This paper problematizes the concept of individual autonomy in the on-going project of attempting to understand and construct global principles of bioethics. We argue that autonomy as it is commonly defined and interpreted, and the emphasis that is placed on it, presupposes an individualistic concept of the self, family, and community that arises out of a Euro-Western liberal tradition and that is often in tension with various non-Western perspectives. We conclude that a more globally dialogical approach to bioethics is required.

I have argued here for a change in a scientific world-view, from that of the study of forms to that of process. In doing so we need to understand as to how process creates form. In showing this I have at first drawn from the history of Buddhist philosophy; with its concepts of ‘Sunyata’ (Emptiness) and radical interdependency (Huayen). Then showed its parallel with modern Fractal geometries, which thru’ rather simple mathematics, shows as to how process could derive form. I (...) have then gone on to Quantum constructions, which is without doubt the most advanced scientific development in modern times, and attempted to show two vital directions which contradict the classical scientific world view. The usual scientific view retains a Descartian, ‘out there’ deterministic framework. I argue that with the break down of determinism, and the non locality of phenomena suggested by Quantum Mechanics allows for an independent functioning of consciousness; which then is not a mere epiphenomena of neural activity within the brain. Such a view has wide implications on how we live and how we die. (shrink)

En el mundo académico contemporáneo han venido tomando fuerza, desde hace varias décadas, los temas de la interdisciplinariedad y la transdisciplinariedad, como respuesta de un sector de la comunidad científica a los problemas de la especialización y a la desconexión entre las ciencias. Como todo elemento o aspecto de la realidad, este tema requiere de una debida fundamentación filosófica que se encuentra en el pensamiento clásico. En el presente artículo se intenta mostrar la relación entre la tradición de la filosofía (...) perenne y este fundamento, atendiendo, sobre todo, a la importancia de la mirada holística del fenómeno ético y pretendiendo sustentar que el diálogo entre las ciencias sólo es posible rescatando el paradigma metafísico, legado por los griegos a la civilización occidental y defendido por MacIntyre en su libro "Ethics in the Conflicts of Modernity. An Essay on Desire, Practical Reasoning, and Narrative" (University of Cambridge, 2016). (shrink)

Increased amyloid beta (Aβ) production by sequential cleavage of the amyloid precursor protein (APP) by the β‐ and γ‐secretases contributes to the etiological basis of Alzheimer's disease (AD). This process requires APP and the secretases to be in the same subcellular compartments, such as the endosomes. Since all membrane organelles in the endomembrane system are kinetically and functionally linked, any defects in the trafficking and sorting machinery would be expected to change the functional properties of the whole system. The (...) class='Hi'>Golgi is a primary organelle for protein trafficking, sorting and modifications, and Golgi defects have been reported in AD. Here we hypothesize that Golgi fragmentation in AD accelerates APP trafficking and Aβ production. Furthermore, Golgi defects may perturb the proper trafficking and processing of many essential neuronal proteins, resulting in compromised neuronal function. Therefore, molecular tools that can restore Golgi structure and function could prove useful as potential drugs for AD treatment. (shrink)

The Golgi apparatus in vertebrate cells consists of individual Golgi stacks fused together in a continuous ribbon structure. The ribbon structure per se is not required to mediate the classical functions of this organelle and the relevance of the “ribbon” structure has been a mystery since first identified ultrastructurally in the 1950s. Recent advances recognize a role for the Golgi apparatus in a range of cellular processes, some mediated by signaling networks which are regulated at the (...) class='Hi'>Golgi. Here we review the cellular processes and signaling events regulated by the Golgi apparatus and, in particular, explore an emerging theme that the ribbon structure of the Golgi contributes directly to the regulation of these higher order functions. The Golgi apparatus has recently emerged as a signaling hub for co-ordinating cellular processes. Here we explore the concept that the Golgi ribbon structure is critical in regulating higher order processes. Changes in Golgi ribbon morphology, that is, fragmentation into mini-stacks, modulate cellular processes, and are associated with diseases including neurodegeneration and cancer. (shrink)

