Search

Hypoxic signaling is a central modulator of cellular physiology in cancer. Core members of oxygen-sensing pathway including the von Hippel-Lindau tumor suppressor protein (pVHL) and the hypoxia inducible factor (HIF) transcription factors have been intensively studied, but improved organismal models might speed advances for both pathobiologic understanding and therapeutic modulation. To study HIF signaling during tumorigenesis and development in zebrafish, we developed a unique in vivo reporter for hypoxia, expressing EGFP driven by prolyl hydroxylase 3 (phd3) promoter/regulatory elements. Modulation of HIF pathway in Tg(phd3::EGFP) embryos showed a specific role for hypoxic signaling in the transgene activation. Zebrafish vhl mutants display a systemic hypoxia response, reflected by strong and ubiquitous transgene expression. In contrast to human VHL patients, heterozygous Vhl mice and vhl zebrafish are not predisposed to cancer. However, upon exposure to dimethylbenzanthracene (DMBA), the vhl heterozygous fish showed an increase in the occurrence of hepatic and intestinal tumors, a subset of which exhibited strong transgene expression, suggesting loss of Vhl function in these tumor cells. Compared with control fish, DMBA-treated vhl heterozygous fish also showed an increase in proliferating cell nuclear antigen-positive renal tubules. Taken together, our findings establish Vhl as a genuine tumor suppressor in zebrafish and offer this model as a tool to noninvasively study VHL and HIF signaling during tumorigenesis and development. Cancer Res; 72(16); 4017–27. ©2012 AACR.

PDF file - 817K, Figure S1 shows in vivo expression of phd3::EGFP in wild-type and vhl-/- Figure S2 shows that phd3::EGFP mRNA expression recapitulates endogenous phd3 expression. Figure S3 shows that EGFP expression in phd3::EGFP embryos is Hif dependent. Figure S4 shows that EGFP expression in phd3::EGFP embryos can be activated by inhibitors of PHD hydroxylases. Figure S5 shows the half life of the fluorescence of the phd3::EGFP line. Figure S6 shows that the phd3::EGFP transgene acts as an in vivo marker for detecting LOH events at the vhl locus in vhl+/- fish. Figure S7 shows morphology of gonadal tumors after DMBA treatment. Figure S8 shows the sequence analysis of the vhl locus in dissected tumors. Figure S9 shows that vhl mRNA levels are decreased in EGFP+ tumors in vhl+/- fish.

PDF file - 438K

PDF file - 56K, Table S1, shows relative increase in EGFP fluorescence levels of phd3: EGFP in vhl-/- embryos vs wild-type. Table S2 shows the effect of DMBA treatment on the rates of LOH for the vhl locus in 2.5 month old wild-type and vhl+/- fish. Table S3 shows the increased number of macroscopic phd3: GFP positive areas induced by DMBA vhl-/+ adults as compared to wild-type, they are likely to correspond to vhl-/- tumors. Table S4 shows preferential induction of renal tubule proliferation in vhl heterozygotes.

The Australian federal government will soon release voluntary sodium reduction targets for 30 packaged food categories through the Healthy Food Partnership. Previous assessments of voluntary targets show variable industry engagement, and little is known about the extent that major food companies and their products contribute to dietary sodium purchases among Australian households.The aim of this cross-sectional study was to identify the relative contribution that food companies and their products made to Australian household sodium purchases in 2018, and to examine differences in sodium purchases by household income level. We used 1 year of grocery purchase data from a nationally representative consumer panel of Australian households who reported their grocery purchases (the Nielsen Homescan panel), combined with database that contains product-specific sodium content for packaged foods and beverages (FoodSwitch). The top food companies and food categories were ranked according to their contribution to household sodium purchases. Differences in per capita sodium purchases by income levels were assessed by 1-factor ANOVA. All analyses were modelled to the Australian population in 2018 using sample weights.Sodium data were available from 7188 households who purchased 26,728 unique products and purchased just under 7.5 million food product units. Out of 1329 food companies, the top 10 accounted for 35% of unique products and contributed to 58% of all sodium purchased from packaged foods and beverages. The top three companies were grocery food retailers each contributing 12-15% of sodium purchases from sales of their private label products, particularly processed meat, cheese and bread. Out of the 67 food categories, the top 10 accounted for 73% of sodium purchased, particularly driven by purchases of processed meat (14%), bread (12%) and sauces (11%). Low-income Australian households purchased significantly more sodium from packaged products than high-income households per capita (452 mg/d, 95%CI: 363-540 mg/d, P 0.001).A small number of food companies and food categories account for most of the dietary sodium purchased by Australian households. Prioritizing government engagement with these groups could deliver a large reduction in population sodium intake.

