Replication time is among the most important components of a bacterial cell's reproductive fitness. Paradoxically, larger cells replicate in less time than smaller cells despite the fact that assembling a larger cell requires collecting and combining increased quantities of raw materials. This feat is accomplished through the prodigious use of parallel processing, chiefly the translation of mRNA into protein by tens of thousands of ribosomes acting in parallel. The massive over-expression of ribosomes permits protein synthesis, the limiting step (...) in replication, to occur at a rate and scale that would be otherwise impossible. In computer science, spatial parallelism is the distribution of work across the nodes of a distributed-memory multicomputer system. Despite the fact that a non-negligible fraction of artificial life research is grounded in spatially parallel substrates, there have been no examples of artificial organisms that exploit spatial parallelism to replicate in less time than smaller organisms. This paper describes artificial cells defined in a combinator-based artificial chemistry that replicate in less time than smaller cells. This is achieved by employing extra copies of programs implementing the limiting steps in the process used by the cells to synthesize their component parts. (shrink)

Estimation of the repartition of asynchronous cells in the cell cycle can be explained by two hypotheses:– - the cells are supposed to be distributed into three groups: cells with a 2c DNA content (G0/1 phase), cells with a 4c DNA content (G2+M phase) and cells with a DNA content ranging from 2c to 4c (S phase); – - there is a linear relationship between the amount of fluorescence emitted by the fluorescent probe which reveals the DNA and (...) the DNA content. According to these hypotheses, the cell cycle can be represented by the following equation. (shrink)

Polyploid cells contain multiple copies of all chromosomes. Polyploidization can be developmentally programmed to sustain tissue barrier function or to increase metabolic potential and cell size. Programmed polyploidy is normally associated with terminal differentiation and poor proliferation capacity. Conversely, non‐programmed polyploidy can give rise to cells that retain the ability to proliferate. This can fuel rapid genome rearrangements and lead to diseases like cancer. Here, the mechanisms that generate polyploidy are reviewed and the possible challenges upon polyploid cell (...) division are discussed. The discussion is framed around a recent study showing that asynchronous cell cycle progression (an event that is named “chronocrisis”) of different nuclei from a polyploid cell can generate DNA damage at mitotic entry. The potential mechanisms explaining how mitosis in non‐programmed polyploid cells can generate abnormal karyotypes and genetic instability are highlighted. (shrink)

During embryogenesis, cell division must be spatially and temporally regulated with respect to other developmental processes. Leech embryos undergo a series of unequal and asynchronous cleavages to produce individually recognizable cells whose lineages, developmental fates and cell cycle properties have been characterized. Thus, leech embryos provide an opportunity to examine the regulation of cell division at the level of individual well‐characterized cells within a community of different types of cells. Isolation of leech homologues of some of (...) the highly conserved regulators of the cell division cycle, and characterization of their patterns of maternal and zygotic expression, indicate that the cell divisions of early leech embryos are regulated by cell type‐specific mechanisms. These studies with leech embryos contribute to the emerging appreciation of the diverse mechanisms by which animals regulate cell division during early development. (shrink)

In many animals, early development of the embryo is characterized by synchronous, biphasic cell divisions. These cell divisions are controlled by maternally inherited proteins and RNAs. A critical question in developmental biology is how the embryo transitions to a later pattern of asynchronous cell divisions and transfers the prior maternal control of development to the zygotic genome. The most‐common model regarding how this transition from maternal to zygotic control is regulated posits that this is a consequence (...) of the limitation of maternal gene products, due to their titration during early cell divisions. Here we discuss a recent article by Crest et al.1 that instead proposes that the balance of Cyclin‐dependent Kinase 1 and Cyclin B (Cdk1‐CycB) activity relative to that of the Drosophila checkpoint kinase Chk1 determines when asynchronous divisions begin. BioEssays 29:949–952, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The development of T cells and B cells from pluripotent hematopoietic precursors occurs through a stepwise narrowing of developmental potential that ends in lineage commitment. During this process, lineage-specific genes are activated asynchronously, and lineage-inappropriate genes, although initially expressed, are asynchronously turned off. These complex gene expression events are the outcome of the changes in expression of multiple transcription factors with partially overlapping roles in early lymphocyte and myeloid cell development. Key transcription factors promoting B-cell development and candidates (...) for this role in T-cell development are discussed in terms of their possible modes of action in fate determination. We discuss how a robust, stable, cell-type–specific gene expression pattern may be established in part by the interplay between endogenous transcription factors and signals transduced by cytokine receptors, and in part by the network of effects of particular transcription factors on each other. BioEssays 21:726–742, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Recent studies indicate that mammalian chromosomes contain discretecis‐acting loci that control replication timing, mitotic condensation, and stability of entire chromosomes. Disruption of the large non‐coding RNA gene ASAR6 results in late replication, an under‐condensed appearance during mitosis, and structural instability of human chromosome 6. Similarly, disruption of the mouse Xist gene in adult somatic cells results in a late replication and instability phenotype on the X chromosome. ASAR6 shares many characteristics with Xist, including random mono‐allelic expression and asynchronous replication (...) timing. Additional “chromosome engineering” studies indicate that certain chromosome rearrangements affecting many different chromosomes display this abnormal replication and instability phenotype. These observations suggest that all mammalian chromosomes contain “inactivation/stability centers” that control proper replication, condensation, and stability of individual chromosomes. Therefore, mammalian chromosomes contain four types ofcis‐acting elements, origins, telomeres, centromeres, and “inactivation/stability centers”, all functioning to ensure proper replication, condensation, segregation, and stability of individual chromosomes. (shrink)