Secretory proteins and membranes move in transfer vesicles from the rough endoplasmic reticulum through the transitional region to the outer saccule of the Golgi complex. In both arthropod and vertebrate cells, the GC beads are a characteristic structural component of the transitional region. The beads are particles about half the size of ribosomes arranged equidistantly from one another and the smooth face of the ER. In an active GC, the beads are in rings through which the ER membrane emerges (...) to form transfer vesicles. The beads may be part of the energy‐dependent step required for the movement of proteins along the secretory pathway, since they lose their ring arrangement under conditions that lower cellular ATP. The beads are organizers for Golgi complexes in the sense that they are the first recognizable components of new GCs as they arise from ER. Arthropod GC beads, but not those of vertebrates, can be visualized through their reaction with bismuth in vivo and in fixed tissue. Useful paradigms for traffic between the ER and the GC need to combine structural and biochemical information. Insect fat body, with its readily resolvable bismuth‐stained beads and easily fractionated cell components may have particular value for this problem. (shrink)

Initially identified as a key phosphoinositide that controls membrane trafficking at the Golgi complex, phosphatidylinositol‐4‐phosphate (PI4P) has emerged as a key molecule in the regulation of a diverse array of cellular functions. In this review we will discuss selected examples of the findings that in the last few years have significantly increased our awareness of the regulation and roles of PI4P in the Golgi complex and beyond. We will also highlight the role of PI4P in infection and cancer. (...) We believe that, with the increasing number of regulators and effectors of PI4P identified, the time is ripe for a more integrated approach of study. A first step in this direction is the delineation of PI4P‐centered molecular networks that we provide using data from low and high throughput studies in yeast and mammals. (shrink)

In the Indian philosophical tradition Arjuna stands out as a major representative of an important ethical and intellectual position, as Socrates stands out in the West. While the cultural contexts of the views of Arjuna and Socrates differ significantly, their views on the axiological status of the physical body have much in common. As an exercise in comparative thought in the area of “the philosophy of the body”, much can be gained through a comparison of the corpological views (...) of these two venerable characters as they are depicted in circumstances that ctystalise their teachings, i.e. in their 'trials': Arjuna as he stands before Krsna just prior to the great battle narrated in the Mah bh rata and Socrates as he sits with his beloved friend Crito just prior to his day of execution. (shrink)

Several complementary approaches have been fruitful in the study of transport from the ER to the Golgi complex in yeast. Mutational analysis has led to the identification of genes required for this process, many of which are now being studied at the molecular and biochemical level. In the case of SEC18, DNA sequence analysis has demonstrated homology to a factor needed for transport in mammalian in vitro systems. In addition, the events that take place at this stage of the (...) secretory pathway have been reconstituted in vitro. (shrink)

In animal cells, the Golgi complex undergoes reversible disassembly during mitosis. The disassembly/reassembly process has been intensively studied in order to understand the mechanisms that govern organelle assembly and inheritance during cell division. A long‐standing controversy in the field has been whether formation of Golgi structure is template‐mediated or self‐organizes from components of the endoplasmic reticulum. A recent study1 however, has demonstrated that a subset of proteins that form a putative Golgi matrix can be inherited during cell (...) division in the absence of membrane input from the endoplasmic reticulum. The outcome of this study suggests that a templating mechanism for the formation of Golgi structure may exist. This study has important implications for understanding mechanisms that govern Golgi biogenesis. BioEssays 24:584–587, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

COPII coated vesicles bud from an ER domain termed the transitional ER (tER), but the mechanism that clusters COPII vesicles at tER sites is unknown. tER sites are closely associated with early Golgi or pre‐Golgi structures, suggesting that the clustering of nascent COPII vesicles could be achieved by tethering to adjacent membranes. This model challenges the prevailing view that COPII vesicles are clustered by a scaffolding protein at the ER surface. Although Sec16 was proposed to serve as such (...) a scaffolding protein, recent data suggest that rather than organizing COPII into higher‐order structures, Sec16 acts at the level of individual COPII vesicles to regulate COPII turnover. A plausible synthesis is that tER sites are created by tethering to Golgi membranes and are regulated by Sec16. Meanwhile, the COPII vesicles that bud from tER sites are thought to nucleate new Golgi cisternae. Thus, an integrated self‐organization process may generate tER‐Golgi units. (shrink)

