High‐throughput genomic technologies are revolutionizing human genetics. So far the focus has been on the 1.5% of the genome, which is coding, in spite of the fact that the great majority of genomic variants fall outside the coding regions. Recent efforts to annotate the non‐coding sequence show that over 80% of the genome is biochemically active. The genome is divided into regulatory domains consisting of sequence regions that enhance and/or silence the expression of nearby genes and are, in (...) some cases, separated by boundaries with insulator activity. In this paper, we review the recent advances in the identification of variations that influence gene regulation and their consequences for human disease. We hypothesize that structural variations outside of the coding genome can interfere with normal gene regulation by disrupting the regulatory landscape. Therefore, the regulatory landscape of the genome has also to be taken into consideration when investigating the pathology of human disease. (shrink)

The interactions between genetic and environmental risk factors contribute to the aetiology of complex human diseases. Genome‐wide association studies (GWAS) have revealed that most of the genetic variants associated with complex diseases are located in the non‐coding part of the genome, preferentially within enhancers. Enhancers are distal cis‐regulatory elements composed of clusters of transcription factors binding sites that positively regulate the expression of their target genes. The generation of genome‐wide maps for histone marks (e.g., H3K27ac), chromatin accessibility and (...) transcription factor and coactivator (e.g., p300) binding profiles have enabled the identification of enhancers across many human cell types and tissues. Nonetheless, the functional and pathological consequences of the majority of disease‐associated genetic variants located within enhancers seem to be rather minor under normal conditions, thus questioning their medical relevance. Here we propose that, due to the prevalence of enhancer redundancy, the pathological effects of many disease‐associated non‐coding genetic variants might be preferentially (or even only) manifested under environmental stress. (shrink)

Deletions, duplications, insertions, inversions, and translocations, collectively called structural variations (SVs), affect more base pairs of the genome than any other sequence variant. The recent technological advancements in genome sequencing have enabled the discovery of tens of thousands of SVs per human genome. These SVs primarily affect non‐coding DNA sequences, but the difficulties in interpreting their impact limit our understanding of human disease etiology. The functional annotation of non‐coding DNA sequences and methodologies to characterize their three‐dimensional (3D) organization in the (...) nucleus have greatly expanded our understanding of the basic mechanisms underlying gene regulation, thereby improving the interpretation of SVs for their pathogenic impact. Here, we discuss the various mechanisms by which SVs can result in altered gene regulation and how these mechanisms can result in rare genetic disorders. Beyond changing gene expression, SVs can produce novel gene‐intergenic fusion transcripts at the SV breakpoints. (shrink)

Until recently, raising a young child as transgender was culturally unintelligible. Most scholarship on transgender identity refers to adults’ experiences and perspectives. Now, the increasing visibility of gender-variant children, as they are identified by the parents who raise them, presents new opportunities to examine how individuals confront the gender binary and imagine more gender-inclusive possibilities. Drawing on Foucault’s notion of “truth regime” to conceptualize the regulatory forces of the gender binary in everyday life, this work examines the strategies of (...) 24 such parents, who represent 16 cases of childhood gender variance. Specifically, I analyze three practices—“gender hedging,” “gender literacy,” and “playing along”—through which these parents develop a critical consciousness about gender binary ideology and work to accommodate their children’s nonconformity in diverse discursive interactions. Taken together, their newfound strategies and perspectives subvert traditional conceptions of “gender-neutral” or “feminist” parenting, and reveal new modes of resistance to the normative transmission and regulation of gender practices. (shrink)

Behavioural variant frontotemporal dementia (bvFTD) is a subtype of frontotemporal dementia characterized by changes in personality, social behaviour, and cognition. Although neural abnormalities cause bvFTD patients to struggle with inhibiting problematic behaviour, they are generally considered fully autonomous individuals. Subsequently, bvFTD patients demonstrate understanding of right and wrong but are unable to act in accordance with moral norms. To investigate the ethical, legal, and social issues associated with bvFTD, we conducted a scoping review of academic literature with inclusion & exclusion (...) criteria and codes derived from our prior work. Among our final sample of fifty-six articles, four mentioned bvFTD patient-offenders as unfit to stand trial by insanity, and sixteen mentioned the use of dementia evidence in a court of law to better understand the autonomy of bvFTD patients. Additional emergent issues that were discovered include: training police officers to handle situations involving bvFTD patients and educating healthcare providers on how to help caregivers navigate bvFTD. The current literature highlights the inadequacy of traditional applications of medico-legal categories such as autonomy, capacity and competence, in informing cognitive capacity assessments in clinical and legal settings and deserves consideration by neuroethicists. (shrink)

The question of how multinational enterprises respond to local corporate social responsibility expectations remains salient, also in the context of many African governments’ attempts to define and regulate business responsibilities. What determines whether MNEs respond to such local, state-driven expectations as congruent with their global commitment to CSR? Adopting an institutional logics perspective, we argue that a higher global CSR commitment will lead to higher local responsiveness when regulatory distance is low, but it will lead to lower local responsiveness (...) when regulatory distance is high. We find support for our hypothesis using data on 93 MNEs’ responses to the South African state’s Broad-Based Black Economic Empowerment policy. We thus contribute to the global–local CSR literature and show how MNEs’ local CSR responsiveness will be shaped by not only the local context but also their home country and firm-internal environments. (shrink)

Precise spatiotemporal control of gene expression during normal development and cell differentiation is achieved by the combined action of proximal (promoters) and distal (enhancers) cis‐regulatory elements. Recent studies have reported that a subset of promoters, termed Epromoters, works also as enhancers to regulate distal genes. This new paradigm opened novel questions regarding the complexity of our genome and raises the possibility that genetic variation within Epromoters has pleiotropic effects on various physiological and pathological traits by differentially impacting multiple proximal (...) and distal genes. Here, we discuss the different observations pointing to an important role of Epromoters in the regulatory landscape and summarize the evidence supporting a pleiotropic impact of these elements in disease. We further hypothesize that Epromoter might represent a major contributor to phenotypic variation and disease. (shrink)

