Several DNA-damage detection and repair mechanisms have evolved to repair double-strand breaks induced by mutagens. Later in evolutionary history, DNA single- and double-strand cuts made possible immune diversity by V(D)J recombination and recombination at meiosis. Such cuts are induced endogenously and are highly regulated and controlled. In meiosis, DNA cuts are essential for the initiation of homologous recombination, and for the formation of joint molecule and crossovers. Many proteins that function during somatic DNA-damage detection and repair are also active during (...) homologous recombination. However, their meiotic functions may be altered from their somatic roles through localization, posttranslational modifications and/or interactions with meiosis-specific proteins. Presumably, somatic repair functions and meiotic recombination diverged during evolution, resulting in adaptations specific to sexual reproduction. BioEssays 27:795–808, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Protein disulfide isomerase (PDI) is one of the most abundant and critical protein folding catalysts in the endoplasmic reticulum of eukaryotic cells. PDI consists of four thioredoxin domains and interacts with a wide range of substrate and partner proteins due to its intrinsic conformational flexibility. PDI plays multifunctional roles in a variety of pathophysiological events, both as an oxidoreductase and a molecular chaperone. Recent studies have revealed that the conformation and activity of PDI can be regulated in multiple ways, including (...) posttranslational modification and substrate/ligand binding. Here, we summarize recent advances in understanding the function and regulation of PDI in different pathological and physiological events. We propose that the multifunctional roles of PDI are regulated by multiple mechanisms. Furthermore, we discuss future directions for the study of PDI, emphasizing how different regulatory modes are linked to the conformational changes and biological functions of PDI in the context of diverse pathophysiologies. (shrink)

The Protein Ontology (PRO) is designed as a formal and principled Open Biomedical Ontologies (OBO) Foundry ontology for proteins. The components of PRO extend from a classification of proteins on the basis of evolutionary relationships at the homeomorphic level to the representation of the multiple protein forms of a gene, including those resulting from alternative splicing, cleavage and/or posttranslational modifications. Focusing specifically on the TGF-beta signaling proteins, we describe the building, curation, usage and dissemination of PRO. PRO provides a (...) framework for the formal representation of protein classes and protein forms in the OBO Foundry. It is designed to enable data retrieval and integration and machine reasoning at the molecular level of proteins, thereby facilitating cross-species comparisons, pathway analysis, disease modeling and the generation of new hypotheses. (shrink)

Autophagy and YAP1‐WWTR1/TAZ signalling are tightly linked in a complex control system of forward and feedback pathways which determine different cellular outcomes in differing cell types at different time‐points after perturbations. Here we extend our previous experimental and modelling approaches to consider two possibilities. First, we have performed additional mathematical modelling to explore how the autophagy‐YAP1 crosstalk may be controlled by posttranslational modifications of components of the pathways. Second, since analogous contrasting results have also been reported for autophagy as (...) a regulator of other transduction pathways engaged in tumorigenesis (Wnt/β‐catenin, TGF‐β/Smads, NF‐kB or XIAP/cIAPs), we have considered if such discrepancies may be explicable through situations involving competing pathways and feedback loops in different cell types, analogous to the autophagy‐YAP/TAZ situation. Since distinct posttranslational modifications dominate those pathways in distinct cells, these need to be understood to enable appropriate cell type‐specific therapeutic strategies for cancers and other diseases. (shrink)

Mild and massive DNA damage are differentially integrated into the cellular signaling networks and, in consequence, provoke different cell fate decisions. After mild damage, the tumor suppressor p53 directs the cellular response to cell cycle arrest, DNA repair, and cell survival, whereas upon severe damage, p53 drives the cell death response. One posttranslational modification of p53, phosphorylation at Serine 46, selectively occurs after severe DNA damage and is envisioned as a marker of the cell death response. However, the (...) molecular mechanism of action of the p53 Ser46 phospho‐isomer, the molecular timing of this phosphorylation event, and its activating effects on apoptosis and ferroptosis still await exploration. In this essay, the current body of evidence on the molecular function of this deadly p53 mark, its evolutionary conservation, and the regulation of the key players of this response, the p53 Serine 46 kinases, are reviewed and dissected. (shrink)

