. • Both hyperinsulinemia and accumulation of BDE47

Toxic mechanisms of 3-monochloropropane-1,2-diol on progesterone production in R2C rat leydig cells.

Science.gov (United States)

Sun, Jianxia; Bai, Shun; Bai, Weibin; Zou, Feiyan; Zhang, Lei; Su, Zhijian; Zhang, Qihao; Ou, Shiyi; Huang, Yadong

2013-10-16

3-Monochloropropane-1,2-diol (3-MCPD) is a well-known food processing contaminant that has been shown to impede the male reproductive function. However, its mechanism of action remains to be elucidated. In this study, the effects of 3-MCPD on progesterone production were investigated using R2C Leydig cells. 3-MCPD caused concentration-dependent inhibition of cell viability at the IC25, IC50, and IC75 levels of 1.027, 1.802, and 3.160 mM, respectively. Single cell gel/comet assay and atomic force microscopy assay showed that 3-MCPD significantly induced early apoptosis. In addition, 3-MCPD significantly reduced progesterone production by reducing the expression of cytochrome P450 side-chain cleavage enzyme, steroidogenic acute regulatory protein, and 3β-hydroxysteroid dehydrogenase in R2C cells. The change in steroidogenic acute regulatory protein expression was highly consistent with progesterone production. Furthermore, the mitochondrial membrane potential and cAMP significantly decreased.

Radiation hardening and irradiation testing of in-cell electronics for MA23/APM

International Nuclear Information System (INIS)

Friant, A.

1988-09-01

We relate briefly the radiation hardening method used to guarantee a gamma resistance of 10 Mrad for the whole electronic equipment associated with the slave arm of MA23 M servomanipulator which will be set up in cell 404 in Marcoule (APM). We describe the radiation testing of electronic devices and of the various subsystems designed by the D. LETI groups involved in the MA23/APM project

In vitro functional screening as a means to identify new plasticizers devoid of reproductive toxicity

Energy Technology Data Exchange (ETDEWEB)

Boisvert, Annie; Jones, Steven; Issop, Leeyah [The Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Erythropel, Hanno C. [Department of Chemical Engineering, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Papadopoulos, Vassilios [The Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Culty, Martine, E-mail: martine.culty@mcgill.ca [The Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada)

2016-10-15

Plasticizers are indispensable additives providing flexibility and malleability to plastics. Among them, several phthalates, including di (2-ethylhexyl) phthalate (DEHP), have emerged as endocrine disruptors, leading to their restriction in consumer products and creating a need for new, safer plasticizers. The goal of this project was to use in vitro functional screening tools to select novel non-toxic plasticizers suitable for further in vivo evaluation. A panel of novel compounds with satisfactory plasticizer properties and biodegradability were tested, along with several commercial plasticizers, such as diisononyl-cyclohexane-1,2-dicarboxylate (DINCH®). MEHP, the monoester metabolite of DEHP was also included as reference compound. Because phthalates target mainly testicular function, including androgen production and spermatogenesis, we used the mouse MA-10 Leydig and C18-4 spermatogonial cell lines as surrogates to examine cell survival, proliferation, steroidogenesis and mitochondrial integrity. The most promising compounds were further assessed on organ cultures of rat fetal and neonatal testes, corresponding to sensitive developmental windows. Dose-response studies revealed the toxicity of most maleates and fumarates, while identifying several dibenzoate and succinate plasticizers as innocuous on Leydig and germ cells. Interestingly, DINCH®, a plasticizer marketed as a safe alternative to phthalates, exerted a biphasic effect on steroid production in MA-10 and fetal Leydig cells. MEHP was the only plasticizer inducing the formation of multinucleated germ cells (MNG) in organ culture. Overall, organ cultures corroborated the cell line data, identifying one dibenzoate and one succinate as the most promising candidates. The adoption of such collaborative approaches for developing new chemicals should help prevent the development of compounds potentially harmful to human health. - Highlights: • Phthalate plasticizers exert toxic effects on male reproduction

In vitro functional screening as a means to identify new plasticizers devoid of reproductive toxicity

International Nuclear Information System (INIS)

Boisvert, Annie; Jones, Steven; Issop, Leeyah; Erythropel, Hanno C.; Papadopoulos, Vassilios; Culty, Martine

2016-01-01

Plasticizers are indispensable additives providing flexibility and malleability to plastics. Among them, several phthalates, including di (2-ethylhexyl) phthalate (DEHP), have emerged as endocrine disruptors, leading to their restriction in consumer products and creating a need for new, safer plasticizers. The goal of this project was to use in vitro functional screening tools to select novel non-toxic plasticizers suitable for further in vivo evaluation. A panel of novel compounds with satisfactory plasticizer properties and biodegradability were tested, along with several commercial plasticizers, such as diisononyl-cyclohexane-1,2-dicarboxylate (DINCH®). MEHP, the monoester metabolite of DEHP was also included as reference compound. Because phthalates target mainly testicular function, including androgen production and spermatogenesis, we used the mouse MA-10 Leydig and C18-4 spermatogonial cell lines as surrogates to examine cell survival, proliferation, steroidogenesis and mitochondrial integrity. The most promising compounds were further assessed on organ cultures of rat fetal and neonatal testes, corresponding to sensitive developmental windows. Dose-response studies revealed the toxicity of most maleates and fumarates, while identifying several dibenzoate and succinate plasticizers as innocuous on Leydig and germ cells. Interestingly, DINCH®, a plasticizer marketed as a safe alternative to phthalates, exerted a biphasic effect on steroid production in MA-10 and fetal Leydig cells. MEHP was the only plasticizer inducing the formation of multinucleated germ cells (MNG) in organ culture. Overall, organ cultures corroborated the cell line data, identifying one dibenzoate and one succinate as the most promising candidates. The adoption of such collaborative approaches for developing new chemicals should help prevent the development of compounds potentially harmful to human health. - Highlights: • Phthalate plasticizers exert toxic effects on male reproduction

Perfluorooctane Sulfonate Concentrations in Amniotic Fluid, Biomarkers of Fetal Leydig Cell Function, and Cryptorchidism and Hypospadias in Danish Boys (1980-1996)

DEFF Research Database (Denmark)

Toft, Gunnar; Jönsson, Bo A; Bonde, Jens P

2016-01-01

BACKGROUND: Exposure to perfluorooctane sulfonate (PFOS) may potentially disturb fetal Leydig cell hormone production and male genital development. OBJECTIVES: We aimed to study the associations between levels of amniotic fluid PFOS, fetal steroid hormone, and insulin-like factor 3 (INSL3...... associations with fetal hormone levels may have long-term implications for reproductive health. CITATION: Toft G, Jönsson BA, Bonde JP, Nørgaard-Pedersen B, Hougaard DM, Cohen A, Lindh CH, Ivell R, Anand-Ivell R, Lindhard MS. 2016. Perfluorooctane sulfonate concentrations in amniotic fluid, biomarkers of fetal...

Malignant tumour stroma gonads Sertoli-Leydig:a communication clinic case and bibliographic review

International Nuclear Information System (INIS)

Krygier Waltier, G.; Rodriguez Lemes, R.; Carlevaro Elizondo, T.

1995-01-01

The malignant tumors of the stroma gonads represent 0.2% of all the tumors of the testicle, and they are almost exclusive of the relatively refractory to the radiotherapy and the chemotherapy, and the medium survive of the illness is of two years. it presents a clinical case of tumour to cells of Sertoli-Leydig in a 45 year-old man that heI consulted for sterility . A review of the literature it is made for finish [es

Cell cycle-dependent SUMO-1 conjugation to nuclear mitotic apparatus protein (NuMA)

Energy Technology Data Exchange (ETDEWEB)

Seo, Jae Sung; Kim, Ha Na; Kim, Sun-Jick; Bang, Jiyoung; Kim, Eun-A; Sung, Ki Sa [Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Yoon, Hyun-Joo [TissueGene Inc. 9605 Medical Center Dr., Rockville, MD 20850 (United States); Yoo, Hae Yong [Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Sungkyunkwan University, Seoul 135-710 (Korea, Republic of); Choi, Cheol Yong, E-mail: choicy@skku.ac.kr [Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)

2014-01-03

Highlights: •NuMA is modified by SUMO-1 in a cell cycle-dependent manner. •NuMA lysine 1766 is the primary target site for SUMOylation. •SUMOylation-deficient NuMA induces multiple spindle poles during mitosis. •SUMOylated NuMA induces microtubule bundling. -- Abstract: Covalent conjugation of proteins with small ubiquitin-like modifier 1 (SUMO-1) plays a critical role in a variety of cellular functions including cell cycle control, replication, and transcriptional regulation. Nuclear mitotic apparatus protein (NuMA) localizes to spindle poles during mitosis, and is an essential component in the formation and maintenance of mitotic spindle poles. Here we show that NuMA is a target for covalent conjugation to SUMO-1. We find that the lysine 1766 residue is the primary NuMA acceptor site for SUMO-1 conjugation. Interestingly, SUMO modification of endogenous NuMA occurs at the entry into mitosis and this modification is reversed after exiting from mitosis. Knockdown of Ubc9 or forced expression of SENP1 results in impairment of the localization of NuMA to mitotic spindle poles during mitosis. The SUMOylation-deficient NuMA mutant is defective in microtubule bundling, and multiple spindles are induced during mitosis. The mitosis-dependent dynamic SUMO-1 modification of NuMA might contribute to NuMA-mediated formation and maintenance of mitotic spindle poles during mitosis.

Anti-Ma2 antibody related paraneoplastic limbic/brain stem encephalitis associated with breast cancer expressing Ma1, Ma2, and Ma3 mRNAs.

Science.gov (United States)

Sahashi, K; Sakai, K; Mano, K; Hirose, G

2003-09-01

A 69 year old woman presented with cognitive impairment and supranuclear gaze palsy caused by paraneoplastic limbic/brain stem encephalitis associated with atypical medullary breast carcinoma. The cerebrospinal fluid from the patient harboured an anti-neuronal cell antibody against Ma2 antigen, but not against Ma1 or Ma3 antigen. Despite the antibody being restricted to the Ma2 antigen, the patient's cancer tissue expressed Ma1, Ma2, and Ma3 mRNAs. These results, and the expression of Ma2 mRNA in an atypical medullar breast carcinoma in another patient without paraneoplastic encephalitis, indicate that the induction of anti-Ma2 antibody depends on host immunoreponsiveness and not on the presence of the antigen itself in the cancer.

Gelatin–PMVE/MA composite scaffold promotes expansion of embryonic stem cells

International Nuclear Information System (INIS)

Chhabra, Hemlata; Gupta, Priyanka; Verma, Paul J.; Jadhav, Sameer; Bellare, Jayesh R.

2014-01-01

We introduce a new composite scaffold of gelatin and polymethyl vinyl ether-alt-maleic anhydride (PMVE/MA) for expansion of embryonic stem cells (ESCs) in an in vitro environment. To optimize the scaffold, we prepared a gelatin scaffold (G) and three composite scaffolds namely GP-1, GP-2, and GP-3 with varying PMVE/MA concentrations (0.2–1%) and characterized them by scanning electron microscopy (SEM), swelling study, compression testing and FTIR. SEM micrographs revealed interconnected porous structure in all the scaffolds. The permissible hemolysis ratio and activation of platelets by scaffolds confirmed the hemocompatibility of scaffolds. Initial biocompatibility assessment of scaffolds was conducted using hepatocarcinoma (Hep G2) cells and adhesion, proliferation and infiltration of Hep G2 cells in depth of scaffolds were observed, proving the scaffold's biocompatibility. Further Oct4B2 mouse embryonic stem cells (mESCs), which harbor a green fluorescence protein transgene under regulatory control of the Oct4 promotor, were examined for expansion on scaffolds with MTT assay. The GP-2 scaffold demonstrated the best cell proliferation and was further explored for ESC adherence and infiltration in depth (SEM and confocal), and pluripotent state of mESCs was assessed with the expression of Oct4-GFP and stage-specific embryonic antigen-1 (SSEA-1). This study reports the first demonstration of biocompatibility of gelatin–PMVE/MA composite scaffold and presents this scaffold as a promising candidate for embryonic stem cell based tissue engineering. - Highlights: • Composite scaffolds of gelatin and PMVE/MA were prepared by freeze-drying method. • SEM micrographs showed porous structure in all scaffolds of varying pore dimension. • GP-2 composite exhibited better cellular response in comparison to other scaffolds. • mESCs proliferated and expressed Oct-4 and SSEA-1, when cultured on GP-2 scaffold

Gelatin–PMVE/MA composite scaffold promotes expansion of embryonic stem cells

Energy Technology Data Exchange (ETDEWEB)

Chhabra, Hemlata [Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai (India); Gupta, Priyanka [Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai (India); IITB-Monash Research Academy, Mumbai (India); Department of Chemical Engineering, Monash University, Melbourne (Australia); Verma, Paul J. [Turretfield Research Centre, South Australian Research and Development Institute, Rosedale, South Australia (Australia); Jadhav, Sameer; Bellare, Jayesh R. [Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai (India)

2014-04-01

We introduce a new composite scaffold of gelatin and polymethyl vinyl ether-alt-maleic anhydride (PMVE/MA) for expansion of embryonic stem cells (ESCs) in an in vitro environment. To optimize the scaffold, we prepared a gelatin scaffold (G) and three composite scaffolds namely GP-1, GP-2, and GP-3 with varying PMVE/MA concentrations (0.2–1%) and characterized them by scanning electron microscopy (SEM), swelling study, compression testing and FTIR. SEM micrographs revealed interconnected porous structure in all the scaffolds. The permissible hemolysis ratio and activation of platelets by scaffolds confirmed the hemocompatibility of scaffolds. Initial biocompatibility assessment of scaffolds was conducted using hepatocarcinoma (Hep G2) cells and adhesion, proliferation and infiltration of Hep G2 cells in depth of scaffolds were observed, proving the scaffold's biocompatibility. Further Oct4B2 mouse embryonic stem cells (mESCs), which harbor a green fluorescence protein transgene under regulatory control of the Oct4 promotor, were examined for expansion on scaffolds with MTT assay. The GP-2 scaffold demonstrated the best cell proliferation and was further explored for ESC adherence and infiltration in depth (SEM and confocal), and pluripotent state of mESCs was assessed with the expression of Oct4-GFP and stage-specific embryonic antigen-1 (SSEA-1). This study reports the first demonstration of biocompatibility of gelatin–PMVE/MA composite scaffold and presents this scaffold as a promising candidate for embryonic stem cell based tissue engineering. - Highlights: • Composite scaffolds of gelatin and PMVE/MA were prepared by freeze-drying method. • SEM micrographs showed porous structure in all scaffolds of varying pore dimension. • GP-2 composite exhibited better cellular response in comparison to other scaffolds. • mESCs proliferated and expressed Oct-4 and SSEA-1, when cultured on GP-2 scaffold.

Leydig cell number and sperm production decrease induced by chronic ametryn exposure: a negative impact on animal reproductive health.

Science.gov (United States)

Dantas, T A; Cancian, G; Neodini, D N R; Mano, D R S; Capucho, C; Predes, F S; Pulz, R Barbieri; Pigoso, A A; Dolder, H; Severi-Aguiar, G D C

2015-06-01

Ametryn is an herbicide used to control broadleaf and grass weeds and its acute and chronic toxicity is expected to be low. Since toxicological data on ametryn is scarce, the aim of this study was to evaluate rat reproductive toxicity. Thirty-six adult male Wistar rats (90 days) were divided into three groups: Co (control) and T1 and T2 exposed to 15 and 30 mg/kg/day of ametryn, respectively, for 56 days. Testicular analysis demonstrated that ametryn decreased sperm number per testis, daily sperm production, and Leydig cell number in both treated groups, although little perceptible morphological change has been observed in seminiferous tubule structure. Lipid peroxidation was higher in group T2, catalase activity decreased in T1 group, superoxide dismutase activity diminished, and a smaller number of sulphydryl groups of total proteins were verified in both exposed groups, suggesting oxidative stress. These results showed negative ametryn influence on the testes and can compromise animal reproductive performance and survival.

Ovarian Sertoli-Leydig Cell Tumor with Elevated Inhibin B as a Cause of Secondary Amenorrhea in an Adolescent with Germ Line DICER1 Mutation.

Science.gov (United States)

Luke, Amy M; Moroney, John W; Snitchler, Andrea; Whiteway, Susan L

2017-10-01

Ovarian tumors, although uncommon in children, can retain endocrine function that disrupts normal feedback mechanisms leading to amenorrhea. Inheritance of germline DICER1 mutations can lead to increased risk for development of ovarian Sertoli-Leydig cell tumors (SLCTs). We report, to our knowledge, the first case of secondary amenorrhea due to elevated inhibin B levels in a female adolescent with an ovarian SLCT. Ovarian tumors should be included in the differential diagnosis for pediatric patients who present with menstrual irregularities. Early evaluation of the hypothalamic-pituitary-ovarian axis and inhibin levels is appropriate. Our case also emphasizes the need for testing for DICER1 mutations in pediatric patients with ovarian SLCTs. Published by Elsevier Inc.

Performance of the 10-kV, 5-MA pulsed-power system for the FRX-C compression experiment

International Nuclear Information System (INIS)

Rej, D.J.; Waganaar, W.J.

1991-01-01

Performance data are presented for the 10-kV, 5-MA, 1.5-MJ pulsed-power system developed for the Los Alamos magnetic fusion facility FRX-C. This system energizes a low-inductance magnet for the high-power, compression heating of compact toroid plasmas. An ignitron-switched, 20-mF, 10-kV, 4-MA capacitor bank is discharged to produce the main compression field, while an inductively-isolated, 10-mF, 10-kV, 1-MA bank generates an initial magnetic field to accept the translated plasma. To date, the complete system has successfully operated for two years and approximately 2000 high-power discharges. Component performance during typical and fault-mode operation is reviewed. 5 refs., 5 figs

Motion of the Rivera plate since 10 Ma relative to the Pacific and North American plates and the mantle

Science.gov (United States)

DeMets, Charles; Traylen, Stephen

2000-03-01

To better understand the influence of Rivera plate kinematics on the geodynamic evolution of western Mexico, we use more than 1400 crossings of seafloor spreading magnetic lineations along the Pacific-Rivera rise and northern Mathematician ridge to solve for rotations of the Rivera plate relative to the underlying mantle and the Pacific and North American plates at 14 times since 9.9 Ma. Our comparison of magnetic anomaly crossings from the undeformed Pacific plate to their counterparts on the Rivera plate indicates that significant areas of the Rivera plate have deformed since 9.9 Ma. Dextral shear along the southern edge of the plate from 3.3-2.2 Ma during a regional plate boundary reorganization deformed the Rivera plate farther into its interior than previously recognized. In addition, seafloor located north of two rupture zones within the Rivera plate sutured to North America after 1.5 Ma. Anomaly crossings from these two deformed regions thus cannot be used to reconstruct motion of the Rivera plate. Finite rotations that best reconstruct Pacific plate anomaly crossings onto their undeformed counterparts on the Rivera plate yield stage spreading rates that decrease gradually by 10% between 10 and 3.6 Ma, decrease rapidly by 20% after ˜3.6 Ma, and recover after 1 Ma. The slowdown in Pacific-Rivera seafloor spreading at 3.6 Ma coincided with the onset of dextral shear across the then-incipient southern boundary of the Rivera plate with the Pacific plate. The available evidence indicates that the Rivera plate has been an independent microplate since at least 10 Ma, contrary to published assertions that it fragmented from the Cocos plate at ˜5 Ma. Motion of the Rivera plate relative to North America has changed significantly since 10 Ma, in concert with significant changes in Pacific-Rivera motion. A significant and robust feature of Rivera-North America motion not previously recognized is the cessation of margin-normal convergence and thus subduction from 2

Evaluation of a new 10 mA DC current reference standard

CERN Document Server

Fernqvist, G; Power, F

2002-01-01

A new DC current reference standard has been developed as a component in a Current calibration hierarchy in the LHC project at CERN. The standard provides 10 mA DC current with an accuracy less than 0.5 ppm, drift less than 2 ppm/year and compliance error less than 0.1 ppm for 0-10 V. The paper gives the results from two years evaluation of a series of 5 units.

Hydrodynamic properties of the gonadotropin receptor from a murine Leydig tumor cell line are altered by desensitization

International Nuclear Information System (INIS)

Rebois, R.V.; Bradley, R.M.; Titlow, C.C.

1987-01-01

The murine Leydig tumor cell line 1 (MLTC-1) contains gonadotropin receptors (GR) that are coupled to adenylate cyclase through the stimulatory guanine nucleotide binding protein (G/sub s/). The binding of human choriogonadotropin (hGC) causes MLTC-1 cells to accumulate cAMP. With time, the ability of MLTC-1 cells to respond to hCG is attenuated by a process called desensitization. The hydrodynamic properties of GR from control and desensitized MLTC-1 cells were studied. Sucrose density gradient sedimentation in H 2 O and D 2 O and gel filtration chromatography were used to estimate the Stokes radius (a), partial specific volume (v/sub c/), sedimentation coefficient (s/sub 20,w/), and molecular weight (M/sub r/) of the detergent-solubilized hormone-receptor complex (hCG-GR). [ 125 I]hCG was bound to MLTC-1 cells under conditions that allow (37 0 C) or prevent (0 0 C) desensitization, and hCG-GR was solubilized in Triton X-100. In the absence of desensitization, control hCG-GR had a M/sub r/ of 213,000, whereas desensitized hCG-GR had a M/sub r/ of 158,000. Deglycosylated hCG (DG-HCG) is an antagonist that binds to GR with high affinity but fails to stimulate adenylate cyclase or cause desensitization. [ 125 I]DG-hCG was bound to MLTC-1 cells and DG-hCG-GR solubilized in Triton X-100. The hydrodynamic properties of DG-hCG-GR were the same as that for control hCG-GR. There was no evidence for the association of adenylate cyclase or G/sub s/ with GR in Triton X-100 solubilized preparations. When hCG was cross-linked to GR and solubilized with sodium dodecyl sulfate (SDS), the M/sub r/ was found to be 116,000, which was similar to that determined by SDS-polyacrylamide gel electrophoresis and less than that of the Triton X-100 solubilized control hCG-GR

1,3-Dichloro-2-propanol inhibits progesterone production through the expression of steroidogenic enzymes and cAMP concentration in Leydig cells.

Science.gov (United States)

Sun, Jianxia; Bai, Shun; Bai, Weibin; Zou, Feiyan; Zhang, Lei; Li, Guoqiang; Hu, Yunfeng; Li, Mingwei; Yan, Rian; Su, Zhijian; Huang, Yadong

2014-07-01

1,3-Dichloro-2-propanol (1,3-DCP) is a well-known food processing contaminant that has been shown to impede male reproductive function. However, its mechanism of action remains elusive. In this study, the effects of 1,3-DCP on progesterone production were investigated using the R2C Leydig cell model. 1,3-DCP significantly reduced cell viability from 7.48% to 97.4% at doses comprised between 0.5 and 6mM. Single cell gel/comet assays and atomic force microscopy assays showed that 1,3-DCP induced early phase cell apoptosis. In addition, 1,3-DCP significantly reduced progesterone production detected by radioimmunoassay (RIA). The results from quantitative polymerase chain reaction and western blotting demonstrated that the mRNA expression levels of steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase were significantly down-regulated in R2C cells. Particularly, the change rhythm of Star expression was highly consistent with progesterone production. Furthermore, the cyclic adenosine monophosphate (cAMP) and the mitochondrial membrane potential mediated by ROS, which are involved in regulating progesterone synthesis were also decreased in response to the 1,3-DCP treatment. Overall, the data presented here suggested that 1,3-DCP interferes with the male steroidogenic capacity mainly by down-regulating the level of cAMP and the key enzymes involved in the androgen synthesis pathway. Copyright © 2014 Elsevier Ltd. All rights reserved.

Arsenic activates the expression of 3β-HSD in mouse Leydig cells through repression of histone H3K9 methylation

DEFF Research Database (Denmark)

Alamdar, Ambreen; Xi, Guochen; Huang, Qingyu

2017-01-01

methylation. The results showed that H3K9me2/3 demethylase (JMJD2A) inhibitor, quercetin (Que) significantly attenuated the decrease of H3K9me2/3 and increase of 3β-HSD expression induced by arsenic. To further elucidate the mechanism for the activation of 3β-HSD, we determined the histone H3K9 methylation......Arsenic exposure has been associated with male reproductive dysfunction by disrupting steroidogenesis; however, the roles of epigenetic drivers, especially histone methylation in arsenic-induced steroidogenic toxicity remain not well documented. In this study, we investigated the role of histone H3...... lysine 9 (H3K9) methylation in steroidogenesis disturbance in mouse Leydig cells (MLTC-1) due to arsenic exposure. Our results indicated that mRNA and protein expression levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) were both significantly up-regulated while the rest of key genes involved...

Cimetidine-induced Leydig cell apoptosis and reduced EG-VEGF (PK-1) immunoexpression in rats: Evidence for the testicular vasculature atrophy.

Science.gov (United States)

Beltrame, Flávia L; Cerri, Paulo S; Sasso-Cerri, Estela

2015-11-01

The antiulcer drug cimetidine has shown to cause changes in the testicular microvasculature of adult rats. Since Leydig cells (LCs) produce the pro-angiogenic factor, EG-VEGF (endocrine gland-derived vascular endothelial growth factor), also known as prokineticin 1 (PK-1), this study examined the effect that cimetidine might have on LCs in testes with damaged vasculature. Rats received intraperitoneal injections of 100mg/kg of cimetidine (cimetidine group) or saline vehicle (control group) for 50 days. Serum testosterone levels were measured by chemiluminescence immunoassay and testicular sections were subjected to TUNEL and immunohistochemical reactions for caspase-3, 17β-HSD6, CD163 (ED2 macrophage), PK-1 and androgen receptor (AR). LCs in the cimetidine group showed TUNEL and caspase-3 positive labeling and apoptotic ultrastructural features. Moreover, the presence of 17β-HSD6-positive inclusions inside macrophages and the reduced number of LCs, AR immunoreactivity and serum testosterone levels correlated with a decrease in either the number of PK-1-immunostained LCs or PK-1 immunoreactivity. Although it is not clear which cell type is the primary target of cimetidine in the testicular interstitial compartment, these findings support a direct link between cimetidine-induced testicular vascular atrophy and LCs damage. Copyright © 2015 Elsevier Inc. All rights reserved.

Autoradiographic studies on the kinetics of fetal supporting cells and wall cells in rats 19 days after conception

International Nuclear Information System (INIS)

Lugani-Mehta, S.

1980-01-01

The duration of the S-phase of supporting cells and wall cells of rat fetuses aged 19 days was determined by the ''labelled mitosis'' method. The supporting cells are predecessors of the sertoli cells while the wall cells are predecessors of the boundary tissue and, possibly, of part of the peritubular Leydig cell system. The S-phase of the supporting cells was found to last 10.1 h while the S-phase of the wall cells lasted 9.2 h. The data were not in agreement with the data of other authors. (orig./MG) [de

A novel synthetic analog of militarin, MA-1 induces mitochondrial dependent apoptosis by ROS generation in human lung cancer cells

International Nuclear Information System (INIS)

Yoon, Deok Hyo; Lim, Mi-Hee; Lee, Yu Ran; Sung, Gi-Ho; Lee, Tae-Ho; Jeon, Byeong Hwa; Cho, Jae Youl; Song, Won O.; Park, Haeil; Choi, Sunga; Kim, Tae Woong

2013-01-01

A synthetic Militarin analog-1[(2R,3R,4R,5R)-1,6-bis(4-(2,4,4-trimethylpentan-2-yl)phenoxy) hexane-2,3,4,5-tetraol] is a novel derivative of constituents from Cordyceps militaris, which has been used to treat a variety of chronic diseases including inflammation, diabetes, hyperglycemia and cancers. Here, we report for the first time the synthesis of Militarin analog-1 (MA-1) and the apoptotic mechanism of MA-1 against human lung cancer cell lines. Treatment with MA-1 significantly inhibited the viability of 3 human lung cancer cell lines. The inhibition of viability and growth in MA-1-treated A549 cells with an IC 50 of 5 μM were mediated through apoptosis induction, as demonstrated by an increase in DNA fragmentation, sub-G 0 /G 1 -DNA fraction, nuclear condensation, and phosphatidylserine exposure. The apoptotic cell death caused mitochondrial membrane permeabilization through regulation of expression of the Bcl-2 family proteins, leading to cytochrome c release in a time-dependent manner. Subsequently, the final stage of apoptosis, activation of caspase-9/-3 and cleavage of poly (ADP ribose) polymerase, was induced. Furthermore, A549 lung cancer cells were more responsive to MA-1 than a bronchial epithelial cell line (BEAS-2B), involving the rapid generation of reactive oxygen species (ROS), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation. The pharmacological inhibition of ROS generation and JNK/p38 MAPK exhibited attenuated DNA fragmentation in MA-1-induced apoptosis. Oral administration of MA-1 also retarded growth of A549 orthotopic xenografts. In conclusion, the present study indicates that the new synthetic derivative MA-1 triggers mitochondrial apoptosis through ROS generation and regulation of MAPKs and may be a potent therapeutic agent against human lung cancer. - Highlights: • We report a novel synthesized derivative, militarin analog-1 (MA-1). • MA-1-induced cancer cell death was triggered by the ROS

A novel synthetic analog of militarin, MA-1 induces mitochondrial dependent apoptosis by ROS generation in human lung cancer cells

Energy Technology Data Exchange (ETDEWEB)

Yoon, Deok Hyo; Lim, Mi-Hee [Department of Biochemistry, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Lee, Yu Ran [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Sung, Gi-Ho [Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Suwon 404-707 (Korea, Republic of); Lee, Tae-Ho [R and D Center, Dong-A Pharmaceutical Co, Ltd, Yongin 446-905 (Korea, Republic of); Jeon, Byeong Hwa [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Cho, Jae Youl [Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Song, Won O. [Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States); Park, Haeil [College of Pharmacy, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Choi, Sunga, E-mail: sachoi@cnu.ac.kr [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Kim, Tae Woong, E-mail: tawkim@kangwon.ac.kr [Department of Biochemistry, Kangwon National University, Chuncheon 200-701 (Korea, Republic of)

2013-12-15

A synthetic Militarin analog-1[(2R,3R,4R,5R)-1,6-bis(4-(2,4,4-trimethylpentan-2-yl)phenoxy) hexane-2,3,4,5-tetraol] is a novel derivative of constituents from Cordyceps militaris, which has been used to treat a variety of chronic diseases including inflammation, diabetes, hyperglycemia and cancers. Here, we report for the first time the synthesis of Militarin analog-1 (MA-1) and the apoptotic mechanism of MA-1 against human lung cancer cell lines. Treatment with MA-1 significantly inhibited the viability of 3 human lung cancer cell lines. The inhibition of viability and growth in MA-1-treated A549 cells with an IC{sub 50} of 5 μM were mediated through apoptosis induction, as demonstrated by an increase in DNA fragmentation, sub-G{sub 0}/G{sub 1}-DNA fraction, nuclear condensation, and phosphatidylserine exposure. The apoptotic cell death caused mitochondrial membrane permeabilization through regulation of expression of the Bcl-2 family proteins, leading to cytochrome c release in a time-dependent manner. Subsequently, the final stage of apoptosis, activation of caspase-9/-3 and cleavage of poly (ADP ribose) polymerase, was induced. Furthermore, A549 lung cancer cells were more responsive to MA-1 than a bronchial epithelial cell line (BEAS-2B), involving the rapid generation of reactive oxygen species (ROS), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation. The pharmacological inhibition of ROS generation and JNK/p38 MAPK exhibited attenuated DNA fragmentation in MA-1-induced apoptosis. Oral administration of MA-1 also retarded growth of A549 orthotopic xenografts. In conclusion, the present study indicates that the new synthetic derivative MA-1 triggers mitochondrial apoptosis through ROS generation and regulation of MAPKs and may be a potent therapeutic agent against human lung cancer. - Highlights: • We report a novel synthesized derivative, militarin analog-1 (MA-1). • MA-1-induced cancer cell death was triggered by

Structural bisphenol analoques differentially target steroidogenesis in murine MA-10 Leydig cells as well as the glucocorticoid receptor

NARCIS (Netherlands)

Roelofs, M.J.E.; Berg, van den M.; Bovee, T.F.H.; Piersma, A.H.; Duursen, van M.B.M.

2015-01-01

Although much information on the endocrine activity of bisphenol A (BPA) is available, a proper human hazard assessment of analogues that are believed to have a less harmful toxicity profile is lacking. Here the possible effects of BPA, bisphenol F (BPF), bisphenol S (BPS), as well as the brominated

Structural bisphenol analogues differentially target steroidogenesis in murine MA-10 Leydig cells as well as the glucocorticoid receptor

NARCIS (Netherlands)

Roelofs, Maarke J|info:eu-repo/dai/nl/357301137; van den Berg, Martin|info:eu-repo/dai/nl/08660466X; Bovee, Toine F H; Piersma, Aldert H|info:eu-repo/dai/nl/071276947; van Duursen, Majorie B|info:eu-repo/dai/nl/181957701

2015-01-01

Although much information on the endocrine activity of bisphenol A (BPA) is available, a proper human hazard assessment of analogues that are believed to have a less harmful toxicity profile is lacking. Here the possible effects of BPA, bisphenol F (BPF), bisphenol S (BPS), as well as the brominated

Orchiectomy for suspected microscopic tumor in patients with anti-Ma2-associated encephalitis.

Science.gov (United States)

Mathew, R M; Vandenberghe, R; Garcia-Merino, A; Yamamoto, T; Landolfi, J C; Rosenfeld, M R; Rossi, J E; Thiessen, B; Dropcho, E J; Dalmau, J

2007-03-20

To report the presence of microscopic neoplasms of the testis in men with anti-Ma2-associated encephalitis (Ma2-encephalitis) and to discuss the clinical implications. Orchiectomy specimens were examined using immunohistochemistry with Ma2 and Oct4 antibodies. Among 25 patients with Ma2-encephalitis younger than 50 years, 19 had germ-cell tumors, and 6 had no evidence of cancer. These 6 patients underwent orchiectomy because they fulfilled five criteria: 1) demonstration of anti-Ma2 antibodies in association with MRI or clinical features compatible with Ma2-encephalitis, 2) life-threatening or progressive neurologic deficits, 3) age Ma2 was expressed by neoplastic cells in three of three patients examined. Even though most patients had severe neurologic deficits at the time of orchiectomy (median progression of symptoms, 10 months), 4 had partial improvement and prolonged stabilization (8 to 84 months, median 22.5 months) and two did not improve after the procedure. In young men with Ma2-encephalitis, 1) the disorder should be attributed to a germ-cell neoplasm of the testis unless another Ma2-expressing tumor is found, 2) negative tumor markers, ultrasound, body CT, or PET do not exclude an intratubular germ-cell neoplasm of the testis, and 3) if no tumor is found, the presence of the five indicated criteria should prompt consideration of orchiectomy.

Morotochoerus from Uganda (17.5 Ma and Kenyapotamus from Kenya (13-11 Ma: implications for hippopotamid origins

Directory of Open Access Journals (Sweden)

Pickford, M.

2011-12-01

Full Text Available The aim of this paper is to describe and interpret suiform teeth from Moroto, Uganda, and Ngorora, Kenya, which contribute to the debate about hippo-anthracothere-whale relationships. The early stages of hippopotamid evolution are relatively poorly known on account of the paucity of their fossil record older than 7 Ma. New specimens of Morotochoerus from Uganda reveal that it is not closely related to Hippopotamidae; the superficial resemblances of the cheek teeth to those of hippos represent convergences and not homologies. Restricted samples of Palaeopotamus ternani are available from the Middle Miocene of Kenya {Maboko, ca 16 Ma; Muruyur, ca 14.5 Ma; Fort Ternan, ca 13.7 Ma} while from the base of the late Miocene, Kenyapotamus coryndonae is known from Kenya {Ngerngerwa, ca 10.5-10 Ma; Nakali, ca 10.5 Ma; Samburu Hills, ca 9.5 Ma}, Ethiopia {Ch’orora, ca 10.5 Ma} and Tunisia {Beglia Formation ca 11-10 Ma}. The recovery of specimens of Kenyapotamus from the Ngorora Formation, Kenya, aged ca 11 Ma, is of interest because it includes well preserved teeth, including an m/3 in good condition. These specimens support the hypothesis that hippopotamids descended from palaeochoerids and not from anthracotheres.El objetivo de este trabajo es describir e interpretar los dientes suiformes de Moroto, Uganda, y Ngorora, Kenia, que contribuyen al debate sobre las relaciones hipo-anthracothere-whale. Las primeras etapas de la evolución de los hipopotámidos son relativamente poco conocidas a causa de la escasez de su registro fósil en edades superiors a los 7 Ma. Nuevos ejemplares de Morotochoerus en Uganda revelan que no están estrechamente relacionados con Hippopotamidae, las semejanzas superficiales de los dientes de la mandíbula con los de los hipopótamos representan convergencias y no homologías. Algunas muestras de Palaeopotamus ternani aparecen en el Medio Mioceno de Kenia {Maboko, ca 16 Ma; Muruyur, ca 14.5 Ma; Fort Ternan, ca 13.7 Ma

Design and evaluation of a 10-mA DC current reference standard

CERN Document Server

Fernqvist, G; Pickering, J; Power, F

2003-01-01

A new DC current reference standard has been developed for high- current power converter calibration in the large hadron collider (LHC) project at the European Organization for Nuclear Research (CERN). This standard provides a near ideal 10-mA DC current with long-term drift of one part in 10/sup 6/ per year. The paper describes the requirements and the detailed design and evaluation of the unit. Since similar 10-V standards are commercially available, the paper concentrates on the unique current output capability of this device. (4 refs).

A prospective study on contrast-enhanced magnetic resonance imaging of testicular lesions: distinctive features of Leydig cell tumours

International Nuclear Information System (INIS)

Manganaro, Lucia; Vinci, Valeria; Saldari, Matteo; Bernardo, Silvia; Cantisani, Vito; Catalano, Carlo; Pozza, Carlotta; Gianfrilli, Daniele; Pofi, Riccardo; Lenzi, Andrea; Isidori, Andrea M.; Scialpi, Michele

2015-01-01

Up to 20 % of incidentally found testicular lesions are benign Leydig cell tumours (LCTs). This study evaluates the role of contrast-enhanced magnetic resonance imaging (MRI) in the identification of LCTs in a large prospective cohort study. We enrolled 44 consecutive patients with at least one solid non-palpable testicular lesion who underwent scrotal MRI. Margins of the lesions, signal intensity and pattern of wash-in and wash-out were analysed by two radiologists. The frequency distribution of malignant and benign MRI features in the different groups was compared by using the chi-squared or Fisher's exact test. Sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy were calculated. The sensitivity of scrotal MRI to diagnose LCTs was 89.47 % with 95.65 % specificity; sensitivity for malignant lesions was 95.65 % with 80.95 % specificity. A markedly hypointense signal on T2-WI, rapid and marked wash-in followed by a prolonged washout were distinctive features significantly associated with LCTs. Malignant lesions were significantly associated with blurred margins, weak hypointense signal on T2-WI,and weak and progressive wash-in. The overall diagnostic accuracy was 93 %. LCTs have distinctive contrast-enhanced MRI features that allow the differential diagnosis of incidental testicular lesions. (orig.)

A prospective study on contrast-enhanced magnetic resonance imaging of testicular lesions: distinctive features of Leydig cell tumours

Energy Technology Data Exchange (ETDEWEB)

Manganaro, Lucia; Vinci, Valeria; Saldari, Matteo; Bernardo, Silvia; Cantisani, Vito; Catalano, Carlo [Sapienza University of Rome, Department of Radiology, Rome (Italy); Pozza, Carlotta; Gianfrilli, Daniele; Pofi, Riccardo; Lenzi, Andrea; Isidori, Andrea M. [Sapienza University of Rome, Department of Experimental Medicine, Rome (Italy); Scialpi, Michele [Perugia University, S. Maria della Misericordia Hospital, Department of Surgical and Biomedical Sciences, Division of Radiology 2, Perugia (Italy)

2015-12-15

Up to 20 % of incidentally found testicular lesions are benign Leydig cell tumours (LCTs). This study evaluates the role of contrast-enhanced magnetic resonance imaging (MRI) in the identification of LCTs in a large prospective cohort study. We enrolled 44 consecutive patients with at least one solid non-palpable testicular lesion who underwent scrotal MRI. Margins of the lesions, signal intensity and pattern of wash-in and wash-out were analysed by two radiologists. The frequency distribution of malignant and benign MRI features in the different groups was compared by using the chi-squared or Fisher's exact test. Sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy were calculated. The sensitivity of scrotal MRI to diagnose LCTs was 89.47 % with 95.65 % specificity; sensitivity for malignant lesions was 95.65 % with 80.95 % specificity. A markedly hypointense signal on T2-WI, rapid and marked wash-in followed by a prolonged washout were distinctive features significantly associated with LCTs. Malignant lesions were significantly associated with blurred margins, weak hypointense signal on T2-WI,and weak and progressive wash-in. The overall diagnostic accuracy was 93 %. LCTs have distinctive contrast-enhanced MRI features that allow the differential diagnosis of incidental testicular lesions. (orig.)

Subcellular distribution of [3H]-dexamethasone mesylate binding sites in Leydig cells using electron microscope radioautography

International Nuclear Information System (INIS)

Stalker, A.; Hermo, L.; Antakly, T.

