Rheumatoid arthritis (RA) may not be a multifactorial disease; it can be hypothesized that RA is developed through a series of events following a triggering event, which is the emergence of a chemokine for neutrophils in the synovium. IL‐17A, secreted by infiltrated neutrophils, stimulates synoviocytes to produce CCL20, which attracts various CCR6‐expressing cells, including Th17 cells. Monocytes (macrophages) appear after neutrophil infiltration according to the natural course of inflammation and secrete IL‐1β and TNFα. Then, IL‐17A, IL‐1β, and (...) TNFα stimulate synoviocytes to produce CCL20, amplifying the inflammation. Varieties of chemokines secreted by infiltrating cells accumulate in the synovium and induce synoviocyte proliferation by binding to the corresponding G protein‐coupled receptors, thus expanding the synovial tissue. CCL20 in this tissue attracts circulating monocytes that express both CCR6 and receptor activator of NF‐κB (RANK), which differentiate into osteoclasts in the presence of RANKL. In this way, pannus is formed, and bone destruction begins. (shrink)

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)

Immunity against SARS‐CoV‐2 that is acquired by convalescent COVID‐19 patients is examined in reference to (A) the Th17 cell generation system in psoriatic epidermis and (B) a recently discovered phenomenon in which Th17 cells are converted into tissue‐resident memory T (TRM) cells with Th1 phenotype. Neutrophils that are attracted to the site of infection secrete IL‐17A, which stimulates lung epithelial cells to express CCL20. Natural Th17 (nTh17) cells are recruited to the infection site (...) by CCL20 and expand in the presence of IL‐23. These nTh17 cells are converted to TRM cells upon encounter with SARS‐CoV‐2 and continue to exist as ex‐Th17 cells, which exert Th1‐like immunity during a memory response. G‐CSF can induce nTh17 cell accumulation at the infection site because it promotes neutrophil egress from the bone marrow. Hence, G‐CSF may be effective against COVID‐19. Administration of G‐CSF to patients infected with SARS‐CoV‐2 is worth a clinical trial. (shrink)

Nous étudions dans cet article les différentes formes de prédication seconde détachée en position initiale dans un corpus comparable composé de textes d’économie en anglais et en français. Ce corpus a été annoté sous le logiciel Analec. L’enjeu est de montrer en quoi un même phénomène syntaxique est exploité, sur le plan discursif, de façon divergente dans chacune des deux langues. Une étude qualitative et quantitative des prédications secondes du corpus montre que la prédication seconde prend le plus souvent la (...) forme d’une participiale en –ing en anglais, où elle se spécialise dans un rôle méta-énonciatif de balise textuelle pour le lecteur, ce qui n’est pas le cas en français. (shrink)

This study presents a sociological profile of Peruvian female industrialists and some narratives of their struggle for personal independence and entrepreneurial success within the context of global restructuring and local deindustrialization. The study adopts the classical definition of woman's economic independence as a result of women's participation in the world of paid labor.

Surprise is treated as an affect in Aristotelian philosophy as well as in Cartesian philosophy. In experimental psychology, surprise is considered to be an emotion. In phenomenology, it is only addressed indirectly (Husserl, Heidegger, Levinas), with the important exception of Ricoeur and Maldiney; it is reduced to a break in cognition by cognitivists (Dennett). Only recently was it broached in linguistics, with a focus on lexico-syntactic categories. As for the expression of surprise, it has been studied in connection with evidentiality (...) in languages that encode surprise morphosyntactically. However, how surprise is encoded in languages that lack an evidential morphosyntactic system has been largely unexplored. This book provides new insights into the dynamics of surprise based on a heuristic hypothesis tested against the investigation of time, language and emotion. It is intended to arouse the interest of a multidisciplinary audience keen on crossing the disciplinary borders of phenomenology, cognitive sciences, and pragmatics. The theoretical approaches adopted in this collection of articles rely on experiments and corpus data. They advance knowledge by building on robust empirical results coming from psychology, microphenomenology, linguistics and physiology. (shrink)

