Cancers often express hundreds of genes otherwise specific to germ cells, the germline/cancer (GC) genes. Here, we present and discuss the hypothesis that activation of a “germline program” promotes cancer cell malignancy. We do so by proposing four hallmark processes of the germline: meiosis, epigenetic plasticity, migration, and metabolic plasticity. Together, these hallmarks enable replicative immortality of germ cells as well as cancer cells. Especially meiotic genes are frequently expressed in cancer, implying that genes unique to meiosis may play a (...) role in oncogenesis. Because GC genes are not expressed in healthy somatic tissues, they form an appealing source of specific treatment targets with limited side effects besides infertility. Although it is still unclear why germ cell specific genes are so abundantly expressed in cancer, from our hypothesis it follows that the germline's reproductive program is intrinsic to cancer development. (shrink)

The biological sciences study (bio)complex living systems. Research directed at the mechanistic explanation of the "live" state truly requires a pluralist research program, i.e. BioComplexity research. The program should apply multiple intra-level and inter-level theories and methodologies. We substantiate this thesis with analysis of BioComplexity: metabolic and modular control analysis of metabolic pathways, emergence of oscillations, and the analysis of the functioning of glycolysis.

The progress of the molecular biosciences has been so enormous that a discipline studying how cellular functioning emerges out of the behaviors of their molecular constituents has become reality. Systems biology studies cells as spatiotemporal networks of interacting molecules using an integrative approach of theory , experimental biology , and quantitative network-wide analytical measurement . Its aim is to understand how molecules jointly bring about life. Systems biology is rapidly discovering principles governing the functioning of molecular networks and methods to (...) model and measure them. The application of the conceptual strength of systems sciences such as physics and engineering are opening up new ways of experimentally studying the design and functioning of molecular networks. Typically, in such studies models are used to highlight principles, design experiments, or to act in a predictive mode to specifically modify cellular behavior. In this trend article, theoretical approaches being applied in systems biology will be discussed. A number of books have recently appeared that deal with theoretical aspects of systems biology. In this article they are highlighted to facilitate the communication of systems biology to a broader audience. (shrink)

Microbial systems biology has made enormous advances in relating microbial physiology to the underlying biochemistry and molecular biology. By meticulously studying model microorganisms, in particular Escherichia coli and Saccharomyces cerevisiae, increasingly comprehensive computational models predict metabolic fluxes, protein expression, and growth. The modeling rationale is that cells are constrained by a limited pool of resources that they allocate optimally to maximize fitness. As a consequence, the expression of particular proteins is at the expense of others, causing trade‐offs between cellular objectives (...) such as instantaneous growth, stress tolerance, and capacity to adapt to new environments. While current computational models are remarkably predictive for E. coli and S. cerevisiae when grown in laboratory environments, this may not hold for other growth conditions and other microorganisms. In this contribution, we therefore discuss the relationship between the instantaneous growth rate, limited resources, and long‐term fitness. We discuss uses and limitations of current computational models, in particular for rapidly changing and adverse environments, and propose to classify microbial growth strategies based on Grimes's CSR framework. (shrink)

Schets van een samenwerkingsmodel zoals een neuroloog-psychiater, een psycholoog, een pastor en een verpleegkundige praktiseren in een Vlaamse kliniek.

Este trabajo presenta algunos aspectos introductorios a la lectura de las "Oraciones Inaugurales", el De nostri y el De mente heroica, y la "Sabiduría primitiva de los italianos", tenidas en cuenta por el traductor al español de estas obras viquianas, recientemente publicadas en un volumen .This papers presents some preliminary aspects related with the Inaugural Lectures , the De nostri, De mente heroica and the "Primitive Wisdom of Italians" which the Spanish translator has taken into account shortly before those works (...) appear in one single volume. (shrink)

Amsterdam University Press is a leading publisher of academic books, journals and textbooks in the Humanities and Social Sciences. Our aim is to make current research available to scholars, students, innovators, and the general public. AUP stands for scholarly excellence, global presence, and engagement with the international academic community.