1991-01-01

The present view is that glucocorticoid hormones bind to their cytoplasmic receptors before reaching their nuclear target sites, which include specific DNA sequences. Although it is believed that cytoplasmic sequestration of steroid receptors and other transcription factors (such as NFKB) may regulate the overall activity of these factors, there is little information on the exact subcellular sites of steroid receptors or even of any other transcription factors. Tritiated (3H)-dexamethasone 21-mesylate (DM) is an affinity label that binds covalently to the glucocorticoid receptor (GR), thereby allowing morphological localization of the receptor at the light and electron microscope levels as well as for quantitative radioautographic (RAG) analysis. After injection of 3H-DM into the testis, a specific radioautographic signal was observed in Leydig cells, which correlated with a high level of immunocytochemically demonstrable GR in these cells at the light-microscope level. To localize the 3H-DM binding sites at the electron microscope (EM) level, the testes of 5 experimental and 3 control adrenalectomized rats were injected directly with 20 microCi 3H-DM; control rats received simultaneously a 25-fold excess of unlabeled dexamethasone; 15 min later, rats were fixed with glutaraldehyde and the tissue was processed for EM RAG analysis combined with quantitative morphometry. The radioautographs showed that the cytosol, nucleus, smooth endoplasmic reticulum (sER), and mitochondria were labeled. Since the cytosol was always adjacent to tubules of the sER, the term sER-rich cytosol was used to represent label over sER networks, which may also represent cytosol labeling due to the limited resolution of the radioautographic technique. Labeling was highest in sER-rich cytosol and mitochondria, at 53% and 31% of the total, respectively

The proliferative activity of testicular cell types and the effect of postnatal X-irradiation in the developing mouse testis

International Nuclear Information System (INIS)

Vergouwen, R.P.F.A.; Huiskamp, R.; Davids, J.A.G.; Rooij, D.G. de

1991-01-01

The authors describe the effects of x-irradiation on the developing mouse testis, particularly in relation to A spermatogonia, Sertoli cells, Leydig cells and mesenchymal cells commonly regarded as Leydig precursors. It was concluded that radiosensitivity is highest during the first week after birth and decreases thereafter, with the exception of A spermatogonia which are radiosensitive at all ages. (UK)

Regulation of the fate of dental-derived mesenchymal stem cells using engineered alginate-GelMA hydrogels.

Science.gov (United States)

Ansari, Sahar; Sarrion, Patricia; Hasani-Sadrabadi, Mohammad Mahdi; Aghaloo, Tara; Wu, Benjamin M; Moshaverinia, Alireza

2017-11-01

Mesenchymal stem cells (MSCs) derived from dental and orofacial tissues provide an alternative therapeutic option for craniofacial bone tissue regeneration. However, there is still a need to improve stem cell delivery vehicles to regulate the fate of the encapsulated MSCs for high quality tissue regeneration. Matrix elasticity plays a vital role in MSC fate determination. Here, we have prepared various hydrogel formulations based on alginate and gelatin methacryloyl (GelMA) and have encapsulated gingival mesenchymal stem cells (GMSCs) and human bone marrow MSCs (hBMMSCs) within these fabricated hydrogels. We demonstrate that addition of the GelMA to alginate hydrogel reduces the elasticity of the hydrogel mixture. While presence of GelMA in an alginate-based scaffold significantly increased the viability of encapsulated MSCs, increasing the concentration of GelMA downregulated the osteogenic differentiation of encapsulated MSCs in vitro due to decrease in the stiffness of the hydrogel matrix. The osteogenic suppression was rescued by addition of a potent osteogenic growth factor such as rh-BMP-2. In contrast, MSCs encapsulated in alginate hydrogel without GelMA were successfully osteo-differentiated without the aid of additional growth factors, as confirmed by expression of osteogenic markers (Runx2 and OCN), as well as positive staining using Xylenol orange. Interestingly, after two weeks of osteo-differentiation, hBMMSCs and GMSCs encapsulated in alginate/GelMA hydrogels still expressed CD146, an MSC surface marker, while MSCs encapsulated in alginate hydrogel failed to express any positive staining. Altogether, our findings suggest that it is possible to control the fate of encapsulated MSCs within hydrogels by tuning the mechanical properties of the matrix. We also reconfirmed the important role of the presence of inductive signals in guiding MSC differentiation. These findings may enable the design of new multifunctional scaffolds for spatial and temporal

Geomorphic evidence for post-10 Ma uplift of the western flank of the central Andes 18°30'-22°S

Science.gov (United States)

Hoke, Gregory D.; Isacks, Bryan L.; Jordan, Teresa E.; Blanco, NicoláS.; Tomlinson, Andrew J.; Ramezani, Jahandar

2007-10-01

The western Andean mountain front forms the western edge of the central Andean Plateau. Between 18.5° and 22°S latitude, the mountain front has ˜3000 m of relief over ˜50 km horizontal distance that has developed in the absence of major local Neogene deformation. Models of the evolution of the plateau, as well as paleoaltimetry estimates, all call for continued large-magnitude uplift of the plateau surface into the late Miocene (i.e., younger than 10 Ma). Longitudinal river profiles from 20 catchments that drain the western Andean mountain front contain several streams with knickpoint-bounded segments that we use to reconstruct the history of post-10 Ma surface uplift of the western flank of the central Andean Plateau. The generation of knickpoints is attributed to tectonic processes and is not a consequence of base level change related to Pacific Ocean capture, eustatic change, or climate change as causes for creating the knickpoint-bounded stream segments observed. Minor valley-filling alluvial gravels intercalated with the 5.4 Ma Carcote ignimbrite suggest uplift related river incision was well under way by 5.4 Ma. The maximum age of river incision is provided by the regionally extensive, approximately 10 Ma El Diablo-Altos de Pica paleosurface. The river profiles reveal that relative surface uplift of at least1 km occurred after 10 Ma.

Milk Oligosaccharides Inhibit Human Rotavirus Infectivity in MA104 Cells.

Science.gov (United States)

Laucirica, Daniel R; Triantis, Vassilis; Schoemaker, Ruud; Estes, Mary K; Ramani, Sasirekha

2017-09-01

Background: Oligosaccharides in milk act as soluble decoy receptors and prevent pathogen adhesion to the infant gut. Milk oligosaccharides reduce infectivity of a porcine rotavirus strain; however, the effects on human rotaviruses are less well understood. Objective: In this study, we determined the effect of specific and abundant milk oligosaccharides on the infectivity of 2 globally dominant human rotavirus strains. Methods: Four milk oligosaccharides-2'-fucosyllactose (2'FL), 3'-sialyllactose (3'SL), 6'-sialyllactose (6'SL), and galacto-oligosaccharides-were tested for their effects on the infectivity of human rotaviruses G1P[8] and G2P[4] through fluorescent focus assays on African green monkey kidney epithelial cells (MA104 cells). Oligosaccharides were added at different time points in the infectivity assays. Infections in the absence of oligosaccharides served as controls. Results: When compared with infections in the absence of glycans, all oligosaccharides substantially reduced the infectivity of both human rotavirus strains in vitro; however, virus strain-specific differences in effects were observed. Compared with control infections, the maximum reduction in G1P[8] infectivity was seen with 2'FL when added after the onset of infection (62% reduction, P rotaviruses in MA104 cells, primarily through an effect on the virus. Although breastfed infants are directly protected, the addition of specific oligosaccharides to infant formula may confer these benefits to formula-fed infants. © 2017 American Society for Nutrition.

Earth's youngest exposed granite and its tectonic implications: the 10-0.8 Ma Kurobegawa Granite.

Science.gov (United States)

Ito, Hisatoshi; Yamada, Ryuji; Tamura, Akihiro; Arai, Shoji; Horie, Kenji; Hokada, Tomokazu

2013-01-01

Although the quest for Earth's oldest rock is of great importance, identifying the youngest exposed pluton on Earth is also of interest. A pluton is a body of intrusive igneous rock that crystallized from slowly cooling magma at depths of several kilometers beneath the surface of the Earth. Therefore, the youngest exposed pluton represents the most recent tectonic uplift and highest exhumation. The youngest exposed pluton reported to date is the Takidani Granodiorite (~ 1.4 Ma) in the Hida Mountain Range of central Japan. Using LA-ICP-MS and SHRIMP U-Pb zircon dating methods, this study demonstrates that the Kurobegawa Granite, also situated in the Hida Mountain Range, is as young as ~ 0.8 Ma. In addition, data indicate multiple intrusion episodes in this pluton since 10 Ma with a ~ 2-million-year period of quiescence; hence, a future intrusion event is likely within 1 million years.

Identification and characterization of novel NuMA isoforms

Energy Technology Data Exchange (ETDEWEB)

Wu, Jin, E-mail: petersdu2112@hotmail.com [Key Laboratory for Cell Proliferation and Regulation of the Ministry of Education, Beijing Normal University, Beijing (China); Xu, Zhe [Department of Clinical Laboratory Diagnosis, Beijing Tiantan Hospital, Capital Medical University, Beijing (China); Core Laboratory for Clinical Medical Research, Beijing Tiantan Hospital, Capital Medical University, Beijing (China); He, Dacheng [Key Laboratory for Cell Proliferation and Regulation of the Ministry of Education, Beijing Normal University, Beijing (China); Lu, Guanting, E-mail: guantlv@126.com [Beijing DnaLead Science and Technology Co., LTD, Beijing (China)

2014-11-21

Highlights: • Seven NuMA isoforms generated by alternative splicing were categorized into 3 groups: long, middle and short. • Both exons 15 and 16 in long NuMA were “hotspot” for alternative splicing. • Lower expression of short NuMA was observed in cancer cells compared with nonneoplastic controls. • Distinct localization pattern of short isoforms indicated different function from that of long and middle NuMA. - Abstract: The large nuclear mitotic apparatus (NuMA) has been investigated for over 30 years with functions related to the formation and maintenance of mitotic spindle poles during mitosis. However, the existence and functions of NuMA isoforms generated by alternative splicing remains unclear. In the present work, we show that at least seven NuMA isoforms (categorized into long, middle and short groups) generated by alternative splicing from a common NuMA mRNA precursor were discovered in HeLa cells and these isoforms differ mainly at the carboxyl terminus and the coiled-coil domains. Two “hotspot” exons with molecular mass of 3366-nt and 42-nt tend to be spliced during alternative splicing in long and middle groups. Furthermore, full-length coding sequences of long and middle NuMA obtained by using fusion PCR were constructed into GFP-tagged vector to illustrate their cellular localization. Long NuMA mainly localized in the nucleus with absence from nucleoli during interphase and translocated to the spindle poles in mitosis. Middle NuMA displayed the similar cell cycle-dependent distribution pattern as long NuMA. However, expression of NuMA short isoforms revealed a distinct subcellular localization. Short NuMA were present in the cytosol during the whole cycle, without colocalization with mitotic apparatus. These results have allowed us tentatively to explore a new research direction for NuMA’s various functions.

Lansoprazole increases testosterone metabolism and clearance in male Sprague-Dawley rats: implications for leydig cell carcinogenesis

International Nuclear Information System (INIS)

Coulson, Michelle; Gibson, G. Gordon; Plant, Nick; Hammond, Tim; Graham, Mark

2003-01-01

Leydig cell tumours (LCTs) are frequently observed during rodent carcinogenicity studies, however, the significance of this effect to humans remains a matter of debate. Many chemicals that produce LCTs also induce hepatic cytochromes P450 (CYPs), but it is unknown whether these two phenomena are causally related. Our aim was to investigate the existence of a liver-testis axis wherein microsomal enzyme inducers enhance testosterone metabolic clearance, resulting in a drop in circulating hormone levels and a consequent hypertrophic response from the hypothalamic-pituitary-testis axis. Lansoprazole was selected as the model compound as it induces hepatic CYPs and produces LCTs in rats. Male Sprague-Dawley rats were dosed with lansoprazole (150 mg/kg/day) or vehicle for 14 days. Lansoprazole treatment produced effects on the liver consistent with an enhanced metabolic capacity, including significant increases in relative liver weights, total microsomal CYP content, individual CYP protein levels, and enhanced CYP-dependent testosterone metabolism in vitro. Following intravenous administration of [ 14 C]testosterone, lansoprazole-treated rats exhibited a significantly smaller area under the curve and significantly higher plasma clearance. Significant reductions in plasma and testicular testosterone levels were observed, confirming the ability of this compound to perturb androgen homeostasis. No significant changes in plasma LH, FSH, or prolactin levels were detected under our experimental conditions. Lansoprazole treatment exerted no marked effects on testicular testosterone metabolism. In summary, lansoprazole treatment induced hepatic CYP-dependent testosterone metabolism in vitro and enhanced plasma clearance of radiolabelled testosterone in vivo. These effects may contribute to depletion of circulating testosterone levels and hence play a role in the mode of LCT induction in lansoprazole-treated rats

Pig StAR: mRNA expression and alternative splicing in testis and Leydig cells, and association analyses with testicular morphology traits.

Science.gov (United States)

Zhang, Yanghai; Cui, Yang; Zhang, Xuelian; Wang, Yimin; Gao, Jiayang; Yu, Ting; Lv, Xiaoyan; Pan, Chuanying

2018-05-31

Steroidogenic acute regulatory protein (StAR), primarily expressed in Leydig cells (LCs) in the mammalian testes, is essential for testosterone biosynthesis and male fertility. However, no previous reports have explored the expression profiles, alternative splicing and genetic variations of StAR gene in pig. The aim of current study was to explore the expression profiles in different tissues and different types of testicular cells (LCs; spermatogonial stem cells, SSCs; Sertoli cells, SCs), to identify different splice variants and their expression levels, as well as to detect the indel polymorphism in pig StAR gene. Expression analysis results revealed that StAR was widely expressed in all tested tissues and the expression level in testis was significantly higher than that in other tissues (P StAR mRNA expression level was significantly higher in LCs than others (P StAR-a, StAR-b and StAR-c, were first found in pig. Further study showed StAR-a was highly expressed in both testis and LCs when compared with other variants (P StAR-a was the primary variant at StAR gene post-transcription and may facilitate the combination and transportation of cholesterol with StAR. In addition, a 5-bp duplicated deletion (NC_010457.5:g.5524-5528 delACTTG) was verified in the porcine StAR gene, which was closely related to male testicular morphology traits (P StAR gene might be a positive allele. Briefly, the current findings suggest that StAR and StAR-a play imperative roles in male fertility and the 5-bp indel can be a potential DNA marker for the marker-assisted selection in boar. Copyright © 2018 Elsevier Inc. All rights reserved.

The shift from low to high non-structural protein 1 expression in rotavirus-infected MA-104 cells

Directory of Open Access Journals (Sweden)

Laura Martinez-Alvarez

2013-06-01

Full Text Available A hallmark of group/species A rotavirus (RVA replication in MA-104 cells is the logarithmic increase in viral mRNAs that occurs four-12 h post-infection. Viral protein synthesis typically lags closely behind mRNA synthesis but continues after mRNA levels plateau. However, RVA non-structural protein 1 (NSP1 is present at very low levels throughout viral replication despite showing robust protein synthesis. NSP1 has the contrasting properties of being susceptible to proteasomal degradation, but being stabilised against proteasomal degradation by viral proteins and/or viral mRNAs. We aimed to determine the kinetics of the accumulation and intracellular distribution of NSP1 in MA-104 cells infected with rhesus rotavirus (RRV. NSP1 preferentially localises to the perinuclear region of the cytoplasm of infected cells, forming abundant granules that are heterogeneous in size. Late in infection, large NSP1 granules predominate, coincident with a shift from low to high NSP1 expression levels. Our results indicate that rotavirus NSP1 is a late viral protein in MA-104 cells infected with RRV, presumably as a result of altered protein turnover.

Earth's youngest exposed granite and its tectonic implications: the 10–0.8 Ma Kurobegawa Granite

Science.gov (United States)

Ito, Hisatoshi; Yamada, Ryuji; Tamura, Akihiro; Arai, Shoji; Horie, Kenji; Hokada, Tomokazu

2013-01-01

Although the quest for Earth's oldest rock is of great importance, identifying the youngest exposed pluton on Earth is also of interest. A pluton is a body of intrusive igneous rock that crystallized from slowly cooling magma at depths of several kilometers beneath the surface of the Earth. Therefore, the youngest exposed pluton represents the most recent tectonic uplift and highest exhumation. The youngest exposed pluton reported to date is the Takidani Granodiorite (~ 1.4 Ma) in the Hida Mountain Range of central Japan. Using LA-ICP-MS and SHRIMP U-Pb zircon dating methods, this study demonstrates that the Kurobegawa Granite, also situated in the Hida Mountain Range, is as young as ~ 0.8 Ma. In addition, data indicate multiple intrusion episodes in this pluton since 10 Ma with a ~ 2-million-year period of quiescence; hence, a future intrusion event is likely within 1 million years. PMID:23419636

Scaling of X pinches from 1 MA to 6 MA

International Nuclear Information System (INIS)

Bland, Simon Nicholas; McBride, Ryan D.; Wenger, David Franklin; Sinars, Daniel Brian; Chittenden, Jeremy Paul; Pikuz, Sergei A.; Harding, Eric; Jennings, Christopher A.; Ampleford, David J.; Yu, Edmund P.; Cuneo, Michael Edward; Shelkovenko, Tatiana A.; Hansen, Stephanie B.

2010-01-01

This final report for Project 117863 summarizes progress made toward understanding how X-pinch load designs scale to high currents. The X-pinch load geometry was conceived in 1982 as a method to study the formation and properties of bright x-ray spots in z-pinch plasmas. X-pinch plasmas driven by 0.2 MA currents were found to have source sizes of 1 micron, temperatures >1 keV, lifetimes of 10-100 ps, and densities >0.1 times solid density. These conditions are believed to result from the direct magnetic compression of matter. Physical models that capture the behavior of 0.2 MA X pinches predict more extreme parameters at currents >1 MA. This project developed load designs for up to 6 MA on the SATURN facility and attempted to measure the resulting plasma parameters. Source sizes of 5-8 microns were observed in some cases along with evidence for high temperatures (several keV) and short time durations (<500 ps).

Arsenic activates the expression of 3β-HSD in mouse Leydig cells through repression of histone H3K9 methylation

International Nuclear Information System (INIS)

Alamdar, Ambreen; Xi, Guochen; Huang, Qingyu; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

2017-01-01

Arsenic exposure has been associated with male reproductive dysfunction by disrupting steroidogenesis; however, the roles of epigenetic drivers, especially histone methylation in arsenic-induced steroidogenic toxicity remain not well documented. In this study, we investigated the role of histone H3 lysine 9 (H3K9) methylation in steroidogenesis disturbance in mouse Leydig cells (MLTC-1) due to arsenic exposure. Our results indicated that mRNA and protein expression levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) were both significantly up-regulated while the rest of key genes involved in steroidogenesis were down-regulated. Moreover, arsenic exposure significantly decreased the histone H3K9 di- and tri-methylation (H3K9me2/3) levels in MLTC-1 cells. Since H3K9 demethylation leads to gene activation, we further investigated whether the induction of 3β-HSD expression was ascribed to reduced H3K9 methylation. The results showed that H3K9me2/3 demethylase (JMJD2A) inhibitor, quercetin (Que) significantly attenuated the decrease of H3K9me2/3 and increase of 3β-HSD expression induced by arsenic. To further elucidate the mechanism for the activation of 3β-HSD, we determined the histone H3K9 methylation levels in Hsd3b gene promoter, which also showed significant decrease of H3K9me2/3 in the investigated region after arsenic exposure. Considering these results, we conclude that arsenic exposure induced 3β-HSD up-regulation by suppressing H3K9me2/3 status, which is suggested as a compensatory mechanism for steroidogenic disturbance in MLTC-1 cells. - Highlights: • Epigenetic mechanisms of arsenic-induced male reproductive toxicity remain unclear. • Arsenic disturbs the expression of key steroidogenic genes in MLTC-1 cells. • Histone H3K9 di- and tri-methylation was suppressed in arsenic-exposed cells. • Arsenic activates 3β-HSD expression through repression of histone H3K9 methylation.

Arsenic activates the expression of 3β-HSD in mouse Leydig cells through repression of histone H3K9 methylation

Energy Technology Data Exchange (ETDEWEB)

Alamdar, Ambreen; Xi, Guochen [Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Huang, Qingyu, E-mail: qyhuang@iue.ac.cn [Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Centre for Epigenetics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M (Denmark); Tian, Meiping [Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Eqani, Syed Ali Musstjab Akber Shah [Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Public Health and Environment Division, Department of Biosciences, COMSAT Institute of Information & Technology, Islamabad (Pakistan); Shen, Heqing, E-mail: hqshen@iue.ac.cn [Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China)

2017-07-01

Arsenic exposure has been associated with male reproductive dysfunction by disrupting steroidogenesis; however, the roles of epigenetic drivers, especially histone methylation in arsenic-induced steroidogenic toxicity remain not well documented. In this study, we investigated the role of histone H3 lysine 9 (H3K9) methylation in steroidogenesis disturbance in mouse Leydig cells (MLTC-1) due to arsenic exposure. Our results indicated that mRNA and protein expression levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) were both significantly up-regulated while the rest of key genes involved in steroidogenesis were down-regulated. Moreover, arsenic exposure significantly decreased the histone H3K9 di- and tri-methylation (H3K9me2/3) levels in MLTC-1 cells. Since H3K9 demethylation leads to gene activation, we further investigated whether the induction of 3β-HSD expression was ascribed to reduced H3K9 methylation. The results showed that H3K9me2/3 demethylase (JMJD2A) inhibitor, quercetin (Que) significantly attenuated the decrease of H3K9me2/3 and increase of 3β-HSD expression induced by arsenic. To further elucidate the mechanism for the activation of 3β-HSD, we determined the histone H3K9 methylation levels in Hsd3b gene promoter, which also showed significant decrease of H3K9me2/3 in the investigated region after arsenic exposure. Considering these results, we conclude that arsenic exposure induced 3β-HSD up-regulation by suppressing H3K9me2/3 status, which is suggested as a compensatory mechanism for steroidogenic disturbance in MLTC-1 cells. - Highlights: • Epigenetic mechanisms of arsenic-induced male reproductive toxicity remain unclear. • Arsenic disturbs the expression of key steroidogenic genes in MLTC-1 cells. • Histone H3K9 di- and tri-methylation was suppressed in arsenic-exposed cells. • Arsenic activates 3β-HSD expression through repression of histone H3K9 methylation.

Infant feeding with soy formula milk: effects on puberty progression, reproductive function and testicular cell numbers in marmoset monkeys in adulthood.

Science.gov (United States)

Tan, Karen A L; Walker, Marion; Morris, Keith; Greig, Irene; Mason, J Ian; Sharpe, Richard M

2006-04-01

This marmoset study addresses concerns about feeding human male infants with soy formula milk (SFM). From age 4 to 5 days, seven male co-twin sets were fed standard formula milk (SMA) or SFM for 5-6 weeks; blood samples were subsequently collected at 10-week intervals. Testes from co-twins killed at 120-138 weeks were fixed for cell counts. SFM- and SMA-fed twins showed normal weight gain; puberty started and progressed normally, based on blood testosterone measurements. Body weight, organ weights (prostate, seminal vesicles, pituitary, thymus and spleen) and penis length were comparable in co-twins. All SMA- and 6/7 SFM-fed males were fertile. Unexpectedly, testis weight (P = 0.041), Sertoli (P = 0.025) and Leydig cell (P = 0.026) numbers per testis were consistently increased in SFM-fed co-twins; the increase in Leydig cell numbers was most marked in males with consistently low-normal testosterone levels. Seminiferous epithelium volume per tubule showed a less consistent, non-significant increase in SFM-fed males; raised germ cell numbers per testis, probably due to increased Sertoli cells, conceivably resulted in larger testes. Average lumen size, although greater in SFM-fed group, was inconsistent between co-twins and the difference was not significant. Infant feeding with SFM has no gross adverse reproductive effects in male marmosets, though it alters testis size and cell composition, and there is consistent, if indirect, evidence for possible 'compensated Leydig cell failure'. Similar and perhaps larger changes likely occur in adult men who were fed SFM as infants.

Serum androgen binding protein and follicle stimulating hormone as indices of Sertoli cell function in the irradiated testis

International Nuclear Information System (INIS)

Delic, J.I.; Hendry, J.H.; Shalet, S.M.; Morris, I.D.

1986-01-01

The present study presents evidence of radiation-induced Sertoli cell damage in both the pubertal and adult rat. The indirect measurement of Sertoli cell function, serum follicle stimulating hormone (FSH), in general mirrored the changes seen in androgen binding protein (ABP), again indicating Sertoli cell dysfunction. Although FSH remained elevated in adult rats after 5 Gy and above and in pubertal rats after 10 and 20 Gy, the elevation was not as great as that observed in castrates. This suggests that FSH secretion was still inhibited by some factor. As ABP was reduced to near 'background' (castrate) levels after these high doses, suggesting Sertoli cell dysfunction, this may indicate that serum ABP levels may not adequately reflect all Sertoli cell functions. Alternatively FSH may have been inhibited by by Leydig cell androgens, which have been demonstrated to modulate, in part, FSH secretion. Although the Leydig cells were damaged, androgen secretion was not entirely reduced during the study. In general, FSH was elevated when severe damage to spermatogenesis was noted. Whether the changes were related to the absence of a specific spermatogenic cell type could not be determined. (UK)

Genome-wide analysis of autophagy-related genes in banana highlights MaATG8s in cell death and autophagy in immune response to Fusarium wilt.

Science.gov (United States)

Wei, Yunxie; Liu, Wen; Hu, Wei; Liu, Guoyin; Wu, Chunjie; Liu, Wei; Zeng, Hongqiu; He, Chaozu; Shi, Haitao

2017-08-01

MaATG8s play important roles in hypersensitive-like cell death and immune response, and autophagy is essential for disease resistance against Foc in banana. Autophagy is responsible for the degradation of damaged cytoplasmic constituents in the lysosomes or vacuoles. Although the effects of autophagy have been extensively revealed in model plants, the possible roles of autophagy-related gene in banana remain unknown. In this study, 32 MaATGs were identified in the draft genome, and the profiles of several MaATGs in response to fungal pathogen Fusarium oxysporum f. sp. cubense (Foc) were also revealled. We found that seven MaATG8s were commonly regulated by Foc. Through transient expression in Nicotiana benthamiana leaves, we highlight the novel roles of MaATG8s in conferring hypersensitive-like cell death, and MaATG8s-mediated hypersensitive response-like cell death is dependent on autophagy. Notablly, autophagy inhibitor 3-methyladenine (3-MA) treatment resulted in decreased disease resistance in response to Foc4, and the effect of 3-MA treatment could be rescued by exogenous salicylic acid, jasmonic acid and ethylene, indicating the involvement of autophagy-mediated plant hormones in banana resistance to Fusarium wilt. Taken together, this study may extend our understanding the putative role of MaATG8s in hypersensitive-like cell death and the essential role of autophagy in immune response against Foc in banana.

RITA plus 3-MA overcomes chemoresistance of head and neck cancer cells via dual inhibition of autophagy and antioxidant systems.

Science.gov (United States)

Shin, Daiha; Kim, Eun Hye; Lee, Jaewang; Roh, Jong-Lyel

2017-10-01

Reactivation of p53 and induction of tumor cell apoptosis (RITA) is a small molecule that blocks p53-MDM2 interaction, thereby reactivating p53 in tumors. RITA can induce exclusive apoptosis in cancer cells independently of the p53 pathway; however, the resistance of cancer cells remains a major drawback. Here, we found a novel resistance mechanism of RITA treatment and an effective combined treatment to overcome RITA resistance in head and neck cancer (HNC) cells. The effects of RITA and 3-methyladenine (3-MA) were tested in different HNC cell lines, including cisplatin-resistant and acquired RITA-resistant HNC cells. The effects of each drug alone and in combination were assessed by measuring cell viability, apoptosis, cell cycle, glutathione, reactive oxygen species, protein expression, genetic inhibition of p62 and Nrf2, and a mouse xenograft model of cisplatin-resistant HNC. RITA induced apoptosis of HNC cells at different levels without significantly inhibiting normal cell viability. Following RITA treatment, RITA-resistant HNC cells exhibited a sustained expression of other autophagy-related proteins, overexpressed p62, and displayed activation of the Keap1-Nrf2 antioxidant pathway. The autophagy inhibitor 3-MA sensitized resistant HNC cells to RITA treatment via the dual inhibition of molecules related to the autophagy and antioxidant systems. Silencing of the p62 gene augmented the combined effects. The effective antitumor activity of RITA plus 3-MA was also confirmed in vivo in mouse xenograft models transplanted with resistant HNC cells, showing increased oxidative stress and DNA damage. The results indicate that RITA plus 3-MA can help overcome RITA resistance in HNC cells. This study revealed a novel RITA resistant mechanism associated with the sustained induction of autophagy, p62 overexpression, and Keap1-Nrf2 antioxidant system activation. The combined treatment of RITA with the autophagy inhibitor 3-methyladenine overcomes RITA resistance via dual

Anti-Ma2 paraneoplastic encephalitis associated with testicular germ cell tumor treated by carboplatin, etoposide and bleomycin.

Science.gov (United States)

Kimura, Masaki; Onozawa, Mizuki; Fujisaki, Akira; Arakawa, Takashi; Takeda, Katsuhiko; Dalmau, Joseph; Hattori, Kazunori

2008-10-01

Anti-Ma2-associated encephalitis is a paraneoplastic disorder that predominantly affects the limbic system, diencephalon and brainstem, and is usually associated with tumors of the testis. We report a 35-year-old man with a right testicular mass who presented with multiple neurological complains, and clinical, serological and radiological features compatible with anti-Ma2-associated encephalitis. After three courses of carboplatin, etoposide and bleomycin for metastatic testicular germ-cell tumor, all elevated tumor markers normalized and the retroperitoneal metastases disappeared, but the neurological disorder deteriorated. To our knowledge, this is the first case in which orchiectomy followed by carboplatin, etoposide and bleomycin for a testicular tumor with anti-Ma2 encephalitis was performed.

SiMa Cells for a Serotype Specific and Sensitive Cell-Based Neutralization Test for Botulinum Toxin A and E.

Science.gov (United States)

Bak, Nicola; Rajagopal, Shalini; Stickings, Paul; Sesardic, Dorothea

2017-07-20

Botulinum toxins (BoNTs), of which there are seven serotypes, are among the most potent neurotoxins, with serotypes A, B and E causing human botulism. Antitoxins form the first line of treatment for botulism, and functional, highly sensitive in vitro methods for toxin neutralization are needed to replace the current in vivo methods used for determination of antitoxin potency. In this preliminary proof of concept study, we report the development of a neutralization test using the neuroblastoma SiMa cell line. The assay is serotype specific for either BoNT/A or BoNT/E, which both cleave unique sequences on SNAP-25 within SiMa cells. The end point is simple immunodetection of cleaved SNAP-25 from cell lysates with antibodies detecting only the newly exposed sequence on SNAP-25. Neutralizing antibodies prevent the toxin-induced cleavage of SNAP-25. The toxin neutralization assay, with an EC50 of ~2 mIU/mL determined with a standardized reference antiserum, is more sensitive than the mouse bioassays. Relevance was demonstrated with commercial and experimental antitoxins targeting different functional domains, and of known in vivo neutralizing activities. This is the first report describing a simple, specific, in vitro cell-based assay for the detection of neutralizing antibodies against BoNT/A and BoNT/E with a sensitivity exceeding that of the mouse bioassay.

Origin Of Black Shale (Marl) Formation Aided By Continuous Volcanism For 10Ma Including Oceanic Anoxic Event, OAE2 (93-93.5 Ma) In The Eagle Ford Formation In South Texas

Science.gov (United States)

Chakrabarty, P.; Basu, A. R.

2017-12-01

We report LA-ICPMS U-Pb ages and Hf isotopes of zircons, petrography, major and trace elements and X-ray diffraction (XRD) analyses of whole rock black shales(marls) from volcanic subsurface as well as surface exposure ash beds of the Eagle Ford and Boquillas Formations in South Texas. Zircons from the middle part of the 300ft long Eagle Ford cores yield ages of 93.2±1.66 Ma, 94.13±1.25 Ma and 93.7±1.9 Ma. These ages are consistent with the Cenomanian-Turonian (C-T) age of deposition in three contiguous cores with spatial separation of 140 miles. An approximate 10Ma duration of deposition of volcanic ash and marl, at a rate of 28ft/Ma for the Eagle Ford is suggested from the 85.76 to 95.5 Ma ages. These ages are from the Eagle Ford ash beds, below the Austin Chalk and above the Buda Limestone and cover the Oceanic Anoxic Event 2 at the C-T boundary. Zircons from 7 ash beds in the surface exposures of the Boquillas Formation near Del Rio, yield ages between 84.63 Ma - 90.91 Ma, implying younger than C-T boundary ages for these samples. The mineralogy, major and trace elements of the ash beds suggest their source from nearby arc-derived calc-alkaline volcanism. The ɛHf(T) of the analyzed ash bed zircons yield values between 0 - +8 averaging at +3.5, clearly indicating a mantle component in the host magmas of the zircons. This initial range of ɛHf(T) is similar to arc-volcanism signatures such as the Quaternary andesitic volcanism in Central Mexico. Petrographic analyses of marls away from the visible tuff layer contain phenocrysts of biotite, alkali feldspar and andesitic rock fragments. The whole rock marl with high concentration of some transition metals (V, Zn, Ni, Pb, Mo) and relatively higher MgO and TiO2 contents indicate contemporaneous arc volcanic activity at the time of marl deposition. XRD of subsurface Eagle Ford bulk marl samples from different depths in 4 cores, show volcanogenic clays, such as montmorillonite, vermiculite, dickite and halloysite

MaRIE 1.0: The Matter-Radiation Interactions in Extremes Project, and the Challenge of Dynamic Mesoscale Imaging

Energy Technology Data Exchange (ETDEWEB)

Barnes, Cris William [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Barber, John L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Kober, Edward Martin [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Lookman, Turab [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Sandberg, Richard L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Shlachter, Jack S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Sheffield, Richard L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2015-02-23

The Matter-Radiation Interactions in Extremes project will build the experimental facility for the time-dependent control of dynamic material performance. An x-ray free electron laser at up to 42-keV fundamental energy and with photon pulses down to sub-nanosecond spacing, MaRIE 1.0 is designed to meet the challenges of time-dependent mesoscale materials science. Those challenges will be outlined, the techniques of coherent diffractive imaging and dynamic polycrystalline diffraction described, and the resulting requirements defined for a coherent x-ray source. The talk concludes with the role of the MaRIE project and science in the future.

[Ma2 antibody and multiple mononeuropathies].

Science.gov (United States)

Ayrignac, X; Castelnovo, G; Landrault, E; Fayolle, H; Pers, Y-M; Honnorat, J; Campello, C; Figarella-Branger, D; Labauge, P

2008-01-01

Anti-Ma2 antibodies belong to a family of onconeuronal antibodies that target proteins expressed in brain, testis and several tumors. Previously observed in patients presenting with limbic encephalitis, they seem to be associated with several other paraneoplastic syndromes. We report the case of a 73-year-old woman presenting sensory and motor neuropathy associated with non-small-cell lung cancer who had Ma2-antibodies.

Clinical analysis of anti-Ma2-associated encephalitis.

Science.gov (United States)

Dalmau, Josep; Graus, Francesc; Villarejo, Alberto; Posner, Jerome B; Blumenthal, Deborah; Thiessen, Brian; Saiz, Albert; Meneses, Patricio; Rosenfeld, Myrna R

2004-08-01

Increasing experience indicates that anti-Ma2-associated encephalitis differs from classical paraneoplastic limbic or brainstem encephalitis, and therefore may be unrecognized. To facilitate its diagnosis we report a comprehensive clinical analysis of 38 patients with anti-Ma2 encephalitis. Thirty-four (89%) patients presented with isolated or combined limbic, diencephalic or brainstem dysfunction, and four with other syndromes. Considering the clinical and MRI follow-up, 95% of the patients developed limbic, diencephalic or brainstem encephalopathy. Only 26% had classical limbic encephalitis. Excessive daytime sleepiness affected 32% of the patients, sometimes with narcolepsy-cataplexy and low CSF hypocretin. Additional hormonal or MRI abnormalities indicated diencephalic-hypothalamic involvement in 34% of the patients. Eye movement abnormalities were prominent in 92% of the patients with brainstem dysfunction, but those with additional limbic or diencephalic deficits were most affected; 60% of these patients had vertical gaze paresis that sometimes evolved to total external ophthalmoplegia. Three patients developed atypical parkinsonism, and two a severe hypokinetic syndrome with a tendency to eye closure and dramatic reduction of verbal output. Neurological symptoms preceded the tumour diagnosis in 62% of the patients. Brain MRI abnormalities were present in 74% of all patients and 89% of those with limbic or diencephalic dysfunction. Among the 34 patients with cancer, 53% had testicular germ-cell tumours. Two patients without evidence of cancer had testicular microcalcification and one cryptorchidism, risk factors for testicular germ-cell tumours. After neurological syndrome development, 17 of 33 patients received oncological treatment (nine also immunotherapy), 10 immunotherapy alone, and six no treatment. Overall, 33% of the patients had neurological improvement, three with complete recovery; 21% had long-term stabilization, and 46% deteriorated. Features

Tumor de células de leydig, presentación con pubertad precoz

OpenAIRE

Araque, Maryuali; Uzcátegui, Lilia; Paoli, Mariela; Petrosino Tepedino, Pierina; Milano Molina, Melisse; Contreras, Adriana

2009-01-01

Objetivos: Presentar un caso de pubertad precoz secundaria a tumor de células de Leydig. Caso Clínico: Paciente preescolar masculino de 5 años, quien fue referido por presentar aparición de vello púbico, aumento de tamaño del pene, piel oleosa y crecimiento acelerado para la edad, sin antecedentes de traumatismo craneal o procesos infecciosos cerebrales. Al examen físico: peso 22,7kg y talla 117,2 cm, ambos en el percentil 97, masas musculares evidentes en tórax y miembros superio...

Tumor de células de Leydig, presentación con pubertad precoz

OpenAIRE

Maryuali, Araque; Uzcátegui, Lilia R.; Paoli, Mariela; Petrosino, Pierina; Milano, Melissa; Contreras, Adriana

2007-01-01

Objetivos: Presentar un caso de pubertad precoz secundaria a tumor de células de Leydig. Caso Clínico: Paciente preescolar masculino de 5 años, quien fue referido por presentar aparición de vello púbico, aumento de tamaño del pene, piel oleosa y crecimiento acelerado para la edad, sin antecedentes de traumatismo craneal o procesos infecciosos cerebrales. Al examen físico: peso 22,7kg y talla 117,2 cm, ambos en el percentil 97, masas musculares evidentes en tórax y miembros superiores, vello p...

Opioid system manipulation during testicular development: results on sperm production and sertoli cells population - doi: 10.4025/actascibiolsci.v33i2.5940 Opioid system manipulation during testicular development: results on sperm production and sertoli cells population - doi: 10.4025/actascibiolsci.v33i2.5940

Directory of Open Access Journals (Sweden)

Valdemiro Amaro Silva Júnior

2011-05-01

Full Text Available The Sertoli cell has fundamental importance to the development and maintenance of spermatogenesis, as well as it has a directly proportional numerical relationship to sperm production. The proliferative period of this cell in rats occurs between 13 days pre-natal and 21 days pos-natal, when is established the final population in adult animals. The Leydig cell can modulate the Sertoli cell proliferation during fetal and neonatal period through β-endorphin. The manipulation of opioidergic system can promote changes in parameters related to development of nervous, endocrine and reproductive systems. By the way, the main purpose of this present work was to compare the effects of the blockade of opioid receptor blocking in Sertoli cells using naltrexone (50 mg kg-1 during fetal and neonatal period in Wistar rats. According to the results, the manipulation of opioidergic system during pre-natal period reduced the total length of seminiferous tubule and Sertoli cell population in adult rats, but sperm production was normal because this cell has had a compensatory response for spermatozoids support capacity.The Sertoli cell has fundamental importance to the development and maintenance of spermatogenesis, as well as it has a directly proportional numerical relationship to sperm production. The proliferative period of this cell in rats occurs between 13 days pre-natal and 21 days pos-natal, when is established the final population in adult animals. The Leydig cell can modulate the Sertoli cell proliferation during fetal and neonatal period through β-endorphin. The manipulation of opioidergic system can promote changes in parameters related to development of nervous, endocrine and reproductive systems. By the way, the main purpose of this present work was to compare the effects of the blockade of opioid receptor blocking in Sertoli cells using naltrexone (50 mg kg-1 during fetal and neonatal period in Wistar rats. According to the results

Anti-Ma and anti-Ma2-associated paraneoplastic neurological syndromes.

Science.gov (United States)

Ortega Suero, G; Sola-Valls, N; Escudero, D; Saiz, A; Graus, F

Analyse the clinical profile, associated tumour types, and response to treatment of paraneoplastic neurological syndromes associated with antibodies against Ma proteins. A retrospective study of patients with antibodies against Ma proteins identified in a neuroimmunology laboratory of reference. Of the 32 patients identified, 20 showed reactivity against Ma2 only (anti-Ma2 antibodies), 11 against Ma1 and Ma2 (anti-Ma antibodies), and 1 with reactivity against Ma1 only (anti-Ma1 antibodies). The most common clinical presentations were limbic encephalopathy, diencephalic dysfunction, or brainstem encephalopathy, frequently appearing as a combination of these features. Three patients had isolated cerebellar dysfunction with anti-Ma antibodies, and 2 exhibited peripheral nervous system syndrome with anti-Ma2 antibodies. Testicular tumours were the most common neoplasms (40%) in the anti-Ma2 cases. In the group associated with anti-Ma1 antibodies, the most common were lung tumours (36%), followed by testicular tumours. All idiopathic cases were reactive to Ma2. The clinical outcome was significantly better in the anti-Ma2 group. The patient with anti-Ma1 presented with limbic encephalitis and brainstem dysfunction associated with lymphoepithelioma of the bladder. Specifically determining the different reactivities of anti-Ma protein antibodies in order to differentiate between Ma1 and Ma2 antibodies is important because anti-Ma2-associated paraneoplastic syndromes have a better outcome. Lastly, this study is the first to confirm that there may be cases that react exclusively to antibodies against Ma1. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

46 CFR 308.545 - Facultative cargo policy, Form MA-316.

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2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Facultative cargo policy, Form MA-316. 308.545 Section 308.545 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK... policy, Form MA-316. The standard form of War Risk Facultative Cargo Policy, Form MA-316, may be obtained...

