Aberrant pregnancy-associated plasma protein-A expression in breast cancers prognosticates clinical outcomes
- Authors: Prithviraj, Prashanth , Anaka, Matthew , Thompson, Erik , Sharma, Revati , Walkiewicz, Marzena , Tutuka, Candani , Behren, Andreas , Kannourakis, George , Jayachandran, Aparna
- Date: 2020
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 10, no. 1 (2020), p.
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- Description: Elevated levels of pregnancy-associated plasma protein-A (PAPP-A) have been implicated in the pathogenesis of various malignancies, including breast cancers. Breast cancer is one of the most frequent carcinomas and is the second most common cancer type detected in women of child-bearing age. Throughout pregnancy PAPP-A is produced and secreted by the placental syncytiotrophoblast cells; co-incidentally pregnancy-associated breast cancers often have an aggressive clinical course. The components of the PAPP-A/IGF axis was assessed in a panel of breast cancer cell lines. Using neutralising antibodies the impact of PAPP-A/IGF axis on cell motility was evaluated. PAPP-A was expressed in four of the twelve breast cancer cell lines tested. Blocking PAPP-A and IGFBP4 with neutralising antibodies significantly decreased motiliy of MDA-MB-231 cells. Upregulation of PAPP-A expression in breast tumours resulted in a trend towards worse overall survival. Notably, PAPP-A expression also positively correlated with epithelial-to-mesenchymal transition markers. In conclusion, these results indicate that PAPP-A plays an important role in breast cancer progression and it may be a promising therapeutic target in breast cancer. © 2020, The Author(s).
Evaluating the holistic costs and benefits of corn production systems in Minnesota, US
- Authors: Sandhu, Harpinder , Scialabba, Nadia , Warner, Chris , Behzadnejad, Fatemeh , Keohane, Kieran
- Date: 2020
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 10, no. 1 (2020), p.
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- Description: Global agriculture aims to minimize its impacts on environment and human health while maintaining its productivity. This requires a comprehensive understanding of its benefits and costs to ecosystems and society. Here, we apply a new evaluation framework developed by the Economics of Ecosystems and Biodiversity for Agriculture and Food (TEEBAgriFood) to assess key benefits and costs on the production side of genetically modified (GM) and organic corn systems in Minnesota, USA. The market value of GM corn is $4.5 billion, and only $31.8 million for organic corn using production data and market prices of 2017. GM corn generates revenue of $1488 per hectare (at $121 per MT), which is significantly lower than the organic corn at $2793 per hectare (at $294 per MT). Using a novel three-stage wellbeing valuation, analysis of the associations between corn production intensity and subjective measures of general health and wellbeing indicates that the total non-financial health cost associated with GM corn is $427.50 per hectare or $1.3 billion annually. We also find that the total annual environmental cost associated with GM corn production is $179 per hectare or $557.65 million within Minnesota. The use of the evaluation framework can help to improve decision making at farm and policy level to develop sustainable agriculture in order to minimize environmental and health related costs to society and economy. © 2020, The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Harpinder Sandhu” is provided in this record**
- Description: Global agriculture aims to minimize its impacts on environment and human health while maintaining its productivity. This requires a comprehensive understanding of its benefits and costs to ecosystems and society. Here, we apply a new evaluation framework developed by the Economics of Ecosystems and Biodiversity for Agriculture and Food (TEEBAgriFood) to assess key benefits and costs on the production side of genetically modified (GM) and organic corn systems in Minnesota, USA. The market value of GM corn is $4.5 billion, and only $31.8 million for organic corn using production data and market prices of 2017. GM corn generates revenue of $1488 per hectare (at $121 per MT), which is significantly lower than the organic corn at $2793 per hectare (at $294 per MT). Using a novel three-stage wellbeing valuation, analysis of the associations between corn production intensity and subjective measures of general health and wellbeing indicates that the total non-financial health cost associated with GM corn is $427.50 per hectare or $1.3 billion annually. We also find that the total annual environmental cost associated with GM corn production is $179 per hectare or $557.65 million within Minnesota. The use of the evaluation framework can help to improve decision making at farm and policy level to develop sustainable agriculture in order to minimize environmental and health related costs to society and economy. © 2020, The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “________________” is provided in this record**
Genetic aetiology of self-harm ideation and behaviour
- Authors: Campos, Adrian , Verweij, Karin , Statham, Dixie , Madden, Pamela , Maciejewski, Dominique , Davis, Katrina , John, Ann , Hotopf, Matthew , Heath, Andrew , Martin, Nicholas , Rentería, Miguel
- Date: 2020
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 10, no. 1 (2020), p.
