Balancing self‐renewal and differentiation of stem cells is an important issue in stem cell and cancer biology. Recently, the Drosophila neuroblast (NB), neural stem cell has emerged as an excellent model for stem cell self‐renewal and tumorigenesis. It is of great interest to understand how defects in the asymmetric division of neural stem cells lead to tumor formation. Here, we review recent advances in asymmetric division and the self‐renewal control of Drosophila NBs. We summarize molecular mechanisms (...) of asymmetric cell division and discuss how the defects in asymmetric division lead to tumor formation. Gain‐of‐function or loss‐of‐function of various proteins in the asymmetric machinery can drive NB overgrowth and tumor formation. These proteins control either the asymmetric protein localization or mitotic spindle orientation of NBs. We also discuss other mechanisms of brain tumor suppression that are beyond the control of asymmetric division. (shrink)

Asymmetric cell division generates cell diversity and contributes to cellular aging and rejuvenation. Here, we review the molecular mechanisms enabling budding yeast to recognize spindle pole bodies (SPB, centrosome equivalent) based on their age, and guide their non‐random mitotic segregation: SPB inheritance requires the distinction of old from new SPBs and is regulated by the SPB‐inheritance network (SPIN) and the mitotic exit network (MEN). The SPIN marks the pre‐existing SPB as old and the MEN recognizes these marks translating (...) them into spindle orientation. We next revisit other molecules and structures that partition depending on their age rather than their abundance at mitosis as, for example, DNA, centrosomes, mitochondria, and histones in yeast and other systems. The recurrence of this differential behavior suggests a functional significance for numerous cell types, which we then discuss. We conclude that non‐random segregation may facilitate asymmetric cell fate determination and thereby indirectly aging and rejuvenation. (shrink)

The segregation of damaged components at cell division determines the survival and aging of cells. In cells that divide asymmetrically, such as Saccharomyces cerevisiae, aggregated proteins are retained by the mother cell. Yet, where and how aggregation occurs is not known. Recent work by Zhou and collaborators shows that the birth of protein aggregates, under specific stress conditions, requires active translation, and occurs mainly at the endoplasmic reticulum. Later, aggregates move to the mitochondrial surface through fis1‐dependent association. During replicative (...) aging, aggregate association with the mother‐cell mitochondria contributes to the asymmetric segregation of aggregates, because mitochondria in the daughter cell do not carry aggregates. With increasing age of mother cells, aggregates lose their connection to the mitochondria, and segregation is less asymmetric. Relating these findings to other mechanisms of aggregate segregation in different organisms, we postulate that fusion between aggregates and their tethering to organelles such as the vacuole, nucleus, ER, or mitochondria are common principles that establish asymmetric segregation during stress resistance and aging. (shrink)

Asymmetric cell division generates two cells that contain different regulatory proteins and express different fates. In an example of asymmetric cell division from B. subtilis, a site on the membrane of the dividing cell is chosen to establish the initial asymmetry. Recent results(1,2) show that a key regulatory protein, SpollE, is localized to one side of a sporulating B. subtilis cell, and subsequently functions in an asymmetric manner. SpollE is a phosphatase at the beginning of (...) a regulatory cascade that leads to activation of a cell fate‐determining transcription factor in only one daughter cell. (shrink)

Cells in the basal metazoan phylum Cnidaria are characterized by remarkable plasticity in their differentiation capacity. The mechanism controlling asymmetric cell divisions is not understood in cnidarians or in any other animal group. PIWI proteins recently have been shown to be involved in maintaining the self‐renewal capacity of stem cells in organisms as diverse as ciliates, flies, worms and mammals. Seipel et al.1 find that, in the cnidarian Podocoryne carnea, the Piwi homolog Cniwi is transcriptionally upregulated when the polyp (...) generates buds, which will develop into medusae. Since transdifferentiation of striated muscle cells to smooth muscle cells also activated Cniwi expression, Cniwi appears to play a crucial role in differentiation events. The discovery should facilitate elucidation of the poorly understood factors that control asymmetric cell divisions at the beginning of animal evolution. BioEssays 26:929–931, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Two enzymes involved in the synthesis of pyrimidine and purine nucleotides, CTP synthase (CTPS) and IMP dehydrogenase (IMPDH), can assemble into a single or very few large filaments called rods and rings (RR) or cytoophidia. Most recently, asymmetric cytoplasmic distribution of organelles during cell division has been described as a decisive event in hematopoietic stem cell fate. We propose that cytoophidia, which could be considered as membrane‐less organelles, may also be distributed asymmetrically during mammalian cell division as (...) previously described for Schizosaccharomyces pombe. Furthermore, because each type of nucleotide intervenes in distinct processes (e.g., membrane synthesis, glycosylation, and G protein‐signaling), alterations in the rate of synthesis of specific nucleotide types could influence cell differentiation in multiple ways. Therefore, we hypothesize that whether a daughter cell inherits or not CTPS or IMPDH filaments determines its fate and that this asymmetric inheritance, together with the dynamic nature of these structures enables plasticity in a cell population. (shrink)