This paper extends a stochastic theory for buffer fill distribution for multiple “on‘ and “off‘ sources to a mobile environment. Queue fill distribution is described by a set of differential equations assuming sources alternate asynchronously between exponentially distributed periods in “on‘ and “off‘ states. This paper includes the probabilities that mobile sources have links to a given queue. The sources represent mobile user nodes, and the queue represents the capacity of a switch. This paper presents a method of analysis which (...) uses mobile parameters such as speed, call rates per unit area, cell area, and call duration and determines queue fill distribution at the ATM cell level. The analytic results are compared with simulation results. (shrink)

Zygote cytokinesis produces two symmetric blastomeres, which contain one copy of each parental genome. Contrary to this dogma, we recently discovered that mammalian zygotes can spontaneously segregate entire parental genomes into different blastomeres and coined this novel form of genome segregation heterogoneic division. The molecular mechanisms underlying the emergence of blastomeres with different parental genomes during the first mitotic cycle remain to be elucidated. Here, we speculate on which parental genome asymmetries could provide a mechanistic foundation for these remarkable zygote (...) divisions. In reviewing the field and considering our findings, we revisit the architecture of the first zygotic metaphase by invoking asymmetric interactions between the mitotic spindle and the parental kinetochores. We also speculate on how asynchronous parental cell cycles can be a source of heterogoneic zygote divisions through the formation of parental genome private spindles. (shrink)

The organisation of mammalian mitochondrial DNA (mtDNA) is more complex than usually assumed. Despite often being depicted as a simple circle, the topology of mtDNA can vary from supercoiled monomeric circles over catenanes and oligomers to complex multimeric networks. Replication of mtDNA is also not clear cut. Two different mechanisms of replication have been found in cultured cells and in most tissues: a strand‐asynchronous mode involving temporary RNA coverage of one strand, and a strand‐coupled mode rather resembling conventional nuclear (...) DNA replication. In addition, a recombination‐initiated replication mechanism is likely to be associated with the multimeric mtDNA networks found in human heart. Although an insight into the general principles and key factors of mtDNA organisation and maintenance has been gained over the last few years, there are many open questions regarding replication initiation, termination and physiological factors determining mtDNA organisation and replication mode. However, common themes in mtDNA maintenance across eukaryotic kingdoms can provide valuable lessons for future work. (shrink)

Reinvention of the form of expression is a conceptual approach characteristic for the evolution of all arts. This research study provides one such step forward in the advancement of scientific paper, a standard form of expression in natural sciences, toward more progressive terrains. The paper adopts the form of a theatrical play where a scientific family of four attempts to find the way around a writer’s block (Act I). Their idealess sense of confinement is overcome through arts or, more specifically, (...) through scientific research implementing the aesthetics of music as its key element. The characters record compositions differing in the degrees of consonance, rhythmicity and tonality, and play them to birds to observe their vocal and behavioral responses (Act II). They note that the birdsong volume drops significantly when the piano tunes, especially the compositionally complex ones, are played to the birds and increases signifcantly when the white noise of ocean waves is played. The bird count experiment proves indirectly that the birdsong volume reduction is an auditory response of the birds to music rather than the effect of their migrating to or away from the sound source. This science with the flavor of art elevates the characters beyond the limits of their confinement and they, exalted and uplifted, gain ideas for creative research in their own disciplines of biomedical science (Act III). They relinquish the newly gained freedom in favor of embracing love for humanity that underlies medical research and return to their confinement, where they conduct, in the coda of the paper, a series of experiments that venture beyond musicology and ornithology and fall in the domains of tissue engineering and drug delivery, but also psychology (Act III). First, sparrow nests are used as templates for tissue engineering constructs, which facilitate the growth of human fibroblastic cells better than their artificial, gridded replicas. Next, the shell of an Easter egg, predominantly calcite in composition, is used with success as a drug delivery carrier. Lastly, the bird nest drawing experiment demonstrates a greater mental health of children than that of the adults, correlating with one of the overarching points of the paper, which is to present children as a model for grownups to follow rather than the other way around. Over the course of the play, the characters discuss the value of the various fusions between art and science, question the limits of human language and repeatedly go off-topic to celebrate the freeness of the creative thinking process. The play reports on real-life research methods and scientific results through a narrative, without diminishing their empirical rigor and analytical accuracy. (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)

