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)

The replicon hypothesis, first proposed in 1963 by Jacob and Brenner(1), states that DNA replication is controlled at sites called origins. Replication origins have been well studied in prokaryotes. However, the study of eukaryotic chromosomal origins has lagged behind, because until recently there has been no method for reliably determining the identity and location of origins from eukaryotic chromosomes. Here, we review a technique we developed with the yeast Saccharomyces cerevisiae that allows both the mapping of replication (...) origins and an assessment of their activity. Two‐dimensional agarose gel electrophoresis and Southern hybridization with total genomic DNA are used to determine whether a particular restriction fragment acquires the branched structure diagnostic of replication initiation. The technique has been used to localize origins in yeast chromosomes and assess their initiation efficiency. In some cases, origin activation is dependent upon the surrounding context. The technique is also being applied to a variety of eukaryotic organisms. (shrink)

DNA replication initiates at many sites in eukaryotic chromosomes. It has been difficult to isolate such replication origins, but a family of sequences from the yeast genome have properties which suggest that they may serve this function. The identification of these sequences together with sophisticated methods of genetic analysis, make yeast a useful organism for the study of eukaryotic DNA replication.

During early embryonic development in several metazoans, accurate DNA replication is ensured by high number of replication origins. This guarantees rapid genome duplication coordinated with fast cell divisions. In Xenopus laevis embryos this program switches to one with a lower number of origins at a developmental stage known as mid‐blastula transition (MBT) when cell cycle length increases and gene transcription starts. Consistent with this regulation, somatic nuclei replicate poorly when transferred to eggs, suggesting the existence of an epigenetic (...) memory suppressing replication assembly origins at all available sites. Recently, it was shown that histone H1 imposes a non‐permissive chromatin configuration preventing replication origin assembly on somatic nuclei. This somatic state can be erased by SSRP1, a subunit of the FACT complex. Here, we further develop the hypothesis that this novel form of epigenetic memory might impact on different areas of vertebrate biology going from nuclear reprogramming to cancer development. (shrink)

The chromosomes of eukaryotic cells possess many potential DNA replication origins, of which a subset is selected in response to the cellular environment, such as the developmental stage, to act as active replication start sites. The mechanism of origin selection is not yet fully understood. In this review, we summarize recent observations regarding replication origins and initiator proteins in various organisms. These studies suggest that the DNA‐binding specificities of the initiator proteins that bind to the (...) class='Hi'>replication origins and promote DNA replication are primarily responsible for origin selection. We particularly focus on the importance of transcription factors in the origin selection process. We propose that transcription factors are general regulators of the formation of functional complexes on the chromosome, including the replication initiation complex. We discuss the possible mechanisms by which transcription factors influence the selection of particular origins. BioEssays 27:1107–1106, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

The hardest part of replicating a genome is the beginning. The first step of DNA replication (called “initiation”) mobilizes a large number of specialized proteins (“initiators”) that recognize specific sequences or structural motifs in the DNA, unwind the double helix, protect the exposed ssDNA, and recruit the enzymatic activities required for DNA synthesis, such as helicases, primases and polymerases. All of these components are orderly assembled before the first nucleotide can be incorporated. On the occasion of the 50th anniversary (...) of the discovery of the DNA structure, we review our current knowledge of the molecular mechanisms that control initiation of DNA replication in eukaryotic cells, with particular emphasis on the recent identification of novel initiator proteins. We speculate how these initiators assemble molecular machines capable of performing specific biochemical tasks, such as loading a ring‐shaped helicase onto the DNA double helix. BioEssays 25:1158–1167, 2003. © 2003 Wiley Periodicals, Inc. (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.

It has been almost twenty‐five years since Huberman and Riggs first showed that there are multiple bidirectional origins of replication scattered at ∼100 kb intervals along mammalian chromosomal fibers. Since that time, every conceivable physical property unique to replicating DNA has been taken advantage of to determine whether origins of replication are defined sequence elements, as they are in microorganisms. The most thoroughly studied mammalian locus to date is the dihydrofolate reductase domain of Chinese hamster cells, which will (...) be used as a model to discuss the various methods of investigation. While several laboratories agree on the rough location of the [initiation locus] in this large chromosomal domain, different experimental approaches paint different pictures of the mechanism by which initiation occurs. However, a variety of new techniques and synchronizing agents promises to clarify the picture for this particular locus, and to provide the means for identifying and isolating other origins of replication for comparison. (shrink)

