Clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR‐associated protein (CRISPR/Cas) system has revolutionized genetic research in the life sciences. Four classes of CRISPR/Cas‐derived genome editing agents, such as nuclease, base editor, recombinase, and prime editor have been introduced for engineering the genomes of diverse organisms. The recently introduced prime editing system offers precise editing without many off‐target effects than traditional CRISPR‐based systems. Many researchers have successfully applied this gene‐editing toolbox in diverse systems for various genome‐editing applications. This review presents the mechanism (...) of prime editing and summarizes the details of the prime editing system applied in plants and mammalian cells for precise genome editing. We also discuss the advantages, limitations, and potential future applications of prime editing in these systems. This review enables the researcher to gain knowledge on prime editing tools and their potential applications in plants and mammalian cells. (shrink)

Studies of AGL have frequently used training and test stimuli that might provide multiple cues for learning, raising the question what subjects have actually learned. Using a selected subset of studies on humans and non‐human animals, Trotter et al. demonstrate how a meta‐analysis can be used to identify relevant experimental variables, providing a first step in asssessing the relative contribution of design features of grammars as well as of species‐specific effects on AGL.

Regulation of the subcellular localization of certain proteins is a mechanism for the regulation of their biological activities. FGF‐2 can be produced as distinct isoforms by alternative initiation of translation on a single mRNA and the isoforms are differently sorted in cells. High molecular weight FGF‐2 isoforms are not secreted from the cell, but are transported to the nucleus where they regulate cell growth or behavior in an intracrine fashion. 18 kDa FGF‐2 can be secreted to the extracellular medium where (...) it acts as a conventional growth factor by binding to and activation of cell‐surface receptors. Furthermore, following receptor‐mediated endocytosis, the exogenous FGF‐2 can be transported to the nuclei of target cells, and this is of importance for the transmittance of a mitogenic signal. The growth factor is able to interact with several intracellular proteins. Here, the mode of action and biological role of intracellular FGF‐2 are discussed. BioEssays 28: 504–514, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Regulation of the subcellular localization of certain proteins is a mechanism for the regulation of their biological activities. FGF‐2 can be produced as distinct isoforms by alternative initiation of translation on a single mRNA and the isoforms are differently sorted in cells. High molecular weight FGF‐2 isoforms are not secreted from the cell, but are transported to the nucleus where they regulate cell growth or behavior in an intracrine fashion. 18 kDa FGF‐2 can be secreted to the extracellular medium where (...) it acts as a conventional growth factor by binding to and activation of cell‐surface receptors. Furthermore, following receptor‐mediated endocytosis, the exogenous FGF‐2 can be transported to the nuclei of target cells, and this is of importance for the transmittance of a mitogenic signal. The growth factor is able to interact with several intracellular proteins. Here, the mode of action and biological role of intracellular FGF‐2 are discussed. BioEssays 28: 504–514, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

This article discusses contemporary social psychological approaches to the social relations and appraisals associated with specific emotions; other people’s impact on appraisal processes; effects of emotion on other people; and interpersonal emotion regulation. We argue that single-minded cognitive perspectives restrict our understanding of interpersonal and group-related emotional processes, and that new methodologies addressing real-time interpersonal and group processes present promising opportunities for future progress.

Salient landmarks enhance route learning. We hypothesised that semantically salient nostalgic landmarks would improve route learning compared to non-nostalgic landmarks. In two experiments, participants learned a route through a computer-generated maze using directional arrows and wall-mounted pictures. On the test trial, the arrows were removed, and participants completed the maze using only the pictures. In the nostalgia condition, pictures were of popular music artists and TV characters from 5 to 10 years ago. In the control condition, they were recent pictures (...) of these same artists and characters. In Experiment 1, in the test trial, participants in the nostalgia condition completed the maze faster than controls. Experiment 2 conceptually replicated these findings and extended them by exploring boundary conditions. Participants had to learn two mazes sequentially. In Maze 1, we placed nostalgic/control landmarks only at non-decision points (whereas we placed them at decision points in Experiment 1). In Maze 2, we placed nostalgic/control landmarks at decision points during acquisition but removed them in the test trial (whereas they were present in the test trial in Experiment 1). In both mazes, participants in the nostalgia (compared to control) condition completed the test trial faster. (shrink)

