Current debates about the replication crisis in psychology take it for granted that direct replication is valuable and focus their attention on questionable research practices in regard to statistical analyses. This paper takes a broader look at the notion of replication as such. It is argued that all experimentation/replication involves individuation judgments and that research in experimental psychology frequently turns on probing the adequacy of such judgments. In this vein, I highlight the ubiquity of conceptual and (...) material questions in research, and I argue that replication is not as central to psychological research as it is sometimes taken to be. (shrink)

Replications are often taken to play both epistemic and demarcating roles in science: they provide evidence about the reliability of fields’ methods and, by extension, about which fields “count” as scientific. I argue that, in a field characterized by a high degree of theoretical openness and uncertainty, like comparative cognition, replications do not sit well in these roles. Like other experiments conducted under conditions of uncertainty, replications are often equivocal and open to interpretation. As a result, they are poorly placed (...) to deliver clear judgments about the reliability of comparative cognition’s methods or its scientific bona fides. I suggest that this should encourage us to take a broader view of both the nature of scientific progress and the role of replication in comparative cognition. (shrink)

Replicability and reproducibility of computational models has been somewhat understudied by “the replication movement.” In this paper, we draw on methodological studies into the replicability of psychological experiments and on the mechanistic account of explanation to analyze the functions of model replications and model reproductions in computational neuroscience. We contend that model replicability, or independent researchers' ability to obtain the same output using original code and data, and model reproducibility, or independent researchers' ability to recreate a model without original (...) code, serve different functions and fail for different reasons. This means that measures designed to improve model replicability may not enhance (and, in some cases, may actually damage) model reproducibility. We claim that although both are undesirable, low model reproducibility poses more of a threat to long-term scientific progress than low model replicability. In our opinion, low model reproducibility stems mostly from authors' omitting to provide crucial information in scientific papers and we stress that sharing all computer code and data is not a solution. Reports of computational studies should remain selective and include all and only relevant bits of code. (shrink)

Nowadays, almost everyone seems to agree that science is facing an epistemological crisis – namely the replicability crisis – and that we need to take action. But as to precisely what to do or how...

he theory o f natural selection provides a mechanistic, causal account of how living things came to look as if they had been designed for a purpose. So overwhelming is the appearance of purposeful design that, even in this Darwinian era when we know "better," we still find it difficult, indeed boringly pedantic, to refrain from teleological language when discussing adaptation. Birds' wings are obviously "for" flying, spider webs are for catching insects, chlorophyll molecules are for photosynthesis, DNA molecules are (...) for... What are DNA molecules for? The question takes us aback. In my case it touches off an almost audible alarm siren in the mind. If we accept the view of life that I wish to espouse, it is the forbidden question. DNA is not "for" anything. If we wish to speak teleologically, all adaptations are for the preservation of DNA; DNA itself just is. Following Williams, I have advocated this view at length, and I do not want to repeat myself here. Instead I shall try to clear up an important misunderstanding of the view, a misunderstanding that has constituted an unnecessary barrier to its acceptance. (shrink)

The Developmental Systems approach to evolution is defended against the alternative extended replicator approach of Sterelny, Smith and Dickison (1996). A precise definition is provided of the spatial and temporal boundaries of the life-cycle that DST claims is the unit of evolution. Pacé Sterelny et al., the extended replicator theory is not a bulwark against excessive holism. Everything which DST claims is replicated in evolution can be shown to be an extended replicator on Sterelny et al.s definition. Reasons are given (...) for scepticism about the heuristic value claimed for the extended replicator concept. For every competitive, individualistic insight the replicator theorist has a cooperative, systematic blindspot. (shrink)

According to a once influential view of selection, it consists of repeated cycles of replication and interaction. It has been argued that this view is wrong: replication is not necessary for evolution by natural selection. I analyze the nine most influential arguments for this claim and defend the replication–interaction conception of selection against these objections. In order to do so, however, the replication–interaction conception of selection needs to be modified significantly. My proposal is that replication (...) is not the copying of an entity, the replicator, but the copying of a property. Thus, we can have a replication process without there being a replicator that is being copied. (shrink)

