Cells can transit between a range of stable epithelial and mesenchymal states and this has allowed the evolution of complex body forms. Epithelial to mesenchymal transition (EMT) and its reverse, mesenchymal to epithelial transition (MET), occur sequentially in development and organogenesis. EMT often accompanies transitions between stem‐like cells and their more differentiated progeny, as occurs at gastrulation, although the relevance of this had not been clarified. New findings from the cancer and cell (...) reprogramming fields suggest that EMT and MET can act as essential portals to stem cell character. Here, we review these findings in the broader context of EMT and MET with emphasis on stem cell biology. Using the heart as an example, we also explore the potential role of EMT/MET in organ regeneration. Understanding EMT and MET at a network level will give us new tools to probe stem cell character and enhance tissue repair. (shrink)

Metastasis is one of the clinical parameters that has a strong negative influence on the prognosis of cancer patients. In recent years, significant advances have furthered our understanding of this process at the molecular and biological levels. This paper will discuss recent discoveries relating to the earliest, intra‐tumoral stages of metastasis in cancer cells, specifically focusing on: (i) the development of metastatic traits during primary tumorigenesis; (ii) intrinsic and extrinsic cancer cell programs associated with malignant traits; (iii) the intra‐tumoral migration (...) patterns of cancer cells and the dynamic roles played by the Rho/Rac GTPases and epithelial‐mesenchymal transitions in this process; and (iv) the genetic strategies used by metastatic cancer cells to promote intra‐tumoral cell migration and their subsequent escape to peripheral tissues. Finally, the therapeutic and diagnostic relevance of this information will be discussed, as well as potential future developments. (shrink)

Several molecular mechanisms contribute directly and mechanically to the loss of epithelial phenotype. During epithelial–mesenchymal transition (EMT), adherens junctions and desmosomes are at least partially dissociated. At the same time, a massive cytoskeleton reorganization takes place, involving the rho family and the remodeling of the actin microfilament mesh. Numerous pathways have been described in vitro that control phenotype transition in specific cell models. In vivo developmental studies suggest that transcriptional control, activated by a specific pathway (...) involving Ras, Src and potentially the Wnt pathway, is an essential step. Recent functional and localization experiments indicate that the slug/snail family of transcription factors functions overall as an epithelial phenotype repressor and could represent a key EMT contributor. BioEssays 23:912–923, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The Polycomb group of proteins (PcGs) are transcriptional repressor complexes that regulate important biological processes and play critical roles in cancer. Mutating or deleting EZH2 can have both oncogenic and tumor suppressive functions by increasing or decreasing H3K27me3. In contrast, mutations of SUZ12 and EED are reported to have tumor suppressive functions. EZH2 is overexpressed in many cancers, including prostate cancer, which can lead to silencing of tumor suppressors, genes regulating epithelial to mesenchymal transition (EMT), and interferon (...) signaling. In some cases, EZH2 overexpression also leads to its use of non‐histone substrates. Lastly, PRC2 associated factors can influence the progression of cancer through progressive mutations or by specific binding to certain target genes. Here, we discuss which mutations and deletions of the PRC2 complex have been detected in different cancers, with a specific focus on the overexpression of EZH2 in prostate cancer. (shrink)

Recent studies uncovered critical roles of the adhesion protein E‐cadherin in health and disease. Global inactivation of Cdh1, the gene encoding E‐cadherin in mice, results in early embryonic lethality due to an inability to form the trophectodermal epithelium. To unravel E‐cadherin's functions beyond development, numerous mouse lines with tissue‐specific disruption of Cdh1 have been generated. The consequences of E‐cadherin loss showed great variability depending on the tissue in question, ranging from nearly undetectable changes to a complete loss of tissue structure (...) and function. This review focuses on these studies and discusses how they provided important insights into E‐cadherin's role in cell adhesion, proliferation and differentiation, and its consequences for biological processes as epithelial‐to‐mesenchymal transition, vascularization, and carcinogenesis. Lastly, we present some perspectives and possible approaches for future research. (shrink)

