384 research outputs found

    Circulating sex steroids during pregnancy and maternal risk of non-epithelial ovarian cancer.

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    BACKGROUND: Sex steroid hormones have been proposed to play a role in the development of non-epithelial ovarian cancers (NEOC) but so far no direct epidemiological data are available.METHODS: A case-control study was nested within the Finnish Maternity Cohort, the world's largest bio-repository of serum specimens from pregnant women. Study subjects were selected among women who donated a blood sample during a singleton pregnancy that led to the birth of their last child preceding diagnosis of NEOC. Case subjects were 41 women with sex-cord stromal tumors (SCST) and 21 with germ cell tumors (GCT). Three controls, matching the index case for age, parity at the index pregnancy, and date at blood donation were selected (n=171). Odds ratios (OR) and 95% confidence intervals (CI) associated with concentrations of testosterone, androstenedione, 17-OH-progesterone, progesterone, estradiol and sex hormone binding globulin (SHBG) were estimated through conditional logistic regression.RESULTS: For SCST, doubling of testosterone, androstenedione and 17-OH-progesterone concentrations were associated with about 2-fold higher risk of SCST [ORs and 95% CI of 2.16 (1.25-3.74), 2.16 (1.20-3.87), and 2.62 (1.27-5.38), respectively]. These associations remained largely unchanged after excluding women within 2, 4 or 6 years lag-time between blood donation and cancer diagnosis. Sex steroid hormones concentrations were not related to maternal risk of GCT.CONCLUSIONS: This is the first prospective study providing initial evidence that elevated androgens play a role in the pathogenesis of SCST. Impact: Our study may note a particular need for larger confirmatory investigations on sex steroids and NEOC

    Effects of the whole vine versus single shoot-crop level on fruit growth in Vitis labruscana 'Concord'

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    The fruit growth response to the whole vine and single shoot crop level was studied in Vitis labruscana 'Concord' grown in the North-Eastern United States. In vines thinned to lower and higher yields (equivalent to 12 and 21 t·ha-1), different number of clusters per shoot were retained after cluster thinning one week after set. Results showed that the seasonal accumulation of berry dry weight, fruit fresh weight, and the berry total soluble solids at harvest were only affected by the whole vine crop level. This suggests that under the conditions of this experiment shoots are not autonomous in terms of carbon partitioning to the fruit. Hence, crop level effects on fruit development can be considered and modelled on a whole vine basis.

    Targeted Deletion of the Metastasis-Associated Phosphatase Ptp4a3 (PRL-3) Suppresses Murine Colon Cancer

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    Ptp4a3 (commonly known as PRL-3) is an enigmatic member of the Ptp4a family of prenylated protein tyrosine phosphatases that are highly expressed in many human cancers. Despite strong correlations with tumor metastasis and poor patient prognosis, there is very limited understanding of this gene family's role in malignancy. Therefore, we created a gene-targeted murine knockout model for Ptp4a3, the most widely studied Ptp4a family member. Mice deficient for Ptp4a3 were grossly normal. Fewer homozygous-null males were observed at weaning, however, and they maintained a decreased body mass. Although Ptp4a3 is normally associated with late-stage cancer and metastasis, we observed increased Ptp4a3 expression in the colon of wildtype mice immediately following treatment with the carcinogen azoxymethane. To investigate the role of Ptp4a3 in malignancy, we used the most commonly studied murine colitis-associated colon cancer model. Wildtype mice treated with azoxymethane and dextran sodium sulfate developed approximately 7-10 tumors per mouse in the distal colon. The resulting tumor tissue had 4-fold more Ptp4a3 mRNA relative to normal colon epithelium and increased PTP4A3 protein. Ptp4a3-null mice developed 50% fewer colon tumors than wildtype mice after exposure to azoxymethane and dextran sodium sulfate. Tumors from the Ptp4a3-null mice had elevated levels of both IGF1Rβ and c-MYC compared to tumors replete with Ptp4a3, suggesting an enhanced cell signaling pathway engagement in the absence of the phosphatase. These results provide the first definitive evidence implicating Ptp4a3 in colon tumorigenesis and highlight the potential value of the phosphatase as a therapeutic target for early stage malignant disease. © 2013 Zimmerman et al

