Growth factors and the extracellular matrix provide the environmental cues that control the proliferation of most cell types. The binding of growth factors and matrix proteins to receptor tyrosine kinases and integrins, respectively, regulates several cytoplasmic signal transduction cascades, among which activation of the mitogen-activated protein kinase cascade, ras → Raf → MEK → ERK, is perhaps the best characterized. Curiously, ERK activation has been associated with both stimulation and inhibition of cell proliferation. In this review, we summarize recent (...) studies that connect ERK signaling to G1 phase cell cycle control and suggest that the cellular response to an ERK signal depends on both ERK signal intensity and duration. We also discuss studies showing that receptor tyrosine kinases and integrins differentially regulate the ERK signal in G1 phase. BioEssays 22:818–826, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Focal adhesion kinase (FAK) is a nonreceptor protein‐tyrosine kinase implicated in controlling cellular responses to the engagement of cell‐surface integrins, including cell spreading and migration, survival and proliferation. Aberrant FAK signaling may contribute to the process of cell transformation by certain oncoproteins, including v‐Src. Progress toward elucidating the events leading to FAK activation following integrin‐mediated cell adhesion, as well as events downstream of FAK, has come through the identification of FAK phosphorylation sites and interacting proteins. A signaling partnership is formed (...) between FAK and Src‐family kinases, leading to tyrosine phosphorylation of FAK and associated ‘docking’ proteins Cas and paxillin. Subsequent recruitment of proteins containing Src homology 2 domains, including Grb2 and c‐Crk, to the complex is likely to trigger adhesion‐induced cellular responses, including changes to the actin cytoskeleton and activation of the Ras‐MAP kinase pathway. (shrink)

Walter Map was a twelfth-century courtier and royal servant. He was a prolific writer, but De Nugis Curialium is the only surviving work confidently attributed to him. The book is a collection of short stories and anecdotes about the court, religion and history. Map's references demonstrate that he read widely, not only biblical and theological works, but also classical authors such as Horace, Virgil, Ovid and Juvenal. The only surviving manuscript of the work is a fourteenth-century copy once belonging to (...) the monk John Wells of Ramsey Abbey. The Cambridge bibliographer M. R. James would have been attracted to the breadth of Map's referencing, and the author's light-hearted writing style which was intended to entertain. James' 1914 Oxford publication corrected the earlier work of Thomas Wright who published an edition for the Camden Society in 1850. (shrink)

The “Human Genome Project” was completed in 2003, shifting the focus to proteome and transcriptome research. One approach to proteomics involves the comprehensive visualization of the localization of proteins in all tissues and organs. We discuss in situ phospho‐protein atlases, which are systematized representations of the localization of proteins. Protein atlases provide important information about the identity and presence of proteins in specific organs, tissues and cells under physiological and pathological conditions. Antibody‐based immunohistochemical analysis is a powerful method for generating (...) a protein atlas. However, it is difficult to localize phosphorylated proteins under in vivo physiological conditions, even with immunohistochemistry, because these proteins tend to be dephosphorylated or phosphorylated due to the experimental manipulations. We also discuss an improved immunohistochemical method for precisely detecting phosphorylated protein, using the detection of phosphorylated ERK1/2 as an example. We consider that it is possible and useful to generate a phospho‐protein atlas. (shrink)

Activating the ERK pathway (extracellular signal‐regulated kinase pathway) has proven beneficial in several models of Huntington's disease (HD), and drugs that are protective in HD models have recently been found to activate ERK. Thus, the ERK cascade may be a potential target for therapeutic intervention in this currently untreatable disorder. HD is caused by an expanded polyglutamine repeat in the huntingtin (Htt) protein that actuates a diverse set of pathogenic mechanisms. In response to mutant Htt, ERK is activated and directs (...) a protective transcriptional response and inhibits caspase activation. Paradoxically, Htt also interferes with several signaling events of the ERK pathway. Mutant Htt compromises the ERK‐dependent transcriptional response to corticostriatal BDNF signaling. Mutant Htt also hinders glutamate uptake from the synaptic cleft by down‐regulating ERK‐dependent expression of glutamate transporters, leaving cells vulnerable to excitotoxicity. Some of this cellular complexity can be capitalized on to achieve selective activation of ERK, which can be protective. (shrink)

