Darwinian language evolution

Haider’s target paper presents a fresh and inspiring look at the nature of grammar change. The overall impression of his approach is very convincing, especially his insistence on the point that language was not selected for communication – hence it is no adaptation to communicative use. Nevertheless, I think three topics are in need of further discussion and elaboration. First, I will discuss the question whether Haider’s conception of Darwinian selection covers all aspects of grammar change. Second, I will consider the question of whether an approach that dispenses with UG (as Haider’s does) can explain why grammars are the way they are. Third, I will question Haider’s equation of grammar with the genotype and of speech with the phenotype and develop an alternative and more appropriate proposal where, among others, speech corresponds to behavior.

Acquired ABC-transporter overexpression in cancer cells: transcriptional induction or Darwinian selection?

Acquired multidrug resistance (MDR) in tumor diseases has repeatedly been associated with overexpression of ATP-binding cassette transporters (ABC-transporters) such as P-glycoprotein. Both in vitro and in vivo data suggest that these efflux transporters can cause MDR, albeit its actual relevance for clinical chemotherapy unresponsiveness remains uncertain. The overexpression can experimentally be achieved by exposure of tumor cells to cytotoxic drugs. For simplification, the drug-mediated transporter overexpression can be attributed to two opposite mechanisms: First, increased transcription of ABC-transporter genes mediated by nuclear receptors sensing the respective compound. Second, Darwinian selection of sub-clones intrinsically overexpressing drug transporters being capable of extruding the respective drug. To date, there is no definite data indicating which mechanism truly applies or whether there are circumstances promoting either mode of action. This review summarizes experimental evidence for both theories, suggests an algorithm discriminating between these two modes, and finally points out future experimental approaches of research to answer this basic question in cancer pharmacology.

Predictive evolution of metabolic phenotypes using model-designed selection niches

Traits lacking fitness benefit cannot be directly selected for under Darwinian evolution. Thus, features such as metabolite secretion are currently inaccessible to adaptive laboratory evolution. Here, we utilize environment-dependency of trait correlations to enable Darwinian selection of fitness-neutral or costly traits. We use metabolic models to design selection niches and to identify surrogate traits that are genetically correlated with cell fitness in the selection niche but coupled to the desired trait in the target niche. Adaptive evolution in the selection niche and subsequent return to the target niche is thereby predicted to enhance the desired trait. We experimentally validate the theory by evolving Saccharomyces cerevisiae for increased secretion of aroma compounds in wine fermentation. Genomic, transcriptomic, and proteomic changes in the evolved strains confirmed the predicted flux re-routing to aroma biosynthesis. The use of model-designed selection niches facilitates the predictive evolution of fitness-costly traits for ecological and biotechnological applications.

Optimal Chemotherapy Scheduling for Non-Genetic Drug Resistance

One of the most difficult challenges in cancer therapy is the emergence of drug resistance within tumors. Sometimes drug resistance can emerge as the result of mutations and Darwinian selection. However, recently another phenomenon has been discovered, in which tumor cells switch back and forth between drug-sensitive and pre-resistant states. Upon exposure to the drug, sensitive cells die off, and pre-resistant cells become locked in to a state of permanent drug resistance. In this paper, we explore the implications of this transient state switching for therapy scheduling. We propose a model to describe the phenomenon and estimate parameters from experimental melanoma data. We then compare the performance of continuous and alternating drug schedules, and use sensitivity analysis to explore how different conditions affect the efficacy of each schedule. We find that for our estimated parameters, a continuous therapy schedule is optimal. However we also find that an alternating schedule can be optimal for other, hypothetical parameter sets, depending on the difference in growth rate between pre- drug and post-drug cells, the delay between exposure to the drug and emergence of resistance, and the rate at which pre-resistant cells become resistant relative to the rate at which they switch back to the sensitive state.

A Survey on Enterprise Opportunities and Analysis of Technological Startups and Valuation

Enterprise technological start-ups represent the newly created firms with the possibility to rapidly develop and assume liquidity in the next few decades. The main purpose of this mode of expansion is to enhance finance development over considerably limited collateralizable fiscal assets. However, this is considered unattractive from the ancient banking corporations which have now been replaced by more sophisticated and specialized intermediaries such as the private equity funds or the venture capital that diversify business portfolios in reference to their strategies on multi-annual exit with firm projected increment in investment value that endured the Darwinian selection. In that regard, this paper conducts evaluation of firms and reviews their technological start-ups following traditional approaches, flanked based on certain elements derived from multiple-exit methods and varied probabilistic scenarios. The technological footprints showcase the evaluation analogies with know-how, intangibles and patents that are connected to certain sectors.

Principles and mechanisms of non-genetic resistance in cancer

As well as undergoing genetic evolution, cancer cells can alter their epigenetic state to adapt and resist treatment. This non-genetic evolution is emerging as a major component of cancer resistance. Only now are we beginning to acquire the necessary data and tools to establish some of the underlying principles and mechanisms that define when, why and how non-genetic resistance occurs. Preliminary studies suggest that it can exist in a number of forms, including drug persistence, unstable non-genetic resistance and, most intriguingly, stable non-genetic resistance. Exactly how they each arise remains unclear; however, epigenetic heterogeneity and plasticity appear to be important variables. In this review, we provide an overview of these different forms of non-genetic resistance, before exploring how epigenetic heterogeneity and plasticity influence their emergence. We highlight the distinction between non-genetic Darwinian selection and Lamarckian induction and discuss how each is capable of generating resistance. Finally, we discuss the potential interaction between genetic and non-genetic adaptation and propose the idea of ‘the path of most resistance’, which outlines the variables that dictate whether cancers adapt through genetic and/or epigenetic means. Through these discussions, we hope to provide a conceptual framework that focuses future studies, whose insights might help prevent or overcome non-genetic resistance.

The deep origins of society: An assessment of E.O. Wilson’s Genesis

E.O. Wilson’s Genesis: The Deep Origins of Societies is one of a series of short books where the author has tried to explain human societies using ideas and concepts from biology. While Wilson is to be lauded for his recent efforts to reintroduce the notions of group selection and multilevel selection, he still sustains an emphasis on only Darwinian selection and reveals a bias toward seeing selection for groups as a result of selection on individuals (as is the case for insects), perhaps entangled with selection on groups. The effort to conceive of human societies as an example of eusocieties of social insects ignores most of the sociological works on human and societal evolution; and as a result, the book is not convincing in its argument. Despite the pleasant writing style, Wilson and other biologists writing about human societies need to engage the almost 200 years of sociological work devoted to understanding the evolution of human societies.