We will show that there is a strong form of emergence in cell biology. Beginning with C.D. Broad's classic discussion of emergence, we distinguish two conditions sufficient for emergence. Emergence in biology must be compatible with the thought that all explanations of systemic properties are mechanistic explanations and with their sufficiency. Explanations of systemic properties are always in terms of the properties of the parts within the system. Nonetheless, systemic properties can still be emergent. If the properties of the components (...) within the system cannot be predicted, even in principle, from the behavior of the system's parts within simpler wholes then there also will be systemic properties which cannot be predicted, even in principle, on basis of the behavior of these parts. We show in an explicit case study drawn from molecular cell physiology that biochemical networks display this kind of emergence, even though they deploy only mechanistic explanations. This illustrates emergence and its place in nature. (shrink)

We will show that there is a strong form of emergence in cell biology. Beginning with C.D. Broad’s classic discussion of emergence, we distinguish two conditions sufficient for emergence. Emergence in biology must be compatible with the thought that all explanations of systemic properties are mechanistic explanations and with their sufficiency. Explanations of systemic properties are always in terms of the properties of the parts within the system. Nonetheless, systemic properties can still be emergent. If the properties of the components (...) within the system cannot be predicted, even in principle, from the behavior of the system’s parts within simpler wholes then there also will be systemic properties which cannot be predicted, even in principle, on basis of the behavior of these parts. We show in an explicit case study drawn from molecular cell physiology that biochemical networks display this kind of emergence, even though they deploy only mechanistic explanations. This illustrates emergence and its place in nature. (shrink)

Talkers are recognized more accurately if they are speaking the listeners’ native language rather than an unfamiliar language. This “language familiarity effect” has been shown not to depend upon comprehension and must instead involve language sound patterns. We further examine the level of sound-pattern processing involved, by comparing talker recognition in foreign languages versus two varieties of English, by English speakers of one variety, English speakers of the other variety, and non-native listeners. All listener groups performed better with native than (...) foreign speech, but no effect of language variety appeared: Native listeners discriminated talkers equally well in each, with the native variety never outdoing the other variety, and non-native listeners discriminated talkers equally poorly in each, irrespective of the variety's familiarity. The results suggest that this talker recognition effect rests not on simple familiarity, but on an abstract level of phonological processing. (shrink)

Systems biology is a vigorous and expanding discipline, in many ways a successor to genomics and perhaps unprecendented in its combination of biology with a ...

Ongoing changes in many Western countries have resulted in more healthcare services being transferred to municipalities and taking place in patients’ homes. This greatly impacts nurses’ work in home care, making their work increasingly diverse and demanding. In this study, we explore home‐care nursing through a critical discourse analysis of focus group interviews with home‐care nurses. Drawing on insights from positioning theory, we discuss the content and delineation of their work and the interweaving of contextual changes. Nurses hold a crucial (...) position in home healthcare, particularly in ensuring care for sicker patients with complex needs. Assessing health needs, performing advanced care, and at the same time, providing customized solutions in various homes were identified as distinctive for home‐care nurses’ work. Changes have made nurses’ work become driven by comprehensive tasks and acute medical needs that require much of their competence and time. Urgent care seems to take precedence in nurses’ work, leaving less time and attention for other tasks such as conversations and support for coping with everyday life. This underlines the need to investigate and discuss the content and scope of nurses’ work to help shape the further development of home‐care nursing. (shrink)

Sexual morality is not keeping up with the new sexual practices of young people, even in cultures oriented toward gender equality. The Norwegian high school graduation celebration constitutes an exceptionally liberal context for sexual practices. Many of the 18-year-old participants in this three-week-long celebration engage in “hookup” activities, involving kissing, fondling, and sexual intercourse. Through an analysis of qualitative interviews with 25 women and 16 men, we argue that while they avoided overt slut-shaming, the morally abject position of the “slut” (...) was still sustained by implication. The young women drew symbolic boundaries against anonymous other women who failed to value safety, hygiene, and self-control. This boundary-work was combined with declarations of tolerance of hookup practices, reflecting a sexually liberal culture geared toward gender equality. That young women who hooked up also drew boundaries against “other” women indicates a lack of alternative gender beliefs that allow young women to positively associate with hooking up. The young men also drew symbolic boundaries in their talk about sex, but enjoyed more freedom in their moral positioning. Although the liberal context was evident, the gendered difference in sexual boundary-work may contribute to the persistence of a sexual double standard among young people. (shrink)

After more than a century of research on glycolysis, we have detailed descriptions of its molecular organization, but despite this wealth of knowledge, linking the enzyme properties to metabolic pathway behavior remains challenging. These challenges arise from multi‐layered regulation and the context and time dependence of component functions. However, when viewed as a system that functions according to the principles of supply and demand, a simplifying theoretical framework can be applied to study its regulation logic and to assess the coherence (...) of experimental interpretations. These principles are universally applicable, as they emphasize the common metabolic tasks of glycolysis: the provision of free‐energy carriers, and precursors for biosynthesis and stress‐related compounds. Here we will review the regulation of multi‐tasking by glycolysis and consider how an understanding of this central metabolic pathway can be pursued using general principles, rather than focusing on the biochemical details of constituent components. (shrink)