Recent work suggests that DNA replication origins are regulated by the number of multiple mini‐chromosome maintenance (MCM) complexes loaded. Origins are defined by the loading of MCM – the replicative helicase which initiates DNA replication and replication kinetics determined by origin's location and firing times. However, activation of MCM is heterogeneous; different origins firing at different times in different cells. Also, more MCMs are loaded in G1 than are used in S phase. These aspects of MCM (...) biology are explained by the observation that multiple MCMs are loaded at origins. Having more MCMs at early origins makes them more likely to fire, effecting differences in origin efficiency that define replication timing. Nonetheless, multiple MCM loading raises new questions, such as how they are loaded, where these MCMs reside at origins, and how their presence affects replication timing. In this review, we address these questions and discuss future avenues of research. (shrink)

Chromosomal origins of DNA replication in higher eukaryotes differ significantly from those of E. coli (oriC) and the tumor virus, SV40 (ori sequence). Initiation events appear to occur throughout broad zones rather than at specific origin sequences. Analysis of four chromosomal origin regions reveals that they share common modular sequence elements. These include DNA unwinding elements, pyrimidine tracts that may serve as strong DNA polymerase‐primase start sites, scaffold associated regions, transcriptional regulatory sequences, and, possibly, initiator protein binding (...) sites and inherently destabilized regions. Based on the novel organization of chromosomal origin regions, we propose a model for initiation of DNA replication in higher eukaryotes. Unwinding of duplex DNA during initiation may be uncoupled, both temporally and spatially, from DNA synthesis, resulting in transient single‐stranded intermediates that function in lieu of conventional replication forks during chromosomal DNA replication. DNA synthesis begins subsequently at multiple sites Within the unwound regions rather than at specific origin sequences. (shrink)

Genes are thought to have evolved from long-lived and multiply-interactive molecules in the early stages of the origins of life. However, at that stage there were no replicators, and the distinction between interactors and replicators did not yet apply. Nevertheless, the process of evolution that proceeded from initial autocatalytic hypercycles to full organisms was a Darwinian process of selection of favourable variants. We distinguish therefore between Neo-Darwinian evolution and the related Weismannian and Central Dogma divisions, on the one hand, and (...) the more generic category of Darwinian evolution on the other. We argue that Hull’s and Dawkins’ replicator/interactor distinction of entities is a sufficient, but not necessary, condition for Darwinian evolution to take place. We conceive the origin of genes as a separation between different types of molecules in a thermodynamic state space, and employ a notion of reproducers. (shrink)

The budding yeast Cdc6 protein is important for regulating DNA replication intiation. Cdc6p acts at replication origins, and cdc6‐1 mutants arrest with unreplicated DNA and show elevated minichromosome loss rates. Overexpression of the related Cdc 18 protein in fission yeast results in DNA rereplication; however, Cdc6p overexpression does not cause this result. A recent paper(1) further defines the role of Cdc6p in DNA replication. Cdc6p only promotes DNA replication between the end of mitosis and late G1, (...) and although the Cdc6 protein is highly unstable, neither degradation nor nuclear localization is critical for limiting DNA replication to this interval. (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)

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)

The dynamics of eukaryotic DNA polymerases has been difficult to establish because of the difficulty of tracking them along the chromosomes during DNA replication. Recent work has addressed this problem in the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae through the engineering of replicative polymerases to render them prone to incorporating ribonucleotides at high rates. Their use as tracers of the passage of each polymerase has provided a picture of unprecedented resolution of the organization of replicons and replication origins (...) in the two yeasts and has uncovered important differences between them. Additional studies have found an overlapping distribution of DNA polymorphisms and the junctions of Okazaki fragments along mononucleosomal DNA. This sequence instability is caused by the premature release of polymerase δ and the retention of non proof‐read DNA tracts replicated by polymerase α. The possible implementation of these new experimental approaches in multicellular organisms opens the door to the analysis of replication dynamics under a broad range of genetic backgrounds and physiological or pathological conditions. (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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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.