Formulation of a general model of evolution is presented which is based upon the recognition of the ?biosocial? entity, that is the biosphere and human society, as a component?system. It can be demonstrated that the interactions of the components (moleculas, cells, organisms, ecosystems in the biological realms and people, artifacts and ideas in the societies) have replicative organization. We suggest an explanation for the spontaneous emergence of replicative function and organization, a process called autogenesis. During autogenesis, hierarchical levels of replicative (...) organization emerge and compartmentalization and convergence of replicative information occurs. Questions of the origin and evolution of life are discussed. The replicative paradigm can also be applied to the processes of cultural evolution, in which complex replicative networks of people, ideas, and man?made artifacts show all stages and phenomena of autogenesis. Finally, the present state of evolution of the whole global biosocial system is discussed. (shrink)

The history and theoretical role of the concept of a ``replicator''is discussed, starting with Dawkins' and Hull's classic treatmentsand working forward. I argue that the replicator concept is still auseful one for evolutionary theory, but it should be revised insome ways. The most important revision is the recognition that notall processes of evolution by natural selection require thatsomething play the role of a replicator.

Replication protein A (RPA) is the main eukaryotic single‐stranded DNA (ssDNA) binding protein, having essential roles in all DNA metabolic reactions involving ssDNA. RPA binds ssDNA with high affinity, thereby preventing the formation of secondary structures and protecting ssDNA from the action of nucleases, and directly interacts with other DNA processing proteins. Here, we discuss recent results supporting the idea that one function of RPA is to prevent annealing between short repeats that can lead to chromosome rearrangements by microhomology‐mediated (...) end joining or the formation of hairpin structures that are substrates for structure‐selective nucleases. We suggest that replication fork catastrophe caused by depletion of RPA could result from cleavage of secondary structures by nucleases, and that failure to cleave hairpin structures formed at DNA ends could lead to gene amplification. These studies highlight the important role RPA plays in maintaining genome integrity. (shrink)

Replication protein A (RPA), the major single‐stranded DNA‐binding protein in eukaryotic cells, is required for processing of single‐stranded DNA (ssDNA) intermediates found in replication, repair, and recombination. Recent studies have shown that RPA binding to ssDNA is highly dynamic and that more than high‐affinity binding is needed for function. Analysis of DNA binding mutants identified forms of RPA with reduced affinity for ssDNA that are fully active, and other mutants with higher affinity that are inactive. Single molecule studies (...) showed that while RPA binds ssDNA with high affinity, the RPA complex can rapidly diffuse along ssDNA and be displaced by other proteins that act on ssDNA. Finally, dynamic DNA binding allows RPA to prevent error‐prone repair of double‐stranded breaks and promote error‐free repair. Together, these findings suggest a new paradigm where RPA acts as a first responder at sites with ssDNA, thereby actively coordinating DNA repair and DNA synthesis. (shrink)

Does cultural evolution happen by a process of copying or replication? And how exactly does cultural transmission compare with that paradigmatic case of replication, the copying of DNA in living cells? Theorists of cultural evolution are divided on these issues. The most important objection to the replication model has been leveled by Dan Sperber and his colleagues. Cultural transmission, they argue, is almost always reconstructive and transformative, while strict ‘replication’ can be seen as a rare limiting (...) case at most. By means of some thought experiments and intuition pumps, I clear up some confusion about what qualifies as ‘replication’. I propose a distinction between evocation and extraction of cultural information, applying these concepts at different levels of resolution. I defend a purely abstract and information-theoretical definition of replication, while rejecting more material conceptions. In the end, even after taking Sperber’s valuable and important points on board, the notion of cultural replication remains a valid and useful one. This is fortunate, because we need it for certain explanatory projects. (shrink)

We argue that the epistemic functions of replication in science are best understood by their role in assessing kinds of experimental error. Direct replications serve to assess the reliability of an experiment through its precision: the presence and degree of random error. Conceptual replications serve to assess the validity of an experiment through its accuracy: the presence and degree of systematic errors. To illustrate the aptness of this view, we examine the Hubble constant controversy in astronomy, showing how astronomers (...) have responded to the concordances and discordances in their results by carrying out the different kinds of replication that we identify, with the aim of establishing a precise, accurate value for the Hubble constant. We contrast our view with Machery’s “re-sampling” account of replicability, which maintains that replications only assess reliability. (shrink)