Growth cones are the highly motile structures found at the tips of growing axons and dendrites (neurites), which extend from neurones, during the development of the nervous system. They function both as detectors and transducers of extrinsic guidance cues and as regions where the neurite cytoskeleton is assembled. Without concerted neurite assembly, advance cannot occur. Assembly of the neurite cytoskeleton in growing neurites chiefly involves microtubule assembly at the growth cone. Some of the factors that may influence microtubule assembly in (...) growth cones are becoming apparent and include posttranslational modification of tubulin itself and microtubule associated proteins, particularly tau and MAP1B. (shrink)

Baculovirus vectors have proven useful in producing high levels of biologically active eukaryotic proteins and providing cellular fractions which are enriched in the protein of interest. Expression occurs in infected insect cells which also provide a suitable environment for posttranslational modification and folding of the protein product. Stable baculovirus vectors can be constructed rapidly with a minimum of viral manipulation.

Ubiquitin is the most phylogenetically conserved protein known. This 8,500 Da polypeptide can be covalently attached to cellular proteins as a posttranslational modification. In most cases, the addition of multiple ubiquitin adducts to a protein targets it for rapid degradation by a multisubunit protease known as the 26S proteasome. While the ubiquitin/26S proteasome pathway is responsible for the degradation of the bulk of cellular proteins during homeostasis, it may also be responsible for the rapid loss of protein during (...) the programmed death of certain cells, such as skeletal muscle during insect metamorphosis. In addition, alterations in the expression and regulation of ubiquitin may play significant roles in pathological disorders. For example, dramatic increases in ubiquitin and ubiquitin‐protein conjugates are observed in a wide variety of neurodegenerative disorders, including Alzheimer's disease. Patients suffering from the autoimmune disease systemic lupus erythematosus generate antibodies reacting with ubiquitin and ubiquitinated histones. At present, it is not known whether these changes in ubiquitin expression and regulation initiate pathological changes in these diseases or if they are altered as a consequence of these disorders. (shrink)

Cellular processes are highly dependent on a dynamic proteome that undergoes structural and functional rearrangements to allow swift conversion between different cellular states. By inducing proteasomal degradation of inhibitory or stimulating factors, ubiquitylation is particularly well suited to trigger such transitions. One prominent example is the remodelling of the centrosome upon cell cycle exit, which is required for the formation of primary cilia – antenna‐like structures on the surface of most cells that act as integrative hubs for various extracellular signals. (...) Over the last decade, many reports on ubiquitin‐related events involved in the regulation of ciliogenesis have emerged. Very often, these processes are considered to be initiated ad hoc, that is, directly before its effect on cilia biogenesis becomes evident. While such a temporal restriction may hold true for the majority of events, there is evidence that some of them are initiated earlier during the cell cycle. Here, we provide an overview of ubiquitin‐dependent processes in ciliogenesis and discuss available data that indicate such an early onset of proteolytic regulation within preceding cell cycle stages. (shrink)

The N‐end rule denotes the relationship between the identity of the amino‐terminal residue of a protein and its in vivo half‐life. Since its discovery in 1986, the N‐end rule has generally been described by a defined set of rules for determining whether an amino‐terminal residue is stabilizing or not. However, recent studies are revealing that this N‐end rule (or N‐degron concept) is less straightforward than previously appreciated. For instance, it is unveiled that N‐terminal acetylation of N‐terminal residues may create a (...) degradation signal (Ac‐degron) that promotes the degradation of target proteins. A recent high‐throughput dissection of degrons in yeast proteins amino termini intriguingly suggested that the hydrophobicity of amino‐terminal residues—but not the N‐terminal acetylation status—may be the indispensable feature of amino‐terminal degrons. Herein, these recent advances in N‐terminal acetylation and the complexity of N‐terminal degradation signals in the context of the N‐degron pathway are analyzed. (shrink)