Polarization often happens asymmetrically. One political actor radicalizes, and the results reverberate through the political system. This is how the deep divisions in contemporary American politics arose: the Republican Party radicalized. Republican officeholders began to use extreme legislative tactics. Republican voters became animated by contempt for their political rivals and by the defense of their own social superiority. The party as a whole launched a wide-ranging campaign of voter suppression and its members endorsed violence in the face of electoral defeat. (...) This paper is about how such asymmetric polarization affects everyone else’s obligations. My core claim is that two kinds of relationship – civic friendship and non-subordination – underpin critical democratic norms. Republican misbehavior has severed cross-partisan civic friendships. Their authoritarianism forfeits their claim to non-subordination. The former means that non-Republicans need not justify policy on public grounds. The latter undercuts Republicans’ claim to enjoy minority vetoes when out of power and it gives their rivals reason to disobey the laws that Republicans make when they are in power. More generally, when one political actor contravenes the proper norms of democratic politics, their opposition is not bound by those norms. (shrink)

During development one mechanism for generating different cell types is asymmetric cell division, by which a cell divides and contributes different factors to each of its daughter cells. Asymmetric cell division occurs through out the eukaryotic kingdom, from yeast to humans. Many asymmetric cell divisions occur in a defined orientation. This implies a cellular mechanism for sensing direction, which must ultimately lead to differences in gene expression between two daughter cells. In this review, we describe (...) two classes of molecules: regulatory factors that are differentially expressed upon asymmetric cell division, and components of a signal transduction pathway that may define cell polarity. The lin‐11 and mec‐3 genes of C. elegans, the Isl‐1 gene of mammals and the HO gene of yeast, encode regulatory factors that determine cell type of one daughter after asymmetric cell division. The CDC24 and CDC42 genes of yeast affect both bud positioning and orientation of mating projections, and thus may define a general cellular polarity. We speculate that molecules such as Cdc24 and Cdc42 may regulate expression of genes such as lin‐11, mec‐3, Isl‐1 and HO upon asymmetric cell division. (shrink)

Where does the cognitive system begin and end? Intracranialists maintain that the cognitive system is entirely identifiable with the biological central nervous system. Transcranialists, on the other hand, suggest that the cognitive system can extend beyond the biological CNS. In the second division of Supersizing the Mind, Clark defends the transcranial account against various objections. Of interest for this paper is Clark’s response to what he calls “asymmetry arguments.”Asymmetry arguments can be summarized as follows: subtract the props and aids, (...) and the organism may create replacements. But subtract the organism, and all cognitive activity ceases. Although I am sympathetic to Clark’s overall project, I find his response to the asymmetry arguments inadequate in light of his responses to other objections. For this reason, I maintain that Clark’s response requires revision. By adopting a process metaphysics and appealing to mereological dependencies, I believe that Clark can provide a substantive response to asymmetry arguments that is consistent with his overall theory. This paper unfolds as follows: after summarizing Clark’s response to the asymmetry objection in, I will argue that his response is unsuccessful in. My argument hinges on the claim that Clark does not take into account the full intent of Rupert’s asymmetry argument. In I modify Clark’s response by appealing to mereology and the asymmetrical dependencies found therein. I conclude in that this modification provides Clark with an adequate response to the asymmetry argument and is consistent with his overall transcranialist account. The further question of whether this account assists Clark in responding to other intracranialist objections is beyond the scope of this paper. (shrink)

Recently, Quyn et al. demonstrated that cells within the stem cell zone of human and mouse intestinal crypts tend to align their mitotic spindles perpendicular to the basal membrane of the crypt. This is associated with asymmetric division, whereby particular proteins and individual chromatids are preferentially segregated to one daughter cell. In colonic mucosa containing a heterozygous adenomatous polyposis coli gene (APC) mutation the asymmetry is lost. Here, we discuss asymmetric stem cell division as an anti‐tumourigenic (...) mechanism. We describe how hierarchical tissue structures suppress somatic evolution, and discuss the relative merits of template strand retention to limit the accumulation of DNA replication errors. We suggest experiments to determine whether somatic mutations resulting in loss of spindle alignment confer an advantage within the stem cell niche. Finally, we discuss whether lack of spindle alignment constitutes an oncogenic event per se, with particular reference to studies in model organisms, and the timing of chromosomal instability in human cancers. (shrink)