Ubiquitination of protein species in regulating signal transduction pathways is universally accepted as of fundamental importance for normal development, and defects in this process have been implicated in the progression of many human diseases. One pathway that has received much attention in this context is transforming growth factor‐beta (TGF‐β) signalling, particularly during the regulation of epithelial‐mesenchymal transition (EMT) and tumour progression. While E3‐ubiquitin ligases offer themselves as potential therapeutic targets, much remains to be unveiled regarding mechanisms that (...) culminate in their regulation. With this in mind, the focus of this review highlights the regulation of the ubiquitination pathway and the significance of a recently described group of NEDD4 E3‐ubiquitin ligase isoforms in the context of TGF‐β pathway regulation. Moreover, we now broaden these observations to incorporate a growing number of protein isoforms within the ubiquitin ligase superfamily as a whole, and discuss their relevance in defining a new ‘iso‐ubiquitinome’. (shrink)

The expression of epithelial cell adhesion and cytoskeletal genes is orchestrated by an apparently unique set of rules. No tissue‐specific transactivator proteins have been found to drive them; only ubiquitous factors are utilized. In non‐epithelial cells, they are actively repressed. Moreover, it was recently found that a single protein (adenovirus E1a) coordinately represses non‐epithelial genes while inducing epithelial genes. A simple model is offered to explain how epithelial gene expression is coordinated. Under this model, the (...) epithelial cell gene expression program is a transcriptional ‘default’; that is, it occurs in the absence of tissue‐specific transactivation. Conversion to this default requires only that mesenchymal transactivators are not expressed, or that central ‘integrator’ proteins are inactive. In their absence, mesenchymal gene expression cannot occur. Moreover, because the repressors cease to be expressed, the epithelial genes are induced. Oncogenes generally cause the breakdown of the epithelial phenotype ‐ generating carcinomas ‐ so genes such as E1a that cause epithelial conversion may prove useful for both understanding and controlling cancer. (shrink)

Early morphogenesis of mouse submandibular gland provides an excellent model for the formation of epithelial lobules as a consequence of epithelial‐mesenchymal interactions. Both proteoglycans and a glycosaminoglycan, high molecular weight components which contain amino‐sugars and hexuronic acids, seem to be important in maintaining the lobular structure through the formation of epithelial basal lamina. Collagen also appears to play a crucial role in this morphogenesis. By visualizing the distribution of collagen fibrils and by changing the concentration of (...) collagen in the gland, we have developed a new hypothesis which emphasizes the mechanical role of mesenchyme in epithelial cleft formation. Precise mechanisms for the involvement of these molecules have not been elucidated, yet it is now clear that knowledge of the function of the extracellular matrix components is a prerequisite for understanding the epithelial‐mesenchymal interactions. (shrink)

Early morphogenesis of mouse submandibular gland provides an excellent model for the formation of epithelial lobules as a consequence of epithelial‐mesenchymal interactions. Both proteoglycans and a glycosaminoglycan, high molecular weight components which contain amino‐sugars and hexuronic acids, seem to be important in maintaining the lobular structure through the formation of epithelial basal lamina. Collagen also appears to play a crucial role in this morphogenesis. By visualizing the distribution of collagen fibrils and by changing the concentration of (...) collagen in the gland, we have developed a new hypothesis which emphasizes the mechanical role of mesenchyme in epithelial cleft formation. Precise mechanisms for the involvement of these molecules have not been elucidated, yet it is now clear that knowledge of the function of the extracellular matrix components is a prerequisite for understanding the epithelial‐mesenchymal interactions. (shrink)

