Biology subjects

Seim, I.

Publications and source records attributed to Seim, I..

4 recordsLinked to original sources

bioRxiv2018

Gene expression profiling of The Cancer Genome Atlas supports an inverse association between body mass index (BMI) and major oesophageal tumour subtypes

In the last decade the Cancer Genome Atlas (TCGA) program has revealed significant insights into molecular events of dozens of cancers. These data sets are continuously updated, providing an unprecedented resource to the research community. There is now an emerging link between obesity and the development and progression of cancer. In this study we wished to identify genes related to body mass index (BMI)-related in TCGA datasets. Supporting epidemiological data, our gene expression profiling analyses suggest that oesophageal adenocarcinoma (EAC) can be considered a true obesity-associated cancer subtype, presenting avenues for prevention and treatment.

genetics↗

bioRxiv2018

No effect of administration of unacylated ghrelin on subcutaneous PC3 xenograft growth in a Rag1-/- mouse model of metabolic dysfunction

Ghrelin is a peptide hormone which, when acylated, regulates appetite, energy balance and a range of other biological processes. Ghrelin predominately circulates in its unacylated form (unacylated ghrelin; UAG). UAG has a number of functions independent of acylated ghrelin, including modulation of metabolic parameters and cancer progression. UAG has also been postulated to antagonise some of the metabolic effects of acyl-ghrelin, including its effects on glucose and insulin regulation. In this study, Rag1-/- mice with high-fat diet-induced obesity and hyperinsulinaemia were subcutaneously implanted with PC3 prostate cancer xenografts to investigate the effect of UAG treatment on metabolic parameters and xenograft growth. Daily intraperitoneal injection of 100 g/kg UAG had no effect on xenograft tumour growth in mice fed normal rodent chow or 23% high-fat diet. UAG significantly improved glucose tolerance in host Rag1-/- mice on a high-fat diet, but did not significantly improve other metabolic parameters. We hypothesise that UAG is not likely to be an effective treatment for prostate cancer, with or without associated metabolic syndrome.\n\nConflict of interestThe authors declare no conflict of interest.

cancer biology↗

bioRxiv2018

A survey on information sources used by academic researchers to evaluate scientific instruments

Most scientific research is fueled by research equipment (instruments); typically hardware purchased to suit a particular research question. Examples range from 17th century microscopes to modern particle colliders and high-throughput sequencers. Here, we studied the information sources used by academic researchers to assess scientific instruments, and reveal evidence of a worrying confluence of incentives similar to those that drove the biopharmaceutical industry to adopt controversial practices such as ghostwriting and hidden sponsorship. Our findings suggest there are little understood incentives against disclosure in the peer-reviewed literature on scientific instruments; constituting an underappreciated threat to scientific standards of trustworthiness and transparency. We believe that a public debate and subsequent editorial policy action are urgently required.

scientific communication and education↗

bioRxiv2016

Ghrelin-Reactive Autoantibodies are elevated in Children with Prader-Willi Syndrome

Prader-Willi Syndrome (PWS) is a complex genetic disorder characterized by developmental and growth abnormalities, insatiable appetite, and excessive eating (hyperphagia). The underlying cause of hyperphagia in PWS is currently unknown, however, elevated levels of the peptide hormone ghrelin is believed to contribute. Recently, ghrelin-reactive autoantibodies (isotype IgG) were identified in non-genetic obesity. These autoantibodies act as ghrelin carrier proteins and potentiate its orexigenic effects. Here, we describe the identification of ghrelin-reactive autoantibodies in a cohort of 16 children with PWS. In comparison to unaffected siblings, autoantibody levels are significantly increased in PWS children. We further show that autoantibody levels are unaffected by food intake, unlike plasma ghrelin which declines postprandially in both groups. Critically, we also demonstrate that the autoantibodies bind the major circulating ghrelin isoforms, unacylated ghrelin, which does not stimulate appetite, and the orexigen acylated ghrelin. In excess, unacylated ghrelin may compete with acylated ghrelin for autoantibody binding. Taken together, this is the first report on ghrelin-reactive antibodies in a pediatric population, and the first to demonstrate that the antibodies do not discriminate between orexigenic and non-orexigenic ghrelin isoforms. Our work suggests that ghrelin autoantibodies can be targeted using non-orexigenic forms of ghrelin, thereby providing a novel therapeutic target for PWS and for obesity in general.

physiology↗