The peripheral nervous system has classically been separated into a somatic division composed of both afferent and efferent pathways and an autonomic division containing only efferents. J. N. Langley, who codified this asymmetrical plan at the beginning of the twentieth century, considered different afferents, including visceral ones, as candidates for inclusion in his concept of the “autonomic nervous system”, but he finally excluded all candidates for lack of any distinguishing histological markers. Langley's classification has been enormously influential in (...) shaping modern ideas about both the structure and the function of the PNS. We survey recent information about the PNS and argue that many of the sensory neurons designated as “visceral” and “somatic” are in fact part of a histologically distinct group of afferents concerned primarily autonomic function. These afferents have traditionally been known as “small dark” neurons or B-neurons. In this target article we outline an association between autonomic and B-neurons based on ontogeny, cell phenotype, and functional relations, grouping them together as part of a common reflex system involved in homeostasis. This more parsimonious classification of the PNS, made possible by the identification of a group of afferents associated primarily with the ANS, avoids a number of confusions produced by the classical orientation. It may also have practical implications for an understanding of nociception, homeostatic reflexes, and the evolution of the nervous system. (shrink)

The article is based on the argument that labour market segregation is an important factor contributing to women’s inequality in the labour market. Therefore, any equal opportunities policy has to be combined with a policy to reduce segregation. But up to now segregation has been extremely persistent, as is shown in a short empirical overview of segregation in the Austrian labour market. It is argued that the roots of this phenomenon lie in the assignment of men and women to the (...) market area and the reproduction area according to the breadwinner model. Labour market segregation by sex can be seen as a transformation and continuation of the asymmetrical gender relation in the family to the labour market. Most of the mechanisms and processes that occur every day in the labour market work together to preserve sex segregation. Strategies to reduce segregation should look at these historical roots of segregation and at the connection with the overall gender division of labour. Different perspectives on a reduction of labour market segregation are presented. (shrink)

PurposeExisting research suggests that the competitive advantage provided by technological development depends to a large extent on the speed and coordination of the technology’s implementation, and on how adoptable the technological applications are considered. While accepting this argument, the authors consider the explanatory model to be inadequate. This study aims to contribute to the theoretical discussion by analysing institutionalised industrial relations and other organisation-level factors, which are important for workplace restructuring and societal change.Design/methodology/approachThe analysis is based on a representative nation-wide (...) work and working conditions survey (N= 4,100) from Finland, which includes a variety of themes, including practices, changes and well-being at work. Changes are understood as organisational changes, focusing on modern technologies such as robotisation and digitalisation.FindingsThe results indicate that occupational division at workplace (low-skilled vs high-skilled occupations) affects job insecurity and acceptance of technologies at work. The characteristics of workplaces, such as the employees’ participation and involvement in the development of the organisation, play a significant part in both the acceptance and the implementation and outcomes of the technological transformations in the workplace.Practical implicationsThe research provides new and interesting insights into working life practices. Furthermore, it reveals how technology acceptance and employment perspectives relate to working conditions and lessons learned from past reforms.Originality/valueThe authors consider current theories such as technology acceptance model at the micro level and that way rationalise the need for this study. This study shows the importance of individual, organisational and wider contextual factors in technology acceptance. (shrink)

It has recently been shown that stem and progenitor cells undergo population self‐renewal to maintain epithelial homeostasis. The fate of individual cells is stochastic but the production of proliferating and differentiating cells is balanced across the population. This new paradigm, originating in mouse epidermis and since extended to mouse oesophagus and mouse and Drosophila intestine, is in contrast to the long held model of epithelial maintenance by exclusively asymmetric division of stem cells. Recent lineage tracing studies have now (...) shown that wound responses vary between tissues, and that a stem cell reserve is not essential as cycling progenitors and even differentiating cells contribute to regeneration. (shrink)

Early animal embryos are patterned by localized egg cytoplasmic factors and cell interactions. In invertebrate chordate ascidians, larval tail muscle originates from the posterior marginal zone of the early embryo. It has recently been demonstrated that maternal macho‐1 mRNA encoding transcription factor acts as a localized muscle determinant. Other mesodermal tissues such as notochord and mesenchyme are also derived from the vegetal marginal zone. In contrast, formation of these tissues requires induction from endoderm precursors at the 32‐cell stage. FGF–Ras–MAPK signaling (...) is involved in the induction of both tissues. The responsiveness for induction to notochord or mesenchyme depends on the inheritance of localized egg cytoplasmic factors. Previous studies also point to critical roles of directed signaling in polarization of induced cells and in subsequent asymmetric divisions resulting in the formation of two daughter cells with distinct fates. One cell adopts an induced fate, while the other assumes a default fate. A simple model of mesoderm patterning in ascidian embryos is proposed in comparison with that of vertebrates. BioEssays 24:613–624, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The generation of asymmetric cell shapes is a recurring theme in biology. In budding yeast, one form of cell asymmetry occurs for division and is generated by anisotropic growth of the mother cell to form a daughter cell bud. Previous genetic studies uncovered key roles for the small GTPase Cdc42 in organizing the actin cytoskeleton and vesicle delivery to the site of bud growth,1,2 but a recent paper has also raised questions about how control of Cdc42 activity is (...) integrated into a proposed hierarchical regulatory pathway that specifies a unique site of bud formation.3 BioEssays 25:833–836, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Is the assumption of a fundamental distinction between particulars and universals another unsupported dogma of metaphysics? F. P. Ramsey famously rejected the particular – universal distinction but neglected to consider the many different conceptions of the distinction that have been advanced. As a contribution to the piecemeal investigation of this issue three interrelated conceptions of the particular – universal distinction are examined: universals, by contrast to particulars, are unigrade; particulars are related to universals by an asymmetric tie of exemplification; (...) universals are incomplete whereas particulars are complete. It is argued that these conceptions are wanting in several respects. Sometimes they fail to mark a significant division amongst entities. Sometimes they make substantial demands upon the shape of reality; once these demands are understood aright it is no longer obvious that the distinction merits our acceptance. The case is made via a discussion of the possibility of multigrade universals. (shrink)