    Laser scanning estimation of relative light interception by canopy components in different grapevine training systems

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    The fractional light interception by different parts of vines trained to various systems was estimated by a modified point-quadrat method using an over-row solar are positioning device equipped with a laser to simulate sunbeam position and angle at any latitude and time of the day. Laser readings were also combined with total vine light interception estimates via a line sensor to calculate the total light intercepted by specific canopy components. At each sampling date (late June and September, corresponding to fruit set and full canopy), type and position of organs were directly detected by the laser beam. Regardless of sampling date, the relative amount of light captured by the renewal-fruiting area (nodes 1 to 6) of simple cordon (SC) and double curtain (GDC) was considerably higher than that of spur-pruned cordon (SPC), whose vegetative area (distal to node 6) received about two-thirds of the incoming light. Relative light interception by main and lateral leaves was rather constant for GDC, thus reflecting the negligible regrowth after topping. By contrast, SC and SPC showed a much stronger response to topping which caused an increase of light interception by laterals (19 % for SC and +21 % for SPC). Frequencies of relative intercepted light by main leaves as a function of node position showed a peak around nodes 6-8, a zone where maximum leaf size is attained in all systems and on all dates. Instead, lateral leaves predominantly exposed to light were within the three basal nodes of the lateral shoots. Estimates of relative and total light for different vine parts at any time during the season as detected by laser scanning can objectively assess important characteristics of grapevine training systems, e.g. cluster and basal node exposure to light

    The effects of pre- and post-veraison water stress on growth and physiology of potted Pinot Noir grapevines at varying crop levels

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    The interactions of water stress timing and crop level on growth, gas exchange, water relations and ripening of potted Pinot Noir grapevines were examined. Pre-veraison water stress induced a greater reduction of shoot and berry growth and a more rapid limitation of net photosynthesis (Pn) and stomatal conductance (g(s)) as compared to post-veraison stress. At the end of stress, when mid-day and pre-dawn leaf water potential were below -1.1 and -0.6 MPa, the reduction in Pn of stressed vines was more marked in the 2- and 4-cluster plants versus 1-cluster plant. Crop level had almost no significant effects on gas-exchange, growth and ripening and but few interactions with timing of water stress. These responses seem to reflect the high leaf area-to-fruit ratios at each crop level which probably buffered the effects of reduced leaf function induced by water stress

    The interaction of phylloxera infection, rootstock, and irrigation on young Concord grapevine growth

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    Concord roots are moderately resistant to phylloxera, which form nodosities on the fine roots and weaken the root system. Rootstocks and vineyard floor management both have the potential to eliminate or reduce the effect of phylloxera in New York Concord vineyards. Young, container-grown Concord grapevines were used to evaluate the interaction between rootstock (own-rooted, Couderc 3309), irrigation, and phylloxera infection on vine growth. Phylloxera inoculation alone caused a 21 % decrease in vine dry mass and lack of irrigation (mid-day stem water potential: -0.9 to -1.0 M Pa) alone caused a 34 % decrease in vine dry mass. The combination of phylloxera stress and water stress was additive and caused a 54 % decrease in vine dry mass. Because C3309 rootstock is resistant to phylloxera, the grafted vines showed a response to irrigation but not phylloxera inoculation. This container study shows the potential benefits of irrigating own-rooted Concord grapevines or the use of rootstocks without irrigation to withstand phylloxera infection.

    Alterations in ethanol-induced behaviors and consumption in knock-in mice expressing ethanol-resistant NMDA receptors