Numerous liver specific genes are transcriptionally activated by the binding to their promoter or enhancer of Hepatic Nuclear Factor 1 (HNF1). HNF1 contains a variant homeo‐domain and binds to DNA as either a homod‐imer or a heterodimer with the vHNF1 protein. Surprisingly, HNF1 is not restricted to hepatocytes but is expressed in epithelial cells of several endoderm derived organs and in mesoderm derived kidney tubules. Hence, HNF1 alone can not account for the differentiated state of the hepatic cells. In fact, (...) several other liver‐enriched transcription factors have been cloned. The hepatic phenotype could result from the combinatorial. expression of these regulators. Possible involvement of these trans‐acting factors in liver organogenesis and hepatic differentiation is discussed. (shrink)

Understanding the functional mechanisms underlying genetic signals associated with complex traits and common diseases, such as cancer, diabetes and Alzheimer's disease, is a formidable challenge. Many genetic signals discovered through genome‐wide association studies map to non‐protein coding sequences, where their molecular consequences are difficult to evaluate. This article summarizes concepts for the systematic interpretation of non‐coding genetic signals using genome annotation data sets in different cellular systems. We outline strategies for the global analysis of multiple association intervals and the in‐depth (...) molecular investigation of individual intervals. We highlight experimental techniques to validate candidate (potential causal) regulatory variants, with a focus on novel genome‐editing techniques including CRISPR/Cas9. These approaches are also applicable to low‐frequency and rare variants, which have become increasingly important in genomic studies of complex traits and diseases. There is a pressing need to translate genetic signals into biological mechanisms, leading to prognostic, diagnostic and therapeutic advances. (shrink)

Hidden among the myriad nucleotide variants that constitute each species' gene pool are a few variants that contribute to phenotypic variation. Many of these differences that make a difference are non‐coding cis‐regulatory variants, which, unlike coding variants, can only be identified through laborious experimental analysis. Recently, Cowles et al.1 described a screening method that does an end‐run around this problem by searching for genes whose cis regulation varies without having to find the polymorphic nucleotides that (...) influence transcription. While we will continue to require a diverse arsenal of experimental methods, this versatile method will speed the identification of functional genetic variation. BioEssays 25:421–424, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

In human languages, a palindrome reads the same forward as backward (e.g., ‘madam’). In regulatory DNA, a palindrome is an inverted sequence repeat that allows a transcription factor to bind as a homodimer or as a heterodimer with another type of transcription factor. Regulatory palindromes are typically imperfect, that is, the repeated sequences differ in at least one base pair, but the functional significance of this asymmetry remains poorly understood. Here, we review the use of imperfect palindromes in (...) Drosophila photoreceptor differentiation and mammalian steroid receptor signaling. Moreover, we discuss mechanistic explanations for the predominance of imperfect palindromes over perfect palindromes in these two gene regulatory contexts. Lastly, we propose to elucidate whether specific imperfectly palindromic variants have specific regulatory functions in steroid receptor signaling and whether such variants can help predict transcriptional outcomes as well as the response of individual patients to drug treatments. (shrink)

The major challenge in complex disease genetics is to understand the fundamental features of this complexity and why functional alterations at multiple independent genes conspire to lead to an abnormal phenotype. We hypothesize that the various genes involved are all functionally united through gene regulatory networks (GRN), and that mutant phenotypes arise from the consequent perturbation of one or more rate‐limiting steps that affect the function of the entire GRN. Understanding a complex phenotype thus entails unraveling the details of (...) each GRN, namely, the transcription factors that bind to cis regulatory elements affected by sequence variants altering transcription of specific genes, and their mutual feedback relationships. These GRNs can be identified through their rate‐limiting steps and are best uncovered by genomic analyses of rare, extreme phenotype families, thus providing a coherent molecular basis to complex traits and disorders. (shrink)

Darwinian evolutionary theory has two key terms, variations and biological selection, which finally lead to survival of the fittest variant. With the rise of molecular genetics, variations were explained as results of error replications out of the genetic master templates. For more than half a century, it has been accepted that new genetic information is mostly derived from random error-based events. But the error replication narrative has problems explaining the sudden emergence of new species, new phenotypic traits, and genome innovations (...) as a sudden single event. Meanwhile, it is recognized that errors cannot explain the evolution of genetic information, genetic novelty, and complexity. Now, empirical evidence establishes the crucial role of non-random genetic content editors, such as viruses, diversity generating retroelements, and other RNA networks, to produce new genetic information, complex regulatory control, inheritance vectors, genetic identity, immunity, new sequence space, evolution of complex organisms, and evolutionary transitions. (shrink)

There is a regulatory option for conscientious objection in health care that has yet to be systematically examined by ethicists and policymakers: granting a liberty to request exemption from prescribed work tasks without a companion guarantee that the request is accommodated. For the right-holder, the liberty’s value lies in the ability to seek exemption without duty-violation and a tangible prospect of reassignment. Arguing that such a liberty is too unreliable to qualify as a right to conscientious objection leads to (...) the problem of consistently distinguishing its effects from those of a right to conscientious objection that is made conditional on an individual assessment of the objector’s motivation. These properties require that we distinguish the liberty to request exemption from more restrictive policy choices, and that we subject it to greater scrutiny in the wider moral discourse as a possible variant of a right to conscientious objection. (shrink)

This paper introduces the reconstitutor as a comprehensive unit of heredity within the context of evolutionary research. A reconstitutor is the structure resulting from a set of relationships between different elements or processes that are actively involved in the recreation of a specific phenotypic variant in each generation regardless of the biomolecular basis of the elements or whether they stand in a continuous line of ancestry. Firstly, we justify the necessity of introducing the reconstitutor by showing the limitations of other (...) evolutionary conceptions of the unit of heredity, such as the replicator, the reproducer, and the Darwinian individual. We argue that these conceptions are based on the requirement of lineage formation, which we argue to be unnecessary for the existence of evolutionary heredity. In the second part, we introduce the reconstitutor, which we base on the concept of Stability of Traits, and illustrate how it covers cases of hereditary phenomena not covered by the previous accounts. Secondly, we illustrate how the reconstitutor could serve as a platform to rethink ecological inheritance and other forms of inheritance that have been recently introduced under the song/singer model of evolution. (shrink)