Melatonin is a hormone with complex roles in the pathogenesis of autoimmune disorders. Over the years, it has become clear that melatonin may exacerbate some autoimmune conditions, whereas it alleviates others such as multiple sclerosis. Multiple sclerosis is an autoimmune disorder characterized by a dysregulated immune response directed against the central nervous system. Indeed, the balance between pathogenic CD4+ T cells secreting IFN‐γ (TH1) or IL‐17 (TH17); and FoxP3+ regulatory T cells and IL‐10+ type 1 regulatory T (...) cells (Tr1 cells) is thought to play an important role in disease activity. Recent evidence suggests that melatonin ameliorates multiple sclerosis by controlling the balance between effector and regulatory cells, suggesting that melatonin‐triggered signaling pathways are potential targets for therapeutic intervention. Here, we review the available data on the effects of melatonin on immune processes relevant for MS and discuss its therapeutic potential. (shrink)

Immunity by William Paul is an overview of fundamental principles of immunology and their experimental basis. The book includes not only well- established facts about the immune system but also recent findings (the role of Th17 cells, regulatory T cells, inflammasomes, etc.), which are skillfully incorporated into the framework of immunological understanding. The presentation is clear and emotionally charged, which makes the reading of Immunity enjoyable. Despite the original intentions, though, the book may appear too challenging for (...) a lay reader to serve as a popular introduction to immunology. Instead, it may help to put already acquired immunological knowledge in order benefiting advanced biology students and researchers. At a deeper level, Immunity provokes questions concerning what counts as relevant and what counts as a landmark in immunology. (shrink)

Chemokines (chemotactic cytokines) drive and direct leukocyte traffic. New evidence suggests that the unusual CCR6/CCL20 chemokine receptor/ligand axis provides key homing signals for recently identified cells of the adaptive immune system, recruiting both pro‐inflammatory and suppressive T cell subsets. Thus CCR6 and CCL20 have been recently implicated in various human pathologies, particularly in autoimmune disease. These studies have revealed that targeting CCR6/CCL20 can enhance or inhibit autoimmune disease depending on the cellular basis of pathogenesis and the cell subtype most (...) affected through different CCR6/CCL20 manipulations. Here, we discuss the significance of this chemokine receptor/ligand axis in immune and inflammatory functions, consider the potential for targeting CCR6/CCL20 in human autoimmunity and propose that the shared evolutionary origins of pro‐inflammatory and regulatory T cells may contribute to the reason why both immune activation and regulation might be controlled through the same chemokine pathway. (shrink)

“Stem Cells Dependently Arising and Empty” May 2021, Buddhism and Culture (a Korean-language Buddhist magazine sponsored by the Foundation for the Promotion of Korean Buddhism), Korea.

Between 1940 and 1970 pioneers in the new field of cell biology discovered the operative parts of cells and their contributions to cell life. They offered mechanistic accounts that explained cellular phenomena by identifying the relevant parts of cells, the biochemical operations they performed, and the way in which these parts and operations were organised to accomplish important functions. Cell biology was a revolutionary science but in this book it also provides fuel for yet another revolution, one that (...) focuses on the very conception of science itself. Laws have traditionally been regarded as the primary vehicle of explanation, but in the emerging philosophy of science it is mechanisms that do the explanatory work. Bechtel emphasises how mechanisms were discovered, focusing especially on the way in which new instruments made these inquiries possible. He also describes how new journals and societies provided institutional structure to this new enterprise. (shrink)

Stem cell tourism is a small but growing part of the thriving global medical tourism marketplace. Much stem cell research remains at the experimental stage, with clinical trials still uncommon. However, there are over 700 clinics estimated to be operating in mostly developing countries – from Costa Rica and Argentina to China, India and Russia – that have lured many patients, mostly from industrialized countries, driven by desperation and hope, which in turn continue to fuel the growth of such tourism.While (...) much research has focused on such dimensions as the promotions that allow such businesses to make their services known, media coverage, some patient research, and regulatory conditions for developing country clinics, little attention has been paid to the non‐affected members of the general population, the future potential users of such services. This empirical study based on five focus group discussions with a diverse group of healthy adults in a Canadian city, explored participant views of patients who use stem cell tourism services, the likelihood they would avail themselves of such services if they were to suffer similar illnesses, and the conditions under which they might do so, and the impact that admonitions and advice from international expert bodies might have on their decisions. Our findings suggest that these healthy adults are sympathetic to the drivers of hope and desperation, and, despite cautions about research limitations, may seek such treatments themselves under similar conditions. These findings are discussed in the context of the policy and ethical issues raised by this form of medical tourism. (shrink)

