A simple model of unbounded evolutionary versatility as a largest-scale trend in organismal evolution

The idea that there are any large-scale trends in the evolution of biological organisms is highly controversial. It is commonly believed, for example, that there is a large-scale trend in evolution towards increasing complexity, but empirical and theoretical arguments undermine this belief. Natural selection results in organisms that are well adapted to their local environments, but it is not clear how local adaptation can produce a global trend. In this paper, I present a simple computational model, in which local adaptation to a randomly changing environment results in a global trend towards increasing evolutionary versatility. In this model, for evolutionary versatility to increase without bound, the environment must be highly dynamic. The model also shows that unbounded evolutionary versatility implies an accelerating evolutionary pace. I believe that unbounded increase in evolutionary versatility is a large-scale trend in evolution. I discuss some of the testable predictions about organismal evolution that are suggested by the model

Fritz Müller, 1926-1980

... Fritz first came to the Arctic Institute in 1955 .... He came as a McGill-Carnegie Arctic Research Scholar to undertake the study of pingos, which form the basis of his doctoral dissertation and of the definitive publications on pingos, which were his first major scientific contributions. ... After two very full field expeditions to the Mackenzie Delta and Greenland in connection with the pingo work, Fritz left the Arctic Institute and McGill to accompany the successful Swiss Everest Expedition of 1956. ... Fritz climbed to the 8200-m level, taking the opportunity to extend his studies of patterned ground, begun in Greenland, to levels close to 8000 m in the South Col. ... In 1959, Fritz returned to Canada as a Research Associate at McGill and as leader of the Jacobson-McGill Arctic Research Expedition to Axel Heiberg Island, which has effectively operated ever since. Fritz himself was in the field in the Arctic Islands for eighteen field seasons during the last two decades. ... Although Fritz left Canada in 1970 to become head of the Department of Geography at the Swiss Federal Institute of Technology (ETH) in Zürich, he maintained an expedition office and the title of Honorary Professor at McGill for the remainder of his life. ... [During the Seventies, he was extensively involved] in the North Water Project, a study of the relatively ice-free areas between Devon and Ellesmere islands and Greenland, and its surrounding land and ice masses. ... In addition to his roles as leader of the Axel Heiberg and North Water projects, he set up glaciological teaching and research programs at McGill and ETH, ... [and chaired a number of committees of a number of international organizations across Canada, Germany, Switzerland and the United States.] ... We are pleased to report that the Government of the Northwest Territories has officially re-named the ice cap in central Axel Heiberg Island (70 47 N, 91 30 W) as the Müller Ice Cap, in his memory

NRF2 regulates HER1 signaling pathway to modulate the sensitivity of ovarian cancer cells to lapatinib and erlotinib

NF-E2-related factor 2 (NRF2) regulates the transcription of a battery of metabolic and cytoprotective genes. NRF2 and epidermal growth factor receptors (EGFRs/HERs) are regulators of cellular proliferation and determinants of cancer initiation and progression. NRF2 and HERs confer cancers with resistance to several therapeutic agents. Nevertheless, there is limited understanding of the regulation of HER expression and activation and the link between NRF2 and HER signalling pathways. We show that NRF2 regulates both basal and inducible expression of HER1, as treatment of ovarian cancer cells (PEO1, OVCAR3, and SKOV3) with NRF2 activator tBHQ inducing HER1, while inhibition of NRF2 by siRNA knockdown or with retinoid represses HER1. Furthermore, treatment of cells with tBHQ increased total and phosphorylated NRF2, HER1, and AKT levels and compromised the cytotoxic effect of lapatinib or erlotinib. Treatment with siRNA or retinoid antagonised the effect of tBHQ on NRF2 and HER1 levels and enhanced the sensitivity of ovarian cancer cells to lapatinib or erlotinib. Pharmacological or genetic inhibition of NRF2 and/or treatment with lapatinib or erlotinib elevated cellular ROS and depleted glutathione. This extends the understanding of NRF2 and its regulation of HER family receptors and opens a strategic target for improving cancer therapy

Nano-scale mechanical probing of supported lipid bilayers with atomic force microscopy