The cellular machinery responsible for conveying proteins between the endoplasmic reticulum and the Golgi is being investigated using genetics and biochemistry. A role for vesicles in mediating protein traffic between the ER and the Golgi has been established by characterizing yeast mutants defective in this process, and by using recently developed cell‐free assays that measure ER to Golgi transport. These tools have also allowed the identification of several proteins crucial to intracellular protein trafficking. The characterization and possible (...) functions of several GTP‐binding proteins, peripheral membrane proteins, and an integral membrane protein during ER to Golgi transport are discussed here. (shrink)

We present techniques for integrating low‐level neurobiological constraints into high‐level, functional cognitive models. In particular, we use these techniques to construct a model of eyeblink conditioning in the cerebellum based on temporal representations in the recurrent Granule‐Golgi microcircuit.

Vi sono varie forme di impossibilità normativa. Una prima forma si incontra quando un fatto naturale al quale il diritto attribuisce un significato normativo è impossibile. Una seconda consiste nell’impossibilità di un atto o fatto la quale derivi dalla presenza o assenza di una norma. Vi è poi una terza forma di impossibilità normativa che si incontra quando si afferma che da una certa realtà oggetto di normazione derivano necessariamente limiti all’attività di normazione stessa. Di una quarta forma si può (...) parlare quando ci si riferisce a un’impossibilità derivante dalle specifiche relazioni che intercorrono tra norme di un sistema normativo dinamico. Le forme di impossibilità normativa sono indagate, nei contributi raccolti in questo volume, da diverse angolazioni: la filosofia del diritto, la filosofia morale, la logica, la filosofia della conoscenza, la scienza del diritto penale. (shrink)

The secretory pathway delivers proteins synthesized at the rough endoplasmic reticulum (RER) to various subcellular locations via the Golgi apparatus. Currently, efforts are focused on understanding the molecular machineries driving individual processes at the RER and Golgi that package, modify and transport proteins. However, studies are routinely performed using non‐dividing cells. This obscures the critical issue of how the secretory pathway is affected by cell division. Indeed, several studies have indicated that protein trafficking is down‐regulated during mitosis. Moreover, (...) the RER and Golgi apparatus exhibit gross reorganization in mitosis. Here I provide a relatively neglected perspective of how the mitotic cyclin‐dependent kinase (CDK1) could regulate various stages of the secretory pathway. I highlight several aspects of the mitotic control of protein trafficking that remain unresolved and suggest that further studies on how the mitotic CDK1 influences the secretory pathway are necessary to obtain a deeper understanding of protein transport. (shrink)

The recently uncovered role of Fukutin‐related protein (FKRP) in fibronectin glycosylation has challenged our understanding of the basis of disease pathogenesis in the muscular dystrophies. FKRP is a Golgi‐resident glycosyltransferase implicated in a broad spectrum of muscular dystrophy (MD) pathologies that are not fully attributable to the well‐described α‐Dystroglycan hypoglycosylation. By revealing a new role for FKRP in the glycosylation of fibronectin, a modification critical for the development of the muscle basement membrane (MBM) and its associated muscle linkages, new (...) possibilities for understanding clinical phenotype arise. This modification involves an interaction between FKRP and myosin‐10, a protein involved in the Golgi organization and function. These observations suggest a FKRP nexus exists that controls two critical aspects to muscle fibre integrity, both fibre stability at the MBM and its elastic properties. This review explores the new potential disease axis in the context of our current knowledge of muscular dystrophies. (shrink)

The determining role that tool development plays in neuroscientific progress poses special challenges to the Kuhnian-rooted philosophy of scientific change. Some philosophers of neuroscience argue that revolutions in neuroscience do not involve paradigm shifts, but instead depend exclusively on technical or experimental innovation. By studying the historical episode of the discovery of the neuron (1873-1909), I argue that revolutions in neuroscience, like many other laboratory revolutions, are frequently driven by the intertwining of technical innovations and conceptual change.