Between 1940 and 1970 pioneers in the new field of cell biology discovered the operative parts of cells and their contributions to cell life. They offered mechanistic accounts that explained cellular phenomena by identifying the relevant parts of cells, the biochemical operations they performed, and the way in which these parts and operations were organised to accomplish important functions. Cell biology was a revolutionary science but in this book it also provides fuel for yet another revolution, one that (...) focuses on the very conception of science itself. Laws have traditionally been regarded as the primary vehicle of explanation, but in the emerging philosophy of science it is mechanisms that do the explanatory work. Bechtel emphasises how mechanisms were discovered, focusing especially on the way in which new instruments made these inquiries possible. He also describes how new journals and societies provided institutional structure to this new enterprise. (shrink)

Recent advances in stem cell research suggest that in the future it may be possible to create eggs and sperm from human stem cells through a process that we term in vitro gametogenesis (IVG). IVG would allow treatment of some currently untreatable forms of infertility. It may also allow same-sex couples to have genetically-related children. For example, cells taken from one man could potentially be used to create an egg, which could then be fertilised using naturally produced sperm (...) from another man to create a genetically-related child with half of its DNA from each of the men. In this chapter, we consider whether this technology could justifiably be denied to same-sex couples if it were made available as a fertility treatment to different-sex couples. We argue that it could not. (shrink)

In [12], P. Scowcroft and L. van den Dries proved a cell decomposition theorem for p-adically closed fields. We work here with the notion of P-minimal fields defined by D. Haskell and D. Macpherson in [6]. We prove that a P-minimal field K admits cell decomposition if and only if K has definable selection. A preprint version in French of this result appeared as a prepublication [8].

(Recipient of the 2020 Everett Mendelsohn Prize.) This article revisits the development of the protoplasm concept as it originally arose from critiques of the cell theory, and examines how the term “protoplasm” transformed from a botanical term of art in the 1840s to the so-called “living substance” and “the physical basis of life” two decades later. I show that there were two major shifts in biological materialism that needed to occur before protoplasm theory could be elevated to have equal status (...) with cell theory in the nineteenth century. First, I argue that biologists had to accept that life could inhere in matter alone, regardless of form. Second, I argue that in the 1840s, ideas of what formless, biological matter was capable of dramatically changed: going from a “coagulation paradigm” that had existed since Theophrastus, to a more robust conception of matter that was itself capable of movement and self-maintenance. In addition to revisiting Schleiden and Schwann’s original writings on cell theory, this article looks especially closely at Hugo von Mohl’s definition of the protoplasm concept in 1846, how it differed from his primordial utricle theory of cell structure two years earlier. This article draws on Lakoff and Johnson’s theory of “ontological metaphors” to show that the cell, primordial utricle, and protoplasm can be understood as material container, object, and substance, and that these overlapping distinctions help explain the chaotic and confusing early history of cell theory. (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)

The stunning possibility of “reprogramming” differentiated somatic cells to express a pluripotent stem cell phenotype (iPS, induced pluripotent stem cell) and the “ground state” character of pluripotency reveal fundamental features of cell fate regulation that lie beyond existing paradigms. The rarity of reprogramming events appears to contradict the robustness with which the unfathomably complex phenotype of stem cells can reliably be generated. This apparent paradox, however, is naturally explained by the rugged “epigenetic landscape” with valleys representing “preprogrammed” attractor (...) states that emerge from the dynamical constraints of the gene regulatory network. This article provides a pedagogical primer to the fundamental principles of gene regulatory networks as integrated dynamic systems and reviews recent insights in gene expression noise and fate determination, thereby offering a formal framework that may help us to understand why cell fate reprogramming events are inherently rare and yet so robust. (shrink)

