Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an essential regulator of DNA methylation that is highly expressed in many cancers. Here, we use transgenic zebrafish, cultured cells, and ...human tumors to demonstrate that UHRF1 is an oncogene. UHRF1 overexpression in zebrafish hepatocytes destabilizes and delocalizes Dnmt1 and causes DNA hypomethylation and Tp53-mediated senescence. Hepatocellular carcinoma (HCC) emerges when senescence is bypassed. tp53 mutation both alleviates senescence and accelerates tumor onset. Human HCCs recapitulate this paradigm, as UHRF1 overexpression defines a subclass of aggressive HCCs characterized by genomic instability, TP53 mutation, and abrogation of the TP53-mediated senescence program. We propose that UHRF1 overexpression is a mechanism underlying DNA hypomethylation in cancer cells and that senescence is a primary means of restricting tumorigenesis due to epigenetic disruption.
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•UHRF1 overexpression induces DNA hypomethylation•Liver-specific overexpression of UHRF1 in zebrafish causes senescence and HCC•Human HCCs with high UHRF1 are aggressive and inactivate TP53-mediated senescence•Our studies in zebrafish and human tumors identify UHRF1 as an oncogene in HCC
Mudbhary et al. show that overexpression of UHRF1, a critical DNA methylation regulator, in zebrafish causes DNA hypomethylation, p53-mediated senescence, and hepatocellular carcinoma (HCC) when senescence is bypassed. High UHRF1 expression in human HCC correlates with poor prognosis and TP53 mutation.
The Coping Strategies Questionnaire (CSQ), a measure of coping in chronic pain patients, was subjected to item-level exploratory factor analysis.
A sample of 965 chronic pain patients were used in ...the analysis.
Principal components analysis using a varimax rotation procedure identified nine factors that accounted for 54.5% of the variance. Of these nine factors, the first five represent subscales of the original CSQ subscales. The catastrophizing subscale replicated with significant loadings for all six original items, and ignoring sensations replicated with five of six items. Factors representing reinterpreting pain sensations, coping self-statements, and diverting attention subscales also appeared. The items from the praying and hoping subscale split into separate praying and hoping factors (factors 6 and 8). When reliability coefficients were calculated, factors 7 through 9 had unacceptably low internal consistency and thus were not considered stable factors. Correlations between factors 1 through 6 and other measures of psychological and physical functioning were calculated in the construct validation portion of this study. Previously found relationships were replicated in that the correlations between CSQ factor scores and measures of pain, depression, and disability were in the same direction in this data set as those previously reported.
Background
Infants born small for gestational age (SGA) by customised birthweight centiles are at increased risk of adverse outcomes compared with those SGA by population centiles. Risk factors for ...customised SGA have not previously been described in a general obstetric population.
Aim
To determine independent risk factors for customised SGA in a multi‐ethnic New Zealand population.
Methods
We performed a retrospective cohort analysis of prospectively recorded maternity data from 2006 to 2009 at National Women's Health, Auckland, New Zealand. After exclusion of infants with congenital anomalies and missing data, our final study population was 26,254 singleton pregnancies. Multivariable logistic regression analysis adjusted for ethnicity, body mass index, maternal age, parity, smoking status, social deprivation, hypertensive disease, antepartum haemorrhage (APH), diabetes and relevant pre‐existing medical conditions.
Results
Independent risk factors for SGA included obesity (adjusted odds ratio 1.24 95% CI 1.11–1.39 relative to normal weight), maternal age ≥ 35 years (1.16 1.05–1.30 relative to 20–29 years), nulliparity (1.13 1.04–1.24 relative to parity 1), cigarette smoking (2.01 1.79–2.27), gestational hypertension (1.46 1.21–1.75), pre‐eclampsia (2.94 2.49–3.48), chronic hypertension (1.68 1.34–2.09), placental abruption (2.57 1.74–3.78) and APH of unknown origin (1.71 1.45–2.00). Gestational diabetes (0.80 0.67–0.96) and type 1 diabetes (0.26 0.11–0.64) were associated with reduced risk.
Conclusions
We report independent pregnancy risk factors for customised SGA in a general obstetric population. In contrast to population SGA, obesity is associated with increased risk. Our findings may help identify pregnancies that require increased fetal growth surveillance.
Background
Pre‐eclampsia rates are reported to vary by ethnicity; however, few studies include body mass index (BMI). Increasing BMI has a dose‐dependent relationship with pre‐eclampsia, and rates of ...overweight and obesity as well as ratios of body fat to muscle mass differ between ethnicities. We hypothesised that after adjusting for confounders, including ethnic‐specific BMI, ethnicity would not be an independent risk factor for pre‐eclampsia.
Aim
To assess independent pre‐eclampsia risk factors in a multiethnic New Zealand population.
Methods
We performed a retrospective cohort analysis of prospectively recorded maternity data from 2006 to 2009 at National Women's Health, Auckland, New Zealand. After exclusion of infants with congenital anomalies and missing data, our final study population was 26 254 singleton pregnancies. Multivariable logistic regression analysis adjusted for ethnicity, BMI, maternal age, parity, smoking, social deprivation, diabetes, chronic hypertension and relevant pre‐existing medical conditions was performed.