The mitogenic action of cytokines such as epidermal growth factor (EGF)d̊ or platelet dericed growth factor (PDGF) involves the stimulation of a signal cascade controlled by a small G protein called Ras. Mutations of Ras can cause its constitutive activation and, as a consequence, bypass the regulation of cell growth by cytokines. Both growth factor‐induced and oncogenic activation of Ras involve the conversion of Ras from the GDP‐bound (D‐Ras) to the GTP‐bound (T‐Ras) forms. T‐Ras activates a network of protein (...) class='Hi'>kinases including c‐Mos, c‐Raf‐1 and MAP kinase. Eventually the activation of MAP kinase leads to the activation of the elongation factor 4E and several transcription factors such as c‐Jun, c‐Myc and c‐Fos. There are several modulators of Ras activity, such as the GTPase activating proteins (GAP1 and NF1), which stimulate the coversion of T‐Ras to D‐Ras. A series of small NF1 fragments, which bind T‐Ras, as well as truncated forms or derivatives of c‐Raf‐1, c‐Jun and c‐Myc, are capable of blocking the T‐Ras‐activated mitogenesis in a competitive manner. These agents offer a unique opportunity to control the proliferation of T‐Ras‐associated tumors, which represent more than 30% of total human carcinomas. (shrink)

Interleukin‐15 (IL‐15) is a pleiotropic cytokine of the 4 α‐helix bundle family, which binds to a receptor complex that displays common elements with the IL‐2 receptor and a unique high‐affinity α chain. This review focuses on juxtacrine and reverse signaling levels in the IL‐15/IL‐15R system. Specifically, we discuss how agonistic stimulation of membrane‐bound IL‐15 induces phosphorylation of members of the MAP kinase family and of focal adhesion kinase (FAK), thereby upregulating processes including cytokine secretion, cell adhesion and migration. In addition, (...) we explore IL‐15 trans‐presentation and intracellular signaling, and define promising molecular targets for future pharmacological intervention in infectious diseases and immunological disorders. These frontiers in IL‐15/IL‐15Rα research serve as highly instructive examples for key concepts, unsolved problems and therapeutic opportunities in juxtacrine and reverse signaling in general. BioEssays 28: 362–377, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Fully grown Xenopus oocytes can remain in their immature state essentially indefinitely, or, in response to the steroid hormone progesterone, can be induced to develop into fertilizable eggs. This process is termed oocyte maturation. Oocyte maturation is initiated by a novel plasma membrane steroid hormone receptor. Progesterone brings about inhibition of adenylate cyclase and activation of the Mos/MEK1/p42 MAP kinase cascade, which ultimately brings about the activation of the universal M phase trigger Cdc2/cyclin B. Oocyte maturation provides an interesting example (...) of how signaling cascades entrain the cell cycle clock to environmental changes. BioEssays 21:833–842, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

The Drosophila compound eye is an excellent experimental system for analysing fate induction of identifiable single cells. Each ommatidium, a unit eye, contains eight photoreceptors (R1‐R8), and the differentiation of these photoreceptors occurs in the larval eye imaginal disc in discrete steps: first R8 is determined, then R2/R5, R3/R4, R1/R6 and finally R7. Induction of R7, in particular, has been extensively studied at the molecular level. The R8 photoreceptor presents on its surface a ligand, Bride of Sevenless, that binds and (...) activates Sevenless receptor tyrosine kinase in the R7 precursor. Autophosphorylated Sevenless initiates a Ras1‐mediated cascade, which eventually activates transcription factors in the nucleus via Raf1 and MAP kinases, resulting in R7 development. However, recent studies indicate that Sevenless (Sev) functions just to neuralize the cell and has no role in R7 fate determination per se. It appears that the R7 fate may represent the lowest rung of a ‘neuronal ground state’, which is attained without any specific inductive cue. It is plausible that the R7 precursor is actively prevented from taking on the neuronal fate and this inhibition is removed by activation of Sev. (shrink)

Stimulation of mitogenesis by the epidermal growth factor (EGF) operates through a pathway involving the receptor, the small G‐protein Ras and protein kinases of the MAP kinase cascade. It is proposed that two of the critical steps of that pathway utilize localization of components to the plasma membrane where Ras is located: recruitment of the nucleotide exchange protein Sos to the phosphorylated EGF receptor via a complex with the SH2/SH3‐containing protein Grb2 and recruitment of the protein kinase Raf to (...) activated Ras. Moreover, it is then proposed that Raf associates with the cytoskeleton at the membrane as it is being activated. Other signaling elements, including class I receptor kinases, nonreceptor tyrosine kinases and tyrosine phosphatases, are known to function at specific cellular sites. These observations have led us to propose that localization of signaling components, and particularly sites at membrane‐microfilament interfaces, play critical roles in cellular regulation. (shrink)