Rather than focus on effects, the isolatable and measureable outcomes of events and interventions, the papers assembled here offer different perspectives on the affective dimension of the meaning and politics of human/non-human relations. The authors begin by drawing attention to the constructed discontinuity between humans and non-humans, and to the kinds of knowledge and socialities that this discontinuity sustains, including those underpinned by nature-culture, subject-object, body-mind, individual-society polarities. The articles presented track human/non-human relations through different domains, including: humans/non-humans in history (...) and animal welfare science (Fudge and Buller); the relationship between the way we live, the effects on our natural environment and contested knowledges about ‘nature’ (Whatmore); choreographies of everyday life and everyday science practices with non-human animals such as horses, meerkats, mice, and wolves (Latimer, Candea, Davies, Despret). Each paper also goes on to offer different perspectives on the human/non-human not just as division, or even as an asymmetrical relation, but as relations that are mutually affective, however invisible and inexpressible in the domain of science. Thus the collection contributes to new epistemologies/ontologies that undercut the usual ordering of relations and their dichotomies, particularly in that dominant domain of contemporary culture that we call science. Indeed, in their impetus to capture ‘affect’, the collection goes beyond the usual turn towards a more inclusive ontology, and contributes to the radical shift in the epistemology and philosophy of science’s terms of engagement. (shrink)

In this paper, I argue that the asymmetrical mediated communication of the broad democratic public sphere can profitably be understood through the lens of deliberative democracy only if we adopt a system approach to deliberation. A system approach, however, often introduces a division of labor between ordinary citizens and experts. Although this division of labor is unavoidable and I believe compatible with a deliberative principle of legitimacy, it flirts with elitist theories of democracy: epistemic elites come up with (...) the agendas, ideas, and policy positions and democratic publics ratify or repudiate the agendas but do not generate or really engage with them. This I argue would violate an essential defining feature of deliberative democracy, namely that epistemic quality and equal participation are tightly linked. I turn to Habermas and his idea of a feedback loop as a possible solution to this dilemma. (shrink)

Many philosophic arguments concerned with infinite series depend on the mutual inconsistency of statements of the following five forms: (1) something exists which has R to something; (2) R is asymmetric; (3) R is transitive; (4) for any x which has R to something, there is something which has R to x; (5) only finitely many things are related by R. Such arguments are suspect if the two-place relation R in question involves any conceptual vagueness or inexactness. Traditional sorites (...) arguments show that a statement of form (4) can fail to be true even though it has no clear counter-example. Conceptual vagueness allows a finite series not to have any definite first member. I consider the speculative possibilities that there have been only finitely many non-overlapping hours although there has been no first hour and that space and time are only finitely divisible even though there are no smallest spatial or temporal intervals. (shrink)

What I call "strategic injustice" involves a set of formal and informal regulatory rules and conventions that often lead to grossly unfair outcomes for a class of individuals despite their resistance. My goal in this paper is to provide the necessary conditions for such injustices and for eliminating their instances from our social practices. To do so, I follow Peter Vanderschraaf's analysis of circumstances of justice and expand his account by embedding "asymmetric conflictual coordination games" that summarize fair (...) class='Hi'>division problems in a dynamic social network. I use the network effect on such coordination games to explain the emergence of stable exploitative behavior and conventions by a class of individuals even in the presence of restraining efforts by others. I conclude that such unfair conventions are resilient to uncoordinated individual actions and interventions. In fact, maintaining a rough equality itself turns into another coordination problem. Finally, I show that something similar to a social movement that restructures the network of social relations is necessary to solve such coordination problems. (shrink)

