Autophagy, an essential cellular process for maintaining cellular homeostasis and eliminating harmful cytoplasmic objects, involves the de novo formation of double‐membraned autophagosomes that engulf and degrade cellular debris, protein aggregates, damaged organelles, and pathogens. Central to this process is the phagophore, which forms from donor membranes rich in lipids synthesized at various cellular sites, including the endoplasmic reticulum (ER), which has emerged as a primary source. The ER‐associated omegasomes, characterized by their distinctive omega‐shaped structure and accumulation of phosphatidylinositol 3‐phosphate (PI3P), (...) play a pivotal role in autophagosome formation. Omegasomes are thought to serve as platforms for phagophore assembly by recruiting essential proteins such as DFCP1/ZFYVE1 and facilitating lipid transfer to expand the phagophore. Despite the critical importance of phagophore biogenesis, many aspects remain poorly understood, particularly the complete range of proteins involved in omegasome dynamics, and the detailed mechanisms of lipid transfer and membrane contact site formation. (shrink)

Phosphatidylinositol 3‐phosphate (PtdIns3P) is generated on the cytosolic leaflet of cellular membranes, primarily by phosphorylation of phosphatidylinositol by class II and class III phosphatidylinositol 3‐kinases. The bulk of this lipid is found on the limiting and intraluminal membranes of endosomes, but it can also be detected in domains of phagosomes, autophagosome precursors, cytokinetic bridges, the plasma membrane and the nucleus. PtdIns3P controls cellular functions through recruitment of specific protein effectors, many of which contain FYVE or PX domains. Cellular processes (...) known to be controlled by PtdIns3P and its effectors include endosomal fusion, sorting and motility, autophagy, cytokinesis, regulated exocytosis and signal transduction. Here we discuss how Ptdins3P is generated on specific cellular membranes, how its localizations and functions can be studied, and how its effectors serve to control cellular functions.Editor's suggested further reading in BioEssays:Phosphatidylinositol 4,5‐bisphosphate: Targeted production and signalingAbstractHow does SHIP1/2 balance PtdIns(3,4)P2 and does it signal independently of its phosphatase activity?AbstractPhosphatidylinositol‐3,4,5‐trisphosphate: Tool of choice for class I PI 3‐kinasesAbstractPhosphatidylinositol‐4‐phosphate: The Golgi and beyondAbstract. (shrink)

Volume 23, Issue 3-4, November - December 2024, Page 219-244.

The paper discusses Linda Zagzebski's account of epistemic authority. Building on Joseph Raz's account of political authority, Zagzebski argues that the basic contours of epistemic authority match those Raz ascribes to political authority. This, it is argued, is a mistake. Zagzebski is correct in identifying the pre-emptive nature of reasons provided by an authority as central to our understanding of epistemic authority. However, Zagzebski ignores important differences between practical and epistemic authority. As a result, her attempt to explain the rationality (...) of belief on authority by applying an analogue of Raz's Normal Justification Thesis to the domain of belief fails. A successful explanation of the rationality of belief on authority will need to be attuned to the differences between political and epistemic authorities. (shrink)

This paper argues that private property and rights assignment, especially as applied to communication infrastructure and information, should be informed by advances in both technology and our understanding of psychology. Current law in this area in the United States and many other jurisdictions is founded on assumptions about human behavior that have been shown not to hold empirically. A joint recognition of this fact, together with an understanding of what new technologies make possible, leads one to question basic assumptions about (...) how law is made and what laws we should have in a given area, if any. I begin by analyzing different aspects of U.S. law, from a high-level critique of law making to a critique of rights assignment for what I call 'simple nonrival goods.' I describe my understanding, as a non-lawyer with a background in psychology and computing, of the current conventions in U.S. law, consider the foundational assumptions that justify current conventions, describe advances in psychology and technology that call these conventions into question, and briefly note how the law might normatively change in this light. I then apply this general analysis to the question of domain name assignment by the Internet Corporation for Assigned Names and Numbers (ICANN). (shrink)

Hume maintains that the boundaries of morality are widely drawn in everyday life. We routinely blame characters for traits that we find disgusting, on this account, as well as those which we perceive as being harmful. Contemporary moral psychology provides further evidence that human beings have a natural tendency to moralize traits that produce feelings of repugnance. But recent work also demonstrates a significant amount of individual variation in our sensitivities to disgust. We have sufficient reason to bracket this emotion, (...) therefore, when adopting the general point of view: if we allow idiosyncratic affective responses to shape our fully considered moral judgments, we could no longer reasonably expect spectators with different sensitivities to agree with us. (shrink)

Carrie Figdor presents a critical assessment of how psychological terms are used to describe the non-human biological world. She argues against the anthropocentric attitude which takes human cognition as the standard against which non-human capacities are measured, and offers an alternative basis for naturalistic explanation of the mind.

