A cell contains many copies of mitochondrial DNA. The distribution of a mitochondrial gene mutation in a cell culture is governed by the way in which the mtDNA molecules of a cell are replicated and partitioned between the two daughter cells during mitosis. Assuming that this partition process is random, we describe the evolution of the mitochondrial genetic state of a cell culture. The mutated mtDNA is ultimately segregated and the rate of the trend to segregation is relatively slow. It (...) is nevertheless greatly accelerated if the model takes into account the spatial mtDNA partition by the mitochondrial compartments. (shrink)

A hallmark of positive‐sense RNA viruses is the formation of membranous shelters for safe replication in the cytoplasm. Once considered invisible to the immune system, these viral shelters are now found to be antagonized through the cooperation of autophagy proteins and anti‐microbial GTPases. This coordinated effort of autophagy proteins guiding GTPases functions against not only the shelters of viruses but also cytoplasmic vacuoles containing bacteria or protozoa, suggesting a broad immune‐defense mechanism against disparate vacuolar pathogens. Fundamental questions regarding this (...) process remain: how the host recognizes these membranous structures as a target, how the autophagy proteins bring the GTPases to the shelters, and how the recruited GTPases disrupt these shelters. In this review, these questions are discussed, the answers to which will significantly advance our understanding of the response to vacuole‐like structures of pathogens, thereby paving the way for the development of broadly effective anti‐microbial strategies for public health. (shrink)

The recent development of RNA replicating protocells and capsules that enclose complex biosynthetic cascade reactions are encouraging signs that we are gradually getting better at mastering the complexity of biological systems. The road to truly cellular compartments is still very long, but concrete progress is being made. Compartmentalization is a crucial natural methodology to enable control over biological processes occurring within the living cell. In fact, compartmentalization has been considered by some theories to be instrumental in the creation of life. (...) With the advancement of chemical biology, artificial compartments that can mimic the cell as a whole, or that can be regarded as cell organelles, have recently received much attention. The membrane between the inner and outer environment of the compartment has to meet specific requirements, such as semi‐permeability, to allow communication and molecular transport over the border. The membrane can either be built from natural constituents or from synthetic polymers, introducing robustness to the capsule. (shrink)

Excerpt from Origin of History as Metaphysic The Muse Clio, carted from Pieria to the museums, can no longer be invoked without a libation to her warders, the numerous scribes, who have been busy since her fall correlating her steps, or her metamorphoses, as some say, for she has proved a difficult subject for classification: She is becoming bigger or better, nay she is growing many; she stations one foot in the beginning, but where is the other? Alas, it is (...) in Asia, and the head is a fake in need of restoration! Thus she has become Clio Tymbuchos in the professional hands of the scribes who find lively occupation exhuming and questioning her relics corked into formaldehyde and coffined into airtight compartments called historical facts. Men have speculated her into a new myth, a sepulchre of forms, and they have named the sepulchre History. But observe her resurrections! She has arisen, a mighty thing-in-herself with her own laws and growths and decays, and disembodied, dismembered, this apparition, this butterfly-concept called Clio, is expanding towards infinity. About the Publisher Forgotten Books publishes hundreds of thousands of rare and classic books. Find more at www.forgottenbooks.com This book is a reproduction of an important historical work. Forgotten Books uses state-of-the-art technology to digitally reconstruct the work, preserving the original format whilst repairing imperfections present in the aged copy. In rare cases, an imperfection in the original, such as a blemish or missing page, may be replicated in our edition. We do, however, repair the vast majority of imperfections successfully; any imperfections that remain are intentionally left to preserve the state of such historical works. (shrink)

The mammalian chromosome is longitudinally heterogeneous in structure and function and this is the basis for the specific banding patterns produced by various chromosome staining techniques. The two most frequently used techniques are G, or Giemsa banding and R, or reverse banding. Each type of stained band is characterised by variations in gene density, time of replication, base composition, density of repeat sequences, and chromatin packaging. It is increasingly apparent that R and G bands, which are complementary to each (...) other, represent separate compartments of the euchromatic human genome, with R bands containing the vast majority of genes. R bands are also more GC‐rich, contain a higher density of Alu repeats, and replicate earlier in S phase, than G bands. These properties may be interdependent and may have coevolved. (shrink)