The biological membranes of eukaryotic cells harbor sensitive surveillance systems to establish, sense, and maintain characteristic physicochemical properties that ultimately define organelle identity. They are fundamentally important for membrane homeostasis and play active roles in cellular signaling, protein sorting, and the formation of vesicular carriers. Here, we compare the molecular mechanisms of Mga2 and Ire1, two sensors involved in the regulation of fatty acid desaturation and the response to unfolded proteins and lipid bilayer stress in order to identify their commonalities (...) and specializations. We will speculate on the cellular significance of membrane property sensors in other organelles and discuss their putative mechanisms. Based on these findings, we propose membrane property sensors as an emerging class of proteins with wide implications for organelle communication and function. (shrink)

Wisdom is almost always associated with doing the right thing in the right way under right circumstances in order to achieve the common good. In this paper, however, we propose that wisdom is more associated with deciding between better and worse wrongs; a winless situation we define as tragic. We suggest that addressing the tragic question is something that leaders and managers generally avoid when focusing on business decisions and choices. Yet, raising and confronting the tragic question is important for (...) three main reasons. Firstly, it emphasises that wisdom is about recognising that doing the ethically responsible thing can sometimes lead to acting in ways that violate different ethical norms and values. Secondly, it foregrounds the issue of emotional perception in ethical decision-making. We argue that emotions are salient in directing attention to the tragic question and recognising morally ambiguous situations. Thirdly, the tragic question has important consequences for moral learning, accepting moral culpability for wrongdoing and organisational commitment to righting the wrong. We illustrate our arguments by drawing on three mini-cases: Arjuna’s dilemma in the Mahabharata, Gioia’s deliberations about his role in the Ford Pinto fires and the production of the abortion pill by French company Roussel-Uclaf. (shrink)

A famous Indian argument for jus ad bellum and jus in bello is presented in literary form in the Mahābhārata: it involves events and dynamics between moral conventionalists (who attempt to abide by ethical theories that give priority to the good) and moral parasites (who attempt to use moral convention as a weapon without any desire to conform to these expectations themselves). In this paper I follow the dialectic of this victimization of the conventionally moral by moral parasites to its (...) philosophical culmination in the fateful battle, which the Bhagavad Gītā precedes. Arjuna’s lament is an internalization of the logic of conventional moral expectations that allowed moral parasitism, and Krishna’s push for a purely procedural approach to moral reasoning (bhakti yoga) does away with the good as a primitive of explanation and provides the moral considerations that allow us to see that the jus ad bellum and jus in bello coincide: the just cause is the approximation to the procedural ideal (the Lord), which is also just conduct. Jeff McMahan is correct in claiming that it is wrong for the unjust to attack the just. But it is also not obviously correct that it is the same set of moral considerations in war and peace that mark out the sides, for peace is largely characterizable by conventional morality, which all are forced to abandon in war. Walzer is correct that there are different sets of standards at play at war and peace, and that getting hands dirty in immorality is a price worth paying in war, but Walzer is thereby incorrect for a subtle reason: conventional standards by way of which jus ad bellum and jus in bello appear corrupt are themselves actually corrupt when the need for a just war arises. It is because moral parasites use conventional morality as a means of hostility and not as a means of fair, inclusive social interaction that conventional morality is corrupted and turned into a tool of the unjust. It is hence unjust to employ these standards to judge those whose cause is just, though such a judgement is conventional. Those who fight for a just cause thereby justly get their hands dirty by departing from conventional moral standards. But this is to the disadvantage of parasites who can only function in a climate where the conventionally good are constrained by conventional morality. Just war so understood deprives parasites their weapon of choice. (shrink)

The Bhagavad Gītā has inspired more interpretive controversy than any other religious scripture in India’s history. The Gītā, a philosophical and spiritual poem of approximately seven hundred verses, is part of the ancient Sanskrit epic, the Mahābhārata. In the Gītā, the Lord Kṛṣṇa, who appears in the form of a charioteer, imparts spiritual teachings to the warrior Arjuna and convinces him to fight in a just war that entails the slaughter of many of Arjuna’s own relatives and loved (...) ones. Śaṅkara, the great eighth-century champion of the Advaita school of philosophy, wrote the first extant commentary on the Gītā. In this commentary, Śaṅkara interpreted the Gītā strictly in accordance with Advaita.. (shrink)