Two experiments involving an international collaboration of experimenters sought to replicate and extend a previously published psi experiment on precognition by Daryl Bem that has been the focus of extensive research. The experiment reverses the usual cause–effect sequence of a standard psychology experiment using priming and reaction times. The preregistered confirmatory hypothesis is that response times to incongruent stimuli will be longer than response times to congruent stimuli even though the prime has not yet appeared when the participant records their (...) judgments. The confirmatory hypothesis for Experiment 1 was not supported. Exploratory analyses indicated that those participants who completed the English-language version rather than a translation showed a significant effect, as was the case in the original study; no significant departure from chance was found in data involving non-English translations. Experiment 2 sought to enhance the predicted effect by having each participant read either a pro-psi or an anti-psi statement at the beginning of the experiment to test the pre-recorded hypothesis that a pro-psi statement would produce a larger effect than an anti-psi statement. The results did not support the primary psi hypothesis and there was no effect in the English-language sample. However, there was mixed support for the effect of the psi statement on performance; those participants who received the pro-psi statement had a greater psi score than those who received the anti-psi statement. As in the original experiment, neither the experimenters’ nor participants’ beliefs were significantly associated with the dependent measure. In sum, the pre-registered confirmatory hypotheses were not supported. The importance of the personality variable Sensation Seeking, a component of extraversion, as a correlate of psi performance is discussed as are the challenges and implications for international collaborations and replication in controversial science. Keywords: priming; expectancy effect; retrocausation; consciousness; sociology; precognition; psi; replication Two experiments involving an international collaboration of experimenters sought to replicate and extend a previously published psi experiment on precognition by Daryl Bem that has been the focus of extensive research. The experiment reverses the usual cause-effect sequence of a standard psychology experiment using priming and reaction times. The preregistered confirmatory hypothesis is that response times to incongruent stimuli will be longer than response times to congruent stimuli even though the prime has not yet appeared when the participant records his or her judgments. The confirmatory hypothesis for Study 1 was not supported. Exploratory analyses indicated that those participants who completed the English-language version rather than a translation showed a significant effect, as was the case in the original study; no significant departure from chance was found in data involving non-English translations. Study 2 sought to enhance the predicted effect by having each participant read either a pro-psi or an anti-psi statement at the beginning of the experiment to test the pre-recorded hypothesis that a pro-psi statement would produce a larger effect than an anti-psi statement. The results did not support the primary psi hypothesis and there was no observed association between belief and experience of ESP and psi outcome. However, there was mixed support for the effect of the psi statement on performance; those participants who received the pro-psi statement had a greater psi score than those who received anti-psi statement. As in the original experiment, neither the experimenters’ nor participants’ beliefs or expectations were significantly correlated with the dependent measure. In sum, the pre-registered confirmatory hypotheses were not supported. The importance of the personality variable Sensation Seeking, a component of extraversion, as a correlate of psi performance is discussed as are the challenges and implications for international collaborations and replication in controversial science. (shrink)

Life is perpetuated through a single-cell bottleneck between generations in many organisms. Here, I highlight that this cell holds information in two distinct stores: in the linear DNA sequence that is replicated during cell divisions, and in the three-dimensional arrangement of molecules that can change during development but is recreated at the start of each generation. These two interdependent stores of information – one replicating with each cell division and the other cycling with a period of one generation – coevolve (...) while perpetuating an organism. Unlike the genome sequence, the arrangement of molecules, including DNA, RNAs, proteins, sugars, lipids, etc., is not well understood. Because this arrangement and the genome sequence are transmitted together from one generation to the next, analysis of both is necessary to understand evolution and origins of inherited diseases. Recent developments suggest that tools are in place to examine how all the information to build an organism is encoded within a single cell, and how this cell code is reproduced in every generation. Life relies on the information for making organisms that is encoded in single cells and transmitted between generations. These cell codes include interdependent stores of information that replicate and that cycle. Understanding evolution and the origins of inherited diseases requires analysis of cell codes. (shrink)

I argue that there is no distinction between allographic and autographic representations. One consequence of this is that replicative forgeries have the same aesthetic and artistic value as originals, and are accurate records of actions. I end with some reflections on the pragmatic structure of forgery.

Replicability is widely regarded as one of the defining features of science and its pursuit is one of the main postulates of meta-research, a discipline emerging in response to the replicability crisis. At the same time, replicability is typically treated with caution by philosophers of science. In this paper, we reassess the value of replicability from an epistemic perspective. We defend the orthodox view, according to which replications are always epistemically useful, against the more prudent view that claims that it (...) is useful in very limited circumstances. Additionally, we argue that we can learn more about the original experiment and the limits of the discovered effect from replications at different levels. We hold that replicability is a crucial feature of experimental results and scientists should continue to strive to secure it. (shrink)