Methyl CpG binding protein 2 (MeCP2) was initially isolated as an exclusive reader of DNA methylated at CpG. This recognition site, was subsequently extended to other DNA methylated residues and it has been the persisting dogma that binding to methylated DNA constitutes its physiologically relevant role. As we review here, two very recent papers fundamentally change our understanding of the interactions of this protein with chromatin, as well as its functional attributes. In the first one, the protein has been shown (...) to bind to tri‐methylated histone H3 (H3K27me3), providing a hint for what might turn out to be the first described chromodomain‐containing protein reader in the animal kingdom, and unequivocally demonstrates the ability of MeCP2 to bind to nonmethylated CpG regions of the genome. The second paper reports how the protein dynamically participates in the formation of constitutive heterochromatin condensates. Histone H3K27me3 is a critical component of this form of chromatin. (shrink)

Two posttranslational lipid modifications present on all Hedgehog (Hh) morphogens—an N‐terminal palmitate and a C‐terminal cholesterol—are established and essential regulators of Hh biofunction. Yet, for several decades, the question of exactly how both lipids contribute to Hh signaling remained obscure. Recently, cryogenic electron microscopy revealed different modes by which one or both lipids may contribute directly to Hh binding and signaling to its receptor Patched1 (Ptc). Some of these modes demand that the established release factor Dispatched1 (Disp) extracts dual‐lipidated (...) Hh from the cell surface, and that another known upstream signaling modulator called Scube2 chaperones the dual‐lipidated morphogen to Ptc. By mechanistically and biochemically aligning this concept with established in vivo and recent in vitro findings, this reflection identifies remaining questions in lipidated Hh transport and evaluates additional mechanisms of Disp‐ and Scube2‐regulated release of a second bioactive Hh fraction that has one or both lipids removed. (shrink)

Adverbial modification is probably one of the least understood areas of linguistics. The essays in this volume all address the problem of how to give an analysis of adverbial modifiers within truth-conditional semantics. Chapters I-VI provide analyses of particular modifiers within a possible worlds framework, and were written between 1974 and 1981. Original publication details of these chapters may be found on p. vi. Of these, all but Chapter I make essential use of the idea that the time reference (...) involved in tensed sentences should be a time interval rather than a single instant. The final chapter (Chapter VII) was written especially for this volume and investigates the question of how the 'situation semantics' recently devised by Jon Barwise and John Perry, as a rival to possible-worlds semantics, might deal with adverbs. In addition I have included an appendix to Chapter III and an introduction which links all the chapters together. (shrink)

One of the most difficult issues to sort out morally is our obligation to future generations. Most individuals feel that they do indeed have some kind of obligation, but face difficulty in explaining the exact nature of the obligation. For one, it seems impossible to know the wants and desires of future generations, and furthermore the existence of the persons we are obligated to is entirely dependent upon the choices that we in fact make. In essence, we could shape future (...) generations so that they desire exactly what we provide for them. It seems that no matter what principle we adopt that is based upon these potential individuals we are led to absurd conclusions. Gregory Kavka calls this moral grappling the Paradox of Future Individuals. I believe that the ethical concerns surrounding genetic engineering should be seen as a specific instantiation of this Paradox and that by examining both we may be able to come up with some sort of working solution. Derek Parfit pleads ignorance as to a solution to this Paradox after an extensive exegesis on the issue, but as we may not be that far from shopping a genetic supermarket to determine the characteristics of our children I don’t believe we can settle for that conclusion. We will begin by examining the Paradox and suggested solutions to the Paradox. Next I will address how the Paradox relates directly to genetic engineering and discuss how rights-based arguments aimed against genetic engineering fail because of the nature of identity. Then I will consider how David Heyd’s Genero-centric principle applies to genetic engineering specifically and how a modified version of that principle may guide us out of the Paradox of Future Individuals in general. This solution may not be acceptable to utilitarian sensibilities, but it is because the numbers don’t add up that we may need to appeal to a different principle entirely. (shrink)

The potential of memory modification techniques (MMTs) has raised concerns and sparked a debate in neuroethics, particularly in the context of identity and authenticity. This paper addresses the question whether and how MMTs influence authenticity. I proceed by drawing two distinctions within the received views on authenticity. From this, I conclude that an analysis of MMTs based on a dual-basis, process view of authenticity is warranted, which implies that the influence of MMTs on authenticity crucially depends on the specifics (...) of how memory modification would eventually work. Therefore, I continue with a systematic analysis of possible properties of MMTs in which I distinguish between the dimensions of memories and the kinds of experiences that can be modified as well as the properties of the process of memory modification. The impact of MMTs on authenticity is analyzed regarding the possible properties of MMTs and based on a narrative approach to authenticity which fulfills the requirements of a dual-basis, process view of authenticity. Lastly, I explore the potential of MMTs to shift the balance between self-discovery and self-creation within authenticity and thereby alter the concept itself as well as the value of authenticity. (shrink)

