The intracellular multiprotein complex β‐catenin destruction complex plays a key role in Wnt/β‐catenin signaling. Wnt stimulation induces the assembly of the receptor‐associated signalosome and the inactivation of the destruction complex, leading to β‐catenin accumulation and transcriptional activation of the target genes. The core components of the destruction complex include Axin, APC, GSK3β, CK1α and other proteins. Recent studies demonstrated that Axin and APC undergo liquid–liquid phase separation (LLPS), which is critical for their function to regulate Wnt/β‐catenin signaling. Here, we discuss (...) the possible roles of LLPS in Wnt/β‐catenin signaling and regulation of Axin LLPS by post‐translational modifications. (shrink)

Regulation of microtubule (MT) dynamics is essential for many cellular processes, but the machinery that controls MT dynamics remains poorly understood. MT plus‐end tracking proteins (+TIPs) are a set of MT‐associated proteins that dynamically track growing MT ends and are uniquely positioned to govern MT dynamics. +TIPs associate with each other in a complex array of inter‐ and intra‐molecular interactions known as the “+TIP network.” Why do so many +TIPs bind to other +TIPs? Typical answers include the ideas that these (...) interactions localize proteins where they are needed, deliver proteins to the cortex, and/or create regulatory pathways. We propose an additional and more mechanistic hypothesis: that +TIPs bind each other to create a superstructure that promotes MT assembly by constraining the structural fluctuations of the MT tip, thus acting as a polymerization chaperone. (shrink)

Hawthorne toys with the view that ascriptions of free will are context-sensitive. But the way he formulates the view makes freedom contextualism look like a non-starter. I step into the breach for freedom contextualism. My aim is twofold. On the one hand, I argue that freedom contextualism can be motivated on the basis of our ordinary practice of freedom attribution is not ad hoc. The view explains data which cannot be accounted for by an ambiguity hypothesis. On the other hand, (...) I suggest a more plausible freedom contextualist analysis, which emerges naturally once we pair the assumption that freedom requires that the agent could have acted otherwise with a plausible semantics of "can" statements. I'll dub the resulting view Alternate Possibilities Contextualism, or APC, for short. In contrast to Hawthorne's view, APC is well-motivated in its own right, does not beg the question against the incompatibilist and delivers a context parameter which allows for a wide range of context shifts. I conclude that, far from being a non-starter, freedom contextualism sets an agenda worth pursuing. (shrink)

Australia has experienced difficulties engaging with Asia-Pacific regional integration. Despite Australian attempts to punch above its weight in regional forums and to be a regional leader, it is still not regarded as a full member or as quite fitting into the region. It is an in the Asian context, and has experienced the of being neither here nor there. The former Rudd government's proposal for an (APC) by the year 2020 was a substantive initiative in Australia's ongoing engagement with Asia. (...) It has, however, attracted a high level of criticism both at home and abroad. The main critical analysis of the proposal has focused on institutional building or architecture, or its relationship with existing regional institutions, but overlooks a host of often fraught questions about culture, norms, identities, and international power relations. The APC concept needs to be scrutinized in terms of these questions with a critical eye. This paper examines the cultural, cognitive, and normative dimensions of Rudd's proposal. It analyses four dilemmas or awkward problems that the APC faces. (shrink)

In circulation, T cells are spherical with selectin enriched dynamic microvilli protruding from the surface. Following extravasation, these microvilli serve another role, continuously surveying their environment for antigen in the form of peptide‐MHC (pMHC) expressed on the surface of antigen presenting cells (APCs). Upon recognition of their cognate pMHC, the microvilli are initially stabilized and then flatten into F‐actin dependent microclusters as the T cell spreads over the APC. Within 1–5 min, clathrin is recruited by the ESCRT‐0 component Hrs to (...) mediate release of T cell receptor (TCR) loaded vesicles directly from the plasma membrane by clathrin and ESCRT‐mediated ectocytosis (CEME). After 5‐10 min, Hrs is displaced by the endocytic clathrin adaptor epsin‐1 to induce clathrin‐mediated trans‐endocytosis (CMTE) of TCR‐pMHC conjugates. Here we discuss some of the functional properties of the clathrin machinery which enables it to control these topologically opposite modes of membrane transfer at the immunological synapse, and how this might be regulated during T cell activation. (shrink)

Somatic or inherited mutations in the adenomatous polyposis coli (APC) gene are a frequent cause of colorectal cancer in humans. APC protein has an important tumor suppression function to reduce cellular levels of the signaling protein β‐catenin and, thereby, inhibit β‐catenin and T‐cell‐factor‐mediated gene expression. In addition, APC protein binds to microtubules in vertebrate cells and localizes to actin‐rich adherens junctions in epithelial cells of the fruit fly Drosophila (Fig. 1). Very little is known, however, about the function of these (...) cytoskeletal associations. Recently, Hamada and Bienz have described a potential role for Drosophila E‐APC in cellular adhesion,1 which offers new clues to APC function in embryonic development, and potentially colorectal adenoma formation and tumor progression in humans. BioEssays 24:771–774, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