Interpretations of the ethical significance of the Bhagavadgītā typically understand the debate between Arjuna and Kṛṣṇa in terms of a struggle between consequentialist and deontological doctrines. In this paper, I provide instead a reading of the Gītā which draws on a conception of moral thinking that can be understood to cut across those positions – that developed by Stanley Cavell, which he calls ‘Emersonian Moral Perfectionism’. In so doing, I emphasise how Kṛṣṇa’s consolation of Arjuna can centrally and (...) fruitfully be viewed as concerned with resuscitating the latter’s individuality, thereby allowing Arjuna to overcome an unthinking conformity to the current degenerate state of his society. This leads me to explore the relation between this perfectionist understanding of spiritual reorientation and the Gītā’s religious account of human redemption; and to conclude by suggesting how the text of the Gītā itself might have similar therapeutic designs upon its readers. (shrink)

In The Idea of Justice, Amartya Sen, among other things, discusses certain qualities any adequate theory of justice ought to incorporate. Two important qualities a theory of justice should account for are impartiality/objectivity and sensitivity to consequences. In order to motivate his discussion of sensitivity to consequences, Sen discusses the debate between Krishna and Arjuna from the religio-philosophical Hindu text the Bhagavad Gita. According to Sen, Arjuna represents a sensitivity to consequences while Krishna is an archetypal deontologist. In (...) this paper it will be argued that Sen's interpretation of the Gita is inaccurate. Further, a more adequate interpretation will be presented. What will be of significance is that the more adequate interpretation actually demonstrates the importance of an impartial spectator in moral reasoning. Finally, there will be a discussion of some lessons that can be taken from the Gita regarding justice generally. (shrink)

This paper identifies the different normative ethical arguments stated and suggested by Arjuna and Krishna in the Gītā , analyzes those arguments, examines the interrelations between those arguments, and demonstrates that, contrary to a common view, both Arjuna and Krishna advance ethical theories of a broad consequentialist nature. It is shown that Krishna’s ethical theory, in particular, is a distinctive kind of rule-consequentialism that takes as intrinsically valuable the twin consequences of mokṣa and lokasaṃgraha . It is also (...) argued that Krishna’s teachings in the Gītā gain in depth, coherence, and critical relevance what they lose in simplicity when the ethical theory underlying those teachings is understood as a consequentialism of this kind rather than as a deontology. (shrink)

Bhagwad Gita, also known as the Gita, is an important ancient Indian text, written around the 3rd Century BCE. The Gita appears in the 18th Chapter of the epic, Mahabharata, written by Sage Vyasa. It is set on a war front. The Bhagwad Gita is presented as a dialogue between Arjuna, one of the warriors, and Krishna, his charioteer who was also a king. Arjuna is shown to be confused and conflicted about fighting in the war against his (...) unjust cousins and teachers. Krishna, on the other hand, attempts, through various means, to counsel him about his duty by explaining the workings of mankind and the world. He points out the flawsin Arjuna’s reasoning and helps him clear his clouded judgement. In doing so, Krishna gave away secrets to living a meaningful life. Although the Gita is addressed towards Arjuna, his message applies to each one of us as humans who are at times conflicted, unsure and resentful. It contains eternal wisdom on the best ways to live our lives while also taking into consideration differences in personality and preference. Logic-based therapy is a modality of philosophical counselling developed by Dr. Cohen that suggests that human beings have certain faulty ways or illogical ways of thinking and interpreting life circumstances that manifest in the form of irritation and other day-to-day issues like procrastination, anger, management issues, low self-esteem etc. To solve such issues, which he calls Cardinal Fallacies, it is necessary to think rationally and transgress those illogical thought patterns. Hence, in Logic Based Therapy timeless philosophical ideologies are offered as antidotes by which people can adopt new ways of thinking and solve such everyday problems. This paper attempts to show how different cardinal fallacies can be tackled by using the eternal wisdom presented in the Bhagwad Gita, in the form of uplifting philosophies. (shrink)

Here the collected papers explore the whole question of the relation between the mythopoetic and the moral in the context of the Mahabharata. Here we have a story of extreme complexity, characters that are unforgettable, and a cosmic context in which gods and men alike grapple with destiny. The obligations of kinship and friendship jostle with each other. The women characters, as in everyday life, seem to bear a very heavy load of the burden of life and to stand in (...) a key position in almost every conflict. We are presented with predicaments at every turn. At times these predicaments seem to be aggravated by social structure. At other times they are cushioned by it. Philosophical tangles tied up with karma and dharma are interwoven with the mythopoetic material. Perhaps philosophical issues are pinpointed rather more than they are in Greek epic literature. The essays in this book treat the Mahabharata from an unusual angle, fastening on the moral dilemmas it presents. How universal are the dilemmas faced by the characters in the story, and are the dilemmas in fact resolved? In dealing with these questions, the discussions range over the meaning of the purusarthas, the institutions of marriage and the family, the concept of action in the Gita and the special predicaments faced by Draupadi, Arjuna and others. These studies invite the scholar to reflect afresh on the text and encourage the general reader to find in epic literature much that is relevant to life today. (shrink)