Dependency relationships within the cell cycle allow cells to arrest the cycle reversibly in response to agents or conditions that interfere with specific aspects of its normal progression. In addition, overlapping pathways exist which also arrest the cell cycle in response to DNA damage. Collectively, these control mechanisms have become known as checkpoints. Analysis of checkpoints is facilitated by the fact that dependency relationships within the cell cycle, such as the dependency of mitosis on the completion of DNA synthesis, and (...) the DNA damage checkpoint can be separated genetically. In fission yeast, Schizosaccharomyces pombe, the dependency of mitosis on prior completion of DNA synthesis is mediated through tyrosine‐15 phosphorylation of the ubiquitous mitotic regulator p34cdc2. In contrast, the arrest of mitosis caused by DNA damage acts through a separate mechanism that appears to be independent of tyrosine‐15 phosphorylation. Despite these distinct interactions with the mitotic machinery, the majority of fission yeast mutants that are deficient in mitotic arrest after DNA damage are also unable to respond to inhibition of DNA synthesis. In this essay we survey the current knowledge concerning feedback controls and checkpoints within fission yeast and relate this to information derived from other systems. (shrink)

Decision outcomes sometimes result in negative emotions. This can occur when a decision appears to be wrong in retrospect, and/or when the obtained decision outcome does not live up to expectations. Regret and disappointment are the two emotions that are of central interest in the present article. Although these emotions have a lot in common, they also differ in ways that are relevant to decision making. In this article we review theories and empirical findings concerning regret and disappointment. We first (...) discuss how regret and disappointment differ with respect to their antecedent conditions, appraisals, and phenomenology. We also discuss possible behavioural consequences of experiencing these emotions. Next, we consider how the anticipation of regret and disappointment may influence decision making. We use regret and disappointment theory, developed by the economists Bell (1982, 1985), and Loomes and Sugden (1982, 1986, 1987), as a framework for our discussion. Finally, we argue that combining the theoretical approaches and research paradigms of behavioural decision theory with emotion theories will significantly increase our knowledge of antecedents and consequences of emotions. (shrink)

In the 1960s and 1970s, scuba technology, underwater cameras, and documentarians revealed a long-hidden underwater world to the public. At this time oceanographic science was growing exponentially. Historians of the marine sciences have focused their studies of the period on institutional and military partnerships, and on the scientist-administrators who shaped oceanographic research institutions (such as the Scripps Institution of Oceanography, the Woods Hole Oceanographic Institution, and the British National Institute of Oceanography). Underwater habitat development during the 1960s and 1970s, however, (...) deserves greater attention than it has yet received, as it highlights a peculiar confluence of military, scientific, and popular interest, characteristic of the period, in the colonization of the seafloor. Existing accounts have focused on American habitats, notably Sealab and Tektite, since these were the largest and best funded. But this approach overemphasizes a Cold War narrative in which the sole protagonists of the habitat programs were the United States and the Soviet Union. At least 65 habitats were built between 1962 and 1991. Some were state-sponsored, with significant programs run by French, German, Japanese, and Canadian teams. This essay takes as a case study the Canadian Sublimnos habitat as well as the underwater exploration programs it helped launch in Newfoundland (Lora-I) and in the Arctic (Sub-Igloo). The Canadian case demonstrates that technological expertise and public enthusiasm for underwater exploration should not be solely understood with reference to Cold War interests of the two superpowers. Rather, the international range of habitat programs of the 1960s and 1970s reveals an expanding interest in the vertical underwater dimension that was fueled by numerous national scientific aims and territorial claims. (shrink)

Regret and disappointment have in common the fact that they are experienced when the outcome of a decision is unfavourable: They both concern “what might have been”, had things been different. However, some regret and disappointment theorists regard the differences between these emotions as important, arguing that they differ with respect to the conditions under which they are felt, and how they affect decision making. The goal of the present research was to examine whether and how these emotions also differ (...) with respect to the way in which they are experienced. Participants were asked torecall aninstance of intense regret or disappointment andto indicate what they felt, thought, felt like doing, did, and were motivated to do during this experience (cf. Roseman, Wiest, & Swartz, 1994). Significant differences between regret and disappointment were found in every category. These differences were most pronounced for “action tendencies” (what participants felt like doing) and “emotivations” (what they were motivated to do). These results suggest that the two emotions have differential implications for future behaviour. (shrink)