The replicability of experiment is routinely offered as the gold standard of evidence. I argue that it is not supported by a universal principle of replicability in inductive logic. A failure of replication may not impugn a credible experimental result; and a successful replication can fail to vindicate an incredible experimental result. Rather, employing a material approach to inductive inference, the evidential import of successful replication of an experiment is determined by the prevailing background facts. Commonly, these (...) background facts do support successful replication as a good evidential guide and this has fostered the illusion of a deeper, exceptionless principle. (shrink)

Popper’s (1983, 2002) philosophy of science has enjoyed something of a renaissance in the wake of the replication crisis, offering a philosophical basis for the ensuing science reform movement. However, adherence to Popper’s approach may also be at least partly responsible for the sense of “crisis” that has developed following multiple unexpected replication failures. In this article, I contrast Popper’s approach with Lakatos’ (1978) approach and a related approach called naïve methodological falsificationism (NMF; Lakatos, 1978). The Popperian approach (...) is powerful because it is based on logical refutation, but its theories are noncausal and, therefore, lacking in scientific value. In contrast, the Lakatosian approach considers causal theories, but it concedes that these theories are not logically refutable. Finally, the NMF approach subjects Lakatosian causal theories to Popperian logical refutations. However, its approach of temporarily accepting a ceteris paribus clause during theory testing may be viewed as scientifically inappropriate, epistemically inconsistent, and “completely redundant” (Lakatos, 1978, p. 40). I conclude that the replication “crisis” makes the most sense in the context of the Popperian and NMF approaches because it is only in these two approaches that replication failures represent logical refutations of theories. In contrast, replication failures are less problematic in the Lakatosian approach because they do not logically refute theories. Indeed, in the Lakatosian approach, replication failures can be legitimately ignored or used to motivate theory development. (shrink)

This fascinating study in the sociology of science explores the way scientists conduct, and draw conclusions from, their experiments. The book is organized around three case studies: replication of the TEA-laser, detecting gravitational rotation, and some experiments in the paranormal. "In his superb book, Collins shows why the quest for certainty is disappointed. He shows that standards of replication are, of course, social, and that there is consequently no outside standard, no Archimedean point beyond society from which we (...) can lever the intellects of our fellows. "- -Donald M. McCloskey, Journal of Economic Psychology "Collins is one of the genuine innovators of the sociology of scientific knowledge.... Changing Order is a rich and entertaining book. "- - Isis "The book gives a vivid sense of the contingent nature of research and is generally a good read. "- -Augustine Brannigan, Nature "This provocative book is a review of [Collins's] work, and an attempt to explain how scientists fit experimental results into pictures of the world.... A promising start for new explorations of our image of science, too often presented as infallibly authoritative. "- -Jon Turney, New Scientist. (shrink)

The regulation of DNA replication is a fascinating biological problem both from a mechanistic angle—How is replication timing regulated?—and from an evolutionary one—Why is replication timing regulated? Recent work has provided significant insight into the first question. Detailed biochemical understanding of the mechanism and regulation of replication initiation has made possible robust hypotheses for how replication timing is regulated. Moreover, technical progress, including high‐throughput, single‐molecule mapping of replication initiation and single‐cell assays of replication (...) timing, has allowed for direct testing of these hypotheses in mammalian cells. This work has consolidated the conclusion that differential replication timing is a consequence of the varying probability of replication origin initiation. The second question is more difficult to directly address experimentally. Nonetheless, plausible hypotheses can be made and one—that replication timing contributes to the regulation of chromatin structure—has received new experimental support. (shrink)

The idea of replication is based on the premise that there are permanent laws to be replicated and verified, and the scientific method is adequate for doing so. Scientific truth, however, is not absolute but relative to time and context, and the method used. Time and context are inextricably interwoven, in that time creates different contexts and contexts (e.g., Christmas Day vs. New Year’s Day) create different experiences of time, rendering psychological phenomena inherently variable. This means that internal and (...) external conditions fluctuate and are different in a replication study vs. the original. Thus, a replication experiment is just another empirical investigation that has no special status in the establishment of scientific truth. It is not the final arbiter of whether or not something exists. In their pursuit of homogeneous external conditions, replications have ignored the homogeneity of internal conditions. There is not a single replication reported in the literature that would have shown participants’ feelings and thoughts—both conscious and nonconscious—to be identical to those of the original participants. Experimental instructions can create varying ratios of conscious over nonconscious processing from one study to another. Ironically, every replication is a failure at the fundamentals of human psychology. While patterns can be discovered, they are not permanent or unchangeable laws of human behavior to be proven by the pinpoint statistical verification through replication. As scientific knowledge in physics is temporary and incomplete, should it be any surprise that science can only provide “temporary winners” for psychological knowledge of human behavior? (shrink)