While the clinical promise of much stem cell research remains largely theoretical, patients are nonetheless pursuing unproven stem cell therapies in jurisdictions around the world—a phenomenon referred to as “stem cell tourism.” These treatments are generally advertised on a direct-to-consumer basis via the Internet. Research shows portrayals of stem cell medicine on such websites are overly optimistic and the claims made are unsubstantiated by published evidence. However, anecdotal evidence suggests that parents are pursing these “treatments” for their children, despite potential (...) physical and financial risk. Physicians are in a unique position as they can be expected to be involved in, or privy to, such decisions. In this paper, we consider what duties physicians may have toward minor patients whose parents/guardians wish to engage in stem cell tourism on their behalf. We use the Canadian perspective to address the broadly relevant issues raised by this trend. (shrink)

Robert Sparrow has recently raised the possibility that stem cell technology could in the future be used to create multiple generations of embryos in the laboratory before transferring one embryo to a woman’s womb to create a pregnancy. Sparrow argues that any children produced in this way would be genetic orphans—they would lack living genetic parents—and explores the possible moral implications of this. A number of other authors have raised objections to Sparrow’s moral claims, but his descriptive claim remains unchallenged. (...) In this chapter, we challenge it, arguing that Sparrow’s imagined technology could be performed in such a way that the children produced would have living genetic parents. (shrink)

Talk of different types of cells is commonplace in the biological sciences. We know a great deal, for example, about human muscle cells by studying the same type of cells in mice. Information about cell type is apparently largely projectible across species boundaries. But what defines cell type? Do cells come pre-packaged into different natural kinds? Philosophical attention to these questions has been extremely limited [see e.g., Wilson (Species: New Interdisciplinary Essays, pp 187–207, 1999; Genes and (...) the Agents of Life, 2005; Wilson et al. Philos Top 35(1/2):189–215, 2007)]. On the face of it, the problems we face in individuating cellular kinds resemble those biologists and philosophers of biology encountered in thinking about species: there are apparently many different (and interconnected) bases on which we might legitimately classify cells. We could, for example, focus on their developmental history (a sort of analogue to a species’ evolutionary history); or we might divide on the basis of certain structural features, functional role, location within larger systems, and so on. In this paper, I sketch an approach to cellular kinds inspired by Boyd’s Homeostatic Property Cluster Theory, applying some lessons from this application back to general questions about the nature of natural kinds. (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)

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

Imagine cells that live in a high‐gradient magnetic field (HGMF). Through what mechanisms do the cells sense a non‐uniform magnetic field and how such a field changes the cell fate? We show that magnetic forces generated by HGMFs can be comparable to intracellular forces and therefore may be capable of altering the functionality of an individual cell and tissues in unprecedented ways. We identify the cellular effectors of such fields and propose novel routes in cell biology predicting new (...) biological effects such as magnetic control of cell‐to‐cell communication and vesicle transport, magnetic control of intracellular ROS levels, magnetically induced differentiation of stem cells, magnetically assisted cell division, or prevention of cells from dividing. On the basis of experimental facts and theoretical modeling we reveal timescales of cellular responses to high‐gradient magnetic fields and suggest an explicit dependence of the cell response time on the magnitude of the magnetic field gradient. (shrink)

The aim of this paper is to assess the relevance of somatic evolution by natural selection to our understanding of cancer development. I do so in two steps. In the first part of the paper, I ask to what extent cancer cells meet the formal requirements for evolution by natural selection, relying on Godfrey-Smith’s (2009) framework of Darwinian populations. I argue that although they meet the minimal requirements for natural selection, cancer cells are not paradigmatic Darwinian populations. In (...) the second part of the paper, I examine the most important examples of adaptation in cancer cells. I argue that they are not significant accumulations of evolutionary changes, and that as a consequence natural selection plays a lesser role in their explanation. Their explanation, I argue, is best sought in the previously existing wiring of the healthy cells. (shrink)

