Among emotions, surprise has been extensively studied in psychology. In linguistics, surprise, like other emotions, has mainly been studied through the syntactic patterns involving surprise lexemes. However, little has been done so far to correlate the reaction of surprise investigated in psychological approaches and the effects of surprise on language. This cross-disciplinary volume aims to bridge the gap between emotion, cognition and language by bringing together nine contributions on surprise from different backgrounds - psychology, human-agent interaction, linguistics. Using different (...) methods at different levels of analysis, all contributors concur in defining surprise as a cognitive operation and as a component of emotion rather than as a pure emotion. Surprise results from expectations not being met and is therefore related to epistemicity. Linguistically, there does not exist an unequivocal marker of surprise. Surprise may be either described by surprise lexemes, which are often associated with figurative language, or it may be expressed by grammatical and syntactic constructions. Originally published as a special issue of Review of Cognitive Linguistics 13:2 (2015). (shrink)

The stereotyped pattern of cell commitments during leech embryogenesis is described. The nature of cell commitments during segmentation differs significantly between leech and fruit fly. Despite the constancy of cell fate assignments in normal development, ablation experiments show that cell interactions are essential in setting some of these commitments. Interacting cells follow a positionally determined hierarchy of fate choices. For other cells, which appear to have fates fixed from birth, the possibility of determinative interactions between mother (...) and daughter cells is discussed. (shrink)

A considerable challenge confronts, any developing neuron. Before it can establish a functional and specific connection, it must extend an axon over tens and sometimes hundreds of microns through a complex and mutable environment to reach one out of many possible destinations. The field of axonal guidance concerns the control of this navigation process. To satisfactorily identify the cell interactions and molecular mechanisms that mediate axonal guidance, it is essential to first identify the pertinent cell populations. Embryonic surgeries (...) have provided solid information on which tissues are critical and which are irrelevant to the navigation of motor axons within the chick embryo. The gross anatomical nerve pattern is established as axons respond to both positive (path) and negative (barrier) tissue environments. Analysis of the interactions of motoneurons with these tissues reveals that several cellular interactions – chemotaxis, substratum preference, and perhaps contact paralysis – are important to the common patterns of motor axon advance. Axons simultaneously interact with population‐specific cues that have begun to be identified on the tissue level. (shrink)

DNA transfer directly from cell to cell (conjugation) is common among prokaryotes, particularly Gram‐negative bacteria like Escherichia coli. The phenomenon invariably requires a set of plasmid genes in the DNA donor cell. In addition, E. coli itself makes limited and specific contributions to the donor activity of strains carrying the conjugative plasmid F. These contributions have yet to be defined biochemically, but it is already clear that the cell envelope is an importan nexus between plasmid‐ and (...) chromosome‐encoded proteins required for the establishment and maintenance of DNA donor activity. (shrink)

Recent work by Magnuson, Solomon and Grossman(1) adds to a growing body of evidence indicating that microorganisms possess sophisticated signaling systems that enable them to sense and respond to environmental challenges. Typically, this response results in morphological, physiological and even genetic differentiation, paralleling that observed among higher organisms. These signaling systems may be interpreted as adaptations that maximize the reproductive potential of a population.

Higher plant shoot meristems are multicellular structures that are the site of postembryonic organogenesis. Analysis of chimeric plants has indicated that cells in different regions of the meristem can interact with each other so that their activities are coordinated during developmental processes. Correlations have not been demonstrated between events at a molecular level and the interactions observed at a phenotypic level in chimeras. Two recent papers(1,2) address this problem by reporting that expression of the floricaula gene in one region of (...) chimeric snapdragon meristems is sufficient to promote the transition from inflorescence to floral development and to induce the expression of the downstream organ identity genes deficiens and plena throughout the meristem. (shrink)

Epistemology of science is currently polarized. Descriptive accounts of the social aspects of science coexist uneasily with normative accounts of scientific knowledge. This tension leads students of science to privilege one of these important aspects over the other. I use an episode of recent immunology research to develop an integrative account of scientific inquiry that resolves the tension between sociality and epistemic success. The search for the hematopoietic stem cell by members of Irving Weissman’s laboratory at Stanford University Medical (...) Center exhibits both the goal-oriented character of contemporary immunology and the importance of social interactions in successful achievement of those goals. This episode includes three kinds of epistemic success: characterization of HSC, formation of new interdisciplinary interfaces, and reconciliation of apparently incompatible models. All three depend on coordinating the work of diverse participants via social interactions. Together, they reveal the crucial role of social interactions within and between research groups in producing epistemic success. These features of the search for the HSC generalize to immunology as a whole, and plausibly to other disciplines. This account thus resolves the polarizing tension in epistemology of science, and complements individualistic accounts of scientific knowledge and rationality. (shrink)

