Hypersensitivity and growth adaptation of oestrogen-deprived MCF-7 human breast cancer cells

Background: Efficacy of endocrine therapy is compromised when human breast cancer cells circumvent imposed growth inhibition. The model of long-term oestrogen-deprived MCF-7 human breast cancer cells has suggested the mechanism results from hypersensitivity to low levels of residual oestrogen. Materials and methods: MCF-7 cells were maintained for up to 30 weeks in phenol-red-free medium and charcoal-stripped serum with 10-8 M 17-oestradiol and 10 g/ml insulin (stock 1), 10-8 M 17-oestradiol (stock 2), 10 g/ml insulin (stock 3) or no addition (stock 4). Results: Loss of growth response to oestrogen was observed only in stock 4 cells. Long-term maintenance with insulin in the absence of oestradiol (stock 3) resulted in raised oestrogen receptor alpha (ERlevels (measured by western immunoblotting) and development of hypersensitivity (assayed by oestrogen-responsive reporter gene induction and dose response to oestradiol for proliferation under serum-free conditions), but with no loss of growth response to oestrogen. Conclusion: Hypersensitivity can develop without any growth adaptation and therefore is not a prerequisite for loss of growth response in MCF-7 cells.

Strong armies, slow adaptation: civil-military relations and diffusion of military power

Why are some states more willing to adopt military innovations than others? Why, for example, were the great powers of Europe able to successfully reform their military practices to better adapt to and participate in the so-called military revolution of the sixteenth and seventeenth centuries while their most important extra-European competitor, the Ottoman Empire, failed to do so? This puzzle is best explained by two factors: civil-military relations and historical timing. In the Ottoman Empire, the emergence of an institutionally strong and internally cohesive army during the early stages of state formation—in the late fourteenth century—equipped the military with substantial bargaining powers. In contrast, the great powers of Europe drew heavily on private providers of military power during the military revolution and developed similar armies only by the second half of the seventeenth century, limiting the bargaining leverage of European militaries over their rulers. In essence, the Ottoman standing army was able to block reform efforts that it believed challenged its parochial interests. Absent a similar institutional challenge, European rulers initiated military reforms and motivated officers and military entrepreneurs to participate in the ongoing military revolution.

Metaproteomics analysis reveals the adaptation process for the chicken gut microbiota

The animal gastrointestinal tract houses a large microbial community, the gut microbiota, that confers many benefits to its host, such as protection from pathogens and provision of essential metabolites. Metagenomic approaches have defined the chicken fecal microbiota in other studies, but here, we wished to assess the correlation between the metagenome and the bacterial proteome in order to better understand the healthy chicken gut microbiota. Here, we performed high-throughput sequencing of 16S rRNA gene amplicons and metaproteomics analysis of fecal samples to determine microbial gut composition and protein expression. 16 rRNA gene sequencing analysis identified Clostridiales, Bacteroidaceae, and Lactobacillaceae species as the most abundant species in the gut. For metaproteomics analysis, peptides were generated by using the Fasp method and subsequently fractionated by strong anion exchanges. Metaproteomics analysis identified 3,673 proteins. Among the most frequently identified proteins, 380 proteins belonged to Lactobacillus spp., 155 belonged to Clostridium spp., and 66 belonged to Streptococcus spp. The most frequently identified proteins were heat shock chaperones, including 349 GroEL proteins, from many bacterial species, whereas the most abundant enzymes were pyruvate kinases, as judged by the number of peptides identified per protein (spectral counting). Gene ontology and KEGG pathway analyses revealed the functions and locations of the identified proteins. The findings of both metaproteomics and 16S rRNA sequencing analyses are discussed.

Motherhood, evolutionary psychology and mirror neurons or: ‘Grammar is politics by other means’

Through a close analysis of socio-biologist Sarah Blaffer Hrdy’s work on motherhood and ‘mirror neurons’ it is argued that Hrdy’s claims exemplify how research that ostensibly bases itself on neuroscience, including in literary studies ‘literary Darwinism’, relies after all not on scientific, but on political assumptions, namely on underlying, unquestioned claims about the autonomous, transparent, liberal agent of consumer capitalism. These underpinning assumptions, it is further argued, involve the suppression or overlooking of an alternative, prior tradition of feminist theory, including feminist science criticism.