Insulin-like factor 3 (INSL3 and the HPG axis in the male

Directory of Open Access Journals (Sweden)

Richard eIvell

2014-01-01

Full Text Available The HPG (hypothalamo-pituitary-gonadal axis comprises pulsatile GnRH from the hypothalamus impacting on the anterior pituitary to induce expression and release of both LH and FSH into the circulation. These in turn stimulate receptors on testicular Leydig and Sertoli cells, respectively, to promote steroidogenesis and spermatogenesis. Both Leydig and Sertoli cells exhibit negative feedback to the pituitary and/or hypothalamus via their products testosterone and inhibin B, respectively, thereby allowing tight regulation of the HPG axis. In particular, LH exerts both acute control on Leydig cells by influencing steroidogenic enzyme activity, as well as chronic control by impacting on Leydig cell differentiation and gene expression. Insulin-like peptide 3 (INSL3 represents an additional and different endpoint of the HPG axis. This Leydig cell hormone interacts with specific receptors, called RXFP2, on Leydig cells themselves to modulate steroidogenesis, and on male germ cells, probably to synergize with androgen-dependent Sertoli cell products to support spermatogenesis. Unlike testosterone, INSL3 is not acutely regulated by the HPG axis, but is a constitutive product of Leydig cells, which reflects their number and/or differentiation status and their ability therefore to produce various factors including steroids, together this is referred to as Leydig cell functional capacity. Because INSL3 is not subject to the acute episodic fluctuations inherent in the HPG axis itself, it serves as an excellent marker for Leydig cell differentiation and functional capacity, as in puberty, or in monitoring the treatment of hypogonadal patients, and at the same time buffering the HPG output.

Cosmogenic 10Be signature of geomagnetic dipole moment variations over the last 2 Ma

Science.gov (United States)

Simon, Q.; Thouveny, N.; Bourlès, D. L.; Valet, J. P.; Bassinot, F. C.; Savranskaia, T.; Duvivier, A.; Choy, S.; Gacem, L.; Villedieu, A.

2017-12-01

Long-term variations of the geomagnetic dipole moment (GDM) during periods of stable polarity and in transitional states (reversals and excursions) provide key information for understanding the geodynamo regime. Authigenic 10Be/9Be ratios (Be-ratio, proxy of atmospheric 10Be production) from marine sedimentary cores give independent and additional insights on the evolution of the geomagnetic intensity, completing information from absolute and relative paleointensity (RPI) records. Here we present new Be-ratio results obtained on several marine cores from the North Atlantic, Indian and Pacific Oceans which permit to extent into the Matuyama chron our previous 10Be-derived GDM reconstructions (Simon et al., 2016 JGR 121). Stratigraphic offsets measured between Be-ratio peaks and the corresponding RPI minima in each studied cores are assigned to (post-) detrital remanent magnetization (pDRM) effects leading to magnetization locking-in delays varying from 0 to 16 cm (up to 12 ka). All these results were compiled in order to obtain a continuous Be-ratio record covering the last 2 Ma. 10Be overproduction episodes triggered by geomagnetic dipole moment lows (GDL) linked to polarity reversals and excursions confirm the global control exerted by the GDM on cosmogenic radionuclides production. A dipole moment reconstruction derived from the Be-ratio stack (BeDiMo2Ma) was calibrated using absolute paleointensity data. This independent record completes the available paleomagnetic RPI records and permits: 1) to confront and increase the robustness and precision of GDM reconstructions; and, 2) to better constrain geomagnetic field instabilities during the mid- to late- Matuyama chron. Our new 10Be derived inventory is fully compatible with the GDL series linked to polarity reversals (Matuyama-Brunhes transition, Jaramillo and Olduvai boundaries), geomagnetic events (Cobb Mountain, Réunion) and Brunhes' excursions (e.g. Laschamp, Blake, Iceland-Basin, Big Lost). It further

Molecular and clinical diversity in paraneoplastic immunity to Ma proteins.

Science.gov (United States)

Rosenfeld, M R; Eichen, J G; Wade, D F; Posner, J B; Dalmau, J

2001-09-01

Antibodies to Ma1 and Ma2 proteins identify a paraneoplastic disorder that affects the limbic system, brain stem, and cerebellum. Preliminary studies suggested the existence of other Ma proteins and different patterns of immune response associated with distinct neurologic symptoms and cancers. In this study, our aim was to isolate the full-length sequence of Ma2 and new family members, identify the major autoantigen of the disorder, and extend the dinical-immunological analysis to 29 patients. Sera from selected patients were used to probe a brainstem cDNA library and isolate the entire Ma2 gene and a new family member, Ma3. Ma3 mRNA is ubiquitously expressed in brain, testis, and several systemic tissues. The variable cellular expression of Ma proteins and analysis of protein motifs suggest that these proteins play roles in the biogenesis of mRNA. Immunoblot studies identify Ma2 as the major autoantigen with unique epitopes recognized by all patients' sera. Eighteen patients had antibodies limited to Ma2: they developed limbic, hypothalamic, and brainstem encephalitis, and 78% had germ-cell tumors of the testis. Eleven patients had antibodies to Ma2 and additional antibodies to Ma1 and/or Ma3; they usually developed additional cerebellar symptoms and more intense brainstem dysfunction, and 82% of these patients had tumors other than germ-cell neoplasms. Overall, 17 of 24 patients (71%) with brain magnetic resonance imaging studies had abnormalities within or outside the temporal lobes, some as contrast-enhancing nodular lesions. A remarkable finding of immunity to Ma proteins is that neurologic symptoms may improve or resolve. This improvement segregated to a group of patients with antibodies limited to Ma2.

46 CFR 308.517 - Open Cargo Policy, Form MA-300.

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2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Open Cargo Policy, Form MA-300. 308.517 Section 308.517... Risk Cargo Insurance Ii-Open Policy War Risk Cargo Insurance § 308.517 Open Cargo Policy, Form MA-300. The standard form of War Risk Open Cargo, Form MA-300, may be obtained from the American War Risk...

Erosion in southern Tibet shut down at ∼10 Ma due to enhanced rock uplift within the Himalaya.

Science.gov (United States)

Tremblay, Marissa M; Fox, Matthew; Schmidt, Jennifer L; Tripathy-Lang, Alka; Wielicki, Matthew M; Harrison, T Mark; Zeitler, Peter K; Shuster, David L

2015-09-29

Exhumation of the southern Tibetan plateau margin reflects interplay between surface and lithospheric dynamics within the Himalaya-Tibet orogen. We report thermochronometric data from a 1.2-km elevation transect within granitoids of the eastern Lhasa terrane, southern Tibet, which indicate rapid exhumation exceeding 1 km/Ma from 17-16 to 12-11 Ma followed by very slow exhumation to the present. We hypothesize that these changes in exhumation occurred in response to changes in the loci and rate of rock uplift and the resulting southward shift of the main topographic and drainage divides from within the Lhasa terrane to their current positions within the Himalaya. At ∼17 Ma, steep erosive drainage networks would have flowed across the Himalaya and greater amounts of moisture would have advected into the Lhasa terrane to drive large-scale erosional exhumation. As convergence thickened and widened the Himalaya, the orographic barrier to precipitation in southern Tibet terrane would have strengthened. Previously documented midcrustal duplexing around 10 Ma generated a zone of high rock uplift within the Himalaya. We use numerical simulations as a conceptual tool to highlight how a zone of high rock uplift could have defeated transverse drainage networks, resulting in substantial drainage reorganization. When combined with a strengthening orographic barrier to precipitation, this drainage reorganization would have driven the sharp reduction in exhumation rate we observe in southern Tibet.

Dose and time relationships in the endocrine response of the irradiated adult rat testis

International Nuclear Information System (INIS)

Delic, J.I.; Hendry, J.H.; Morris, I.D.; Shalet, S.M.

1986-01-01

The dose- and time-dependent responses for the interstitial and tubular compartments in irradiated adult rat testes are described. Leydig cell dysfunction, as indicated by increased serum LH (to a maximum of 385% of control after 5 Gy) and decreased serum T (to a minimum of 30% of control after 10 Gy), was observed at 8 weeks postirradiation. Subsequent recovery of Leydig cell function was then observed, so that after 9 months serum T was normal but LH was still marginally elevated. The dysfunction, with a threshold of about 4 to 5 Gy, was associated with a loss of Leydig cells from the testis. Spermatogenic damage was observed; after doses of 3 Gy and above a marked dose-response was recorded as assessed by counts of tubule cross sections exhibiting spermatogenesis. Reduced serum levels of androgen binding protein indicated Sertoli cell dysfunction at 8 weeks after 3 Gy and above, with values of less than one half of those seen in the controls. Serum FSH also was elevated to between 150% and 200% of control, and after 9 months closely reflected androgen binding protein changes. Unlike the Leydig cell, no recovery with time was observed for this aspect of Sertoli cell function

High-content image informatics of the structural nuclear protein NuMA parses trajectories for stem/progenitor cell lineages and oncogenic transformation

International Nuclear Information System (INIS)

Vega, Sebastián L.; Liu, Er; Arvind, Varun; Bushman, Jared; Sung, Hak-Joon; Becker, Matthew L.; Lelièvre, Sophie; Kohn, Joachim; Vidi, Pierre-Alexandre; Moghe, Prabhas V.

2017-01-01

Stem and progenitor cells that exhibit significant regenerative potential and critical roles in cancer initiation and progression remain difficult to characterize. Cell fates are determined by reciprocal signaling between the cell microenvironment and the nucleus; hence parameters derived from nuclear remodeling are ideal candidates for stem/progenitor cell characterization. Here we applied high-content, single cell analysis of nuclear shape and organization to examine stem and progenitor cells destined to distinct differentiation endpoints, yet undistinguishable by conventional methods. Nuclear descriptors defined through image informatics classified mesenchymal stem cells poised to either adipogenic or osteogenic differentiation, and oligodendrocyte precursors isolated from different regions of the brain and destined to distinct astrocyte subtypes. Nuclear descriptors also revealed early changes in stem cells after chemical oncogenesis, allowing the identification of a class of cancer-mitigating biomaterials. To capture the metrology of nuclear changes, we developed a simple and quantitative “imaging-derived” parsing index, which reflects the dynamic evolution of the high-dimensional space of nuclear organizational features. A comparative analysis of parsing outcomes via either nuclear shape or textural metrics of the nuclear structural protein NuMA indicates the nuclear shape alone is a weak phenotypic predictor. In contrast, variations in the NuMA organization parsed emergent cell phenotypes and discerned emergent stages of stem cell transformation, supporting a prognosticating role for this protein in the outcomes of nuclear functions. - Highlights: • High-content analysis of nuclear shape and organization classify stem and progenitor cells poised for distinct lineages. • Early oncogenic changes in mesenchymal stem cells (MSCs) are also detected with nuclear descriptors. • A new class of cancer-mitigating biomaterials was identified based on image

High-content image informatics of the structural nuclear protein NuMA parses trajectories for stem/progenitor cell lineages and oncogenic transformation

Energy Technology Data Exchange (ETDEWEB)

Vega, Sebastián L. [Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ (United States); Liu, Er; Arvind, Varun [Department of Biomedical Engineering, Rutgers University, Piscataway, NJ (United States); Bushman, Jared [Department of Chemistry and Chemical Biology, New Jersey Center for Biomaterials, Piscataway, NJ (United States); School of Pharmacy, University of Wyoming, Laramie, WY (United States); Sung, Hak-Joon [Department of Chemistry and Chemical Biology, New Jersey Center for Biomaterials, Piscataway, NJ (United States); Department of Biomedical Engineering, Vanderbilt University, Nashville, TN (United States); Becker, Matthew L. [Department of Polymer Science and Engineering, University of Akron, Akron, OH (United States); Lelièvre, Sophie [Department of Basic Medical Sciences, Purdue University, West Lafayette, IN (United States); Kohn, Joachim [Department of Chemistry and Chemical Biology, New Jersey Center for Biomaterials, Piscataway, NJ (United States); Vidi, Pierre-Alexandre, E-mail: pvidi@wakehealth.edu [Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC (United States); Moghe, Prabhas V., E-mail: moghe@rutgers.edu [Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ (United States); Department of Biomedical Engineering, Rutgers University, Piscataway, NJ (United States)

2017-02-01

Stem and progenitor cells that exhibit significant regenerative potential and critical roles in cancer initiation and progression remain difficult to characterize. Cell fates are determined by reciprocal signaling between the cell microenvironment and the nucleus; hence parameters derived from nuclear remodeling are ideal candidates for stem/progenitor cell characterization. Here we applied high-content, single cell analysis of nuclear shape and organization to examine stem and progenitor cells destined to distinct differentiation endpoints, yet undistinguishable by conventional methods. Nuclear descriptors defined through image informatics classified mesenchymal stem cells poised to either adipogenic or osteogenic differentiation, and oligodendrocyte precursors isolated from different regions of the brain and destined to distinct astrocyte subtypes. Nuclear descriptors also revealed early changes in stem cells after chemical oncogenesis, allowing the identification of a class of cancer-mitigating biomaterials. To capture the metrology of nuclear changes, we developed a simple and quantitative “imaging-derived” parsing index, which reflects the dynamic evolution of the high-dimensional space of nuclear organizational features. A comparative analysis of parsing outcomes via either nuclear shape or textural metrics of the nuclear structural protein NuMA indicates the nuclear shape alone is a weak phenotypic predictor. In contrast, variations in the NuMA organization parsed emergent cell phenotypes and discerned emergent stages of stem cell transformation, supporting a prognosticating role for this protein in the outcomes of nuclear functions. - Highlights: • High-content analysis of nuclear shape and organization classify stem and progenitor cells poised for distinct lineages. • Early oncogenic changes in mesenchymal stem cells (MSCs) are also detected with nuclear descriptors. • A new class of cancer-mitigating biomaterials was identified based on image

Localization and expression of Orexin A and its receptor in mouse testis during different stages of postnatal development.

Science.gov (United States)

Joshi, Deepanshu; Singh, Shio Kumar

2017-01-15

Orexin A (OXA), a hypothalamic neuropeptide, is involved in regulation of various biological functions and its actions are mediated through G-protein-coupled receptor, OX1R. This neuropeptide has emerged as a central neuroendocrine modulator of reproductive functions. Both OXA and OX1R have been shown to be expressed in peripheral organs such as gastrointestinal and genital tracts. In the present study, localization and expression of OXA and OX1R in mouse testis during different stages of postnatal development have been investigated. Immunohistochemical results demonstrated localization of OXA and OX1R in both the interstitial and the tubular compartments of the testis throughout the period of postnatal development. In testicular sections on 0day postpartum (dpp), gonocytes, Sertoli cells and foetal Leydig cells showed OXA and OX1R-immunopositive signals. At 10dpp, Sertoli cells, spermatogonia, early spermatocytes and Leydig cells showed immunopositive signals for both, the ligand and the receptor. On 30 and 90dpp, the spermatogonia, Sertoli cells, spermatocytes, spermatids and Leydig cells showed the OXA and OX1R-immunopositive signals. At 90dpp, strong OXA-positive signals were seen in Leydig cells, primary spermatocytes and spermatogonia, while OX1R-immunopositive intense signals were observed in Leydig cells and elongated spermatids. Further, semiquantitative RT-PCR and immunoblot analyses showed that OXA and OX1R were expressed in the testis both at transcript and protein levels during different stages of postnatal development. The expression of OXA and OX1R increased progressively from day of birth (0dpp) until adulthood (90dpp), with maximal expression at 90 dpp. The results suggest that OXA and OX1R are expressed in the testis and that they may help in proliferation and development of germ cells, Leydig cells and Sertoli cells, and in the spermatogenic process and steroidogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

[Anti-Ma2-associated encephalitis and paraneoplastic limbic encephalitis].

Science.gov (United States)

Yamamoto, Tomotaka; Tsuji, Shoji

2010-08-01

proportion of the patients, approximately one-third show neurological improvement and another 20 - 40% stabilize in response to treatment, including immunotherapy and/or tumor treatment. Patients who have limited CNS involvement and testicular tumors with complete response to therapy are more likely to show neurological improvement. This fact emphasizes the importance of early diagnosis and prompt initiation of therapy. However, it should be noted that even carcinoma in situ, which is difficult to detect can cause severe neurological disorders. In this respect, it is useful to highlight that anti-Ma2 encephalitis is almost always associated with testicular germ cell tumors in men younger than 50 years. We experienced a 40-year-old patient with severe hypokinesis caused by anti-Ma2 encephalitis associated with bilateral intratubular germ-cell neoplasm of the testes. In older men and women, non-small-cell lung cancer is most common but various types of cancers are reported to be associated. In this study,in addition to reviewing the above case we have reviewed the significance of anti-Ma2 antibodies in the diagnosis of anti-Ma2 encephalitis and the clinical features of this disease.

42 CFR 422.2268 - Standards for MA organization marketing.

Science.gov (United States)

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Standards for MA organization marketing. 422.2268 Section 422.2268 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM MEDICARE ADVANTAGE PROGRAM Medicare Advantage Marketing Requirements § 422.2268 Standards for MA organizatio...

Myeloid cell leukemia-1 (Mc1-1 is a candidate target gene of hypoxia-inducible factor-1 (HIF-1 in the testis

Directory of Open Access Journals (Sweden)

Palladino Michael A

2012-12-01

Full Text Available Abstract Background Spermatic cord torsion can lead to testis ischemia (I and subsequent ischemia-reperfusion (I/R causing germ cell-specific apoptosis. Previously, we demonstrated that the hypoxia-inducible factor-1 (HIF-1 transcription factor, a key regulator of physiological responses to hypoxia, is abundant in Leydig cells in normoxic and ischemic testes. We hypothesize that testicular HIF-1 activates the expression of antiapoptotic target genes to protect Leydig cells from apoptosis. In silico analysis of testis genes containing a consensus hypoxia response element (HRE, 5’-RCGTG-3’ identified myeloid cell leukemia-1 (Mcl-1 as a potential HIF-1 target gene. The purpose of this study was to determine whether HIF-1 shows DNA-binding activity in normoxic and ischemic testes and whether Mcl-1 is a target gene of testicular HIF-1. Methods The testicular HIF-1 DNA-binding capacity was analyzed in vitro using a quantitative enzyme-linked immunosorbent assay (ELISA and electrophoretic mobility shift assays (EMSA. MCL-1 protein expression was evaluated by immunoblot analysis and immunohistochemistry. The binding of testicular HIF-1 to the Mcl-1 gene was examined via chromatin immunoprecipitation (ChIP analysis. Results The ELISA and EMSA assays demonstrated that testicular HIF-1 from normoxic and ischemic testes binds DNA equally strongly, suggesting physiological roles for HIF-1 in the normoxic testis, unlike most tissues in which HIF-1 is degraded under normoxic conditions and is only activated by hypoxia. MCL-1 protein was determined to be abundant in both normoxic and ischemic testes and expressed in Leydig cells. In a pattern identical to that of HIF-1 expression, the steady-state levels of MCL-1 were not significantly affected by I or I/R and MCL-1 co-localized with HIF-1α in Leydig cells. Chromatin immunoprecipitation (ChIP analysis using a HIF-1 antibody revealed sequences enriched for the Mcl-1 promoter. Conclusions The results

NuMA and nuclear lamins are cleaved during viral infection - inhibition of caspase activity prevents cleavage and rescues HeLa cells from measles virus-induced but not from rhinovirus 1B-induced cell death

International Nuclear Information System (INIS)

Taimen, Pekka; Berghaell, Heidi; Vainionpaeae, Raija; Kallajoki, Markku

2004-01-01

Nuclear matrix is a structural framework of important nuclear processes. We studied the effect of two different types of viral infections on nuclear matrix. HeLa cells were infected with human rhinovirus 1B (HRV 1B) or measles virus (MV), and Nuclear Mitotic Apparatus protein (NuMA) and lamins A/C and B were used as markers for internal nuclear matrix and peripheral nuclear lamina, respectively. We show that NuMA, lamins, and poly(ADP-ribose) polymerase-1 are cleaved during viral infection in a virus family-specific manner suggesting that these viruses activate different sets of proteases. Morphologically, NuMA was excluded from the condensed chromatin, lamins showed a folded distribution, and both proteins finally remained around the nuclear fragments. A general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-FMK) prevented the nuclear disintegration and the cleavage of the proteins studied. Interestingly, z-VAD-FMK rescued MV-infected but not HRV 1B-infected cells from cell death. These results show for the first time that NuMA and lamins are specific target proteins during virus-induced programmed cell death

Estrogen receptor alpha localization in the testes of men with normal spermatogenesis Estrogen receptor alpha localization in the testes of men with normal spermatogenesis

Directory of Open Access Journals (Sweden)

Eliza Filipiak

2012-10-01

Full Text Available It is known that estrogens act on the male reproductive tract by binding to estrogen receptors (ER a and
b. However, studies on ER localization in the human testis are discordant. The aim of this study was to investigate
the localization of ERa in the testes of adult men with normal spermatogenesis. Semen analysis of ten adult men
revealed azoospermia. FSH, LH and testosterone serum concentrations were within normal values, and the volume
of the testes was normal, hence obstructive azoospermia was suspected. The tissues from testicular surgical
biopsies were fixed in Bouin’s fluid and embedded in paraffin. Assessments of the seminiferous epithelium (scoring
10 to –1, the number of Leydig cells (scoring 1 to 5, the areal fraction of intertubular space (IS, measurements
of seminiferous tubule diameter, and the thickness of the tubular wall, were performed on microscopic
sections. Immunohistochemical staining was applied with monoclonal antibodies against ERa. The mean spermatogenesis
score was 10 points; IS — 30.6 ± 8.1%; seminiferous tubule diameter — 193.9 ± 19.4 μm; thickness of
tubular wall — 7.44 ± 1.1 μm; number of Leydig cells — 1.6 ± 1.1 points. Immunohistochemical staining showed
the localization of ERa to be in the Sertoli and Leydig cell cytoplasm, while ERa was absent in germ cells. The
results of testicular tissue analysis confirmed its normal structure and normal, full spermatogenesis. The presence
of ERa in Sertoli and Leydig cells in normal human testis demonstrated in this study suggests that estrogens may
affect testicular function.It is known that estrogens act on the male reproductive tract by binding to estrogen receptors (ER a and
b. However, studies on ER localization in the human testis are discordant. The aim of this study was to investigate
the localization of ERa in the testes of adult men with normal spermatogenesis. Semen

33 CFR 80.135 - Hull, MA to Race Point, MA.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Hull, MA to Race Point, MA. 80... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Atlantic Coast § 80.135 Hull, MA to Race Point, MA. (a... the east coast of Massachusetts from the easternmost radio tower at Hull, charted in approximate...

42 CFR 495.202 - Identification of qualifying MA organizations, MA-EPs and MA-affiliated eligible hospitals.

Science.gov (United States)

2010-10-01

... qualifying MA-affiliated eligible hospitals under the MA EHR incentive program are required to identify...-EPs and MA-affiliated eligible hospitals. 495.202 Section 495.202 Public Health CENTERS FOR MEDICARE... STANDARDS FOR THE ELECTRONIC HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to Medicare...

11beta-hydroxysteroid dehydrogenase type 2 expression in the newly formed Leydig cells after ethane dimethanesulphonate treatment of adult rats.

Directory of Open Access Journals (Sweden)

Katerina Georgieva

2008-01-01

Full Text Available The enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD catalyzes the reversible conversion of physiologically active corticosterone to the biologically inert 11beta-dehydrocorticosterone in rat testis and protect the Leydig cells (LCs against the suppressive effect of glucocorticoids. The developmental pathway of the adult LCs population is accompanied with an increase in the 11beta-HDS activity. Thus, 11beta-HDS together with its role in controlling the toxicological effect of glucocorticoids on LCs can be used as a marker for their functional maturity. Ethane 1,2-dimethanesulphonate (EDS treatment of adult rats become unique appropriate model, which enable to answer many questions related to the differentiation of adult LCs in the prepubertal rat testis. The aim of the present study was to investigate the specific changes in the 11beta-HDS type 2 immunoreactivity in tandem with the expression of androgen receptor (AR during renewal of LCs population after EDS treatment. In the present study, we observed the first appearance of immunostaining for 11beta-HSD2 in new LCs population on day 14 after EDS administration when the progenitor LCs were detected. Our immunohistochemical analysis revealed progressive increases in the 11beta-HSD2 reaction intensity on 21 days after EDS treatment and reached a maximum on day 35. AR immunoexpression was found in new LCs on day 14 and 21 after EDS injection with an increasing curve of intensity. The most prominent AR immunostaining in new population LCs was evident by 35 days after EDS and that coincided with the increased number of LCs and restoration of adult LCs population. Our results demonstrated similar pattern of immunoreactivity for 11beta-HSD2 and AR in new LCs population after EDS treatment and suggested that the changes in 11beta-HSD2 expression can be used for evaluation of adult LCs differentiation in rat testis.

Effects of prenatal Leydig cell function on the ratio of the second to fourth digit lengths in school-aged children.

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Takahiko Mitsui

Full Text Available Prenatal sex hormones can induce abnormalities in the reproductive system and adversely impact on genital development. We investigated whether sex hormones in cord blood influenced the ratio of the second to fourth digit lengths (2D/4D in school-aged children. Of the 514 children who participated in a prospective cohort study on birth in Sapporo between 2002 and 2005, the following sex hormone levels were measured in 294 stored cord blood samples (135 boys and 159 girls; testosterone (T, estradiol (E, progesterone, LH, FSH, inhibin B, and insulin-like factor 3 (INSL3. A total of 350 children, who were of school age and could be contacted for this survey, were then requested via mail to send black-and-white photocopies of the palms of both the left and right hands. 2D/4D was calculated in 190 children (88 boys and 102 girls using photocopies and derived from participants with the characteristics of older mothers, a higher annual household income, higher educational level, and fewer smokers among family members. 2D/4D was significantly lower in males than in females (p<0.01. In the 294 stored cord blood samples, T, T/E, LH, FSH, Inhibin B, and INSL3 levels were significantly higher in samples collected from males than those from females. A multivariate regression model revealed that 2D/4D negatively correlated with INSL3 in males and was significantly higher in males with <0.32 ng/mL of INSL3 (p<0.01. No correlations were observed between other hormones and 2D/4D. In conclusion, 2D/4D in school-aged children, which was significantly lower in males than in females, was affected by prenatal Leydig cell function.

The Preparation of an Electron Beam Machine 500 keV/10 mA Instrumentation

International Nuclear Information System (INIS)

Sudiyanto; Prayitno; Dewita; Bambang-Supardiyono; Widi-Setyawan

2000-01-01

The preparation of an Electron Beam Machine 500 keV/10 mA instrumentation by using a Distributed Instrumentation System have been done. The system consisting of industrial interfaces PCL-718 ADC 12 bit, PCLD-889 Mux/Prog Gain Amp PCLD-786 Driver Relay with solid state relays, PCL 745 serial com, DC motor 12-24 V/8.6 A with reduction gear 10:1 and a pair of PC's connected with twisted cable and an isolated amplifier AD-210 equipped with high voltage divider. The operation can be done using animation Pascal program on the remote mode using twisted cable and a pair of RS-485 interfaces, some operation sequences such as switch on/off blower unit, water pump cooling unit, filament voltage, anode voltage and some timer's have already been adapted on the computer program. Non intercepting beam monitoring technique have been discussed in this paper. (author)

Preliminary experiments to estimate the PE.MA.M (PElagic MArine Mesocosm) offshore behaviour

Science.gov (United States)

Albani, Marta; Piermattei, Viviana; Stefanì, Chiara; Marcelli, Marco

2016-04-01

The phytoplankton community is controlled not only by local environmental conditions but also by physical processes occurring on different temporal and spatial scales. Hydrodynamic local conditions play an important role in marine ecosystems. Several studies have shown that hydrodynamic conditions can influence the phytoplankton settling velocity, vertical and horizontal distribution and formation of cyanobacterial blooms. Mesocosms are useful structures to simulate marine environment at mesoscale resolution; allowing to closely approximate biotic or abiotic parameters of interest directly in nature. In this work an innovative structure named PE.MA.M (PElagic MArine Mesocosm) is presented and tested. Laboratory experiments have been conducted in order to observe seasonal variations of biomass behaviour in two different hydrodynamic conditions: outside as well as whithin the PE.MA.M. We have evaluated whether it is possible to isolate a natural system from external water mass hydrodynamic exchanges and to assume that phytoplankton cells' transition is limited at the net and sea interface. Preliminary experiments test the isolating capacity of the net, to determine the currents' attenuation rate and to estimate the possible PE.MA.M. offshore behaviour. In the first investigation, we monitored the diffusion of phytoplankton cells. The PE.MA.M. exterior and interior were simulated using a plexiglass tank divided into two half-tanks (Aout-Bin) by a septum consisting of a net like a PE.MA.M. The tank was filled up with 10 L of water and only the half-tank Aout was filled up with 10 ml of phytoplankton culture (Clorella sp.). We monitored the chlorophyll concentrations for 24 hours. The two tanks had similar concentrations after 4 hours (2.70322 mg/m³ Aout and 2.37245 mg/m3 Bin) and this constant relationship was maintened until the end of the test. In the second investigation we used clod cards to measure water motions.We conducted two experiments within tank, the first

[Relationship between phthalates and testicular dysgenesis syndrome].

Science.gov (United States)

Chen, Guo-Rong; Dong, Lei; Ge, Ren-Shan; Hardy, Matthew P

2007-03-01

Recent epidemiological evidence demonstrates that boys born to women exposed to phthalates during pregnancy have an increased incidence of cryptorchidism, hypospadias, testicular cancer and spermatogenic dysfunction, which are collectively referred to as testicular dysgenesis syndrome (TDS). TDS may be attributed to the dysfunction of Leydig cells and Sertoli cells during their differentiation after exposure to phthalates in utero. Fox example, Leydig cell functions are significantly affected by phthalates, leading to the decrease of two Leydig cell products--insulin-like growth factor 3 (INSL3) and testosterone, which are critical factors for testis descent. The disorientation of Leydig cells and Sertoli cells in the adult testis may be the cause of spermatogenic dysfunction.

46 CFR 308.306 - Second Seamen's War Risk Policy, Form MA-242.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Second Seamen's War Risk Policy, Form MA-242. 308.306... RISK INSURANCE Second Seamen's War Risk Insurance § 308.306 Second Seamen's War Risk Policy, Form MA-242. (a) The standard form of Second Seamen's War Risk Policy Form MA-242, may be obtained from the...

Estrogen receptor alpha localization in the testes of men with normal spermatogenesis.

Science.gov (United States)

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

2013-10-08

It is known that estrogens act on the male reproductive tract by binding to estrogen receptors (ER) α and β. However, studies on ER localization in the human testis are discordant. The aim of this study was to investigate the localization of ERα in the testes of adult men with normal spermatogenesis. Semen analysis of ten adult men revealed azoospermia. FSH, LH and testosterone serum concentrations were within normal values, and the volume of the testes was normal, hence obstructive azoospermia was suspected. The tissues from testicular surgical biopsies were fixed in Bouin's fluid and embedded in paraffin. Assessments of the seminiferous epithelium (scoring 10 to -1), the number of Leydig cells (scoring 1 to 5), the areal fraction of intertubular space (IS), measurements of seminiferous tubule diameter, and the thickness of the tubular wall, were performed on microscopic sections. Immunohistochemical staining was applied with monoclonal antibodies against ERα. The mean spermatogenesis score was 10 points; IS - 30.6 ± 8.1%; seminiferous tubule diameter - 193.9 ± 19.4 μm; thickness of tubular wall - 7.44 ± 1.1 μm; number of Leydig cells - 1.6 ± 1.1 points. Immunohistochemical staining showed the localization of ERα to be in the Sertoli and Leydig cell cytoplasm, while ERα was absent in germ cells. The results of testicular tissue analysis confirmed its normal structure and normal, full spermatogenesis. The presence of ERα in Sertoli and Leydig cells in normal human testis demonstrated in this study suggests that estrogens may affect testicular function.

Ma

Directory of Open Access Journals (Sweden)

Ingrid Berthon-Moine

2012-01-01

Full Text Available Ma (2009 is a single channel video of a mother and child walking together side by side, holding hands. The title is reminiscent of the affectionate nickname for a mother, 'Ma', but also a concealed way to convey maternal ambivalence. Maternal ambivalence is the result of the tension between the idealisation of motherhood and women’s lived experience of mothering. The maternal struggle finds its source in the difficulty of identifying with the ideological representation of the mother. This image still conveys an idealistic and nostalgic, patriarchal image of maternal love bounded by culture and history. http://podcast.ulcc.ac.uk/accounts/BirkbeckCollege/mamsie/MA.mov

42 CFR 422.52 - Eligibility to elect an MA plan for special needs individuals.

Science.gov (United States)

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Eligibility to elect an MA plan for special needs..., and Enrollment § 422.52 Eligibility to elect an MA plan for special needs individuals. (a) General rule. In order to elect a specialized MA plan for a special needs individual (Special Needs MA plan, or...

2,2′,4,4′-Tetrabromodiphenyl ether (BDE-47) decreases progesterone synthesis through cAMP-PKA pathway and P450scc downregulation in mouse Leydig tumor cells

International Nuclear Information System (INIS)

Han, Xiumei; Tang, Rong; Chen, Xiaojiao; Xu, Bo; Qin, Yufeng; Wu, Wei; Hu, Yanhui; Xu, Bin; Song, Ling; Xia, Yankai; Wang, Xinru

2012-01-01

Polybrominated diphenyl ethers (PBDEs) are commonly used as flame retardants in textiles, plastics and electronics and represent a group of persistent environmental contaminants. They have been found to accumulate in human and marine mammals. Previous studies have shown that PBDEs have endocrine-disrupting properties and reproductive toxicity. However, the mechanisms under the reproductive disruptions are still not well understood. In this study, we explored the effects of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) on progesterone biosynthesis and possible mechanisms in mouse Leydig tumor cells (mLTC-1). Our results showed that BDE-47 could reduce progesterone production and decrease the intracellular cAMP level induced by hCG or forskolin. These suggested that BDE-47 decreasing progesterone production in mLTC-1 cells may be associated with the decline of intracellular cAMP level. Moreover, our data also indicated that the site G protein in cAMP-PKA pathway may be involved in this process. Furthermore, the addition of cAMP analog, 8-Br-cAMP, could not reverse the decrease of progesterone biosynthesis, indicating that a post-cAMP site (or sites) might be involved into the BDE-47-decreased progesterone production. In addition, we found BDE-47 reduced the activity of P450 side chain cleavage enzyme (P450scc), which was companied with the decline of P450scc mRNA and protein level in mLTC-1 cells. Put all together, these results suggested that progesterone synthesis decrease induced by BDE-47 may be associated with attenuation of cAMP generation and reduction of P450scc activity.

Canine ovarian neoplasms: a clinicopathologic study of 71 cases, including histology of 12 granulosa cell tumors.

Science.gov (United States)

Patnaik, A K; Greenlee, P G

1987-11-01

In a retrospective study of 71 primary ovarian tumors in the dog, epithelial tumors (46%) were more common than sex cord stromal (34%) and germ cell tumors (20%). There were more adenocarcinomas (64%) than adenomas. Sex cord stromal tumors were equally divided into Sertoli-Leydig (12/24) and granulosa cell tumors (12/24). There were equal numbers (7/14) of dysgerminomas and teratomas among the germ cell tumors. Most teratomas (6/7) were malignant. Most granulosa cell tumors were solid; two were mostly cystic. Patterns included sheets of round and ovoid to spindle-shaped cells separated by thin, fibrovascular stroma; neoplastic cells formed rosettes or Call-Exner bodies. In some areas, neoplastic cells were in cords or columns and formed cyst-like structures. Four granulosa cell tumors were macrofollicular, having cysts lined with granulosa cells. Median ages of dogs with different ovarian neoplasms were similar; all were more than 10 years old, except the dogs with teratoma (mean age, 4 years). Most neoplasms were unilateral (84%), except the Sertoli-Leydig cell tumors, many of which were bilateral (36%). Size of ovarian neoplasms varied (2 cm3 to 15,000 cm3). Twenty-nine percent of neoplasms metastasized; adenocarcinomas (48%) and malignant teratomas (50%) had the highest rates, and distant metastasis was more common in malignant teratoma. Endometrial hyperplasia was in 67% of the dogs; it was most common in dogs with sex cord stromal tumors (95%). Uterine malignancy was not seen in dogs with granulosa cell tumors, although hyperplasia endometrium was in all dogs with this tumor. Cysts in the contralateral ovaries were most common in dogs with sex cord stromal tumors.

Mechanism of testosterone deficiency in the transgenic sickle cell mouse.

Directory of Open Access Journals (Sweden)

Biljana Musicki

Full Text Available Testosterone deficiency is associated with sickle cell disease (SCD, but its underlying mechanism is not known. We investigated the possible occurrence and mechanism of testosterone deficiency in a mouse model of human SCD. Transgenic sickle male mice (Sickle exhibited decreased serum and intratesticular testosterone and increased luteinizing hormone (LH levels compared with wild type (WT mice, indicating primary hypogonadism in Sickle mice. LH-, dbcAMP-, and pregnenolone- (but not 22-hydroxycholesterol- stimulated testosterone production by Leydig cells isolated from the Sickle mouse testis was decreased compared to that of WT mice, implying defective Leydig cell steroidogenesis. There also was reduced protein expression of steroidogenic acute regulatory protein (STAR, but not cholesterol side-chain cleavage enzyme (P450scc, in the Sickle mouse testis. These data suggest that the capacity of P450scc to support testosterone production may be limited by the supply of cholesterol to the mitochondria in Sickle mice. The sickle mouse testis exhibited upregulated NADPH oxidase subunit gp91phox and increased oxidative stress, measured as 4-hydroxy-2-nonenal, and unchanged protein expression of an antioxidant glutathione peroxidase-1. Mice heterozygous for the human sickle globin (Hemi exhibited intermediate hypogonadal changes between those of WT and Sickle mice. These results demonstrate that testosterone deficiency occurs in Sickle mice, mimicking the human condition. The defects in the Leydig cell steroidogenic pathway in Sickle mice, mainly due to reduced availability of cholesterol for testosterone production, may be related to NADPH oxidase-derived oxidative stress. Our findings suggest that targeting testicular oxidative stress or steroidogenesis mechanisms in SCD offers a potential treatment for improving phenotypic changes associated with testosterone deficiency in this disease.

Fetal antigen 1, an EGF multidomain protein in the sex hormone-producing cells of the gonads and the microenvironment of germ cells

DEFF Research Database (Denmark)

Jensen, Charlotte Harken; Erb, K; Westergaard, L G

1999-01-01

Fetal antigen 1 (FA1), an epidermal growth factor (EGF) multidomain glycoprotein, was investigated in the human reproductive system. Immunohistochemical analysis of the male reproductive system revealed staining for FA1 in the Leydig cells only. Concentrations of FA1 in seminal plasma and serum w...

Prenatal and early postnatal NOAEL-dose clothianidin exposure leads to a reduction of germ cells in juvenile male mice.

Science.gov (United States)

Yanai, Shogo; Hirano, Tetsushi; Omotehara, Takuya; Takada, Tadashi; Yoneda, Naoki; Kubota, Naoto; Yamamoto, Anzu; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

2017-07-07

Neonicotinoids are pesticides used worldwide. They bind to insect nicotinic acetylcholine receptors (nAChRs) with high affinity. We previously reported that clothianidin (CTD), one of the latest neonicotinoids, reduced antioxidant expression and induced germ cell death in the adult testis of vertebrates. Here, we investigated the male reproductive toxicity of prenatal and early postnatal exposure to CTD, because it is likely that developmental exposure more severely affects the testis compared to adults due to the absence of the blood-testis barrier. Pregnant C57BL/6 mice were given water gel blended with CTD (0, 10 or 50 mg/kg/day; no-observed-adverse-effect-level [NOAEL for mice]: 47.2 mg/kg/day) between gestational day 1 and 14 days post-partum. We then examined the testes of male offspring at postnatal day 14. The testis weights and the numbers of germ cells per seminiferous tubule were decreased in the CTD-50 group, and abnormal tubules containing no germ cells appeared. Nevertheless, the apoptotic cell number and proliferative activity were not significantly different between the control and CTD-exposed groups. There were no significant differences in the androgen-related parameters, such as the Leydig cell volume per testis, the Sertoli cell number and the tubule diameter. The present study is the first demonstration that in utero and lactational exposures to CTD at around the NOAEL for mice reduce the germ cell number, but our findings suggest that these exposures do not affect steroidogenesis in Leydig cells during prenatal or early postnatal life.

Molecular mechanisms and in vitro antioxidant effects of Lactobacillus plantarum MA2.

Science.gov (United States)

Tang, Wei; Xing, Zhuqing; Li, Chao; Wang, Jinju; Wang, Yanping

2017-04-15

Lactobacillus plantarum MA2 was isolated from Chinese traditional Tibetan kefir grains. The antioxidant activities in vitro of this strain were evaluated extensively. The results showed that L. plantarum MA2 can tolerate hydrogen peroxide up to 2.0mM, and its fermentate (fermented supernatant, intact cell and cell-free extract) had strong reducing capacities, lipid peroxidation inhibition capacities, Fe 2+ -chelating abilities, as well as various free radical scavenging capacities. Additionally, both the fermented supernatant and cell homogenate exhibited glutathione peroxidase activity and superoxide dismutase activity. In order to investigate the antioxidant mechanism of L. plantarum MA2 at the molecular level, eight antioxidant-related genes were identified, and further analyzed. Three groups of genes cat, gshR and npx, were found up-regulated under H 2 O 2 challenge. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alumni careers : MA Comparative European Social Studies Zuyd University

NARCIS (Netherlands)

Albert Riga

2004-01-01

In the preparation of the celebration of the 10th anniversary of the MA CESS all alumni were invited to participate in an alumni survey. The purpose of the survey was to thoroughly investigate the professional activities of MA CESS alumni and the way they build an alumni community. Another reason

High-content image informatics of the structural nuclear protein NuMA parses trajectories for stem/progenitor cell lineages and oncogenic transformation.

Science.gov (United States)

Vega, Sebastián L; Liu, Er; Arvind, Varun; Bushman, Jared; Sung, Hak-Joon; Becker, Matthew L; Lelièvre, Sophie; Kohn, Joachim; Vidi, Pierre-Alexandre; Moghe, Prabhas V

2017-02-01

Stem and progenitor cells that exhibit significant regenerative potential and critical roles in cancer initiation and progression remain difficult to characterize. Cell fates are determined by reciprocal signaling between the cell microenvironment and the nucleus; hence parameters derived from nuclear remodeling are ideal candidates for stem/progenitor cell characterization. Here we applied high-content, single cell analysis of nuclear shape and organization to examine stem and progenitor cells destined to distinct differentiation endpoints, yet undistinguishable by conventional methods. Nuclear descriptors defined through image informatics classified mesenchymal stem cells poised to either adipogenic or osteogenic differentiation, and oligodendrocyte precursors isolated from different regions of the brain and destined to distinct astrocyte subtypes. Nuclear descriptors also revealed early changes in stem cells after chemical oncogenesis, allowing the identification of a class of cancer-mitigating biomaterials. To capture the metrology of nuclear changes, we developed a simple and quantitative "imaging-derived" parsing index, which reflects the dynamic evolution of the high-dimensional space of nuclear organizational features. A comparative analysis of parsing outcomes via either nuclear shape or textural metrics of the nuclear structural protein NuMA indicates the nuclear shape alone is a weak phenotypic predictor. In contrast, variations in the NuMA organization parsed emergent cell phenotypes and discerned emergent stages of stem cell transformation, supporting a prognosticating role for this protein in the outcomes of nuclear functions. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of environmental Bisphenol A exposures on germ cell development and Leydig cell function in the human fetal testis.