Philosophers of science and metascientists alike typically model scientists’ behavior as driven by credit maximization. In this article I argue that this modeling assumption cannot account for how scientists have a default level of trust in each other’s assertions. The normative implication of this is that science policy should not focus solely on incentive reform.

In this paper, I articulate an argument for incompatibilism about moral responsibility and determinism. My argument comes in the form of an extended story, modeled loosely on Peter van Inwagen’s “rollback argument” scenario. I thus call it “the replication argument.” As I aim to bring out, though the argument is inspired by so-called “manipulation” and “original design” arguments, the argument is not a version of either such argument—and plausibly has advantages over both. The result, I believe, is a more (...) convincing incompatibilist argument than those we have considered previously. (shrink)

Fourteen subjects were tape‐recorded while they undertook to find a law to summarize numerical data they were given. The source of the data was not identified, nor were the variables labeled semantically. Unknown to the subjects, the data were measurements of the distances of the planets from the sun and the periods of their revolutions about it—equivalent to the data used by Johannes Kepler to discover his third law of planetary motion.Four of the 14 subjects discovered the same law as (...) Kepler did (the period varies as the 3/2 power of the distance), and a fifth came very close to the answer. The subiects' protocols provide a detailed picture of the problem‐solving searches they engaged in, which were mainly, but not exclusively, in the space of possible functions for fitting the data, and provide explanations as to why some succeeded and the others failed.The search heuristics used by the subjects are similar to those embodied in the BACON program, computer simulation of certain scientific discovery processes. The experiment demonstrates the feasibility of examining some of the processes of scientific discovery by recreating, in the laboratory, discovery situations of substantial historical relevance. It demonstrates also, that under conditions rather similar to those of the original discoverer, a law can be rediscovered by persons of ordinary intelligence (i.e., the intelligence needed for academic success in a good university). The data for the successful subjects reveal no “creative” processes in this kind of a discovery situation different from those that are regularly observed in all kinds of problem‐solving settings. (shrink)

This special issue on what some regard as a crisis of replicability in cognitive science (i.e. the observation that a worryingly large proportion of experimental results across a number of areas cannot be reliably replicated) is informed by three recent developments. -/- First, philosophers of mind and cognitive science rely increasingly on empirical research, mainly in the psychological sciences, to back up their claims. This trend has been noticeable since the 1960s (see Knobe, 2015). This development has allowed philosophers to (...) draw on a wider range of relevant resources, but it also makes them vulnerable to relying on claims that may not survive further scrutiny. If we have reasons to believe that a large proportion of findings in the psychological sciences cannot be reliably replicated, this would be a problem for philosophers who use such findings in their work. Second, philosophers are increasingly designing and carrying out their own experiments to back up claims, or to test claims earlier made from the armchair, for example, on the perceived permissibility of diverting trolleys or on the nature of free will. This growing field of experimental philosophy has diversified the intellectual field in philosophy, but may also be vulnerable to issues of replicability that philosophers did not face before. -/- Third, the recent evidence of apparently widespread non-replicability in the social sciences (and other fields) has forced philosophers of science to grapple with long standing questions from their field from a new perspective. To what extent does replicability matter for theory construction? How do the notions of replicability and scientific progress interact? How can normative insights from philosophy of science be used in order to improve scientific practice? -/- It is with these three developments in mind—the increasing importance of empirically-informed philosophy, of experimental philosophy, and of philosophy of science around replicability—that this special issue has been conceived. (shrink)