Chromosome segregation requires the ordered separation of the newly replicated chromosomes between the two daughter cells. In most cells, this requires nuclear envelope (NE) disassembly during mitotic entry and its reformation at mitotic exit. Nuclear envelope breakdown (NEB) results in the mixture of two cellular compartments. This process is controlled through phosphorylation of multiple targets by cyclin‐dependent kinase 1 (Cdk1)‐cyclin B complexes as well as other mitotic enzymes. Experimental evidence also suggests that nucleo‐cytoplasmic transport of critical cell cycle regulators such (...) as Cdk1‐cyclin B complexes or Greatwall, a kinase responsible for the inactivation of PP2A phosphatases, plays a major role in maintaining the boost of mitotic phosphorylation thus preventing the potential mitotic collapse derived from NEB. These data suggest the relevance of nucleo‐cytoplasmic transport not only to communicate cytoplasmic and nuclear compartments during interphase, but also to prepare cells for the mixture of these two compartments during mitosis. (shrink)

Toxoplasma gondii is a highly successful parasite capable of infecting virtually all warm-blooded animals by actively invading nucleated host cells and forming a modified compartment where it replicates within the cytosol. The parasite-containing vacuole provides a safe haven, even in professional phagocytes such as macrophages, which normally destroy foreign microbes. In an effort to eliminate the parasite, the host up-regulates a family of immunity-related p47 GTPases (IRGs), which are recruited to the parasite-containing vacuole, resulting in membrane rupture and digestion (...) of the parasite. To avoid this fate, highly virulent strains of Toxoplasma coat the external surface of their vacuole with a secretory serine/threonine kinase, known as ROP18. At this host-pathogen interface, ROP18 phosphorylates and inactivates IRGs, thereby protecting the parasite from killing. These findings reveal a novel molecular mechanism by which the parasite disarms host innate immunity. (shrink)

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)

Many philosophers of science and methodologists have argued that the ability to repeat studies and obtain similar results is an essential component of science. A finding is elevated from single observation to scientific evidence when the procedures that were used to obtain it can be reproduced and the finding itself can be replicated. Recent replication attempts show that some high profile results – most notably in psychology, but in many other disciplines as well – cannot be replicated consistently. These (...) replication attempts have generated a considerable amount of controversy, and the issue of whether direct replications have value has, in particular, proven to be contentious. However, much of this discussion has occurred in published commentaries and social media outlets, resulting in a fragmented discourse. To address the need for an integrative summary, we review various types of replication studies and then discuss the most commonly voiced concerns about direct replication. We provide detailed responses to these concerns and consider different statistical ways to evaluate replications. We conclude there are no theoretical or statistical obstacles to making direct replication a routine aspect of psychological science. (shrink)

The appendages of Drosophila develop from the imaginal discs. During the extensive growth of these discs cell lineages are for the most part unfixed, suggesting a strong role for cell‐cell interactions in controlling the final pattern of differentiation. However, during early and middle stages of development, discs are subdivided by strict lineage restrictions into a small number of spatially distinct compartments. These compartments appear to be maintained by stably inheriting states of gene expression; the compartmentspecific expression of two such ‘selector’ (...) ‐ like genes, engrailed and apterous, are critical for anterior‐posterior and dorso‐ventral compartmentalization, respectively. Recent work suggests that one purpose of compartmentalization is to establish regions of specialized cells near compartment boundaries via intercompartmental induction, using molecules like the hedgehog protein. Thus, compartments can act as organizing centers for patterning within compartments. Evidence for non‐compartmental patterning mechanisms will also be discussed. (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)

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)

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)

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)

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)

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)

Biological objects are often constructive dynamic systems whose structures evolve as a consequence of their internal dynamics, which in turn is affected by the overall structure. As very few tools are presently adapted to tackle constructive dynamic systems, they constitute fascinating challenges for modeling/simulation. In cell biology, the secretory process in eukaryotic cells corresponds to this type of system, as it appears to autonomously generate new structures as a result of its molecular dynamics. Here I briefly review the only documented (...) case of a membrane-bounded intracellular compartment whose very existence strictly depends on its continued functioning. Indeed, the Golgi apparatus of the yeast Saccharomyces cerevisiae appears at steady-state as a continuously renewed set of transitory membrane-bounded structures that self-mature, rather than as a permanent entity. On the basis of this case and of recent advances in related molecular studies, a detailed model is proposed, that encompasses the birth of a yeast Golgi element and bridges its molecular and morphogenetic aspects. This model is extended to briefly outline three evolutionary inventions, from S. cerevisiae to another yeast, Pichia pastoris, on to plant, and on to animal cells: stacking, stabilizing and aggregating the primary Golgi elements. (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 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)