Directory of Open Access Journals (Sweden)

Soria Eladak

Full Text Available Using an organotypic culture system termed human Fetal Testis Assay (hFeTA we previously showed that 0.01 μM BPA decreases basal, but not LH-stimulated, testosterone secreted by the first trimester human fetal testis. The present study was conducted to determine the potential for a long-term antiandrogenic effect of BPA using a xenograft model, and also to study the effect of BPA on germ cell development using both the hFETA and xenograft models.Using the hFeTA system, first trimester testes were cultured for 3 days with 0.01 to 10 μM BPA. For xenografts, adult castrate male nude mice were injected with hCG and grafted with first trimester testes. Host mice received 10 μM BPA (~ 500 μg/kg/day in their drinking water for 5 weeks. Plasma levels of total and unconjugated BPA were 0.10 μM and 0.038 μM respectively. Mice grafted with second trimester testes received 0.5 and 50 μg/kg/day BPA by oral gavage for 5 weeks.With first trimester human testes, using the hFeTA model, 10 μM BPA increased germ cell apoptosis. In xenografts, germ cell density was also reduced by BPA exposure. Importantly, BPA exposure significantly decreased the percentage of germ cells expressing the pluripotency marker AP-2γ, whilst the percentage of those expressing the pre-spermatogonial marker MAGE-A4 significantly increased. BPA exposure did not affect hCG-stimulated androgen production in first and second trimester xenografts as evaluated by both plasma testosterone level and seminal vesicle weight in host mice.Exposure to BPA at environmentally relevant concentrations impairs germ cell development in first trimester human fetal testis, whilst gonadotrophin-stimulated testosterone production was unaffected in both first and second trimester testis. Studies using first trimester human fetal testis demonstrate the complementarity of the FeTA and xenograft models for determining the respective short-term and long term effects of environmental exposures.

Alumni careers : MA Comparative European Social Studies Zuyd University

OpenAIRE

Riga, Albert

2004-01-01

In the preparation of the celebration of the 10th anniversary of the MA CESS all alumni were invited to participate in an alumni survey. The purpose of the survey was to thoroughly investigate the professional activities of MA CESS alumni and the way they build an alumni community. Another reason for starting the project is that it may play a part in maintaining and enhancing a mutually beneficial relationship between MA CESS and its alumni. All over Europe there are graduates working in the ...

Enhancing MA transmutation by irradiation of (MA, Zr)Hx in FBR blanket region - 5383

International Nuclear Information System (INIS)

Konashi, K.; Ikeda, K.; Itoh, K.; Hirai, M.; Koyama, T.; Kurosaki, K.

2015-01-01

Minor actinide (MA) hydride is proposed as transmutation target in sodium-cooled mixed oxide fuelled fast reactor. Preliminarily calculations have been done to check the transmutation efficiency of MA hydride targets. Three different types of MA target, MA-Zr alloy, (MA, Zr)O 2 and (MA, Zr)H x , have been compared on MA transmutation rate. The targets are assumed to be loaded around an active core in a 280 MWe sodium-cooled reactor; 54 MA target assemblies are respectively arranged in a row in the radial blanket zone. They are supposed to be irradiated for one year and then be cooled for 60 days. The transmuted mass has been evaluated by three-dimensional diffusion calculation to be 25, 15, 61 kg/EFPY for the alloy, the oxide and the hydride respectively, where production of MA in the active core is taken into account. The transmutation mass by (MA, Zr)H x is much larger than those by the other types of targets, while the core characteristics remain sound by locating MA targets outside of the active core. On top of that, two kinds of (MA, Zr)O 2 targets which are combined with ZrH x (x=1.7) pins have been calculated. Major Research/Development items are selected to establish the MA hydride transmutation method by reviewing technologies applicable to the transmutation system. The practical use of the MA hydride transmutation method is not far ahead technically, since this method can be developed by the extension of existing technologies. (authors)

Different roles of prepubertal and postpubertal germ cells and Sertoli cells in the regulation of serum inhibin B levels

DEFF Research Database (Denmark)

Andersson, A M; Müller, J; Skakkebaek, N E

1998-01-01

testis, intense immunostaining for the betaB-subunit was evident in germ cells from the pachytene spermatocyte to early spermatid stages and to a lesser degree in Leydig cells, but not in Sertoli cells or other stages of germ cells. Thus, surprisingly, in adult men the two subunits constituting inhibin B......-subunit. The correlation in adult men between serum inhibin B levels and spermatogenesis may be due to the fact that inhibin B in adult men is possibly a joint product of Sertoli cells and germ cells, including the stages from pachytene spermatocytes to early spermatids....

Science and technology of the 10-MA Spherical Tori

International Nuclear Information System (INIS)

Peng, M.; Reiersen, W.; Kaye, S.

2001-01-01

The scientific parameters and the technology issues for a modest-size Spherical Torus (ST) at 10 MA in plasma current are discussed. This class of devices include a D-T-capable ST experiments (DTST, R 0 =1.2 m) for Proof of Performance for limited pulse lengths and neutron fluences, and a steady-state volume neutron source (VNS, R 0 =1.1 m) for testing Fusion Energy Components to high neutron fluences. The scientific issues of interest to the DTST include noninductive ramp up of plasma current in a limited time scale (∼40 s), confinement needed for high-Q burn, behavior of energetic particles, physics and techniques to handle intense plasma exhaust, and the possibility of high performance plasma regimes free of disruptions or large disruption impact. Also of interest to the VNS would be steady state operation using large external current drive possibly at a modest Q (∼1-2) achieving significant neutron wall loading (∼1MW/m 2 ) and a configuration relatively amenable for remote maintenance. A much longer time scale would be permitted for noninductive current ramp up. The center leg of the TF coils, possibly multi-turn for DTST and necessarily single-turn for VNS without significant nuclear shielding, is a technical and material issue of unique importance to the ST. Positive-ion Neutral Beam Injection (NBI) and HHFW (∼80 MHz) heating and current drive systems already available to date are likely adequate for the DTST following pulse length extension to ∼50 s. For the high densities needed for enhancing the neutron wall loading (to ∼ a few MW/m 2 ) in a VNS, a negative-ion NBI system may become desired. Given an adequate physics database, the remaining enabling technologies needed by the VNS appear largely similar in nature to those of the ITER EDA design. (author)

Science and technology of the 10-MA spherical tori

International Nuclear Information System (INIS)

Peng, M.; Reiersen, W.; Kaye, S.

1999-01-01

The scientific parameters and the technology issues for a modest-size Spherical Torus (ST) at 10 MA in plasma current are discussed. This class of devices include a D-T-capable ST experiments (DTST, R 0 = 1.2 m) for Proof of Performance for limited pulse lengths and neutron fluences, and a steady-state volume neutron source (VNS, R 0 = 1.1 m) for testing Fusion Energy Components to high neutron fluences. The scientific issues of interest to the DTST include noninductive ramp up of plasma current in a limited time scale (∼40 s), confinement needed for high-Q burn, behavior of energetic particles, physics and techniques to handle intense plasma exhaust, and the possibility of high performance plasma regimes free of disruptions or large disruption impact. Also of interest to the VNS would be steady state operation using large external current drive possibly at a modest Q (∼ 1-2) achieving significant neutron wall loading (∼1 MW/m 2 ) and a configuration relatively amenable for remote maintenance. A much longer time scale would be permitted for noninductive current ramp up. The center leg of the TF coils, possibly multi-turn for DTST and necessarily single-turn for VNS without significant nuclear shielding, is a technical and material issue of unique importance to the ST. Positive-ion Neutral Beam Injection (NBI) and HHFW (∼80 MHz) heating and current drive systems already available to date are likely adequate for the DTST following pulse length extension to ∼50 s. For the high densities needed for enhancing the neutron wall loading (to ∼ a few MW/m 2 ) in a VNS, a negative-ion NBI system may become desired. Given an adequate physics database, the remaining enabling technologies needed by the VNS appear largely similar in nature to those of the ITER EDA design. (author)

Zhigang Ma

Indian Academy of Sciences (India)

Home; Journals; Bulletin of Materials Science. Zhigang Ma. Articles written in Bulletin of Materials Science. Volume 35 Issue 4 August 2012 pp 575-578. Degradation and miscibility of poly(DL-lactic acid)/poly(glycolic acid) composite films: Effect of poly(DL-lactic-co-glycolic acid) · Zhigang Ma Na Zhao Chengdong Xiong.

Design and performance of the 10-kV, 5-MA pulsed-power system for the FRX-C compression experiment

International Nuclear Information System (INIS)

Rej, D.J.; Barnes, G.A.; Gribble, R.J.; Hinckley, J.E.; Kreider, T.W.; Waganaar, W.J.

1989-05-01

The design and performance of the pulsed-power system for the FRX-C compact toroid compression heating experiment are reviewed. Two inductively-isolated, 10-kV capacitor banks (total energy = 1.5 MJ) are discharged through a common, low-inductance load. The 5-MA currents are switched and crowbarred with parallel arrays of size-D ignitrons. Power supplies are constructed in simple 25 and 50 kJ modules, each capable of supplying 100 kA at 10 kV. Non-negligible source inductance and the addition of high-power resistors maintain module isolation and protect the system during fault modes. 21 refs., 31 figs

46 CFR 308.521 - Application for Open Cargo Policy, Form MA-301.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Application for Open Cargo Policy, Form MA-301. 308.521... RISK INSURANCE War Risk Cargo Insurance Ii-Open Policy War Risk Cargo Insurance § 308.521 Application for Open Cargo Policy, Form MA-301. The standard form of application for a War Risk Open Cargo Policy...

Mapping Nearby Galaxies at APO: The MaNGA IFU Galaxy Survey

Science.gov (United States)

Law, David R.; MaNGA Team

2014-01-01

MaNGA is a new survey that will begin in August 2014 as part of SDSS-IV with the aim of obtaining integral-field spectroscopy for an unprecedented sample of 10,000 nearby galaxies. MaNGA's key goals are to understand the "life cycle" of present day galaxies from imprinted clues of their birth and assembly, through their ongoing growth via star formation and merging, to their death from quenching at late times. To achieve these goals, MaNGA will channel the impressive capabilities of the SDSS-III BOSS spectrographs in a fundamentally new direction by marshaling the unique power of 2D spectroscopy. MaNGA will deploy 17 pluggable Integral Field Units (IFUs) made by grouping fibers into hexagonal bundles ranging from 19 to 127 fibers each. The spectra obtained by MaNGA will cover the wavelength range 3600-10,000 Angstroms (with a velocity resolution of ~ 60 km/s) and will characterize the internal composition and the dynamical state of a sample of 10,000 galaxies with stellar masses greater than 10^9 Msun and an average redshift of z ~ 0.03. Such IFU observations enable a leap forward because they provide an added dimension to the information available for each galaxy. MaNGA will provide two-dimensional maps of stellar velocity and velocity dispersion, mean stellar age and star formation history, stellar metallicity, element abundance ratio, stellar mass surface density, ionized gas velocity, ionized gas metallicity, star formation rate, and dust extinction for a statistically powerful sample. This legacy dataset will address urgent questions in our understanding of galaxy formation, including 1) The formation history of galaxy subcomponents, including the disk, bulge, and dark matter halo, 2) The nature of present-day galaxy growth via merging and gas accretion, and 3) The processes responsible for terminating star formation in galaxies. Finally, MaNGA will also play a vital role in the coming era of advanced IFU instrumentation, serving as the low-z anchor for

Anti-Ma-associated encephalitis due to dysgerminoma in a woman with Swyer syndrome.

Science.gov (United States)

Al-Thubaiti, Ibtisam; Al-Hayek, Kefah; Binfalah, Mohammed

2013-04-09

Paraneoplastic limbic encephalitis (PLE)/diencephalitis associated with anti-Ma2 antibodies was linked to testicular cancer and non-small-cell lung cancer (non-SCLC).(1,2) We report a case of anti-Ma-associated PLE/diencephalitis due to dysgerminoma in a woman with gonadal dysgenesis, or Swyer syndrome.

Immunoexpression of androgen receptors and aromatase in testes of patient with Klinefelter's syndrome.

Directory of Open Access Journals (Sweden)

Stanisław Fracki

2005-02-01

Full Text Available Klinefelter's syndrome (47, XXY is the most common chromosome aneuploidy in men and is usually characterized by underdeveloped testes and sterility. The aim of the present study was to detect cellular distribution of androgen receptors (AR and aromatase in testes of patient with KS. The tissue sections were processed for morphological and immunohistochemical staining. Additionally, levels of FSH, LH, PRL, estradiol, and testosterone were measured in the plasma. Morphological analysis revealed a complete absence of spermatogenesis. No germ cells were present in seminiferous tubules. In some tubules, nests of apparently degenerating Sertoli cells were found. In the interstitium, Leydig cell hyperplasia was observed. Using immunohistochemistry, nuclear AR staining was detected in Sertoli cells and peritubular cells, whereas in Leydig cells the staining was exclusively cytoplasmic. The immunostaining of aromatase was detected in the cytoplasm of Sertoli cells and Leydig cells. Increased levels of gonadotropins and decreased level of testosterone concomitantly with the cytoplasmic localization of AR in Leydig cells might contribute to the impaired testicular function in patient with KS.

46 CFR 308.522 - Collateral deposit fund, letter of transmittal, Form MA-302.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Collateral deposit fund, letter of transmittal, Form MA... Collateral deposit fund, letter of transmittal, Form MA-302. The standard form of letter of transmittal for use in establishing a collateral deposit fund, may be obtained from the American War Risk Agency or...

Lipoprotein lipase and endothelial lipase in human testis and in germ cell neoplasms

DEFF Research Database (Denmark)

Nielsen, J E; Lindegaard, M L; Friis-Hansen, L

2009-01-01

. The results suggest that both EL and LPL participate in the supply of nutrients and steroidogenesis in the testes, and that especially EL may be important for the supply of cholesterol for testosterone production in the Leydig cells. The partial cellular separation of the expression of the two lipases...

Serum insulin-like factor 3 levels during puberty in healthy boys and boys with Klinefelter syndrome

DEFF Research Database (Denmark)

Wikström, Anne M; Bay, Katrine; Hero, Matti

2006-01-01

Levels of the Leydig cell-specific hormone insulin-like factor 3 (INSL3) are incompletely characterized in boys during pubertal development.......Levels of the Leydig cell-specific hormone insulin-like factor 3 (INSL3) are incompletely characterized in boys during pubertal development....

MaNGA: Mapping Nearby Galaxies at Apache Point Observatory

Science.gov (United States)

Weijmans, A.-M.; MaNGA Team

2016-10-01

MaNGA (Mapping Nearby Galaxies at APO) is a galaxy integral-field spectroscopic survey within the fourth generation Sloan Digital Sky Survey (SDSS-IV). It will be mapping the composition and kinematics of gas and stars in 10,000 nearby galaxies, using 17 differently sized fiber bundles. MaNGA's goal is to provide new insights in galaxy formation and evolution, and to deliver a local benchmark for current and future high-redshift studies.

Discovery and utilization of sorghum genes (Ma5/Ma6)

Science.gov (United States)

Mullet, John E; Rooney, William L; Klein, Patricia E; Morishige, Daryl; Murphy, Rebecca; Brady, Jeff A

2012-11-13

Methods and composition for the production of non-flowering or late flowering sorghum hybrid. For example, in certain aspects methods for use of molecular markers that constitute the Ma5/Ma6 pathway to modulate photoperiod sensitivity are described. The invention allows the production of plants having improved productivity and biomass generation.

Delivery of folates to the cytoplasm of MA104 cells is mediated by a surface membrane receptor that recycles

International Nuclear Information System (INIS)

Kamen, B.A.; Wang, M.T.; Streckfuss, A.J.; Peryea, X.; Anderson, R.G.

1988-01-01

MA104 cells, as well as several other rapidly dividing tissue culture cells, have a folate-binding protein associated with their cell surface. The protein has the properties of a membrane receptor: (a) 5-methyl[ 3 H]tetrahydrofolic acid binds with high affinity (Kd approximately equal to 3 nM); (b) the protein is an integral membrane protein; (c) it appears to deliver physiological concentrations of 5-methyl[ 3 H]tetrahydrofolic acid to the inside of the cell; (d) binding activity is regulated by the concentration of folate within the cell. To better understand the mechanism of action of this receptor, we have studied the pathway of folate internalization. We present evidence that during internalization: (a) folate binds to the membrane receptor; (b) the ligand-receptor complex moves into the cell; (c) the ligand is released from the receptor in an acidic intracellular compartment and moves into the cytoplasm; and (d) the unoccupied receptor returns to the cell surface

Design of an accelerator tube for 500 keV/10 mA electron beam machine

International Nuclear Information System (INIS)

Maksum, W.; Sudjatmoko; Suprapto

1999-01-01

A design of an accelerator tube for 500 keV/10 mA electron beam machine was carried out. This tube was used for focussing and accelerating of electron beams. The tube was designed to consist of some electrodes insulator tubes and a voltage divider. The electrodes was made of stainless steel due to its low outgassing constant and stainless, the insulator was made of pyrex glass due to its low outgassing constant and high temperature proof and the voltage divider was made of high-ohmic resistors used for accelerating potential distribution at the electrodes. The stainless steel electrodes were comic shaped 3 mm thick with 134 mm inlet diameter and 60 mm outlet diameter. The number for this electrodes was 34 so that the potential gap between adjacent electrodes not exceed 15 kV. The insulators were 5 mm thick, 150 mm outer diameter, 140 mm inner diameter and 32 mm long. The insulators were joined to the electrodes by using an epoxy form an accelerator tube. The designed accelerator tube could be constructed and operated at a vacuum of 10 -6 torr and accelerated electron beam at an energy of 500 keV. (author)

Probiotic Properties and Cellular Antioxidant Activity of Lactobacillus plantarum MA2 Isolated from Tibetan Kefir Grains.

Science.gov (United States)

Tang, Wei; Li, Chao; He, Zengguo; Pan, Fen; Pan, Shuo; Wang, Yanping

2017-11-20

Lactobacillus plantarum MA2 was isolated from traditional Chinese Tibetan kefir grains. Its antioxidant properties had been demonstrated in vitro and in vivo previously. In the present study, the probiotic characteristics of this strain were further evaluated by investigating its acid and bile salt tolerances, cell surface hydrophobicity, and autoaggregation, respectively. In addition, the cellular antioxidant activity (CAA) assay was applied to test the antioxidant capacity of the isolate in different growth phases. Same method was also used to evaluate the antioxidant capacity of its fermentation supernatant, cell-free extract, and intact cell quantitatively. The results of probiotic characteristic tests showed that MA2 could survive at pH 2.5 and 0.3% bile salt. Meanwhile, the measurements of cell surface hydrophobicity and autoaggregation were 45.29 ± 2.15 and 6.30 ± 0.34%, respectively. The results of cellular antioxidant activity tests indicated that MA2 had high antioxidant potential. The CAA value of logarithmic phase cell-free extract of MA2 (39,450.00 ± 424.05 μmol quercetin equivalents/100 g sample) was significantly higher than that in stationary phase cell-free extract (3395.98 ± 126.06 μmol quercetin equivalents/100 g sample) and that of fermentation supernatant in logarithmic phase (2174.41 ± 224.47 μmol quercetin equivalents/100 g sample) (p < 0.05). The CAA method was successively applied to evaluate the antioxidant capacity of MA2 in this study, which suggests that it could be used as a useful method for lactic acid bacteria antioxidant potential evaluation.

Essential role of miR-200c in regulating self-renewal of breast cancer stem cells and their counterparts of mammary epithelium

International Nuclear Information System (INIS)

Feng, Zhong-Ming; Qiu, Jun; Chen, Xie-Wan; Liao, Rong-Xia; Liao, Xing-Yun; Zhang, Lu-Ping; Chen, Xu; Li, Yan; Chen, Zheng-Tang; Sun, Jian-Guo

2015-01-01

Breast cancer stem cells (BCSCs) have been reported as the origin of breast cancer and the radical cause of drug resistance, relapse and metastasis in breast cancer. BCSCs could be derived from mutated mammary epithelial stem cells (MaSCs). Therefore, comparing the molecular differences between BCSCs and MaSCs may clarify the mechanism underlying breast carcinogenesis and the targets for gene therapy. Specifically, the distinct miRNome data of BCSCs and MaSCs need to be analyzed to find out the key miRNAs and reveal their roles in regulating the stemness of BCSCs. MUC1 − ESA + cells were isolated from normal mammary epithelial cell line MCF-10A by fluorescence-activated cell sorting (FACS) and tested for stemness by clonogenic assay and multi-potential differentiation experiments. The miRNA profiles of MaSCs, BCSCs and breast cancer MCF-7 cells were compared to obtain the candidate miRNAs that may regulate breast tumorigenesis. An miRNA consecutively upregulated from MaSCs to BCSCs to MCF-7 cells, miR-200c, was chosen to determine its role in regulating the stemness of BCSCs and MaSCs in vitro and in vivo. Based on bioinformatics, the targets of miR-200c were validated by dual-luciferase report system, western blot and rescue experiments. In a 2-D clonogenic assay, MUC1 − ESA + cells gave rise to multiple morphological colonies, including luminal colonies, myoepithelial colonies and mixed colonies. The clonogenic potential of MUC1 − ESA + (61.5 ± 3.87 %) was significantly higher than that of non-stem MCF-10A cells (53.5 ± 3.42 %) (P < 0.05). In a 3-D matrigel culture, MUC1 − ESA + cells grew into mammospheres with duct-like structures. A total of 12 miRNAs of interest were identified, 8 of which were upregulated and 4 downregulated in BCSCs compared with MaSCs. In gain- and lost-of-function assays, miR-200c was sufficient to inhibit the self-renewal of BCSCs and MaSCs in vitro and the growth of BCSCs in vivo. Furthermore, miR-200c negatively regulated

46 CFR 308.524 - Application for cancellation of Open Cargo Policy, Form MA-304.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Application for cancellation of Open Cargo Policy, Form... § 308.524 Application for cancellation of Open Cargo Policy, Form MA-304. The standard form of application for cancellation of an Open Cargo Policy Form MA-304 may be obtained from the American War Risk...

MaMiCo: Software design for parallel molecular-continuum flow simulations

KAUST Repository

Neumann, Philipp

2015-11-19

The macro-micro-coupling tool (MaMiCo) was developed to ease the development of and modularize molecular-continuum simulations, retaining sequential and parallel performance. We demonstrate the functionality and performance of MaMiCo by coupling the spatially adaptive Lattice Boltzmann framework waLBerla with four molecular dynamics (MD) codes: the light-weight Lennard-Jones-based implementation SimpleMD, the node-level optimized software ls1 mardyn, and the community codes ESPResSo and LAMMPS. We detail interface implementations to connect each solver with MaMiCo. The coupling for each waLBerla-MD setup is validated in three-dimensional channel flow simulations which are solved by means of a state-based coupling method. We provide sequential and strong scaling measurements for the four molecular-continuum simulations. The overhead of MaMiCo is found to come at 10%-20% of the total (MD) runtime. The measurements further show that scalability of the hybrid simulations is reached on up to 500 Intel SandyBridge, and more than 1000 AMD Bulldozer compute cores. Program summary: Program title: MaMiCo. Catalogue identifier: AEYW_v1_0. Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AEYW_v1_0.html Program obtainable from: CPC Program Library, Queen\\'s University, Belfast, N. Ireland. Licensing provisions: BSD License. No. of lines in distributed program, including test data, etc.: 67905. No. of bytes in distributed program, including test data, etc.: 1757334. Distribution format: tar.gz. Programming language: C, C++II. Computer: Standard PCs, compute clusters. Operating system: Unix/Linux. RAM: Test cases consume ca. 30-50 MB. Classification: 7.7. External routines: Scons (http:www.scons.org), ESPResSo, LAMMPS, ls1 mardyn, waLBerla. Nature of problem: Coupled molecular-continuum simulation for multi-resolution fluid dynamics: parts of the domain are resolved by molecular dynamics whereas large parts are covered by a CFD solver, e.g. a lattice Boltzmann automaton

Effects of Lactobacillus plantarum MA2 isolated from Tibet kefir on lipid metabolism and intestinal microflora of rats fed on high-cholesterol diet.

Science.gov (United States)

Wang, Yanping; Xu, Nv; Xi, Aodeng; Ahmed, Zaheer; Zhang, Bin; Bai, Xiaojia

2009-08-01

The objective of this study was to evaluate the effects of Lactobacillus plantarum MA2, an isolate from Chinese traditional Tibet kefir, on cholesterol-lowering and microflora of rat in vivo. Rats were fed on cholesterol-enriched experimental diet, supplemented with lyophilized L. plantarum MA2 powder, with a dose of 10(11) cells/day per mice. The results showed that L. plantarum MA2 feeding significantly lowered serum total cholesterol, low-density lipoprotein cholesterol, and triglycerides level, while there was no change in high-density lipoprotein cholesterol. In addition, liver total cholesterol and triglycerides was also decreased. However, fecal cholesterol and triglycerides was increased significantly (P MA2 increased the population of lactic acid bacteria and bifidobacteria in the fecal, but it did not change the number of Escherichia coli as compared to control. Moreover, pH, moisture, and organic acids in the fecal were also measured. The present results indicate the probiotic potential of the L. plantarum MA2 strain in hypocholesterolemic effect and also increasing the probiotic count in the intestine.

46 CFR 308.523 - Application for revision of Open Cargo Policy, Form MA-303.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Application for revision of Open Cargo Policy, Form MA... Application for revision of Open Cargo Policy, Form MA-303. An application for the revision of an Open Cargo Policy shall be filed in duplicate with the Underwriting Agent on a form which may be obtained from the...

Diet of Theropithecus from 4 to 1 Ma in Kenya.

Science.gov (United States)

Cerling, Thure E; Chritz, Kendra L; Jablonski, Nina G; Leakey, Meave G; Manthi, Fredrick Kyalo

2013-06-25

Theropithecus was a common large-bodied primate that co-occurred with hominins in many Plio-Pleistocene deposits in East and South Africa. Stable isotope analyses of tooth enamel from T. brumpti (4.0-2.5 Ma) and T. oswaldi (2.0-1.0 Ma) in Kenya show that the earliest Theropithecus at 4 Ma had a diet dominated by C4 resources. Progressively, this genus increased the proportion of C4-derived resources in its diet and by 1.0 Ma, had a diet that was nearly 100% C4-derived. It is likely that this diet was comprised of grasses or sedges; stable isotopes cannot, by themselves, give an indication of the relative importance of leaves, seeds, or underground storage organs to the diet of this primate. Theropithecus throughout the 4- to 1-Ma time range has a diet that is more C4-based than contemporaneous hominins of the genera Australopithecus, Kenyanthropus, and Homo; however, Theropithecus and Paranthropus have similar proportions of C4-based resources in their respective diets.

Distributional map of the terminal and sub-terminal sugar residues of the glycoconjugates in the prepubertal and postpubertal testis of a subject affected by complete androgen insensitivity syndrome (Morris's syndrome): lectin histochemical study.

Science.gov (United States)

Gheri, G; Vannelli, G B; Marini, M; Zappoli Thyrion, G D; Gheri, R G; Sgambati, E

2004-01-01

In the present research we have investigated the distribution of the sugar residues of the glycoconjugates in the prepubertal and postpubertal testes of a subject with Morris's syndrome (CAIS, Complete Androgen Insensitivity Syndrome). For this purpose a battery of six horseradish peroxidase-conjugated lectins was used (SBA, PNA, WGA, ConA, LTA and UEAI). We have obtained a complete distributional map of the terminal and sub-terminal oligosaccharides in the tunica albuginea, interstitial tissue, lamina propria of the seminiferous tubules, Leydig cells, Sertoli cells, spermatogonia, mastocytes and endothelial cells. Furthermore the present study has shown that a large amount of sugar residues were detectable in the prepubertal and postpubertal testes but that some differences exist with particular regard to the Sertoli cells. The Sertoli cells and the Leydig cells of the retained prepubertal testis of the patient affected by Morris's syndrome were characterized by the presence of alpha-L-fucose, which was absent in the retained prepubertal testis of the normal subjects. Comparing the results on the postpubertal testis with those obtained on the same aged testis of healthy subjects we have demonstrated that alpha-L-fucose in the Sertoli and Leydig cells and D-galactose-N-acetyl-D-galactosamine in the Leydig cells are a unique feature of the subject affected by Morris's syndrome. D-galactose (ss1,3)-N-acetyl-D-galactosamine and sialic acid, which are present in the Leydig cells of the normal testis were never observed in the same cells of the postpubertal testis of the CAIS patient.

Model for Analysis of the Energy Demand (MAED) users' manual for version MAED-1

International Nuclear Information System (INIS)

1986-09-01

This manual is organized in two major parts. The first part includes eight main sections describing how to use the MAED-1 computer program and the second one consists of five appendices giving some additional information about the program. Concerning the main sections of the manual, Section 1 gives a summary description and some background information about the MAED-1 model. Section 2 extends the description of the MAED-1 model in more detail. Section 3 introduces some concepts, mainly related to the computer requirements imposed by the program, that are used throughout this document. Sections 4 to 7 describe how to execute each of the various programs (or modules) of the MAED-1 package. The description for each module shows the user how to prepare the control and data cards needed to execute the module and how to interpret the printed output produced. Section 8 recapitulates about the use of MAED-1 for carrying out energy and electricity planning studies, describes the several phases normally involved in this type of study and provides the user with practical hints about the most important aspects that need to be verified at each phase while executing the various MAED modules

Germ cell transplantation in an azoospermic Klinefelter bull.

Science.gov (United States)

Joerg, Hannes; Janett, Fredi; Schlatt, Stefan; Mueller, Simone; Graphodatskaya, Daria; Suwattana, Duangsmorn; Asai, Mika; Stranzinger, Gerald

2003-12-01

Germ cell transplantation is a technique that transfers donor testicular cells into recipient testes. A population of germ cells can colonize the recipient testis, initiate spermatogenesis, and produce sperm capable of fertilization. In the present study, a nonmosaic Klinefelter bull was used as a germ cell recipient. The donor cell suspension was introduced into the rete testis using ultrasound-guided puncture. A pulsatile administration of GnRH was performed to stimulate spermatogenesis. The molecular approach to detect donor cells was done by a quantitative polymerase chain reaction with allele discrimination based on a genetic mutation between donor and recipient. Therefore, a known genetic mutation, associated with coat-color phenotype, was used to calculate the ratio of donor to recipient cells in the biopsy specimens and ejaculates for 10 mo. After slaughtering, meiotic preparations were performed. The injected germ cells did not undergo spermatogenesis. Six months after germ cell transplantation, the donor cells were rejected, which indicates that the donor cells could not incorporate in the testis. The hormone stimulation showed that the testosterone-producing Leydig cells were functionally intact. Despite subfertility therapy, neither the recipient nor the donor cells underwent spermatogenesis. Therefore, nonmosaic Klinefelter bulls are not suitable as germ cell recipients. Future germ cell recipients in cattle could be mosaic Klinefelters, interspecies hybrids, bulls with Sertoli cell-only syndrome, or bulls with disrupted germ cell migration caused by RNA interference.

Isoform-specific functions of Mud/NuMA mediate binucleation of Drosophila male accessory gland cells.

Science.gov (United States)

Taniguchi, Kiichiro; Kokuryo, Akihiko; Imano, Takao; Minami, Ryunosuke; Nakagoshi, Hideki; Adachi-Yamada, Takashi

2014-12-20

In standard cell division, the cells undergo karyokinesis and then cytokinesis. Some cells, however, such as cardiomyocytes and hepatocytes, can produce binucleate cells by going through mitosis without cytokinesis. This cytokinesis skipping is thought to be due to the inhibition of cytokinesis machinery such as the central spindle or the contractile ring, but the mechanisms regulating it are unclear. We investigated them by characterizing the binucleation event during development of the Drosophila male accessory gland, in which all cells are binucleate. The accessory gland cells arrested the cell cycle at 50 hours after puparium formation (APF) and in the middle of the pupal stage stopped proliferating for 5 hours. They then restarted the cell cycle and at 55 hours APF entered the M-phase synchronously. At this stage, accessory gland cells binucleated by mitosis without cytokinesis. Binucleating cells displayed the standard karyokinesis progression but also showed unusual features such as a non-round shape, spindle orientation along the apico-basal axis, and poor assembly of the central spindle. Mud, a Drosophila homolog of NuMA, regulated the processes responsible for these three features, the classical isoform Mud(PBD) and the two newly characterized isoforms Mud(L) and Mud(S) regulated them differently: Mud(L) repressed cell rounding, Mud(PBD) and Mud(S) oriented the spindle along the apico-basal axis, and Mud(S) and Mud(L) repressed central spindle assembly. Importantly, overexpression of Mud(S) induced binucleation even in standard proliferating cells such as those in imaginal discs. We characterized the binucleation in the Drosophila male accessory gland and examined mechanisms that regulated unusual morphologies of binucleating cells. We demonstrated that Mud, a microtubule binding protein regulating spindle orientation, was involved in this binucleation. We suggest that atypical functions exerted by three structurally different isoforms of Mud regulate

Steroid Cell Ovarian Neoplasm, Not Otherwise Specified: A Case Report and Review of the Literature

Directory of Open Access Journals (Sweden)

Paul Singh

2012-01-01

Full Text Available Background. Steroid cell ovarian tumors, not otherwise specified, represent a unique cause of female virilization. Most commonly encountered in premenopausal women, these tumors can exist throughout a women’s lifetime, from before puberty until after menopause. Case. Steroid cell, not otherwise specified, was diagnosed in a 70-year-old female significant for hirsutism. The patient demonstrated elevated total testosterone levels with normal gonadotropins, DHEA, and DHEA-S levels. CT imaging revealed a right ovarian mass and subsequent laparoscopic right oophorectomy yielded clinical improvement promptly. Conclusion. Virilization in females can occur based on ovarian or adrenal pathology. In terms of ovarian-based female virilization, many tumors exist that may induce women to demonstrate masculine features, such as pure Sertoli, pure Leydig, Sertoli-Leydig combinations, and gynandroblastomas. Each of these tumor types possesses a unique histologic pattern that allows for pathologic identification after removal. A rare source of ovarian-based female virilization is steroid cell neoplasms, not otherwise specified, that do not demonstrate these specific histologic characteristics and thus represent a diagnosis of exclusion after other causes of ovarian-based female virilization have been ruled out.

1-Hydroxy-3-[(E)-4-(piperazine-diium)but-2-enyloxy]-9,10-anthraquinone ditrifluoroactate induced autophagic cell death in human PC3 cells.

Science.gov (United States)

Huang, A-Mei; Lin, Kai-Wei; Lin, Wei-Hong; Wu, Li-Hung; Chang, Hao-Chun; Ni, Chujun; Wang, Danny Ling; Hsu, Hsue-Yin; Su, Chun-Li; Shih, Chiaho

2018-02-01

The autophagy of human prostate cancer cells (PC3 cells) induced by a new anthraquinone derivative, 1-Hydroxy-3-[(E)-4-(piperazine-diium)but-2-enyloxy]-9,10-anthraquinone ditrifluoroactate (PA) was investigated, and the relationship between autophagy and reactive oxygen species (ROS) generation was studied. The results indicated that PA induced PC3 cell death in a time- and dose-dependent manner, could inhibit PC3 cell growth by G1 phase cell cycle arrest and corresponding decrease in the G2/M cell population and induced S-phase arrest accompanied by a significant decrease G2/M and G1 phase numbers after PC3 cells treated with PA for 48 h, and increased the accumulation of autophagolysosomes and microtubule-associated protein LC3-ll, a marker of autophagy. However, these phenomenon were not observed in the group pretreated with the autophagy inhibitor 3-MA or Bafilomycin A1 (BAF), suggesting that PA induced PC3 cell autophagy. In addition, we found that PA triggered ROS generation in cells, while the levels of ROS decreased in the N-acetylcysteine (NAC) co-treatment, indicating that PA-mediated autophagy was partly blocked by NAC. In summary, the autophagic cell death of human PC3 cells mediated by PA-triggered ROS generation. Copyright © 2017 Elsevier B.V. All rights reserved.

Stereological Quantification of Leydig and Sertoli Cells: Technique ...

African Journals Online (AJOL)

A total of 105 adult male and 50 female wistar rats weighing 170±10g (70-90 day old) were used for the experiment. The rats were randomly divided into a control and experimental groups. There were four major groups with 5 subgroups consisting of 5 rats each. Varying doses of metronidazole were used depending on the ...

Cold Gas in Quenched Dwarf Galaxies using HI-MaNGA

Science.gov (United States)

Bonilla, Alaina

2017-01-01

MaNGA (Mapping of Nearby Galaxies at Apache Point Observatory) is a 6-year Sloan Digital Sky Survey fourth generation (SDSS-IV) project that will obtain integral field spectroscopy of a catalogue of 10,000 nearby galaxies. In this study, we explore the properties of the passive dwarf galaxy sample presented in Penny et al. 2016, making use of MaNGA IFU (Integral Field Unit) data to plot gas emission, stellar velocity, and flux maps. In addition, HI-MaNGA, a legacy radio-survey of MaNGA, collects single dish HI data retrieved from the GBT (Green Bank Telescope), which we use to study the the 21cm emission lines present in HI detections. Studying the HI content of passive dwarves will help us reveal the processes that are preventing star formation, such as possible AGN feedback. This work was supported by the SDSS Research Experience for Undergraduates program, which is funded by a grant from the Sloan Foundation to the Astrophysical Research Consortium.

[Herbological studies on Chinese crude drug Ma-huang. Part 1-On the botanical origin of Ma-huang in ancient China and the origin of Japanese Ma-huang].

Science.gov (United States)

Yoshizawa, Chieko; Kitade, Makiko; Mikage, Masayuki

2005-01-01

The botanical origin of a Chinese crude drug Ma-huang in ancient China and the origin of Japanese Ma-huang were herbologically studied. The results showed that the plants of Ephedra sinica Stapf, E. intermedia Schrenk & C. A. Meyer and E. equisetina Bunge were used as Ma-huang in China, and the first species was considered to be of high quality. The characters of Mao-zhou Ma-huang and Tong-zhou Ma-huang printed in Tu-jing-ben-cao, published in the Song Dynasty in China, were identified as E. likiangensis Florin and E. intermedia, respectively, and both species were recognized as excellent Ma-huang in the Ming Dynasty. The word origin of Katsune-kusa, the Japanese name for Ma-huang in the Heian Era, was etymologically considered as meaning the plant having reddish brown roots. In Japan, the plant of Equisetum ramosissimum Desf. var.japonicum Milde, of the family Equisetaceae, was substituted for Ma-huang in the middle of Edo Era, and it was designated that this action was based on the confusion of Ephedra plants and Equisetum plants those days in China.

The Data Reduction Pipeline for the SDSS-IV MaNGA IFU Galaxy Survey

Science.gov (United States)

Law, David R.; Cherinka, Brian; Yan, Renbin; Andrews, Brett H.; Bershady, Matthew A.; Bizyaev, Dmitry; Blanc, Guillermo A.; Blanton, Michael R.; Bolton, Adam S.; Brownstein, Joel R.; Bundy, Kevin; Chen, Yanmei; Drory, Niv; D'Souza, Richard; Fu, Hai; Jones, Amy; Kauffmann, Guinevere; MacDonald, Nicholas; Masters, Karen L.; Newman, Jeffrey A.; Parejko, John K.; Sánchez-Gallego, José R.; Sánchez, Sebastian F.; Schlegel, David J.; Thomas, Daniel; Wake, David A.; Weijmans, Anne-Marie; Westfall, Kyle B.; Zhang, Kai

2016-10-01

Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) is an optical fiber-bundle integral-field unit (IFU) spectroscopic survey that is one of three core programs in the fourth-generation Sloan Digital Sky Survey (SDSS-IV). With a spectral coverage of 3622-10354 Å and an average footprint of ˜500 arcsec2 per IFU the scientific data products derived from MaNGA will permit exploration of the internal structure of a statistically large sample of 10,000 low-redshift galaxies in unprecedented detail. Comprising 174 individually pluggable science and calibration IFUs with a near-constant data stream, MaNGA is expected to obtain ˜100 million raw-frame spectra and ˜10 million reduced galaxy spectra over the six-year lifetime of the survey. In this contribution, we describe the MaNGA Data Reduction Pipeline algorithms and centralized metadata framework that produce sky-subtracted spectrophotometrically calibrated spectra and rectified three-dimensional data cubes that combine individual dithered observations. For the 1390 galaxy data cubes released in Summer 2016 as part of SDSS-IV Data Release 13, we demonstrate that the MaNGA data have nearly Poisson-limited sky subtraction shortward of ˜8500 Å and reach a typical 10σ limiting continuum surface brightness μ = 23.5 AB arcsec-2 in a five-arcsecond-diameter aperture in the g-band. The wavelength calibration of the MaNGA data is accurate to 5 km s-1 rms, with a median spatial resolution of 2.54 arcsec FWHM (1.8 kpc at the median redshift of 0.037) and a median spectral resolution of σ = 72 km s-1.