La publicación en abierto de los artículos conlleva unos gastos conocidos como cargos por procesamiento de artículos. El objetivo de este trabajo es determinar el coste de los artículos publicados en abierto mediante APC de autoría española en cinco categorías temáticas de las ciencias sociales: Humanities, Sociology, Information Science & Library Science, Education & Educational Research y Communication de la Colección Principal de la Web of Science durante el periodo 2012-2019. Se han identificado las revistas, las instituciones financiadoras y los (...) modelos de publicación más frecuentes. El estudio indica que de las 223 revistas que publicaron artículos con APC las que más lo hicieron fueron Communication & Society, Comunicar y el Profesional de la Información. El gasto total en APC fue de 481.120,4 € y el coste medio de 1.129 €. Las revistas con mayor coste fueron Computers & Education, Scientometrics y IEEE Transactions on Learnig Technologies. Los modelos de publicación más frecuentes fueron DOAJ Gold, Green Published y Green Accepted. En el 53% de los artículos constaba que la financiación procedía del gobierno de España, en el 25% de gobiernos autonómicos, en el 21% de la Unión Europea y en el 20% de las universidades. El coste medio de los APC de las publicaciones estudiadas está dentro de las cantidades habituales a nivel mundial, siendo más caros los APC en revistas con impacto más alto y en las áreas Information Science & Library Science y Sociology. Conocer los APC puede orientar las políticas y el apoyo institucional al acceso abierto y mejorar de los recursos académicos. (shrink)

Orthodox church life in Ukraine from the summer of 1941 to the spring of 1944 was characterized by a sharp confrontation between two Orthodox churches, administrative centers of which were located in Volyn, in Lutsk and Kremenets. The Autonomous Orthodox Church was headed by an archbishop Alex. After his tragic death on May 7, 1943, the APC remained virtually without a chapter, since at this time the occupation authorities abolished the traditional system of church management. The Ukrainian Autocephalous Orthodox Church (...) throughout its time was headed by an archbishop, and from May 1942 Metropolitan Polycarp. (shrink)

We prove the following theorems: (1) If X has strong measure zero and if Y has strong first category, then their algebraic sum has property s 0 . (2) If X has Hurewicz's covering property, then it has strong measure zero if, and only if, its algebraic sum with any first category set is a first category set. (3) If X has strong measure zero and Hurewicz's covering property then its algebraic sum with any set in APC ' is a (...) set in APC '. (APC ' is included in the class of sets always of first category, and includes the class of strong first category sets.) These results extend: Fremlin and Miller's theorem that strong measure zero sets having Hurewicz's property have Rothberger's property, Galvin and Miller's theorem that the algebraic sum of a set with the γ-property and of a first category set is a first category set, and Bartoszynski and Judah's characterization of SR M -sets. They also characterize the property (*) introduced by Gerlits and Nagy in terms of older concepts. (shrink)

When its atmosphere processing plant's fusion reactor exploded, it turned it into a desolate, irradiated hunk of rock uninhabitable by humans for thousands of years. The explosion was not far off from what the surviving humans in Aliens were planning anyway: nuke the site from orbit. To set the stage for considering the military decisions of Colonial Marines from an ethical perspective, strap in like it's a simulated combat drop from low orbit. This chapter looks at the Aliens future of (...) the twenty‐second century. After the first tragic encounter with the Xenos in Aliens, the remaining humans are trying to figure out their next steps in the back of the armored personnel carrier (APC). Many of the ideas being tossed around in the APC (even slimy Carter Burke's) keep the Xenos distant and so actually reduce the threat, backing the humans away from the need to make decisions in a “supreme emergency”. (shrink)

Cadherins are a large family of single‐pass transmembrane proteins principally involved in Ca2+‐dependent homotypic cell adhesion. The cadherin molecules comprise three domains, the intracellular domain, the transmembrane domain and the extracellular domain, and form large complexes with a vast array of binding partners (including cadherin molecules of the same type in homophilic interactions and cellular protein catenins), orchestrating biologically essential extracellular and intracellular signalling processes. While current, contrasting models for classic cadherin homophilic interaction involve varying numbers of specific repeats found (...) in the extracellular domain, the structure of the domain itself clearly remains the main determinant of cell stability and binding specificity. Through intracellular interactions, cadherin enhances its adhesive properties binding the cytoskeleton via cytoplasmic associated factors α‐ catenin, β‐catenin and p120ctn. Recent structural studies on classic cadherins and these catenin molecules have provided new insight into the essential mechanisms underlying cadherin‐mediated cell interaction and catenin‐mediated cellular signalling. Remarkable structural diversity has been observed in β‐catenin recognition of other cellular factors including APC, Tcf and ICAT, proteins that contribute to or compete with cadherin/catenin functioning. BioEssays 26:497–511, 2004. © 2004 Wiley Periodicals, Inc. (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)