Programmed cell death (PCD) in unicellular organisms is in some instances an altruistic trait. When the beneficiaries are clones or close kin, kin selection theory may be used to explain the evolution of the trait, and when the trait evolves in groups of distantly related individuals, group or multilevel selection theory is invoked. In mixed microbial communities, the benefits are also available to unrelated taxa. But the evolutionary ecology of PCD in communities is poorly understood. Few hypotheses have been offered (...) concerning the community role of PCD despite its far-reaching effects. The hypothesis we consider here is that PCD is a black queen. The Black Queen Hypothesis (BQH) outlines how public goods arising from a leaky function are exploited by other taxa in the community. Black Queen (BQ) traits are essential for community survival, but only some members bear the cost of possessing them, while others lose the trait In addition, BQ traits have been defined in terms of adaptive gene loss, and it is unknown whether this has occurred for PCD. Our conclusion is that PCD fulfils the two most important criteria of a BQ (leakiness and costliness), but that more empirical data are needed for assessing the remaining two criteria. In addition, we hold that for viewing PCD as a BQ, the original BQH needs to include social traits. Thus, despite some empirical and conceptual shortcomings, the BQH provides a helpful avenue for investigating PCD in microbial communities. (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)

The research on stem cell-based therapies has greatly expanded in recent years. Our text attempts to seek those religious and ethical challenges that stem cell therapy and research bring into debate. Our thesis is that bioethics can defend its principle without a religious background. We will develop our argumentation on three major points: firstly, a comparison between secular ethics and religious views will clarify why stem cell therapy and research are important from a scientific point of view, addressing the very (...) center of the human being; in our view, being based on secular society, bioethics can answer the challenges of stem cell therapy and research; secondly, following Hans Jonas' perspective on experimenting on humans, we seek to understand the philosophical guidance that sciences dealing with stem cell need; thirdly, we will map the ethical guidelines for clinical translational research that have been adopted by the International Society for Stem Cell Research. . (shrink)

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)

What is a stem cell? The answer is seemingly obvious: a cell that is also a stem, or point of origin, for something else. Upon closer examination, however, this combination of ideas leads directly to fundamental questions about biological development. A cell is a basic category of living thing; a fundamental 'unit of life.' A stem is a site of growth; an active source that supports or gives rise to something else. Both concepts are deeply rooted in biological thought, with (...) rich and complex histories. The idea of a stem cell unites them, but the union is neither simple nor straightforward. This book traces the origins of the stem cell concept, its use in stem cell research today, and implications of the idea for stem cell experiments, their concrete results, and hoped-for clinical advances. (shrink)

Cell membranes experience frequent stretching and poking: from cytoskeletal elements, from osmotic imbalances, from fusion and budding of vesicles, and from forces from the outside. Are the ensuing changes in membrane tension localized near the site of perturbation, or do these changes propagate rapidly through the membrane to distant parts of the cell, perhaps as a mechanical mechanism of long‐range signaling? Literature statements on the timescale for membrane tension to equilibrate across a cell vary by a factor of ≈106. This (...) study reviews and discusses how apparently contradictory findings on tension propagation in cells can be evaluated in the context of 2D hydrodynamics and poroelasticity. Localization of tension in the cell membrane is likely critical in governing how membrane forces gate ion channels, set the subcellular distribution of vesicle fusion, and regulate the dynamics of cytoskeletal growth. Furthermore, in this study, it is proposed that cells can actively regulate the degree to which membrane tension propagates by modulating the density and arrangement of immobile transmembrane proteins. Also see the video abstract here https://youtu.be/T6K7AIAqqBs. (shrink)

(2013). Sickle Cell Disease and the “Difficult Patient” Conundrum. The American Journal of Bioethics: Vol. 13, No. 4, pp. 3-10. doi: 10.1080/15265161.2013.767954.

The cell is not only the structural, physiological, and developmental unit of life, but also the reproductive one. So far, however, this aspect of the cell has received little attention from historians and philosophers of biology. I will argue that cell theory had far-reaching consequences for how biologists conceptualized the reproductive relationships between germs and adult organisms. Cell theory, as formulated by Theodor Schwann in 1839, implied that this relationship was a specific and lawful one, that is, that germs of (...) a certain kind, all else being equal, would produce adult organisms of the same kind, and vice versa. Questions of preformation and epigenesis took on a new meaning under this presupposition. The question then became one of whether cells could be considered as autonomous agents producing adult organisms of a given species, or whether they were the product of external, organizing forces and thus only a stage in the development of the whole organism. This question became an important issue for nineteenth-century biology. As I will demonstrate, it was the view of cells as autonomous agents which helped both Charles Darwin and Gregor Mendel to think of inheritance as a lawful process. (shrink)