Recent studies indicate that mammalian chromosomes contain discretecis‐acting loci that control replication timing, mitotic condensation, and stability of entire chromosomes. Disruption of the large non‐coding RNA gene ASAR6 results in late replication, an under‐condensed appearance during mitosis, and structural instability of human chromosome 6. Similarly, disruption of the mouse Xist gene in adult somatic cells results in a late replication and instability phenotype on the X chromosome. ASAR6 shares many characteristics with Xist, including random mono‐allelic expression and (...) asynchronous replication timing. Additional “chromosome engineering” studies indicate that certain chromosome rearrangements affecting many different chromosomes display this abnormal replication and instability phenotype. These observations suggest that all mammalian chromosomes contain “inactivation/stability centers” that control proper replication, condensation, and stability of individual chromosomes. Therefore, mammalian chromosomes contain four types ofcis‐acting elements, origins, telomeres, centromeres, and “inactivation/stability centers”, all functioning to ensure proper replication, condensation, segregation, and stability of individual chromosomes. (shrink)

In this paper, I discuss cases of replication in the visual arts, with particular focus on paintings. In the first part, I focus on painted copies, that is, manual reproductions of paintings created by artists. Painted copies are sometimes used for the purpose of aesthetic education on the original. I explore the relation between the creation of painted copies and their use as aesthetic surrogates of the original artwork and draw a positive conclusion on the aesthetic benefits of replica (...) production by artists. A skeptical conclusion follows regarding the use of such replicas as surrogates for the original painting. The second part of the paper concerns mechanically produced replicas, such as photographs and 3-D prints. On the basis of some of the claims made in the first part, I set conditions that mechanically produced replicas need to meet in order to function as aesthetic surrogates of an original. I argue that perfect aesthetic surrogates are either already available or at least possible. I conclude by considering two possible objections. (shrink)

Wigner's quantum mechanical formulation of the problem of biological replication is examined with special reference to DNA. His necessary condition for replication is that the number of independent equations in his formulation should not exceed the number of unknowns. Explicit hypotheses concerning the relevant collision matrix are proposed without assuming biotonic modifications of quantum mechanics. Schrödinger's description of the gene as a low-temperature solid, combined with the concept of template, is given mathematical expression which fails to satisfy Wigner's (...) necessary condition. The condition is satisfied by a further specialization of the collision matrix, which also implies metabolic stability of the replicating unit. Such metabolic stability is in fact a distinguishing feature of the DNA molecule. (shrink)

Replication of the main chromosome in the halophilic archaeon Haloferax volcanii was recently reported to continue despite deletion of all active replication origins. Equally surprising, the deletion strain grew faster than the parent strain. It was proposed that origin‐less H. volcanii duplicate their chromosomes via recombination‐dependent replication. Here, we recall our present knowledge of this mode of chromosome replication in different organisms. We consider the likelihood that it accounts for the viability of H. volcanii deleted for (...) its main specific replication origins, as well as possible alternative interpretations of the results. The selective advantages of having defined chromosome replication origins are discussed from a functional and evolutionary perspective. (shrink)

This paper shows the relevance of an evolutionary model for the study of language change. We focus on a cognitive and usage-based approach to language change, namely the Theory of Utterance Selection developed by Croft (2000). Croft's evolutionary approach takes its inspiration from neo-Darwinian evolutionary theory, particularly the Generalized Theory of Selection developed by Hull (1988), a philosopher of science. Language is viewed as a system of use governed by convention, and language change results from breaking with convention and propagating (...) this innovation through the linguistic community until it becomes a new convention. Crucially, altered replication can be equated with language innovation, and propagation of individual changes is the linguistic counterpart of the differential perpetuation or selection of replicators. We will argue within the framework of Cognitive Linguistics (Geeraerts & Cuyckens, 2007) for a more systematic integration of cognitive and social factors in the explanation of language change. The mechanisms for language innovation are cognitive, as the pnnciples of cognitive efficiency like prototypicality constitute the main motivations for language change and metaphor and metonymy the main cognitive mechanisms of semantic change. The mechanisms for propagation are essentially social, including processes such as accommodation, identity and prestige. All of these mechanisms occur in individual communicative acts and operate like an "invisible hand" (Keller, 1994). We illustrate the sociocognitive evolutionary model of language change with some case studies on semantic change in Portuguese. (shrink)