Abstractβ1,4‐galactosyltransferase is unusual among the glycosyltransferases in that it is found in two subcellular compartments where it performs two distinct functions. In the trans‐Golgi complex, galactosyltransferase participates in oligosaccharide biosynthesis, as do the other glycosyltransferases. On the cell surface, however, galactosyltransferase associates with the cytoskeleton and functions as a receptor for extracellular oligosaccharide ligands. Although we now know much regarding galactosyltransferase function in these two compartments, little is known about how it is targeted to these different sites. By cloning (...) the galactosyltransferase gene products, certain features of the protein have been identified that may be critical for its expression on the cell surface or retention within the Golgi complex. This article discusses recent studies which suggest that a cytoplasmic sequence unique to one galactosyltransferase isoform is required for targeting a portion of this protein to the plasma membrane, enabling it to function as a cell adhesion molecule. These findings allow one to manipulate surface galactosyltransferase expression, either positively or negatively, and perturb galactosyltransferase‐dependent cellular interactions during fertilization and development. (shrink)

A path to personal and community liberation through yoga philosophy on service from yoga teacher, activist, and accessible yoga advocate Jivana Heyman. Yoga is now a mainstream form of exercise across the West, and it is time to address the dissonance between the superficial way yoga is currently being practiced and the depth of yoga's ancient universal spiritual teachings. In this clarion call to action, Jivana Heyman shares the ways that yoga is truly revolutionary--creating an inner revolution in our heart (...) and mind, as well as an outer revolution in the form of service and social justice. He provides us with a framework he calls "Rainbow Mind" to bridge this gap and share a new vision of what yogic enlightenment can look like. Having a Rainbow Mind requires open -heartedness, courage, and a fierce commitment to inclusivity and accessibility. It is about tackling the challenge that Arjuna faces in the Bhagavad Gita--"Should I act?"--and cultivating a state of mind that helps us figure out one of the hardest challenges of life: when to speak up and when to step back. In Yoga Revolution, you will be introduced to the yogic mandate of seva--or acts of service that see, care for, and uplift those around us--as a way to serve the world without losing your way or making it about yourself-all while still maintaining your own self-care. Through practice prompts such as "Failure as a Practice" and stories from yoga teachers who are implementing seva, including Michelle Cassandra Johnson, Octavia Raheem, and Amber Karnes, Heyman shows you what it means to serve, how to serve, and how to reject white supremacy through your service. Our job is not to clear our mind through yoga practice, but rather to expand it so widely that it can embrace the entire universe. (shrink)