SummaryGene transcription is strictly controlled by the interplay of regulatory events at gene promoters and gene‐distal regulatory elements called enhancers. Despite extensive studies of enhancers, we still have a very limited understanding of their mechanisms of action and their restricted spatio‐temporal activities. A better understanding would ultimately lead to fundamental insights into the control of gene transcription and the action of regulatory genetic variants involved in disease. Here, I review and discuss pros and cons of state‐of‐the‐art (...) genomics methods to localize and infer the activity of enhancers. Among the different approaches, profiling of enhancer RNAs yields the highest specificity and may be superior in detecting in vivo activity. I discuss their apparent similarities to promoters, which challenge the established view of enhancers and promoters as distinct entities, and present a unifying model of regulatory elements in transcriptional regulation, in which activity, transcriptional output and regulatory function is context specific. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Rhetoric and Power: An Inquiry into Foucault’s Critique of ConfessionDave TellOn October 10, 1979, Michel Foucault revised his thesis on confession. On that day, some three years after the publication of his magisterial treatment of confession in the first volume of The History of Sexuality, Foucault argued that the Pythagoreans, Stoics, and Epicureans had, before the advent of Christianity, their own practices of confession. Yet these practices, unlike their (...) Christian variants, were not complicit with practices of domination (OS 310, 312). In the context of Foucault’s thought theretofore, in which the confession consistently figured as an essential component in the exercise of modern power, this is a radical shift. In lectures given at both Berkeley and Dartmouth in the fall of 1980, Foucault made similar arguments. On these occasions he argued that Seneca’s De ira constituted a “stoic confession,” the object of which was to enable the subject to “live differently, better, more happily, than other people” (AB 210, 205). Judith Butler captures the gravity of the shift: “In the last years of his life, Foucault returned to the question of confession, reversing his earlier critique in the first volume of the History of Sexuality, where he indicts confession as a forcible extraction of sexual truth, a practice in the service of a regulatory power” (2005, 112).This reversal was short lived. Although Foucault would celebrate ancient Greek techniques of the self for the rest of his life, he would not [End Page 95] long refer to these techniques in terms of confession. Thus, in another reading of De ira, this one in March 1982, Foucault again noted that the Stoics have “confessional practices” that are “very close to what is found in Christianity” (Herm 482). This time, however, he insisted that the Stoic practices were fundamentally different: “However, all these elements seem to me to be profoundly different from what we should call ‘confession’ in the strict, or anyway, spiritual sense of the word” (Herm 365). In The Care of the Self, Foucault again conceded that De ira—what he now called “the most detailed description” of antique practices of the self—looked “at first glance” like a Christian confession, but he again maintained that it is something quite different: “The purpose of the examination is not therefore to discover one’s own guilt, down to its most trifling forms” (CS 61–62). Foucault concluded that the various “discourses of the self”—the confession and the Greek techniques of the self—could not be placed into a single category (see GE 250). Indeed, the “profound difference” (Herm 299) between these two discourses of the self was perhaps Foucault’s most repeated claim of the 1980s (see Herm 222, 237–44, 299, 308; GE 247–48; WS 237; AB 207–8; RFT 27; UP 89; CS 239; SS 5; FI 5, 12; FS 30, 35, 44, 87, 96, 97, 143–45, 147).It is worth asking why Foucault returned so consistently to the distinction between these two discursive forms. This question gains even more relevance for readers of this journal when we remember that, on at least two occasions, Foucault defined one of these forms, the ancient techniques of the self, in terms of its opposition to rhetoric: the techniques of the self, he claimed, are “nonrhetorical” (Herm 368; FS 20). Thus the question that drives this essay is not so much why Foucault attached such importance to the distinction but rather how rhetoric itself might differentiate the confession from the techniques of the self. Stated differently, Foucault’s work on the confession vis-à-vis the technologies of the self provides a valuable opportunity to study the role of rhetoric in Foucault’s thought—not because they are both rhetorical forms but, curiously, because Foucault insists that one is not.In order to foreground the work of rhetoric in Foucault’s thought, I situate his discourses of the self in the context of Nietzsche’s critique of metonymy. Although this may seem arbitrary, it gains initial plausibility from three facts. First, we know that Foucault understood rhetoric in terms of tropes (OT 84; Cooper 1988, 4). Second, we know too that Foucault had a deep... (shrink)