THE DATA REDUCTION PIPELINE FOR THE SDSS-IV MaNGA IFU GALAXY SURVEY

International Nuclear Information System (INIS)

Law, David R.; Cherinka, Brian; Yan, Renbin; Andrews, Brett H.; Bershady, Matthew A.; Bizyaev, Dmitry; Blanc, Guillermo A.; Blanton, Michael R.; Bolton, Adam S.; Brownstein, Joel R.; Bundy, Kevin; Chen, Yanmei; Drory, Niv; D’Souza, Richard; Jones, Amy; Kauffmann, Guinevere; Fu, Hai

2016-01-01

Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) is an optical fiber-bundle integral-field unit (IFU) spectroscopic survey that is one of three core programs in the fourth-generation Sloan Digital Sky Survey (SDSS-IV). With a spectral coverage of 3622–10354 Å and an average footprint of ∼500 arcsec 2 per IFU the scientific data products derived from MaNGA will permit exploration of the internal structure of a statistically large sample of 10,000 low-redshift galaxies in unprecedented detail. Comprising 174 individually pluggable science and calibration IFUs with a near-constant data stream, MaNGA is expected to obtain ∼100 million raw-frame spectra and ∼10 million reduced galaxy spectra over the six-year lifetime of the survey. In this contribution, we describe the MaNGA Data Reduction Pipeline algorithms and centralized metadata framework that produce sky-subtracted spectrophotometrically calibrated spectra and rectified three-dimensional data cubes that combine individual dithered observations. For the 1390 galaxy data cubes released in Summer 2016 as part of SDSS-IV Data Release 13, we demonstrate that the MaNGA data have nearly Poisson-limited sky subtraction shortward of ∼8500 Å and reach a typical 10 σ limiting continuum surface brightness μ  = 23.5 AB arcsec −2 in a five-arcsecond-diameter aperture in the g -band. The wavelength calibration of the MaNGA data is accurate to 5 km s −1 rms, with a median spatial resolution of 2.54 arcsec FWHM (1.8 kpc at the median redshift of 0.037) and a median spectral resolution of σ  = 72 km s −1 .

21 CFR 640.10 - Red Blood Cells.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Red Blood Cells. 640.10 Section 640.10 Food and... ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Red Blood Cells § 640.10 Red Blood Cells. The proper name of this product shall be Red Blood Cells. The product is defined as red blood cells remaining...

78 FR 35756 - Drawbridge Operation Regulations; Charles River, Boston, MA

Science.gov (United States)

2013-06-14

... Regulations; Charles River, Boston, MA AGENCY: Coast Guard, DHS. ACTION: Notice of temporary deviation from...) Bridge across the Charles River, mile 1.0, at Boston, Massachusetts. Under this temporary deviation the... Metropolitan District Commission (Craigie) Bridge, across the Charles River, mile 1.0, at Boston, Massachusetts...

Cytotoxic effects of ZnO nanoparticles on mouse testicular cells

Directory of Open Access Journals (Sweden)

Han Z

2016-10-01

Full Text Available Zhe Han,1,* Qi Yan,1,* Wei Ge,2 Zhi-Guo Liu,1 Sangiliyandi Gurunathan,3 Massimo De Felici,4 Wei Shen,2 Xi-Feng Zhang1 1College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, People’s Republic of China; 2Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, People’s Republic of China; 3Department of Stem Cell and Regenerative Biology, Konkuk University, Seoul, Republic of Korea; 4Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy *These authors contributed equally to this work Background: Nanoscience and nanotechnology are developing rapidly, and the applications of nanoparticles (NPs have been found in several fields. At present, NPs are widely used in traditional consumer and industrial products, however, the properties and safety of NPs are still unclear and there are concerns about their potential environmental and health effects. The aim of the present study was to investigate the potential toxicity of ZnO NPs on testicular cells using both in vitro and in vivo systems in a mouse experimental model. Methods: ZnO NPs with a crystalline size of 70 nm were characterized with various analytical techniques, including ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and atomic force microscopy. The cytotoxicity of the ZnO NPs was examined in vitro on Leydig cell and Sertoli cell lines, and in vivo on the testes of CD1 mice injected with single doses of ZnO NPs.Results: ZnO NPs were internalized by Leydig cells and Sertoli cells, and this resulted in cytotoxicity in a time- and dose-dependent manner through the induction of apoptosis. Apoptosis likely occurred as a consequence of DNA damage (detected as γ-H2AX and RAD51 foci caused by increase in reactive oxygen

Paraneoplastic brain stem encephalitis in a woman with anti-Ma2 antibody.

Science.gov (United States)

Barnett, M; Prosser, J; Sutton, I; Halmagyi, G M; Davies, L; Harper, C; Dalmau, J

2001-02-01

A woman developed brain stem encephalopathy in association with serum anti-Ma2 antibodies and left upper lobe lung mass. T2 weighted MRI of the brain showed abnormalities involving the pons, left middle and superior cerebellar peduncles, and bilateral basal ganglia. Immunohistochemical analysis for serum antineuronal antibodies was confounded by the presence of a non-neuronal specific antinuclear antibody. Immunoblot studies showed the presence of anti-Ma2 antibodies. A premortem tissue diagnosis of the lung mass could not be established despite two CT guided needle biopsies, and the patient died as a result of rapid neurological deterioration. The necropsy showed that the lung lesion was an adenocarcinoma which expressed Ma2 immunoreactive protein. Neuropathological findings included prominent perivascular inflammatory infiltrates, glial nodules, and neuronophagia involving the brain stem, basal ganglia, hippocampus and the dentate nucleus of the cerebellum. Ma2 is an autoantigen previously identified in patients with germ cell tumours of the testis and paraneoplastic brain stem and limbic encephalitis. Our patient's clinical and immunopathological findings indicate that this disorder can affect women with lung adenocarcinoma, and that the encephalitic changes predominate in those regions of the brain known to express high concentrations of Ma proteins.

DMS-MaPseq for genome-wide or targeted RNA structure probing in vivo.

Science.gov (United States)

Zubradt, Meghan; Gupta, Paromita; Persad, Sitara; Lambowitz, Alan M; Weissman, Jonathan S; Rouskin, Silvi

2017-01-01

Coupling of structure-specific in vivo chemical modification to next-generation sequencing is transforming RNA secondary structure studies in living cells. The dominant strategy for detecting in vivo chemical modifications uses reverse transcriptase truncation products, which introduce biases and necessitate population-average assessments of RNA structure. Here we present dimethyl sulfate (DMS) mutational profiling with sequencing (DMS-MaPseq), which encodes DMS modifications as mismatches using a thermostable group II intron reverse transcriptase. DMS-MaPseq yields a high signal-to-noise ratio, can report multiple structural features per molecule, and allows both genome-wide studies and focused in vivo investigations of even low-abundance RNAs. We apply DMS-MaPseq for the first analysis of RNA structure within an animal tissue and to identify a functional structure involved in noncanonical translation initiation. Additionally, we use DMS-MaPseq to compare the in vivo structure of pre-mRNAs with their mature isoforms. These applications illustrate DMS-MaPseq's capacity to dramatically expand in vivo analysis of RNA structure.

NMR characterisation of the minimal interacting regions of centrosomal proteins 4.1R and NuMA1: effect of phosphorylation

Directory of Open Access Journals (Sweden)

Bruix Marta

2010-01-01

Full Text Available Abstract Background Some functions of 4.1R in non-erythroid cells are directly related with its distinct sub-cellular localisation during cell cycle phases. During mitosis, 4.1R is implicated in cell cycle progression and spindle pole formation, and co-localizes with NuMA1. However, during interphase 4.1R is located in the nucleus and only partially co-localizes with NuMA1. Results We have characterized by NMR the structural features of the C-terminal domain of 4.1R and those of the minimal region (the last 64 residues involved in the interaction with NuMA1. This subdomain behaves as an intrinsically unfolded protein containing a central region with helical tendency. The specific residues implicated in the interaction with NuMA1 have been mapped by NMR titrations and involve the N-terminal and central helical regions. The segment of NuMA1 that interacts with 4.1R is phosphorylated during mitosis. Interestingly, NMR data indicates that the phosphorylation of NuMA1 interacting peptide provokes a change in the interaction mechanism. In this case, the recognition occurs through the central helical region as well as through the C-terminal region of the subdomain meanwhile the N-terminal region do not interact. Conclusions These changes in the interaction derived from the phosphorylation state of NuMA1 suggest that phosphorylation can act as subtle mechanism of temporal and spatial regulation of the complex 4.1R-NuMA1 and therefore of the processes where both proteins play a role.

THE DATA REDUCTION PIPELINE FOR THE SDSS-IV MaNGA IFU GALAXY SURVEY

Energy Technology Data Exchange (ETDEWEB)

Law, David R. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Cherinka, Brian [Center for Astrophysical Sciences, Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218 (United States); Yan, Renbin [Department of Physics and Astronomy, University of Kentucky, 505 Rose Street, Lexington, KY 40506-0055 (United States); Andrews, Brett H. [Department of Physics and Astronomy and PITT PACC, University of Pittsburgh, 3941 O’Hara Street, Pittsburgh, PA 15260 (United States); Bershady, Matthew A. [Department of Astronomy, University of Wisconsin-Madison, 475 N. Charter Street, Madison, WI 53706 (United States); Bizyaev, Dmitry [Apache Point Observatory, P.O. Box 59, Sunspot, NM 88349 (United States); Blanc, Guillermo A. [Departamento de Astronomía, Universidad de Chile, Camino del Observatorio 1515, Las Condes, Santiago (Chile); Blanton, Michael R. [Center for Cosmology and Particle Physics, Department of Physics, New York University, 4 Washington Place, New York, NY 10003 (United States); Bolton, Adam S.; Brownstein, Joel R. [Department of Physics and Astronomy, University of Utah, 115 S 1400 E, Salt Lake City, UT 84112 (United States); Bundy, Kevin [Kavli Institute for the Physics and Mathematics of the universe, Todai Institutes for Advanced Study, the University of Tokyo, Kashiwa, 277-8583 (Kavli IPMU, WPI) (Japan); Chen, Yanmei [School of Astronomy and Space Science, Nanjing University, Nanjing 210093 (China); Drory, Niv [McDonald Observatory, Department of Astronomy, University of Texas at Austin, 1 University Station, Austin, TX 78712-0259 (United States); D’Souza, Richard; Jones, Amy; Kauffmann, Guinevere [Max Planck Institute for Astrophysics, Karl-Schwarzschild-Str. 1, D-85748 Garching (Germany); Fu, Hai, E-mail: dlaw@stsci.edu [Department of Physics and Astronomy, University of Iowa, Iowa City, IA 52242 (United States); and others

2016-10-01

Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) is an optical fiber-bundle integral-field unit (IFU) spectroscopic survey that is one of three core programs in the fourth-generation Sloan Digital Sky Survey (SDSS-IV). With a spectral coverage of 3622–10354 Å and an average footprint of ∼500 arcsec{sup 2} per IFU the scientific data products derived from MaNGA will permit exploration of the internal structure of a statistically large sample of 10,000 low-redshift galaxies in unprecedented detail. Comprising 174 individually pluggable science and calibration IFUs with a near-constant data stream, MaNGA is expected to obtain ∼100 million raw-frame spectra and ∼10 million reduced galaxy spectra over the six-year lifetime of the survey. In this contribution, we describe the MaNGA Data Reduction Pipeline algorithms and centralized metadata framework that produce sky-subtracted spectrophotometrically calibrated spectra and rectified three-dimensional data cubes that combine individual dithered observations. For the 1390 galaxy data cubes released in Summer 2016 as part of SDSS-IV Data Release 13, we demonstrate that the MaNGA data have nearly Poisson-limited sky subtraction shortward of ∼8500 Å and reach a typical 10 σ limiting continuum surface brightness μ  = 23.5 AB arcsec{sup −2} in a five-arcsecond-diameter aperture in the g -band. The wavelength calibration of the MaNGA data is accurate to 5 km s{sup −1} rms, with a median spatial resolution of 2.54 arcsec FWHM (1.8 kpc at the median redshift of 0.037) and a median spectral resolution of σ  = 72 km s{sup −1}.

y comercialización de maíz de Sinaloa

Directory of Open Access Journals (Sweden)

José Alberto García Salazar

2006-01-01

Full Text Available La política comercial instrumentada por el Gobierno de México dirigida al mercado de maíz se ha caracterizado por la autorización de importaciones libres de arancel superiores a la cuota establecida en el Tratado de Libre Comercio de América del Norte. Con el objetivo de analizar cómo esta política podría afectar la comercialización de la producción de maíz de Sinaloa, se usó un modelo de distribución de la producción del grano que incorpora características espaciales e intertemporales. Los resultados indican que si el consumo nacional real de maíz fuera menor en 10%, respecto al consumo nacional aparente, las mayores importaciones determinarían que 954 mil toneladas de la producción de la entidad no pudrían comercializarse. Debido a que esta situación resta competitividad al productor de maíz, puesto que la producción no comercializada tiene que almacenarse, los productores sinaloenses deberán estar pendientes y vigilar las decisiones del Gobierno en materia de cupos de importación de maíz.

Occurrence of FSH, inhibin and other hypothalamic-pituitary-intestinal hormones in normal fertility, subfertility, and tumors of human testes.

Science.gov (United States)

Mehta, M K; Garde, S V; Sheth, A R

1995-01-01

To compare the distribution of peptide hormones in presumably normal human testicular tissues and specimens exhibiting any of five pathologies. Biopsies from patients having testicular malfunctions were prepared as sections and specifically immunohistochemically stained for inhibin, FSH, serotonin, AUP, and oxytocin. Immunocytochemical studies revealed the presence of various hypophysial-pituitary-intestinal hormones, viz., FSH, inhibin, arginine vasopressin (AVP), calcitonin, serotonin, oxytocin, adrenocorticotropin (ACTH), gastrin, secretin, and somatostatin in human testicular biopsies exhibiting normal spermatogenesis, Sertoli-cell-only syndrome, spermatogenic arrest, Leydig cell hyperplasia, Leydig cell tumor, and seminoma. Intensity of immunostaining for all peptides except FSH was stronger in cases of subfertile as compared to normal testis. Intensity of immunostaining with inhibin was maximum in Leydig cell tumor. These regulatory peptides may be involved in the pathophysiology of the testes.

Anti Ma2-associated myeloradiculopathy: expanding the phenotype of anti-Ma2 associated paraneoplastic syndromes

OpenAIRE

Murphy, Sinead M; Khan, Usman; Alifrangis, Constantine; Hazell, Steven; Hrouda, David; Blake, Julian; Ball, Joanna; Gabriel, Carolyn; Markarian, Pierre; Rees, Jeremy; Karim, Abid; Seckl, Michael J; Lunn, Michael P; Reilly, Mary M

2011-01-01

Anti-Ma2 associated paraneoplastic syndrome usually presents as limbic encephalitis in association with testicular tumours.1, 2 Only four patients have been reported with involvement outside the CNS, two of whom also had limbic or brainstem encephalitis.2, 3 We report a man with anti- Ma2 associated myeloradiculopathy and previous testicular cancer whose neurological syndrome stabilised and anti-Ma2 titres fell following orchidectomy of a microscopically normal testis.

Antioxidative effects in vivo and colonization of Lactobacillus plantarum MA2 in the murine intestinal tract.

Science.gov (United States)

Tang, Wei; Xing, Zhuqing; Hu, Wei; Li, Chao; Wang, Jinju; Wang, Yanping

2016-08-01

Lactobacillus plantarum MA2 was isolated from traditional Chinese Tibet kefir grains, which possess several excellent properties and functions. We previously demonstrated the antioxidant activities of this bacterium in vitro. However, the maintenance and survival of L. plantarum MA2 inside the murine intestinal tract, where it exerts its probiotic properties, and whether its effects are elicited directly on the host remain unknown. Therefore, this study investigated the mechanisms of L. plantarum MA2 in aging mice following D-galactose administration. The levels of malondialdehyde decreased significantly in the L. plantarum MA2 groups after oral ingestion compared to the D-galactose model group, and total antioxidant capacity and glutathione peroxidase and superoxide dismutase activities increased significantly in the serum and liver. We combined fluorescein isothiocyanate labeling and green fluorescent protein expression to dynamically monitor the colonization and distribution of L. plantarum MA2 in the murine intestinal tract. The results indicated that L. plantarum MA2 was detected in the ileum, colon, and feces after single and continuous oral administration at day 21 and was maintained at 10(4)-10(5) CFU/g. These results suggest that L. plantarum MA2 colonizes and survives in the murine intestinal tract to exert its antioxidative effects.

46 CFR 7.20 - Nantucket Sound, Vineyard Sound, Buzzards Bay, Narragansett Bay, MA, Block Island Sound and...

Science.gov (United States)

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Nantucket Sound, Vineyard Sound, Buzzards Bay, Narragansett Bay, MA, Block Island Sound and easterly entrance to Long Island Sound, NY. 7.20 Section 7.20... Atlantic Coast § 7.20 Nantucket Sound, Vineyard Sound, Buzzards Bay, Narragansett Bay, MA, Block Island...

Regioselective hydroxylation of isoflavones by Streptomyces avermitilis MA-4680.

Science.gov (United States)

Roh, Changhyun; Seo, Su-Hyun; Choi, Kwon-Young; Cha, Minho; Pandey, Bishnu Prasad; Kim, June-Hyung; Park, Jun-Seong; Kim, Duck Hee; Chang, Ih Seop; Kim, Byung-Gee

2009-07-01

Screening of bacterial whole cells was performed for regioselective hydroxylation of daidzein and genistein. Among the strains examined, Streptomyces avermitilis MA-4680 showed high ortho-dihydroxylation activity to produce 3',4',7-trihydroxyisoflavone and 3',4',5,7-tetrahydroxyisoflavone from daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), respectively. Using 100 mg cells (wet wt.) and 1% (v/v) Triton X100 in 1 ml of total reaction volume, where 100 microl of the substrate solution (0.5 mM in 10% (v/v) mixed solvent of DMSO:MeOH = 3:7) was added to 900 microl of potassium phosphate buffer (100 mM, pH 7.2), a 16% molar conversion yield of 3',4',7-trihydroxyisoflavone was obtained from 0.5 mM daidzein after 24 h of reaction time at 28 degrees C and 200 rpm. Ketoconazole significantly (ca. 90%) inhibited the ortho-hydroxylation activity of daidzein, suggesting that cytochrome P450 enzymes putatively play roles in regiospecific daidzein hydroxylation. The analysis of the reaction products was determined by gas chromatography/mass spectrometry (GC/MS) and (1)H NMR.

Second primary tumor in anti-Ma1/2-positive paraneoplastic limbic encephalitis.

Science.gov (United States)

Leyhe, T; Schüle, R; Schwärzler, F; Gasser, T; Haarmeier, T

2006-05-01

Memory loss can be a symptom of paraneoplastic limbic encephalitis (PLE) a neuropsychiatric disorder associated mostly with small-cell lung cancer and anti-Hu antibodies or with testicular tumors and anti-Ma2 antibodies. We present the case of a patient with temporal coincidence of beginning cognitive decline and diagnosis of a carcinoma of the prostate in whom we diagnosed anti-Ma1/Ma2-positive PLE. The tumor had been completely resected but memory impairment further deteriorated. As the effective treatment of the cancer is considered as the most efficient treatment of a paraneoplastic neurological syndrome (PNS) a second neoplasia was suspected in the patient. By the aid of whole body positron emission tomography with 18-fluorine fluoro-2-deoxy-glucose (FDG-PET) an adenocarcinoma of the cecum could be detected. Two months after surgery anti-Ma antibodies were negative. We conclude that a second neoplasia should be considered, if effective cancer treatment does not lead to improvement or stabilisation of a PNS. Tumor search should be exhaustive and include PET when conventional imaging fails to show a malignancy.

Reduced fetal androgen exposure compromises Leydig cell function in adulthood

NARCIS (Netherlands)

Teerds, K.J.; Keijer, J.

2015-01-01

Disruption of normal fetal development can influence functioning of organs and cells in adulthood. Circumstantial evidence suggests that subtle reductions in fetal androgen production may be the cause of adult male reproductive disorders due to reduced testosterone production. The mechanisms through

Decreasing Slip Rates From 12.8 Ma to Present on the Solitario Canyon Fault at Yucca Mountain, Nevada

International Nuclear Information System (INIS)

D. Buesch

2006-01-01

The Solitario Canyon fault, which bounds the west side of Yucca Mountain, Nevada, is the closest fault with Quaternary offset adjacent to the proposed spent nuclear fuel and high-level radioactive waste repository. Dip-slip offset between 12.8 and 10.7 Ma is determined from lithostratigraphic displacement in boreholes USW H-3 and USW WT-7, drilled in the footwall and hanging wall, respectively. The base of the 12.8-Ma Topopah Spring Tuff is interpreted to have 463.3 m of separation across the fault, an average dip slip rate of 0.036 mm/yr. Previous researchers identified a geothermal system active from 11.5 to 10.0 Ma with peak activity at 10.7 Ma that resulted in pervasive alteration of vitric rock to zeolitic minerals where the rocks were in the ground-water saturated zone. The contact between vitric (V) and pervasively zeolitic (Z) rocks cuts across the lithostratigraphic section and offset of this V-Z boundary can be used to measure slip rates between 12.8 and 10.7 Ma. In H-3, the V-Z boundary is 138.4 m below the base of the vitric, densely welded subzone of the Topopah Spring Tuff (Tptpv3). In WT-7, although the V-Z boundary is identified at the base of the Tptpv3, borehole video, cuttings, and geophysical log data indicate the Tptpv3 has well-developed zeolitic alteration along fractures, and this implies 19.5 m of the total thickness of Tptpv3 (and probably additional overlying crystallized rocks) also were in the saturated zone by 10.7 Ma. The V-Z relations across the Solitario Canyon fault in H-3 and WT-7 indicate a minimum of 157.9 m of separation before 10.7 Ma, which is 34.1 percent of the total slip of the Topopah Spring Tuff, and a minimum dip slip rate of 0.075 mm/yr from 12.8 to 10.7 Ma. These data are consistent with the broader structural history of the area near Yucca Mountain. Previous workers used angular unconformities, tilting of structural blocks, and paleomagnetic data to constrain the main period of extensional faulting between 12.7 and 8

Cellular changes in the hamster testicular interstitium with ageing and after exposure to short photoperiod.

Science.gov (United States)

Beltrán-Frutos, E; Seco-Rovira, V; Ferrer, C; Madrid, J F; Sáez, F J; Canteras, M; Pastor, L M

2016-04-01

The aim of this study was to evaluate the cellular changes that occur in the hamster testicular interstitium in two very different physiological situations involving testicular involution: ageing and exposure to a short photoperiod. The animals were divided into an 'age group' with three subgroups - young, adult and old animals - and a 'regressed group' with animals subjected to a short photoperiod. The testicular interstitium was characterised by light and electron microscopy. Interstitial cells were studied histochemically with regard to their proliferation, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end labelling (TUNEL+) and testosterone synthetic activity. We identified two types of Leydig cell: Type A cells showed a normal morphology, while Type B cells appeared necrotic. With ageing, pericyte proliferation decreased but there was no variation in the index of TUNEL-positive Leydig cells. In the regressed group, pericyte proliferation was greater and TUNEL-positive cells were not observed in the interstitium. The testicular interstitium suffered few ultrastructural changes during ageing and necrotic Leydig cells were observed. In contrast, an ultrastructural involution of Leydig cells with no necrosis was observed in the regressed group. In conclusion, the testicular interstitium of Mesocricetus auratus showed different cellular changes in the two groups (age and regressed), probably due to the irreversible nature of ageing and the reversible character of changes induced by short photoperiod.

Asymmetrical squaraines for high-performance small-molecule organic solar cells with a short circuit current of over 12 mA cm(-2).

Science.gov (United States)

Chen, Yao; Zhu, Youqin; Yang, Daobin; Luo, Qian; Yang, Lin; Huang, Yan; Zhao, Suling; Lu, Zhiyun

2015-04-11

An asymmetrical squaraine dye (Py-3) with its two electron-donating aryl groups directly linked to the electron-withdrawing squaric acid core possesses an ideal bandgap of 1.33 eV, together with an intense and broad absorption band in the range 550-950 nm. Hence, the resulting solution-processed solar cells display an impressive Jsc of 12.03 mA cm(-2) and a PCE of 4.35%.

Neutron radiographic characteristics of MA-ND type (allyl-diglycol-carbonate) nuclear track detectors

Energy Technology Data Exchange (ETDEWEB)

Ilic, R.; Rant, J.; Humar, M.; Somogyi, G.; Hunyadi, I.

1986-01-01

Neutron radiographic properties of recently developed new nuclear track detectors (MA-ND/..cap alpha.., MA-ND/p and MA-ND/p1), manufactured from allyl diglycol carbonate, were studied. It was found that the quality of radiographic image has an optimum at a removed layer thickness of about 0.8 ..mu..m. The image obtained under this condition is characterized by high detection sensitivity to neutrons (approx. 8.10/sup -3/ tracks/nsub(th) when using B converter) and by excellent inherent unsharpness (approx. 5 ..mu..m) as well as high image contrast (maximum value of net optical density is approx. 1.4).

OVERVIEW OF THE SDSS-IV MaNGA SURVEY: MAPPING NEARBY GALAXIES AT APACHE POINT OBSERVATORY

Energy Technology Data Exchange (ETDEWEB)

Bundy, Kevin [Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU, WPI), Todai Institutes for Advanced Study, the University of Tokyo, Kashiwa 277-8583 (Japan); Bershady, Matthew A.; Wake, David A.; Tremonti, Christy; Diamond-Stanic, Aleksandar M. [Department of Astronomy, University of Wisconsin-Madison, 475 North Charter Street, Madison, WI 53706 (United States); Law, David R.; Cherinka, Brian [Dunlap Institute for Astronomy and Astrophysics, University of Toronto, 50 St. George Street, Toronto, Ontario M5S 3H4 (Canada); Yan, Renbin; Sánchez-Gallego, José R. [Department of Physics and Astronomy, University of Kentucky, 505 Rose Street, Lexington, KY 40506-0055 (United States); Drory, Niv [McDonald Observatory, Department of Astronomy, University of Texas at Austin, 1 University Station, Austin, TX 78712-0259 (United States); MacDonald, Nicholas [Department of Astronomy, Box 351580, University of Washington, Seattle, WA 98195 (United States); Weijmans, Anne-Marie [School of Physics and Astronomy, University of St Andrews, North Haugh, St Andrews KY16 9SS (United Kingdom); Thomas, Daniel; Masters, Karen; Coccato, Lodovico [Institute of Cosmology and Gravitation, University of Portsmouth, Portsmouth (United Kingdom); Aragón-Salamanca, Alfonso [School of Physics and Astronomy, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom); Avila-Reese, Vladimir [Instituto de Astronomia, Universidad Nacional Autonoma de Mexico, A.P. 70-264, 04510 Mexico D.F. (Mexico); Badenes, Carles [Department of Physics and Astronomy and Pittsburgh Particle Physics, Astrophysics and Cosmology Center (PITT PACC), University of Pittsburgh, 3941 OHara St, Pittsburgh, PA 15260 (United States); Falcón-Barroso, Jésus [Instituto de Astrofísica de Canarias, E-38200 La Laguna, Tenerife (Spain); Belfiore, Francesco [Cavendish Laboratory, University of Cambridge, 19 J. J. Thomson Avenue, Cambridge CB3 0HE (United Kingdom); and others

2015-01-01

We present an overview of a new integral field spectroscopic survey called MaNGA (Mapping Nearby Galaxies at Apache Point Observatory), one of three core programs in the fourth-generation Sloan Digital Sky Survey (SDSS-IV) that began on 2014 July 1. MaNGA will investigate the internal kinematic structure and composition of gas and stars in an unprecedented sample of 10,000 nearby galaxies. We summarize essential characteristics of the instrument and survey design in the context of MaNGA's key science goals and present prototype observations to demonstrate MaNGA's scientific potential. MaNGA employs dithered observations with 17 fiber-bundle integral field units that vary in diameter from 12'' (19 fibers) to 32'' (127 fibers). Two dual-channel spectrographs provide simultaneous wavelength coverage over 3600-10300 Å at R ∼ 2000. With a typical integration time of 3 hr, MaNGA reaches a target r-band signal-to-noise ratio of 4-8 (Å{sup –1} per 2'' fiber) at 23 AB mag arcsec{sup –2}, which is typical for the outskirts of MaNGA galaxies. Targets are selected with M {sub *} ≳ 10{sup 9} M {sub ☉} using SDSS-I redshifts and i-band luminosity to achieve uniform radial coverage in terms of the effective radius, an approximately flat distribution in stellar mass, and a sample spanning a wide range of environments. Analysis of our prototype observations demonstrates MaNGA's ability to probe gas ionization, shed light on recent star formation and quenching, enable dynamical modeling, decompose constituent components, and map the composition of stellar populations. MaNGA's spatially resolved spectra will enable an unprecedented study of the astrophysics of nearby galaxies in the coming 6 yr.

OVERVIEW OF THE SDSS-IV MaNGA SURVEY: MAPPING NEARBY GALAXIES AT APACHE POINT OBSERVATORY

International Nuclear Information System (INIS)

Bundy, Kevin; Bershady, Matthew A.; Wake, David A.; Tremonti, Christy; Diamond-Stanic, Aleksandar M.; Law, David R.; Cherinka, Brian; Yan, Renbin; Sánchez-Gallego, José R.; Drory, Niv; MacDonald, Nicholas; Weijmans, Anne-Marie; Thomas, Daniel; Masters, Karen; Coccato, Lodovico; Aragón-Salamanca, Alfonso; Avila-Reese, Vladimir; Badenes, Carles; Falcón-Barroso, Jésus; Belfiore, Francesco

2015-01-01

We present an overview of a new integral field spectroscopic survey called MaNGA (Mapping Nearby Galaxies at Apache Point Observatory), one of three core programs in the fourth-generation Sloan Digital Sky Survey (SDSS-IV) that began on 2014 July 1. MaNGA will investigate the internal kinematic structure and composition of gas and stars in an unprecedented sample of 10,000 nearby galaxies. We summarize essential characteristics of the instrument and survey design in the context of MaNGA's key science goals and present prototype observations to demonstrate MaNGA's scientific potential. MaNGA employs dithered observations with 17 fiber-bundle integral field units that vary in diameter from 12'' (19 fibers) to 32'' (127 fibers). Two dual-channel spectrographs provide simultaneous wavelength coverage over 3600-10300 Å at R ∼ 2000. With a typical integration time of 3 hr, MaNGA reaches a target r-band signal-to-noise ratio of 4-8 (Å –1 per 2'' fiber) at 23 AB mag arcsec –2 , which is typical for the outskirts of MaNGA galaxies. Targets are selected with M * ≳ 10 9 M ☉ using SDSS-I redshifts and i-band luminosity to achieve uniform radial coverage in terms of the effective radius, an approximately flat distribution in stellar mass, and a sample spanning a wide range of environments. Analysis of our prototype observations demonstrates MaNGA's ability to probe gas ionization, shed light on recent star formation and quenching, enable dynamical modeling, decompose constituent components, and map the composition of stellar populations. MaNGA's spatially resolved spectra will enable an unprecedented study of the astrophysics of nearby galaxies in the coming 6 yr

Cyclic adenosine 3',5'-monophosphate (cAMP) enhances cAMP-responsive element binding (CREB) protein phosphorylation and phospho-CREB interaction with the mouse steroidogenic acute regulatory protein gene promoter.

Science.gov (United States)

Clem, Brian F; Hudson, Elizabeth A; Clark, Barbara J

2005-03-01

Steroidogenic acute regulatory protein (StAR) transcription is regulated through cAMP-protein kinase A-dependent mechanisms that involve multiple transcription factors including the cAMP-responsive element binding protein (CREB) family members. Classically, binding of phosphorylated CREB to cis-acting cAMP-responsive elements (5'-TGACGTCA-3') within target gene promoters leads to recruitment of the coactivator CREB binding protein (CBP). Herein we examined the extent of CREB family member phosphorylation on protein-DNA interactions and CBP recruitment with the StAR promoter. Immunoblot analysis revealed that CREB, cAMP-responsive element modulator (CREM), and activating transcription factor (ATF)-1 are expressed in MA-10 mouse Leydig tumor cells, yet only CREB and ATF-1 are phosphorylated. (Bu)2cAMP treatment of MA-10 cells increased CREB phosphorylation approximately 2.3-fold within 30 min but did not change total nuclear CREB expression levels. Using DNA-affinity chromatography, we now show that CREB and ATF-1, but not CREM, interact with the StAR promoter, and this interaction is dependent on the activator protein-1 (AP-1) cis-acting element within the cAMP-responsive region. In addition, (Bu)2cAMP-treatment increased phosphorylated CREB (P-CREB) association with the StAR promoter but did not influence total CREB interaction. In vivo chromatin immunoprecipitation assays demonstrated CREB binding to the StAR proximal promoter is independent of (Bu)2cAMP-treatment, confirming our in vitro analysis. However, (Bu)2cAMP-treatment increased P-CREB and CBP interaction with the StAR promoter, demonstrating for the first time the physical role of P-CREB:DNA interactions in CBP recruitment to the StAR proximal promoter.

Phorbol ester and vasopressin activate phospholipase D in Leydig cells

DEFF Research Database (Denmark)

Vinggaard, Anne Marie; Hansen, Harald S.

1991-01-01

]PEt) in a dose-dependent manner at the expense of [H]phosphatidic acid ([H]PA). In cells prelabelled with [H]choline, PMA caused a rapid increase in intracellular free [H]choline. The time course of [H]PEt formation was similar to the time course of intracellular [H]choline formation. The data taken together...

75 FR 62469 - Drawbridge Operation Regulations; Charles River, Boston, MA, Maintenance

Science.gov (United States)

2010-10-12

... Operation Regulations; Charles River, Boston, MA, Maintenance AGENCY: Coast Guard, DHS. ACTION: Notice of... Craigie Bridge across the Charles River at mile 1.0, has a vertical clearance of 10.25 feet at normal pool... temporary deviation from the regulation governing the operation of the Craigie Bridge across the Charles...

Correlating The Star Formation Histories Of MaNGA Galaxies With Their Past AGN Activity

Science.gov (United States)

Gonzalez Ortiz, Andrea

2017-01-01

We investigate active galactic nuclei (AGN) as a primary mechanism affecting star formation in MaNGA galaxies. Using the Pipe3D code, we modeled the stellar population from MaNGA spectra and derived the star formation histories of 53 AGN host galaxies. We seek to compare the star formation histories of the host galaxies of AGN with the ages of their radio lobes to better understand the role of AGN feedback in the star formation histories of MaNGA galaxies. MaNGA (Mapping Nearby Galaxies at APO) is one of the three core programs in the fourth generation Sloan Digital Sky Survey(SDSS). MaNGA will investigate the internal kinematics of nearly 10,000 local galaxies through dithered observations using fiber integral field units (IFUs) that vary in diameter from 12" (19 fibers) to 32" (127 fibers). In this poster, we present initial results on the star formation histories of MaNGA AGN host galaxies. This work was supported by the SDSS Research Experience for Undergraduates program, which is funded by a grant from Sloan Foundation to the Astrophysical Research Consortium.

Early pathologic findings and long-term improvement in anti-Ma2-associated encephalitis.

Science.gov (United States)

Blumenthal, D T; Salzman, K L; Digre, K B; Jensen, R L; Dunson, W A; Dalmau, J

2006-07-11

A 67-year-old man sequentially developed anti-Ma2-associated paraneoplastic encephalitis (PNE) and contralateral herpes simplex encephalitis (HSE). Brain biopsy 1 month before HSE revealed extensive infiltrates of T cells, B cells, and plasma cells. Most T cells expressed the cytotoxic granule-associated protein TIA-1 and the membranolytic protein granzyme-B. Although recovery was thought to be unlikely, treatment of the PNE with corticosteroids and resection of the associated lung cancer resulted in dramatic improvement for 21 months.

Study of homogeneous fuel cells type 10 x 10

International Nuclear Information System (INIS)

Montes, J.L.; Perusquia, R.; Ortiz, J.J.; Francois, J.L.; Marquez, C.M.

2005-01-01

At the moment in the National Institute of Nuclear Research (ININ) are carried out studies with the purpose of to establish a methodology that allows to carry out the neutron design of fuel cells of type 10 x 10. During the initial stage of the process of cells design, starting from the data that have to do with the planned energy demand it requires to be estimated the average value of the enrichment in U 235 w/o of the one assemble. The experience has shown that the accuracy that is achieved in this estimate it depends, among other factors, of the information (e.g. concentrations of U 235 and Gd 2 O 3 ) of the cells that its are disposed in that moment. For what we consider convenient to enlarge the available information by means of a series of calculations of cell physics; and to the one same time some aspects can be studied on the parameters that define the characteristics of a fuel cell. In this work the effect of the presence of different distributions of the concentrations of the fissile material is analyzed and of burnup poisons on the reactivity parameters of the cell as well as in the peak factor of local power (LPPF-Local Power Peaking Factor). (Author)

The Ste12-like transcription factor MaSte12 is involved in pathogenicity by regulating the appressorium formation in the entomopathogenic fungus, Metarhizium acridum.

Science.gov (United States)

Wei, Qinglv; Du, Yanru; Jin, Kai; Xia, Yuxian

2017-12-01

Homeodomain transcription factor Ste12 is a key target activated by the pathogenic mitogen-activated-protein kinase pathway, and the activated Ste12p protein regulates downstream gene expression levels to modulate phenotypes. However, the functions of Ste12-like genes in entomopathogenic fungi remain poorly understood and little is known about the downstream genes regulated by Ste12. In this study, we characterized the functions of a Ste12 orthologue in Metarhizium acridum, MaSte12, and identified its downstream target genes. The deletion mutant (ΔMaSte12) is defective in conidial germination but not in hyphal growth, conidiation, or stress tolerance. Bioassays showed that ΔMaSte12 had a dramatically decreased virulence in topical inoculations, but no significant difference was found in intrahemolymph injections when the penetration process was bypassed. The mature appressorium formation rate of ΔMaSte12 was less than 10% on locust wings, with the majority hyphae forming appressorium-like, curved but no swollen structures. Digital gene expression profiling revealed that some genes involved in cell wall synthesis and remodeling, appressorium development, and insect cuticle penetration were downregulated in ΔMaSte12. Thus, MaSte12 has critical roles in the pathogenicity of the entomopathogenic fungus M. acridum, and our study provides some explanations for the impairment of fungal virulence in ΔMaSte12. In addition, virulence is very important for fungal biocontrol agents to control insect pests effectively. This study demonstrated that MaSte12 is involved in fungal virulence but not conidial yield or fungal stress tolerance in M. acridum. Thus, MaSte12 and its downstream genes may be candidates for enhancing fungal virulence to improve mycoinsecticides.

The (mis)Measurement of M&A Performance

DEFF Research Database (Denmark)

Meglio, Olimpia; Risberg, Annette

2011-01-01

This paper seeks to further the understanding of the variety of meanings M&A scholars attach to the label “M&A performance” by providing an alternative way to interpret the claimed inconsistency of M&A research findings. While many scholars contend that the problem stems from the multiplicity of M......&A performance measures, we believe the problem rests in trying to compare different measures as if they were measuring the same feature of the organization. Through our narrative review of empirical research we analyze factors shaping the M&A – as well as the organizational – performance measurement process....... The conclusion is that it is not possible to talk about M&A performance as if it was a universal construct....

Pancreatic β-Cell-Derived IP-10/CXCL10 Isletokine Mediates Early Loss of Graft Function in Islet Cell Transplantation.

Science.gov (United States)

Yoshimatsu, Gumpei; Kunnathodi, Faisal; Saravanan, Prathab Balaji; Shahbazov, Rauf; Chang, Charles; Darden, Carly M; Zurawski, Sandra; Boyuk, Gulbahar; Kanak, Mazhar A; Levy, Marlon F; Naziruddin, Bashoo; Lawrence, Michael C

2017-11-01

Pancreatic islets produce and secrete cytokines and chemokines in response to inflammatory and metabolic stress. The physiological role of these "isletokines" in health and disease is largely unknown. We observed that islets release multiple inflammatory mediators in patients undergoing islet transplants within hours of infusion. The proinflammatory cytokine interferon-γ-induced protein 10 (IP-10/CXCL10) was among the highest released, and high levels correlated with poor islet transplant outcomes. Transgenic mouse studies confirmed that donor islet-specific expression of IP-10 contributed to islet inflammation and loss of β-cell function in islet grafts. The effects of islet-derived IP-10 could be blocked by treatment of donor islets and recipient mice with anti-IP-10 neutralizing monoclonal antibody. In vitro studies showed induction of the IP-10 gene was mediated by calcineurin-dependent NFAT signaling in pancreatic β-cells in response to oxidative or inflammatory stress. Sustained association of NFAT and p300 histone acetyltransferase with the IP-10 gene required p38 and c-Jun N-terminal kinase mitogen-activated protein kinase (MAPK) activity, which differentially regulated IP-10 expression and subsequent protein release. Overall, these findings elucidate an NFAT-MAPK signaling paradigm for induction of isletokine expression in β-cells and reveal IP-10 as a primary therapeutic target to prevent β-cell-induced inflammatory loss of graft function after islet cell transplantation. © 2017 by the American Diabetes Association.

Coenzyme Q10 protects hair cells against aminoglycoside.

Directory of Open Access Journals (Sweden)

Kazuma Sugahara

Full Text Available It is well known that the production of free radicals is associated with sensory cell death induced by an aminoglycoside. Many researchers have reported that antioxidant reagents protect sensory cells in the inner ear, and coenzyme Q10 (CoQ10 is an antioxidant that is consumed as a health food in many countries. The purpose of this study was to investigate the role of CoQ10 in mammalian vestibular hair cell death induced by aminoglycoside. Cultured utricles of CBA/CaN mice were divided into three groups (control group, neomycin group, and neomycin + CoQ10 group. In the neomycin group, utricles were cultured with neomycin (1 mM to induce hair cell death. In the neomycin + CoQ10 group, utricles were cultured with neomycin and water-soluble CoQ10 (30-0.3 µM. Twenty-four hours after exposure to neomycin, the cultured tissues were fixed, and vestibular hair cells were labeled using an anti-calmodulin antibody. Significantly more hair cells survived in the neomycin + CoQ10 group than in the neomycin group. These data indicate that CoQ10 protects sensory hair cells against neomycin-induced death in the mammalian vestibular epithelium; therefore, CoQ10 may be useful as a protective drug in the inner ear.

Maïs beperkt nitraatverlies van gras

NARCIS (Netherlands)

Verloop, J.; Boumans, L.

2006-01-01

Maïs staat bekend als een gewas dat veel nitraat naar het grondwater lekt. Maar maïs heeft ook goeie kanten. Nieuw in dit rijtje is dat maïs, in vruchtwisseling met gras, ook het nitraatverlies van grasland beperkt. Dit blijkt uit de metingen van het RIVM op De Marke.