Epistemology of science is currently polarized. Descriptive accounts of the social aspects of science coexist uneasily with normative accounts of scientific knowledge. This tension leads students of science to privilege one of these important aspects over the other. I use an episode of recent immunology research to develop an integrative account of scientific inquiry that resolves the tension between sociality and epistemic success. The search for the hematopoietic stem cell (HSC) by members of Irving Weissman’s laboratory at Stanford University (...) Medical Center exhibits both the goal-oriented character of contemporary immunology and the importance of social interactions in successful achievement of those goals. This episode includes three kinds of epistemic success: characterization of HSC, formation of new interdisciplinary interfaces, and reconciliation of apparently incompatible models. All three depend on coordinating the work of diverse participants via social interactions. Together, they reveal the crucial role of social interactions within and between research groups in producing epistemic success. These features of the search for the HSC generalize to immunology as a whole, and plausibly to other disciplines. This account thus resolves the polarizing tension in epistemology of science, and complements individualistic accounts of scientific knowledge and rationality. (shrink)

The transparent sea urchin embryo provides a laboratory for study of morphogenesis. The calcareous endoskeleton is formed by a syncytium of mesenchyme cells in the blastocoel. The locations of mesenchyme in the blastocoel, the size of the skeleton, and even the branching pattern of the skeletal rods, are governed by interactions with the blastula wall. Now Guss and Ettensohn(1) show that the rate of deposition of CaCO3 in the skeleton is locally controlled in the mesenchymal syncytium, as is the pattern (...) of expression of three genes involved in skeleton formation. They propose that short range signals emanating from the blastula wall regulate many aspects of the biomineralization process. (shrink)

Multicellularity in the cellular slime mold Dictyostelium discoideum is achieved by the expression of two types of cell–cell adhesion sites. The EDTA‐sensitive adhesion sites are expressed very early in the developmental cycle and a surface glycoprotein of 24000 Da is known to be responsible for these sites. The EDTA‐resistant contact sites begin to accumulate on the cell surface at the aggregation stage of development. Several glycoproteins have been implicated in the EDTA‐resistant type of cell–cell binding (...) and the best characterized one has an Mr of 80000 (gp80). gp80 mediates cell–cell binding via homophilic interaction and its cell binding site has been mapped to an octapeptide sequence. The mechanism by which gp80 mediates cell–cell adhesion will be discussed. (shrink)

The sophisticated function of the central nervous system (CNS) is largely supported by proper interactions between neural cells and blood vessels. Accumulating evidence has demonstrated that neurons and glial cells support the formation of blood vessels, which in turn, act as migratory scaffolds for these cell types. Neural progenitors are also involved in the regulation of blood vessel formation. This mutual interaction between neural cells and blood vessels is elegantly controlled by several chemokines, growth factors, extracellular matrix, and (...) adhesion molecules such as integrins. Recent research has revealed that newly migrating cell types along blood vessels repel other preexisting migrating cell types, causing them to detach from the blood vessels. In this review, we discuss vascular formation and cell migration, particularly during development. Moreover, we discuss how the crosstalk between blood vessels and neurons and glial cells could be related to neurodevelopmental disorders. (shrink)

This essay examines the role of social interactions in the search for blood stem cells, in a recent episode of biomedical research. Linked to mid-20th century cell biology, genetics and radiation research, the search for blood stem cells coalesced in the 1960s and took a developmental turn in the late 1980s, with significant ramifications for immunology, stem cell and cancer biology. Like much contemporary biomedical research, this line of inquiry exhibits a complex social structure and includes several prominent (...) scientific successes, recognized as such by participating researchers. I use personal interviews and the published record to trace the social interactions crucial for scientific success in this episode. All recognized successes in this episode have two aspects: improved models of blood cell development, and new interfaces with other lines of research. The narrative of the search for blood stem cells thus yields a robust account of scientific success in practice, which generalizes to other scientific episodes and lends itself to expansion to include wider social contexts. (shrink)

Microfilament interactions with the plasma membranes of animal cells appear to vary with cell type and localization. In the erythrocyte, actin oligomers are associated with the membrane via spectrin and ankyrin. The ends of stress fibers in cultured cells, such as fibroblasts, are attached to the plasma membrane at focal adhesion sites and may involve the protein vinculin as a linking protein. In intestinal brush border microvilli a 110,000 dalton protein links the microfilament bundles to sites on the microvillus. (...) A transmembrane complex containing actin stably associated with a cell surface glycoprotein can be isolated from ascites tumor cell microvilli and can be obtained still associated with microfilaments by gentle extraction and gradient centrifugation of the microvilli. These varied interaction mechanisms are believed to be needed to satisfy the different structural and dynamic requirements of the particular systems. (shrink)