The paper discusses Rawls’ and Habermas’ theories of deliberative democracy, focusing on the question of religious reasons in political discourse. Whereas Rawls as well as Habermas defend a fully inclusivist position on the use of religious reasons in the ‘background culture’ or ‘informal public sphere’, we defend a moderately inclusivist position. Moderate inclusivism welcomes religiously inspired contributions to public debate, but it also makes normative demands on public argumentation beyond the ‘public forum’ or ‘formal public sphere’. In particular, moderate inclusivism (...) implies what we call a ‘conversational translation proviso’ according to which citizens have a duty to supplement religious with proper political arguments if – but only if – they are asked to do so by their co-discussants. This position, we argue, is more in line with the deeper intuitions behind Rawls’ political liberalism and Habermas’ deliberative model than is the fully inclusivist alternative. _Keywords_: conversational translation proviso, deliberative democracy, ethics of citizenship, Habermas, moderate inclusivism, public reason, Rawls. (shrink)

Research into the use of videogames in education is on the rise, and they are cementing their position as part of the modernized, digital classroom. Sustainability education has also become a subject of interest among environmentally minded game developers and understanding the educational impact of such games is rapidly becoming an important field. This study examined the educational potential of the digital simulated ecosystem known as Eco, in order to reveal how playing Eco might promote environmental literacy and consciousness surrounding (...) ecosystems. Qualitative data from 7 respondents were subjected to a thematic analysis, revealing two main themes that highlight both game-based learning outcomes as well as barriers against learning. The findings indicate that Eco is a viable tool for promoting environmental literacy about ecosystems, and suggestions for future implementation of Eco are provided. (shrink)

Biochemistry and molecular biology have been focusing on the structural, catalytic, and regulatory proper- ties of individual macromolecules from the perspective of clarifying the mechanisms of metabolism and gene expression. Complete genomes of ‘primitive’ living organisms seem to be substantially larger than necessary for metabolism and gene expression alone. This is in line with the findings of silent phenotypes for supposedly important genes, apparent redundancy of functions, and variegated networks of signal transduction and transcription factors. Here we propose that evolutionary (...) optimization has been much more intensive than to lead to the bare minima necessary for autonomous life. Much more complex organisms prevail. Much of this complexity arises in the nonlinear interactions between cellular macromolecules and in subtle differences between paralogs (isoenzymes). The complexity can only be understood when analyzed quantitatively, for which quantitative experimentation is needed in living systems that are as simple and manipulatable as possible, yet complex in the above sense. We illustrate this for the glutamine synthetase cascade in Escherichia coli. By reviewing recent molecular findings, we show that this cascade is much more complex than necessary for simple regulation of ammonia assimilation. Simulations suggest that the function of this complexity may lie in quasi-intelligent behavior, including conditioning and learning. (shrink)

Mechanistic models in molecular systems biology are generally mathematical models of the action of networks of biochemical reactions, involving metabolism, signal transduction, and/or gene expression. They can be either simulated numerically or analyzed analytically. Systems biology integrates quantitative molecular data acquisition with mathematical models to design new experiments, discriminate between alternative mechanisms and explain the molecular basis of cellular properties. At the heart of this approach are mechanistic models of molecular networks. We focus on the articulation and development of mechanistic (...) models, identifying five constraints which guide the articulation of models in molecular systems biology. These constraints are not independent of one another, with the result that modeling becomes an iterative process. We illustrate the use of these constraints in the modeling of the mechanism for bistability in the lac operon. (shrink)

Collaboration in the arts is no longer a conscious choice to make a deliberate artistic statement, but instead a necessity of artistic survival. In today’s hybrid world of virtual mobility, collaboration decentralizes creative strategies, enabling artists to carve new territories and maintain practice-based autonomy in an increasingly commercial and saturated art world. Collaboration now transforms not only artistic practices but also the development of cultural institutions, communities and personal lifestyles. This book explores why collaboration has become so integrated into a (...) greater understanding of creative artistic practice. It draws on an emerging generation of contributors—from the arts, art history, sociology, political science, and philosophy—to engage directly with the diverse and interdisciplinary nature of collaborative practice of the future. (shrink)