During development of the anterior eye segment, cells that originate from the surface epithelium or the neuroepithelium need to interact with mesenchymal cells, which predominantly originate from the neural crest. Failures of proper interaction result in a complex of developmental disorders such Peters' anomaly, Axenfeld–Rieger's syndrome or aniridia. Here we review the role of transcription factors that have been identified to be involved in the coordination of anterior eye development. Among these factors is PAX6, which is active in both (...) epithelial and mesenchymal cells during ocular development, albeit at different doses and times. We propose that PAX6 is a key element that synchronizes the complex interaction of cell types of different origin, which are all needed for proper morphogenesis of the anterior eye. We discuss several molecular mechanisms that might explain the effects of haploinsufficiency of PAX6 and other transcription factors, and the broad variation of the resulting phenotypes. BioEssays 26:374–386, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Epithelia can be defined morphologically as tissues that line surfaces, and ultrastructurally with reference to their cells' apico‐basal polarity and possession of specific cell‐cell junctions. Defining the epithelial phenotype at a molecular level is more problematic ‐ while it is easy to name proteins (e.g. keratins) expressed by a “typical” epithelium, no known molecules are expressed by every epithelium but by no other tissues. Cells can differentiate to and from the epithelial state as part of normal development, as (...) a response to disease or when manipulated in culture. Many factors (matrix components, adhesion molecules, growth factors, transcription factors) have been identified that can trigger these transitions of phenotype in specific cases, but to date no general master regulators of the epithelial state have been found. The epithelial state may therefore be controlled by multiple regulatory genes so that there is no single molecule responsible for all of the diverse types of epithelium that exist in higher animals. (shrink)

The c‐ros, c‐met and c‐neu genes encode receptor‐type tyrosine kinases and were originally identified because of their oncogenic potential. However, recent progress in the analysis of these receptors and their respective ligands indicate that they do not mediate exclusively mitogenic signals. Rather, they can induce cell movement, differentiation or morphogenesis of epithelial cells in culture. Interestingly, the discussed receptors are expressed in embryonal epithelia, whereas direct and indirect evidence shows that the corresponding ligands are produced in mesenchymal cells. (...) In development, signals given by mesenchymal cells are major driving forces for differentiation and morphogenesis of epithelia; embryonal epithelia are generally unable to differentiate without the appropriate mesenchymal factors. The observed activities of these receptor/ligand systems in cultured cells and their expression patterns indicate that they regulate epithelial differentiation and morphogenesis also during embryogenesis and suggest thus a molecular basis for mesenchymal epithelial interactions. (shrink)

Ethicists and economists commonly assume that if A is all things considered better than B, and B is all things considered better than C, then A is all things considered better than C. Call this principle Transitivity. Although it has great conceptual, intuitive, and empirical appeal, I argue against it. Larry S. Temkin explains how three types of ethical principle, which cannot be dismissed a priori, threaten Transitivity: (a) principles implying that in some cases different factors are relevant to comparing (...) A to C than to comparing A to B or B to C; (b) principles of limited scope; (c) principles implying that morally relevant differences in degree can amount to differences in kind. My counterexamples employ a principle of type (c): pleasures and pains enormously different in intensity differ in kind. Temkin has also endorsed this type of counterexample, using arguments based on earlier drafts of this paper. (shrink)

I discuss three recent counterexamples to the transitivity of grounding due to Jonathan Schaffer. I argue that the counterexamples don’t work and draw some conclusions about the relationship between grounding and explanation.

There is a mistake in the definition of the covering criterion on page 6.

The book contains twelve essays by Stephen Holmes, Frances M. Kamm, Mária Ludassy, Steven Lukes, Gyorgy Markus, András Sajó, Gáspár Miklós Tamás, Andrew Arato, Timothy Garton Ash, Béla Greskovits, Will Kymlicka, and Aleksander Smolar. The studies explore a wide scope of subjects that belong to disciplines ranging from moral philosophy, through theory of human rights, democratic transition, constitutionalism, to political economy. The common denominator of the studies collected is their reference to the scholarly output of János Kis, in honor (...) of his sixtieth birthday. János Kis is a distinguished political philosopher who, after many years spent as a dissident under the Communist regime, emerged as an important political figure in Hungary's transition to democracy. Currently he is University Professor of Philosophy at Central European University, Budapest. (shrink)