Traditionally, nature has often been thought to be structured by essential forms providing the generic features of natural things and thus the foundations for scientific explanations. In contrast, human history and the social domain have been thought to be the realm of ever-changing appearances, where contingency prevails. The paper argues that the existence of essential forms is compatible with the contingent, mind-dependent and historical character of the social world, and that essential forms can also be found in the social (...) domain. Two categories of entities are discussed that suggest themselves to be identified as social forms, namely social kinds and social identities. To this end, it is shown that standard arguments for the existence of essential forms also apply to the social domain, and objections to the existence of social forms are rebutted. Particular attention is paid to the explanatory appeal of social forms. The paper concludes by suggesting that, far from being oppressive, essential social forms are presupposed by liberating social practices. (shrink)

If contemporary political theory in the area of international justice is to accomplish its aim of clarifying and making coherent the meaning of justice in an international context, the question of the appropriate role and responsibility of international criminal law must be answered. International criminal law must be more than simply domestic laws that are prosecuted at the international level. However, the question of what makes an international crime such that it deserves this special classification and international condemnation has not (...) been adequately theorized. This paper examines the character of international law as expressed by two theorists, Allen Buchanan and Larry May, and reveals the deficiencies of their theories. Then, it offers the first steps to a better theory, one that demands that two thresholds be met for an action to be considered international crime: the severity threshold and the agency threshold. It argues that these two thresholds restrict the domain of international criminal law to crimes that are of significant concern to the global community by way of their threat to political organization. International crimes are the jurisdiction of the international community because they threaten the most basic physical security human rights and because they originate out of the fundamental nature of humans as social entities and maliciously distort and threaten this natural inclination. (shrink)

Digital Earth applications provide a common ground for visualizing, simulating, and modeling real-world situations. The potential of Digital Earth applications has increased significantly with the evolution of artificial intelligence systems and the capacity to collect and process complex amounts of geospatial data. Yet, the widespread techno-optimism at the root of Digital Earth must now confront concerns over high-risk artificial intelligence systems and power asymmetries of a datafied society. In this commentary, we claim that not only can current debates about data (...) governance and ethical artificial intelligence inform development in the field of Digital Earth, but that the specificities of geospatial data, together with the expectations surrounding Digital Earth applications, offer a fruitful lens through which to examine current debates on data governance and artificial intelligence ethics. In particular, we argue that for the implementation of ethical artificial intelligence and inclusive approaches to data governance, Digital Earth initiatives need to involve stakeholders and communities at the local level and be sensitive to social, legal, cultural, and institutional contexts, including conflicts that might arise within those contexts. (shrink)

The revolution involving the foundations of the physical sciences heralded by relativity and quantum theories has been stimulating philosophers for many years. Both of these comprehensive sets of concepts have involved profound challenges to traditional theories of epistemology, ontology, and language. This volume gathers six experts in physics, logic and philosophy to discuss developments in space exploration and nuclear science and their impact on the philosophy of science.

The main thrust of the present work is to show why truth and truth bearers lie essentially beyond the descriptive reach of semantics, and to outline a theory of ...

I show explicitly how concerns about wave function collapse and ontology can be decoupled from the bulk of technical analysis necessary to recover localized, approximately Newtonian trajectories from quantum theory. In doing so, I demonstrate that the account of classical behavior provided by decoherence theory can be straightforwardly tailored to give accounts of classical behavior on multiple interpretations of quantum theory, including the Everett, de Broglie-Bohm and GRW interpretations. I further show that this interpretation-neutral, decoherence-based account conforms to a general (...) view of inter-theoretic reduction in physics that I have elaborated elsewhere, which differs from the oversimplified and often ambiguous picture that treats reduction simply as a matter of taking limits. This interpretation-neutral account rests on a general three-pronged strategy for reduction between quantum and classical theories that combines decoherence, an appropriate form of Ehrenfest's Theorem, and a decoherence-compatible mechanism for collapse. It also incorporates a novel argument as to why branch-relative trajectories should be approximately Newtonian, which is based on a little-discussed extension of Ehrenfest's Theorem to open systems, rather than on the more commonly cited but less germane closed-systems version. In the Conclusion, I briefly suggest how the strategy for quantum-classical reduction described here might be extended to reduction between other classical and quantum theories, including classical and quantum field theory and classical and quantum gravity. (shrink)