Stomata, the most influential components in gas exchange with the atmosphere, represent a revealing system for studying cell fate determination. Studies in Arabidopsis thaliana have demonstrated that many of the components, functioning in a signaling cascade, guide numerous cell fate transitions that occur during stomatal development. The signaling cascade is initiated at the cell surface through the activation of the membrane receptors TOO MANY MOUTHS (TMM) and/or ERECTA (ER) family members by the secretory peptide EPIDERMAL PATTERNING FACTOR1 (EPF1) and/or a (...) substrate processed proteolytically by the subtilase STOMATAL DENSITY AND DISTRIBUTION1 (SDD1) and transduced through cytoplasmic MAP kinases (YODA (YDA), MKK4/MKK5, and MPK3/MPK6) towards the nucleus. In the nucleus, these MAP kinases regulate the activity of the basic helix‐loop‐helix (bHLH) proteins SPEECHLESS (SPCH), MUTE, and FAMA, which act in concert with the bHLH‐Leu zipper protein SCREAM (SCRM) (and/or its closely related paralog, SCREAM2). This article reviews current insights into the role of this signaling cascade during stomatal development. (shrink)

Ligand binding to cellular receptors initiates a series of signal transducing cascades that are essential to cellular responses. The Ras pathway is activated in response to a variety of ligands and has been extensively studied. More recently, a novel family of transcription factors (Stats) has been found to be activated in response to many ligands. Three recent publications(1–3) have presented evidence to suggest that these two pathways converge at the level of modulation of Stat function by phosphorylation by MAP (...) class='Hi'>kinases. However, each proposes radically different models that are not easily reconciled but invite further experimentation. (shrink)

Extensive regions of chromosomes can be transcriptionally repressed through silencing mechanisms mediated by complex chromatin structures. One of the most refined molecular portraits of silenced chromatin comes from studies of the silent mating‐type loci and telomeres of S. cerevisiae. In this budding yeast, the Sir3p silent information regulator emerges as a critically important silencing component that interacts with nucleosomes and other silencing proteins. Not only is it essential for silencing, but Sir3p is also capable of spreading silenced chromatin when its (...) dosage is increased. Sir3p is a target of mitogen‐activated protein (MAP) kinase cascade regulation and has significant similarity to the Orc1p subunit of the DNA replication origin recognition complex. Thus, in concert with other silencing proteins, Sir3p appears poised to respond to cellular signals and reprogram silencing through replication‐associated assembly of repressive chromatin structures. BioEssays 20:30–40, 1998. © 1998 John Wiley & Sons, Inc. -/- . (shrink)

In the yeast Saccharomyces cerevisiae three positive transcriptional control elements are activated by stress conditions: heat shock elements (HSEs), stress response elements (STREs) and AP‐1 responsive elements (AREs). HSEs bind heat shock transcription factor (HSF), which is activated by stress conditions causing accumulation of abnormal proteins. STREs mediate transcriptional activation by multiple stress conditions. They are controlled by high osmolarity via the HOG signal pathway, which comprises a MAP kinase module and a two‐component system homologous to prokaryotic signal transducers. AREs (...) bind the transcription factor Yap1p. The three types of control elements seem to have overlapping, but distinct functions. Some stress proteins encoded by HSE‐regulated genes are necessary for growth of yeast under moderate stress, products of STRE‐activated genes appear to be important for survival under severe stress and ARE‐controlled genes may mainly function during oxidative stress and in the response to toxic conditions, such as caused by heavy metal ions. (shrink)

Recent discoveries have suggested the concept that intracellular signals are the sum of multiple, site‐specified subsignals, rather than single, homogeneous entities. In the context of cancer, searching for compounds that selectively block subsignals essential for tumor progression, but not those regulating “house‐keeping” functions, could help in producing drugs with reduced side effects compared to compounds that block signaling completely. The Ras‐ERK pathway has become a paradigm of how space can differentially shape signaling. Today, we know that Ras proteins are found (...) in different plasma membrane microdomains and endomembranes. At these localizations, Ras is subject to site‐specific regulatory mechanisms, distinctively engaging effector pathways and switching‐on diverse genetic programs to generate different biological responses. The Ras effector pathway leading to ERKs activation is also under strict, space‐related regulatory processes. These findings may open a gate for aiming at the Ras‐ERK pathway in a spatially restricted fashion, in our quest for new anti‐tumor therapies. (shrink)