Development of ITER 15 MA ELMy H-mode Inductive Scenario

International Nuclear Information System (INIS)

C. E. Kessel, D. Campbell, Y. Gribov, G. Saibene, G. Ambrosino, T. Casper, M. Cavinato, H. Fujieda, R. Hawryluk, L. D. Horton, A. Kavin, R. Kharyrutdinov, F. Koechl, J. Leuer, A. Loarte, P. J. Lomas, T. Luce, V. Lukash, M. Mattei, I.Nunes, V. Parail, A. Polevoi, A. Portone, R. Sartori, A.C.C. Sips, P. R. Thomas, A. Welander and J. Wesley

2008-01-01

The poloidal field (PF) coil system on ITER, which provides both feedforward and feedback control of plasma position, shape, and current, is a critical element for achieving mission performance. Analysis of PF capabilities has focused on the 15 MA Q = 10 scenario with a 300-500 s flattop burn phase. The operating space available for the 15 MA ELMy H-mode plasma discharges in ITER and upgrades to the PF coils or associated systems to establish confidence that ITER mission objectives can be reached have been identified. Time dependent self-consistent free-boundary calculations were performed to examine the impact of plasma variability, discharge programming, and plasma disturbances. Based on these calculations a new reference scenario was developed based upon a large bore initial plasma, early divertor transition, low level heating in L-mode, and a late H-mode onset. Equilibrium analyses for this scenario indicate that the original PF coil limitations do not allow low li (<0.8) operation or lower flux states, and the flattop burn durations were predicted to be less than the desired 400 s. This finding motivates the expansion of the operating space, considering several upgrade options to the PF coils. Analysis was also carried out to examine the feedback current reserve required in the CS and PF coils during a series of disturbances and a feasibility assessment of the 17 MA scenario was undertaken. Results of the studies show that the new scenario and modified PF system will allow a wide range of 15 MA 300-500 s operation and more limited but finite 17 MA operation

Differential testosterone secretory capacity of the testes of aggressive and nonaggressive house mice during ontogeny

OpenAIRE

de Ruiter, Anne J H; Koolhaas, Jaap M; van Oortmerssen, Geert A; Bohus, Bela

1992-01-01

In this study, testosterone secretory capacity of testicular Leydig cells during ontogeny was determined in males of an aggressive and a nonaggressive genetic selection line of wild house mice. Neonates, 23-day-old prepubertals, and adult male mice were studied. A morphometric method was used to quantify 3-beta-hydroxy steroid dehydrogenase (3-beta-HSD)-stained Leydig cells in testicular sections to determine testosterone secretory capacity. We consider this parameter to reflect circulating t...

Effect of Spermidine Analogues on Cell Growth of Escherichia coli Polyamine Requiring Mutant MA261.

Directory of Open Access Journals (Sweden)

Taketo Yoshida

Full Text Available The effects of spermidine analogues [norspermidine (NSPD, 33, spermidine (SPD, 34, homospermidine (HSPD, 44 and aminopropylcadaverine (APCAD, 35] on cell growth were studied using Escherichia coli polyamine-requiring mutant MA261. Cell growth was compared at 32°C, 37°C, and 42°C. All four analogues were taken up mainly by the PotABCD spermidine-preferential uptake system. The degree of stimulation of cell growth at 32°C and 37°C was NSPD ≥ SPD ≥ HSPD > APCAD, and SPD ≥ HSPD ≥ NSPD > APCAD, respectively. However, at 42°C, it was HSPD » SPD > NSPD > APCAD. One reason for this is HSPD was taken up effectively compared with other triamines. In addition, since natural polyamines (triamines and teteraamines interact mainly with RNA, and the structure of RNA is more flexible at higher temperatures, HSPD probably stabilized RNA more tightly at 42°C. We have thus far found that 20 kinds of protein syntheses are stimulated by polyamines at the translational level. Among them, synthesis of OppA, RpoE and StpA was more strongly stimulated by HSPD at 42°C than at 37°C. Stabilization of the initiation region of oppA and rpoE mRNA was tighter by HSPD at 42°C than 37°C determined by circular dichroism (CD. The degree of polyamine stimulation of OppA, RpoE and StpA synthesis by NSPD, SPD and APCAD was smaller than that by HSPD at 42°C. Thus, the degree of stimulation of cell growth by spermidine analogues at the different temperatures is dependent on the stimulation of protein synthesis by some components of the polyamine modulon.

Testosterone Production is Better Preserved After 16 than 20 Gray Irradiation Treatment Against Testicular Carcinoma In Situ Cells

International Nuclear Information System (INIS)

Bang, Anne K.; Petersen, Jorgen H.; Petersen, Peter M.; Andersson, Anna-Maria; Daugaard, Gedske; Jorgensen, Niels

2009-01-01

Purpose: To study the effect of 16 Gy radiotherapy (RT) vs. 20 Gy RT on Leydig cell function in men treated with radiotherapy against carcinoma in situ (CIS) of the testis. Methods and Materials: Fifty-one men who were treated between 1985 and 2005 were included. Fourteen men had been treated with 20 Gy and 37 with 16 Gy RT. Measurements of sex hormone-binding globulin and basic and stimulated testosterone, as well as luteinizing hormone levels were performed. Results: The follow-up periods for the patients treated without additional chemotherapy were for the 20 Gy and 16 Gy group mean/median/min-max: 9.0/10.0/1.0-20.3 years and 4.0/3.1/0.4-14.1 years, respectively. During the follow-up period, men treated with 16 Gy RT had stable testosterone levels (-1.1%/year, p = 0.4), whereas men treated with 20 Gy had an annual decrease of 2.4% (p = 0.008). For the latter group, the testosterone decrease was most pronounced in the first 5 years, leveling off during the following 5 years. Additionally, more men treated with 20 Gy needed androgen substitution treatment. Our study showed an increased luteinizing hormone level for the men treated with 16 Gy, although this was not significant (p = 0.5). We anticipated a similar increase in the patients treated with 20 Gy but instead observed a decrease (-3.1%, p = 0.01). Conclusion: RT at 16 and 20 Gy seem to affect Leydig cell function differently, with 16 Gy RT better preserving testosterone levels and thus being preferred from an endocrinological point of view.

Bovine mammary stem cells: Cell biology meets production agriculture

Science.gov (United States)

Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue ...

Ultrastructure of the Interstitial Tissue in the Testis of the Egyptian Dromedary Camel (Camelus dromedarius

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M. I. Abd-Elaziz, A. M. Kassem, D. M. Zaghloul*, A. E. Derbalah and M. H. Bolefa

2012-01-01

Full Text Available The ultrastructural examination of the testicular interstitial tissue of Egyptian dromedary camel was performed to observe the seasonal changes. The activity of the interstitial tissue increased largely in spring. This was indicated by the large number of mature Leydig cells and two to three layers of myofibroblasts around the basal laminae of the seminiferous tubules with large blood vessels in the interstitial tissue. The testicular activity was moderate in winter as indicated by the lower number of immature Leydig cells. The lowest activity was in summer when Leydig cells became inactive with pyknotic nuclei. The cells of interstitial tissue lost their junctions with each other, leaving large intercellular spaces and myofibroblasts transformed to fibrocytes. The testicular activity began again to increase in autumn. The testicular activity of camel, however, did not stop in any season of the year, because even in non-breeding seasons a part of the interstitial tissue of the testis was active.

Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population.

Science.gov (United States)

Zhang, Bin; Liu, Rui; Shi, Dan; Liu, Xingxia; Chen, Yuan; Dou, Xiaowei; Zhu, Xishan; Lu, Chunhua; Liang, Wei; Liao, Lianming; Zenke, Martin; Zhao, Robert C H

2009-01-01

Mesenchymal stem cells (MSCs), in addition to their multilineage differentiation, exert immunomodulatory effects on immune cells, even dendritic cells (DCs). However, whether they influence the destiny of full mature DCs (maDCs) remains controversial. Here we report that MSCs vigorously promote proliferation of maDCs, significantly reduce their expression of Ia, CD11c, CD80, CD86, and CD40 while increasing CD11b expression. Interestingly, though these phenotypes clearly suggest their skew to immature status, bacterial lipopolysaccharide (LPS) stimulation could not reverse this trend. Moreover, high endocytosic capacity, low immunogenicity, and strong immunoregulatory function of MSC-treated maDCs (MSC-DCs) were also observed. Furthermore we found that MSCs, partly via cell-cell contact, drive maDCs to differentiate into a novel Jagged-2-dependent regulatory DC population and escape their apoptotic fate. These results further support the role of MSCs in preventing rejection in organ transplantation and treatment of autoimmune disease.

IPN hydrogels based on PNIPAAm and PVA-Ma networks: characterization through measure of LCST, swelling ratio and mechanical properties - doi: 10.4025/actascitechnol.v34i2.15019

Directory of Open Access Journals (Sweden)

Adriana Cristina Wenceslau

2012-03-01

Full Text Available IPN hydrogels based on chemically modified poly(vinyl alcohol (or PVA-Ma, with different degrees of substitution (DS, and poly(N-isopropylacrylamide (or PNIPAAm were obtained and characterized through measures of LCST, swelling ratio and mechanical properties. Linear PVA-Ma with several DS were obtained through the chemical reaction of PVA with glycidyl methacrylate (GMA. The DS of various PVA-Ma were determined through 1H NMR spectroscopy. Two steps were used for preparation the PVA-Ma/PNIPAAm membrane hydrogels. In the first step the PVA-Ma hydrogels (using PVA-Ma with different DS were prepared by reaction of double bonds on PVA-Ma, using the persulfate/TEMED system. Using a photoreaction pathway in the second step, PNIPAAm network was prepared within the parent PVA-Ma network at different PVA-Ma/NIPAAm ratios. The studies show that degree of swelling ratio (SR of PVA-Ma/PNIPAAm IPN hydrogels is dependent of temperature. The LCST for each IPN-hydrogel was determined by measuring the intensity of light transmitted through the hydrogel. The LCST of the IPN hydrogels ranged from 34.6 to 38.1oC. The elastic modules of swollen IPN hydrogels increased from 25 to 35oC but decreased by further warming to 45oC. The LCST, swelling ratio and mechanical properties of PVA-Ma/PNIPAAm IPN hydrogels can be tailored by tuning the PVA-Ma/NIPAAm ratio.

Isolation of MA-ACS Gene Family and Expression Study of MA-ACS1 Gene in Musa acuminata Cultivar Pisang Ambon Lumut

Directory of Open Access Journals (Sweden)

LISTYA UTAMI KARMAWAN

2009-03-01

Full Text Available Musa acuminata cultivar pisang ambon lumut is a native climacteric fruit from Indonesia. Climacteric fruit ripening process is triggered by the gaseous plant hormone ethylene. The rate limiting enzyme involved in ethylene biosynthesis is ACC synthase (ACS which is encoded by ACS gene family. The objective of this study is to identify MA-ACS gene family in M. acuminata cultivar pisang ambon lumut and to study the MA-ACS1 gene expression. The result showed that there were nine M. acuminata ACS gene family members called MA-ACS1–9. Two of them (MA-ACS1 and MA-ACS2 were assessed using reverse transcriptase PCR (RT-PCR for gene expression study and it was only MA-ACS1 correlated with fruit ripening. The MA-ACS1 gene fragment has been successfully isolated and characterized and it has three introns, four exons, and one stop codon. It also shows highest homology with MACS1 gene from M. acuminata cultivar Hsian Jien Chiao (GenBank accession number AF056164. Expression analysis of MA-ACS1 using quantitative PCR (qPCR showed that MA-ACS1 gene expression increased significantly in the third day, reached maximum at the fifth day, and then decreased in the seventh day after harvesting. The qPCR expression analysis result correlated with the result of physical analysis during fruit ripening.

Hyperandrogenism from an ovarian interstitial-cell tumor in an alpaca.

Science.gov (United States)

Gilbert, Rosanne; Kutzler, Michelle; Valentine, Beth A; Semevolos, Stacy

2006-11-01

An 8-year-old intact female Huacaya alpaca (Lama pacos) was presented for recent development of male behavior. Serum testosterone concentration was determined to be 969.1 pg/ml by using radioimmunoassay, while the range in 33 healthy female adult intact alpacas was 11.7-62.1 pg/ml. An ovarian mass was suspected, and an exploratory laparotomy was performed. A tan mass was present on the left ovary. Histologically, the mass was composed of closely packed, plump, polygonal cells with central round nuclei with granular chromatin and abundant eosinophilic finely granular to vesiculate cytoplasm. An ovarian benign interstitial (Leydig) cell tumor was diagnosed.

30 kV/10 mA solid state anode modulator for gyrotron plasma heating: design issues and results

International Nuclear Information System (INIS)

Fasel, D.; Lucia, C.; Ganuza, D.; Doyharzabal, I.

2001-01-01

Three 30 kV/10 mA solid state pulsed modulators have been delivered to the CRPP in Lausanne, by the company JEMA. Each modulator supplies the anode grid of a triode type gyrotron, used for heating purpose at the third harmonic in the TCV Tokamak. The main parameters of the final design are: the use of solid state technology, a floating output referred to the -80 kV of the gyrotron cathode potential, an output voltage range of -5 to 30 kV, 1 kHz square and sinusoidal modulation, fast switching off to -5 kV (10 μs) and pulsed operation (duty cycle of 1%). After studying and testing a solution based on regulated Mosfet transistors in series, a more stable alternative has been adopted. The final topology consists of a rectifier fed from an insulated 230 V input, a chopper, two inverter steps (for +30 and -5 kV) supplying two diode rectifiers bridges through HV transformers with two switches which commute the load to the positive or negative voltage, connected in series. This article presents the most significant aspects of the design, with special emphasis on the control principle. The final results will be presented in the context of normal operation, supplying a triode gyrotron

Mucinous cystadenoma of the ovary with stromal luteinization and hilar cell hyperplasia during pregnancy.

Science.gov (United States)

Pascal, R R; Grecco, L A

1988-02-01

A 32-year-old woman was delivered of a healthy, full-term infant by cesarean section, at which time a large ovarian cyst was removed. The cyst proved to be a mucinous cystadenoma with prominent luteinization of the stroma subtending the epithelium and with numerous foci of hyperplastic Leydig cells in the cyst wall and ovarian hilum. These hormonally induced changes must be recognized in order to avoid mistaking them for invasive epithelial components.

Suppression of Natural Killer Cell Activity by Regulatory NKT10 Cells Aggravates Alcoholic Hepatosteatosis

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Kele Cui

2017-10-01

Full Text Available We and others have found that the functions of hepatic natural killer (NK cells are inhibited but invariant NKT (iNKT cells become activated after alcohol drinking, leaving a possibility that there exists interplay between NK cells and iNKT cells during alcoholic liver disease. Here, in a chronic plus single-binge ethanol consumption mouse model, we observed that NK cells and interferon-γ (IFN-γ protected against ethanol-induced liver steatosis, as both wild-type (WT mice treated with anti-asialo GM1 antibody and IFN-γ-deficient GKO mice developed more severe alcoholic fatty livers. As expected, IFN-γ could directly downregulate lipogenesis in primary hepatocytes in vitro. On the contrary, iNKT cell-deficient Jα18−/− or interleukin-10 (IL-10−/− mice showed fewer alcoholic steatosis, along with the recovered number and IFN-γ release of hepatic NK cells, and exogenous IL-10 injection was sufficient to compensate for iNKT cell deficiency. Furthermore, NK cell depletion in Jα18−/− or IL-10−/− mice caused more severe hepatosteatosis, implying NK cells are the direct effector cells to inhibit liver steatosis. Importantly, adoptive transfer of iNKT cells purified from normal but not IL-10−/− mice resulted in suppression of the number and functions of NK cells and aggravated alcoholic liver injury in Jα18−/− mice, indicating that IL-10-producing iNKT (NKT10 cells are the regulators on NK cells. Conclusion: Ethanol exposure-triggered NKT10 cells antagonize the protective roles of NK cells in alcoholic hepatosteatosis.

Post 4 Ma initiation of normal faulting in southern Tibet. Constraints from the Kung Co half graben

Science.gov (United States)

Mahéo, G.; Leloup, P. H.; Valli, F.; Lacassin, R.; Arnaud, N.; Paquette, J.-L.; Fernandez, A.; Haibing, L.; Farley, K. A.; Tapponnier, P.

2007-04-01

The timing of E-W extension of the Tibetan plateau provides a test of mechanical models of the geodynamic evolution of the India-Asia convergence zone. In this work we focus on the Kung Co half graben (Southern Tibet, China), bounded by an active N-S normal fault with a minimum vertical offset of 1600 m. To estimate the onset of normal faulting we combined high and medium temperature (U-Pb, Ar/Ar) and low temperature ((U-Th)/He) thermochronometry of the Kung Co pluton, a two-mica granite of the northern Himalayan granitic belt that outcrop in the footwall of the fault. Biotite and muscovite Ar/Ar ages , are close from each other [˜ 16 Ma ± 0.2 (Ms) and ˜ 15 ± 0.4 Ma (Bt)], which is typical of fast cooling. The zircon and apatite (U-Th)/He ages range from 11.3 to 9.6 Ma and 9.9 to 3.7 Ma respectively. These He ages are indicative of (1) fast initial cooling, from 11.3 to ˜ 9 Ma, gradually decreasing with time and (2) a high geothermal gradient (˜ 400 °C/km), close to the surface at ˜ 10 Ma. The Kung Co pluton was emplaced at about 22 Ma (U-Pb on zircon) at less than 10 km depth and 520-545 °C. Subsequent to its shallow emplacement, the pluton underwent fast thermal re-equilibration ending around 7.5 Ma, followed by a period of slow cooling caused either by the end of the thermal re-equilibration or by very slow exhumation (0.02-0.03 mm/yr) from ˜ 7.5 Ma to at least 4 Ma. In either case the data suggest that the exhumation rate increased after 4 Ma. We infer this increase to be related to the initiation of the Kung Co normal fault. A critical examination of previously published data show that most ˜ N-S Tibetan normal faults may have formed less than 5 Ma ago rather than in the Miocene as assumed by several authors. Such a young age implies that E-W extension is not related to the Neogene South Tibetan magmatism (25 to 8 Ma). Consequently, models relating E-W extension to magmatism, such as convective removal of the lower lithosphere, may be inappropriate

Localization of thymosin ß10 in breast cancer cells

DEFF Research Database (Denmark)

Mælan, A.ase Elisabeth; Rasmussen, Trine Kring; Larsson, Lars-Inge

2007-01-01

as in cell motility and spreading. We have studied the distribution of endogenously expressed thymosin ß10 in cultured human breast cancer cell lines. Both unperturbed monolayer cultures and wound-healing models were examined using double-staining for thymosin ß10 and polymerized (F-) actin. Our findings...... show that thymosin ß10 is expressed in all three-cancer cell lines (SK-BR-3, MCF-7 and MDA-MB-231) studied. No or little staining was detected in confluent cells, whereas strong staining occurred in semiconfluent cells and in cells populating monolayer wounds. Importantly, the distribution of staining...... for thymosin ß10 was inverse of staining for F-actin. These data support a physiological role for thymosin ß10 in sequestration of G-actin as well as in cancer cell motility....

The Banana Fruit SINA Ubiquitin Ligase MaSINA1 Regulates the Stability of MaICE1 to be Negatively Involved in Cold Stress Response.

Science.gov (United States)

Fan, Zhong-Qi; Chen, Jian-Ye; Kuang, Jian-Fei; Lu, Wang-Jin; Shan, Wei

2017-01-01

The regulation of ICE1 protein stability is important to ensure effective cold stress response, and is extensively studied in Arabidopsis . Currently, how ICE1 stability in fruits under cold stress is controlled remains largely unknown. Here, we reported the possible involvement of a SEVEN IN ABSENTIA (SINA) ubiquitin ligase MaSINA1 from banana fruit in affecting MaICE1 stability. MaSINA1 was identified based on a yeast two-hybrid screening using MaICE1 as bait. Further yeast two-hybrid, pull-down, bimolecular fluorescence complementation (BiFC) and co-immunoprecipitation (CoIP) assays confirmed that MaSINA1 interacted with MaICE1. The expression of MaSINA1 was repressed by cold stress. Subcellular localization analysis in tobacco leaves showed that MaSINA1 was localized predominantly in the nucleus. In vitro ubiquitination assay showed that MaSINA1 possessed E3 ubiquitin ligase activity. More importantly, in vitro and semi- in vivo experiments indicated that MaSINA1 can ubiquitinate MaICE1 for the 26S proteasome-dependent degradation, and therefore suppressed the transcriptional activation of MaICE1 to MaNAC1, an important regulator of cold stress response of banana fruit. Collectively, our data reveal a mechanism in banana fruit for control of the stability of ICE1 and for the negative regulation of cold stress response by a SINA E3 ligase via the ubiquitin proteasome system.

Adole, MA

African Journals Online (AJOL)

Adole, MA. Vol 4, No 1 (2011) - Articles Effects of Groundnut Husk Ash-blended Cement on Chemical Resistance of Concrete Abstract PDF. ISSN: 1596-6035. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and ...

MaHog1, a Hog1-type mitogen-activated protein kinase gene, contributes to stress tolerance and virulence of the entomopathogenic fungus Metarhizium acridum.

Science.gov (United States)

Jin, Kai; Ming, Yue; Xia, Yu Xian

2012-12-01

Fungal biocontrol agents have great potential in integrated pest management. However, poor efficacy and sensitivity to various adverse factors have hampered their wide application. In eukaryotic cells, Hog1 kinase plays a critical role in stress responses. In this study, MaHog1 (GenBank accession no. EFY85878), encoding a member of the Hog1/Sty1/p38 mitogen-activated protein kinase family in Metarhizium (Me.) acridum, was identified. Targeted gene disruption was used to analyse the role of MaHog1 in virulence and tolerance of adverse factors. Mutants with MaHog1 depletion showed increased sensitivity to high osmotic stress, high temperature and oxidative stress, and exhibited remarkable resistance to cell wall-disturbing agents. These results suggest that Hog1 kinase has a conserved function in regulating multistress responses among fungi, and that MaHog1 might influence cell wall biogenesis in Me. acridum. Bioassays conducted with topical inoculation and intrahaemocoel injection revealed that MaHog1 is required for both penetration and postpenetration development of Me. acridum. MaHog1 disruption resulted in a significant reduction in virulence, likely due to the combination of a decrease in conidial germination, a reduction in appressorium formation and a decline in growth rate in insect haemolymph, which might be caused by impairing fungal tolerance of various stresses during infection.

PCDH10 is required for the tumorigenicity of glioblastoma cells

International Nuclear Information System (INIS)

Echizen, Kanae; Nakada, Mitsutoshi; Hayashi, Tomoatsu; Sabit, Hemragul; Furuta, Takuya; Nakai, Miyuki; Koyama-Nasu, Ryo; Nishimura, Yukiko; Taniue, Kenzui; Morishita, Yasuyuki; Hirano, Shinji; Terai, Kenta; Todo, Tomoki; Ino, Yasushi; Mukasa, Akitake; Takayanagi, Shunsaku; Ohtani, Ryohei; Saito, Nobuhito; Akiyama, Tetsu

2014-01-01

Highlights: • PCDH10 is required for the proliferation, survival and self-renewal of glioblastoma cells. • PCDH10 is required for glioblastoma cell migration and invasion. • PCDH10 is required for the tumorigenicity of glioblastoma cells. • PCDH10 may be a promising target for the therapy of glioblastoma. - Abstract: Protocadherin10 (PCDH10)/OL-protocadherin is a cadherin-related transmembrane protein that has multiple roles in the brain, including facilitating specific cell–cell connections, cell migration and axon guidance. It has recently been reported that PCDH10 functions as a tumor suppressor and that its overexpression inhibits proliferation or invasion of multiple tumor cells. However, the function of PCDH10 in glioblastoma cells has not been elucidated. In contrast to previous reports on other tumors, we show here that suppression of the expression of PCDH10 by RNA interference (RNAi) induces the growth arrest and apoptosis of glioblastoma cells in vitro. Furthermore, we demonstrate that knockdown of PCDH10 inhibits the growth of glioblastoma cells xenografted into immunocompromised mice. These results suggest that PCDH10 is required for the proliferation and tumorigenicity of glioblastoma cells. We speculate that PCDH10 may be a promising target for the therapy of glioblastoma

Architecture, cinéma et utopie. Pierre Kast sur Claude-Nicolas Ledoux et Le Corbusier

OpenAIRE

Denis, Sébastien

2013-01-01

La fin des années 40 et les années 50 sont celles de l’émergence du film d’art, et les courts métrages de Pierre Kast (1920-1984) qu’on analysera ici, produits au milieu des années 50, s’intègrent dans ce mouvement plus large dont Claude-Jean Philippe, dans son Encyclopédie filmée, a pu dire que, loin d’être des « films au passé », ils montrent un « présent à vif, dont le cinéma capte et condense l’intensité ». Ces années sont justement celles de la montée vers la « libération » du cinéma lui...

SDSS-IV MaNGA: Probing the Kinematic Morphology–Density Relation of Early-type Galaxies with MaNGA

Science.gov (United States)

Greene, J. E.; Leauthaud, A.; Emsellem, E.; Goddard, D.; Ge, J.; Andrews, B. H.; Brinkman, J.; Brownstein, J. R.; Greco, J.; Law, D.; Lin, Y.-T.; Masters, K. L.; Merrifield, M.; More, S.; Okabe, N.; Schneider, D. P.; Thomas, D.; Wake, D. A.; Yan, R.; Drory, N.

2017-12-01

The “kinematic” morphology–density relation for early-type galaxies posits that those galaxies with low angular momentum are preferentially found in the highest-density regions of the universe. We use a large sample of galaxy groups with halo masses {10}12.5MaNGA) survey to examine whether there is a correlation between local environment and rotational support that is independent of stellar mass. We find no compelling evidence for a relationship between the angular momentum content of early-type galaxies and either local overdensity or radial position within the group at fixed stellar mass.

FuSuMaTech workshop

CERN Multimedia

Olofsson, Simon

2018-01-01

The goal of the FuSuMaTecH IP workshop, organised at CERN Ideaquare 19-20 April, was to educate superconductivity and magnet experts about intellectual property. About 30 participants from multiple institutes and companies worked together in this two day interactive program which was facilitated by CERN Knowledge Transfer. Great progress was made in shaping the FuSuMaTech industrial demonstrator projects as well as the R&D&I subjects.

Data on chemical activation of Wnt/β-catenin during axolotl limb regeneration

Directory of Open Access Journals (Sweden)

Sabina Wischin

2017-04-01

Full Text Available Limb amputation in axolotls was performed to obtain data demonstrating that a chemical agonist of Wnt (int-related protein/β-catenin signalling can have a role in axolotl limb regeneration (Wischin et al., 2017 [1]. The data revealed that active β-catenin protein was present during limb regeneration in some Leydig cells in the epithelium; after the chemical treatment, it was observed in more Leydig cells. In addition, the chemical agonist of Wnt generated distinct limb malformation.

Secular decline in male testosterone and sex hormone binding globulin serum levels in Danish population surveys

DEFF Research Database (Denmark)

Andersson, Anna-Maria; Jensen, Tina K; Juul, Anders

2007-01-01

Adverse secular trends in male reproductive health have been reported to be reflected in increased testicular cancer risk and decreased semen quality in more recently born men. These secular trends may also be reflected by changes in Leydig cell function.......Adverse secular trends in male reproductive health have been reported to be reflected in increased testicular cancer risk and decreased semen quality in more recently born men. These secular trends may also be reflected by changes in Leydig cell function....

Upbeat nystagmus in anti-Ma2 encephalitis.

Science.gov (United States)

Garcia-Reitboeck, Pablo; Thompson, Graham; Johns, Paul; Al Wahab, Yasir; Omer, Salah; Griffin, Colette

2014-02-01

Anti-Ma2 encephalitis is a paraneoplastic disorder characterised by brainstem and/or limbic involvement. Eye movement abnormalities can occur in this condition, often with confusion or somnolence. We describe a patient with progressive oscillopsia (with upbeat nystagmus) and unsteadiness, followed by acute pancreatitis. She did not respond to immunomodulatory treatment and subsequently died of complications related to pancreatitis and sepsis. There was no tumour identified at autopsy, but the anti-Ma2 antibodies in her serum and the discovery of a brainstem-predominant inflammatory infiltrate at autopsy strongly suggest a paraneoplastic disorder. Our case illustrates that upbeat nystagmus can be a predominant feature in anti-Ma2 encephalitis; clinicians should consider testing for anti-Ma2 antibodies in patients with upbeat nystagmus of unknown cause.

MicroRNA 10a marks regulatory T cells

DEFF Research Database (Denmark)

Jeker, Lukas T; Zhou, Xuyu; Gershberg, Kseniya

2012-01-01

MicroRNAs (miRNAs) are crucial for regulatory T cell (Treg) stability and function. We report that microRNA-10a (miR-10a) is expressed in Tregs but not in other T cells including individual thymocyte subsets. Expression profiling in inbred mouse strains demonstrated that non-obese diabetic (NOD......) mice with a genetic susceptibility for autoimmune diabetes have lower Treg-specific miR-10a expression than C57BL/6J autoimmune resistant mice. Inhibition of miR-10a expression in vitro leads to reduced FoxP3 expression levels and miR-10a expression is lower in unstable "exFoxP3" T cells. Unstable...... and phenotype of natural Treg nor the capacity of conventional T cells to induce FoxP3 in response to TGFβ, RA, or a combination of the two. Thus, miR-10a is selectively expressed in Treg but inhibition by antagomiRs or genetic ablation resulted in discordant effects on FoxP3....

Comprehensive investigation of core-shell dimer nanoparticles size, distance and thicknesses on performance of a hybrid organic-inorganic halide perovskite solar cell

Science.gov (United States)

Heidarzadeh, Hamid

2018-03-01

Significant performance enhancement in an ultrathin perovskite (CH3NH3PbI3) solar cell is done using plasmonic embedded core–shell dimer nanoparticles. Three-dimensional finite difference time-domain (FDTD) method is used. A perovskite absorber with a volume of 400 × 400 × 200 nm3 is considered. At first, a cell with one embedded nanoparticle is simulated. Absorptance of CH3NH3PbI3 absorber and gold nanoparticle are obtained. An optimization is done. Then a cell with embedded dimer nanoparticles is evaluated. The results show higher photocurrent enhancement for that in compared to a cell with one embedded nanoparticle. To further photocurrent enhancement, gold-SiO2 core–shell nanoparticles are used. Photocurrents of 23.37 mA cm‑2, 23.3 mA cm‑2, 22.5 mA cm‑2 and 21.47 mA cm‑2 are obtained for a cell with two embedded core–shell nanoparticles with core radius of 60 nm and shell thickness of 2 nm, 5 nm, 10 nm and 20 nm, respectively. It is important to mention that the photocurrent is 17.9 mA cm‑2 for reference cell and 19.8 mA cm‑2 for a cell with one embedded nanoparticle. Higher photocurrent is due to the near-field plasmonic effect.

Upgrade of a 30 kV/10 mA anode power supply for triode type gyrotron

Energy Technology Data Exchange (ETDEWEB)

Siravo, Ugo, E-mail: ugo.siravo@epfl.ch; Alberti, Stefano; Dubray, Jérémie; Fasel, Damien; Hogge, Jean-Philippe; Marlétaz, Blaise; Marmillod, Philippe; Perez, Albert; Silva, Miguel

2015-10-15

Highlights: • Triode type gyrotron is fed by 3 power supplies: the main, an anode PS(APS) and a heater. • This paper presents the upgrade of 3APS, supplied in 1999, that never fulfilled the specs. • The new working principle is very efficient, easy to implement, for a minimal cost. • Upgraded APS provides extended modulation capabilities, no overshoot and lowerripple. • This upgrade will allow exploring new operation regimes for the 3 TCV X3 gyrotrons. - The RF power of a gyrotron with a triode type magnetron-injection-gun (MIG) can be directly controlled via the voltage applied between its anode and its cathode. Hence, the performance of this type of gyrotron relies directly on the possibilities offered by the power supply controlling the anode to cathode voltage. For a system of gyrotrons connected to the same main high-voltage power supply, with a triode MIG one has the additional advantage of independently controlling each individual gyrotron. This paper presents the modifications brought to the three existing 30 kV/10 mA anode power supplies connected to the 500 kW/118 GHz/2s X3 gyrotrons operated on the TCV Tokamak. The new working principle based on phase-shift modulation (PSM) is described in detail. Experimental results obtained on dummy load are compared to simulations performed during the design phase. With respect to the initial working principle, the modulation frequency capability has been increased by a factor 10 reaching more than 5 kHz, whereas the output voltage ripple as well as the overshoot/undershoot have been significantly reduced.

A Precise 6 Ma Start Date for Fluvial Incision of the Northeastern Colorado Plateau Canyonlands

Science.gov (United States)

Thomson, S. N.; Soreghan, G. S.; Reiners, P. W.; Peyton, S. L.; Murray, K. E.

2015-12-01

Outstanding questions regarding late Cenozoic Colorado Plateau landscape evolution include: (1) the relative roles of isostatic rebound as result Colorado River incision versus longer-term geodynamic processes in driving overall rock uplift of the plateau; and (2) whether incision was triggered by river integration or by a change in deep-seated mantle lithosphere dynamics. A key to answering these questions is to date more precisely the onset of incision to refine previous estimates of between 6 and 10 Ma. We present new low-temperature thermochronologic results from bedrock and deep borehole samples in the northeastern Colorado Plateau to show that rapid river incision began here at 6 Ma (5.93±0.66 Ma) with incision rates increasing from 15-50 m/Myr to 160-200 m/Myr. The onset time is constrained independently by both inverse time-temperature modeling and by the break-in-slope in fission track age-elevation relationships. This new time constraint has several important implications. First, the coincidence in time with 5.97-5.3 Ma integration of the lower Colorado River through the Grand Canyon to the Gulf of California strongly favors downstream river integration triggering carving of the canyonlands of the upper Colorado River system. Second, it implies integration of the entire Colorado River system in less than 2 million years. Third, rock uplift of the plateau driven by the flexural isostatic response to river incision is restricted to just the last 6 Ma, as is associated increased sediment budget. Fourth, incision starting at 6 Ma means that previous estimates of upper Colorado River incision rates based on 10-12 Ma basalt datum levels are too low. This also changes the dependency of measured time interval on incision rate from a non-steady-state negative power-law dependence (exponent of -0.24) to a near steady-state dependence (exponent of 0.07) meaning that long-term upper Colorado river incision rates can provide a reliable proxy for rock uplift rates.

ADAM10 regulates Notch function in intestinal stem cells of mice.

Science.gov (United States)

Tsai, Yu-Hwai; VanDussen, Kelli L; Sawey, Eric T; Wade, Alex W; Kasper, Chelsea; Rakshit, Sabita; Bhatt, Riha G; Stoeck, Alex; Maillard, Ivan; Crawford, Howard C; Samuelson, Linda C; Dempsey, Peter J

2014-10-01

A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is a cell surface sheddase that regulates physiologic processes, including Notch signaling. ADAM10 is expressed in all intestinal epithelial cell types, but the requirement for ADAM10 signaling in crypt homeostasis is not well defined. We analyzed intestinal tissues from mice with constitutive (Vil-Cre;Adam10(f/f) mice) and conditional (Vil-CreER;Adam10(f/f) and Leucine-rich repeat-containing GPCR5 [Lgr5]-CreER;Adam10(f/f) mice) deletion of ADAM10. We performed cell lineage-tracing experiments in mice that expressed a gain-of-function allele of Notch in the intestine (Rosa26(NICD)), or mice with intestine-specific disruption of Notch (Rosa26(DN-MAML)), to examine the effects of ADAM10 deletion on cell fate specification and intestinal stem cell maintenance. Loss of ADAM10 from developing and adult intestine caused lethality associated with altered intestinal morphology, reduced progenitor cell proliferation, and increased secretory cell differentiation. ADAM10 deletion led to the replacement of intestinal cell progenitors with 2 distinct, post-mitotic, secretory cell lineages: intermediate-like (Paneth/goblet) and enteroendocrine cells. Based on analysis of Rosa26(NICD) and Rosa26(DN-MAML) mice, we determined that ADAM10 controls these cell fate decisions by regulating Notch signaling. Cell lineage-tracing experiments showed that ADAM10 is required for survival of Lgr5(+) crypt-based columnar cells. Our findings indicate that Notch-activated stem cells have a competitive advantage for occupation of the stem cell niche. ADAM10 acts in a cell autonomous manner within the intestinal crypt compartment to regulate Notch signaling. This process is required for progenitor cell lineage specification and crypt-based columnar cell maintenance. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Du « national » appliqué au cinéma

OpenAIRE

Tortajada, Maria

2011-01-01

La parution de l’Histoire du cinéma suisse, 1966-2000, dont l’auteur est co-éditrice avec Hervé Dumont, est l’occasion de reposer la question du « cinéma national » pour la confronter à celle « d’identité ». L’ambition encyclopédique de l’ouvrage qui recense tous les longs-métrages sortis en salle pour la période donnée, impose des limites au « national », en opérant certains choix de corpus. À partir de quels critères ? D’autre part ce corpus se révèle particulièrement hétérogène dès qu’il s...

Local Actions of Melatonin in Somatic Cells of the Testis.

Science.gov (United States)

Frungieri, Mónica Beatriz; Calandra, Ricardo Saúl; Rossi, Soledad Paola

2017-05-31

The pineal hormone melatonin regulates testicular function through the hypothalamic-adenohypophyseal axis. In addition, direct actions of melatonin in somatic cells of the testis have been described. Melatonin acts as a local modulator of the endocrine activity in Leydig cells. In Sertoli cells, melatonin influences cellular growth, proliferation, energy metabolism and the oxidation state, and consequently may regulate spermatogenesis. These data pinpoint melatonin as a key player in the regulation of testicular physiology (i.e., steroidogenesis, spermatogenesis) mostly in seasonal breeders. In patients with idiopathic infertility, melatonin exerts anti-proliferative and anti-inflammatory effects on testicular macrophages, and provides protective effects against oxidative stress in testicular mast cells. Consequently, melatonin is also involved in the modulation of inflammatory and oxidant/anti-oxidant states in testicular pathology. Overall, the literature data indicate that melatonin has important effects on testicular function and male reproduction.

Mammary Stem Cells and Breast Cancer Stem Cells: Molecular Connections and Clinical Implications.

Science.gov (United States)

Celià-Terrassa, Toni

2018-05-04

Cancer arises from subpopulations of transformed cells with high tumor initiation and repopulation ability, known as cancer stem cells (CSCs), which share many similarities with their normal counterparts. In the mammary gland, several studies have shown common molecular regulators between adult mammary stem cells (MaSCs) and breast cancer stem cells (bCSCs). Cell plasticity and self-renewal are essential abilities for MaSCs to maintain tissue homeostasis and regenerate the gland after pregnancy. Intriguingly, these properties are similarly executed in breast cancer stem cells to drive tumor initiation, tumor heterogeneity and recurrence after chemotherapy. In addition, both stem cell phenotypes are strongly influenced by external signals from the microenvironment, immune cells and supportive specific niches. This review focuses on the intrinsic and extrinsic connections of MaSC and bCSCs with clinical implications for breast cancer progression and their possible therapeutic applications.

IPN hydrogels based on PNIPAAm and PVA-Ma networks: characterization through measure of LCST, swelling ratio and mechanical properties - doi: 10.4025/actascitechnol.v34i2.15019

OpenAIRE

Wenceslau, Adriana Cristina; Universidade Estadual de Maringá - UEM; Rubira, Adley Forti; Universidade Estadual de Maringá - UEM; Muniz, Edvani Curti; UEM, Maringá, Paraná

2011-01-01

IPN hydrogels based on chemically modified poly(vinyl alcohol) (or PVA-Ma), with different degrees of substitution (DS), and poly(N-isopropylacrylamide) (or PNIPAAm) were obtained and characterized through measures of LCST, swelling ratio and mechanical properties. Linear PVA-Ma with several DS were obtained through the chemical reaction of PVA with glycidyl methacrylate (GMA). The DS of various PVA-Ma were determined through 1H NMR spectroscopy. Two steps were used for preparation the PVA-Ma...

Increase in physical activities in kindergarten children with cerebral palsy by employing MaKey-MaKey-based task systems.

Science.gov (United States)

Lin, Chien-Yu; Chang, Yu-Ming

2014-09-01

In this study, we employed Flash- and Scratch-based multimedia by using a MaKey-MaKey-based task system to increase the motivation level of children with cerebral palsy to perform physical activities. MaKey MaKey is a circuit board that converts physical touch to a digital signal, which is interpreted by a computer as a keyboard message. In this study, we used conductive materials to control this interaction. This study followed single-case design using ABAB models in which A indicated the baseline and B indicated the intervention. The experiment period comprised 1 month and a half. The experimental results demonstrated that in the case of two kindergarten children with cerebral palsy, their scores were considerably increased during the intervention phrases. The developmental applications of the results are also discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Measurements of photocathode operational lifetime at beam currents up to 10-mA using an improved DC high voltage GaAs photogun

International Nuclear Information System (INIS)

J. Grames; M. Poelker; P. Adderley; J. Brittian; J. Clark; J. Hansknecht; D. Machie; M.L. Stutzman; K. Surles-Law

2007-01-01

This work extends past research at Jefferson Lab aimed at better appreciating the mechanisms that limit photocathode operational lifetime at high current (> 1 mA). Specifically, the performance of an improved 100 kV DC high voltage load locked photogun will be described. Although difficult to measure directly, we believe the new gun has better vacuum conditions compared to the original gun, as indicated by enhanced photocathode lifetimes exceeding 2000 C using a 1.55 mm diameter drive laser spot at the photocathode. In addition, the dependence of the lifetime on the laser spot size at the photocathode was measured and a charge density lifetime exceeding 10 6 C/cm 2 was measured with a 0.32 mm laser spot diameter

Growth and characterization of low composition Ge, x in epi-Si1‑x Gex (x  ⩽  10%) active layer for fabrication of hydrogenated bottom solar cell

Science.gov (United States)

Ajmal Khan, M.; Sato, R.; Sawano, K.; Sichanugrist, P.; Lukianov, A.; Ishikawa, Y.