Appellate Court Modifications Extraction consists of, given an Appellate Court decision, identifying the proposed modifications by the upper Court of the lower Court judge’s decision. In this work, we propose a system to extract Appellate Court Modifications for Portuguese. Information extraction for legal texts has been previously addressed using different techniques and for several languages. Our proposal differs from previous work in two ways: our corpus is composed of Brazilian Appellate Court decisions, in which we look for a set of (...) modifications provided by the Court; and to automatically extract the modifications, we use a traditional Machine Learning approach and a Deep Learning approach, both as alternative solutions and as a combined solution. We tackle the Appellate Court Modifications Extraction task, experimenting with a wide variety of methods. In order to train and evaluate the system, we have built the KauaneJunior corpus, using public data disclosed by the Appellate State Court of Rio de Janeiro jurisprudence database. Our best method, which is a Bidirectional Long Short-Term Memory network combined with Conditional Random Fields, obtained an \ score of 94.79%. (shrink)

In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the (...) development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. (shrink)

Summary The present paper constitutes an elaboration of a previous work by one of us which, among other things, proposed some modifications of Popper's tetradic schema. Here, in the first part, we consider critically and develop further these modifications and elaborate on methods which prove more satisfactory for the mapping of the problem solving processes in Physics. We also find the opportunity to make some comments on Physics and on its relation to Mathematics. In the second part, there is an (...) attempt to test the above ideas on the genesis and development of the Special Relativity Theory. In doing this, we concentrate mainly on Einstein's 1905 paper and try to explicitate its relation with the situation Physics found itself in that period as well as to clarify the epistemological status of Einstein's two postulates. (shrink)

Bellʼs 1964 theorem causes a severe problem for the notion that correlations require explanation, encapsulated in Reichenbachʼs principle of common cause. Despite being a hallmark of scientific thought, dropping the principle has been widely regarded as much less bitter medicine than the perceived alternative—dropping relativistic causality. Recently, however, some authors have proposed that modified forms of Reichenbachʼs principle could be maintained even with relativistic causality. Here we break down Reichenbachʼs principle into two independent assumptions—the principle of common cause proper and (...) factorization of probabilities. We show how Bellʼs theorem can be derived from these two assumptions plus relativistic causality and the law of total probability for actual events, and we review proposals to drop each of these assumptions in light of the theorem. In particular, we show that the non-commutative common causes of Hofer-Szabó and Vecsernyés fail to have an analogue of the notion that the common causes can explain the observed correlations. Moreover, we show that their definition can be satisfied trivially by any quantum product state for any quantum correlations. We also discuss how the conditional states approach of Leifer and Spekkens fares in this regard. (shrink)

In this paper, Carnap's modal logic C is reconstructed. It is shown that the Carnapian approach enables us to create some epistemic logics in a relatively straightforward way. These epistemic modifications of C are axiomatized and one of them is compared with intuitionistic logic. At the end of the paper, some connections between this epistemic logic and Medvedev's logic of finite problems and inquisitive semantics are shortly discussed.

The complexity of the Hedgehog (Hh) signaling cascade has increased over the course of evolution; however, it does not suffice to accommodate the dynamic yet robust requirements of differential Hh signaling activity needed for embryonic development and adult homeostatic maintenance. One solution to solve this dilemma is to apply multiple forms of post‐translational modifications (PTMs) to the core Hh signaling components, modulating their abundance, localization, and signaling activity. This review summarizes various forms of protein modifications utilized to regulate Hh signaling, (...) with a special emphasis on crosstalk between different forms of PTMs and their feedback regulation by Hh signaling. (shrink)

In this article I reply to Thomas Schramme's argument that there are no good reasons for the prohibition of severe forms of voluntary non‐therapeutic body modification. I argue that on paternalistic assumptions there is, in fact, a perfectly good reason.