Just as the faithful replication of DNA is an essential process for the cell, chromatin structures of active and inactive genes have to be copied accurately. Under certain circumstances, however, the activity pattern has to be changed in specific ways. Although analysis of specific aspects of these complex processes, by means of model systems, has led to their further elucidation, the mechanisms of chromatin replication in vivo are still controversial and far from being understood completely. Progress has been (...) achieved in understanding: 1. The initiation of chromatin replication, indicating that a nucleosome‐free origin is necessary for the initiation of replication; 2. The segregation of the parental nucleosomes, where convincing data support the model of random distribution of the parental nucleosomes to the daughter strands; and 3. The assembly of histones on the newly synthesized strands, where growing evidence is emerging for a two‐step mechanism of nucleosome assembly, starting with the deposition of H3/H4 tetramers onto the DNA, followed by H2A/H2B dimers. (shrink)

A classic finding reported in Beck (1966a) is that observers tend to indicate a more natural texture break between a set of T’s and tilted T’s than between a set of T’s and backward L’s. This finding has played a prominent role in discussions about the properties of texture segmentation and in the development of computational theories of texture segmentation. Due to the small sample size of the original study, we replicated the original experiment with a larger sample. Regrettably, we (...) discovered that the description in Beck (1966a) is insufficient to allow us to reproduce the stimuli. For our replication, we created stimuli that seem consistent with the spirit of the original study. The results of the replication study partly matchBeck’s original data (r = .59), but conclusions indicated by these results deviate from some of Beck’s key conclusions.We also further explored the influential claim derived from a second experiment in Beck (1966a) that texture segmentation was not related to the perceived similarity of elements. Contrary to this claim, a re-analysis of Beck’s data indicates the counterintuitive conclusion that observers tend to indicate stronger texture segmentation between regions that are rated as being more similar. In a replication of the second experiment, this relation flipped so that the replication observers indicated stronger texture segmentation for regions with lower similarity ratings. Despite being influential, we conclude that there are substantial problems with the stimuli, analyses, and conclusions in Beck (1966a). (shrink)

I reappraise in detail Hertz's cathode ray experiments. I show that, contrary to Buchwald 's evaluation, the core experiment establishing the electrostatic properties of the rays was successfully replicated by Perrin and Thomson. Buchwald 's discussion of 'current purification' is shown to be a red herring. My investigation of the origin of Buchwald 's misinterpretation of this episode reveals that he was led astray by a focus on what Hertz 'could do'-his experimental resources. I argue that one should focus (...) instead on what Hertz wanted to achieve-his experimental goals. Focusing on these goals, I find that his explicit and implicit requirements for a successful investigation of the rays' properties are met by Perrin and Thomson. Thus, even by Hertz's standards, they did indeed replicate his experiment. (shrink)

Error‐free genome duplication and accurate cell division are critical for cell survival. In all three domains of life, bacteria, archaea, and eukaryotes, initiator proteins bind replication origins in an ATP‐dependent manner, play critical roles in replisome assembly, and coordinate cell‐cycle regulation. We discuss how the eukaryotic initiator, Origin recognition complex (ORC), coordinates different events during the cell cycle. We propose that ORC is the maestro driving the orchestra to coordinately perform the musical pieces of replication, chromatin organization, (...) and repair. (shrink)

The replicability crisis refers to the apparent failures to replicate both important and typical positive experimental claims in psychological science and biomedicine, failures which have gained increasing attention in the past decade. In order to provide evidence that there is a replicability crisis in the first place, scientists have developed various measures of replication that help quantify or “count” whether one study replicates another. In this nontechnical essay, I critically examine five types of replication measures used in the (...) landmark article “Estimating the reproducibility of psychological science” (Open Science Collaboration, Science, 349, ac4716, 2015) based on the following techniques: subjective assessment, null hypothesis significance testing, comparing effect sizes, comparing the original effect size with the replication confidence interval, and meta-analysis. The first four, I argue, remain unsatisfactory for a variety of conceptual or formal reasons, even taking into account various improvements. By contrast, at least one version of the meta-analytic measure does not suffer from these problems. It differs from the others in rejecting dichotomous conclusions, the assumption that one study replicates another or not simpliciter. I defend it from other recent criticisms, concluding however that it is not a panacea for all the multifarious problems that the crisis has highlighted. (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)

Cellular identity and its response to external or internal signalling variations are encoded in a cell's genome as regulatory information. The genomic regions that specify this type of information are highly variable and degenerated in their sequence determinants, as it is becoming increasingly evident through the application of genome‐scale methods to study gene expression. Here, we speculate that the same scenario applies to the regulatory regions controlling where DNA replication starts in the metazoan genome. We propose that replication (...) origins cannot be defined as unique genomic features, but rather that DNA synthesis initiates opportunistically from accessible DNA sites, making cells highly robust and adaptable to environmental or developmental changes. (shrink)