Maps and mapping raise questions about models and modeling and in science. This chapter archives map discourse in the founding generation of philosophers of science (e.g., Rudolf Carnap, Nelson Goodman, Thomas Kuhn, and Stephen Toulmin) and in the subsequent generation (e.g., Philip Kitcher, Helen Longino, and Bas van Fraassen). In focusing on these two original framing generations of philosophy of science, I intend to remove us from the heat of contemporary discussions of abstraction, representation, and practice of science and thereby (...) see in a more distant and neutral light the many productive ways in which maps can stand in analytically for scientific theories and models. The chapter concludes by complementing the map analogy – i.e., a scientific theory is a map of the world – with a model analogy, viz., a scientific model is a vehicle for understanding. (shrink)

Geographic Information Science (GIS) is an interdisciplinary science aiming to detect and visually represent patterns in spatial data. GIS is used by businesses to determine where to open new stores and by conservation biologists to identify field study locations with relatively little anthropogenic influence. Products of GIS include topographic and thematic maps of the Earth’s surface, climate maps, and spatially referenced demographic graphs and charts. In addition to its social, political, and economic importance, GIS is of intrinsic philosophical interest due (...) to its methodological richness and because it is an instructive analogue to other sciences. This chapter works towards a philosophy of GIS and cartography, or PGISC. In particular, it examines practices of classifying geographic space, objects, and relations. By focusing on the use of natural kinds in data modeling and map generalization practices, I show how the making and using of kinds is contextual, fallible, plural, and purposive. (shrink)

Schönau et al. (2021) identified four dimensions of agency (authenticity, privacy, self–trust, and responsibility) that may be influenced by the use of neurotechnologies, such as deep brain stimulation (DBS) or brain–computer–interfaces (BCI). The Agency Map they proposed depicts the role of each dimension, and indicates how they may interact. The authors emphasize that a strength of their approach is that it allows to capture the agency dimensions that were previously seen as disconnected and independent as intricately interwoven parts of the (...) person’s experience. This intended unification may help to understand personal agency more fully in various contexts important in neuroethical considerations. However, what is missing in Schönau et al.’s analysis is the mechanism—the very link— by which these various dimensions can come together. As Zawadzki (2020) points out discussing his account of the self (PTS–moral aspects)—which also includes the agency dimensions indicated by Schönau et al. (both authenticity, and responsibility, but also autonomy)—what is crucial in order to unify these various dimensions is narrative. (shrink)

Phosphatidylinositol‐3‐kinases (PI3Ks) are lipid kinases that produce 3‐phosphorylated derivatives of phosphatidylinositol upon activation by various cues. These 3‐phosphorylated lipids bind to various protein effectors to control many cellular functions. Lipid phosphatases such as phosphatase and tensin homolog (PTEN) terminate PI3K‐derived signals and are critical to ensure appropriate signaling outcomes. Many lines of evidence indicate that PI3Ks and PTEN, as well as some specific lipid effectors are highly compartmentalized, either in plasma membrane nanodomains or in endosomal compartments. We examine (...) the evidence for specific recruitment of PI3Ks, PTEN, and other related enzymes to membrane nanodomains and endocytic compartments. We then examine the hypothesis that scaffolding of the sources (PI3Ks), terminators (PTEN), and effectors of these lipid signals with a common plasma membrane nanodomain may achieve highly localized lipid signaling and ensure selective activation of specific effectors. This highlights the importance of spatial regulation of PI3K signaling in various physiological and disease contexts. (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)

Wnt proteins form a family of secreted signaling proteins that play a key role in various developmental events such as cell differentiation, cell migration, cell polarity and cell proliferation. It is currently thought that Wnt proteins activate at least three different signaling pathways by binding to seven transmembrane receptors of the Frizzled family and the co-receptor LRP6. Despite our growing knowledge of intracellular components that mediate a Wnt signal, the molecular events at the membrane have remained rather unclear. Now several (...) publications1-4 indicate that Frizzled receptors are G-protein coupled and kinases were identified that phosphorylate the co-receptor LRP6. These data deepen our understanding of Wnt-mediated signal transduction and provide more insight into how specificity may be achieved. BioEssays 28: 339–343, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Homologies in amino‐acid sequence indicate that all known protein kinases share a conserved catalytic core, and, thus, belong to a related family of proteins that have evolved in part from a common ancestoral origin. This family includes cellular kinases, oncogenic viral kinases and their protooncogene counterparts, and growth factor receptors. One of the simplest and certainly the best characterized of the protein kinases at the biochemical level is the kinase that is activated in response to cAMP. (...) The properties of this cAMP‐dependent protein kinase are reviewed with particular emphasis on the features of nucleotide binding and catalytic mechanism that are likely to be shared by all protein kinases. In spite of this conserved catalytic core, these kinases vary widely in overall structure and in the mechanisms by which each is regulated, and these differences also are compared. (shrink)