Background: The Australian federal government will soon release voluntary sodium reduction targets for 30 packaged food categories through the Healthy Food Partnership. Previous assessments of voluntary targets show variable industry engagement, and little is known about the extent that major food companies and their products contribute to dietary sodium purchases among Australian households. Methods: The aim of this cross-sectional study was to identify the relative contribution that food companies and their products made to Australian household sodium purchases in 2018, and to examine differences in sodium purchases by household income level. We used 1 year of grocery purchase data from a nationally representative consumer panel of Australian households who reported their grocery purchases (the Nielsen Homescan panel), combined with database that contains product-specific sodium content for packaged foods and beverages (FoodSwitch). The top food companies and food categories were ranked according to their contribution to household sodium purchases. Differences in per capita sodium purchases by income levels were assessed by 1-factor ANOVA. All analyses were modelled to the Australian population in 2018 using sample weights. Results: Sodium data were available from 7188 households who purchased 26,728 unique products and purchased just under 7.5 million food product units. Out of 1329 food companies, the top 10 accounted for 35% of unique products and contributed to 58% of all sodium purchased from packaged foods and beverages. The top three companies were grocery food retailers each contributing 12-15% of sodium purchases from sales of their private label products, particularly processed meat, cheese and bread. Out of the 67 food categories, the top 10 accounted for 73% of sodium purchased, particularly driven by purchases of processed meat (14%), bread (12%) and sauces (11%). Low-income Australian households purchased significantly more sodium from packaged products than high-income households per capita (452 mg/d, 95%CI: 363-540 mg/d, P Correction to: Int J Behav Nutr Phys Act 17, 81 (2020) https://doi.org/10.1186/s12966-020-00982-z Following publication of the original article [1], the authors identified errors in Table 2 and Table 3.ACorrection to this article was published on 04 December 2020. The Original Article was published on 23 June 2020. The original article [1] has been corrected.

This stopwatch session provided an update on the first year's implementation of the TOME (Toward an Open Monograph Ecosystem) initiative, a collaboration of the Association of American Universities, the Association of Research Libraries, and the Association of University Presses. The initiative is a five-year experiment in an institutional funding model for open access monographs.

Background Lateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour. Methods LFDs were initially reviewed by a Department of Health and Social Care team, part of the UK government, from which 64 were selected for further evaluation from 1st August to 15th December 2020. Standardised laboratory evaluations, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots were performed (UK COVID-19 testing centres, hospital, schools, armed forces). Findings 4/64 LFDs so far have desirable performance characteristics (orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1–6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20–0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists was 78.8% (156/198, 95% CI 72.4–84.3). Interpretation Our results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission. Funding Department of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research.

Hypoxic signaling is a central modulator of cellular physiology in cancer. Core members of oxygen-sensing pathway including the von Hippel-Lindau tumor suppressor protein (pVHL) and the hypoxia inducible factor (HIF) transcription factors have been intensively studied, but improved organismal models might speed advances for both pathobiologic understanding and therapeutic modulation. To study HIF signaling during tumorigenesis and development in zebrafish, we developed a unique in vivo reporter for hypoxia, expressing EGFP driven by prolyl hydroxylase 3 (phd3) promoter/regulatory elements. Modulation of HIF pathway in Tg(phd3::EGFP) embryos showed a specific role for hypoxic signaling in the transgene activation. Zebrafish vhl mutants display a systemic hypoxia response, reflected by strong and ubiquitous transgene expression. In contrast to human VHL patients, heterozygous Vhl mice and vhl zebrafish are not predisposed to cancer. However, upon exposure to dimethylbenzanthracene (DMBA), the vhl heterozygous fish showed an increase in the occurrence of hepatic and intestinal tumors, a subset of which exhibited strong transgene expression, suggesting loss of Vhl function in these tumor cells. Compared with control fish, DMBA-treated vhl heterozygous fish also showed an increase in proliferating cell nuclear antigen-positive renal tubules. Taken together, our findings establish Vhl as a genuine tumor suppressor in zebrafish and offer this model as a tool to noninvasively study VHL and HIF signaling during tumorigenesis and development. Cancer Res; 72(16); 4017–27. ©2012 AACR.