In vertebrates, single cell analyses of replication timing patterns brought to light a very well controlled program suggesting a tight regulation on initiation sites. Mapping of replication origins with different methods has revealed discrete preferential sites, enriched in promoters and potential G‐quadruplex motifs, which can aggregate into initiation zones spanning several tens of kilobases (kb). Another characteristic of replication origins is a nucleosome‐free region (NFR). A modified yeast strain containing a humanized origin recognition complex (ORC) fires new origins at NFRs (...) revealing their regulatory role. In cooperation with NFRs, the histone variant H2A.Z facilitates ORC loading through di‐methylation of lysine 20 of histone H4. Recent studies using genome editing methods show that efficient initiation sites associated with transcriptional activity can synergize over several tens of kb by establishing physical contacts and lead to the formation of early domains of DNA replication demonstrating a co‐regulation between replication initiation and transcription. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Rhetoric and Power: An Inquiry into Foucault’s Critique of ConfessionDave TellOn October 10, 1979, Michel Foucault revised his thesis on confession. On that day, some three years after the publication of his magisterial treatment of confession in the first volume of The History of Sexuality, Foucault argued that the Pythagoreans, Stoics, and Epicureans had, before the advent of Christianity, their own practices of confession. Yet these practices, unlike their (...) Christian variants, were not complicit with practices of domination (OS 310, 312). In the context of Foucault’s thought theretofore, in which the confession consistently figured as an essential component in the exercise of modern power, this is a radical shift. In lectures given at both Berkeley and Dartmouth in the fall of 1980, Foucault made similar arguments. On these occasions he argued that Seneca’s De ira constituted a “stoic confession,” the object of which was to enable the subject to “live differently, better, more happily, than other people” (AB 210, 205). Judith Butler captures the gravity of the shift: “In the last years of his life, Foucault returned to the question of confession, reversing his earlier critique in the first volume of the History of Sexuality, where he indicts confession as a forcible extraction of sexual truth, a practice in the service of a regulatory power” (2005, 112).This reversal was short lived. Although Foucault would celebrate ancient Greek techniques of the self for the rest of his life, he would not [End Page 95] long refer to these techniques in terms of confession. Thus, in another reading of De ira, this one in March 1982, Foucault again noted that the Stoics have “confessional practices” that are “very close to what is found in Christianity” (Herm 482). This time, however, he insisted that the Stoic practices were fundamentally different: “However, all these elements seem to me to be profoundly different from what we should call ‘confession’ in the strict, or anyway, spiritual sense of the word” (Herm 365). In The Care of the Self, Foucault again conceded that De ira—what he now called “the most detailed description” of antique practices of the self—looked “at first glance” like a Christian confession, but he again maintained that it is something quite different: “The purpose of the examination is not therefore to discover one’s own guilt, down to its most trifling forms” (CS 61–62). Foucault concluded that the various “discourses of the self”—the confession and the Greek techniques of the self—could not be placed into a single category (see GE 250). Indeed, the “profound difference” (Herm 299) between these two discourses of the self was perhaps Foucault’s most repeated claim of the 1980s (see Herm 222, 237–44, 299, 308; GE 247–48; WS 237; AB 207–8; RFT 27; UP 89; CS 239; SS 5; FI 5, 12; FS 30, 35, 44, 87, 96, 97, 143–45, 147).It is worth asking why Foucault returned so consistently to the distinction between these two discursive forms. This question gains even more relevance for readers of this journal when we remember that, on at least two occasions, Foucault defined one of these forms, the ancient techniques of the self, in terms of its opposition to rhetoric: the techniques of the self, he claimed, are “nonrhetorical” (Herm 368; FS 20). Thus the question that drives this essay is not so much why Foucault attached such importance to the distinction but rather how rhetoric itself might differentiate the confession from the techniques of the self. Stated differently, Foucault’s work on the confession vis-à-vis the technologies of the self provides a valuable opportunity to study the role of rhetoric in Foucault’s thought—not because they are both rhetorical forms but, curiously, because Foucault insists that one is not.In order to foreground the work of rhetoric in Foucault’s thought, I situate his discourses of the self in the context of Nietzsche’s critique of metonymy. Although this may seem arbitrary, it gains initial plausibility from three facts. First, we know that Foucault understood rhetoric in terms of tropes (OT 84; Cooper 1988, 4). Second, we know too that Foucault had a deep... (shrink)

It is well established that microRNAs (miRNAs) induce mRNA degradation by binding to 3′ untranslated regions (UTRs). The functionality of sites in the coding domain sequence (CDS), on the other hand, remains under discussion. Such sites have limited impact on target mRNA abundance and recent work suggests that miRNAs bind in the CDS to inhibit translation. What then could be the regulatory benefits of translation inhibition through CDS targeting compared to mRNA degradation following 3′ UTR binding? We propose that (...) these domain‐dependent effects serve to diversify the functional repertoire of post‐transcriptional gene expression control. Possible regulatory benefits may include tuning the time‐scale and magnitude of post‐transcriptional regulation, regulating protein abundance depending on or independently of the cellular state, and regulation of the protein abundance of alternative splice variants. Finally, we review emerging evidence that these ideas may generalize to RNA‐binding proteins beyond miRNAs and Argonaute proteins. (shrink)

Network motifs are small patterns of connections, found over‐represented in gene regulatory networks. An example is the negative feedback loop (e.g. factor A represses itself). This opposes its own state so that when ‘on’ it tends towards ‘off’ – and vice versa. Here, we argue that such self‐opposition, if considered dimensionlessly, is analogous to the liar paradox: ‘This statement is false’. When ‘true’ it implies ‘false’ – and vice versa. Such logical constructs have provided philosophical consternation for over 2000 (...) years. Extending the analogy, other network topologies give strikingly varying outputs over different dimensions. For example, the motif ‘A activates B and A. B inhibits A’ can give switches or oscillators with time only, or can lead to Turing‐type patterns with both space and time (spots, stripes or waves). It is argued here that the dimensionless form reduces to a variant of ‘The following statement is true. The preceding statement is false’. Thus, merely having a static topological description of a gene network can lead to a liar paradox. Network diagrams are only snapshots of dynamic biological processes and apparent paradoxes can reveal important biological mechanisms that are far from paradoxical when considered explicitly in time and space. (shrink)

Background: As genetics technology proceeds, practices of genetic testing have become more heterogeneous: many different types of tests are finding their way to the public in different settings and for a variety of purposes. This diversification is relevant to the discourse on ethical, legal and societal issues (ELSI) surrounding genetic testing, which must evolve to encompass these differences. One important development is the rise of personal genome testing on the basis of genetic profiling: the testing of multiple genetic variants (...) simultaneously for the prediction of common multifactorial diseases. Currently, an increasing number of companies are offering personal genome tests directly to consumers and are spurring ELSI-discussions, which stand in need of clarification. This paper presents a systematic approach to the ELSI-evaluation of personal genome testing for multifactorial diseases along the lines of its test characteristics.DiscussionThis paper addresses four test characteristics of personal genome testing: its being a non-targeted type of testing, its high analytical validity, low clinical validity and problematic clinical utility. These characteristics raise their own specific ELSI, for example: non-targeted genetic profiling poses serious problems for information provision and informed consent. Questions about the quantity and quality of the necessary information, as well as about moral responsibilities with regard to the provision of information are therefore becoming central themes within ELSI-discussions of personal genome testing. Further, the current low level of clinical validity of genetic profiles raises questions concerning societal risks and regulatory requirements, whereas simultaneously it causes traditional ELSI-issues of clinical genetics, such as psychological and health risks, discrimination, and stigmatization, to lose part of their relevance. Also, classic notions of clinical utility are challenged by the newer notion of 'personal utility.'SummaryConsideration of test characteristics is essential to any valuable discourse on the ELSI of personal genome testing for multifactorial diseases. Four key characteristics of the test - targeted/non-targeted testing, analytical validity, clinical validity and clinical utility - together determine the applicability and the relevance of ELSI to specific tests. The paper identifies and discusses four areas of interest for the ELSI-debate on personal genome testing: informational problems, risks, regulatory issues, and the notion of personal utility. (shrink)