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)

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)

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)

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)

This article focuses on the role of the interchromatin compartment (IC) in shaping nuclear landscapes. The IC is connected with nuclear pore complexes (NPCs) and harbors splicing speckles and nuclear bodies. It is postulated that the IC provides routes for imported transcription factors to target sites, for export routes of mRNA as ribonucleoproteins toward NPCs, as well as for the intranuclear passage of regulatory RNAs from sites of transcription to remote functional sites (IC hypothesis). IC channels are lined by (...) less‐compacted euchromatin, called the perichromatin region (PR). The PR and IC together form the active nuclear compartment (ANC). The ANC is co‐aligned with the inactive nuclear compartment (INC), comprising more compacted heterochromatin. It is postulated that the INC is accessible for individual transcription factors, but inaccessible for larger macromolecular aggregates (limited accessibility hypothesis). This functional nuclear organization depends on still unexplored movements of genes and regulatory sequences between the two compartments. (shrink)

This paper evaluates and criticises the developmental systems conception of evolution and develops instead an extension of the gene's eye conception of evolution. We argue (i) Dawkin's attempt to segregate developmental and evolutionary issues about genes is unsatisfactory. On plausible views of development it is arbitrary to single out genes as the units of selection. (ii) The genotype does not carry information about the phenotype in any way that distinguishes the role of the genes in development from that other factors. (...) (iii) There is no simple and general causal criterion which distinguishes the role of genes in development and evolution. (iv) There is, however, an important sense in which genes but not every other developmental factor represent the phenotype. (v) The idea that genes represent features of the phenotype forces us to recognise that genes are not the only, or almost the only, replicators. Many mechanisms of replication are involved in both development and evolution. (vi) A conception of evolutionary history which recognises both genetic and non-genetic replicators, lineages of replicators and interactors has advantages over both the radical rejection of the replicator/interactor distinction and the conservative restriction of replication to genetic replication. (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)

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)

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)

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)

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)

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)

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.

The replication crisis has spawned discussions on the meaning of replication. In fact, in order to determine whether an experiment fails to replicate, it is necessary to establish what replication is. This is, however, a difficult task, as it is possible to attribute different meanings to it. This paper offers a solution to this problem of ambiguity by engineering a concept of replication that, if compared to other proposals, stands out for being not only broadly applicable (...) but also sufficiently specific. It features a minimal level of operationalism, which would otherwise limit its applicability, while it heavily relies on replication’s specific epistemic functions, which are inter-disciplinary. Another merit is its context sensitivity, which enables it to differentiate instances of replication from non-instances of replication in every scientific discipline according to the discipline’s own standards. (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...

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)

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)

An idea is not a replicator because it does not consist of coded self-assembly instructions. It may retain structure as it passes from one individual to another, but does not replicate it. The cultural replicator is not an idea but an associatively-structured network of them that together form an internal model of the world, or worldview. A worldview is a primitive, uncoded replicator, like the autocatalytic sets of polymers widely believed to be the earliest form of life. Primitive replicators generate (...) self-similar structure, but because the process happens in a piecemeal manner, through bottom-up interactions rather than a top-down code, they replicate with low fidelity, and acquired characteristics are inherited. Just as polymers catalyze reactions that generate other polymers, the retrieval of an item from memory can in turn trigger other items, thus cross-linking memories, ideas, and concepts into an integrated conceptual structure. Worldviews evolve idea by idea, largely through social exchange. An idea participates in the evolution of culture by revealing certain aspects of the worldview that generated it, thereby affecting the worldviews of those exposed to it. If an idea influences seemingly unrelated fields this does not mean that separate cultural lineages are contaminating one another, because it is worldviews, not ideas, that are the basic unit of cultural evolution. (shrink)