Although “transition” is an established area of educational research, there has been little empirically exploration of how shifts in the ways that knowledge is packaged and valued impact on students’ reading and writing as they transition into higher education. This article draws on a longitudinal ethnographic study that traced the experiences, practices and understandings of 11 students from their last year of A-levels through to their second year of undergraduate study. Analysis shows that the forms of knowledge privileged (...) and the ways that knowledge is packaged vary significantly between the two educational contexts, impacting on students’ engagement with texts as they transition into university. This article further illustrates that as a result of shifts in what counts as knowledge between these levels, students face challenges adapting to undergraduate literacies, which disrupts the simplistic notion of transition evoked in the dominant positioning of “the transition to uni... (shrink)

Existing research has examined if undergraduate factors influence chemistry and physics, or physical science, doctoral degree entry and whether variables during PhD programs associate with graduation. Yet research on the transition from bachelor’s degree to doctoral degree entry (i.e., PhD entry in less than 6 months, attainment of a master’s degree prior to doctoral degree entry, or working in a science-related job for more than a year prior to doctoral degree entry) on PhD degree graduation remains scarce. Our study (...) examines the transition from bachelor’s to doctoral degrees to see if experiences therein associate with female PhD graduation, after doctoral degree enrollment. Our logistic regression analysis, of female chemistry and physics doctorates (n = 867), indicated that attainment of a master’s degree did not change the likelihood of graduation, when compared to direct entry into physical science doctoral programs. Meanwhile working in a science-related job for a year or more is associated with a significantly lower likelihood of physical science doctoral graduation when compared to women who entered directly into PhD programs or received a master’s degree prior to enrollment. (shrink)

It is well established that single crystals of B2-structured Fe-Al change from paramagnetic to ferromagnetic upon plastic deformation. This strain-induced ferromagnetism arises mostly from Fe atoms which have three or more like nearest neighbours in antiphase-boundary tubes. Such Fe atoms carry magnetic moments according to their local environment. In this study, the saturation magnetizations, M S , of cold-rolled Fe-34 at.% Al, Fe-40 at.% Al and Fe-43 at.% Al single crystals were measured in a vibrating-sample magnetometer from 77 K to (...) room temperature and transmission electron microscopy was used to confirm the presence of APB tubes. After magnetic measurements, rolled single crystals were heated in a differential scanning calorimeter at 20 K min m 1 to 973 K and the enthalpy associated with the removal of the APB tubes measured. From the enthalpy measurement, the APB tube density and the number of Fe NNs were estimated. Hence, the M S values at 0 K were calculated. These were in good agreement with the experimentally determined values. (shrink)

The Covid-19 crisis raises questions of resilience, sustainable transitions and global trade in the wake of a pandemic. Port cities require new scenarios to deal with these questions, and over the past year several online initiatives were held to discuss this challenge. So does the European Urban Knowledge Network (EUKN) ‘Thinking Beyond the Crisis’ series, which explores the urban impacts of and responses to the coronavirus outbreak in EUKN member countries. The online webinar “Port cities and Mega-Trends: Glocal Approaches to (...) Sustainable Transitions,” - held on 26 January 2021 and organised with the French National Agency for Territorial Cohesion (ANCT) and the port city of Le Havre - offered a platform to reflect on the global impact and local effects of mega-trends on port cities, including the recent, far-reaching impacts of Covid-19. The event specifically explored the strategies and experiences of the ports of Le Havre (France), Incheon (South Korea), Rotterdam (Netherlands) and Hamburg (Germany). -/- . (shrink)