We apply molecular code theory to a rule-based model of the human inner kinetochore and study how complex formation in general can give rise to molecular codes. We analyze 105 reaction networks generated from the rule-based inner kinetochore model in two variants: with and without dissociation of complexes. Interestingly, we found codes only when some but not all complexes are allowed to dissociate. We show that this is due to the fact that in the kinetochore model proteins can only (...) bind at kinetochores by attaching to already attached proteins and cannot form complexes in free solution. Using a generalized linear mixed model we study which centromere protein can take which role in a molecular code . By this, associations between CENPs and code roles are found. We observed that CenpA is a major risk factor while CenpQ is a major protection factor . Finally we show, using an abstract model of copolymer formation, that molecular codes can also be realized solely by the formation of stable complexes, which do not dissociate. For example, with particular dimers as context a molecular code mapping from two different monomers to two particular trimers can be realized just by non-selective complex formation. We conclude that the formation of protein complexes can be utilized by the cell to implement molecular codes. Living cells thus facilitate a subsystem allowing for an enormous flexibility in the realization of mappings, which can be used for specific regulatory processes, e.g. via the context of a mapping. (shrink)

Open peer commentary on the article “Interactivity and Enaction in Human Cognition” by Matthew Isaac Harvey, Rasmus Gahrn-Andersen & Sune Vork Steffensen. Upshot: In contrasting an interactivity account alternative to variants on the enactive approach, the authors discuss the role of sense-making. They claim that their interactivity perspective, unlike enactive approaches, accounts for a dependency on “non-local” resources characteristic of many organisms. I draw attention to the cybernetic-enactivist perspective on homeostatic sense-making, which may fundamentally fail to explain the operationally (...) open nature of organismic regulatory processes better captured by Sterling’s notion of “allostasis.” This sense-making model appears to be more in line with Harvey et al.’s interactivity framework, focusing as it does on the regulatory effect of extrinsic “norms” rather than the cybernetic-enactivist focus on intrinsic “norms.”. (shrink)

A gene is considered essential when its loss of function results in a deleterious phenotype, hugely reducing the organism's viability or fitness. However, the link between the essentiality of a gene and its degree of polymorphism is unclear. In this review, we show that there is a place for a certain degree of variability, even for essential genes. We first study the role of infectious diseases in the prevalence of genetic disorders among humans: balancing selection has selected harmful variants (...) due to the selective pressure of pathogens because the heterozygous carrier can resist them. Then we show that the environment can induce adaptation of species by rapidly evolving genes. We also study the role of positive selection on speciation, particularly upon genes of the immune, reproductive and nervous systems. Finally, we highlight the role of regulatory sequences in changes in morphology between species and adaptation to the environment within species. (shrink)

Have the large-scale evolutionary patterns illustrated by the fossil record been driven by fluctuations in environmental opportunity, by biotic factors, or by changes in the types of phenotypic variants available for evolutionary change? Since the Modern Synthesis most evolutionary biologists have maintained that microevolutionary processes carrying on over sufficient time will generate macroevolutionary patterns, with no need for other pattern-generating mechanisms such as punctuated equilibrium or species selection. This view was challenged by paleontologists in the 1970s with proposals that (...) the differential sorting and selection of species and clades, and the effects of biotic crises such as mass extinctions, were important extensions to traditional evolutionary theory. More recently those interested in macroevolution have debated the relative importance of abiotic and biotic factors in driving macroevolutionary patterns and have introduced comparative phylogenetic methods to analyze the rates of change in taxonomic diversity. Applying Peter Godfrey-Smith’s distinction between distributional explanations and explanations focusing on the origin of variation, most macroevolutionary studies have provided distributional explanations of macroevolutionary patterns. Comparative studies of developmental evolution, however, have implicated the origin of variants as a driving macroevolution force. In particular, the repatterning of gene regulatory networks provides new insights into the origins of developmental novelties. This raises the question of whether macroevolution has been pulled by the generation of environmental opportunity, or pushed by the introduction of new morphologies. The contrast between distributional and origination scenarios has implications for understanding evolutionary novelty and innovation and how macroevolutionary process may have evolved over time. (shrink)

In the article the author analyzes the phenomenon of ideological work from the socio-philosophical point of view and conducts general conceptualization of ideological work process in the Armed Forces of Ukraine. The author proposes his own variant of definition of object, functions, the main tasks of ideological work in the Ukrainian army. The main goal of ideological work in the Armed Forces of Ukraine is to achieve and maintain high morale of the Armed Forces personnel, to train in military servicemen (...) the sense of personal responsibility for protection of Motherland, to understand the principles of state policy and measures taken in the interest of ensuring national and international security. The above goal is achieved through realization of the objective function, which lies in the ideological motivation of military servicemen towards conscientious performance of military duty and defense of the homeland, implemented under the formula "knowledge - attitude - motivation." After decomposition of the objective function of ideological work in the Armed Forces of Ukraine, the author has singled out a number of working functions - genetic, epistemological, logical, methodological, methodical, informational, propagandistic, agitational, worldview, regulatory, mobilizational, educational, counter propagandistic, protective, cultural educational, spiritually educational, evaluative ones. The author has defined situations in which genetic function of ideological work in the Armed Forces can be noticeably manifested: the formation of a qualitatively new principles of state construction in the context of social transformation; formation of a qualitatively new principles of military construction and military-political course of the state in the context of military and political changes in the international arena, as well as in the middle of military- political alliances; in the period of preparation for the war, during the direct military operations, in the postwar period with the aim of establishing of "victory image" and "victorious war image " in the media and in the public consciousness. (shrink)