The PIWI-interacting RNA pathway, one of the major eukaryotic small RNA silencing pathways, is a genome surveillance system that silences selfish genes in animal gonads. piRNAs guide PIWI protein to target genes through Watson–Crick RNA–RNA base-parings. Loss of piRNA function causes genome instability, inducing failure in gametogenesis and infertility. Studies using fruit flies and mice as key experimental models have resulted in tremendous progress in understanding the mechanism underlying the piRNA pathway. Recent work using cultured silkworm germline cells has also (...) expanded our knowledge of piRNA biogenesis in particular, since these silkworm cells are the only cells of germline origin that can be cultured. In this review, we describe elucidation of the piRNA pathway using cultured silkworm cells as an experimental model by focusing on recent work in biochemistry and structural biology. Earlier studies that made important contributions to the field are also described. PIWI-interacting RNAs are germline-enriched small RNAs that silence transposons to maintain genome integrity. Recently, cultured silkworm germline cells such as BmN4 made great contributions to understand the mechanism underlying piRNA biogenesis in particular. In this review, we highlight the recent progress in biochemical and structural biology. (shrink)

Here I present and discuss a model that, among other things, appears able to describe the dynamics of cancer cell origin from the perspective of stable and unstable gene expression profiles. In identifying suchaberrantgene expression profiles as lying outside the normal stable states attracted through development and normal cell differentiation, the hypothesis explains why cancer cells accumulate mutations, to which they are not robust, and why these mutations create a new stable state far from the normal gene expression (...) profile space. Such cells are in strong contrast with normal cell types that appeared as an attractor state in the gene expression dynamical system under cell‐cell interaction and achieved robustness to noise through evolution, which in turn also conferred robustness to mutation. In complex gene regulation networks, otheraberrantcellular states lacking such high robustness are expected to remain, which would correspond to cancer cells. (shrink)

Interactions among membrane proteins regulate numerous cellular processes, including cell growth, cell differentiation and apoptosis. We need to understand which proteins interact, where they interact and to which extent they interact. This article describes a set of novel approaches to measure, on the surface of living cells, the number of clusters of proteins, the number of proteins per cluster, the number of clusters or membrane domains that contain pairs of interacting proteins and the fraction of one protein species (...) that interacts with another protein within these domains. These data can then be interpreted in terms of the function of the protein‐protein interactions. BioEssays 26:196–203, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

All the conserved detailed results of evolution stored in DNA must be read, transcribed, and translated via an RNAmediated process. This is required for the development and growth of each individual cell. Thus, all known living organisms fundamentally depend on these RNA-mediated processes. In most cases, they are interconnected with other RNAs and their associated protein complexes and function in a strictly coordinated hierarchy of temporal and spatial steps (i.e., an RNA network). Clearly, all cellular life as we know (...) it could not function without these key agents of DNA replication, namely rRNA, tRNA, and mRNA. Thus, any definition of life that lacks RNA functions and their networks misses an essential requirement for RNA agents that inherently regulate and coordinate (communicate to) cells, tissues, organs, and organisms. The precellular evolution of RNAs occurred at the core of the emergence of cellular life and the question remained of how both precellular and cellular levels are interconnected historically and functionally. RNA-networks andRNA-communication can interconnect these levels.With the reemergence of virology in evolution, it became clear that communicating viruses and subviral infectious genetic parasites are bridging these two levels by invading, integrating, coadapting, exapting, and recombining constituent parts in host genomes for cellular requirements in gene regulation and coordination aims. Therefore, a 21st century understanding of life is of an inherently social process based on communicating RNA networks, in which viruses and cells continuously interact. (shrink)

The hemolysin toxin (HlyA) is secreted across both the cytoplasmic and outer membranes of pathogenic Escherichia coli and forms membrane pores in cells of the host immune system, causing cell dysfunction and death. The processes underlying the interaction of HlyA with the bacterial and mammalian cell membranes are remarkable. Secretion of HlyA occurs without a periplasmic intermediate and is directed by an uncleaved C‐terminal targetting signal and the HlyB and HlyD translocator proteins, the former being a member (...) of a transporter superfamily central to import and export of a wide range of substrates by prokaryotic and eukaryotic cells. The separate process by which HlyA is targetted to mammalian cell membranes is dependent upon fatty acylation of a non‐toxic precursor, proHlyA. This is achieved by a novel mechanism directed by the activator protein HlyC, which binds to an internal proHlyA recognition sequence and provides specificity for the transfer of fatty acid from cellular acyl carrier protein. (shrink)

Conceptual developments have defined concrete questions about the timing and precise location of cellular pattern formation. Plants in general, and the trichomes of Arabidopsis in particular, are remarkably suited for research on these problems. Genetic analysis requires the quantitative characterizations of the developmental processes by which patterning occurs. Larkin et al.(1) have provided measures of the non‐random distances between trichomes. They have also obtained evidence about the cell lineages leading to trichome development, and this evidence constrains the possible role (...) of intracellular programs. Continued genetic analysis may call for the identification of mutations that are expressed only during development and whose effects are corrected before the phenotype matures. (shrink)