Expression of sexually dimorphic behaviors critical for reproduction depends on the organizational actions of steroid hormones on the developing brain. We offer the new hypothesis that transcriptional activities in brain regions executing these sexually dimorphic behaviors are modulated by estrogen‐induced modifications of histone proteins. Specifically, in preoptic nerve cells responsible for facilitating male sexual behavior in rodents, gene expression is fostered by increased histone acetylation and reduced methylation (Me), and, that the opposite set of histone modifications will be found in (...) females. Conversely, in ventromedial hypothalamic neurons that are responsible for coordinating female sexual behavior, transcriptional activities in genetic females are fostered by increased histone acetylation and reduced Me, and, further, that the opposite set of histone modifications will be found in males. Thus, these epigenetic events will guarantee that effects of sex hormone exposure during the neonatal critical period will be translated into lasting sex differences in adult reproductive behaviors. (shrink)

One objection to enhancement technologies is that they might lead us to live inauthentic lives. Memory modification technologies (MMTs) raise this worry in a particularly acute manner. In this paper I describe four scenarios where the use of MMTs might be said to lead to an inauthentic life. I then undertake to justify that judgment. I review the main existing accounts of authenticity, and present my own version of what I call a “true self” account (intended as a complement, (...) rather than a substitute, to existing accounts). I briefly describe current and prospective MMTs, distinguishing between memory enhancement and memory editing . Moving then to an assessment of the initial scenarios in the light of the accounts previously described, I argue that memory enhancement does not, by its very nature, raise serious concerns about authenticity. The main threat to authenticity posed by MMTs comes, I suggest, from memory editing. Rejecting as inadequate the worries about identity raised by the President’s Council on Bioethics in Beyond Therapy , I argue instead that memory editing can cause us to live an inauthentic life in two main ways: first, by threatening its truthfulness, and secondly, by interfering with our disposition to respond in certain ways to some past events, when we have reasons to respond in such ways. This consideration allows us to justify the charge of inauthenticity in cases where existing accounts fail. It also gives us a significant moral reason not to use MMTs in ways that would lead to such an outcome. (shrink)

The state currently grants the medical profession a monopolistic entitlement on the legal use of medical technology. As physicians are duty bound to not expose people to medically unnecessary harm, individuals who wish to engage in Body Modification Practices are effectively precluded from doing so as only physicians are legally entitled to use medical technology. In this article, I argue this is incompatible with respect for persons. Abolishing the medical monopoly allows us to meet the demands of respect for (...) persons by granting access to technology, whilst still upholding physicians’ right to refuse to provide requested services and thereby determine the boundaries of their profession according to what they consider to be the internal morality of medicine. (shrink)

Much recent discussion has focused on the nature of artifacts, particularly on whether they have essences. While it is often held that artifacts are intention-dependent and necessarily have functions, it is equally commonly held, though far less discussed, that artifacts are the result of physical modification of some material objects. This paper argues that the physical modification condition on artifacts is false. First, it formulates the physical modification condition perspicuously for the first time. Second, it offers counterexamples (...) to this condition, both concrete and abstract. Third, it considers, and rejects, two responses to these counterexamples, one which appeals to the distinction between being a K and being used as a K and another which argues that the counterexamples are merely of functional, not artifactual, kinds. Finally, it considers, and rejects, a more general objection that appropriation makes artifact creation too easy. As a consequence, artifacts can be created by appropriating pre-existing objects and it sketches some success conditions for such appropriation. (shrink)

In this article, I focus on the media's framing of non-mainstream body modification as a social problem. I demonstrate, through an analysis of a sample of 35 newspaper articles on body modification, that a mutilation discourse is one of the dominant frames of meaning used to make sense of body modifiers in the mainstream media. This framing, which effects the pathologization of body modifiers, utilizes the claims making of mental-health experts and relies on a gendered account of body (...) modification as a social problem. While news accounts are a medium for presenting body modification to a large `community of speakers', I find that they have precluded the legitimacy of the claims of subcultural actors. I argue from a poststructuralist perspective that body modifiers' `claims from the underside' are subjugated by accounts that problematize body modification through the dominant discourse of the mental-health model. I suggest that this frame is problematic for its silencing of `underside' or marginal embodied knowledges, which include, for example, alternative accounts of female embodiment. (shrink)