Increasing genetic knowledge over the last decade has enabled hundreds of genetic variants associated with inherited cardiac conditions to be identified, many of which cause increased risk of sudden cardiac death. While individually these conditions are rare, taken together they impose a significant burden. The severity of these conditions—the possibility that they might cause sudden unheralded death of a teenager or young adult—juxtaposed with uncertainty about the pathology linked with many of the genetic variants is significant in terms (...) of professional practice because, increasingly, clinicians have been encouraged to cascade out genetic testing from the proband or consultand to other family members who may be at risk of developing the same condition. This process often involves sharing human tissue samples, DNA or personal information. This paper reviews the legal and regulatory frameworks which may apply when tissue and DNA samples are collected, used and retained, both for the purpose of diagnosis and for benefiting other family members, when a suspected or definitive diagnosis of an inherited cardiovascular condition is made. Sometimes the interests of family members may conflict, and it may be difficult for practitioners to reconcile the interests of one family member with another, particularly if the balance of benefits and harms from testing is unclear. The paper then examines some of the ethical tensions which may arise in practice and concludes that all involved should be conversant with the legal and ethical frameworks that apply. (shrink)

The nomination of candidate genes underlying complex traits is often focused on genetic variations that alter mRNA abundance or result in non‐conservative changes in amino acids. Although inconspicuous in complex trait analysis, genetic variants that affect splicing or RNA editing can also generate proteomic diversity and impact genetic traits. Indeed, it is known that splicing and RNA editing modulate several traits in humans and model organisms. Using high‐throughput RNA sequencing (RNA‐seq) analysis, it is now possible to integrate the genetics (...) of transcript abundance, alternative splicing (AS) and editing with the analysis of complex traits. We recently demonstrated that both AS and mRNA editing are modulated by genetic and environmental factors, and potentially engender phenotypic diversity in a genetically segregating mouse population. Therefore, the analysis of splicing and RNA editing can expand not only the regulatory landscape of transcriptome and proteome complexity, but also the repertoire of candidate genes for complex traits. (shrink)

This theoretical paper examines the context-sensitivity of the impact of cultural norms on prejudice regulation. Granting the importance of understanding intergroup dynamics in cultural-ecological contexts, we focus on the peculiarities of the French diversity approach. Indeed, the major cultural norm, the Laïcité is declined today in two main variants: The Historic Laïcité, a longstanding egalitarian norm coexisting with its amended form: The New Laïcité, an assimilationist norm. In fact, these co-encapsulated Laïcité variants constitute a fruitful ground to cast (...) light on the processes underlying prejudice regulation. Indeed, it is documented that the assimilationist New Laïcité is linked to higher levels of prejudice as compared to the egalitarian Historic Laïcité. To this day, research mainly explored interindividual determinants of Laïcité endorsements and specified how these endorsements shape prejudice. Crucially, this “indirect-endorsement path” does not account for the more straightforward causal relationship between Laïcité and prejudice. Moreover, recent experimental evidence suggests that the normative salience of both Laïcité norms shape intergroup attitudes beyond personal endorsement. Therefore, in this contribution, we complement previous work by investigating the possible socio-cognitive processes driving this “direct-contextual path.” In doing so, we seek to bridge the gap of causality by investigating how the Laïcité norms can set the stage for specific regulatory strategies. Our reasoning derives from an application of the Justification-Suppression Model bolstered by classical work on mental control, modern racism and diversity ideology. From this, we sketch out the operative functioning of two distinct regulation processes: one that prevents prejudicial attitudes but which can have unexpected consequences on stereotyping within the Historic Laïcité context and one that helps realize prejudice within the New Laïcité context. From this analysis, we discuss the consequences for intergroup relations within and beyond the French context. In particular, we outline the importance of an adequate framing of egalitarian ideologies so that they achieve their goal to foster harmonious intergroup relations. (shrink)

Waddington’s experiments on genetic assimilation showed that selection on environmentally induced phenotypic variants can cause inherited evolutionary changes in the phenotype. We have recently extended this work by demonstrating that it is possible to select for a polyphenism in a monophenic species . We found that a mutation in the juvenile hormone regulatory pathway in Manduca sexta enabled heat stress to reveal a hidden reaction norm of larval coloration. Artificial selection for increased color change in response to heat-shock (...) resulted in the genetic accommodation of a black/green larval color polyphenism, caused by an environment-sensitive threshold switch mediated by the endocrine system. (shrink)

Protein complexes perform many important functions in the cell. Large‐scale studies of protein–protein interactions have not only revealed new complexes but have also placed many proteins into multiple complexes. Whilst the advocates of hypothesis‐free research touted the discovery of these shared components as new links between diverse cellular processes, critical commentators denounced many of the findings as artefacts, thus questioning the usefulness of large‐scale approaches. Here, we survey proteins known to be shared between complexes, as established in the literature, and (...) compare them to shared components found in high‐throughput screens. We discuss the various challenges to the identification and functional interpretation of bona fide shared components, namely contaminants, variant and megacomplexes, and transient interactions, and suggest that many of the novel shared components found in high‐throughput screens are neither the results of contamination nor central components, but appear to be primarily regulatory links in cellular processes. BioEssays 26:1333–1343, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

This paper discusses the varieties of capitalism in transitional societies in Latin America and Central / Eastern Europe. The intended purpose of these transitions from semi-closed import-substituting economies in the first case and state socialist ones in the second was to institutionalize open-market economies. Twenty or thirty years later, there is a variety of types of capitalism in these countries, which I classify into three: open-market, neo-mercantilist, and anemic. The question for sociology is whether these quite different variants represent (...) temporary stages or distortions in the same process of transition or whether, on the contrary, they may institutionalize as discrete forms of peripheral capitalism. Neither standard “legacy” argu­ments nor institutionalist theories offer satisfactory answers to this question. The multiple modernities approach, on the other hand, is more appropriate as a theoretical perspective, but it has not produced yet specific propositions applicable to this question. My paper makes two claims. First, the successful transfer of institutions depends on the congruence between these institutions and the broader institutional framework of the recipient economies, a point not developed by institutionalist theories. I offer a hypothesis in this regard: Two critical nodes of congruence are the regulatory and extractive capacity of the state and the strength of civil society. Second, market capitalism (as liberal democracy as well) is a complex institution, and some of its components “travel” more easily across societies and institutional frameworks, and therefore are easier to institutionalize. This is the source of the hybrid variants. (shrink)