The deeper teachings of yoga state that "We are a soul, and have a body," but how do yogis respond when confronted with death-with their own time of passing? In Transitioning in Grace (based on the teachings of Paramhansa Yogananda, author of the classic Autobiography of a Yogi), Nalini Graeber presents true accounts of how longtime yogis and meditators have left their bodies. Some struggled with pain or illness. Others passed suddenly or unexpectedly. Most of these accounts are inspiring; all (...) have something to teach about the transitioning experience. More than just a collection of uplifting stories, this work can serve as a handbook for individuals helping family or friends to leave this world-for those soon to make the transition themselves-and for all thoughtful souls who recognize the wisdom of gaining important insights into early preparation for "Life's Final Exam." Included in these pages: How to prepare for death. A yogic "astral ascension" ceremony (funeral/memorial service) that can be adapted for your particular needs. A description, by a great master of yoga, of what we experience during the moments when we leave our bodies. A simple meditation technique that can help greatly to bring calmness to the event. Stories, descriptions, and poems that offer helpful insights and inspiration. (shrink)

Linguists, biological anthropologists, and cognitive scientists come together in this book to explore the origins and early evolution of phonology, syntax, and semantics. They consider the nature of pre- and proto-linguistic communication, the internal and external triggers that led to its transformation into language, and whether and how language may be considered to have evolved after its inception. Evidence is drawn from many domains, including computer simulations of language emergence, the songs of finches, problem-solving abilities in monkeys, sign language, and (...) the structure of languages today. (shrink)

In lower quadrupedal vertebrates locomotor efficiency seems to result from the associate movements of the axial and appendicular systems, which are totally independent in structure and embryological origin. The curvature of the trunk, produced by a standing wave, magnifies the propulsive action of the limbs. In intermediate forms, the association of an elongate trunk with limbs reduced in size brings about functional consequences which may be noticeably diverse according to the degree of trunk elongation and limb reduction. According to environmental (...) constraints, animals search for better locomotor efficiency, which implies the maintenance or breakage of this association of both locomotor systems. In some cases, limb action on the ground is added to the axial wave action through a perfect mutual adjustment of rhythmic activity, until mechanical inefficiency of the limbs is reached by possible loss of contact with the ground. In other cases, the limbs dragged on the ground during the stance phase act against the axial action or, on the contrary, are inhibited by the axial system. A review of available data tries to contribute to an understanding of the respective roles of both systems in the transition to limblessness. (shrink)

Natural conditions are provided that are sufficient to ensure that causality as defined by approaches that use counterfactual dependence and structural equations will be transitive.

Procrastination as putting off until tomorrow what one had intended to do today is well-known tendency in everyday life. In an attempt to understand the character of procrastination in different life-domains, a large body of research has been accumulated over the last decades. This article was aimed to evaluate a specific decisional procrastination of school-to-work transition that is treated as maturity postponement. Two studies are reported examining SWT procrastination defined as career indecision among Polish students graduating universities. In Study (...) 1, attitudinal and identity statuses were analyzed as correlates of career procrastination. A path analysis conducted for the model, which was aimed to explain the influence of career self-efficacy and occupational commitment on career indecision, revealed its very good fitness. Those two independent variables explain 10% of career indecision variance. Stepwise multiple regression analyses conducted to ascertain relationship of five identity statuses to procrastination measure showed that Commitment Making and Ruminative Exploration are strongest predictor variables. In study 2, the stepwise multiple regression analyses conducted to ascertain the independent relationship of each of Big Five personality factor revealed that Neuroticism and Extraversion accounts of the most of explained variance of school-to-work transition procrastination. (shrink)

We sketch a group-theoretical framework, based on the Heisenberg–Weyl group, encompassing both quantum and classical statistical descriptions of unconstrained, non-relativistic mechanical systems. We redefine in group-theoretical terms a kinematical arena and a space of statistical states of a system, achieving a unified quantum-classical language and an elegant version of the quantum-to-classical transition. We briefly discuss the structure of observables and dynamics within our framework.