Wnt glycoproteins are signaling molecules that control a wide range of developmental processes in organisms ranging from the simple metazoan Hydra to vertebrates. Wnt signaling also plays a key role in the development of the nematode C. elegans, and is involved in cell fate specification and determination of cell polarity and cell migration. Surprisingly, the first genetic studies of Wnt signaling in C. elegans revealed major differences with the established (canonical) Wnt signaling pathways of Drosophila and vertebrates. Thus, the Wnt-dependent (...) induction of endoderm in the early embryo and the specification of several asymmetric cell divisions during larval development are mediated by as yet novel Wnt signaling pathways that repress, rather than activate the TCF/LEF-1 transcription factor POP-1. Recently, however, it has been shown that, in addition to these divergent Wnt pathways, C. elegans also has a canonical Wnt pathway that converts POP-1 into an activator and controls the expression of several homeobox genes. Interestingly, these different Wnt pathways use distinct beta-catenins to control POP-1 function: the endoderm induction pathway requires the beta-catenin WRM-1 and parallel input from a mitogen-activated kinase (MAPK) pathway to downregulate POP-1, whereas the canonical Wnt pathway employs the beta-catenin BAR-1 to activate Wnt target gene expression. (shrink)

I take 'informal logic' to be the (descriptive and normative) study of 'real arguments'-arguments which are or have been used with the aim of convincing others of a point of view. I argue that the informal logic tradition thus conceived (i) lends strong support to something like Quine's view that our beliefs really support one another like the filaments in a spider's web--and thus that the traditional view that implication is an asymmetric relation is false; (ii) suggests that the (...) classic division of arguments into deductive and inductive has distorted our thinking about the evaluation of real arguments; and (iii) implies that naturalised epistemology is on the right track. (shrink)

Prominent neo-Marxists have recently acknowledged longstanding criticisms of Marx's labor theory of value as at best a cumbersome and redundant price model but continue to variously defend the doctrine as an interpretation of historically observed class conflict between exploiters and exploited. This essay counters that value theory also fails badly as a "labor theory of exploitation." The fundamental flaw is the canonical premise that labor alone is productive, with normative implications closer to the entrepreneurial work ethic than to socialist standards (...) of distributive justice. The essay then identifies an alternative theory of exploitation implied by Marx's earlier writings on alienation but obscured by his later association of exploitation with surplus value. What capital appropriates is not "surplus value" produced by labor, but the capacity to produce it, creating asymmetric interdependence within the division of labor. Exploitation arises in the mediation of this interdependence through the exchange of commodities. (shrink)

ABSTRACT Some scholars tend to argue that Black marginality is due largely to the exclusion of Blacks from meaningful economic participation as well as generalized social exclusions. This, owing to the division of the world’s populations along a racial hierarchy on the one hand, and in geopolitical terms along the dichotomy of Metropoles and dependencies. While there have been some cosmetic changes, particularly in relation to the complexion of the ruling personnel in the aftermath of Independence, the view adopted (...) here is that the colonial structure remains largely intact. This is because the material base of colonial countries or regions remains fundamentally predisposed toward satisfying the economic interest of industrialized Western powers, the former colonizers. The argument advanced here therefore, is that such marginality is due not from exclusions per se but rather from inclusion albeit only as junior, and therefore inferior, partners. So at the root of the problem is the problem of “white supremacy,” which establishes and maintains asymmetrical relations between the races. This system underlies as it underpins the standard contract and thus functions as a clandestine and unofficial political system. The article thus delves into the social contract theory, particularly the works of Charles Mills and Jean-Jacques Rousseau, with the view of ascertaining how their ideas help us understand the modern world in terms of race relations. Furthermore, Walter Rodney’s concept of “white power” is appropriated as it provides a useful framework within which to understand the white power complex. (shrink)

Stomata are microscopic pores on the surface of land plants used for gas and water vapor exchange. A pair of highly specialized guard cells surround the pore and adjust pore size. Studies in Arabidopsis have revealed that cell–cell communication is essential to coordinate the asymmetric cell divisions required for proper stomatal patterning. Initial research in this area identified signaling molecules that negatively regulate stomatal differentiation. However, genes promoting cell‐fate transition leading to mature guard cells remained elusive. Now, three closely (...) related basic helix–loop–helix (bHLH) proteins, SPEECHLESS, MUTE and FAMA have been identified as positive regulators that direct three consecutive cell‐fate decisions during stomatal development. The identification of these genes opens a new direction to investigate the evolution of stomatal development and the conserved functions of bHLH proteins in cell type differentiation adopted by plants and animals. BioEssays 29:861–870, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

In recent years, live imaging has been adopted to study stem cells in their native environment at cellular resolution. In the skeletal muscle field, this has led to visualising the initial events of muscle repair in mouse, and the entire regenerative response in zebrafish. Here, we review recent discoveries in this field obtained from live imaging studies. Tracking of tissue resident stem cells, the satellite cells, following injury has captured the morphogenetic dynamics of stem/progenitor cells as they facilitate repair. (...) class='Hi'>Asymmetric satellite cell division generated a clonogenic progenitor pool, providing in vivo validation for this mechanism. Furthermore, there is an emerging role of stem/progenitor cell guidance at the injury site by cellular protrusions. This review concludes that live imaging is a critical tool for discovering the distinct processes that occur during regeneration, emphasising the importance of imaging in diverse animal models to capture the entire scope of stem cell functions. (shrink)