In neuroethology, the nervous system and behavior are analyzed in the context of the animal's natural habitat and evolutionary history. For the last 30 years the influence of genetics on neuroethology has steadily grown, particularly in Drosophila. Genetic variants reveal new properties of neurons; they help to dissect neuronal circuits and complex behavioral systems; genetics provides new methods to visualize certain brain structures and to assign behavioral functions to them; and, finally, genetic variants can be used to test (...) ecological models. While single‐gene mutations can have highly specific behavioral effects, molecular analysis of the corresponding genes reveals that the latter normally have a much broader functional scope. The ‘graininess’ of a functional model of the brain, therefore, is defined by the independent regulatory units of the genes rather than by the genes themselves. (shrink)

This article examines the way in which public controversies affect regulatory science. It describes the controversy that unfolded in Europe around the use of the ninety-day rat-feeding tests for the risk assessment of genetically modified plants. This type of test had been criticized for almost two decades by toxicologists, nongovernmental organizations, and industry alike for its inability to capture the specific health effects of GM plants. But GM risk assessment experts showed great reluctance to move toward a more systematic (...) use of other tests, such as chronic two-year studies or toxicogenomic techniques, and made sure that official guidance continues to recommend the use of the ninety-day rat-feeding study. The article shows that these tactics of standardization are a defining feature of regulatory science, and a resource for toxicity experts to defend their authority and credibility against competing expertises that arise during controversies. (shrink)

The need to better balance the promotion of scientific and technological innovation with risk management for consumer protection has inspired several recent reforms attempting to make regulations more flexible and adaptive. The pharmaceutical sector has a long, established regulatory tradition, as well as a long history of controversies around how to balance incentives for needed therapeutic innovations and protecting patient safety. The emergence of disruptive biotechnologies has provided the occasion for regulatory innovation in this sector. This article investigates (...) the regulation of advanced biotherapeutics in the European Union and shows that it presents several defining features of an adaptive regulation regime, notably institutionalized processes of planned adaptation that allow regulators to gather, generate, and mobilize new scientific and risk evidence about innovative products. However, our in-depth case analysis highlights that more attention needs to be paid to the consequences of the introduction of adaptive regulations, especially for critical stakeholders involved in this new regulatory ecosystem, the capacity and resource requirements placed on them to adapt, and the new tradeoffs they face. In addition, our analysis highlights a deficit in how we currently evaluate the performance and public value proposition of adaptive regulations vis-à-vis their stated goals and objectives. (shrink)

This chapter contains sections titled: What I s Regulation? How Should We Morally Evaluate Regulation? Welfarism; the Pareto Principle; Kaldor‐Hicks Efficiency versus Social Welfare Functions The Two Fundamental Theorems of Welfare Economics and the Market Failure Framework Externalities Public Goods and Monopoly Power The Coase Theorem Information and Paternalism as Rationales for Regulation Regulatory Forms and Regulatory Choice Criteria References.

An efficient variant of the double-negation translation explains the relationship between Shoenfield’s and G¨odel’s versions of the Dialectica interpretation.

Various connexive FDE-based modal logics are studied. Some of these logics contain a conditional that is both connexive and strict, thereby highlighting that strictness and connexivity of a conditional do not exclude each other. In particular, the connexive modal logics cBK-\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-}$$\end{document}, cKN4, scBK-\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-}$$\end{document}, scKN4, cMBL, and scMBL are introduced semantically by means of classes of Kripke models. The logics cBK-\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} (...) \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-}$$\end{document} and cKN4 are connexive variants of the FDE-based modal logics BK-\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-}$$\end{document} and KN4 with a weak and a strong implication, respectively. The system cMBL is a connexive variant of the modal bilattice logic MBL. The latter is a modal extension of Arieli and Avron’s logic of logical bilattices and is characterized by a class of Kripke models with a four-valued accessibility relation. In the systems scBK-\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-}$$\end{document}, scKN4, and scMBL, the conditional is both connexive and strict. Sound and complete tableau calculi for all these logics are presented and used to show that the entailment relations of the systems under consideration are decidable for finite premise set. Moreover, the logics cBK-\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathbf {cBK}^-$$\end{document} and cMBL\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathbf {cMBL}$$\end{document} are shown to be algebraizable. The algebraizability of cMBL\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathbf {cMBL}$$\end{document} is derived from proving cMBL\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathbf {cMBL}$$\end{document} to be definitionally equivalent to MBL\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathbf {MBL}$$\end{document}. All connexive modal logics studied in this paper are decidable, paraconsistent, and inconsistent but non-trivial logics. (shrink)

The financial sector has seen a transformation towards ‘sustainable’ finance particularly in Europe, driven also by unprecedented regulatory reforms. At the same time, many are sceptical about the real impact of these reforms, fearing that they are triggering a paradoxical financialisation of sustainability. Building on recent research on institutional logics and institutional fields formation, we examine changes in the EU regulatory dynamics as characterised by shifts in framing the relationship between sustainability and finance. Deploying a longitudinal approach, consisting (...) of archival data and semi-structured interviews, we explore the development of EU sustainable finance regulation as an extended, interactive and contested process. Specifically, we suggest that regulatory dynamics depend on the hybrid configuration of the social constituencies supporting sustainable finance reforms and on shifts in the overall prevalence of the financial logic in society. Our paper sheds light on the inherent contradictions and limitations of sustainable finance as a means for transformative sustainability reforms. (shrink)

Regulating technologies, innovations and risks is an activity that, as much as scientific research needs proofs and evidence. It is the site of development of a distinct kind of science, regulatory science. This special issue addresses the question of the standards of knowledge governing how we test, assess and monitor technologies and their effects. This topic is relevant and timely in the light of problematics of regulation of innovation, regulatory failure and capture. Given the enormous decisions and stakes (...) regulatory science commends, it becomes crucial to ask where its standards come from and gain credibility, but also what valuations of technology and appreciations of their risks or benefits do they embed, and who controls them? This paper introduces the four contributions comprising the special issue, and outlines a perspective from which to question the construction of regulatory science or, in the terminology adopted here, the authorization and standardization of regulatory knowledge, particularly the role of networks of scientific experts therein. (shrink)