In evolutionary biology and ecology, ontological and epistemological perspectives based on the replicator and the interactor have become the background that makes it possible to transcend traditional biological levels of organization and to achieve a unified view of evolution in which replication and interaction are fundamental operating processes. Using the transactional perspective proposed originally by John Dewey and Arthur Fisher Bentley, a new ontological and methodological category is proposed here: the transactor. The transactional perspective, based on the concept of (...) the transactor, bridges the dichotomy between organisms and environment that characterizes the interactional perspective on evolution and provides epistemological support for the emergentist, systemic view of evolutionary and developmental processes. (shrink)

The replication crisis has caused researchers to distinguish between exact replications, which duplicate all aspects of a study that could potentially affect the results, and direct replications, which duplicate only those aspects of the study that are thought to be theoretically essential to reproduce the original effect. The replication crisis has also prompted researchers to think more carefully about the possibility of making Type I errors when rejecting null hypotheses. In this context, the present article considers the utility (...) of two types of Type I error probability: the Neyman–Pearson long run Type I error rate and the Fisherian sample-specific Type I error probability. It is argued that the Neyman–Pearson Type I error rate is inapplicable in social science because it refers to a long run of exact replications, and social science deals with irreversible units that make exact replications impossible. Instead, the Fisherian sample-specific Type I error probability is recommended as a more meaningful way to conceptualize false positive results in social science because it can be applied to each sample-specific decision about rejecting the same substantive null hypothesis in a series of direct replications. It is concluded that the replication crisis may be partly due to researchers’ unrealistic expectations about replicability based on their consideration of the Neyman–Pearson Type I error rate across a long run of exact replications. (shrink)

Inhibiting the progress of replication forks in E. coli makes them susceptible to breakage. Broken replication forks are evidently reassembled by the RecBCD recombinational repair pathway. These findings explain a particular pattern of DNA degradation during inhibition of chromosomal replication, the role of recombination in the viability of mutants with displaced replication origin, and hyper‐recombination observed in the Terminus of the E. coli chromosome in rnh mutants. Breakage and repair of inhibited replication forks could (...) be the reason for the recombination‐dependence of inducible stable DNA replication. A mechanism by which RecABCD‐dependent recombination between very short inverted repeats may help E. coli to invert an operon, transcribed in the direction opposite to that of DNA replication, is discussed. (shrink)

Several factors are contributing to an increased air of excitement about the eukaryotic DNA replication problem: new insights into the nature of origins of replication, a better appreciation of the factors that control initiation, and studies of a DNA polymerase α‐primase enzyme complex. In this review, recent research on the initiation, elongation and termination phases of DNA replication is critically examined and a coherent picture is formulated. In the not‐far‐distant future we expect to reproduce these processes in (...) biochemically defined systems. (shrink)

Previous research reported that college students' symbolic addition and subtraction fluency improved after training with non-symbolic, approximate addition and subtraction. These findings were widely interpreted as strong support for the hypothesis that the Approximate Number System (ANS) plays a causal role in symbolic mathematics, and that this relation holds into adulthood. Here we report four experiments that fail to find evidence for this causal relation. Experiment 1 examined whether the approximate arithmetic training effect exists within a shorter training period than (...) originally reported (2 vs 6 days of training). Experiment 2 attempted to replicate and compare the approximate arithmetic training effect to a control training condition matched in working memory load. Experiments 3 and 4 replicated the original approximate arithmetic training experiments with a larger sample size. Across all four experiments (N = 318) approximate arithmetic training was no more effective at improving the arithmetic fluency of adults than training with control tasks. Results call into question any causal relationship between approximate, non-symbolic arithmetic and precise symbolic arithmetic. (shrink)

. Scientists, for the most part, want to get it right. However, the social structures that govern their work undermine that aim, and this leads to nonreplicable findings in many fields. Because the social structure of science is a decentralized system, it is difficult to intervene. In this article, I discuss how we might do so, focusing on self-corrective-labor schemes. First, I argue that we need to implement a scheme that makes replication work outcome independent, systematic, and sustainable. Second, (...) I use these three criteria to evaluate extant proposals, which place the responsibility for replication on original researchers, consumers of their research, students, or many labs. Third, on the basis of a philosophical analysis of the reward system of science and the benefits of the division of cognitive labor, I propose a scheme that satisfies the criteria better: the professional scheme. This scheme has two main components. First, the scientific community is organized into two groups: discovery researchers, who produce new findings, and confirmation researchers, whose primary function is to do confirmation work. Second, a distinct reward system is established for confirmation researchers so that their career advancement is separated from whether they obtain positive experimental results. (shrink)