Adherens junctions play pivotal roles in cell and tissue organization and patterning by mediating cell adhesion and cell signaling. These junctions consist of large multiprotein complexes that join the actin cytoskeleton to the plasma membrane to form adhesive contacts between cells or between cells and extracellular matrix. The best-known adherens junction is the zonula adherens (ZA) that forms a belt surrounding the apical pole of epithelial cells. Recent studies in Drosophila have further illuminated the structure of adherens junctions. Scaffolding proteins (...) encoded by the stardust gene are novel components of the Crumbs complex, which plays a critical role in ZA assembly.1-3 The small GTPase Rap1 controls the symmetric re-assembly of the ZA after cell division.4 Finally, the asymmetric distribution of adherens junction material regulates spindle orientation during asymmetric cell division in the sensory organ lineage.5 BioEssays 24:690–695, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

In the 4 1/2 to 5 days between fertilization and implantation, the mouse conceptus must gain the abilities to implant and produce an embryo. Each of these is the sole developmental responsibility of one of two cell types forming the blastocyst, trophectoderm and inner cell mass (ICM), respectively. Trophectoderm is a polarized transporting epithelium while the ICM is an aggregate of non‐epithelial pluripotent stem cells. These two cell types originate from the division of polar blastomeres when their cleavage furrows (...) parallel their apical surfaces. Blastomeres polarize in response to asymmetric cell–cell contact, and understanding the mechanism of this induction is regarded as the key to understanding the origin of trophectoderm and ICM. Here we propose a model based on transcellular ion current loops for the induction of cell polarity during the development of the first epithelium, trophectoderm. (shrink)

Feedback control in neural systems is ubiquitous. Here we study the mathematics of nonlinear feedback control. We compare models in which the input is multiplied by a dynamic gain (multiplicative control) with models in which the input is divided by a dynamic attenuation (divisive control). The gain signal (resp. the attenuation signal) is obtained through a concatenation of an instantaneous nonlinearity and a linear low-pass filter operating on the output of the feedback loop. For input steps, the dynamics of gain (...) and attenuation can be very different, depending on the mathematical form of the nonlinearity and the ordering of the nonlinearity and the filtering in the feedback loop. Further, the dynamics of feedback control can be strongly asymmetrical for increment versus decrement steps of the input. Nevertheless, for each of the models studied, the nonlinearity in the feedback loop can be chosen such that immediately after an input step, the dynamics of feedback control is symmetric with respect to increments versus decrements. Finally, we study the dynamics of the output of the control loops and find conditions under which overshoots and undershoots of the output relative to the steady-state output occur when the models are stimulated with low-pass filtered steps. For small steps at the input, overshoots and undershoots of the output do not occur when the filtering in the control path is faster than the low-pass filtering at the input. For large steps at the input, however, results depend on the model, and for some of the models, multiple overshoots and undershoots can occur even with a fast control path. (shrink)

We study a dynamic game in which players can steal parts of a homogeneous and perfectly divisible pie from each other. The effectiveness of a player’s theft is a random function which is stochastically increasing in the share of the pie the agent currently owns. We show how the incentives to preempt or to follow the rivals change with the number of players involved in the game and investigate the conditions that lead to the occurrence of symmetric or asymmetric (...) equilibria. (shrink)

A key moment in the development of Deleuze’s Difference and Repetition is signaled by the introduction, during the discussion of the asymmetric synthesis of the sensible, of the concepts of spatium and intensive quantities. The description of the characteristics of this field of individuation and the type of entities that inhabit it is necessary for thinking the relationship between the differential elements that compose ideas and the state of affairs in which they become incarnated. In other words, in order (...) to define the passage between the virtual and the actual, it is necessary to make use of a “non-divisible transcendental principle” that works as a stage in which certain agents—the spatio-temporal dynamisms—play the role of the genetic principle behind extended reality and its quantitative and qualitative determinations. This dynamic process is what Deleuze calls “the method of dramatisation”. However, even if this reference to theater is crucial in the book’s conceptual economy, it is particularly obscure and elliptical. The aim of this article is to clarify the sense of this reference and the reach of the link between individuation and theater. To achieve this purpose, we will examine closely the use that Deleuze makes of some of Friedrich Hölderlin’s poetological categories in his description of the third passive synthesis of time. (shrink)

