Genetic background influences tumour development in heterozygous Men1 knockout mice

Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder caused by MEN1 germline mutations, is characterised by parathyroid, pancreatic and pituitary tumours. MEN1 mutations also cause familial isolated primary hyperparathyroidism (FIHP), a milder condition causing hyperparathyroidism only. Identical mutations can cause either MEN1 or FIHP in different families, thereby implicating a role for genetic modifiers in altering phenotypic expression of tumours. We therefore investigated the effects of genetic background and potential for genetic modifiers on tumour development in adult Men1+/- mice, which develop tumours of the parathyroids, pancreatic islets, anterior pituitary, adrenal cortex and gonads, that had been backcrossed to generate C57BL/6 and 129S6/SvEv congenic strains. A total of 275 Men1+/- mice, aged 5–26 months were macroscopically studied, and this revealed that genetic background significantly influenced the development of pituitary, adrenal and ovarian tumours, which occurred in mice over 12 months of age and more frequently in C57BL/6 females, 129S6/SvEv males and 129S6/SvEv females, respectively. Moreover, pituitary and adrenal tumours developed earlier, in C57BL/6 males and 129S6/SvEv females, respectively, and pancreatic and testicular tumours developed earlier in 129S6/SvEv males. Furthermore, glucagon-positive staining pancreatic tumours occurred more frequently in 129S6/SvEv Men1+/- mice. Whole genome sequence analysis of 129S6/SvEv and C57BL/6 Men1+/- mice revealed >54,000 different variants in >300 genes. These included, Coq7, Dmpk, Ccne2, Kras, Wnt2b, Il3ra and Tnfrsf10a, and qRT-PCR analysis revealed that Kras was significantly higher in pituitaries of male 129S6/SvEv mice. Thus, our results demonstrate that Kras and other genes could represent possible genetic modifiers of Men1

Fairness as “appropriate impartiality” and the problem of the self-serving bias

Garrett Cullity contends that fairness is appropriate impartiality (See Cullity (2004) Chapters 8 and 10 and Cullity (2008)). Cullity deploys his account of fairness as a means of limiting the extreme moral demand to make sacrifices in order to aid others that was posed by Peter Singer in his seminal article ‘Famine, Affluence and Morality’. My paper is founded upon the combination of (1) the observation that the idea that fairness consists in appropriate impartiality is very vague and (2) the fact that psychological studies show the self-serving bias is especially likely to infect one’s judgements when the ideas involved are vague. I argue that Cullity’s solution to extreme moral demandingness is threatened by these findings. I then comment on whether some other theories of fairness are vulnerable to the same objection

Can Modus Vivendi Save Liberalism from Moralism? A Critical Assessment of John Gray’s Political Realism

This chapter assesses John Gray’s modus vivendi-based justification for liberalism. I argue that his approach is preferable to the more orthodox deontological or teleological justificatory strategies, at least because of the way it can deal with the problem of diversity. But then I show how that is not good news for liberalism, for grounding liberal political authority in a modus vivendi undermines liberalism’s aspiration to occupy a privileged normative position vis-à-vis other kinds of regimes. So modus vivendi can save liberalism from moralism, but at cost many liberals will not be prepared to pay

WiseEye: next generation expandable and programmable camera trap platform for wildlife research

Funding: The work was supported by the RCUK Digital Economy programme to the dot.rural Digital Economy Hub; award reference: EP/G066051/1. The work of S. Newey and RJI was part funded by the Scottish Government's Rural and Environment Science and Analytical Services (RESAS). Details published as an Open Source Toolkit, PLOS Journals at: http://dx.doi.org/10.1371/journal.pone.0169758Peer reviewedPublisher PD

Collateral Quality and Loan Default Risk: The Case of Vietnam

In the transition economy of Vietnam, financial market is dominated by banking sector but commercial banks heavily rely on collateral-based lending. While the relationship between collateral and implied credit risk is still in debate, this paper provides additional empirical evidence regarding the heterogeneous effects and transmission channels of collateral characteristics on loan delinquency. Applying instrumental variable probit analysis on a unique dataset of 2295 internal loan accounts in Vietnam, we find the significantly negative impact of collateral quality on the probability of default of consumer loans, supporting the dominance of borrower selection and risk-shifting over lender selection effects. The finding implies that high-quality collateral not only signals more credible borrower but also fosters good behavior in using loan, enabling bank to mitigate adverse selection and moral hazard problems