Results
Independent associations with pre‐eclampsia were observed in Chinese (adjusted odds ratio (aOR) 0.56, 95% CI 0.41–0.76) and Māori (aOR 1.51, 1.16–1.96) compared with European women. Other independent risk factors for pre‐eclampsia were overweight and obesity, nulliparity, type 1 diabetes, chronic hypertension and pre‐existing medical conditions.
Conclusions
Contrary to our hypothesis, we report an independent reduced risk of pre‐eclampsia in Chinese and increased risk of pre‐eclampsia in Māori women. Prospective studies are required to further explore these relationships. Other independent risk factors are consistent with international literature. Our findings may assist clinicians to stratify risk of pre‐eclampsia in clinical practice.
Ammonia (NH3) volatilization is an undesirable mechanism for the removal of nitrogen (N) from wastewater treatment wetlands. To minimize the potential for NH3 volatilization, it is important to ...determine how wetland design affects NH3 volatilization. The objective of this research was to determine how the presence of a pond section affects NH3 volatilization from constructed wetlands treating wastewater from a confined swine operation. Wastewater was added at different N loads to six constructed wetlands of the marsh-pond-marsh design that were located in Greensboro, North Carolina, USA. A large enclosure was used to measure NH3 volatilization from the marsh and pond sections of each wetland in July and August of 2001. Ammonia volatilized from marsh and pond sections at rates ranging from 5 to 102 mg NH3-N m(-2) h(-1). Pond sections exhibited a significantly greater increase in the rate of NH3 volatilization (p < 0.0001) than did either marsh section as N load increased. At N loads greater than 15 kg ha(-1) d(-1), NH3 volatilization accounted for 23 to 36% of the N load. Furthermore, NH3 volatilization was the dominant (54-79%) N removal mechanism at N loads greater than 15 kg ha(-1) d(-1). Without the pond sections, NH3 volatilization would have been a minor contributor (less than 12%) to the N balance of these wetlands. To minimize NH3 volatilization, continuous marsh systems should be preferred over marsh-pond-marsh systems for the treatment of wastewater from confined animal operations.
We have assembled an 8.4 GHz survey of bright, flat-spectrum ( unk > -0.5) radio sources with nearly uniform extragalactic (|b| > 10 degree ) coverage for sources brighter than S 4.8GHz = 65 mJy. The ...catalog is assembled from existing observations (especially CLASS and the Wright et al. PMN-CA survey), augmented by reprocessing of archival VLA and ATCA data and by new observations to fill in coverage gaps. We refer to this program as CRATES, the Combined Radio All-Sky Targeted Eight GHz Survey. The resulting catalog provides precise positions, subarcsecond structures, and spectral indices for some 11,000 sources. We describe the morphology and spectral index distribution of the sample and comment on the survey's power to select several classes of interesting sources, especially high-energy blazars. Comparison of CRATES with other high-frequency surveys also provides unique opportunities for identification of high-power radio sources.
Interactions between galaxies are common, and influence physical properties such as the global morphology and star-formation rate (Hubble type). Galaxies can interact in many different ways: they can ...merge together; they can pass through each other, with gas being stripped from the smaller of the two and compressed in the larger; and they can interact gravitationally (including, for example, tides in clusters). The relative importance of these mechanisms is often not clear, as the strength of each depends on poorly known parameters such as the density, extent and nature of the dark-matter haloes that surround galaxies. A nearby example of a galaxy interaction where the mechanism is controversial is that between our Galaxy and two of its neighbours, the Magellanic Clouds. Here we present the results of an atomic-hydrogen survey that help to elucidate this mechanism. Our data reveal a new stream of gas that lies in the opposite direction to the trailing Magellanic Stream and leads the motion of the Clouds. The existence of both leading and trailing streams supports a gravitational interaction whereby the streams are torn from the bodies of the Magellanic Clouds by tidal forces.
The H i Parkes All Sky Survey (HIPASS) is a blind extragalactic H i 21-cm emission-line survey covering the whole southern sky from declination −90° to +25°. The HIPASS catalogue (HICAT), containing ...4315 H i-selected galaxies from the region south of declination +2°, is presented in Meyer et al. (Paper I). This paper describes in detail the completeness and reliability of HICAT, which are calculated from the recovery rate of synthetic sources and follow-up observations, respectively. HICAT is found to be 99 per cent complete at a peak flux of 84 mJy and an integrated flux of 9.4 Jy km s −1. The overall reliability is 95 per cent, but rises to 99 per cent for sources with peak fluxes >58 mJy or integrated flux >8.2 Jy km s −1. Expressions are derived for the uncertainties on the most important HICAT parameters: peak flux, integrated flux, velocity width and recessional velocity. The errors on HICAT parameters are dominated by the noise in the HIPASS data, rather than by the parametrization procedure.
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