2018-05-01

Semiconducting epi-Si1‑x Ge x alloys have promising features as solar cell materials and may be equally important for some other semiconductor device applications. Variation of the germanium compositional, x in epi-Si1‑x Ge x , makes it possible to control the bandgap between 1.12 eV and 0.68 eV for application in bottom solar cells. A low proportion of Ge in SiGe alloy can be used for photovoltaic application in a bottom cell to complete the four-terminal tandem structure with wide bandgap materials. In this research, we aimed to use a low proportion of Ge—about 10%—in strained or relaxed c-Si1‑x Ge x /c-Si heterojunctions (HETs), with or without insertion of a Si buffer layer grown by molecular beam epitaxy, to investigate the influence of the relaxed or strained SiGe active layer on the performance of HET solar cells grown using the plasma enhanced chemical vapor deposition system. Thanks to the c-Si buffer layer at the hetero-interface, the efficiency of these SiGe based HET solar cells was improved from 2.3% to 3.5% (fully strained and with buffer layer). The Jsc was improved, from 8 mA cm‑2 to 15.46 mA cm‑2, which might be supported by strained c-Si buffer layer at the hetero-interface, by improving the crystalline quality.

MaRIE Undulator & XFEL Systems

Energy Technology Data Exchange (ETDEWEB)

Nguyen, Dinh Cong [Los Alamos National Laboratory; Marksteiner, Quinn R. [Los Alamos National Laboratory; Anisimov, Petr Mikhaylovich [Los Alamos National Laboratory; Buechler, Cynthia Eileen [Los Alamos National Laboratory

2015-03-23

The 22 slides in this presentation treat the subject under the following headings: MaRIE XFEL Performance Parameters, Input Electron Beam Parameters, Undulator Design, Genesis Simulations, Risks, and Summary It is concluded that time-dependent Genesis simulations show the MaRIE XFEL can deliver the number of photons within the required bandwidth, provided a number of assumptions are met; the highest risks are associated with the electron beam driving the XFEL undulator; and risks associated with the undulator and/or distributed seeding technique may be evaluated or retired by performing early validation experiments.

Programmed cell death-10 enhances proliferation and protects malignant T cells from apoptosis

DEFF Research Database (Denmark)

Lauenborg, Britt; Kopp, Katharina; Krejsgaard, Thorbjørn

2010-01-01

is associated with serine/threonine kinases and phosphatases and modulates the extracellular signal-regulated kinase pathway suggesting a role in the regulation of cellular growth. Here we provide evidence of a constitutive expression of PDCD10 in malignant T cells and cell lines from peripheral blood......, whereas an activator of Jak3 and NF-¿B, interleukin-2 (IL-2), enhances PDCD10 expression. Functional data show that PDCD10 depletion by small interfering RNA induces apoptosis and decreases proliferation of the sensitive cells. To our knowledge, these data provide the first functional link between PDCD10...

Roadway management plan based on rockfall modelling calibration and validation. Application along the Ma-10 road in Mallorca (Spain)

Science.gov (United States)

Mateos, Rosa Maria; Garcia, Inmaculada; Reichenbach, Paola; Herrera, Gerardo; Sarro, Roberto; Rius, Joan; Aguilo, Raul

2016-04-01

The Tramuntana range, in the northwestern sector of the island of Mallorca (Spain), is frequently affected by rockfalls which have caused significant damage, mainly along the road network. The Ma-10 road constitutes the main transportation corridor on the range with a heavy traffic estimated at 7,200 vehicles per day on average. With a length of 111 km and a tortuous path, the road is the connecting track for 12 municipalities and constitutes a strategic road on the island for many tourist resorts. For the period spanning from 1995 to current times, 63 rockfalls have affected the Ma-10 road with volumes ranging from 0.3m3 to 30,000 m3. Fortunately, no fatalities occurred but numerous blockages on the road took place which caused significant economic losses, valued of around 11 MEuro (Mateos el al., 2013). In this work we present the procedure we have applied to calibrate and validate rockfall modelling in the Tramuntana region, using 103 cases of the available detailed rockfall inventory (Mateos, 2006). We have exploited STONE (Guzzetti et al. 2002), a GIS based rockfall simulation software which computes 2D and 3D rockfall trajectories starting from a DTM and maps of the dynamic rolling friction coefficient and of the normal and tangential energy restitution coefficients. The appropriate identification of these parameters determines the accuracy of the simulation. To calibrate them, we have selected 40 rockfalls along the range which include a wide variety of outcropping lithologies. Coefficients values have been changed in numerous attempts in order to select those where the extent and shape of the simulation matched the field mapping. Best results were summarized with the average statistical values for each parameter and for each geotechnical unit, determining that mode values represent more precisely the data. Initially, for the validation stage, 10 well- known rockfalls exploited in the calibration phase have been selected. Confidence tests have been applied

Development and validation of a mass spectrometry-based assay for quantification of insulin-like factor 3 in human serum

DEFF Research Database (Denmark)

Albrethsen, Jakob; Frederiksen, Hanne; Andersson, Anna-Maria

2018-01-01

BACKGROUND: The circulating level of the peptide hormone insulin-like factor 3 (INSL3) is a promising diagnostic marker reflecting Leydig cell function in the male. Few commercial immunoassays of varying quality exist. Therefore, we decided to develop and validate a precise method for quantificat......BACKGROUND: The circulating level of the peptide hormone insulin-like factor 3 (INSL3) is a promising diagnostic marker reflecting Leydig cell function in the male. Few commercial immunoassays of varying quality exist. Therefore, we decided to develop and validate a precise method...

Hypocretin-1 CSF levels in anti-Ma2 associated encephalitis.

Science.gov (United States)

Overeem, S; Dalmau, J; Bataller, L; Nishino, S; Mignot, E; Verschuuren, J; Lammers, G J

2004-01-13

Idiopathic narcolepsy is associated with deficient hypocretin transmission. Narcoleptic symptoms have recently been described in paraneoplastic encephalitis with anti-Ma2 antibodies. The authors measured CSF hypocretin-1 levels in six patients with anti-Ma2 encephalitis, and screened for anti-Ma antibodies in patients with idiopathic narcolepsy. Anti-Ma autoantibodies were not detected in patients with idiopathic narcolepsy. Four patients with anti-Ma2 encephalitis had excessive daytime sleepiness; hypocretin-1 was not detectable in their cerebrospinal fluid, suggesting an immune-mediated hypocretin dysfunction.

A 600kV 15mA Cockcroft-Walton high-voltage power supply with high stability and low-ripple voltage

International Nuclear Information System (INIS)

Su Tongling; Zhang Yimin; Chen Shangwen; Liu Yantong; Lv Huiyi; Liu Jiangtao

2006-01-01

A Cockcroft-Walton high-voltage power supply with high stability and low-ripple voltage has been developed. This power supply has been operated in a ns pulse neutron generator. The maximum non-load voltage is 600kV while the working voltage and load current are 550kV and 15mA, respectively. The tested results indicate that when the power supply is operated at 300kV, 6.7mA and the input voltage varies +/-10%, the long-term stability of the output voltage is S=(0.300-1.006)x10 -3 . The ripple voltage is δU P-P =6.2V at 300kV, 6.8-8.3mA and the ratio of δU P-P to the output voltage V H is δU P-P /V H =2.1x10 -5

PuMA: the Porous Microstructure Analysis software

Science.gov (United States)

Ferguson, Joseph C.; Panerai, Francesco; Borner, Arnaud; Mansour, Nagi N.

2018-01-01

The Porous Microstructure Analysis (PuMA) software has been developed in order to compute effective material properties and perform material response simulations on digitized microstructures of porous media. PuMA is able to import digital three-dimensional images obtained from X-ray microtomography or to generate artificial microstructures. PuMA also provides a module for interactive 3D visualizations. Version 2.1 includes modules to compute porosity, volume fractions, and surface area. Two finite difference Laplace solvers have been implemented to compute the continuum tortuosity factor, effective thermal conductivity, and effective electrical conductivity. A random method has been developed to compute tortuosity factors from the continuum to rarefied regimes. Representative elementary volume analysis can be performed on each property. The software also includes a time-dependent, particle-based model for the oxidation of fibrous materials. PuMA was developed for Linux operating systems and is available as a NASA software under a US & Foreign release.

Microscopic morphology and testis morphometry of captivity-bred Adult bullfrogs (Lithobates catesbeianus Shaw, 1802

Directory of Open Access Journals (Sweden)

Jaqueline Carlos

2009-12-01

Full Text Available The aim of this work was to study the testicular morphometry of captivity-bred adult bullfrogs. Fifteen young adult male were studied, in the rainy season and a lengthy photoperiod. The GSI was established at 0.15%. The nuclear diameter of germinative and Leydig cells, the nucleolus diameter of Sertoli cells and the area of cysts and tubules were determined and the mean number of ISPC, IISPC and SPT per cyst and the mean number of cysts per tubule was estimated. The nucleoplasmatic proportion of the nucleus of the Leydig cell was 76.22%, indicating less cytoplasmic activity. Eight generations of spermatogonia were found. The spermatogenesis efficiency in meiosis and in mitosis was 63 and 49%, respectively. The spermatogenesis of bullfrog fited in the pattern of other captivity Anurans, with differences as the morphology of Sertoli and Leydig cells nuclei.A morfometria é uma importante ferramenta para a biologia estrutural, permitindo estudos estereológicos e análises quantitativas. Existem muitos pontos a serem esclarecidos sobre a morfometria testicular desta espécie, que objetivamos desvendar neste trabalho. Quinze machos adultos foram estudados, em período chuvoso e de fotoperíodo longo (dezembro, 2000. O IGS encontrado foi de 0.15%. O diâmetro nuclear das células germinativas e da célula de Leydig, o diâmetro nucleolar das células de Sertoli e a área dos cistos e túbulos foram determinados. O número médio de ISPC, IISPC e SPT por cisto e o número médio de cisto por túbulo foi estimado. A proporção nucleoplasmática do núcleo da célula de Leydig foi de 76.22%, indicando pouca atividade citoplasmática. Oito gerações de espermatogônia foram estimadas. A eficiência da espermatogênese na meiose e mitose foi de 63% e49%, respectivamente. A espermatogênese de rãtouro segue os padrões dos demais Anuros de cativeiro, apresentando diferenças nos núcleos das c��lulas de Sertoli e Leydig.

Model for Analysis of Energy Demand (MAED-2)

International Nuclear Information System (INIS)

2007-01-01

The IAEA has been supporting its Member States in the area of energy planning for sustainable development. Development and dissemination of appropriate methodologies and their computer codes are important parts of this support. This manual has been produced to facilitate the use of the MAED model: Model for Analysis of Energy Demand. The methodology of the MAED model was originally developed by. B. Chateau and B. Lapillonne of the Institute Economique et Juridique de l'Energie (IEJE) of the University of Grenoble, France, and was presented as the MEDEE model. Since then the MEDEE model has been developed and adopted to be appropriate for modelling of various energy demand system. The IAEA adopted MEDEE-2 model and incorporated important modifications to make it more suitable for application in the developing countries, and it was named as the MAED model. The first version of the MAED model was designed for the DOS based system, which was later on converted for the Windows system. This manual presents the latest version of the MAED model. The most prominent feature of this version is its flexibility for representing structure of energy consumption. The model now allows country-specific representations of energy consumption patterns using the MAED methodology. The user can now disaggregate energy consumption according to the needs and/or data availability in her/his country. As such, MAED has now become a powerful tool for modelling widely diverse energy consumption patterns. This manual presents the model in details and provides guidelines for its application

SDSS-IV/MaNGA: SPECTROPHOTOMETRIC CALIBRATION TECHNIQUE

Energy Technology Data Exchange (ETDEWEB)

Yan, Renbin; Sánchez-Gallego, José R. [Department of Physics and Astronomy, University of Kentucky, 505 Rose St., Lexington, KY 40506-0057 (United States); Tremonti, Christy; Bershady, Matthew A.; Eigenbrot, Arthur; Wake, David A. [Department of Astronomy, University of Winsconsin-Madison, 475 N. Charter Street, Madison, WI 53706-1582 (United States); Law, David R. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Schlegel, David J. [Physics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720-8160 (United States); Bundy, Kevin [Kavli IPMU (WPI), UTIAS, The University of Tokyo, Kashiwa, Chiba 277-8583 (Japan); Drory, Niv [McDonald Observatory, Department of Astronomy, University of Texas at Austin, 1 University Station, Austin, TX 78712-0259 (United States); MacDonald, Nicholas [Department of Astronomy, Box 351580, University of Washington, Seattle, WA 98195 (United States); Bizyaev, Dmitry [Apache Point Observatory, P.O. Box 59, sunspot, NM 88349 (United States); Blanc, Guillermo A. [Departamento de Astronomía, Universidad de Chile, Camino el Observatorio 1515, Las Condes, Santiago (Chile); Blanton, Michael R.; Hogg, David W. [Center for Cosmology and Particle Physics, Department of Physics, New York University, 4 Washington Place, New York, NY 10003 (United States); Cherinka, Brian [Dunlap Institute for Astronomy and Astrophysics, University of Toronto, 50 St. George Street, Toronto, Ontario M5S 3H4 (Canada); Gunn, James E. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Harding, Paul [Department of Astronomy, Case Western Reserve University, Cleveland, OH 44106 (United States); Sánchez, Sebastian F., E-mail: yanrenbin@uky.edu [Instituto de Astronomia, Universidad Nacional Autonoma de Mexico, A.P. 70-264, 04510 Mexico D.F. (Mexico); and others

2016-01-15

Mapping Nearby Galaxies at Apache Point Observatory (MaNGA), one of three core programs in the Sloan Digital Sky Survey-IV, is an integral-field spectroscopic survey of roughly 10,000 nearby galaxies. It employs dithered observations using 17 hexagonal bundles of 2″ fibers to obtain resolved spectroscopy over a wide wavelength range of 3600–10300 Å. To map the internal variations within each galaxy, we need to perform accurate spectral surface photometry, which is to calibrate the specific intensity at every spatial location sampled by each individual aperture element of the integral field unit. The calibration must correct only for the flux loss due to atmospheric throughput and the instrument response, but not for losses due to the finite geometry of the fiber aperture. This requires the use of standard star measurements to strictly separate these two flux loss factors (throughput versus geometry), a difficult challenge with standard single-fiber spectroscopy techniques due to various practical limitations. Therefore, we developed a technique for spectral surface photometry using multiple small fiber-bundles targeting standard stars simultaneously with galaxy observations. We discuss the principles of our approach and how they compare to previous efforts, and we demonstrate the precision and accuracy achieved. MaNGA's relative calibration between the wavelengths of Hα and Hβ has an rms of 1.7%, while that between [N ii] λ6583 and [O ii] λ3727 has an rms of 4.7%. Using extinction-corrected star formation rates and gas-phase metallicities as an illustration, this level of precision guarantees that flux calibration errors will be sub-dominant when estimating these quantities. The absolute calibration is better than 5% for more than 89% of MaNGA's wavelength range.

SDSS-IV/MaNGA: SPECTROPHOTOMETRIC CALIBRATION TECHNIQUE

International Nuclear Information System (INIS)

Yan, Renbin; Sánchez-Gallego, José R.; Tremonti, Christy; Bershady, Matthew A.; Eigenbrot, Arthur; Wake, David A.; Law, David R.; Schlegel, David J.; Bundy, Kevin; Drory, Niv; MacDonald, Nicholas; Bizyaev, Dmitry; Blanc, Guillermo A.; Blanton, Michael R.; Hogg, David W.; Cherinka, Brian; Gunn, James E.; Harding, Paul; Sánchez, Sebastian F.

2016-01-01

Mapping Nearby Galaxies at Apache Point Observatory (MaNGA), one of three core programs in the Sloan Digital Sky Survey-IV, is an integral-field spectroscopic survey of roughly 10,000 nearby galaxies. It employs dithered observations using 17 hexagonal bundles of 2″ fibers to obtain resolved spectroscopy over a wide wavelength range of 3600–10300 Å. To map the internal variations within each galaxy, we need to perform accurate spectral surface photometry, which is to calibrate the specific intensity at every spatial location sampled by each individual aperture element of the integral field unit. The calibration must correct only for the flux loss due to atmospheric throughput and the instrument response, but not for losses due to the finite geometry of the fiber aperture. This requires the use of standard star measurements to strictly separate these two flux loss factors (throughput versus geometry), a difficult challenge with standard single-fiber spectroscopy techniques due to various practical limitations. Therefore, we developed a technique for spectral surface photometry using multiple small fiber-bundles targeting standard stars simultaneously with galaxy observations. We discuss the principles of our approach and how they compare to previous efforts, and we demonstrate the precision and accuracy achieved. MaNGA's relative calibration between the wavelengths of Hα and Hβ has an rms of 1.7%, while that between [N ii] λ6583 and [O ii] λ3727 has an rms of 4.7%. Using extinction-corrected star formation rates and gas-phase metallicities as an illustration, this level of precision guarantees that flux calibration errors will be sub-dominant when estimating these quantities. The absolute calibration is better than 5% for more than 89% of MaNGA's wavelength range

Condições de atmosfera controlada para a maçã ?Pink Lady?

Directory of Open Access Journals (Sweden)

Brackmann Auri

2005-01-01

Full Text Available O objetivo do presente trabalho foi avaliar o efeito de diferentes temperaturas e pressões parciais de O2 e CO2 sobre a manutenção da qualidade da maçã (Malus domestica Borkh. cultivar Pink Lady durante o armazenamento em atmosfera controlada. Os tratamentos avaliados foram 1,5kPa de O2 + 1,0kPa de CO2 na temperatura de -0,5degreesC, e 1,5kPa de O2 + 1,0kPa de CO2; 1,5kPa de O2 + 2,0kPa de CO2; 1,0kPa de O2 + 1,0kPa de CO2; 1,0kPa de O2 + <0,5kPa de CO2; armazenamento refrigerado (20,8kPa de O2 + <0,5kPa de CO2 na temperatura de +0,5degreesC. As avaliações foram realizadas após nove meses de armazenamento, seguidos de sete dias de exposição dos frutos a 20degreesC. Os frutos mantidos em atmosfera controlada apresentaram menor ocorrência de podridões, maior firmeza de polpa e maior teor de sólidos solúveis totais, em comparação com os frutos conservados em armazenamento refrigerado. As melhores condições de atmosfera controlada para conservação da qualidade da maçã ?Pink Lady? foram 1,5kPa de O2 + 1,0kPa de CO2 na temperatura de -0,5degreesC, e 1,5kPa de O2 + 1,0kPa de CO2; 1,5kPa de O2 + 2,0kPa de CO2 na temperatura de +0,5degreesC, já as pressões parciais 1,0kPa de O2 + 1,0kPa de CO2 e 1,0kPa de O2 + <0,5kPa de CO2 apresentaram maiores valores de podridão e degenerescência senescente, respectivamente. A atmosfera controlada, com exceção da atmosfera refrigerada, mantém conservada a qualidade da maçã ?Pink Lady?.

75 FR 38411 - Drawbridge Operation Regulations; Charles River, Boston, MA, Public Event

Science.gov (United States)

2010-07-02

... Operation Regulations; Charles River, Boston, MA, Public Event AGENCY: Coast Guard, DHS. ACTION: Notice of..., telephone 202-366-9826. SUPPLEMENTARY INFORMATION: The Craigie Bridge, across the Charles River at mile 1.0... elevation above the Charles River Dam. The existing drawbridge operation regulations are listed at 33 CFR...

Cinéma en France

Directory of Open Access Journals (Sweden)

Michel VIGOUROUX

1992-06-01

Full Text Available Le cinéma est l’objet de bases de données exhaustives sur les équipements et les fréquentations. Les données sur les salles permettent d’identifier le phénomène de concentration de propriété et d’exploitation. La perspective dynamique peut être observée sur 45 ans. À l’échelle régionale, on peut apprécier le dynamisme du cinéma en haute montagne alpine et la différence de réseaux sur le territoire (France de l’Ouest.

Echt und modern? Diskurse über Männlichkeit

Directory of Open Access Journals (Sweden)

Florian Kahofer

2014-09-01

Full Text Available Der vorliegende Artikel befasst sich mit Repräsentationen von Männlichkeit im österreichischen Lifestyle-Magazin für Männer Wiener. Durch eine korpusbasierte Diskursanalyse wird ein umfassendes Korpus aller Ausgaben des Wieners von Anfang 2002 bis Ende 2012 untersucht. Auf theoretischer Ebene wird dabei eine Verbindung von Kritischer Männlichkeitsforschung (KMF und Feministisch Kritischer Diskursanalyse (FCDA unternommen. Es werden aktuelle Veröffentlichungen zu Kritischer Diskursanalyse und Männlichkeit vorgestellt und diskutiert. Durch den Einsatz einer Konkordanzsoftware werden Konkordanzen des Nomens MANN analysiert. Diese werden allerdings insofern eingeschränkt betrachtet, als nur Nominationen in der Form der häufigsten Adjektiv-Konstruktionen untersucht werden. Die Ergebnisse zeigen, dass neben den Diskursen über Krise und Neue Männlichkeit Themen wie Alter, Körper oder Beziehung auftauchen. Männlichkeit wird als ambivalent und vielfältig dargestellt. Deutungskämpfe um Männlichkeit lassen sich ausmachen.

Treatment of anti-Ma2/Ta paraneoplastic syndrome.

Science.gov (United States)

Kraker, Jessica

2009-01-01

The paraneoplastic syndrome caused by Ma2/Ta antibodies alone (not in conjunction with Ma1 or Ma3 antibodies) varies in presentation from classic limbic encephalitis. The Ma2 syndrome may present with symptoms referable to the brainstem, diencephalon, and limbic system. These clinical symptoms are accompanied by MRI changes and abnormal electroencephalographic findings. It is important to recognize when the encephalitic syndrome is secondary to Ma2 paraneoplastic antibodies, as the patients improve or stabilize most often when the underlying carcinoma is treated. Treatment of the paraneoplastic syndrome begins with recognition of the symptoms, such as memory impairment, seizures, sleep disturbances, bradykinesia or hypokinesia, and eye movement abnormalities. If a primary tumor is discovered during the workup, it should be removed and treated with the most up-to-date oncologic treatment available. In addition to oncologic treatment, the syndrome may be treated with an immunosuppressant regimen to optimize the neurologic outcome. Leaving the patient untreated will result in decline and eventual death from the cancer itself or from complications of the paraneoplastic syndrome.

CXCL10 can inhibit endothelial cell proliferation independently of CXCR3.

Directory of Open Access Journals (Sweden)

Gabriele S V Campanella

2010-09-01

Full Text Available CXCL10 (or Interferon-inducible protein of 10 kDa, IP-10 is an interferon-inducible chemokine with potent chemotactic activity on activated effector T cells and other leukocytes expressing its high affinity G protein-coupled receptor CXCR3. CXCL10 is also active on other cell types, including endothelial cells and fibroblasts. The mechanisms through which CXCL10 mediates its effects on non-leukocytes is not fully understood. In this study, we focus on the anti-proliferative effect of CXCL10 on endothelial cells, and demonstrate that CXCL10 can inhibit endothelial cell proliferation in vitro independently of CXCR3. Four main findings support this conclusion. First, primary mouse endothelial cells isolated from CXCR3-deficient mice were inhibited by CXCL10 as efficiently as wildtype endothelial cells. We also note that the proposed alternative splice form CXCR3-B, which is thought to mediate CXCL10's angiostatic activity, does not exist in mice based on published mouse CXCR3 genomic sequences as an in-frame stop codon would terminate the proposed CXCR3-B splice variant in mice. Second, we demonstrate that human umbilical vein endothelial cells and human lung microvascular endothelial cells that were inhibited by CXL10 did not express CXCR3 by FACS analysis. Third, two different neutralizing CXCR3 antibodies did not inhibit the anti-proliferative effect of CXCL10. Finally, fourth, utilizing a panel of CXCL10 mutants, we show that the ability to inhibit endothelial cell proliferation correlates with CXCL10's glycosaminoglycan binding affinity and not with its CXCR3 binding and signaling. Thus, using a very defined system, we show that CXCL10 can inhibit endothelial cell proliferation through a CXCR3-independent mechanism.

Compter mes jours : recherche explorant l'espace entre ma pratique artistique et ma pratique comptable

OpenAIRE

Picard, Julie

2017-01-01

Cette recherche propose d’investiguer l’espace entre ma pratique artistique et ma pratique comptable à travers une approche qui déploie des activités de recherches théoriques sur l’art, des activités de recherches théoriques en comptabilité, la réalisation d’un protocole de création en atelier, et la prestation d’une conférence. L’approche flexible, multifocale et exploratoire adoptée se situe en affinité avec Intermedia, développé par Dick Higgins. Partant de ces deux figures type d’oppositi...

Synthesis of 9,9,9-trideutero-1,4-dihydroxynonane mercapturic acid (d3-DHN-MA), a useful internal standard for DHN-MA urinalysis.

Science.gov (United States)

Chantegrel, B; Deshayes, C; Doutheau, A; Steghens, J P

2002-10-01

Racemic 1,4-dihydroxynonane mercapturic acid (DHN-MA) and 9,9,9-trideutero-1,4-dihydroxynonane mercapturic acid (d3-DHN-MA) are synthesized on a 400-mg scale (overall yield approximately 40%) by a two-step sequence involving Michael addition of N-acetyl-L-cysteine to methyl 4-hydroxynon-2(E)-enoate or methyl 9,9,9-trideutero-4-hydroxynon-2 (E)-enoate, followed by reduction of the intermediate adducts with lithium borohydride. The requisite starting methyl esters are obtained, respectively, from heptanal or 7,7,7-trideuteroheptanal and methyl 4-chlorophenylsulfinylacetate via a sulfoxide piperidine and carbonyl reaction described in the literature. The 7,7,7-trideuteroheptanal is easily prepared by classical methods in four steps from 6-bromo-1-hexanol. 13C NMR data indicate that DHN-MA as well as d3-DHN-MA are obtained as mixtures of four diastereomers. Preliminary results show that d3-DHN-MA could be used as an internal standard for mass spectrometric quantification of DHN-MA in human urine.

The Effect of Early Mosquito Insecticides Exposure on Spraque Dawley Rat Testis: A Histopathological Feature Towards Malignancy?

Science.gov (United States)

Indah Winarni, Tri; Auzan Aziman, Milzam; Abshar Andar, Anindyo; Pawitra, Ika

2017-02-01

The incidence of health problems associated with endocrine-disruption have increased. Many studies suggesting that endocrine disruptor chemicals (EDC) do contribute to cancer through estrogen-related receptors. Many chemicals have EDCs properties including insecticides. Early life exposure to EDCs can increased the risk of testicular cancer have been reported in the last decade. This study was aimed to determine the effect of insecticides exposure on histopathological tumor cell development of germ and Leydig cell. True experiment research design with posttest only control group design was applied. Sprague Dawley (SD) rat (n = 25) were randomly divided into 5 groups (control group, 25 mg β estradiol 3-benzoate, spiral mosquito coil repellent, 3 ml of liquid mosquito repellent, and 4 ml of liquid mosquito repellent). The exposure were administered for 20 days started at aged 3 days. At the age of 100 days (older adult), testis was stained using Hematoxyllin Eosin (HE) and histological features predicting malignancy were observed. The number of tumor cell development in both testicular germ cells and Leydig cells significantly increased in all treated group compared to those of control and the changes towards malignancy were also observed in all treated group. Exposure to mosquito insecticides causes significant changes in testicular germ and Leydig cell histological features that leads to malignancy.

NK cell-derived IL-10 is critical for DC-NK cell dialogue at the maternal-fetal interface.

Science.gov (United States)

Blois, Sandra M; Freitag, Nancy; Tirado-González, Irene; Cheng, Shi-Bin; Heimesaat, Markus M; Bereswill, Stefan; Rose, Matthias; Conrad, Melanie L; Barrientos, Gabriela; Sharma, Surendra

2017-05-19

DC-NK cell interactions are thought to influence the development of maternal tolerance and de novo angiogenesis during early gestation. However, it is unclear which mechanism ensures the cooperative dialogue between DC and NK cells at the feto-maternal interface. In this article, we show that uterine NK cells are the key source of IL-10 that is required to regulate DC phenotype and pregnancy success. Upon in vivo expansion of DC during early gestation, NK cells expressed increased levels of IL-10. Exogenous administration of IL-10 was sufficient to overcome early pregnancy failure in dams treated to achieve simultaneous DC expansion and NK cell depletion. Remarkably, DC expansion in IL-10 -/- dams provoked pregnancy loss, which could be abrogated by the adoptive transfer of IL-10 +/+ NK cells and not by IL-10 -/- NK cells. Furthermore, the IL-10 expressing NK cells markedly enhanced angiogenic responses and placental development in DC expanded IL-10 -/- dams. Thus, the capacity of NK cells to secrete IL-10 plays a unique role facilitating the DC-NK cell dialogue during the establishment of a healthy gestation.

Nigerapyrones A-H, α-pyrone derivatives from the marine mangrove-derived endophytic fungus Aspergillus niger MA-132.

Science.gov (United States)

Liu, Dong; Li, Xiao-Ming; Meng, Li; Li, Chun-Shun; Gao, Shu-Shan; Shang, Zhuo; Proksch, Peter; Huang, Cai-Guo; Wang, Bin-Gui

2011-08-26

Eight new α-pyrone derivatives, namely, nigerapyrones A-E (1-5) and nigerapyrones F-H (8-10), along with two known congeners, asnipyrones B (6) and A (7), were isolated from Aspergillus niger MA-132, an endophytic fungus obtained from the fresh tissue of the marine mangrove plant Avicennia marina. The structures of these compounds were elucidated on the basis of spectroscopic analysis. The undescribed geometries of the trisubstituted double bonds (C-9 and C-11) for asnipyrone B (6) have now been explicitly determined, while the incorrect placement of the methyl group at C-5 of asnipyrone A (7) has now been revised at C-3. The cytotoxic activities of the isolated α-pyrone derivatives against eight tumor cell lines as well as antimicrobial activities against two bacteria and four plant-pathogenic fungi of these compounds were evaluated. Compounds 2, 4, 5, and 7 showed weak cytotoxicity against some of the tested tumor cell lines.

MA-burners efficiency parameters allowing for the duration of transmutation process

International Nuclear Information System (INIS)

Gulevich, A.; Zemskov, E.; Kalugin, A.; Ponomarev, L.; Seliverstov, V.; Seregin, M.

2010-01-01

Transmutation of minor actinides (MA) means their transforming into the fission products. Usually, MA-burner's transmutation efficiency is characterized by the static parameters only, such as the number of neutrons absorbed and the rate of MA feeding. However, the proper characterization of MA-burner's efficiency additionally requires the consideration of parameters allowing for the duration of the MA transmutation process. Two parameters of that kind are proposed: a) transmutation time τ - mean time period from the moment a mass of MA is loaded into the burner's fuel cycle to be transmuted to the moment this mass is completely transmuted; b) number of reprocessing cycles n rep - effective number of reprocessing cycles a mass of loaded MA has to undergo before being completely transmuted. Some of MA-burners' types have been analyzed from the point of view of these parameters. It turned out that all of them have the value of parameters too high from the practical point of view. It appears that some new approaches to MA-burner's design have to be used to significantly reduce the value of these parameters in order to make the large-scale MA transmutation process practically reasonable. Some of such approaches are proposed and their potential efficiency is discussed. (authors)

Study of homogeneous fuel cells type 10 x 10; Estudio de celdas de combustible homogeneas tipo 10 x 10

Energy Technology Data Exchange (ETDEWEB)

Montes, J.L.; Perusquia, R.; Ortiz, J.J. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico); Francois, J.L.; Marquez, C.M. [FI-UNAM, 04510 Mexico D.F. (Mexico)]. e-mail: jlmt@nuclear.inin.mx

2005-07-01

At the moment in the National Institute of Nuclear Research (ININ) are carried out studies with the purpose of to establish a methodology that allows to carry out the neutron design of fuel cells of type 10 x 10. During the initial stage of the process of cells design, starting from the data that have to do with the planned energy demand it requires to be estimated the average value of the enrichment in U{sup 235} w/o of the one assemble. The experience has shown that the accuracy that is achieved in this estimate it depends, among other factors, of the information (e.g. concentrations of U{sup 235} and Gd{sub 2}O{sub 3}) of the cells that its are disposed in that moment. For what we consider convenient to enlarge the available information by means of a series of calculations of cell physics; and to the one same time some aspects can be studied on the parameters that define the characteristics of a fuel cell. In this work the effect of the presence of different distributions of the concentrations of the fissile material is analyzed and of burnup poisons on the reactivity parameters of the cell as well as in the peak factor of local power (LPPF-Local Power Peaking Factor). (Author)

IL-10 and IL-27 producing dendritic cells capable of enhancing IL-10 production of T cells are induced in oral tolerance.

Science.gov (United States)

Shiokawa, Aya; Tanabe, Kosuke; Tsuji, Noriko M; Sato, Ryuichiro; Hachimura, Satoshi

2009-06-30

Oral tolerance is a key feature of intestinal immunity, generating systemic tolerance to ingested antigens (Ag). Dendritic cells (DC) have been revealed as important immune regulators, however, the precise role of DC in oral tolerance induction remains unclear. We investigated the characteristics of DC in spleen, mesenteric lymph node (MLN), and Peyer's patch (PP) after oral Ag administration in a TCR-transgenic mouse model. DC from PP and MLN of tolerized mice induced IL-10 production but not Foxp3 expression in cocultured T cells. IL-10 production was markedly increased after 5-7-day Ag administration especially in PP DC. On the other hand, IL-27 production was increased after 2-5-day Ag administration. CD11b(+) DC, which increased after ingestion of Ag, prominently expressed IL-10 and IL-27 compared with CD11b(-) DC. These results suggest that IL-10 and IL-27 producing DC are increased by interaction with antigen specific T cells in PP, and these DC act as an inducer of IL-10 producing T cells in oral tolerance.

MCF-10A-NeoST: A New Cell System for Studying Cell-ECM and Cell-Cell Interactions in Breast Cancer

Energy Technology Data Exchange (ETDEWEB)

Zantek, Nicole Dodge; Walker-Daniels, Jennifer; Stewart, Jane; Hansen, Rhonda K.; Robinson, Daniel; Miao, Hui; Wang, Bingcheng; Kung, Hsing-Jien; Bissell, Mina J.; Kinch, Michael S.

2001-08-22

There is a continuing need for genetically matched cell systems to model cellular behaviors that are frequently observed in aggressive breast cancers. We report here the isolation and initial characterization of a spontaneously arising variant of MCF-10A cells, NeoST, which provides a new model to study cell adhesion and signal transduction in breast cancer. NeoST cells recapitulate important biological and biochemical features of metastatic breast cancer, including anchorage-independent growth, invasiveness in threedimensional reconstituted membranes, loss of E-cadherin expression, and increased tyrosine kinase activity. A comprehensive analysis of tyrosine kinase expression revealed overexpression or functional activation of the Axl, FAK, and EphA2 tyrosine kinases in transformed MCF-10A cells. MCF-10A and these new derivatives provide a genetically matched model to study defects in cell adhesion and signaling that are relevant to cellular behaviors that often typify aggressive breast cancer cells.

Synthesis, Biodistribution and In vitro Evaluation of Brain Permeable High Affinity Type 2 Cannabinoid Receptor Agonists [11C]MA2 and [18F]MA3.

Science.gov (United States)

Ahamed, Muneer; van Veghel, Daisy; Ullmer, Christoph; Van Laere, Koen; Verbruggen, Alfons; Bormans, Guy M

2016-01-01

The type 2 cannabinoid receptor (CB2) is a member of the endocannabinoid system and is known for its important role in (neuro)inflammation. A PET-imaging agent that allows in vivo visualization of CB2 expression may thus allow quantification of neuroinflammation. In this paper, we report the synthesis, radiosynthesis, biodistribution and in vitro evaluation of a carbon-11 ([ 11 C]MA2) and a fluorine-18 ([ 18 F]MA3) labeled analog of a highly potent N -arylamide oxadiazole CB2 agonist (EC 50 = 0.015 nM). MA2 and MA3 behaved as potent CB2 agonist (EC 50 : 3 nM and 0.1 nM, respectively) and their in vitro binding affinity for h CB2 was found to be 87 nM and 0.8 nM, respectively. Also MA3 (substituted with a fluoro ethyl group) was found to have higher binding affinity and EC 50 values when compared to the originally reported trifluoromethyl analog 12 . [ 11 C]MA2 and [ 18 F]MA3 were successfully synthesized with good radiochemical yield, high radiochemical purity and high specific activity. In mice, both tracers were efficiently cleared from blood and all major organs by the hepatobiliary pathway and importantly these compounds showed high brain uptake. In conclusion, [ 11 C]MA2 and [ 18 F]MA3 are shown to be high potent CB2 agonists with good brain uptake, these favorable characteristics makes them potential PET probes for in vivo imaging of brain CB2 receptors. However, in view of its higher affinity and selectivity, further detailed evaluation of MA3 as a PET tracer for CB2 is warranted.

Paleomagnetic study of 1765 Ma dyke swarm from the Singhbhum Craton: Implications to the paleogeography of India

Science.gov (United States)

Shankar, Ravi; Srinivasa Sarma, D.; Ramesh Babu, N.; Parashuramulu, V.

2018-05-01

We report the first key paleopole as a result of paleomagnetic study on a precisely dated 1765.3 ± 1.0 Ma WNW-ESE trending dyke swarm from Singhbhum Craton. This pole has been used in this study to propose the paleogeographic reconstruction of India with Baltica Craton and North China Craton. Incremental alternating field (AF) and thermal demagnetization, isolated high coercivity components with north to north-westerly declination and shallow negative inclination from 9 sampling sites which are representing different individual dykes. The primary origin of the ChRM is supported by the positive baked contact test. The WNW-ESE trending dykes yield a mean paleomagnetic direction with a declination = 329.2° and an inclination = -22.8° (k = 31.6; α95 = 9.3°). The positive bake contact test proves the primary nature of remanence. The pole position of Singhbhum Craton at 1765 Ma is 45°N, 311°E (dp = 5.2 and dm = 9.9). Paleogeographic reconstruction at ca. 1770 Ma, supported by geological, tectonic and metallogenic evidences indicate that the Baltica Craton and India linkage can be stable for at least ∼370 Ma (∼1770-1400 Ma). There is also reasonable evidence in support of India-North China Craton spatial proximity at ∼1770 Ma.

Sceny kulturowe a polityki kultury w Małopolsce

OpenAIRE

Kowalik, Wojciech; Krzyżowski, Łukasz; Noworól, Zofia; Knaś, Piotr

2010-01-01

Książka zawiera diagnozę kultury w oparciu o pogłębioną analizę scen kultury w 10 gminach Małopolski. Wskazano w nim zależności pomiędzy działaniami kulturowymi podejmowanymi przez lokalnych aktorów kultury (instytucje kultury, III sektor, inicjatywy indywidualne, sektor przemysłów kultury) a lokalną polityką kulturową (przede wszystkim w kwestii roli samorządu lokalnego). Ministerstwo Kultury i Dziedzictwa Narodowego Wojciech Kowalik

MA-burners efficiency parameters allowing for the duration of transmutation process

Energy Technology Data Exchange (ETDEWEB)

Gulevich, A.; Zemskov, E. [Institute of Physics and Power Engineering, Bondarenko Square 1, Obninsk, Kaluga Region 249020 (Russian Federation); Kalugin, A.; Ponomarev, L. [Russian Research Center ' ' Kurchatov Institute' ' Kurchatov Square 1, Moscow 123182 (Russian Federation); Seliverstov, V. [Institute of Theoretical and Experimental Physics ul.B. Cheremushkinskaya 25, Moscow 117259 (Russian Federation); Seregin, M. [Russian Research Institute of Chemical Technology Kashirskoe Shosse 33, Moscow 115230 (Russian Federation)

2010-07-01

Transmutation of minor actinides (MA) means their transforming into the fission products. Usually, MA-burner's transmutation efficiency is characterized by the static parameters only, such as the number of neutrons absorbed and the rate of MA feeding. However, the proper characterization of MA-burner's efficiency additionally requires the consideration of parameters allowing for the duration of the MA transmutation process. Two parameters of that kind are proposed: a) transmutation time {tau} - mean time period from the moment a mass of MA is loaded into the burner's fuel cycle to be transmuted to the moment this mass is completely transmuted; b) number of reprocessing cycles n{sub rep} - effective number of reprocessing cycles a mass of loaded MA has to undergo before being completely transmuted. Some of MA-burners' types have been analyzed from the point of view of these parameters. It turned out that all of them have the value of parameters too high from the practical point of view. It appears that some new approaches to MA-burner's design have to be used to significantly reduce the value of these parameters in order to make the large-scale MA transmutation process practically reasonable. Some of such approaches are proposed and their potential efficiency is discussed. (authors)

SCA-1 Labels a Subset of Estrogen-Responsive Bipotential Repopulating Cells within the CD24+ CD49fhi Mammary Stem Cell-Enriched Compartment

Directory of Open Access Journals (Sweden)

Genevieve V. Dall

2017-02-01

Full Text Available Estrogen stimulates breast development during puberty and mammary tumors in adulthood through estrogen receptor-α (ERα. These effects are proposed to occur via ERα+ luminal cells and not the mammary stem cells (MaSCs that are ERαneg. Since ERα+ luminal cells express stem cell antigen-1 (SCA-1, we sought to determine if SCA-1 could define an ERα+ subset of EpCAM+/CD24+/CD49fhi MaSCs. We show that the MaSC population has a distinct SCA-1+ population that is abundant in pre-pubertal mammary glands. The SCA-1+ MaSCs have less stem cell markers and less in vivo repopulating activity than their SCA-1neg counterparts. However, they express ERα and specifically enter the cell cycle at puberty. Using estrogen-deficient aromatase knockouts (ArKO, we showed that the SCA-1+ MaSC could be directly modulated by estrogen supplementation. Thus, SCA-1 enriches for an ERα+, estrogen-sensitive subpopulation within the CD24+/CD49fhi MaSC population that may be responsible for the hormonal sensitivity of the developing mammary gland.

Impaired pubertal development and testicular hormone function in males with sickle cell anemia.