The ebbing hegemon? An evolutionary perspective on the emergence of holistic governance and the efficient role of Institutional Investors in Environmental, Social and Governance issues (ESG)

This paper seeks to chronicle the roots of corporate governance form its narrow shareholder perspective to the current bourgeoning stakeholder approach while giving cognizance to institutional investors and their effective role in ESG in light of the King Report III of South Africa. It is aimed at a critical review of the extant literature from the shareholder Cadbury epoch to the present day King Report novelty. We aim to: (i) offer an analytical state of corporate governance in the Anglo-Saxon world, Middle East and North Africa (MENA), Far East Asia and Africa; and (ii) illuminate the lead role the king Report of South Africa is playing as the bellwether of the stakeholder approach to corporate governance as well as guiding the role of institutional investors in ESG.

Workaround motivation model (WAMM): an adaptation of the Theory of Interpersonal Behaviour

The study of workarounds (WA) has increased in importance due to their impact on patient safety and efficiency. However, there are no adequate theories to explain the motivation to create and use a workaround in a healthcare sitting. Although theories of technology acceptance help to understand the reasons to accept or reject technology, they fail to explain drivers for alternatives. Also workarounds involve creators and performers that have different motivations. Models such as Theory of Planned Behaviour (TPB) or Theory of Reasoned Action (TRA) can help to explain the role of workaround users, but lack explanation of workaround creators’ dynamics. Our aim is to develop a theoretical foundation to explain workaround motivation behaviour models with norms that relate to sanctions to provide an integrated Workaround Motivation Model; WAMM. The development of WAMM model is explained in this paper based on workaround cases as part of further research to establish the model.

Patterns of maximum body size evolution in Cenozoic land mammals: eco-evolutionary processes and abiotic forcing

There is accumulating evidence that macroevolutionary patterns of mammal evolution during the Cenozoic follow similar trajectories on different continents. This would suggest that such patterns are strongly determined by global abiotic factors, such as climate, or by basic eco-evolutionary processes such as filling of niches by specialization. The similarity of pattern would be expected to extend to the history of individual clades. Here, we investigate the temporal distribution of maximum size observed within individual orders globally and on separate continents. While the maximum size of individual orders of large land mammals show differences and comprise several families, the times at which orders reach their maximum size over time show strong congruence, peaking in the Middle Eocene, the Oligocene and the Plio-Pleistocene. The Eocene peak occurs when global temperature and land mammal diversity are high and is best explained as a result of niche expansion rather than abiotic forcing. Since the Eocene, there is a significant correlation between maximum size frequency and global temperature proxy. The Oligocene peak is not statistically significant and may in part be due to sampling issues. The peak in the Plio-Pleistocene occurs when global temperature and land mammal diversity are low, it is statistically the most robust one and it is best explained by global cooling. We conclude that the macroevolutionary patterns observed are a result of the interplay between eco-evolutionary processes and abiotic forcing

Towards cost-sensitive adaptation: when is it worth updating your predictive model?

Our digital universe is rapidly expanding,more and more daily activities are digitally recorded, data arrives in streams, it needs to be analyzed in real time and may evolve over time. In the last decade many adaptive learning algorithms and prediction systems, which can automatically update themselves with the new incoming data, have been developed. The majority of those algorithms focus on improving the predictive performance and assume that model update is always desired as soon as possible and as frequently as possible. In this study we consider potential model update as an investment decision, which, as in the financial markets, should be taken only if a certain return on investment is expected. We introduce and motivate a new research problem for data streams ? cost-sensitive adaptation. We propose a reference framework for analyzing adaptation strategies in terms of costs and benefits. Our framework allows to characterize and decompose the costs of model updates, and to asses and interpret the gains in performance due to model adaptation for a given learning algorithm on a given prediction task. Our proof-of-concept experiment demonstrates how the framework can aid in analyzing and managing adaptation decisions in the chemical industry.