Through an empirical analysis of YouTube videos, blogs, and interviews, this article explores how partners experience intimacy and desire in relation to trans men’s body modifications. Building on Salamon’s conception of trans bodies as emerging within relations of desire, I argue that partners’ experiences of trans men’s bodies are crucially shaped by their intimate bonds with trans men as people, rather than reducible to generic parts. Partners continue to experience trans men as essentially the same people through gender transition, despite (...) fears that testosterone might alter their personalities. Their intimate bonds with trans men also open up space for new relations of desire to emerge, including attraction to bodily changes they might otherwise find unattractive. These partnerships work to expand ideas about which bodies can be desired as male or masculine, and undercut the literalness of sexual identity labels. Thus, the lived realities of gender transition, as they materialize within this context, challenge hegemonic conceptions of gender, sexuality, and desire. (shrink)

Long‐term modification of synaptic strength is thought to be the basic mechanism underlying the activity‐dependent refinement of neural circuits and the formation of memories engrammed on them. Studies ranging from cell culture preparations to humans subjects indicate that the decision of whether a synapse will undergo strengthening or weakening critically depends on the temporal order of presynaptic and postsynaptic activity. At many synapses, potentiation will be induced only when the presynaptic neuron fires an action potential within milliseconds before the (...) postsynaptic neuron fires, whereas weakening will occur when it is the postsynaptic neuron that fires first. Such processes might be important for the remodeling of neural circuits by activity during development and for network functions such as sequence learning and prediction. Ultimately, this synaptic property might also be fundamental for the cognitive process by which we structure our experience through cause and effect relations. BioEssays 24:212–222, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10060. (shrink)

Bioconservative commentators argue that parents should not take steps to modify the genetics of their children even in the name of enhancement because of the damage they predict for values, identities and relationships. Some commentators have even said that adults should not modify themselves through genetic interventions. One commentator worries that genetic modifications chosen by adults for themselves will undermine moral agency, lead to less valuable experiences and fracture people's sense of self. These worries are not justified, however, since the (...) effects of modification will not undo moral agency as such. Adults can still have valuable experiences, even if some prior choices no longer seem meaningful. Changes at the genetic level will not always, either, alienate people from their own sense of self. On the contrary, genetic modifications can help amplify choice, enrich lives and consolidate identities. Ultimately, there is no moral requirement that people value their contingent genetic endowment to the exclusion of changes important to them in their future genetic identities. Through weighing risks and benefits, adults also have the power to consent to—and assume the risks of—genetic modifications for themselves in a way not possible in prenatal genetic interventions. (shrink)

In ‘Freedom and Resentment’ P. F. Strawson argues that reactive attitudes like resentment and indignation cannot be eliminated altogether, because doing so would involve exiting interpersonal relationships altogether. I describe an alternative to resentment: a form of moral sadness about wrongdoing that, I argue, preserves our participation in interpersonal relationships. Substituting this moral sadness for resentment and indignation would amount to a deep and far‐reaching change in the way we relate to each other – while keeping in place the interpersonal (...) relationships, which, Strawson rightfully believes, cannot be eliminated. (shrink)

This article examines one aspect of the criticism of inauthenticity that can be levelled against the trustworthiness of professional relationships in general and nurse-patient relationships in particular. The overall question is: are such relationships inherently trustworthy or untrustworthy, from the patient’s point of view? The author concludes that, in spite of legitimate grounds for concern, and while it remains true that nurse-patient relationships may be untrustworthy, they are not inherently so for reasons of inauthenticity relating to emotional labour. The arguments (...) used to defend this claim take their force from the idea that different criteria may be needed to assess the authenticity of nurse-patient relationships from those used to evaluate authenticity in ordinary social relationships. The utility of Hochschild’s idea of ‘deep’ acting, as offering a useful model for the management of emotions in nursing, is examined and rejected. (shrink)