Science.gov (United States)

Martins, Paulo Roberto Juliano; Kerbauy, José; Moraes-Souza, Helio; Pereira, Gilberto de Araújo; Figueiredo, Maria Stella; Verreschi, Ieda Therezinha

2015-01-01

Changes in weight/height ratio, delayed sexual maturation, hypogonadism and impaired fertility have been demonstrated in sickle cell disease (SCD). This study aimed to evaluate the clinical and laboratory views of the Leydig cells function after stimulation with hCG in adults with sickle cell disease. We studied 15 patients with SCD (18 to 40 years; median=27 years old), fourteen homozygous S, and one with SC disease. The control group, composed by adult males, was divided into two groups: I - 10 relatives (18-39 years, median=26 years) with the same socioeconomic level of the patients, and II - 9 normal individuals (23-28, median=31 years) randomly chosen. Clinically it was observed a slight degree of malnutrition, important puberty delay, rarefaction of chest, underarm and pubic hair, and important reduction of the testis and penis size, featuring a mild hypogonadism in patients with SCD. The hormonal level assessment of testosterone at baseline and at 24, 48 and 72 h after hCG stimulation showed no significant differences between the groups studied. We can presume that adult men with SCD showed clinical hypoandrogenism with normal testicular hormonal function, a fact inconsistent with the hypothesis of primary hypogonadism. Copyright © 2014 Elsevier Inc. All rights reserved.

redMaPPer. I. Algorithm and SDSS DR8 catalog

Energy Technology Data Exchange (ETDEWEB)

Rykoff, E. S.; Rozo, E.; Reddick, R.; Wechsler, R. H. [SLAC National Accelerator Laboratory, Menlo Park, CA 94025 (United States); Busha, M. T. [Institute for Theoretical Physics, University of Zürich, 8057 Zürich (Switzerland); Cunha, C. E. [Kavli Institute for Particle Astrophysics and Cosmology, Stanford University, Palo Alto, CA 94305 (United States); Finoguenov, A. [Department of Physics, University of Helsinki, FI-00014 Helsinki (Finland); Evrard, A.; Koester, B. P. [Physics Department, University of Michigan, Ann Arbor, MI 48109 (United States); Hao, J.; Nord, B. [Center for Particle Astrophysics, Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States); Leauthaud, A. [Kavli Institute for the Physics and Mathematics of the Universe, University of Tokyo, Kashiwa 277-8583 (Japan); Pierre, M.; Sadibekova, T. [Service d' Astrophysique, CEA Saclay, F-91191 Gif sur Yvette Cedex (France); Sheldon, E. S. [Brookhaven National Laboratory, Upton, NY 11973 (United States)

2014-04-20

We describe redMaPPer, a new red sequence cluster finder specifically designed to make optimal use of ongoing and near-future large photometric surveys. The algorithm has multiple attractive features: (1) it can iteratively self-train the red sequence model based on a minimal spectroscopic training sample, an important feature for high-redshift surveys. (2) It can handle complex masks with varying depth. (3) It produces cluster-appropriate random points to enable large-scale structure studies. (4) All clusters are assigned a full redshift probability distribution P(z). (5) Similarly, clusters can have multiple candidate central galaxies, each with corresponding centering probabilities. (6) The algorithm is parallel and numerically efficient: it can run a Dark Energy Survey-like catalog in ∼500 CPU hours. (7) The algorithm exhibits excellent photometric redshift performance, the richness estimates are tightly correlated with external mass proxies, and the completeness and purity of the corresponding catalogs are superb. We apply the redMaPPer algorithm to ∼10, 000 deg{sup 2} of SDSS DR8 data and present the resulting catalog of ∼25,000 clusters over the redshift range z in [0.08, 0.55]. The redMaPPer photometric redshifts are nearly Gaussian, with a scatter σ {sub z} ≈ 0.006 at z ≈ 0.1, increasing to σ {sub z} ≈ 0.02 at z ≈ 0.5 due to increased photometric noise near the survey limit. The median value for |Δz|/(1 + z) for the full sample is 0.006. The incidence of projection effects is low (≤5%). Detailed performance comparisons of the redMaPPer DR8 cluster catalog to X-ray and Sunyaev-Zel'dovich catalogs are presented in a companion paper.

Synthesis, biodistribution and in vitro evaluation of brain permeable high affinity type 2 cannabinoid receptor agonists [11C]MA2 and [18F]MA3

Directory of Open Access Journals (Sweden)

Muneer Ahamed

2016-09-01

Full Text Available Abstract The type 2 cannabinoid receptor (CB2 is a member of the endocannabinoid system and is known for its important role in (neuroinflammation. A PET-imaging agent that allows in vivo visualization of CB2 expression may thus allow quantification of neuroinflammation. In this paper, we report the synthesis, radiosynthesis, biodistribution and in vitro evaluation of a carbon-11 ([11C]MA2 and a fluorine-18 ([18F]MA3 labeled analogue of a highly potent N-arylamide oxadiazole CB2 agonist (EC50 = 0.015 nM. MA2 and MA3 behaved as potent CB2 agonist (EC50: 3 nM and 0.1 nM, respectively and their in vitro binding affinity for hCB2 was found to be 87 nM and 0.8 nM, respectively. Also MA3 (substituted with a fluoro ethyl group was found to have higher binding affinity and EC50 values when compared to the originally reported trifluoromethyl analogue 12. [11C]MA2 and [18F]MA3 were successfully synthesized with good radiochemical yield, high radiochemical purity and high specific activity. In mice, both tracers were efficiently cleared from blood and all major organs by the hepatobiliary pathway and importantly these compounds showed high brain uptake. In conclusion, [11C]MA2 and [18F]MA3 are shown to be high potent CB2 agonists with good brain uptake, these favorable characteristics makes them potential PET probes for in vivo imaging of brain CB2 receptors. However in view of its higher affinity and selectivity, further detailed evaluation of MA3 as a PET tracer for CB2 is warranted.

The HectoMAP Cluster Survey. I. redMaPPer Clusters

Science.gov (United States)

Sohn, Jubee; Geller, Margaret J.; Rines, Kenneth J.; Hwang, Ho Seong; Utsumi, Yousuke; Diaferio, Antonaldo

2018-04-01

We use the dense HectoMAP redshift survey to explore the properties of 104 redMaPPer cluster candidates. The redMaPPer systems in HectoMAP cover the full range of richness and redshift (0.08 systems included in the Subaru/Hyper Suprime-Cam public data release are bona fide clusters. The median number of spectroscopic members per cluster is ∼20. We include redshifts of 3547 member candidates listed in the redMaPPer catalog whether they are cluster members or not. We evaluate the redMaPPer membership probability spectroscopically. The purity (number of real systems) in redMaPPer exceeds 90% even at the lowest richness. Three massive galaxy clusters (M ∼ 2 × 1013 M ⊙) associated with X-ray emission in the HectoMAP region are not included in the public redMaPPer catalog with λ rich > 20, because they lie outside the cuts for this catalog.

Regulation of Banana Phytoene Synthase (MaPSY) Expression, Characterization and Their Modulation under Various Abiotic Stress Conditions

Science.gov (United States)

Kaur, Navneet; Pandey, Ashutosh; Shivani; Kumar, Prateek; Pandey, Pankaj; Kesarwani, Atul K.; Mantri, Shrikant S.; Awasthi, Praveen; Tiwari, Siddharth

2017-01-01

Phytoene synthase (PSY) is a key regulatory enzyme of carotenoid biosynthesis pathway in plants. The present study examines the role of PSY in carotenogenesis and stress management in banana. Germplasm screening of 10 Indian cultivars showed that Nendran (3011.94 μg/100 g dry weight) and Rasthali (105.35 μg/100 g dry weight) contained the highest and lowest amounts of β-carotene, respectively in ripe fruit-pulp. Nendran ripe pulp also showed significantly higher antioxidant activity as compared to Rasthali. Meta-analysis of three banana PSY genes (MaPSY1, MaPSY2, and MaPSY3) was performed to identify their structural features, subcellular, and chromosomal localization in banana genome. The distinct expression patterns of MaPSY1, MaPSY2, and MaPSY3 genes were observed in various tissues, and fruit developmental stages of these two contrasting cultivars, suggesting differential regulation of the banana PSY genes. A positive correlation was observed between the expression of MaPSY1 and β-carotene accumulation in the ripe fruit-peel and pulp of Nendran. The presence of stress responsive cis-regulatory motifs in promoter region of MaPSY genes were correlated with the expression pattern during various stress (abscisic acid, methyl jasmonate, salicylic acid and dark) treatments. The positive modulation of MaPSY1 noticed under abiotic stresses suggested its role in plant physiological functions and defense response. The amino acid sequence analysis of the PSY proteins in contrasting cultivars revealed that all PSY comprises conserved domains related to enzyme activity. Bacterial complementation assay has validated the functional activity of six PSY proteins and among them PSY1 of Nendran (Nen-PSY1) gave the highest activity. These data provide new insights into the regulation of PSY expression in banana by developmental and stress related signals that can be explored in the banana improvement programs. PMID:28421096

Does Fetal antigen 1 (FA1) identify cells with regenerative, endocrine and neuroendocrine potentials?

DEFF Research Database (Denmark)

Jensen, Charlotte Floridon; Jensen, Charlotte Harken; Thorsen, Poul

2000-01-01

Fetal antigen 1 (FA1) is a circulating EGF multidomain glycoprotein. FA1 and its membrane-associated precursor is defined by the mRNAs referred to as delta-like (dlk), preadipocyte factor 1 (pref-1) or zona glomerulosa-specific factor (ZOG). Using a polyclonal antibody recognising both forms......, the localisation of FA1/dlk was analysed in embryonic and fetal tissues between week 5 to 25 of gestation and related to germinal origin and development. FA1 was observed in endodermally derived hepatocytes, glandular cells of the pancreas anlage, and in respiratory epithelial cells. FA1 was also present...... in mesodermally derived cells of the renal proximal tubules, adrenal cortex, Leydig and Hilus cells of the testes and ovaries, fetal chondroblasts, and skeletal myotubes. Ectodermally derived neuro- and adenohypophysial cells, cells in the floor of the 3rd ventricle and plexus choroideus were also FA1 positive...

Mass and Reliability System (MaRS)

Science.gov (United States)

Barnes, Sarah

2016-01-01

The Safety and Mission Assurance (S&MA) Directorate is responsible for mitigating risk, providing system safety, and lowering risk for space programs from ground to space. The S&MA is divided into 4 divisions: The Space Exploration Division (NC), the International Space Station Division (NE), the Safety & Test Operations Division (NS), and the Quality and Flight Equipment Division (NT). The interns, myself and Arun Aruljothi, will be working with the Risk & Reliability Analysis Branch under the NC Division's. The mission of this division is to identify, characterize, diminish, and communicate risk by implementing an efficient and effective assurance model. The team utilizes Reliability and Maintainability (R&M) and Probabilistic Risk Assessment (PRA) to ensure decisions concerning risks are informed, vehicles are safe and reliable, and program/project requirements are realistic and realized. This project pertains to the Orion mission, so it is geared toward a long duration Human Space Flight Program(s). For space missions, payload is a critical concept; balancing what hardware can be replaced by components verse by Orbital Replacement Units (ORU) or subassemblies is key. For this effort a database was created that combines mass and reliability data, called Mass and Reliability System or MaRS. The U.S. International Space Station (ISS) components are used as reference parts in the MaRS database. Using ISS components as a platform is beneficial because of the historical context and the environment similarities to a space flight mission. MaRS uses a combination of systems: International Space Station PART for failure data, Vehicle Master Database (VMDB) for ORU & components, Maintenance & Analysis Data Set (MADS) for operation hours and other pertinent data, & Hardware History Retrieval System (HHRS) for unit weights. MaRS is populated using a Visual Basic Application. Once populated, the excel spreadsheet is comprised of information on ISS components including

Millennium Ecosystem Assessment: MA Ecosystems

Data.gov (United States)

National Aeronautics and Space Administration — The Millennium Ecosystem Assessment: MA Ecosystems provides data and information on the extent and classification of ecosystems circa 2000, including coastal,...

Millennium Ecosystem Assessment: MA Biodiversity

Data.gov (United States)

National Aeronautics and Space Administration — The Millennium Ecosystem Assessment: MA Biodiversity provides data and information on amphibians, disease agents (extent and distribution of infectious and parasitic...

MicroRNA Regulation of CD44+ Prostate Tumor Stem/Progenitor Cells and Prostate Cancer Development/Metastasis

Science.gov (United States)

2013-05-01

cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007;445:106–10. 11. Goodell MA, Brose K, Paradis G, Conner AS, Mulligan...broad-lineage differentiation potential and were able to regenerate mam- mary ductal structures in vivo. Likewise, breast cancer cells with high ALDH

Suppression of thymosin β10 increases cell migration and metastasis of cholangiocarcinoma

International Nuclear Information System (INIS)

Sribenja, Sirinapa; Sawanyawisuth, Kanlayanee; Kraiklang, Ratthaphol; Wongkham, Chaisiri; Vaeteewoottacharn, Kulthida; Obchoei, Sumalee; Yao, Qizhi; Wongkham, Sopit; Chen, Changyi

2013-01-01

Thymosin β10 (Tβ10) expression is associated with malignant phenotypes in many cancers. However, the role and mechanisms of Tβ10 in liver fluke-associated cholangiocarcinoma (CCA) are not fully understood. In this study, we investigated the expression of Tβ10 in CCA tumor tissues and cell lines as well as molecular mechanisms of Tβ10 in tumor metastasis of CCA cell lines. Tβ10 expression was determined by real time RT-PCR or immunocytochemistry. Tβ10 silence or overexpression in CCA cells was achieved using gene delivery techniques. Cell migration was assessed using modified Boyden chamber and wound healing assay. The effect of silencing Tβ10 on CCA tumor metastasis was determined in nude mice. Phosphorylation of ERK1/2 and the expression of EGR1, Snail and matrix metalloproteinases (MMPs) were studied. Ten pairs of CCA tissues (primary and metastatic tumors) and 5 CCA cell lines were studied. With real time RT-PCR and immunostaining analysis, Tβ10 was highly expressed in primary tumors of CCA; while it was relatively low in the metastatic tumors. Five CCA cell lines showed differential expression levels of Tβ10. Silence of Tβ10 significantly increased cell migration, invasion and wound healing of CCA cells in vitro; reversely, overexpression of Tβ10 reduced cell migration compared with control cells (P<0.05). In addition, silence of Tβ10 in CCA cells increased liver metastasis in a nude mouse model of CCA implantation into the spleen. Furthermore, silence of Tβ10 activated ERK1/2 and increased the expression of Snail and MMPs in CCA cell lines. Ras-GTPase inhibitor, FPT inhibitor III, effectively blocked Tβ10 silence-associated ERK1/2 activation, Snail expression and cell migration. Low expression of Tβ10 is associated with metastatic phenotype of CCA in vitro and in vivo, which may be mediated by the activation of Ras, ERK1/2 and upregulation of Snail and MMPs. This study suggests a new molecular pathway of CCA pathogenesis and a novel strategy to

M&A information technology best practices

CERN Document Server

Roehl-Anderson, Janice M

2013-01-01

Add value to your organization via the mergers & acquisitions IT function  As part of Deloitte Consulting, one of the largest mergers and acquisitions (M&A) consulting practice in the world, author Janice Roehl-Anderson reveals in M&A Information Technology Best Practices how companies can effectively and efficiently address the IT aspects of mergers, acquisitions, and divestitures. Filled with best practices for implementing and maintaining systems, this book helps financial and technology executives in every field to add value to their mergers, acquisitions, and/or divestitures via the IT

42 CFR 422.4 - Types of MA plans.

Science.gov (United States)

2010-10-01

... availability, service area, and quality. (ii) Coordinated care plans may include mechanisms to control... requirements of sections 138 and 220 of the Internal Revenue Code. (3) MA private fee-for-service plan. An MA... Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

Ma(d)skulinitet

DEFF Research Database (Denmark)

Leer, Jonatan

Når tv-kokke som Jamie Oliver, Gordon Ramsay og brødrene Price toner frem på skærmen, laver de ikke kun mad. De mixer også maskulinitet. For når en mand laver mad, laver maden også manden. Det mener postdoc Jonatan Leer, der i Ma(ds)kulinitet. Kønskamp i tv-køkkenet præsenterer, hvordan og hvorfor...

Mulberry anthocyanins improves thyroid cancer progression mainly by inducing apoptosis and autophagy cell death

Directory of Open Access Journals (Sweden)

Hou-Long Long

2018-05-01

Full Text Available Dietary anthocyanin compounds have multiple biological effects, including antioxidant, anti-inflammatory, and anti-atherosclerotic characteristics. The present study evaluated the anti-tumor capacity of mulberry anthocyanins (MA in thyroid cancer cells. Our data showed that MA suppressed SW1736 and HTh-7 cell proliferation in a time- and dose-dependent manner. Meanwhile, flow cytometry results indicated that MA significantly increased SW1736 and HTh-7 cell apoptosis. We additionally observed that SW1736 and HTh-7 cell autophagy was markedly enhanced after MA treatment. Importantly, anthocyanin-induced cell death was largely abolished by 3-methyladenine (3-MA or chloroquine diphosphate salt (CQ treatment, suggesting that MA-induced SW1736 and HTh-7 cell death was partially dependent on autophagy. In addition, activation of protein kinase B (Akt, mammalian target of rapamycin (mTOR, and ribosomal protein S6 (S6 were significantly suppressed by anthocyanin exposure. In summary, MA may serve as an adjunctive therapy for thyroid cancer patients through induction of apoptosis and autophagy-dependent cell death. Keywords: Mulberry anthocyanins, Thyroid cancer, Apoptosis, Autophagic death

HoCaMA: Home Care Hybrid Multiagent Architecture

Science.gov (United States)

Fraile, Juan A.; Bajo, Javier; Abraham, Ajith; Corchado, Juan M.

Home Care is one of the main objectives of Ambient Intelligence. Nowadays, the disabled and elderly population, which represents a significant part of our society, requires novel solutions for providing home care in an effective way. In this chapter, we present HoCaMA, a hybrid multiagent architecture that facilitates remote monitoring and care services for disabled patients at their homes. HoCaMA combines multiagent systems and Web services to facilitate the communication and integration with multiple health care systems. In addition, HoCaMA focuses on the design of reactive agents capable of interacting with different sensors present in the environment, and incorporates a system of alerts through SMS and MMS mobile technologies. Finally, it uses Radio Frequency IDentification and JavaCard technologies to provide advanced location and identification systems, as well as automatic access control facilities. HoCaMA has been implemented in a real environment and the results obtained are presented within this chapter.

The Prevalence of Ionized Gas Outflow Signatures in SDSS-IV MaNGA Active Galactic Nuclei

Science.gov (United States)

Flores, Anthony M.; Wylezalek, Dominika; Zakamska, Nadia

2018-01-01

Actively accreting supermassive black holes (AGN) can have a variety of effects on their host galaxies, from generating large regions of hot, photoionized gas, to driving AGN feedback in the form of galaxy wide outflows that may affect the evolution of the galaxy over time by quenching their star formation and by thus setting limits to the total mass of their host galaxy. The focus of this work is to assess the prevalence of AGN-driven outflows in low-redshift AGN of moderate power using IFU observations of 2778 galaxies available through SDSS-IV MaNGA.SDSS-IV MaNGA is an optical spectroscopic IFU survey which will have obtained spatially resolved spectroscopic observations of ~10,000 galaxies at z ≤ 0.1 and with stellar masses >10^9 solar masses over the next three years, allowing us to describe the kinematic properties of a large galaxy sample across different spatial regions.We have re-mapped the kinematics of the [O III] emission line to account for asymmetries and secondary kinematic components in the emission line brought on by potential AGN-driven outflows. Using all galaxies currently in the MaNGA survey, we implement a new fitting procedure to help determine the prevalence of these secondary components. Specifically, we use the non-parametric W80 value as a proxy for velocity dispersion, which we expect to be affected especially in the case of asymmetries and broadening of the emission lines. Separating these galaxies into two samples of independently identified AGN candidates and non-AGN, I will show that broad secondary components are twice as common in MaNGA-selected AGN compared to galaxies in MaNGA not classified as AGN. Moreover, when the underlying distribution of W80 values are compared between samples, I will show that the differences in these distributions are statistically significant. This demonstrates that large IFU survey like SDSS-IV MaNGA will uncover many previously unknown AGN and AGN feedback signatures. Outflows and feedback from low

Assessment of testicular function after acute and chronic irradiation: Further evidence for an influence of late spermatids on Sertoli cell function in the adult rat

International Nuclear Information System (INIS)

Pineau, C.; Velez de la Calle, J.F.; Pinon-Lataillade, G.; Jegou, B.

1989-01-01

To study cell to cell communications within the testis of adult Sprague-Dawley rats, we used acute whole body neutron plus gamma-irradiation over 7-121 days postirradiation and chronic whole body gamma-irradiation over 14-84 days of irradiation and 7-86 days postirradiation. Neither irradiation protocol had an effect on the body weight of the animals. Neutron plus gamma-rays induced dramatic damages to spermatogonia, preleptotene spermatocytes, spermatozoa, and, to a lesser extent, pachytene spermatocytes. In contrast, gamma-rays induced a selective destruction of spermatogonia. Subsequently, in both experiments a maturation-depletion process led to a marked decrease in all germ cell types. A complete or near complete recovery of the different germ cell types and spermatozoa took place during the two postirradiation periods. Under both irradiation protocols Sertoli cells number was unchanged. Androgen-binding protein and FSH levels were normal in spite of the disappearance of most germ cells from spermatogonia to early spermatids. However, the decline of androgen-binding protein as well as the rise of FSH and their subsequent recovery were highly correlated to the number of late spermatids and spermatozoa. Moreover, it appeared that spermatocytes may also interfere with the production of inhibin (Exp B). With neither irradiation was Leydig cell function altered, except in Exp B in which elevated LH levels were temporarily observed. Correlation analysis suggested a relationship between preleptotene spermatocytes and Leydig cell function. In conclusion, this study establishes that chronic gamma-irradiation is particularly useful in the study of intratesticular paracrine regulation in vivo and provides further support to the concept that late spermatids play a major role in controlling some aspects of Sertoli cell function in the adult rat

Adherence of B16-F10 melanoma cells to elastin

International Nuclear Information System (INIS)

Zetter, B.R.; Netland, P.A.

1986-01-01

B16-F10 melanoma cells selectivity colonize lung tissue in vivo. The authors have previously shown that these cells adhere preferentially to lung tissue in vitro. To quantify the binding of B16-F10 cells to isolated components of lung tissue, the authors devised a dot-blot cell adhesion assay. Samples were absorbed to 4 mm dots of nylon based paper under non-denaturing conditions, blocked with albumin or hemoglobin, and incubated with radiolabelled cells for 30 min. at 4 0 C. 125 -I labelled B16-F10 cells demonstrated a dose dependent binding to mouse lung elastin. Autoradiography and scanning electron microscopy demonstrated that cells localized preferentially to the elastin dots. The melanoma cells bound more strongly to elastin relative to laminin, fibronectin, collagen types I and IV or heparan sulfate. Neither elastin-associated microfibrillar protein nor fragments of elastin produced by alkali or acid treatment demonstrated significant binding activity for these cells. The findings demonstrate that in addition to its unique mechanical properties that confer elasticity to tissues, elastin can also function as a cell adhesion molecule. The localization of elastin in the lung and its adhesive properties reported here suggest that elastin may facilitate the arrest and eventual colonization of circulating B16-F10 melanoma cells in the mouse lung

46 CFR 308.526 - Certificate for repayment of decrease of collateral deposit fund, Form MA-306.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Certificate for repayment of decrease of collateral... TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Ii-Open Policy War Risk Cargo Insurance § 308.526 Certificate for repayment of decrease of collateral deposit fund, Form MA-306. The...

Immunohistochemical expression of CD 10 in Cutaneous basal ,and Squamous Cell Carcinomas

International Nuclear Information System (INIS)

AIAD, H.A.; HANOUT, H.M.

2007-01-01

Background: CD 10 is a zinc-dependent metallo peptidase known as common acute lymphoblastic leukemia antigen (CALLA). Although CD I 0 expression has been investigated in some cutaneous tumors, to our knowledge, data regarding its expression in cutaneous epithelial neoplasms are very limited. We aimed to determine the immunohistochemical expression of Cd 10 in basal cell carcinoma (BCC) and squamous cell carcinoma (Succ) and to associate it with the available clinico pathological parameters in both tumors. Patients and Methods: This study included 16 Succ and 21 BCC cases (17 solid type, 2 morphea type and 2 adenoid basal types). BCC cases were divided into 12 cases with microscopic infiltrative base and 9 cases with well-circumscribed base. The localization of anti-CD 10 to the tumor and/or stromal cells was determined in each case. Results: Positive CD 10 staining was identified as brown cytoplasmic, with or without cell membrane staining. In all the 16 SCC cases, tumor cells failed to stain with CD 10 in contrast to the stromal cells that showed CD 10 expression in 13 cases (81%). In BCC cases, the expression of CD 10 was noted in tumor cells in 10 cases (476%) and in stromal cells of 20 cases (95.24%). Most of CD 10+ (7/10) BCC showed well-circumscribed deep margin, however, most of CD 10- cases (9/11) showed infiltrating base (p=0.030). BCCs with infiltrating deep margins (12 cases) tended to show CD 10 negative basaloid cells (9/12) and CD 10 positive stromal cells (12/12) (p=0.0003). Conclusion: From our results we suggest that CD 10 might be a useful immunohistochemical marker to differentiate between BCC and SCC. At least, if tumor cells were CD 10 positive, this would favor BCC over SCC. Absence of CD 10 in all the SCC and in infiltrating BCC together with its overexpression in the surrounding stromal cells might confer invasive properties to such tumors. However, its relation to other poor prognostic factors needs larger studies to be confirmed

3D bioprinting mesenchymal stem cell-laden construct with core-shell nanospheres for cartilage tissue engineering

Science.gov (United States)

Zhu, Wei; Cui, Haitao; Boualam, Benchaa; Masood, Fahed; Flynn, Erin; Rao, Raj D.; Zhang, Zhi-Yong; Zhang, Lijie Grace

2018-05-01

Cartilage tissue is prone to degradation and has little capacity for self-healing due to its avascularity. Tissue engineering, which provides artificial scaffolds to repair injured tissues, is a novel and promising strategy for cartilage repair. 3D bioprinting offers even greater potential for repairing degenerative tissue by simultaneously integrating living cells, biomaterials, and biological cues to provide a customized scaffold. With regard to cell selection, mesenchymal stem cells (MSCs) hold great capacity for differentiating into a variety of cell types, including chondrocytes, and could therefore be utilized as a cartilage cell source in 3D bioprinting. In the present study, we utilize a tabletop stereolithography-based 3D bioprinter for a novel cell-laden cartilage tissue construct fabrication. Printable resin is composed of 10% gelatin methacrylate (GelMA) base, various concentrations of polyethylene glycol diacrylate (PEGDA), biocompatible photoinitiator, and transforming growth factor beta 1 (TGF-β1) embedded nanospheres fabricated via a core-shell electrospraying technique. We find that the addition of PEGDA into GelMA hydrogel greatly improves the printing resolution. Compressive testing shows that modulus of the bioprinted scaffolds proportionally increases with the concentrations of PEGDA, while swelling ratio decreases with the increase of PEGDA concentration. Confocal microscopy images illustrate that the cells and nanospheres are evenly distributed throughout the entire bioprinted construct. Cells grown on 5%/10% (PEGDA/GelMA) hydrogel present the highest cell viability and proliferation rate. The TGF-β1 embedded in nanospheres can keep a sustained release up to 21 d and improve chondrogenic differentiation of encapsulated MSCs. The cell-laden bioprinted cartilage constructs with TGF-β1-containing nanospheres is a promising strategy for cartilage regeneration.

Bioprinting 3D cell-laden hydrogel microarray for screening human periodontal ligament stem cell response to extracellular matrix

International Nuclear Information System (INIS)

Ma, Yufei; Ji, Yuan; Huang, Guoyou; Zhang, Xiaohui; Xu, Feng; Ling, Kai

2015-01-01

Periodontitis is an inflammatory disease negatively affecting up to 15% of adults worldwide. Periodontal ligament stem cells (PDLSCs) hold great promises for periodontal tissue regeneration, where it is necessary to find proper extracellular matrix (ECM) materials (e.g., composition, concentration). In this study, we proposed a bioprinting-based approach to generate nano-liter sized three-dimensional (3D) cell-laden hydrogel array with gradient of ECM components, through controlling the volume ratio of two hydrogels, such as gelatin methacrylate (GelMA) and poly(ethylene glycol) (PEG) dimethacrylate. The resulting cell-laden array with a gradient of GelMA/PEG composition was used to screen human PDLSC response to ECM. The behavior (e.g., cell viability, spreading) of human PDLSCs in GelMA/PEG array were found to be depended on the volume ratios of GelMA/PEG, with cell viability and spreading area decreased along with increasing the ratio of PEG. The developed approach would be useful for screening cell-biomaterial interaction in 3D and promoting regeneration of functional tissue. (paper)

Liver sinusoidal endothelial cells induce immunosuppressive IL-10-producing Th1 cells via the Notch pathway.

Science.gov (United States)

Neumann, Katrin; Rudolph, Christine; Neumann, Christian; Janke, Marko; Amsen, Derk; Scheffold, Alexander

2015-07-01

Under homeostasis, liver sinusoidal endothelial cells (LSECs) shift intrahepatic T-cell responses towards tolerance. However, the role of LSECs in the regulation of T-cell-induced liver inflammation is less clear. Here, we studied the capacity of LSECs to modulate pro-inflammatory Th1-cell differentiation in mice. Using in vitro co-culture systems and subsequent cytokine analysis, we showed that LSECs induced high amounts of the anti-inflammatory cytokine IL-10 in developing Th1 cells. These LSEC-stimulated Th1 cells had no pro-inflammatory capacity in vivo but instead actively suppressed an inflammatory Th1-cell-induced delayed-type hypersensitivity reaction. Blockage of IL-10 signaling in vivo inhibited immunosuppressive activity of LSEC-stimulated Th1 cells. We identified the Notch pathway as a mechanism how LSECs trigger IL-10 expression in Th1 cells. LSECs expressed high levels of the Delta-like and Jagged family of Notch ligands and induced expression of the Notch target genes hes-1 and deltex-1 in Th1 cells. Blockade of Notch signaling selectively inhibited IL-10 induction in Th1 cells by LSECs. Our findings suggest that LSEC-induced IL-10 expression in Th1 cells via the Notch pathway may contribute to the control of hepatic inflammatory immune responses by induction of a self-regulatory mechanism in pro-inflammatory Th1 cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Millennium Ecosystem Assessment: MA Population

Data.gov (United States)

National Aeronautics and Space Administration — The Millennium Ecosystem Assessment: MA Population data sets provide baseline population information as one of the drivers of ecosystem change. The data helped in...

Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors.

Directory of Open Access Journals (Sweden)

Tao Cui

Full Text Available BACKGROUND: Small intestine neuroendocrine tumors (SI-NETs belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2 as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. METHODOLOGY/PRINCIPAL FINDINGS: A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC, to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. CONCLUSION: Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA for the risk of recurrence after radical operation of these tumors.

Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors.

Science.gov (United States)

Cui, Tao; Hurtig, Monica; Elgue, Graciela; Li, Su-Chen; Veronesi, Giulia; Essaghir, Ahmed; Demoulin, Jean-Baptiste; Pelosi, Giuseppe; Alimohammadi, Mohammad; Öberg, Kjell; Giandomenico, Valeria

2010-12-30

Small intestine neuroendocrine tumors (SI-NETs) belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2) as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC), to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA) for the risk of recurrence after radical operation of these tumors.

Microcap M&A: An Exploratory Study

Directory of Open Access Journals (Sweden)

Keith Turpie

2014-06-01

Full Text Available A substantial body of accounting and finance literature has been devoted to the study of Mergers and Acquisitions (M&As dominated by discussions relating to the gains and losses that accrue from transactions involving large public companies. This paper makes a unique contribution to the literature by investigating the M&A experience of microcap businesses. Transactions involving microcap M&A are substantially different to those involving large companies on a number of dimensions. This paper explores the determinants of microcap M&A success and pitfalls and problems from an integration perspective. Due to the paucity of research in the area an exploratory research design is employed, conducting interviews with five CEOs of companies that had each managed multiple transactions. We find microcap M&As are successful when measured against identified goals but generally take longer and cost more than expected. Further, culture and communication are key issues in determining success/failure. We also find the in-house management of integration aspects is problematic for these businesses and suggest this warrants further study.

IL-10 polymorphism and cell-mediated immune response to Chlamydia trachomatis

DEFF Research Database (Denmark)

Öhman, H.; Tiitinen, A; Halttunen, M.

2006-01-01

background. To study a relationship between interleukin-10 (IL-10) promoter -1082 polymorphism and cell-mediated immune response during C trachomatis infection in vitro, lymphocyte proliferation and cytokine (IL-10, IFN-gamma, TNF-alpha, IL-2, IL-4 and IL-5) secretion were analysed in subjects with different...... IL-10 genotypes. Enhanced IL-10 secretion and reduced antigen-specific lymphocyte proliferative and IFN-gamma responses were found in subjects with IL-10 -1082 GG genotype when compared to those with -1082 AA genotype. CD14+ monocytes were main source of IL-10 indicating that these cells...... are important regulators of the antigen-specific cell-mediated responses during active C trachomatis infection. We conclude that impaired cell-mediated response to C trachomatis is associated with IL-10 genotype in subjects with high IL-10 producing capacity. A comparison of immune markers between subjects...

Changing the S and MA [Safety and Mission Assurance] Paradigm

Science.gov (United States)

Malone, Roy W., Jr.

2010-01-01

Objectives: 1) Optimize S&MA organization to best facilitate Shuttle transition in 2010, successfully support Ares developmental responsibilities, and minimize the impacts of the gap between last Shuttle flight and start of Ares V Project. 2) Improve leveraging of critical skills and experience between Shuttle and Ares. 3) Split technical and supervisory functions to facilitate technical penetration. 4) Create Chief Safety and Mission Assurance Officer (CSO) stand-alone position for successfully implementation of S&MA Technical Authority. 5) Minimize disruption to customers. 6) Provide early involvement of S&MA leadership team and frequent/open communications with S&MA team members and steak-holders.

46 CFR 308.525 - Application for decrease in amount of cash collateral fund, Form MA-305.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Application for decrease in amount of cash collateral... TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Ii-Open Policy War Risk Cargo Insurance § 308.525 Application for decrease in amount of cash collateral fund, Form MA-305. Application for...

Regulatory Eosinophils Suppress T Cells Partly through Galectin-10.

Science.gov (United States)

Lingblom, Christine; Andersson, Jennie; Andersson, Kerstin; Wennerås, Christine

2017-06-15

Eosinophils have the capacity to regulate the function of T cell subsets. Our aim was to test the hypothesis of the existence of a regulatory subset of eosinophils. Human eosinophils were incubated with T cells that were stimulated with allogeneic leukocytes or CD3/CD28 cross-linking. After 2 d of coculture, 11% of the eosinophils gained CD16 expression. A CD16 hi subset of eosinophils, encompassing 1-5% of all eosinophils, was also identified in the blood of healthy subjects. FACS sorting showed that these CD16 hi eosinophils were significantly stronger suppressors of T cell proliferation than were conventional CD16 neg eosinophils. Human eosinophils contain stores of the immunoregulatory protein galectin-10. We found that Ab-mediated neutralization of galectin-10 partially abrogated the suppressive function of the eosinophils. Moreover, recombinant galectin-10 by itself was able to suppress T cell proliferation. Finally, we detected galectin-10-containing immune synapses between eosinophils and lymphocytes. To conclude, we describe a subset of suppressive eosinophils expressing CD16 that may escape detection because CD16-based negative selection is the standard procedure for the isolation of human eosinophils. Moreover, we show that galectin-10 functions as a T cell-suppressive molecule in eosinophils. Copyright © 2017 by The American Association of Immunologists, Inc.

FİLMLERLE İLETİŞİM VE YABANCILAŞMA

OpenAIRE

ÖZTÜRK, Serdar

2018-01-01

Yabancılaşma konusu genellikle iktisadi, sosyolojik ve psikoloji boyutlarıyla tartışılmıştır. Oysa bir anlam paylaşımı olarak iletişim, yabancılaşmayla doğrudan ilişkilidir. Buna karşın iletişim ile yabancılaşma ilişkisini, analize filmleri de katarak inceleyen çok az çalışma bulunmaktadır. Bu çalışma, yabancılaşma kavramını tartışarak, yabancılaşmanın iletişim ile ilişkisini incelemektedir. Buna göre insanın kendi ürettiği sembollerine, medyanın üretim bölgesinde üretilen sembollere yabancıl...

Suppression of Cpn10 increases mitochondrial fission and dysfunction in neuroblastoma cells.

Directory of Open Access Journals (Sweden)

So Jung Park

Full Text Available To date, several regulatory proteins involved in mitochondrial dynamics have been identified. However, the precise mechanism coordinating these complex processes remains unclear. Mitochondrial chaperones regulate mitochondrial function and structure. Chaperonin 10 (Cpn10 interacts with heat shock protein 60 (HSP60 and functions as a co-chaperone. In this study, we found that down-regulation of Cpn10 highly promoted mitochondrial fragmentation in SK-N-MC and SH-SY5Y neuroblastoma cells. Both genetic and chemical inhibition of Drp1 suppressed the mitochondrial fragmentation induced by Cpn10 reduction. Reactive oxygen species (ROS generation in 3-NP-treated cells was markedly enhanced by Cpn10 knock down. Depletion of Cpn10 synergistically increased cell death in response to 3-NP treatment. Furthermore, inhibition of Drp1 recovered Cpn10-mediated mitochondrial dysfunction in 3-NP-treated cells. Moreover, an ROS scavenger suppressed cell death mediated by Cpn10 knockdown in 3-NP-treated cells. Taken together, these results showed that down-regulation of Cpn10 increased mitochondrial fragmentation and potentiated 3-NP-mediated mitochondrial dysfunction in neuroblastoma cells.

Genetically Modified Lactococcus lactis for Delivery of Human Interleukin-10 to Dendritic Cells

Directory of Open Access Journals (Sweden)

Inge L. Huibregtse

2012-01-01

Full Text Available Interleukin-10 (IL-10 plays an indispensable role in mucosal tolerance by programming dendritic cells (DCs to induce suppressor Th-cells. We have tested the modulating effect of L. lactis secreting human IL-10 (L.  lactisIL-10 on DC function in vitro. Monocyte-derived DC incubated with L.  lactisIL-10 induced effector Th-cells that markedly suppressed the proliferation of allogenic Th-cells as compared to L. lactis. This suppressive effect was only seen when DC showed increased CD83 and CD86 expression. Furthermore, enhanced production of IL-10 was measured in both L.  lactisIL-10-derived DC and Th-cells compared to L. lactis-derived DC and Th-cells. Neutralizing IL-10 during DC-Th-cell interaction and coculturing L.  lactisIL-10-derived suppressor Th-cells with allogenic Th-cells in a transwell system prevented the induction of suppressor Th-cells. Only 130 pg/mL of bacterial-derived IL-10 and 40 times more exogenously added recombinant human IL-10 were needed during DC priming for the generation of suppressor Th-cells. The spatially restricted delivery of IL-10 by food-grade bacteria is a promising strategy to induce suppressor Th-cells in vivo and to treat inflammatory diseases.

File list: Oth.ALL.10.daf-16.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.ALL.10.daf-16.AllCell ce10 TFs and others daf-16 All cell types SRX005634,SRX00...5631 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Oth.ALL.10.daf-16.AllCell.bed ...

Possible fetal determinants of male infertility

DEFF Research Database (Denmark)

Juul, Anders; Almstrup, Kristian; Andersson, Anna-Maria

2014-01-01

with regard to testicular cancer, levels of testosterone and semen quality, but also from histopathological observations. Many infertile men have histological signs of testicular dysgenesis, including Sertoli-cell-only tubules, immature undifferentiated Sertoli cells, microliths and Leydig cell nodules...

Orf virus IL-10 reduces monocyte, dendritic cell and mast cell recruitment to inflamed skin.

Science.gov (United States)

Bennett, Jared R; Lateef, Zabeen; Fleming, Stephen B; Mercer, Andrew A; Wise, Lyn M

2016-02-02

Orf virus (ORFV) is a zoonotic parapoxvirus that causes pustular dermatitis of sheep, and occasionally humans. Despite causing sustained infections, ORFV induces only a transient increase in pro-inflammatory signalling and the trafficking of innate immune cells within the skin seems to be impaired. An explanation for this tempered response to ORFV infection may lie in its expression of a homolog of the anti-inflammatory cytokine, interleukin (IL)-10. Using a murine model in which inflammation was induced by bacterial lipopolysaccharide, we examined the effects of the ORFV-IL-10 protein on immune cell trafficking to and from the skin. ORFV-IL-10 limited the recruitment of blood-derived Gr-1(int)/CD11b(int) monocytes, CD11c(+ve)/MHC-II(+ve) dendritic cells and c-kit(+ve)/FcεR1(+ve) mature mast cells into inflamed skin. ORFV-IL-10 also suppressed the activation of CD11c(+ve)/MHC-II(+ve) dendritic cells within the skin, reducing their trafficking to the draining lymph node. These findings suggest that expression of IL-10 by ORFV may contribute to the impaired trafficking of innate immune cells within infected skin. Copyright © 2015 Elsevier B.V. All rights reserved.

Structure of Oxide Nanoparticles in Fe-16Cr MA/ODS Ferritic Steel

Energy Technology Data Exchange (ETDEWEB)

Hsiung, L; Fluss, M; Kimura, A

2010-04-06

Oxide nanoparticles in Fe-16Cr ODS ferritic steel fabricated by mechanical alloying (MA) method have been examined using high-resolution transmission electron microscopy (HRTEM) techniques. A partial crystallization of oxide nanoparticles was frequently observed in as-fabricated ODS steel. The crystal structure of crystalline oxide particles is identified to be mainly Y{sub 4}Al{sub 2}O{sub 9} (YAM) with a monoclinic structure. Large nanoparticles with a diameter larger than 20 nm tend to be incoherent and have a nearly spherical shape, whereas small nanoparticles with a diameter smaller than 10 nm tend to be coherent or semi-coherent and have faceted boundaries. The oxide nanoparticles become fully crystallized after prolonged annealing at 900 C. These results lead us to propose a three-stage formation mechanism of oxide nanoparticles in MA/ODS steels.