This study compares Pairs of subjects with Single subjects in a task of discovering scientific laws with the aid of experiments. Subjects solved a molecular genetics task in a computer micro‐world (Dunbar, 1993). Pairs were more successful in discovery than Singles and participated more actively in explanatory activities (i.e., entertaining hypotheses and considering alternative ideas and justifications). Explanatory activities were effective for discovery only when the subjects also conducted crucial experiments. Explanatory activities were facilitated when paired subjects made requests of (...) each other for explanation and focused on them. The study extends from individual to collaborative discovery activities the importance to the discovery process of setting goals to find hypotheses and evidence (Dunbar, 1993) and to construct explanations of phenomena and processes encountered in examples (Chi, Bassok, Lewis, & Glaser, 1989). (shrink)

The concept of the cortical column refers to vertical cell bands with similar response properties, which were initially observed by Vernon Mountcastle’s mapping of single cell recordings in the cat somatic cortex. It has subsequently guided over 50 years of neuroscientific research, in which fundamental questions about the modularity of the cortex and basic principles of sensory information processing were empirically investigated. Nevertheless, the status of the column remains controversial today, as skeptical commentators proclaim that the vertical cell bands are (...) a functionally insignificant by-product of ontogenetic development. This paper inquires how the column came to be viewed as an elementary unit of the cortex from Mountcastle’s discovery in 1955 until David Hubel and Torsten Wiesel’s reception of the Nobel Prize in 1981. I first argue that Mountcastle’s vertical electrode recordings served as criteria for applying the column concept to electrophysiological data. In contrast to previous authors, I claim that this move from electrophysiological data to the phenomenon of columnar responses was concept-laden, but not theory-laden. In the second part of the paper, I argue that Mountcastle’s criteria provided Hubel Wiesel with a conceptual outlook, i.e. it allowed them to anticipate columnar patterns in the cat and macaque visual cortex. I argue that in the late 1970s, this outlook only briefly took a form that one could call a ‘theory’ of the cerebral cortex, before new experimental techniques started to diversify column research. I end by showing how this account of early column research fits into a larger project that follows the conceptual development of the column into the present. (shrink)

What is the function of morality—what is it all about? What is the basis of morality—what explains our moral agency and patiency? This essay defends a unique Kantian answer to these questions. Morality is about securing our independence from each other by giving each other equal discretion over whether and how we interact. The basis of our moral agency and patiency is practical reason. The first half addresses objections that this account cannot explain the moral patiency of beings who are (...) not also moral agents such as infantile, elderly, and infirm human beings and the other animals who are not moral agents. The second half argues that this account is preferable, on grounds of consistency with the basic Kantian account of the function and content of morality, to the familiar account of our moral patiency, popular especially though not exclusively with contemporary Kantians, in terms of the value of humanity. (shrink)

Metaphors abound in descriptions of the COVID-19 pandemic: it is described, among other things, as a war, a flood, and a marathon. However, not all metaphors may resonate equally well with members...

The paper interrogates the status, nature and significance of epistemological relativism as a key element of constructionism and critical realism. It finds that epistemological relativism is espoused by authorities in critical realism and marginalized or displaced in the field of management and organization studies, resulting in forms of analysis that are empirically, but not fully critically, realist. This evaluation prompts reflection on the question of whether, how and with what implications epistemological relativism might be recast at the heart of critical (...) realist studies of management and organization. (shrink)

When producing a description of a target referent in a visual context, speakers need to choose a set of properties that distinguish it from its distractors. Computational models of language production/generation usually model this as a search process and predict that the time taken will increase both with the number of distractors in a scene and with the number of properties required to distinguish the target. These predictions are reminiscent of classic findings in visual search; however, unlike models of reference (...) production, visual search models also predict that search can become very efficient under certain conditions, something that reference production models do not consider. This paper investigates the predictions of these models empirically. In two experiments, we show that the time taken to plan a referring expression—as reflected by speech onset latencies—is influenced by distractor set size and by the number of properties required, but this crucially depends on the discriminability of the properties under consideration. We discuss the implications for current models of reference production and recent work on the role of salience in visual search. (shrink)

Institute of Theoretical Astronomy, University of Cambridge, Cambridge, UK 3fS. received 28th August 1970, in final revised form 1st July 1971..