En una aproximación cualitativa y una perspectiva analítica performativa relevamos la presencia de lenguajes musicales diversos en la educación intercultural, teniendo como caso de estudio a educadores tradicionales mapuches que incorporan dispositivos curriculares en escuelas con programas de educación intercultural bilingüe, localizadas en la ciudad de Puerto Montt. Nuestras reflexiones principales apuntan al relevamiento de estrategias etnomusicales descolonizadoras puestas en juego en el aula, en las que se evidencia la ampliación de repertorio musical en la noción tradicional del canto mapuche (...) que manifiestan los docentes. Para los y las docentes entrevistados, esta noción se abre para incluir, entre otros, algunos epewkantun, además de canciones con funciones didácticas y canciones winka, estas últimas en la forma de re-mixtura de expresiones musicales urbanas. Estas nuevas prácticas musicales apuntan a favorecer la reafirmación étnica de sus estudiantes, desde un posicionamiento de identidad mapuche urbana, en ruptura con la noción esencialista de cultura. Estas transiciones curriculares estarían constituyendo un nuevo escenario en las prácticas musicales dentro del aula intercultural, caracterizadas de manera tradicional por la incorporación de canciones políticamente ingenuas. From a qualitative approach and a performative analytical perspective, we surveyed the presence of various musical languages, taking as case of study the traditional Mapuche educators who incorporate curricular devices in schools with bilingual education programs, in Puerto Montt, Chile. Our main reflections point to survey decolonization strategies applied in the classroom, which appeal to the growth of musical repertoire extending the traditional notion of the Mapuche song. For traditional teachers, this new notion includes some epewkantun, besides songs with didactic functions, and winka songs. These new musical practices aim at favoring the ethnic reaffirmation of students from a disruptive paradigm with the essentialist notion of culture. These curricular transitions create a new framework in the musical practices in the intercultural education, characterized by the incorporation of “politically naive” songs. (shrink)

Davenport and Rudd’s 2001 publication of Kierkegaard After MacIntyre has been a catalyst for renewed interest in Kierkegaard’s Either/Or. An issue that has received special attention is the Kierkegaardian transition from the aesthetic to ethical. In this paper, I examine the most recent and notable contributions to this discussion: the work of John J. Davenport, Anthony Rudd, and John Lippitt. After drawing attention to several explanatory gaps in Davenport and Rudd, I turn to provide my own account of Kierkegaard’s (...) aesthetic-to-ethical transition, aspiring to correct certain missteps that have plagued interpretations up to this point. (shrink)

(No abstract is available for this citation).

The widespread distribution of fibroblasts underlines their central role in mammalian physiology, development and ageing. The existence of developmentally regulated and site‐specific phenotypic variation in fibroblasts is well documented. Recent evidence has revealed heterogeneity within the fibroblast population of a given tissue at a specified development stage. The relative proportion and tissue distribution of distinct fibroblast subsets must have important consequences in the control of connective tissue and adjacent epithelial functions in health and disease.

The Cambrian explosion is characterized by the sudden outburst of organized animal plans, which occurred circa 530 M years ago. Around that time, many forms of animal life appeared, including several which have since disappeared. There is no general consensus about “why” this happened, and why it had any form of suddenness. However, all organized animal plans share a common feature: they are triploblastic, i.e., composed of 3 layers of tissue, endoderm, ectoderm and mesoderm. I show here that, within simple (...) hypotheses, the formation of the mesoderm has intrinsically a physical exponential dynamics, leading rapidly to triploblastism, and eventually, to animal formation. A novel physico-mathematical framework including epithelium-mesenchyme transition, visco-elastic constitutive equations, and conservation laws, is presented which allows one to describe gastrulation as a self-wetting phenomenon of a soft solid onto itself. This phenomenon couples differentiation and migration during gastrulation, and leads in a closed form to an exponential scaling law for the formation of the mesoderm. Therefore, the Cambrian explosion might have started, actually, by a true visco-elastic “explosion”: the exponential run-away of mesenchymal cells. (shrink)