This study proposes that Neoplatonism, while not a modern philosophy, is philosophy in the modern sense. Lloyd analyzes the key structures that underlie the dogmas of the Neoplatonic world picture, including the concept of emanation, the return of the soul to the One, the place of mystical knowledge, epistemology, and Porphyry's theory of predication, and shows that they rest on original but intelligible concepts and arguments.

ABSTRACTIn this paper I reassess the place of Plato’s Laws in the history of legal thought. The Laws has been traditionally considered to present a natural law theory of law. I argue instead that it presents a positivist account of the nature of law. Through analysis of some key passages of the Laws I argue that in that dialogue law is identified with conclusions of enkratic civic reason that may systematically conflict with precepts of substantive moral reason. I also argue (...) that in the Laws the rule of law is a precondition of a legal system but lacks inherent moral significance. For the rule of law to obtain there needs to be some compromise between the political interests of rulers and subjects which is grounded on political pragmatism and not on moral considerations. (shrink)

Insults elicit intense emotion. This study tests the hypothesis that one's social image, which is especially salient in honour cultures, influences the way in which one reacts to an insult. Seventy-seven honour-oriented and 72 non-honour oriented participants answered questions about a recent insult episode. Participants experienced both anger and shame in reaction to the insult. However, these emotions resulted in different behaviours. Anger led to verbal attack (i.e., criticising, insulting in return) among all participants. This relationship was explained by participants’ (...) motivation to punish the wrongdoer. Shame, on the other hand, was moderated by honour. Shame led to verbal disapproval of the wrongdoers behaviour, but only among the honour-oriented participants. This relationship was explained by these participants’ motivation to protect their social image. By contrast, shame led to withdrawal among non-honour-oriented participants. (shrink)

Many researchers believe the tremendous industrial development over the past two centuries is unsustainable because it has led to unintended ecological deterioration. Despite the ever-growing attention sustainable supply-chain management has received, most SSCM research and models look at the consequences, rather than the antecedents or motives of such responsible practices. The few studies that explore corporate motives have remained largely qualitative, and large-scale empirical analyses are scarce. Drawing on multiple theories and combining supply-chain and business ethics literature, we purport that (...) instrumental, relational, and moral motives are behind a firm’s engagement in SSCM practices. Specifically, we examine the links between corporate motives, SSCM practices, and firm performance. Using a sample of 259 supply-chain firms in Germany, we empirically test five hypothesized relationships. Our results reveal that relational and moral motives are key drivers, and that firms exhibiting high levels of moral obligations tend to outperform those primarily driven by amoral considerations. Findings of this study contribute to multiple literatures espousing sustainability management and can help policy makers, stakeholder groups, and scholars develop more robust strategies for encouraging firms to practice SSCM. (shrink)

The current legal status and medical ethics of routine or religious penile circumcision of minors is a matter of ongoing controversy in many countries. We focus on the United Kingdom as an illustrative example, giving a detailed analysis of the most recent British Medical Association guidance from 2019. We argue that the guidance paints a confused and conflicting portrait of the law and ethics of the procedure in the UK context, reflecting deeper, unresolved moral and legal tensions surrounding child genital (...) cutting practices more generally. Of particular note is a lack of clarity around how to apply the “best interests” standard—ordinarily associated with time-sensitive proxy decision making regarding therapeutic options for a medically unwell patient—to a parental request for a medically unnecessary surgery to be carried out on the genitalia of a healthy child. Challenges arise in measuring and assigning weights to intended sociocultural or religious/spiritual benefits, and even to health-related prophylactic benefits, and in balancing these against potential physical, functional, and psychosexual risks or harms. Also of concern are apparently inconsistent safeguarding standards being applied to children based on their birth sex categorization or gender of rearing. We identify and discuss recent trends in British and international medical ethics and law, finding gradual movement toward a more unified standard for evaluating the permissibility of surgically modifying healthy children's genitals before they can meaningfully participate in the decision. (shrink)