This study shows that double thymidine block treatment efficiently arrests the EO771 cells in the S‐phase without altering cell growth or survival. A long‐term analysis of cell behavior, using 5(6)‐carboxyfluorescein diacetate N‐succinimidyl ester (CFSE) staining, show synchronization to be stable and consistent over time. The EO771 cell line is a medullary breast‐adenocarcinoma cell line isolated from a spontaneous murine mammary tumor, and can be used to generate murine tumor implantation models. Different biological (serum or amino acid deprivation), physical (elutriation, (...) mitotic shake‐off), or chemical (colchicine, nocodazole, thymidine) treatments are widely used for cell synchronization. Of the different methods tested, the double thymidine block is the most efficient for synchronization of murine EO771 cells if a large quantity of highly synchronized cells is recommended to study functional and biochemical events occurring in specific points of cell cycle progression. (shrink)

The differentiation of male and female characteristics in vertebrates and insects has long been thought to proceed via different mechanisms. Traditionally, vertebrate sexual development was thought to occur in two phases: a primary and a secondary phase, the primary phase involving the differentiation of the gonads, and the secondary phase involving the differentiation of other sexual traits via the influence of sex hormones secreted by the gonads. In contrast, insect sexual development was thought to depend exclusively on cell‐autonomous expression of (...) sex‐specific genes. Recently, however, new evidence indicates that both vertebrates and insects rely on sex hormones as well as cell‐autonomous mechanisms to develop sexual traits. Collectively, these new data challenge the traditional vertebrate definitions of primary and secondary sexual development, call for a redefinition of these terms, and indicate the need for research aimed at explaining the relative dependence on cell‐autonomous versus hormonally guided sexual development in animals. (shrink)

The closely related debates concerning abortion, the protection of the embryo and stem cell science have captured the legislative agenda in Mexico in recent years. This paper examines some contemporary debates related to stem cell science and the legal and political action that has followed in the wake of the latest Supreme Court judgment on abortion, which debates are directly linked to the degrees of protection of the embryo stipulated in the Mexican Constitution. While some Mexican states have opted to (...) take no further action, others, where conservative political forces are in the majority, have been very active in seeking to ensure that their constitutions are amended to protect human life from conception onwards. This intense legislative activity has not, however, been repeated at the federal level, where there is currently no overarching national regulatory framework governing stem cell research. Although major efforts have been made by the conservative block within the Senate to bring forward legislative proposals for the prohibition of human embryonic stem cell research, and despite the public expression by the federal government of its commitment to encourage inward investment and innovation in the area of biotechnology, stem cell science has, so far, remained unregulated. The legislative challenge is to resist the pressure that has been injected by religious leaders and to act in accordance with the values and principles adopted by the community in the Mexican Constitution. In the final analysis, Mexico faces particular difficulties in accommodating conservative political forces on one hand, while recognising on the other its need, as an emerging economy, to promote a progressive approach to innovation in biotechnology. (shrink)

Ontologies of living things are increasingly grounded on the concepts and practices of current life science. Biological development is a process, undergone by living things, which begins with a single cell and (in an important class of cases) ends with formation of a multicellular organism. The process of development is thus prima facie central for ideas about biological individuality and organismality. However, recent accounts of these concepts do not engage developmental biology. This paper aims to fill the gap, proposing the (...) lineage view of stem cells as an ontological framework for conceptualizing organismal development. This account is grounded on experimental practices of stem cell research, with emphasis on new techniques for generating biological organization in vitro. On the lineage view, a stem cell is the starting point of a cell lineage with a specific organismal source, time-interval of existence, and ‘tree topology’ of branch-points linking the stem to developmental termini. The concept of ‘enkapsis’ accommodates the cell-organism relation within the lineage view; this hierarchical notion is further explicated by considering the methods and results of stem cell experiments. Results of this examination include a (partial) characterization of stem cells’ developmental versatility, and the context-dependence of developmental processes involving stem cells. (shrink)