With the aid of new technologies, science has found creative ways to investigate nature. Through the use of a highly sensitive, low-noise, cooled camera, previously applied to exploring dark sky, scientific laboratories around the world have been looking at the weak emission of light from cells in a living organism. Biophoton emission, as so-called by Fritz Albert Popp, was introduced to science in the 1920s by the Russian embryologist Alexander Gurwitsh, receiving the name of mitogenetic rays. Since 1974, systematic research (...) carried out by Fritz Albert Popp and his colleagues in many parts of the world has been focused on conducting experiments and working towards a biophoton theory to inform us about its properties. One of the main hypotheses is that biophoton plays an important biological function and due to evidence of coherence of its light, i.e. a high degree of order with an extremely stable intensity (Bischof 2005), biophoton is supposed to operate as a biological laser, able to manage a network of information in the organism as well as to form electromagnetic field patterns. Interactive art based on digital technologies uses numerical data to produce interactions between our body and lit pixels on the screen. Maybe, with the correct tools and equations, data from subtle fields of energy in living systems could be used to connect different systems of information, conjugating micro and macro levels of energy. This paper intends to examine biophoton research as a possible model to interactive art and consider the way it could lead to new forms for perception and consciousness. (shrink)

The discovery and engineering of novel fluorescent proteins (FPs) from diverse organisms is yielding fluorophores with exceptional characteristics for live‐cell imaging. In particular, the development of FPs for fluorescence (or Förster) resonance energy transfer (FRET) microscopy is providing important tools for monitoring dynamic protein interactions inside living cells. The increased interest in FRET microscopy has driven the development of many different methods to measure FRET. However, the interpretation of FRET measurements is complicated by several factors including the high fluorescence (...) background, the potential for photoconversion artifacts and the relatively low dynamic range afforded by this technique. Here, we describe the advantages and disadvantages of four methods commonly used in FRET microscopy. We then discuss the selection of FPs for the different FRET methods, identifying the most useful FP candidates for FRET microscopy. The recent success in expanding the FP color palette offers the opportunity to explore new FRET pairs. (shrink)

Germ cells are cross-roads of development and evolution. They define the origin of every new generation and, at the same time, represent the biological end-product of any mature organism. Germ cells are endowed with the following capacities: to store a self-descriptive program, to accumulate a protein-synthesizing machinery, and to incorporate enough nourishment to sustain embryonic development. To accomplish this goal, germ cells do not simply unfold a pre-determined program or realize a sole instructive role. On the contrary, due to the (...) complexity of their cytoarchitecture and the nature of the soma-to-germ interactions, they are heavily involved in processes of sign recognition and meaningful tissue exploration. At each stage of their inward migration, germ plasma membranes act as semiotic interfaces allowing cells to interact with the surrounding extracellular milieu and experience the compatibility of selected developmental sequences. The question of which signaling pathways are activated at each developmental stage does not result from a strictly predetermined program instructing germ cell stemness. Rather, each developmental sequence is an open-ended semiotic relationship explored and gradually defined during evolution by the context-dependency of specific cell-to-cell interactions. In this way, any structural and functional novelty that has emerged in the course of germ cell interactions may be interpreted as an exaptation fixed in the species genome in response to specific environmental constraints. (shrink)

We examine the consequences of long-range effects on tumour cell migration. Our starting point are previous results of ours where we have shown that the migration patterns of glioma cells are best interpreted if one assumes attractive interactions between cells. Here we complement the cellular automaton model previously introduced by the assumption of the existence of a chemorepellent produced by the main bulk of large spheroids (in the hypoxic/necrotic areas). Visible effects due to the presence of such a substance (...) can be found in the density profiles of cells migrating out of a single spheroid as well as in the angular distribution of cells coming from two close-lying spheroids. These effects depend crucially on the diffusion speed of the chemorepellent. A comparison of the simulation results to experimental data of Werbowetski et al. allows to draw (tentative) conclusions on the existence of a chemorepellent and its properties. (shrink)

Research in the field of planarian regeneration on the one hand, and a general survey of embryology on the other, throw doubt upon the reality of supra-cellular controls, which are still at the basis of all modern concepts of morphogenesis. The necessity of referring to such controls, which have never been convincingly demonstrated, is probably due to the fact that two aspects of cell behaviour have been underestimated: 1) the capacity of cells to change their individualities for a time (...) independently of other cells; 2) the social behaviour of cells, which is the consequence of the reciprocal exchange of information. Pattern formation and pattern remodeling in normal development results from readjustments of cell populations to local or global changes. The common responses of cell populations to disturbances are enhanced mitotic activity, cessation of specific syntheses and cell migration. In the young embryo these may promptly restore the unity of the injured primordium, leading to so-called restitution; this is based on a normal sequence of further readjustments in the primordium. In older organisms the same responses give rise to cell interactions which may be the starting point for further sequential readjustments — in some instances these are comparable to those that originally organized the primordium in question during development. The desirability of giving up the notion of morphogenetic field is discussed. (shrink)