A key feature of facial behavior is its dynamic quality. However, most previous research has been limited to the use of static images of prototypical expressive patterns. This article explores the role of facial dynamics in the perception of emotions, reviewing relevant empirical evidence demonstrating that dynamic information improves coherence in the identification of affect (particularly for degraded and subtle stimuli), leads to higher emotion judgments (i.e., intensity and arousal), and helps to differentiate between genuine and fake expressions. The findings (...) underline that using static expressions not only poses problems of ecological validity, but also limits our understanding of what facial activity does. Implications for future research on facial activity, particularly for social neuroscience and affective computing, are discussed. (shrink)

We examined social facilitation and emotional convergence in amusement, sadness, and fear in dynamic interactions. Dyads of friends or strangers jointly watched emotion-eliciting films while they either could or could not communicate nonverbally. We assessed three components of each emotion (expressions, appraisals, and feelings), as well as attention to and social motives toward the co-participant. In Study 1, participants interacted through a mute videoconference. In Study 2, they sat next to each other and either were or were not separated by (...) a partition. Results revealed that facilitation and convergence are not uniform across different emotions and emotion components. Particularly strong supporting patterns emerged for the facilitation of and convergence in smiling. When direct interaction was possible (Study 2), friends showed a general tendency for strong convergence, with the exception of fear-related appraisals. This suggests that underlying processes of emotional contagion and social appraisal are differentially relevant for different emotions. (shrink)

Following the pattern set by the early German Romantics, Kierkegaard conveys many of his insights through literature rather than academic prose. What makes him a valuable member of this tradition is the theory he develops to support it, his so-called “theory of indirect communication.” The most exciting aspect of this theory concerns the alleged importance of indirect communication: Kierkegaard claims that there are some projects only it can accomplish. This paper provides a critical account of two arguments Kierkegaard offers in (...) defense of this claim. The first argument is that he needs to use indirect communication in order to discourage people from losing themselves in the “crowd”. The second argument is that he needs to use it in order to help people out of a “monstrous illusion”. It is shown that while both arguments justify Kierkegaard’s decision to use indirect communication, neither one supports the original claim about its indispensability. (shrink)

This paper provides an account of Kierkegaard’s central criticism of the Danish Hegelians. Contrary to recent scholarship, it is argued that this criticism has a substantive theoretical basis and is not merely personal or ad hominem in nature. In particular, Kierkegaard is seen as criticizing the Hegelians for endorsing an unacceptable form of intellectual elitism, one that gives them pride of place in the realm of religion by dint of their philosophical knowledge. A problem arises, however, because this criticism threatens (...) to apply to Kierkegaard himself. It is shown that Kierkegaard manages to escape this problem by virtue of the humorous aspect of his work. (shrink)

To many readers of The Prince, Machiavelli appears to be deeply un-Christian or even anti-Christian, a cynic who thinks rulers should use religion only to keep their subjects in check. But in Machiavelli's God, Maurizio Viroli, one of the world's leading authorities on Machiavelli, argues that Machiavelli, far from opposing Christianity, thought it was crucial to republican social and political renewal--but that first it needed to be renewed itself. And without understanding this, Viroli contends, it is impossible to comprehend Machiavelli's (...) thought. Viroli places Machiavelli in the context of Florence's republican Christianity, which was founded on the idea that the true Christian is a citizen who serves the common good. In this tradition, God participates in human affairs, supports and rewards those who govern justly, and desires men to make the earthly city similar to the divine one. Building on this tradition, Machiavelli advocated a religion of virtue, and he believed that, without this faith, free republics could not be established, defend themselves against corruption, or survive. Viroli makes a powerful case that Machiavelli, far from being a pagan or atheist, was a prophet of a true religion of liberty, a way of moral and political living that would rediscover and pursue charity and justice.The translation of this work has been funded by SEPS - Segretariato Europeo per le Pubblicazioni Scientifiche. (shrink)