Zygote cytokinesis produces two symmetric blastomeres, which contain one copy of each parental genome. Contrary to this dogma, we recently discovered that mammalian zygotes can spontaneously segregate entire parental genomes into different blastomeres and coined this novel form of genome segregation heterogoneic division. The molecular mechanisms underlying the emergence of blastomeres with different parental genomes during the first mitotic cycle remain to be elucidated. Here, we speculate on which parental genome asymmetries could provide a mechanistic foundation for these remarkable (...) zygote divisions. In reviewing the field and considering our findings, we revisit the architecture of the first zygotic metaphase by invoking asymmetric interactions between the mitotic spindle and the parental kinetochores. We also speculate on how asynchronous parental cell cycles can be a source of heterogoneic zygote divisions through the formation of parental genome private spindles. (shrink)

There are scenarios in which letting one’s own views on the question whether p direct one’s inquiry into that question brings about individual and collective epistemic benefits. However, these scenarios are also such that one’s evidence doesn’t support believing one’s own views. So, how to vindicate the epistemic benefits of directing one’s inquiry in such an asymmetric way, without asking one to hold a seemingly irrational doxastic attitude? To answer this question, the paper understands asymmetric inquiry direction in (...) terms of having one’s inquiry be guided by a doxastic attitude, which I call hypothesis, that’s governed by the following norm: One’s hypothesis that p is rational just in case it is a manifestation of the best feasible way to form a doxastic attitude regarding p that promotes the best feasible ways to advance towards settling the question of p’s (or of any other suitably related proposition’s) truth-value. (shrink)

Tissues are shaped and patterned by mechanical and chemical processes. A key mechanical process is the positioning of the mitotic spindle, which determines the size and location of the daughter cells within the tissue. Recent force and position-fluctuation measurements indicate that pushing forces, mediated by the polymerization of astral microtubules against­ the cell cortex, maintain the mitotic spindle at the cell center in Caenorhabditis elegans embryos. The magnitude of the centering forces suggests that the physical limit on the accuracy and (...) precision of this centering mechanism is determined by the number of pushing microtubules rather than by thermally driven fluctuations. In cells that divide asymmetrically, anti-centering, pulling forces generated by cortically located dyneins, in conjunction with microtubule depolymerization, oppose the pushing forces to drive spindle displacements away from the center. Thus, a balance of centering pushing forces and anti-centering pulling forces localize the mitotic spindles within dividing C. elegans cells. We discuss microtubule-based mechanisms of the mitotic spindle positioning, a key mechanical process that shapes and patterns tissues. The magnitude of the centering forces indicates that the physical limit on the accuracy and precision of centering is set by the number of contributing microtubules rather than by thermally driven fluctuations. (shrink)

Tissues are shaped and patterned by mechanical and chemical processes. A key mechanical process is the positioning of the mitotic spindle, which determines the size and location of the daughter cells within the tissue. Recent force and position-fluctuation measurements indicate that pushing forces, mediated by the polymerization of astral microtubules against­ the cell cortex, maintain the mitotic spindle at the cell center in Caenorhabditis elegans embryos. The magnitude of the centering forces suggests that the physical limit on the accuracy and (...) precision of this centering mechanism is determined by the number of pushing microtubules rather than by thermally driven fluctuations. In cells that divide asymmetrically, anti-centering, pulling forces generated by cortically located dyneins, in conjunction with microtubule depolymerization, oppose the pushing forces to drive spindle displacements away from the center. Thus, a balance of centering pushing forces and anti-centering pulling forces localize the mitotic spindles within dividing C. elegans cells. We discuss microtubule-based mechanisms of the mitotic spindle positioning, a key mechanical process that shapes and patterns tissues. The magnitude of the centering forces indicates that the physical limit on the accuracy and precision of centering is set by the number of contributing microtubules rather than by thermally driven fluctuations. (shrink)

Localized mRNA translation is a biological process that allows mRNA to be translated on‐site, which is proposed to provide fine control in protein regulation, both spatially and temporally within a cell. We recently reported that Vasa, an RNA‐helicase, is a promising factor that appears to regulate this process on the spindle during the embryonic development of the sea urchin, yet the detailed roles and functional mechanisms of Vasa in this process are still largely unknown. In this review article, to elucidate (...) these remaining questions, we first summarize the prior knowledge and our recent findings in the area of Vasa research and further discuss how Vasa may function in localized mRNA translation, contributing to efficient protein regulation during rapid embryogenesis and cancer cell regulation. (shrink)

In a quantum universe with a strong arrow of time, we postulate a low-entropy boundary condition to account for the temporal asymmetry. In this paper, I show that the Past Hypothesis also contains enough information to simplify the quantum ontology and define a unique initial condition in such a world. First, I introduce Density Matrix Realism, the thesis that the quantum universe is described by a fundamental density matrix that represents something objective. This stands in sharp contrast to Wave Function (...) Realism, the thesis that the quantum universe is described by a wave function that represents something objective. Second, I suggest that the Past Hypothesis is sufficient to determine a unique and simple density matrix. This is achieved by what I call the Initial Projection Hypothesis: the initial density matrix of the universe is the normalized projection onto the special low-dimensional Hilbert space. Third, because the initial quantum state is unique and simple, we have a strong case for the \emph{Nomological Thesis}: the initial quantum state of the universe is on a par with laws of nature. This new package of ideas has several interesting implications, including on the harmony between statistical mechanics and quantum mechanics, the dynamic unity of the universe and the subsystems, and the alleged conflict between Humean supervenience and quantum entanglement. (shrink)