Signal transduction pathways constructed around a core module of three consecutive protein kinases, the most distal being a member of the extracellular signal‐regulated kinase (ERK) family, are ubiquitous among eukaryotes. Recent work has defined two cascades activated preferentially by the inflammatory cytokines TNF‐α and IL‐1‐β, as well as by a wide variety of cellular stresses such as UV and ionizing radiation, hyperosmolarity, heat stress, oxidative stress, etc. One pathway converges on the ERK subfamily known as the ‘stress activated’ protein (...) kinases (SAPKs, also termed Jun N‐terminal kinases, JNKs), whereas the second pathway recruits the p38 kinases. Upstream inputs are diverse, and include small GTPases (primarily Rac and Cdc42; secondarily Ras) acting through mammalian homologs of the yeast Ste20 kinase, other kinase subfamilies (e.g. GC kinase) and ceramide, a putative second messenger for certain TNF‐α actions. These two cascades signal cell cycle delay, cellular repair or apoptosis in most cells, as well as activation of immune and reticuloendothelial cells. (shrink)

Intercellular signaling by growth factors, hormones and neurotransmitters produces second messenger molecules such as cyclic adenosine monophosphate (cAMP) and diacylglycerol (DAG). Protein Kinase A and Protein Kinase C are the principal effector proteins of these prototypical second messengers in certain cell types. Recently, novel receptors for cAMP and DAG have been identified. These proteins, designated EPAC (Exchange Protein directly Activated by cAMP) or cAMP‐GEF (cAMP regulated Guanine nucleotide Exchange Factor) and CalDAG‐GEF (Calcium and Diacylglycerol regulated Guanine nucleotide Exchange Factor) or (...) RasGRP (Ras Guanine nucleotide Releasing Protein) are able to mediate some of the physiologic effects of the second messengers in a protein‐kinase‐independent fashion. These proteins are exchange factors for Ras family GTPases that operate in pathways that run parallel to the classic kinase‐dependent pathways. The rapidly emerging recognition of the functions of these “non‐kinase” effectors in diverse processes such as insulin secretion, thymocyte development, asthma and malignant transformation creates new opportunities for discovery and identifies potential new therapeutic targets. BioEssays 26:730–738, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Mammalian AMP‐activated protein kinase is the central component of a protein kinase cascade which inactivates three key enzymes involved in the synthesis or release of free fatty acids and cholesterol inside the cell. The kinase cascade is activated by elevation of AMP, and perhaps also by fatty acid and cholesterol metabolites. The system may fulfil a protective function, preventing damage caused by depletion of ATP or excessive intracellular release of free lipids, a type of stress response. Recent evidence suggests that (...) it may have been in existence for at least a billion years, since a very similar protein kinase cascade is present in higher plants. This system therefore represents an early eukaryotic protein kinase cascade, which is unique in that it is regulated by intracellular metabolites rather than extracellular signals or cell cycle events. (shrink)

Neural devices have the capacity to enable users to regain abilities lost due to disease or injury – for instance, a deep brain stimulator (DBS) that allows a person with Parkinson’s disease to regain the ability to fluently perform movements or a Brain Computer Interface (BCI) that enables a person with spinal cord injury to control a robotic arm. While users recognize and appreciate the technologies’ capacity to maintain or restore their capabilities, the neuroethics literature is replete with examples of (...) concerns expressed about agentive capacities: A perceived lack of control over the movement of a robotic arm might result in an altered sense of feeling responsible for that movement. Clinicians or researchers being able to record and access detailed information of a person’s brain might raise privacy concerns. A disconnect between previous, current, and future understandings of the self might result in a sense of alienation. The ability to receive and interpret sensory feedback might change whether someone trusts the implanted device or themselves. Inquiries into the nature of these concerns and how to mitigate them has produced scholarship that often emphasizes one issue – responsibility, privacy, authenticity, or trust – selectively. However, we believe that examining these ethical dimensions separately fails to capture a key aspect of the experience of living with a neural device. In exploring their interrelations, we argue that their mutual significance for neuroethical research can be adequately captured if they are described under a unified heading of agency. On these grounds, we propose an “Agency Map” which brings together the diverse neuroethical dimensions and their interrelations into a comprehensive framework. With this, we offer a theoretically-grounded approach to understanding how these various dimensions are interwoven in an individual’s experience of agency. (shrink)