To many readers of The Prince, Machiavelli appears to be deeply un-Christian or even anti-Christian, a cynic who thinks rulers should use religion only to keep their subjects in check. But in Machiavelli's God, Maurizio Viroli, one of the world's leading authorities on Machiavelli, argues that Machiavelli, far from opposing Christianity, thought it was crucial to republican social and political renewal--but that first it needed to be renewed itself. And without understanding this, Viroli contends, it is impossible to comprehend Machiavelli's (...) thought. Viroli places Machiavelli in the context of Florence's republican Christianity, which was founded on the idea that the true Christian is a citizen who serves the common good. In this tradition, God participates in human affairs, supports and rewards those who govern justly, and desires men to make the earthly city similar to the divine one. Building on this tradition, Machiavelli advocated a religion of virtue, and he believed that, without this faith, free republics could not be established, defend themselves against corruption, or survive. Viroli makes a powerful case that Machiavelli, far from being a pagan or atheist, was a prophet of a true religion of liberty, a way of moral and political living that would rediscover and pursue charity and justice.The translation of this work has been funded by SEPS - Segretariato Europeo per le Pubblicazioni Scientifiche. (shrink)

The present article commences analyzing the origins and influences of the religious discourse on the configuration of the modern constitutional discourse and the contributions of the jus-positivism in the consolidation of this sacred-civil language. The second issue is the definition of the U.S. Constitution as a mixed and not as a democratic constitution, with regard to the influences of Plato, Aristotle, Cicero and Polybius to the Drafters of the first modern constitutional text; stability and equilibrium took preference over democracy in (...) a wide sense. I also analyze how the Drafter’s decision has conditioned the modern constitutional system up to the present. (shrink)

In the late nineteenth century, French naturalists were global leaders in microbial research. Louis Pasteur advanced sterilization techniques and demonstrated that dust particles in the air could contaminate a putrefiable liquid. Pasteur’s discoveries prompted a new research program for the naturalists of the Talisman and Travailleur expeditions: to recover uncontaminated water and mud samples from the deep sea. French naturalists Adrien Certes and Paul Regnard both independently conducted experiments to address the question of whether microorganisms inhabited the oceans and whether (...) organic material in the deep sea was subject to decomposition. The experiments of Certes and Regnard have largely been omitted from histories of microbiology and marine science. However, an examination of their work is crucial for understanding the context in which marine microbiology first developed. At the end of the nineteenth century, marine microbiology emerged from the disciplinary melding of terrestrial microbial ecology, experimental physiology, and the then-nascent field of deep-sea biology. (shrink)

Currently, testimony is studied extensively in Anglo-American philosophy. However, most of this work is done from a justificationist perspective in which philosophers try to justify our reliance on testimony in some way. I agree with Popper that justificationism is radically mistaken. Thus, I construct an account of how we respond to testimony that in no way attempts to justify our reliance on it. This account is not a straightforward exegesis of Popper, as he never tackled testimony systematically. It makes use, (...) however, of several of Popper's key insights and incorporates them into a viable theory of testimony. Key Words: testimony • anti-justificationism • social epistemology • situational analysis • defeasibility. (shrink)

Gender dysphoria is a persistent distress about one’s assigned gender. Referrals regarding gender dysphoria have recently greatly increased, often of a form that is rapid in onset. The sex ratio ha...

This paper deals with Hobbes's theory of optical images, developed in his optical magnum opus, ‘A Minute or First Draught of the Optiques’, and published in abridged version in De homine. The paper suggests that Hobbes's theory of vision and images serves him to ground his philosophy of man on his philosophy of body. Furthermore, since this part of Hobbes's work on optics is the most thoroughly geometrical, it reveals a good deal about the role of mathematics in Hobbes's philosophy. (...) The paper points to some difficulties in the thesis of Shapin and Schaffer, who presented geometry as a ‘paradigm’ for Hobbes's natural philosophy. It will be argued here that Hobbes's application of geometry to optics was dictated by his metaphysical and epistemological principles, not by a blind belief in the power of geometry. Geometry supported causal explanation, and assisted reason in making sense of appearances by helping the philosopher understand the relationships between the world outside us and the images it produces in us. Finally the paper broadly suggests how Hobbes's theory of images may have triggered, by negative example, the flourishing of geometrical optics in Restoration England. (shrink)