Rémi Tison Dans cet article, je traite de la nature des processus cognitifs sous-tendant nos attributions d’états mentaux aux animaux non humains. Selon la conception traditionnelle, nous n’avons qu’un accès indirect aux états mentaux d’autrui, qui doivent être inférés sur la base du comportement. Cette conception traditionnelle influence autant les débats conceptuels concernant l’esprit des animaux que les recherches empiriques sur la cognition animale. Or de récents travaux sur la cognition sociale humaine avancent plutôt une conception « interactionniste », selon (...) laquelle les états mentaux peuvent parfois être directement perçus dans le comportement. J’applique dans cet article la conception interactionniste à l’attribution d’états mentaux aux animaux. Je conclus que celle-ci rend mieux compte des attitudes du sens commun à l’égard des états mentaux des animaux et est plus féconde pour la recherche empirique sur la cognition animale que la conception traditionnelle. (shrink)

Cell communication is crucial for many aspects of growth and differentiation during the development of the nematode Caenorhabditis elegans. Two genes, glp‐1 and lin‐12, mediate a number of known cell–cell interactions. Genetic and molecular analyses of these two genes lead to the conclusion that they are structurally and functionally related. We summarize these studies as well as those involving the identification of other genes that interact with glp‐1 and / or lin‐12.

Research in many fields of biology has been extremely successful in decomposing biological mechanisms to discover their parts and operations. It often remains a significant challenge for scientists to recompose these mechanisms to understand how they function as wholes and interact with the environments around them. This is true of the eukaryotic cell. Although initially identified in nineteenth-century cell theory as the fundamental unit of organisms, researchers soon learned how to decompose it into its organelles and chemical constituents (...) and have been highly successful in understanding how these carry out many operations important to life. The emphasis on decomposition is particularly evident in modern cell biology, which for the most part has viewed the cell as merely a locus of the mechanisms responsible for vital phenomena. The cell, however, is also an integrated system and for some explanatory purposes it is essential to recompose it and understand it as an organized whole. I illustrate both the virtues of decomposition (treating the cell as a locus) and recomposition (treating the cell as an object) with recent work on circadian rhythms. Circadian researchers have both identified critical intracellular operations that maintain endogenous oscillations and have also addressed the integration of cells into multicellular systems in which cells constitute units. Ó 2010 Elsevier Ltd. All rights reserved. (shrink)

Variations in levels of apolipoprotein E have been tied to the risk and progression of Alzheimer's disease . Our group has previously compared and contrasted the promoters of the mouse and human ApoE gene promoter sequences and found notable similarities and significant differences that suggest the importance of the APOE promoter's role in the human disease. We examine here three specific single-nucleotide polymorphisms within the human APOE promoter region, specifically at -491 , -427 , and at -219 upstream from the (...) +1 transcription start site. The -219 and -491 polymorphic variations have significant association with instance of AD, and -491AA has significant risk even when stratified for the APOEepsilon4 allele. We also show significant effects on reporter gene expression in neuronal cell cultures, and, notably, these effects are modified by species origin of the cells. The -491 and -219 polymorphisms may have an interactive effect in addition to any independent activity. DNA-protein interactions differ between each polymorphic state. We propose SP1 and GATA as candidates for regulatory control of the -491 and -219 polymorphic sites. This work's significance lies in drawing connection among APOE promoter polymorphisms' associations with AD to functional promoter activity differences and specific changes in DNA-protein interactions in cell culture-based assays. Taken together, these results suggest that APOE expression levels are a risk factor for AD irrespective of APOEepsilon4 allele status. (shrink)

Multicellular organisms develop on a predictable schedule that depends on both cell‐intrinsic timers and sequential cell‐cell interactions mediated by extracellular signals. The interplay between intracellular timers and extracellular signals is well illustrated by the development of oligodendrocytes, the cells that make the myelin in the vertebrate central nervous system. An intrinsic timing mechanism operates in each oligodendrocyte precursor cell to limit the length of time the cell divides before terminally differentiating. This mechanism consists of two (...) components, a timing component, which depends on the mitogen platelet‐derived growth factor (PDGF) and measures elapsed time, and an effector component, which depends on thyroid hormone and stops cell division and initiates differentiation at the appropriate time. The cell‐cycle inhibitor p27/Kip1 accumulates in the precursor cells as they proliferate and is part of both components of the timer. It seems likely that similar timing mechanisms operate in other cell lineages. BioEssays 22:64–71, 2000. ©2000 John Wiley & Sons, Inc. (shrink)