Passage through the cell cycle requires the successive activation of different cyclin‐dependent protein kinases (CDKs). These enzymes are controlled by transient associations with cyclin regulatory subunits, binding of inhibitory polypeptides and reversible phosphorylation reactions. To promote progression towards DNA replication, CDK/cyclin complexes phosphorylate proteins required for the activation of genes involved in DNA synthesis, as well as components of the DNA replication machinery. Subsequently, a different set of CDK/cyclin complexes triggers the phosphorylation of numerous proteins to promote the profound (...) structural reorganizations that accompany the entry of cells into mitosis. At present, much research is focused on elucidating the links between CDK/cyclin complexes and signal transduction pathways controlling cell growth, differentiation and death. In future, a better understanding of the cell cycle machinery and its deregulation during oncogenesis may provide novel opportunities for the diagnostic and therapeutic management of cancer and other proliferation‐related diseases. (shrink)

Provided we agree about the thing, it is needless to dispute about the terms. —David Hume, A treatise of human nature, Book 1, section VIIMap-like representations are frequently invoked as an alternative type of representational vehicle to a language of thought. This view presupposes that map-systems and languages form legitimate natural kinds of cognitive representational systems. I argue that they do not, because the collections of features that might be taken as characteristic of maps or languages do not themselves provide (...) scientifically useful information above and beyond what the individual features provide. To bring this out, I sketch several allegedly distinctive features of maps, and show how they can easily be grafted onto a simple logical language, resulting in a hybrid “manguage.” The ease with which these linguistic and map-like properties can be integrated into a single representational system raises the question of what work broader categories like language and map are doing. I maintain that, as an empirical matter of fact, they serve no particular purpose in cognitive science, and thus do not characterize distinct kinds of cognitive architectures. (shrink)

In recent years, academics and educators have begun to use software mapping tools for a number of education-related purposes. Typically, the tools are used to help impart critical and analytical skills to students, to enable students to see relationships between concepts, and also as a method of assessment. The common feature of all these tools is the use of diagrammatic relationships of various kinds in preference to written or verbal descriptions. Pictures and structured diagrams are thought to be more comprehensible (...) than just words, and a clearer way to illustrate understanding of complex topics. Variants of these tools are available under different names: “concept mapping”, “mind mapping” and “argument mapping”. Sometimes these terms are used synonymously. However, as this paper will demonstrate, there are clear differences in each of these mapping tools. This paper offers an outline of the various types of tool available and their advantages and disadvantages. It argues that the choice of mapping tool largely depends on the purpose or aim for which the tool is used and that the tools may well be converging to offer educators as yet unrealised and potentially complementary functions. (shrink)

How different neural crest derivatives differentiate in distinct embryonic locations in the vertebrate embryo is an intriguing issue. Many attempts have been made to understand the underlying mechanism of specific pathway choices made by migrating neural crest cells. In this speculative review we suggest a new mechanism for the regulation of neural crest cell migration patterns in avian and mammalian embryos, based on recent progress in understanding the expression and activity of receptor tyrosine kinases during embryogenesis. Distinct subpopulations of (...) crest‐derived cells express specific receptor tyrosine kinases while residing in a migration staging area. We postulate that the differential expression of receptor tyrosine kinases by specific subpopulations of neural crest cells allows them to respond to localized growth factor ligand activity in the embryo. Thus, the migration pathway taken by neural crest subpopulations is determined by their receptor tyrosine kinase response to the differential localization of their cognate ligand. (shrink)