Vittorio Guidano, fondatore della psicoterapia cognitivista post-razionalista, ha offerto alcuni spunti di riflessione sui cambiamenti del senso di identità che presumibilmente si sono succeduti nel corso delle epoche storiche in relazione ai diversi contesti di vita. Dell’interesse per questo tema testimonia una lezione, di cui l’autrice riporta alcuni stralci sinora inediti. La lezione si è tenuta a Roma, presso l’APC- Associazione di Psicoterapia Cognitiva, in data 26 gennaio del 1999, nell’ambito di un training di formazione in psicoterapia. Il tema discusso (...) è l’influenza della scrittura alfabetica nel dar forma all’esperienza umana, un argomento su cui è possibile intrecciare proficuamente le analisi di Guidano e le riflessioni di Carlo Sini. (shrink)

Die folgende Bibliographie wurde erstellt auf Anregungen mehrerer Autoren aus der ehemaligen DDR auf der vom APC organisierten Diskussionsrunde „Perspektiven der Philosophie der Chemie“ im November 1995 in der Humboldt-Universität Berlin (s. Mitteilungsblatt 1 (1995)). Im Sinne einer „unzensierten“ Bestandsaufnahme soll sie einen Überblick über chemiephilosophische Aktivitäten der DDR für sowohl systematische Anknüpfungen als auch philosophiehistorische Forschungen bieten. Unter den ebenfalls zahlreich vorliegenden chemiehistorischen Arbeiten sind nur ausgewählte begriffs-, theorien- und disziplinenhistorische sowie philosophiehistorisch relevante Texte berücksichtigt. Ebenfalls aufgenommen sind einige (...) chemiedidaktische Texte mit weltanschaulich-philosophischen oder erkenntnistheoretischen Inhalten. Das thematische Spektrum ist zwar weitgehend auf theoretisch-philosophische Fragen beschränkt, aber hierin durchaus weit gefächert. Hinsichtlich der wissenschaftlichen Originalität und Qualität sind ganz beträchtliche Differenzen festzustellen. Es bleibt dem Leser überlassen, zwischen den zahlreichen Kurzbemerkungen und Paraphrasierungen „offizieller“ Grundsätze des dialektischen Materialismus diejenigen Forschungsarbeiten zu selektieren, die eigenständig reflektierend chemiephilosophisches Neuland beschreiten und eine Grundlage für weitere Forschungen darstellen sollten. Die Bibliographie wurde z.T. aus Angaben der Autoren, überwiegend jedoch durch eigene Recherchen in Bibliographien, den Inhaltverzeichnissen diverser Zeitschriften sowie den Katalogbeständen der Deutschen Bibliothek Leipzig erstellt. Die Angaben sind zum größten Teil kontrolliert und vervollständigt. Mein Dank gilt Prof. Dr. Hubert Laitko (Berlin), Prof. Dr. Gustav Kertscher (Mühlhausen), Dr. Alfred Neubauer (Berlin), Dr. Reinhardt Pester (Berlin), Dr. habil. Horst Remane (Halle), Dr. Wolf-Dietrich Sprung (Rostock) für die Bereitstellung von Veröffentlichungsverzeichnissen sowie insbesondere Prof.. (shrink)

How can we deal with the diversity of theories in mathematics education? This was the main question that led the authors of this book to found the Networking Theories Group. Starting from the shared assumption that the existence of different theories is a resource for mathematics education research, the authors have explored the possibilities of interactions between theories, such as contrasting, coordinating, and locally integrating them. The book explains and illustrates what it means to network theories; it presents networking as (...) a challenging but fruitful research practice and shows how the Group dealt with this challenge considering five theoretical approaches, namely the approach of Action, Production, and Communication (APC), the Theory of Didactical Situations (TDS), the Anthropological Theory of the Didactic (ATD), the approach of Abstraction in Context (AiC), and the Theory of Interest-Dense Situations (IDS). A synthetic presentation of each theory and their connections shows how the activity of networking generates questions at the theoretical, methodological and practical levels and how the work on these questions leads to both theoretical and practical progress. The core of the book consists of four new networking case studies which illustrate what exactly can be gained by this approach and what kind of difficulties might arise. (shrink)

How can we deal with the diversity of theories in mathematics education? This was the main question that led the authors of this book to found the Networking Theories Group. Starting from the shared assumption that the existence of different theories is a resource for mathematics education research, the authors have explored the possibilities of interactions between theories, such as contrasting, coordinating, and locally integrating them. The book explains and illustrates what it means to network theories; it presents networking as (...) a challenging but fruitful research practice and shows how the Group dealt with this challenge considering five theoretical approaches, namely the approach of Action, Production, and Communication (APC), the Theory of Didactical Situations (TDS), the Anthropological Theory of the Didactic (ATD), the approach of Abstraction in Context (AiC), and the Theory of Interest-Dense Situations (IDS). A synthetic presentation of each theory and their connections shows how the activity of networking generates questions at the theoretical, methodological and practical levels and how the work on these questions leads to both theoretical and practical progress. The core of the book consists of four new networking case studies which illustrate what exactly can be gained by this approach and what kind of difficulties might arise. (shrink)