The replication crisis is perceived by many as one of the most significant threats to the reliability of research. Though reporting of the crisis has emphasized social science, all signs indicate that it extends to many other fields. This paper investigates the possibility that the crisis and related challenges to conducting research also extend to philosophy. According to one possibility, philosophy inherits a crisis similar to the one in science because philosophers rely on unreplicated or unreplicable findings from science (...) when conducting philosophical research. According to another possibility, the crisis likely extends to philosophy because philosophers engage in similar research practices and face similar structural issues when conducting research that have been implicated by the crisis in science. Proposals for improving philosophical research are offered in light of these possibilities. (shrink)

One of the most important characteristics of modern science is its replicability and objectivity. This means that a scientific result is taken as such only when it has been reproduced by other scientists. Indeed, the replicability of a scientific result in an objective and independent way by members of a scientific community is the cornerstone of science. Experimental laser physics is an example of “normal” science, where it is no doubt that the phenomenon could be replicated; however, the replication (...) process may not be straightforward since it requires a good understanding of the physics behind it, as well as good technical skills. In this article, two laboratory cases of experiments on laser physics are presented: the first one deals with a Nitrogen N2 laser with a Polloni excitation circuit, and the second one deals with a transversally excited TEA carbon dioxide laser. For the nitrogen laser, it will be shown that reproducibility failed, and therefore, the reported experiment cannot be taken as a valid contribution to the advancement and understanding of nitrogen laser physics and technology. On the other hand, for the case of the TEA carbon dioxide laser, several comments are presented on the development of this finally successful experiment. Both cases show the importance of being technically up-dated in order to reproduce or improve the results reported by other researchers. Finally, a discussion about: What can we learn about the research practice from these two cases? It is presented, as well as the conclusions about the case studies; we hope they may be useful to philosophers of science and young scientists alike. (shrink)

The piRNA class of small RNAs are distinct from other small RNAs by their ∼26–31 nucleotide size, single‐strandedness and strand‐specificity as well as by the clustered arrangement of their origins. Here, we highlight how these features are reminiscent of the mechanisms of DNA replication, and then present three models suggesting that the origin of piRNAs may be mechanistically similar to key processes in DNA replication. BioEssays 29:382–385, 2007. © 2007 Wiley Periodicals, Inc.

The reward system of science is the priority rule. The first scientist making a new discovery is rewarded with prestige, while second runners get little or nothing. Michael Strevens, following Philip Kitcher, defends this reward system, arguing that it incentivizes an efficient division of cognitive labor. I argue that this assessment depends on strong implicit assumptions about the replicability of findings. I question these assumptions on the basis of metascientific evidence and argue that the priority rule systematically discourages replication. (...) My analysis leads us to qualify Kitcher and Strevens’s contention that a priority-based reward system is normatively desirable for science. (shrink)

The role or function of experimental and observational replication within empirical science has implications for how replication should be measured. Broadly, there seems to be consensus that replication’s central goal is to confirm or vouchsafe the reliability of scientific findings. I argue that if this consensus is correct, then most of the measures of replication used in the scientific literature are actually poor indicators of this reliability or confirmation. Only meta-analytic measures of replication align functionally (...) with the goals of replication. I conclude by addressing some objections to meta-analysis. (shrink)

A large number of scientists and several news platforms have, over the last few years, been speaking of a replication crisis in various academic disciplines, especially the biomedical and social sciences. This paper answers the novel question of whether we should also pursue replication in the humanities. First, I create more conceptual clarity by defining, in addition to the term “humanities,” various key terms in the debate on replication, such as “reproduction” and “replicability.” In doing so, I (...) pay attention to what is supposed to be the object of replication: certain studies, particular inferences, of specific results. After that, I spell out three reasons for thinking that replication in the humanities is not possible and argue that they are unconvincing. Subsequently, I give a more detailed case for thinking that replication in the humanities is possible. Finally, I explain why such replication in the humanities is not only possible, but also desirable. (shrink)

In bacteria, PriA protein, a conserved DEXH‐type DNA helicase, plays a central role in replication restart at stalled replication forks. Its unique DNA‐binding property allows it to recognize and stabilize stalled forks and the structures derived from them. Cells must cope with fork stalls caused by various replication stresses to complete replication of the entire genome. Failure of the stalled fork stabilization process and eventual restart could lead to various forms of genomic instability. The low viability (...) of priA null cells indicates a frequent occurrence of fork stall during normal growth that needs to be properly processed. PriA specifically recognizes the 3′‐terminus of the nascent leading strand or the invading strand in a displacement (D)‐loop by the three‐prime terminus binding pocket (TT‐pocket) present in its unique DNA binding domain. Elucidation of the structural basis for recognition of arrested forks by PriA should provide useful insight into how stalled forks are recognized in eukaryotes. (shrink)