The DAP (Death Associated Protein) kinase family is a novel subfamily of pro-apoptotic serine/threonine kinases. All five DAP kinase family members identified to date are ubiquitously expressed in various tissues and are capable of inducing apoptosis. The sequence homology of the five kinases is largely restricted to the N-terminal kinase domain. In contrast, the adjacent C-terminal regions are very diverse and link individual family members to specific signal transduction pathways. There is increasing evidence that DAP kinase family members (...) are involved in both extrinsic and intrinsic pathways of apoptosis and may play a role in tumor progression. This review will focus on structural composition and subcellular localization of DAP kinase family members and on signal transduction pathways leading to their activation. Potential mechanisms of DAP kinase family-mediated apoptosis will be discussed. BioEssays 23:352–358, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Map making and, ultimately, _map thinking_ is ubiquitous across literature, cosmology, mathematics, psychology, and genetics. We partition, summarize, organize, and clarify our world via spatialized representations. Our maps and, more generally, our representations seduce and persuade; they build and destroy. They are the ultimate record of empires and of our evolving comprehension of our world. This book is about the promises and perils of map thinking. Maps are purpose-driven abstractions, discarding detail to highlight only particular features of a territory. By (...) preserving certain features at the expense of others, they can be used to reinforce a privileged position. -/- _When Maps Become the World_ shows us how the scientific theories, models, and concepts we use to intervene in the world function as maps, and explores the consequences of this, both good and bad. We increasingly understand the world around us in terms of models, to the extent that we often take the models for reality. Winther explains how in time, our historical representations in science, in cartography, and in our stories about ourselves replace individual memories and become dominant social narratives—they become reality, and they can remake the world. -/- Available on The University of Chicago Press website, etc. (shrink)

"Provides an extremely valuable introduction to the work of Michel Serres for an English-speaking audience, as well as offering useful critical approaches for those already familiar with its outlines." ---Robert Harrison, Stanford University [blurb from review pending permission] The work of Michel Serres---including the books Hermes, The Parasite, The Natural Contract, Genesis, The Troubadour of Knowledge, and Conversations on Science, Culture, and Time---has stimulated readers for years, as it challenges the boundaries of science, literature, culture, language, and epistemology. The essays (...) in Mapping Michel Serres, written by the leading interpreters of his work, offer perspectives from a range of disciplinary positions, including literature, language studies, and cultural theory. Contributors include Maria Assad, Hanjo Berressem, Stephen Clucas, Steven Connor, Andrew Gibson, René Girard, Paul Harris, Marcel Hé naff, William Johnsen, William Paulson, Marjorie Perloff, Philipp Schweighauser, Isabella Winkler, and Julian Yates. (shrink)

Background The worldwide increase in older persons demands technological solutions to combat the shortage of caregiving and to enable aging in place. Smart home health technologies (SHHTs) are promoted and implemented as a possible solution from an economic and practical perspective. However, ethical considerations are equally important and need to be investigated. Methods We conducted a systematic review according to the PRISMA guidelines to investigate if and how ethical questions are discussed in the field of SHHTs in caregiving for older (...) persons. Results 156 peer-reviewed articles published in English, German and French were retrieved and analyzed across 10 electronic databases. Using narrative analysis, 7 ethical categories were mapped: privacy, autonomy, responsibility, human vs. artificial interactions, trust, ageism and stigma, and other concerns. Conclusion The findings of our systematic review show the (lack of) ethical consideration when it comes to the development and implementation of SHHTs for older persons. Our analysis is useful to promote careful ethical consideration when carrying out technology development, research and deployment to care for older persons. Registration We registered our systematic review in the PROSPERO network under CRD42021248543. (shrink)

Research over the last two decades has identified a group of meiosis‐specific proteins, consisting of budding yeast Spo13, fission yeast Moa1, mouse MEIKIN, and Drosophila Mtrm, with essential functions in meiotic chromosome segregation. These proteins, which we call meiosis I kinase regulators (MOKIRs), mediate two major adaptations to the meiotic cell cycle to allow the generation of haploid gametes from diploid mother cells. Firstly, they promote the segregation of homologous chromosomes in meiosis I (reductional division) by ensuring that sister kinetochores (...) face towards the same pole (mono‐orientation). Secondly, they safeguard the timely separation of sister chromatids in meiosis II (equational division) by counteracting the premature removal of pericentromeric cohesin, and thus prevent the formation of aneuploid gametes. Although MOKIRs bear no obvious sequence similarity, they appear to play functionally conserved roles in regulating meiotic kinases. Here, the known functions of MOKIRs are reviewed and their possible mechanisms of action are discussed. Also see the video abstract here https://youtu.be/tLE9KL89bwk. (shrink)