The paper presents the territorial and axiological context and the peculiarities of the participatory project developed by the Polis Research Centre and the Bon Pastor Neighbourhood Association, as well as the first steps in the design of two interventions. The first intervention, the Wall and Party Walls in Rodriguez de la Fuente Square, is proposed within the framework of the sustainable development strategies of Barcelona City Council. Its main objective is to achieve thermal insula­tion of the affected dwellings, thus contributing (...) to the well being of the residents and to the reduc­tion of CO 2 emissions into the atmosphere. Besides, it is aimed to solve landscape discontinuity. In the lower part of the party walls, there is a wall, a kind of plinth that the residents have chosen as a site for the expansion of the work on the civic remembrance of the neighbourhood. There, the “Living Memory” space will be set up, reserved for interventions by children from the quarter’s schools through a work programme run in cooperation with them. The second intervention is the case of the centennial Mulberry Tree classified as a tree of local interest. In 2018, the mulberry tree suffered some damage from thugs who threw firecrackers inside. Therefore, the need was pointed out to reorganise the space around the tree in order to create dissuasive effects and preserve its integrity. These are preliminary studies to be discussed by the agents involved in the project: the Sant Andreu District, the IMPUQV (Institut Municipal del Paisatge Urbài la Qualitat de Vida), and the Bon Pastor Neighbourhood Association. (shrink)

We investigated the role of honour concerns in mediating the effect of nationality and gender on the reported intensity of anger and shame in reaction to insult vignettes. Spain, an honour culture, and The Netherlands, where honour is of less central significance, were selected for comparison. A total of 260 (125 Dutch, 135 Spanish) persons participated in the research. Participants completed a measure of honour concerns and answered questions about emotional reactions of anger and shame to vignettes depicting insults in (...) which type of threat was manipulated. It was found that Spanish participants responded especially intensely to insults that threaten family honour, and that this effect of nationality on emotional reactions to threats to family honour was mediated by individual differences in concern for family honour. (shrink)

Material Engagement Theory is currently driving a conceptual change in the archaeology of mind. Drawing upon the dictates of enactivism and active externalism, it specifically calls for a radical reconceptualization of mind and material culture. Unpersuaded by the common assumption that cognition is brain-bound, Malafouris argues in favour of a process ontology that situates thinking in action. In granting ontological primacy to material engagement, MET seeks to illuminate the emergence of human ways of thinking through the practical effects of the (...) material world. Considering that this is a characteristic example of a pragmatic take on cognition, this contemporary theoretical platform appears to share a lot with pragmatism. As of late, scholars working at the intersection of philosophy, semiotics, and cognitive science have made important steps towards the rapprochement between pragmatism and externalism. Looking to contribute to this growing corpus of work, the present paper focuses on MET’s relation to the pragmatism of Peirce, Dewey, and Mead. Having elsewhere recognized the overlap and complementarity between Malafouris’ and Peirce’s theories in particular, I developed a pragmatic and enactive theory of cognitive semiotics that is suitably geared to trace the nature, emergence, and evolution of material signs. Therefore, besides noting some obvious historical connections, I hereby aim to establish the theoretical backdrop upon which this composite theory is supposed to function, while also exploring new potential avenues. Given that this cognitive semiotic framework can be seen as a pragmatic extension of Malafouris’ enactivist approach to archaeology, the current paper delves into MET’s theoretical underpinnings, seeking to complement its working hypotheses and concepts with philosophical notions and ideas advanced long ago. This synthesis ultimately concludes with a call for the reconceptualization of ‘representation’ as a heuristic concept. (shrink)

Recent scholarship has shown that the success of Pascal’s wager rests on precarious grounds. To avoid notorious problems, it must appeal to considerations such as what probability we assign to the existence of various gods and what religion we think provides the greatest happiness in this life. Rational judgments concerning these matters are subject to change over time. Some claim that the wager therefore cannot support a steadfast commitment to God. I argue that this conclusion does not follow. By drawing (...) upon the line of reasoning employed in getting married, I explain how unstable considerations can provide a sufficient rational foundation for a stable commitment. (shrink)