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- Description: Family studies have identified a heritable component to self-harm that is partially independent from comorbid psychiatric disorders. However, the genetic aetiology of broad sense (non-suicidal and suicidal) self-harm has not been characterised on the molecular level. In addition, controversy exists about the degree to which suicidal and non-suicidal self-harm share a common genetic aetiology. In the present study, we conduct genome-wide association studies (GWAS) on lifetime self-harm ideation and self-harm behaviour (i.e. any lifetime self-harm act regardless of suicidal intent) using data from the UK Biobank (n > 156,000). We also perform genome wide gene-based tests and characterize the SNP heritability and genetic correlations between these traits. Finally, we test whether polygenic risk scores (PRS) for self-harm ideation and self-harm behaviour predict suicide attempt, suicide thoughts and non-suicidal self-harm (NSSH) in an independent target sample of 8,703 Australian adults. Our GWAS results identified one genome-wide significant locus associated with each of the two phenotypes. SNP heritability (hsnp2) estimates were ~10%, and both traits were highly genetically correlated (LDSC rg > 0.8). Gene-based tests identified seven genes associated with self-harm ideation and four with self-harm behaviour. Furthermore, in the target sample, PRS for self-harm ideation were significantly associated with suicide thoughts and NSSH, and PRS for self-harm behaviour predicted suicide thoughts and suicide attempt. Follow up regressions identified a shared genetic aetiology between NSSH and suicide thoughts, and between suicide thoughts and suicide attempt. Evidence for shared genetic aetiology between NSSH and suicide attempt was not statistically significant. © 2020, The Author(s).
- Description: This research was conducted using data from the UK Biobank resource under application number 25331. AC-G is supported by a UQ Research Training Scholarship from The University of Queensland (UQ). MER thanks the support of the NHMRC and Australian Research Council (ARC), and National Health and Medical Research Council (NHMRC) through a Research Fellowship (GNT1102821) and NHMRC Centre for Research Excellence in Suicide Prevention (GNT1042580). This research was made possible thanks to support from the US National Institutes of Health (grants AA013326, AA07535, AA0758O, AA07728, AA10249, AA13320, AA13321, AA14041, AA11998, AA17688, DA00272, DA012854, DA07261, DA018267, DA018660, DA23668 and DA019951); the Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498, 628911 1047956); the Australian Research Council (A7960034, A79906588, A79801419, DP0770096, DP0212016 and DP0343921).
Integration of palaeo-and-modern food webs reveal slow changes in a river floodplain wetland ecosystem
- Authors: Kattel, Giri , Eyre, Bradley , Gell, Peter
- Date: 2020
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 10, no. 1 (2020), p.
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- Description: Large rivers, including the Murray River system in southeast Australia, are disturbed by many activities. The arrival of European settlers to Australia by the mid-1800s transformed many floodplain wetlands of the lower Murray River system. River impoundment and flow regulation in the late 1800s and, from the 1930s, resulted in species invasion, and elevated nutrient concentrations causing widespread eutrophication. An integrated palaeoecology, and palaeo-and-modern food web approach, incorporating mixing models, was undertaken to reveal changes in a regulated wetland (i.e. Kings Billabong). The lack of preserved sediment suggests the wetland was naturally intermittent before 1890. After this time, when used as a water retention basin, the wetland experienced net sediment accumulation. Subfossil cladocerans, and δ13C of Daphnia, chironomid, and bulk sediment, all reflected an early productive, likely clear water state and shifts in trophic state following river regulation in the 1930s. Food web mixing models, based on δ13C and δ15N in subfossil and modern Daphnia, fish, and submerged and emergent macrophytes, also indicated a shift in the trophic relationships between fish and Daphnia. By the 1970s, a new state was established but a further significant alteration of nitrogen and carbon sources, and trophic interactions, continued through to the early 2000s. A possible switch from Daphnia as a prey of Australian Smelt could have modified the food web of the wetland by c. 2006. The timing of this change corresponded to the expansion of emergent macrophytes possibly due to landscape level disruptions. The evidence of these changes suggests a need for a broader understanding of the evolution of wetlands for the management of floodplains in the region. © 2020, The Author(s).
- Description: Funding details: National Key Research and Development Program of China Stem Cell and Translational Research, #2016YFC0402900 Funding details: National Key Research and Development Program of China Stem Cell and Translational Research, #2016YFE0201900 Funding details: Centre of Excellence for Electromaterials Science, Australian Research Council, ARC;ACES, DP160100248 Funding details: Centre of Excellence for Electromaterials Science, Australian Research Council, ARC;ACES, LE0668495
The influences of low protein diet on the intestinal microbiota of mice
- Authors: Masuoka, Hiroaki , Suda, Wataru , Tomitsuka, Eriko , Shindo, Chie , Takayasu, Lena , Horwood, Paul , Greenhill, Andrew , Hattori, Masahira , Umezaki, Masahiro , Hirayama, Kazuhiro
- Date: 2020
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 10, no. 1 (2020), p.
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- Description: Recent research suggests that protein deficiency symptoms are influenced by the intestinal microbiota. We investigated the influence of low protein diet on composition of the intestinal microbiota through animal experiments. Specific pathogen-free (SPF) mice were fed one of four diets (3, 6, 9, or 12% protein) for 4 weeks (n = 5 per diet). Mice fed the 3% protein diet showed protein deficiency symptoms such as weight loss and low level of blood urea nitrogen concentration in their serum. The intestinal microbiota of mice in the 3% and 12% protein diet groups at day 0, 7, 14, 21 and 28 were investigated by 16S rRNA gene sequencing, which revealed differences in the microbiota. In the 3% protein diet group, a greater abundance of urease producing bacterial species was detected across the duration of the study. In the 12% diet protein group, increases of abundance of Streptococcaceae and Clostridiales families was detected. These results suggest that protein deficiency may be associated with shifts in intestinal microbiota. © 2020, The Author(s).