The principles of automation (automatism and programming) in the unfolding of spatio-temporal patterns during animal development are deduced from experimental data reconsidered from the point of view of cell sociology. The developmental programme in the egg is not part of the genetic information but a part of the cytoplasmic information. Throughout development cells store extra-cellular information released by their neighbours in the form of cytoplasmic information. Successive determinations cannot be considered as successive reprogrammings of cells: each one consists of (...) a selection of one specific programme from the total information previously stored. This programme specifies cell interactions in the determined population as a whole; it is very imprecise and is progressively completed during the course of further differentiation by information released by neighbouring cell populations. Complicated patterns may emerge from only two homogeneous populations involved in distinct differentiation pathways and confronting each other. Consequently the egg developmental programme provides gene effectors and specific physico-chemical conditions necessary for the starting of at least two distinct differentation pathways. Experimental data suggest that there are two components in this programme. One is a molecular machinery which starts at fertilization in the whole cytoplasm. It yields two programmes of differentiation, typically first an endodermal and then an ectodermal one. The other component of the egg developmental programme, which does not require specific information, allows the interception of the first (endodermal) programme. The application of informatics to developmental automatism is discussed in the latter part of the paper. (shrink)

The expression of certain eukaryotic genes is – at least in part – controlled at the level of mRNA translation. The step of translational initiation represents the primary target for regulation. The regulation of the intracellular iron storage protein ferritin in response to iron levels provides a good example of translational control by a reversible RNA/protein interaction in the 5' untranslated region of an mRNA. We consider mechanisms by which mRNA/protein interactions may impede translation initiation and discuss recent data (...) suggesting that the ferritin example may represent the ‘tip of the iceberg’ of a more general theme for translational control. (shrink)

In 2015 the first mass migration and the first geopolitical and transnational crisis of the digital age began. This brought along the awakening of a new phase in slavery trade and trafficking of human beings (THB) at the European borders. In this article I introduce an ongoing field study I began in January 2016, in collaboration with experts from Spanish and European institutions, that so far has taken me to hotspots and borders, and to the accumulation of a vast multimedia (...) archive. This led to the creation of zonaautonomamilitarizada.eu, an immersive/360°, interactive and reactive audio-visual performative system conceptually rooted in military technologies, second-order cybernetics and mass media developments. (shrink)

The expression of products encoded by the major histocompatibility complex (MHC) on tumor cells has recently been studied extensively. It has been found that many malignant tumor cells have their MHC antigens ‘switched‐off’ but that these antigens are re‐expressed following DNA‐mediated gene transfer, with increased tumor immunogenicity as a result and the consequence that these ‘transformed’ tumor cells are rejected in vivo.: This review will discuss approaches that have been taken to induce strong tumor‐specific immunity by the manipulation of MHC (...) expression on tumor cells. (shrink)

Although interactions of proteins with glycosaminoglycans (GAGs), such as heparin and heparan sulphate, are of great biological importance, structural requirements for protein‐GAG binding have not been well‐characterised. Ionic interactions are important in promoting protein‐GAG binding. Polyelectrolyte theory suggests that much of the free energy of binding comes from entropically favourable release of cations from GAG chains. Despite their identical charges, arginine residues bind more tightly to GAGs than lysine residues. The spacing of these residues may determine protein‐GAG affinity and specificity. (...) Consensus sequences such as XBBBXXBX, XBBXBX and a critical 20 Å spacing of basic residues are found in some protein sites that bind GAG. A new consensus sequence TXXBXXTBXXXTBB is described, where turns bring basic interacting amino acid residues into proximity. Clearly, protein‐GAG interactions play a prominent role in cell‐cell interaction and cell growth. Pathogens including virus particles might target GAG‐binding sites in envelope proteins leading to infection. BioEssays 20:156–167, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

Cell adhesion complexes are critical for the physical coordination of cell–cell interactions and the morphogenesis of tissues and organs. Many adhesion receptors are anchored to the plasma membrane by a glycosylphosphatidylinositol (GPI) moiety and are thereby partitioned into membrane rafts. In this review, we focus on reciprocal interactions between rafts and adhesion molecules, leading to receptor clustering and raft expansion and stability. A model for a three‐stage adhesion complex assembly process is also proposed. First, GPI‐anchored adhesion molecules (...) are recruited into rafts, which in turn promote receptor cis‐oligomerization and thereby produce precursory complexes primed for avid trans‐interactions. Second, trans‐interactions of the receptors cross‐link and stabilize large amalgams of rafts at sites of adhesion complex assembly. Finally, the enlarged and stabilized rafts acquire enhanced abilities to recruit the cytoskeleton and induce signaling. This process exemplifies how the domain structure of the plasma membrane can impact the function of its receptors. BioEssays 24:996–1003, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