It is often claimed that pre-attentive vision has an ‘iconic’ format. This is seen to explain pre-attentive vision's characteristically high processing capacity and to make sense of an overlap in the mechanisms of early vision and mental imagery. But what does the iconicity of pre-attentive vision amount to? This paper considers two prominent ways of characterising pre-attentive visual icons and argues that neither is adequate: one approach renders the claim ‘pre-attentive vision is iconic’ empirically false while the other obscures its (...) ability to do the explanatory work, which motivates positing pre-attentive visual icons in the first place. With this noted, I introduce the notion of an ‘Analogue Map’ and argue that it provides a superior characterisation of pre-attentive vision's iconicity. I then argue that this forces a reassessment of debates which have traditionally presupposed the iconicity of pre-attentive vision, emphasising ramifications for the viability of a format-based perception-thought border. (shrink)

This paper presents the first bibliometric mapping analysis of the field of computer and information ethics (C&IE). It provides a map of the relations between 400 key terms in the field. This term map can be used to get an overview of concepts and topics in the field and to identify relations between information and communication technology concepts on the one hand and ethical concepts on the other hand. To produce the term map, a data set of over thousand articles (...) published in leading journals and conference proceedings in the C&IE field was constructed. With the help of various computer algorithms, key terms were identified in the titles and abstracts of the articles and co-occurrence frequencies of these key terms were calculated. Based on the co-occurrence frequencies, the term map was constructed. This was done using a computer program called VOSviewer. The term map provides a visual representation of the C&IE field and, more specifically, of the organization of the field around three main concepts, namely privacy, ethics, and the Internet. (shrink)

Computer-based argument mapping greatly enhances student critical thinking, more than tripling absolute gains made by other methods. I describe the method and my experience as an outsider. Argument mapping often showed precisely how students were erring (for example: confusing helping premises for separate reasons), making it much easier for them to fix their errors.

Three multifunctional protein kinases, cyclic AMP‐dependent protein kinase, protein kinase C, and calmodulin‐dependent protein kinase II, are involved in signal transduction in response to their respective second messengers, cyclic AMP, diacylglycerol, and Ca2+. This review will summarize the key findings on calmodulin‐dependent protein kinase II.

Medical research is widely thought to have a fundamentally therapeutic orientation, in spite of the fact that clinical research is thought to be ethically distinct from medical care. We need an entirely new conception of clinical research ethics—one that looks to science instead of the doctor‐patient relationship.

Value Sensitive Design (VSD) is an established method for integrating values into technical design. It has been applied to different technologies and, more recently, to artificial intelligence (AI). We argue that AI poses a number of challenges specific to VSD that require a somewhat modified VSD approach. Machine learning (ML), in particular, poses two challenges. First, humans may not understand how an AI system learns certain things. This requires paying attention to values such as transparency, explicability, and accountability. Second, ML (...) may lead to AI systems adapting in ways that ‘disembody’ the values embedded in them. To address this, we propose a threefold modified VSD approach: 1) integrating a known set of VSD principles (AI4SG) as design norms from which more specific design requirements can be derived; 2) distinguishing between values that are promoted and respected by the design to ensure outcomes that not only do no harm but also contribute to good; and 3) extending the VSD process to encompass the whole life cycle of an AI technology in order to monitor unintended value consequences and redesign as needed. We illustrate our VSD for AI approach with an example use case of a SARS-CoV-2 contact tracing app. (shrink)

The moral domain is broader than the empathy and justice concerns assessed by existing measures of moral competence, and it is not just a subset of the values assessed by value inventories. To fill the need for reliable and theoretically grounded measurement of the full range of moral concerns, we developed the Moral Foundations Questionnaire on the basis of a theoretical model of 5 universally available sets of moral intuitions: Harm/Care, Fairness/Reciprocity, Ingroup/Loyalty, Authority/Respect, and Purity/Sanctity. We present evidence for the (...) internal and external validity of the scale and the model, and in doing so we present new findings about morality: Comparative model fitting of confirmatory factor analyses provides empirical justification for a 5-factor structure of moral concerns; convergent/discriminant validity evidence suggests that moral concerns predict personality features and social group attitudes not previously considered morally relevant; and we establish pragmatic validity of the measure in providing new knowledge and research opportunities concerning demographic and cultural differences in moral intuitions. These analyses provide evidence for the usefulness of Moral Foundations Theory in simultaneously increasing the scope and sharpening the resolution of psychological views of morality. (shrink)