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

In lieu of an abstract, here is a brief excerpt of the content:Political AuthorityThe Two Wheels of the DharmaWhalen Lai“The twin wheels of the dharma The two wings of the dove”The twin wheels of the dharma, one of power and the other of righteousness, is the classic metaphor in the Buddhist view of the state and the saṅgha. We will first register the distinction of that metaphor by going back to its historical roots, showing how and why it is more (...) meaningful for Buddhists than for Hindus. Then we will map its structural growth sociologically, weigh its overall strengths and weaknesses, and consider other Buddhist options for civil order and interstate relationships. Finally we will examine the price of modernity and the crisis of authority that Buddhist culture faces.Toward a Genealogy of the Twin WheelsThe legend of the Buddha is by now well known. Prince Siddhārtha left family and home, and renounced the kingdom and the world. He had seen the inevitability of suffering. He vowed to find its cause to eliminate that result. After his enlightenment, he reflected upon releasing that path to the world. When the Buddha so taught the Four Noble Truths and the Noble Eightfold Path to his old companions at Benares, tradition then remembers that as the Buddha “turning the wheel of dharma.” The wheel (cakra) is a metaphor; it refers to the wheel of a sun chariot and is now on the national flag of India. That cosmic wheel has rolled on since time immemorial; as saṃsāra, it has been endless suffering. That is, until the Buddha so turned the sun wheel anew, marking it possible for the first time end that cycle and point the way to nirvāṇic liberation. History was so changed with that act of the Buddha at Benares. Mankind turned a corner. Christianity sees the event on the cross to be, likewise, a break in time. History as we know it had ended. The end time, the eschatological kingdom with its promise of a new heaven and a new earth, have dawned. The price of Adam’s sin was death. Christ’s resurrection turned that around.In Buddhism, the normal course of life and death (rebirth: saṃsāra) also ended [End Page 171] with the Buddha’s enlightenment under the Bodhi tree. The path to nirvāṇa was open. The city of nirvāṇa is in sight. Or as a Buddhist miracle would tell it, the water of the Ganges flowed backward in response to an act of truth (satyāgraha).The event at Benares when the Buddha turned the wheel of dharma anew may be a major inspiration for the ideology of the twin wheels. In general, Hinduism needs only to presume one wheel; it does not count a second. Although Hinduism knows its share of renunciation and liberation (mokṣa), the Brahmanical system set down by the Vedas is committed to safeguarding the sanctity of the caste system. It can absorb mokṣa under the larger law for its varṇāśramadharma. The renunciation is ideally the last station in life, coming after formal retirement from active household duties, and well approaching old age and a good time for learning how to transcend it. Buddhism challenged the caste system by setting up the saṅgha, a new Buddhist community. Hinduism lacks that call for reconstituting society. It does not know the “saṅgha and state” tension that Buddhists know like Christians would the tension between church and state. In the end, the Vedānta philosophy in Hinduism does not postulate that tension. The ātman-brahman identity of self and universe is inherently monistic.This is not to say Hindus do not face a basic conflict between two contrary worlds. It does but it solves it differently. The tragic dilemma in the Bhagavadgītā is that Arjuna, who came to embrace nonviolence like a Buddhist or a Jain would, was eventually persuaded to fight, namely, to perform his caste duty of being a warrior, ready to kill and be killed. That, in a Greek tragic term, is the dike of some cosmic dharma wheel. Oedipus Rex, in the end, must bow to his fate and lot... (shrink)

An entirely different mechanism and localization were recently proposed for the COPII coat complex, challenging its well‐accepted function to select and concentrate cargo into small COPII‐coated spherical transport vesicles. Instead, the COPII complex is suggested to form a dynamic yet stationary collar that forms a boundary between the ER and the ER export membrane domain. This membrane domain, the ER exit site (ERES), is the site of COPII‐mediated sorting and concentration of transport competent proteins. Subsequently, the ERES is implicated to (...) mature and bud to form a sizeable pleiomorphic transport carrier that translocate on microtubules to fuse with the Golgi apparatus. Despite this drastic mechanistic dogma shift, most of the underlying protein‐protein and protein‐membrane interactions remain unchanged. Here, we attempt to provide a detailed description of the newly proposed model of how ER to Golgi transport works by describing the role of several essential proteins of the transport machinery. (shrink)

The plasma membrane of polarized epithelial cells is divided into apical and basolateral surfaces, with different compositions. Proteins can be sent directly from the trans‐Golgi network (TGN) to either surface, or can be sent first to one surface and then transcytosed to the other. The glycosyl phosphatidylinositol anchor is a signal for apical targeting. Signals in the cytoplasmic domain containing a β‐turn determine basolateral targeting and retrieval, and are related to other sorting signals. Transcytosed proteins, such as the polymeric (...) immunoglobulin receptor (plgR), are endocytosed from the basolateral surface and then accumulate in a tubular compartment concentrated underneath the apical surface. This compartment, tentatively termed the apical recycling compartment, may be a central sorting station, as it apparently receives material from both surfaces and sorts them for delivery to the correct surface. Delivery to the apical surface from both the TGN and the apical recycling compartment appears to be regulated by protein kinases A and C, and endocytosis from the apical surface is also regulated by kinases. Transcytosis of the plgR is additionally regulated by phosphorylation of the plgR and by ligand binding to the plgR. Regulation of traffic in polarized epithelial cells plays a central role in cellular homeostasis, response to external signals and differentiation. (shrink)

The Bhagavad-gita is the main source-book on yoga and a concise summary of India's Vedic wisdom. Yet remarkably, the setting for this classic of spiritual literature is an ancient Indian battlefield. At the last moment, the great warrior Arjuna begins to wonder about the real meaning of his life. In the Bhagavadgita, Lord Krsna brings His disciple from perplexity to spiritual enlightenment. Bhagavad-gita As It Is is the largest-selling, most widely used edition of the Gita in the world.