Evolutionary resurrection of flagellar motility via rewiring of the nitrogen regulation system

A central process in evolution is the recruitment of genes to regulatory networks. We engineered immotile strains of the bacterium Pseudomonas fluorescens that lack flagella due to deletion of the regulatory gene fleQ. Under strong selection for motility, these bacteria consistently regained flagella within 96 hours via a two-step evolutionary pathway. Step 1 mutations increase intracellular levels of phosphorylated NtrC, a distant homologue of FleQ, which begins to commandeer control of the fleQ regulon at the cost of disrupting nitrogen uptake and assimilation. Step 2 is a switch-of-function mutation that redirects NtrC away from nitrogen uptake and towards its novel function as a flagellar regulator. Our results demonstrate that natural selection can rapidly rewire regulatory networks in very few, repeatable mutational steps.

High-level face adaptation without awareness

When a visual stimulus is suppressed from awareness, processing of the suppressed image is necessarily reduced. Although adaptation to simple image properties such as orientation still occurs, adaptation to high-level properties such as face identity is eliminated. Here we show that emotional facial expression continues to be processed even under complete suppression, as indexed by substantial facial expression aftereffects.

Researching farmer behaviour in climate change adaptation and sustainable agriculture: lessons learned from five case studies

Understanding farmer behaviour is needed for local agricultural systems to produce food sustainably while facing multiple pressures. We synthesize existing literature to identify three fundamental questions that correspond to three distinct areas of knowledge necessary to understand farmer behaviour: 1) decision-making model; 2) cross-scale and cross-level pressures; and 3) temporal dynamics. We use this framework to compare five interdisciplinary case studies of agricultural systems in distinct geographical contexts across the globe. We find that these three areas of knowledge are important to understanding farmer behaviour, and can be used to guide the interdisciplinary design and interpretation of studies in the future. Most importantly, we find that these three areas need to be addressed simultaneously in order to understand farmer behaviour. We also identify three methodological challenges hindering this understanding: the suitability of theoretical frameworks, the trade-offs among methods and the limited timeframe of typical research projects. We propose that a triangulation research strategy that makes use of mixed methods, or collaborations between researchers across mixed disciplines, can be used to successfully address all three areas simultaneously and show how this has been achieved in the case studies. The framework facilitates interdisciplinary research on farmer behaviour by opening up spaces of structured dialogue on assumptions, research questions and methods employed in investigation.

Experimental evolution for generalists and specialists reveals multivariate genetic constraints on thermal reaction norms

Theory predicts the emergence of generalists in variable environments and antagonistic pleiotropy to favour specialists in constant environments, but empirical data seldom support such generalist–specialist trade-offs. We selected for generalists and specialists in the dung fly Sepsis punctum (Diptera: Sepsidae) under conditions that we predicted would reveal antagonistic pleiotropy and multivariate trade-offs underlying thermal reaction norms for juvenile development. We performed replicated laboratory evolution using four treatments: adaptation at a hot (31 °C) or a cold (15 °C) temperature, or under regimes fluctuating between these temperatures, either within or between generations. After 20 generations, we assessed parental effects and genetic responses of thermal reaction norms for three correlated life-history traits: size at maturity, juvenile growth rate and juvenile survival. We find evidence for antagonistic pleiotropy for performance at hot and cold temperatures, and a temperature-mediated trade-off between juvenile survival and size at maturity, suggesting that trade-offs associated with environmental tolerance can arise via intensified evolutionary compromises between genetically correlated traits. However, despite this antagonistic pleiotropy, we found no support for the evolution of increased thermal tolerance breadth at the expense of reduced maximal performance, suggesting low genetic variance in the generalist–specialist dimension.

Evolutionary rewiring of bacterial regulatory networks

Bacteria have evolved complex regulatory networks that enable integration of multiple intracellular and extracellular signals to coordinate responses to environmental changes. However, our knowledge of how regulatory systems function and evolve is still relatively limited. There is often extensive homology between components of different networks, due to past cycles of gene duplication, divergence, and horizontal gene transfer, raising the possibility of cross-talk or redundancy. Consequently, evolutionary resilience is built into gene networks – homology between regulators can potentially allow rapid rescue of lost regulatory function across distant regions of the genome. In our recent study [Taylor, et al. Science (2015), 347(6225)] we find that mutations that facilitate cross-talk between pathways can contribute to gene network evolution, but that such mutations come with severe pleiotropic costs. Arising from this work are a number of questions surrounding how this phenomenon occurs.