We present theory and experiments for the force-distance curve $F(z_0)$ of an atomic force microscope (AFM) tip (radius $R$) indenting a supported fluid bilayer (thickness $2d$). For realistic conditions the force is dominated by the area compressibility modulus $\kappa_A$ of the bilayer, and, to an excellent approximation, given by $F= \pi \kappa_A R z_0^2/(2d-z_0)^2$. The experimental AFM force curves from coexisting liquid ordered and liquid disordered domains in 3-component lipid bilayers are well-described by our model, and provides $\kappa_A$ in agreement with literature values. The liquid ordered phase has a yield like response that we model by hydrogen bond breaking.Comment: 6 pages, 6 figures, accepted for publication in Physical Review

The impact of spatial and social structure on an SIR epidemic on a weighted multilayer network

A key factor in the transmission of infectious diseases is the structure of disease transmitting contacts. In the context of the current COVID-19 pandemic and with some data based on the Hungarian population we develop a theoretical epidemic model (susceptible-infected-removed, SIR) on a multilayer network. The layers include the Hungarian household structure, with population divided into children, adults and elderly, as well as schools and workplaces, some spatial embedding and community transmission due to sharing communal spaces, service and public spaces. We investigate the sensitivity of the model (via the time evolution and final size of the epidemic) to the different contact layers and we map out the relation between peak prevalence and final epidemic size. When compared to the classic compartmental model and for the same final epidemic size, we find that epidemics on multilayer network lead to higher peak prevalence meaning that the risk of overwhelming the health care system is higher. Based on our model we found that keeping cliques/bubbles in school as isolated as possible has a major effect while closing workplaces had a mild effect as long as workplaces are of relatively small size

Eliciting density ratio classes

AbstractThe probability distributions of uncertain quantities needed for predictive modelling and decision support are frequently elicited from subject matter experts. However, experts are often uncertain about quantifying their beliefs using precise probability distributions. Therefore, it seems natural to describe their uncertain beliefs using sets of probability distributions. There are various possible structures, or classes, for defining set membership of continuous random variables. The Density Ratio Class has desirable properties, but there is no established procedure for eliciting this class. Thus, we propose a method for constructing Density Ratio Classes that builds on conventional quantile or probability elicitation, but allows the expert to state intervals for these quantities. Parametric shape functions, ideally also suggested by the expert, are then used to bound the nonparametric set of shapes of densities that belong to the class and are compatible with the stated intervals. This leads to a natural metric for the size of the class based on the ratio of the total areas under upper and lower bounding shape functions. This ratio will be determined by the characteristics of the shape functions, the scatter of the elicited values, and the explicit expert imprecision, as characterized by the width of the stated intervals. We provide some examples, both didactic and real, and conclude with recommendations for the further development and application of the Density Ratio Class

Gametocyte carriage in Plasmodium falciparum-infected travellers.

BACKGROUND: Gametocytes are the sexual stage of Plasmodium parasites. The determinants of gametocyte carriage have been studied extensively in endemic areas, but have rarely been explored in travellers with malaria. The incidence of gametocytaemia, and factors associated with gametocyte emergence in adult travellers with Plasmodium falciparum malaria was investigated at the Hospital for Tropical Diseases in London. METHODS: Clinical, parasitological and demographic data for all patients presenting with P. falciparum malaria between January 2001 and December 2011 were extracted from a prospective database. These data were supplemented by manual searches of laboratory records and patient case notes. RESULTS: Seven hundred and seventy three adult patients with laboratory-confirmed P. falciparum malaria were identified. Four hundred and sixty five (60%) were born in a country where malaria is endemic. Patients presented to hospital a median of four days into their illness. The median maximum parasite count was 0.4%. One hundred and ninety six patients (25%) had gametocytes; 94 (12%) on admission, and 102 (13%) developing during treatment. Gametocytaemia on admission was associated with anaemia and a lower maximum parasitaemia. Patients with gametocytes at presentation were less likely to have thrombocytopenia or severe malaria. Patients who developed gametocytes during treatment were more likely to have had parasitaemia of long duration, a high maximum parasitaemia and to have had severe malaria. There was no apparent association between the appearance of gametocytes and treatment regimen. CONCLUSIONS: The development of gametocytaemia in travellers with P. falciparum is associated with factors similar to those reported among populations in endemic areas. These data suggest that acquired immunity to malaria is not the only determinant of patterns of gametocyte carriage among patients with the disease