Much of the current research in regenerative medicine concentrates on stem-cell therapy that exploits the regenerative capacities of stem cells when injected into different types of human tissues. Although new therapeutic paths have been opened up by induced pluripotent cells and human mesenchymal cells, the rate of success is still low and mainly due to the difficulties of managing cell proliferation and differentiation, giving rise to non-controlled stem cell differentiation that ultimately leads to cancer. Despite being still (...) far from becoming a reality, these studies highlight the role of physical and biological constraints (e.g., cues and morphogenetic fields) placed by tissue microenvironment on stem cell fate. This asks for a clarification of the coupling of stem cells and microenvironmental factors in regenerative medicine. We argue that extracellular matrix and stem cells have a causal reciprocal and asymmetric relationship in that the 3D organization and composition of the extracellular matrix establish a spatial, temporal, and mechanical control over the fate of stem cells, which enable them to interact and control (as well as be controlled by) the cellular components and soluble factors of microenvironment. Such an account clarifies the notions of stemness and stem cell regeneration consistently with that of microenvironment. (shrink)

Recent developments in 3D cultures exploiting the self‐organization ability of pluripotent stem cells have enabled the generation of powerful in vitro systems termed brain organoids. These 3D tissues recapitulate many aspects of human brain development and disorders occurring in vivo. When combined with improved differentiation methods, these in vitro systems allow the generation of more complex “assembloids,” which are able to reveal cell diversities, microcircuits, and cell–cell interactions within their 3D organization. Here, the ways in which human (...) brain organoids have contributed to demystifying the complexities of brain development and modeling of developmental disorders is reviewed and discussed. Furthermore, challenging questions that are yet to be addressed by emerging brain organoid research are discussed. (shrink)

Cell communication plays a key role in multicellular organisms. In developing embryos as in adult organisms, cells communicate by coordinating their differentiation through the establishment and/or renewal of a variety of cell communication channels. Under both these conditions, cells interact by either receptor signalling, surface recognition of specific cell adhesion molecules or transfer of cytoplasmic components through junctional coupling. In recent years, it has become apparent that cells may also communicate through the extracellular release of microvesicles. They (...) may originate as either exosomes from the endosomal compartment upon fusion of multivesicular bodies with the plasma membrane or be shed directly from the plasma membrane via extensions of the cell surface. Microvesicles may disperse over long distances through body fluids and deliver their molecular cargo onto a variety of target cells. As a general rule, the metabolic fate of these cells is determined by the molecular nature of the vesicular cargo, while targeting itself depends on the affinity of the molecules expressed on the enclosing membrane. In this paper, we will be arguing that intercellular vesicular transfer is substantially different from other types of cell communication, allowing cells and molecules to interact on varying levels. Cells interacting via ligand signalling owe their specificity to the steric coupling with cognate receptor molecules. As such, it is a pure molecular process that affects target cells only upon integration into their responding repertoire. In this relationship, coupled cells are reciprocally adapted to each other through the selection of their respective signalling capacities, following exploration of their receptor specificity. Interaction by intercellular vesicles realizes a substantially different type of cell communication. Vesicular traffic allows donor cells to carry out a horizontal type of gene transfer and target this information over long distances via independently controlled mechanisms. Because of this independence, cells interacting via vesicular traffic are not expected to adapt their signalling correspondences, but to control instead the efficiency of their cargo delivery irrespective of the receptor repertoire expressed by the target tissue. In this paper, the multifaceted functions of the intercellular vesicular traffic will be discussed in a multilevel biosemiotic perspective with the aim of unravelling the cellular mechanisms devised by nature to accomplish communication. (shrink)

Embryogenesis requires the precise movement and reorganization of many cell and tissue types. Presumably, cell surface receptors allow cells to interact selectively with adjacent cells and with the extracellular environment, as well as initiate differentiative events by transducing appropriate signals across the plasma membrane. One cell surface component that serves as a receptor during a variety of cellular interactions is β1,4‐galactosyltransferase. Cell surface galactosyltransferase participates in diverse cellular interactions by binding its specific glycoconjugate substrate on adjacent (...) cell surfaces or in the extracellular matrix. Biochemical, immunological, and molecular probes are being used to better define cell surface galactosyl‐transferase functional in cellular interactions during fertilization, intercellular adhesion, cell migration, and growth control. (shrink)