Recent studies based on next‐generation DNA sequencing have revealed that the female inactive X chromosome is replicated in a rapid, unorganized manner, and undergoes increased rates of mutation. These observations link the organization of DNA replication timing to gene regulation on one hand, and to the generation of mutations on the other hand. More generally, the exceptional biology of the inactive X chromosome highlights general principles of genome replication. Cells may control replication timing by a combination of (...) intrinsic replication origin properties, local chromatin states and global levels of replication factors, leading to a functional separation between the activity of genes and their mutation. (shrink)

There are many layers of regulation governing DNA replication to ensure that genetic information is accurately transmitted from mother cell to daughter cell. While much of the control occurs at the level of origin selection and firing, less is known about how replication fork progression is controlled throughout the genome. In Drosophila polytene cells, specific regions of the genome become repressed for DNA replication, resulting in underreplication and decreased copy number. Importantly, underreplicated domains share properties with common (...) fragile sites. The Suppressor of Underreplication protein SUUR is essential for this repression. Recent work established that SUUR functions by directly inhibiting replication fork progression, raising several interesting questions as to how replication fork progression and stability can be modulated within targeted regions of the genome. Here we discuss potential mechanisms by which replication fork inhibition can be achieved and the consequences this has on genome stability and copy number control. (shrink)

For evolution by natural selection to occur it is classically admitted that the three ingredients of variation, difference in fitness and heredity are necessary and sufficient. In this paper, I show using simple individual-based models, that evolution by natural selection can occur in populations of entities in which neither heredity nor reproduction are present. Furthermore, I demonstrate by complexifying these models that both reproduction and heredity are predictable Darwinian products (i.e. complex adaptations) of populations initially lacking these two properties but (...) in which new variation is introduced via mutations. Later on, I show that replicators are not necessary for evolution by natural selection, but rather the ultimate product of such processes of adaptation. Finally, I assess the value of these models in three relevant domains for Darwinian evolution. (shrink)

The present paper attempts to define an experimental ethnography as an approach to the understanding of scientific thinking. Such an ethnography relies upon the replication of contemporary and historical scientific practices as a means of capturing the cultural and cognitive meanings of the practices in question. The approach is contrasted to the typical kind of laboratory experiment in psychology, and it is argued that replications of scientific practices can reveal dimensions of the microstructure of science and of its context (...) that otherwise may remain invisible. An extended example is presented, based upon replications of the experimental procedures used by Michael Faraday in 1856 during his examination of the optical properties of gold. (shrink)

A lot of Indian research is replicative in nature. This is because originality is at a premium here and mediocrity is in great demand. But replication has its merit as well because it helps in corroboration. And that is the bedrock on which many a fancied scientific hypothesis or theory stands, or falls. However, to go from replicative to original research will involve a massive effort to restructure the Indian psyche and an all round effort from numerous quarters. The (...) second part of this paper deals with the essence of scientific temper, which need not have any basic friendship, or animosity, with religion, faith, superstition and other such entities. A true scientist follows two cardinal rules. He is never unwilling to accept the worth of evidence, howsoever damning to the most favourite of his theories. Second, and perhaps more important, for want of evidence, he withholds comment. He says neither yes nor no. Where will Science ultimately lead Man is the third part of this essay. One argument is that the conflict between Man and Science will continue till either of them is exhausted or wiped out. The other believes that it is Science which has to be harnessed for Man and not Man used for Science. And with the numerous checks and balances in place, Science will remain an effective tool for man's progress. The essential value-neutrality of Science will have to be supplemented by the values that man has upheld for centuries as fundamental, and which religious thought and moral philosophy have continuously professed. (shrink)

