The expression of the ubiquitin ligase SIAH2 (seven in absentia homolog 2) is mediated through gene copy number in breast cancer and is associated with a basal-like phenotype and p53 expression

Introduction: The seven in absentia homolog 2 (SIAH2) protein plays a significant role in the hypoxic response by regulating the abundance of hypoxia-inducible factor-α; however, its role in breast carcinoma is unclear. We investigated the frequency and expression pattern of SIAH2 in two independent cohorts of sporadic breast cancers.Methods: Immunohistochemical evaluation of SIAH2protein expression was conducted in normal breast tissues and in tissue microarrays comprising ductal carcinoma in situ (DCIS) and a cohort of invasive breast carcinomas. Correlation analysis was performed between SIAH2 and clinicopathological variables and intrinsic breast cancer subgroups and validated in a cohort of 293 invasive ductal carcinomas. Promoter methylation, gene copy number and mRNA expression of SIAH2 were determined in a panel of basal-like tumors and cell lines.Results: There was a significant increase in nuclear SIAH2 expression from normal breast tissues through to DCIS and progression to invasive cancers. A significant inverse correlation was apparent between SIAH2 and estrogen receptor and progesterone receptor and a positive association with tumor grade, HER2, p53 and an intrinsic basal-like subtype. Logistic regression analysis confirmed the significant positive association between SIAH2 expression and the basal-like phenotype. No SIAH2 promoter methylation was identified, yet there was a significant correlation between SIAH2 mRNA and gene copy number. SIAH2-positive tumors were associated with a shorter relapse-free survival in univariate but not multivariate analysis.Conclusions: SIAH2 expression is upregulated in basal-like breast cancers via copy number changes and/or transcriptional activation by p53 and is likely to be partly responsible for the enhanced hypoxic drive through abrogation of the prolyl hydroxylases

Eating in the absence of hunger in adolescents: intake after a large-array meal compared with that after a standardized meal123

Background: Eating in the absence of hunger (EAH) is typically assessed by measuring youths’ intake of palatable snack foods after a standard meal designed to reduce hunger. Because energy intake required to reach satiety varies among individuals, a standard meal may not ensure the absence of hunger among participants of all weight strata

FLUXNET-CH4: A global, multi-ecosystem dataset and analysis

Methane (CH4) emissions from natural landscapes constitute roughly half of global CH4 contributions to the atmosphere, yet large uncertainties remain in the absolute magnitude and the seasonality of emission quantities and drivers. Eddy covariance (EC) measurements of CH4 flux are ideal for constraining ecosystem-scale CH4 emissions, including their seasonality, due to quasi-continuous and high temporal resolution of flux measurements, coincident measurements of carbon, water, and energy fluxes, lack of ecosystem disturbance, and increased availability of datasets over the last decade. Here, we 1) describe the newly published dataset, FLUXNET-CH4 Version 1.0, the first global dataset of CH4 EC measurements (available at https://fluxnet.org/data/fluxnet-ch4- community-product/). FLUXNET-CH4 includes half-hourly and daily gap-filled and non gap-filled aggregated CH4 fluxes and meteorological data from 79 sites globally: 42 freshwater wetlands, 6 brackish and saline wetlands, 7 formerly drained ecosystems, 7 rice paddy sites, 2 lakes, and 15 uplands. Then, we 2) evaluate FLUXNET-CH4 representativeness for freshwater wetland coverage globally, because the majority of sites in FLUXNET-CH4 Version 1.0 are freshwater wetlands and because freshwater wetlands are a substantial source of total atmospheric CH4 emissions; and 3) provide the first global estimates of the seasonal variability and seasonality predictors of freshwater wetland CH4 fluxes. Our representativeness analysis suggests that the freshwater wetland sites in the dataset cover global wetland bioclimatic attributes (encompassing energy, moisture, and vegetation-related parameters) in arctic, boreal, and temperate regions, but only sparsely cover humid tropical regions. Seasonality metrics of wetland CH4 emissions vary considerably across latitudinal bands. In freshwater wetlands (except those between 20° S to 20° N) the spring onset of elevated CH4 emissions starts three days earlier, and the CH4 emission season lasts 4 days longer, for each degree C increase in mean annual air temperature. On average, the onset of increasing CH4 emissions lags soil warming by one month, with very few sites experiencing increased CH4 emissions prior to the onset of soil warming. In contrast, roughly half of these sites experience the spring onset of rising CH4 emissions prior to the spring increase in gross primary productivity (GPP). The timing of peak summer CH4 emissions does not correlate with the timing for either peak summer temperature or peak GPP. Our results provide seasonality parameters for CH4 modeling, and highlight seasonality metrics that cannot be predicted by temperature or GPP (i.e., seasonality of CH4 peak). The FLUXNET-CH4 dataset provides an open-access resource for CH4 flux synthesis, has a range of applications, and is unique in that it includes coupled measurements of important CH4 drivers such as GPP and temperature. Although FLUXNET-CH4 could certainly be improved by adding more sites in tropical ecosystems and by increasing the number of site-years at existing sites, it is a powerful new resource for diagnosing and understanding the role of terrestrial ecosystems and climate drivers in the global CH4 cycle. All seasonality parameters are available at https://doi.org/10.5281/zenodo.4408468. Additionally, raw FLUXNET-CH4 data used to extract seasonality parameters can be downloaded from https://fluxnet.org/data/fluxnet-ch4-community-product/, and a complete list of the 79 individual site data DOIs is provided in Table 2 in the Data Availability section of this document.ISSN:1866-359