Since their derivation, human embryonic stem (hES) cells have been used for a variety of applications including developmental biology, pathology, chemical biology, genomics, and proteomics. However, their most important potential application is the generation of cells and tissues, which can be used for cell‐based therapies. One of the main drawbacks of hES cell culture is that they are particularly sensitive to dissociation, which is required for passaging, expansion, cryopreservation, and other applications. Recently, it has been discovered that an (...) inhibitor of Rho kinase (ROCKi; Y‐27632) increases the survival rate of dissociated, single hES cells. This breakthrough has allowed new methods in hES cell culture to be developed, with the promise of increasing hES cell numbers into the realm of clinical relevance. In our studies demonstrating that ROCKi dramatically increases hES cell cryopreservation efficiency, we have observed that ROCKi treatment does not decrease hES cell's susceptibility to apoptosis. Rather, we hypothesize that ROCKi treatment desensitizes single hES cells to their environment reducing the odds that individual cells will undergo anoikis. (shrink)

The role of fixed charges present at the surface of biological membranes is usually described by the Gouy-Chapman-Grahame theory of the electric double-layer where the Grahame equation is applied independently on each side of the membrane and where the capacitive charges are disregarded. In this article, we generalize the Gouy-Chapman-Grahame theory by taking into account both intrinsic charges and capacitive charges, in the density value of the membrane surface charges. In the first part, we show that capacitive charges couple electrostatic (...) potentials present on both sides of the membrane. The intensity of this coupling depends both on the value of the membrane specific capacitance and the transmembrane electric potential difference. In the second part, we suggest some physiological implications of membrane electric double-layers. (shrink)

Stem cell research has entered the public consciousness through the media. Proponents and opponents of all such research, or of human embryonic stem cell research specifically, engage in heated exchanges in the modern public forum where stakeholders negotiate, the agora. One common claim that emerges from the fray is that a particular type of stem cell research should be pursued as the most promising path toward the reduction of suffering and untimely death for all of humanity. Upon (...) evaluation, experimental data regarding the potential role of stem cells in regenerative therapies for three conditions—spinal cord injury, type 1 diabetes, and cardiovascular disease—tell distinct, complex, and inconclusive stories. Further analyses in this article incorporate realistic considerations of a broad range of relevant factors--limited funding for biomedical research, media motives, the discordance hypothesis of evolutionary medicine, the relationship between religion and science, medical care in developing nations, and culture wars over abortion. Holistic investigation inspired by the current agora conversation supports the need to drastically change interactions regarding stem cell research so that its potential to benefit humanity may be more fully realized. (shrink)

Development and maintenance of diverse organ systems require context‐specific regulation of stem cell behaviour. We hypothesize that this is achieved via reciprocal regulation between the cell cycle machinery and differentiation factors. This idea is supported by the parallel evolutionary emergence of differentiation pathways, cell cycle components and complex multicellularity. In addition, the activities of different cell cycle phases have been found to bias cells towards stem cell maintenance or differentiation. Finally, several direct mechanistic links between (...) these two processes have been established. Here, we focus on interactions between cyclin‐CDK complexes and differentiation regulators of the Notch pathway and Sox family of transcription factors within the context of pluripotent and neural stem cells. Thus, this hypothesis formalizes the links between these two processes as an integrated network. Since such factors are common to all stem cells, better understanding their interconnections will help to explain their behaviour in health and disease. (shrink)

New molecular markers for epidermal stem cells have enabled their isolation both in vitro and from the epidermis lying between hair follicles. Micro‐dissection experiments have localised a second population of stem cells within hair follicles. Epidermal stem cells have a patterned distribution in vivo. The patterning can be reconstituted in vitro, showing that it is generated by interactions between keratinocytes and that the differentiation of epidermal stem cells is regulated by signals from other keratinocytes. Recent evidence from transgenic mice suggests (...) that stem cell behaviour in the gut may be regulated by similar cell‐cell interactions in vivo. Candidate genes for mediating these interactions are the homologues of Drosophila cell fate patterning genes such as Notch and Wingless and the Cadherin family of cell‐cell adhesion molecules. The roles of stem cells and of mutations of the Patched gene in epithelial carcinogenesis are discussed. (shrink)

The mode and timing of germ-cell specification has been studied in diverse organisms, however, the molecular mechanism regulating germ-cell-fate determination remains to be elucidated. In some model organisms, maternal germ-cell determinants play a key role. In mouse embryos, some germ-line-specific gene products exist as maternal molecules and play critical roles in a pluripotential cell population at preimplantation stages. From those cells, primordial germ cells (PGCs) are specified by extracellular signaling mediated by tissue, as well as (...) class='Hi'>cell–cell interaction during gastrulation. Thus, establishment of germ-cell lineage in mammalian embryos appears to be regulated by a multistep process, including formation and maintenance of a pluripotential cell population, as well as specification of PGCs. PGCs can be generated from pluripotential embryonic stem (ES) cells in a simple monolayer culture in which tissue interaction does not occur. This raises the possibility that ES cells, as well as, possibly, pluripotential cells in preimplantation embryos, are more closely related to the PGC precursors than pluripotential cells after implantation. BioEssays 27:136–143, 2005. © 2005 Wiley Periodicals, Inc. (shrink)