The recent discovery and structure determination of a novel ubiquitin‐like dimerization domain in protein kinase D (PKD) has significant implications for its activation. PKD is a serine/threonine kinase activated by the lipid second messenger diacylglycerol (DAG). It is an essential and highly conserved protein that is implicated in plasma membrane directed trafficking processes from the trans‐Golgi network. However, many open questions surround its mechanism of activation, its localization, and its role in the biogenesis of cargo transport carriers. In reviewing (...) this field, the focus is primarily on the mechanisms that control the activation of PKD at precise locations in the cell. In light of the new structural findings, the understanding of the mechanisms underlying PKD activation is critically evaluated, with particular emphasis on the role of dimerization in PKD autophosphorylation, and the provenance and recognition of the DAG that activates PKD. (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 signaling AbstractHow 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‐kinases AbstractPhosphatidylinositol‐4‐phosphate: The Golgi and beyond Abstract. (shrink)

Coiled‐coils are found in proteins throughout all three kingdoms of life. Coiled‐coil domains of some proteins are almost invariant in sequence and length, betraying a structural and functional role for amino acids along the entire length of the coiled‐coil. Other coiled‐coils are divergent in sequence, but conserved in length, thereby functioning as molecular spacers. In this capacity, coiled‐coil proteins influence the architecture of organelles such as centrioles and the Golgi, as well as permit the tethering of transport vesicles. Specialized (...) coiled‐coils, such as those found in motor proteins, are capable of propagating conformational changes along their length that regulate cargo binding and motor processivity. Coiled‐coil domains have also been identified in enzymes, where they function as molecular rulers, positioning catalytic activities at fixed distances. Finally, while coiled‐coils have been extensively discussed for their potential to nucleate and scaffold large macromolecular complexes, structural evidence to substantiate this claim is relatively scarce. (shrink)

I will here apply the classical Indian model of the dramatic actor as a methodology for interpreting the soteriological psychology of the Bhagavad Gītā, paying special attention to the usefulness of this approach for clarifying Kṛṣṇa's rationale in showing his divine form in Chapter 11. I argue that the Gītā advocates creative role-play as both the means and the end of liberation. Further, while Kṛṣṇa's teachings can be understood in terms of orthodox Hindu soteriologies that have in view an overcoming (...) of the emotions, I argue that Kṛṣṇa looks to transform Arjuna into an ‘athlete of emotion’, much like traditional Indian-based training methods do for theatrical actors. (shrink)

The paper presents a method for interpreting religious texts for use in psychotherapy. In particular, the paper takes the example of the pivotal character Arjuna in Bhagavad-Gita as having low frustration tolerance and uses the collective philosophy of the Bhagavad-Gita and Bhagavata-Purana through six steps of Logic-Based Therapy to overcome it. Although the paper uses Hindu religious texts, the treatment of these texts will speak to anyone interested in the possibility of integrating religious texts into psychotherapy.

Lysosomes are the site of degradation of obsolete intracellular material during autophagy and of extracellular macromolecules following endocytosis and phagocytosis. The membrane of lysosomes and late endosomes is enriched in highly glycosylated transmembrane proteins of largely unknown function. Significant progress has been made in recent years towards elucidating the pathways by which these lysosomal membrane proteins are delivered to late endosomes and lysosomes. While some lysosomal membrane proteins follow the constitutive secretory pathway and reach lysosomes indirectly via the cell surface (...) and endocytosis, others exit the trans‐Golgi network in clathrin‐coated vesicles for direct delivery to endosomes and lysosomes. Sorting from the Golgi or the plasma membrane into the endosomal system is mediated by signals encoded by the short cytosolic domain of these proteins. This review will discuss the role of lysosomal membrane proteins in the biogenesis of the late endosomal and lysosomal membranes, with particular emphasis on the structural features and molecular mechanisms underlying the intracellular trafficking of these proteins. (shrink)