The replication (replicability, reproducibility) crisis in social psychology and clinical medicine arises from the fact that many apparently well-confirmed experimental results are subsequently overturned by studies that aim to replicate the original study. The culprit is widely held to be poor science: questionable research practices, failure to publish negative results, bad incentives, and even fraud. In this article I argue that the high rate of failed replications is consistent with high-quality science. We would expect this outcome if the field (...) of science in question produces a high proportion of false hypotheses prior to testing. If most of the hypotheses under test are false, then there will be many false hypotheses that are apparently supported by the outcomes of well conducted experiments and null hypothesis significance tests with a type-I error rate (α) of 5%. Failure to recognize this is to commit the fallacy of ignoring the base rate. I argue that this is a plausible diagnosis of the replication crisis and examine what lessons we thereby learn for the future conduct of science. (shrink)

During replication, the topology of DNA changes continuously in response to well‐known activities of DNA helicases, polymerases, and topoisomerases. However, replisomes do not always progress at a constant speed and can slow‐down and even stall at precise sites. The way these changes in the rate of replisome progression affect DNA topology is not yet well understood. The interplay of DNA topology and replication in several cases where progression of replication forks reacts differently to changes in DNA topology (...) ahead is discussed here. It is proposed, there are at least two types of replication fork barriers: those that behave also as topological barriers and those that do not. Two‐Dimensional (2D) agarose gel electrophoresis is the method of choice to distinguish between these two different types of replication fork barriers. (shrink)

Replicability is a term that not only comes with different meanings in the literature of many domains but is often associated or confused with other terms such as ‘reproducibility,’ ‘repeatability,’ ‘reliability,’ ‘validity,’ and so on. To add to the confusion, it can even be used differently across diverse disciplines. Though all named concepts are important, what makes them barely advantageous is that they do not cover some peculiar aspects of the replicability and validation processes, i.e., appropriateness of conceptualization; trustworthiness of (...) operational definition and operational acts; accuracy of researcher’s description, categorization and/or measurement; successfulness of observational (or field) relation. Moreover, in social sciences and organization studies, the concept of validity of data is highly questionable due to the quite frequent shortage of real statuses of the observed objects. The present paper aims to challenge the received view on the concept of ‘replicability,’ by proposing a “situational approach” based on the idea that replicability works under certain organizational and socio-technic conditions, and that it is heavily influenced by the way that different stakeholders (scientists, technicians, participants artifacts, and technologies) respond to them. Consequently, it is important to understand how and why replicability works in different contexts. Its main purpose, without denying the importance of current conventional perspectives on replicability and its siblings, is to widen and change them to include an organizational setting and a reflexive epistemology. This implies the pursuit of a third way of replicability, between the postmodernist negation of its possibility and its opposite, i.e., a naïve naturalism. A way asserting that replicability is a jigsaw puzzle or a mosaic, constituted by discursive practices (poetics) and organizational achievements guiding the politics of accountability, validation and legitimation. The domain here considered pertains to the social and organizational sciences. However, though going beyond the aim of this essay, many issues could be reframed and adapted to medical, natural and physical sciences, as some of the following examples can show. (shrink)

A published simulation model Riolo et al. 2001 ) was replicated in two independent implementations so that the results as well as the conceptual design align. This double replication allowed the original to be analysed and critiqued with confidence. In this case, the replication revealed some weaknesses in the original model, which otherwise might not have come to light. This shows that unreplicated simulation models and their results can not be trusted - as with other kinds of experiment, (...) simulations need to be independently replicated. (shrink)

Cancer cells accumulate widespread local and global chromatin changes and the source of this instability remains a key question. Here we hypothesize that chromatin alterations including unscheduled silencing can arise as a consequence of perturbed histone dynamics in response to replication stress. Chromatin organization is transiently disrupted during DNA replication and maintenance of epigenetic information thus relies on faithful restoration of chromatin on the new daughter strands. Acute replication stress challenges proper chromatin restoration by deregulating histone H3 (...) lysine 9 mono‐methylation on new histones and impairing parental histone recycling. This could facilitate stochastic epigenetic silencing by laying down repressive histone marks at sites of fork stalling. Deregulation of replication in response to oncogenes and other tumor‐promoting insults is recognized as a significant source of genome instability in cancer. We propose that replication stress not only presents a threat to genome stability, but also jeopardizes chromatin integrity and increases epigenetic plasticity during tumorigenesis. (shrink)