The use of preimplantation genetic diagnosis, the powerful technique employed during fertility treatment to select embryos based on their genes, is currently unregulated in the United States—unlike in nearly all other countries where PGD is available. Of course, the analytical quality of the genetic tests, the laboratories where they are performed, and the technicians who carry them out are subject to the Clinical Laboratory Improvement Amendment requirements. And as the Food and Drug Administration prepares to begin regulating laboratory‐developed tests, including (...) many genetic tests, the clinical validity of the tests may also need to be demonstrated. But neither CLIA nor the U.S. Food and Drug Administration is responsible for governing medical practice, and state law and the relevant medical associations have largely fallen silent on the questions of when and why PGD ought to be performed. The result of this regulatory lacuna is that while PGD was originally intended for screening embryos for severe heritable disorders, it is now also employed for a variety of more controversial purposes. (shrink)

The marketing of unproven direct-to-consumer stem cell interventions is becoming widespread in Canada. There is little evidence supporting their use and they have been associated with a range of harms. Canada has been slower to act against clinics offering these interventions than other jurisdictions, including the United States. Here, we outline the regulatory and policy tools available in Canada to address this growing problem. Health Canada’s regulations governing cell therapies are complex, but recent statements make it clear that Health (...) Canada believes it has jurisdiction over many of the currently marketed stem cell interventions. Still, further regulatory clarity is needed from Health Canada, as are increased directed enforcement efforts on interventions that fall within their scope. The Competition Bureau, via the Competition Act, prohibits advertisers from making materially false or misleading promotional representations. The Competition Bureau could collaborate with the scientific community to analyze the claims of existing clinics in Canada, and impose sanctions upon those who breach the established standard. Professional regulators, including provincial colleges of physicians and surgeons, have considerable power over what products and services their members can offer. Every college of physicians in Canada requires, via policy and codes of ethics, that doctors maintain evidence-based practices. This requirement is incompatible with offering many unproven stem cell interventions. Litigation may be another tool, including the use of fraud, misrepresentation and/or negligence claims for failing to meet the required standard of care. Finally, political pressure on federal and provincial lawmakers could encourage changes to marketing, cell therapy and professional regulations that would allow a more comprehensive response. In sum, there are many existing tools that can be used to protect the public from unproven stem cell interventions. Increased bureaucratic will and grassroots efforts are needed in order to effect a positive policy response. (shrink)

This Article examines the regulatory state through the lens of evolving political economy, arguing that a significant reconstruction is now underway. The ongoing shift from an industrial mode of development to an informational one has created existential challenges for regulatory models and constructs developed in the context of the industrial economy. Contemporary contests over the substance of regulatory mandates and the shape of regulatory institutions are most usefully understood as moves within a larger struggle to chart (...) a new direction for the regulatory state in the era of informational capitalism. A regulatory state optimized for the information economy must develop rubrics for responding to three problems that have confounded existing regulatory regimes: platform power — the power to link facially separate markets and/or to constrain participation in markets by using technical protocols; infoglut — unmanageably voluminous, mediated information flows that create information overload; and systemic threat — nascent, probabilistically-defined harm to be realized at some point in the future. Additionally, it must develop institutions capable of exercising effective oversight of informationera activities. The information-era regulatory models that have begun to emerge are procedurally informal, mediated by networks of professional and technical expertise that define relevant standards, and financialized. Such models, however, also have tended to be both opaque to external observation and highly prone to capture. New institutional forms that might ensure their legal and political accountability have been slow to develop. (shrink)

This chapter contains sections titled: Introduction Background Incentives and guidance from the criminal law Other regulatory incentives and guidance Civil incentives Conclusion.

This timely book examines the interaction of health research and regulation with law through empirical analysis and the application of key anthropological concepts to reveal the inner workings of human health research. Through ground-breaking empirical inquiry, Regulatory Stewardship of Health Research explores how research ethics committees (RECs) work in practice to both protect research participants and promote ethical research.This thought-provoking book provides new perspectives on the regulation of health research by demonstrating how RECs and other regulatory actors seek (...) to fulfil these two functions by performing a role of 'regulatory stewardship'. This involves guiding researchers through stages of research approval, as well as seeking to maximise benefits for participants and society while minimising risks. Arguing that participant protection and research promotion should rightly be treated as twin objectives for health research regulators, this book asserts that there is a need for more overt recognition of the importance and function of the deliberative space in which RECs can negotiate the risks relevant to a research application.This book is a key resource for academics and students interested in health research and regulation, and the dynamic interaction of ethics and the law. Regulators and policy-makers will also find it to be an insightful and illuminating text for the practical insights that it reveals about research governance in action. (shrink)

L’article de Karl Popper « Indeterminism in Quantum Physics and in Classical Physics » est tombé injustement dans l’oubli. Popper jugeait le déterminisme faux : l’avenir est ouvert. En principe, remplacer la variante de Laplace de la pré-détermination par une prédétermination prévisible permet de rendre scienti-fique, donc réfutable, le déterminisme « scientifique ». Popper a affirmé qu’il l’avait réfuté. Maintenant, un système métaphysique peut avoir une extension – au sens mathématique – qui le rend explicatif et testable. Si une extension (...) existe, alors elle n’est pas unique, et de nombreuses autres extensions alterna-tives existent. La preuve de Popper n’est alors pas concluante. (shrink)

Capitalist dynamics in knowledge production are not limited to situations in which economic interests influence researchers’ practices. Building on laboratory studies and the French “pragmatic” tradition in sociology, this article proposes an approach to tackle more pervasive capitalist logics at work in contemporary research and their consequences. It uses the term epistemic capitalism to denote the accumulation of capital, as worth made durable, through the act of doing research, in and beyond academia. In doing so, it conceptualizes capitalism primarily not (...) as a system of circulation and accumulation of monetary value but rather as a cultural way of producing, attributing, and accumulating specific forms of worth, which need not be monetary. Empirically, the article studies variants in epistemic capitalism by addressing the differing role of the accumulation of different forms of capital and the regimes connected to it in two institutional settings in Austria, academic life science laboratories and biotechnology start-up companies. Concluding, it argues that analytically dissociating the concept of capitalism from its link to economic value allows a finer-grained cultural analysis of the importance and effects of processes of accumulation in contemporary research. It ends with discussing the normative implications of these findings for debates about the commercialization of academia. (shrink)