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    Ethanol's action on the brain likely reflects altered function of key ion channels such as glutamatergic N-methyl-D-aspartate receptors (NMDARs). In this study, we determined how expression of a mutant GluN1 subunit (F639A) that reduces ethanol inhibition of NMDARs affects ethanol-induced behaviors in mice. Mice homozygous for the F639A allele died prematurely while heterozygous knock-in mice grew and bred normally. Ethanol (44 mM; ∼0.2 g/dl) significantly inhibited NMDA-mediated EPSCs in wild-type mice but had little effect on responses in knock-in mice. Knock-in mice had normal expression of GluN1 and GluN2B protein across different brain regions and a small reduction in levels of GluN2A in medial prefrontal cortex. Ethanol (0.75-2.0 g/kg; IP) increased locomotor activity in wild-type mice but had no effect on knock-in mice while MK-801 enhanced activity to the same extent in both groups. Ethanol (2.0 g/kg) reduced rotarod performance equally in both groups but knock-in mice recovered faster following a higher dose (2.5 g/kg). In the elevated zero maze, knock-in mice had a blunted anxiolytic response to ethanol (1.25 g/kg) as compared to wild-type animals. No differences were noted between wild-type and knock-in mice for ethanol-induced loss of righting reflex, sleep time, hypothermia or ethanol metabolism. Knock-in mice consumed less ethanol than wild-type mice during daily limited-access sessions but drank more in an intermittent 24 h access paradigm with no change in taste reactivity or conditioned taste aversion. Overall, these data support the hypothesis that NMDA receptors are important in regulating a specific constellation of effects following exposure to ethanol. © 2013 den Hartog et al

    Using C. elegans to discover therapeutic compounds for ageing-associated neurodegenerative diseases

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    Age-associated neurodegenerative disorders such as Alzheimer’s disease are a major public health challenge, due to the demographic increase in the proportion of older individuals in society. However, the relatively few currently approved drugs for these conditions provide only symptomatic relief. A major goal of neurodegeneration research is therefore to identify potential new therapeutic compounds that can slow or even reverse disease progression, either by impacting directly on the neurodegenerative process or by activating endogenous physiological neuroprotective mechanisms that decline with ageing. This requires model systems that can recapitulate key features of human neurodegenerative diseases that are also amenable to compound screening approaches. Mammalian models are very powerful, but are prohibitively expensive for high-throughput drug screens. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for neuroprotective compound screening. Here we describe how C. elegans has been used to model various human ageing-associated neurodegenerative diseases and provide an extensive list of compounds that have therapeutic activity in these worm models and so may have translational potential

    Relation of carbohydrate reserves with the forthcoming crop, flower formation and photosynthetic rate, in the alternate bearing Salustiana sweet orange (Citrus sinensis L.)

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    [EN] The aim of this work was to assess the relation between carbohydrate levels and flower and fruit production, as well as the role of carbohydrates on CO(2) fixation activity, by analysis of leaves, twigs and roots from the alternate bearing 'Salustiana' cultivar of sweet orange (Citrus sinensis [L.] Osbeck). A heavy crop load (on year) did not affect photosynthesis activity when compared to non-fruiting trees (off year). Fruiting trees accumulated most of the fixed carbon in mature fruits, whilst no accumulation was observed in roots before harvest. Non-fruiting trees transported part of the fixed carbon to the roots and mobilize it for growth processes and, at the end of the season (December), store it as reserves. Reserve carbohydrates accumulation in leaves started by early December for both tree types, showing the same levels in on and off trees until spring bud sprouting. A heavy flowering after an off year caused the rapid mobilization of the stored reserves, which were exhausted at full bloom. We found no evidence on carbon fixation regulation by either fruit demand or carbohydrate levels in leaves. Carbohydrate reserves played little or no role over fruit set, which actually relied on current photosynthesisWe thank Ing. Agr. J.M. Torres (ANECOOP, Valencia, Spain) for providing the orchard facilities and logistic help, the R + D + i Linguistic Assistance Office at the Universidad Politecnica de Valencia for their help in revising this article and Y. Bordon for her cooperation in some experiments. Thanks are due also to Dr. Olivares for the critical review of the manuscript. This research was funded by grants from the Conselleria de Agricultura, Pesca y Alimentacion (GV-CAPA00-11) and the Conselleria diEmpresa, Universitat i Ciencia, Generalitat Valenciana (Grupos 04/059).Monerri Huguet, MC.; Fortunato De Almeida, A.; Molina Romero, RV.; González Nebauer, S.; García Luís, MD.; Guardiola Barcena, JL. (2011). Relation of carbohydrate reserves with the forthcoming crop, flower formation and photosynthetic rate, in the alternate bearing Salustiana sweet orange (Citrus sinensis L.). Scientia Horticulturae. 129(1):71-78. https://doi.org/10.1016/j.scienta.2011.03.009S7178129
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