For nearly two decades, ethicists have expressed concerns that the further development and use of memory modification technologies (MMTs)—techniques allowing to intentionally and selectively alter memories—may threaten the very foundations of who we are, our personal identity, and thus pose a threat to our well-being, or even undermine our “humaneness.” This paper examines the potential ramifications of memory-modifying interventions such as changing the valence of targeted memories and selective deactivation of a particular memory as these interventions appear to be (...) at the same time potentially both most promising clinically as well as menacing to identity. However, unlike previous works discussing the potential consequences of MMTs, this article analyzes them in the context of the narrative relational approach to personal identity and potential issues related to autonomy. I argue that such a perspective brings to light the ethical aspects and moral issues arising from the use of MMTs that have been hidden from previously adopted approaches. In particular, this perspective demonstrates how important the social context in which an individual lives is for the ethical evaluation of a given memory-modifying intervention. I conclude by suggesting that undertaking memory modifications without taking into account the social dimension of a person’s life creates the risk that she will not be able to meet one of the basic human needs—the autonomous construction and maintenance of personal identity. Based on this conclusion, I offer some reflections on the permissibility and advisability of MMTs and what these considerations suggest for the future. (shrink)

The article is devoted to the consideration of the issue of influential modifications of the genre system of modern mass media. It has been established that the mass media are one of the main means of communication for the wide audience. The meaning of the words "modification", "mass media", "mobile journalism", "new media" has been studied. The article notes that "new media" appeared in the 60s of the XX century. The main characteristics of the media are presented. It is (...) noted that the most common examples of mass media are television, radio, newspapers, magazines, social media, digital media, the Internet. The textbooks and publications of domestic and foreign scientists, which raise the issue of influential modifications of the genre system of modern mass media are highlighted. It was found that the first media were newspaper, telegraph, radio, television. The study of the main types of media is emphasized: traditional media, print media, electronic broadcasting media, external media, transit media and new media. It is noted that new media is a reconceptualization of traditional media. The aspect of media in the role of a social institution has been studied. It was noted about the significant impact of digitalization on the global media system. The significant influence of the use of the Internet in the political life of the United States is given as an illustrative example. The use of the "video story" technology as one of the strategies for holding the attention of the reader or listener is considered. The focus is on the interactive storytelling made possible by digital media and provides advantages for interactive television and cinema, as well as helping to create virtual and mixed reality in games, contributing to the emergence of new forms of voice games. (shrink)

Bioconservative commentators argue that parents should not take steps to modify the genetics of their children even in the name of enhancement because of the damage they predict for values, identities and relationships. Some commentators have even said that adults should not modify themselves through genetic interventions. One commentator worries that genetic modifications chosen by adults for themselves will undermine moral agency, lead to less valuable experiences and fracture people's sense of self. These worries are not justified, however, since the (...) effects of modification will not undo moral agency as such. Adults can still have valuable experiences, even if some prior choices no longer seem meaningful. Changes at the genetic level will not always, either, alienate people from their own sense of self. On the contrary, genetic modifications can help amplify choice, enrich lives and consolidate identities. Ultimately, there is no moral requirement that people value their contingent genetic endowment to the exclusion of changes important to them in their future genetic identities. Through weighing risks and benefits, adults also have the power to consent to—and assume the risks of—genetic modifications for themselves in a way not possible in prenatal genetic interventions. (shrink)

This thesis aims to understand Popper’s falsificationism and Lakatos’ methodology of scientific research programmes right and to grasp why and how Lakatos modifies Popper’s falsificationism to be the methodology of scientific research programmes. Firstly, it sets forth a background in which Lakatos makes the modification. The background is a basis on which we study why Lakatos modifies Popper’s falsificationism. In order to understand Lakatos’ motivation for making the modification better, the section will be described according to Lakatos’ view. (...) It briefly reviews some methodologies of science before Popper, and then explains the two phases of Popper’s methodological falsificationism--naïve methodological falsificationism and sophisticated methodological falsificationism--and makes a comparison between them. Secondly, this thesis states Lakatos’ comments about Popper’s methodological falsificationism, and then explains why and how Lakatos makes the modification and what his modification is. Moreover, it also makes a comparison between Popper’s falsificationism and the modification. Thirdly, having made comments about the influences of their theories, this thesis shows some criticisms raised by contemporary philosophers of science and discusses some of their potential problems. Finally, it makes a brief summary about the whole discussion and draws a conclusion that Lakatos modifies Popper’s falsificationism effectively and improves it more sophisticated. (shrink)