What is the quantum state of the universe? Although there have been several interesting suggestions, the question remains open. In this paper, I consider a natural choice for the universal quantum state arising from the Past Hypothesis, a boundary condition that accounts for the time-asymmetry of the universe. The natural choice is given not by a wave function but by a density matrix. I begin by classifying quantum theories into two types: theories with a fundamental wave function and theories with (...) a fundamental density matrix. The Past Hypothesis is compatible with infinitely many initial wave functions, none of which seems to be particularly natural. However, once we turn to density matrices, the Past Hypothesis provides a natural choice---the normalized projection onto the Past Hypothesis subspace in the Hilbert space. Nevertheless, the two types of theories can be empirically equivalent. To provide a concrete understanding of the empirical equivalence, I provide a novel subsystem analysis in the context of Bohmian theories. Given the empirical equivalence, it seems empirically underdetermined whether the universe is in a pure state or a mixed state. Finally, I discuss some theoretical payoffs of the density-matrix theories and present some open problems for future research. (Bibliographic note: the thesis was submitted for the Master of Science in mathematics at Rutgers University.). (shrink)

It is fairly uncontroversial that when you encounter disagreement with some view of yours, you are often epistemically required to become at least somewhat less confident in that view. This includes political disagreements, where your level of confidence might in various ways affect your voting and other political behavior. But suppose that your opponents don’t comply with the epistemic norms governing disagreement – that is, they never reduce their confidence in their views in response to disagreement. If you always reduce (...) your confidence, but your opponents never reduce theirs – and everyone participates in the political process accordingly – then it seems like the deliberative process will be unfairly skewed in favor of your opponents. In this paper, I do two things. First, I try to explain how this can be so, even though the process by stipulation represents everyone’s beliefs equally. Second, I defend the view that in such cases, you should remedy the unfairness by voting out of accord with your beliefs. By introducing a distinct state that I call a “personal take,” which you can vote on the basis of in such a case, I explain how doing this need not be problematically insincere, nor incoherent from the inside. The discussion has a number of independent upshots for both democratic theory and the epistemology of disagreement. (shrink)

mix of the concrete and the abstract (if we include universals, laws, propositions and the like), but whichever of these is the case, the world is not purely abstract, as a formal structure is. One might claim, however, that the world is a structure1 in the sense that it instantiates a structure and is nothing else. In other words, all there is to the..

Women continue to be in charge of most childrearing; men continue to be responsible for most breadwinning. There is no consensus on whether this state of affairs, and the informal norms that encourage it, are matters of justice to be tackled by state action. Feminists have criticized political liberalism for its alleged inability to embrace a full feminist agenda, inability explained by political liberals’ commitment to the ideal of state neutrality. The debate continues on whether neutral states can accommodate two (...) feminist demands: to enact policies aimed at dismantling the feminization of caregiving, especially childrearing, and to compensate women for some of the disadvantages they incur by being primary care-givers. I contribute to this debate with three arguments in support of policies meant to de-gender care-giving and compensate care-givers. The first appeals to equality of opportunity to positions of advantage and justifies policies that prevent or mitigate statistical discrimination and implicit biases. The second draws attention to a possible causal relationship between the specialization of women in early childcare and misogyny; since the latter is incompatible with political liberal justice, it yields the conclusion that political liberals ought to further investigate the causal hypothesis with the aim of establishing or refuting it. The third argument concludes that legitimate childrearing prohibits adults from socializing children or, at least girls, into gender norms; it justifies duties of justice on the side of parents, educators, and economic agents, and state policies meant to offset foreseeable breaches of some of these duties. (shrink)

In the first book of the Prior Analytics, Aristotle sets out, for the first time in Greek philosophy, a logical system. It consists of a deductive system (I.4-22), meta-logical results (I.23-26), and a method for finding and giving deductions (I.27-29) that can apply in “any art or science whatsoever” (I.30). After this, Aristotle compares this method with Plato’s method of division, a procedure designed to find essences of natural kinds through systematic classification. This critical comparison in APr I.31 raises (...) an interpretive puzzle: how can Aristotle reasonably juxtapose two methods that differ so much in their aims and approach? What can be gained by doing so? Previous interpreters have failed to show how this comparison is legitimate or what important point Aristotle is making. The goal of this paper is to resolve the puzzle. In resolving this puzzle we not only learn more about the relationship be- tween division and the syllogistic in Aristotle. We will also learn something about the motivation for the syllogistic itself, by seeing the role that it plays in his philosophy of science. (shrink)