Since the advent of the twenty-first century, science has experienced a crisis pertaining to the replicability of quantitative research findings, which has become known as the ‘replication crisis’. The replication crisis has particularly afflicted research in the behavioural sciences, and psychology in particular. Given the relevance of psychology to education, it is unsurprising that the replication crisis also presents an issue for quantitative educational research, thus potentially compromising its practical usefulness. This article outlines the replication crisis (...) in psychology, and highlights its significance for quantitative educational research. Greater methodological rigour, aimed at addressing methodological deficiencies in the conduct of scientific research, has been suggested as a response to the replication crisis. Following a review of various calls for greater methodological rigour, the current article argues that, whilst methodological deficiencies may be a contributory factor, there is potentially a more fundamental reason for the replication crisis. The case is made that the non-separability of a measured attribute from the measurement instrument, and the irreducible uncertainty in unmeasured attributes, may be the principal reasons for the replication crisis in psychology and education. Implications of such an explanation for the crisis are articulated in relation to the evidence-based policy agenda in education. (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)

Brain states, which correlate with specific motor, cognitive, and emotional states, may be monitored with noninvasive techniques such as electroencephalography and magnetoencephalography that measure macroscopic cortical activity manifested as oscillatory network dynamics. These rhythmic cortical signatures provide insight into the neuronal activity used to identify pathological cortical function in numerous neurological and psychiatric conditions. Sensory and transcranial stimulation, entraining the brain with specific brain rhythms, can effectively induce desired brain states correlated with such cortical rhythms. Because brain states have distinct (...) neural correlates, it may be possible to induce a desired brain state by replicating these neural correlates through stimulation. To do so, we propose recording brain waves from a “donor” in a particular brain state using EEG/MEG to extract cortical signatures of the brain state. These cortical signatures would then be inverted and used to entrain the brain of a “recipient” via sensory or transcranial stimulation. We propose that brain states may thus be transferred between people by acquiring an associated cortical signature from a donor, which, following processing, may be applied to a recipient through sensory or transcranial stimulation. This technique may provide a novel and effective neuromodulation approach to the noninvasive, non-pharmacological treatment of a variety of psychiatric and neurological disorders for which current treatments are mostly limited to pharmacotherapeutic interventions. (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)

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)

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)

Before replication becomes mainstream, the potential for generating theoretical knowledge better be clear. Replicating statistically significant nonrandom data shows that an original study made a discovery; replicating a specified theoretical effect shows that an original study corroborated a theory. Yet only in the latter case is replication a necessary, sound, and worthwhile strategy.

Replication forks inevitably stall at damaged DNA in every cell cycle. The ability to overcome DNA lesions is an essential feature of the replication machinery. A variety of specialized polymerases have recently been discovered, which enable cells to replicate past various forms of damage by a process termed translesion synthesis. Alternatively, homologous recombination can be used to restart DNA replication across the lesion. Genetic and biochemical studies have shed light on the impact of these two post‐replication (...) repair pathways in bacteria and yeast. In vertebrates, however, a genetic approach to study post‐replication repair has been compromised because many of the genes involved appear to be essential for embryonic development. We have taken advantage of the chicken cell line DT40 to perform a genetic analysis of translesion synthesis and homologous recombination and to characterize genetic interactions between these two pathways in vertebrates. In this article, we aim to summarize our current understanding of post‐replication repair in DT40 in the perspective of bacterial, yeast and mammalian genetics. BioEssays 26:151–158, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The information contained within the linear sequence of bases (the genome) must be faithfully replicated in each cell cycle, with a balance of constancy and variation taking place over the course of evolution. Recently, it has become clear that additional information important for genetic regulation is contained within the chromatin proteins associated with DNA (the epigenome). Epigenetic information also must be faithfully duplicated in each cell cycle, with a balance of constancy and variation taking place during the course of development (...) to achieve differentiation while maintaining identity within cell lineages. Both the genome and the epigenome are synthesized at the replication fork, so the events occurring during S‐phase provide a critical window of opportunity for eliciting change or maintaining existing genetic states. Cells discriminate between different states of chromatin through the activities of proteins that selectively modify the structure of chromatin. Several recent studies report the localization of certain chromatin modifying proteins to replication forks at specific times during S‐phase. Since transcriptionally active and inactive chromosome domains generally replicate at different times during S‐phase, this spatiotemporal regulation of chromatin assembly proteins may be an integral part of epigenetic inheritance. BioEssays 25:647–656, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Data collection in psychology increasingly relies on “open populations” of participants recruited online, which presents both opportunities and challenges for replication. Reduced costs and the possibility to access the same populations allows for more informative replications. However, researchers should ensure the directness of their replications by dealing with the threats of participant nonnaiveté and selection effects.

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)