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)

Biological atomism postulates that all life is composed of elementary and indivisible vital units. The activity of a living organism is thus conceived as the result of the activities and interactions of its elementary constituents, each of which individually already exhibits all the attributes proper to life. This paper surveys some of the key episodes in the history of biological atomism, and situates cell theory within this tradition. The atomistic foundations of cell theory are subsequently dissected and discussed, (...) together with the theory’s conceptual development and eventual consolidation. This paper then examines the major criticisms that have been waged against cell theory, and argues that these too can be interpreted through the prism of biological atomism as attempts to relocate the true biological atom away from the cell to a level of organization above or below it. Overall, biological atomism provides a useful perspective through which to examine the history and philosophy of cell theory, and it also opens up a new way of thinking about the epistemic decomposition of living organisms that significantly departs from the physicochemical reductionism of mechanistic biology. (shrink)

The article focuses on a method for collecting qualitative data. The method is the asynchronous email interview. The authors assess the advantages, challenges and best practices of the asynchronous email interview method. They base their assessment on the academic literature and their own experiences using this data collection method in qualitative research on women who had experienced perinatal loss. The asynchronous email interview will never fully replace traditional face-to-face interviews, but it could gain a solid position as (...) a qualitative research method thanks to its unique benefits. (shrink)

The present study aimed to integrate findings from technology acceptance research with research on applicant reactions to new technology for the emerging selection procedure of asynchronous video interviewing. One hundred six volunteers experienced asynchronous video interviewing and filled out several questionnaires including one on the applicants’ personalities. In line with previous technology acceptance research, the data revealed that perceived usefulness and perceived ease of use predicted attitudes toward asynchronous video interviewing. Furthermore, openness revealed to moderate the relation (...) between perceived usefulness and attitudes toward this particular selection technology. No significant effects revealed for computer self-efficacy, job interview self-efficacy, extraversion, neuroticism, and conscientiousness. Theoretical and practical implications are discussed. (shrink)

Stem cell-based human embryo models (SCBEMs), generated in vitro from stem cells, currently exist outside the scope of regulatory frameworks that govern in vitro embryo research in most jurisdictions. A widely discussed proposal suggests using a "Turing test" framework, whereby regulatory oversight is triggered if a SCBEM is found to be “equivalent” to a human embryo. In this paper, we argue that such a proposal faces two major complications. First, sophisticated laboratory techniques such as trophoblast replacement allow researchers to (...) manipulate normal embryogenesis, obscuring whether a given SCBEM meets embryo-like regulatory thresholds. Second, attempts to assess SCBEMs’ developmental potential—especially through non-human analogues—rest on tenuous epistemic assumptions that may not align with human-specific developmental trajectories. Given SCBEMs’ potential manipulability and uncertain biological and potentiality benchmarks, we argue that reliance on equivalence-based frameworks alone is highly problematic. We conclude by urging a cautious, flexible approach that recognizes both the scientific promise of SCBEMs and the normative need to prevent the circumvention of regulatory safeguards. (shrink)

Embryonic Stem Cell Research raises ethical issues. In the process of research, embryos may be destroyed and, to some, such an act entails the ‘killing of human life’. Past studies have sought the views of scientists and the general public on the ethics of ESCR. This study, however, explores multi-faith ethical viewpoints, in particular, those of Buddhists, Hindus and Catholics in Malaysia, on ESCR. Responses were gathered via semi-structured, face-to-face interviews. Three main ethical quandaries emerged from the data: sanctity (...) of life, do no harm, and ‘intention’ of the research. Concerns regarding the sanctity of life are directed at particular research protocols which interfere with religious notions of human ensoulment and early consciousness. The principle of ‘do no harm’ which is closely related to ahimsa prohibits all acts of violence. Responses obtained indicate that respondents either discourage research that inflicts harm on living entities or allow ESCR with reservations. ‘Intention’ of the research seems to be an interesting and viable rationale that would permit ESCR for the Buddhists and Hindus. Research that is intended for the purpose of alleviating human suffering is seen as being ethical. This study also notes that Catholics oppose ESCR on the basis of the inviolability of human life. (shrink)

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)

Despite the therapeutic potential of human embryonic stem (HES) cells, many people believe that HES cell research should be banned. The reason is that the present method of extracting HES cells involves the destruction of the embryo, which for many is the beginning of a person. This paper examines a number of compromise solutions such as parthenogenesis, the use of defective embryos, genetically creating a "pseudo embryo" that can never form a placenta, and determining embryo death, and argues that (...) none of these proposals are likely to satisfy embryoists, that is, those who regard the embryo as a person. This paper then proposes a method of extracting HES cells, what might be called the Blastocyst Transfer Method, that meets the ethical requirements of embryoists, and it considers some possible concerns regarding this method. It concludes by encouraging future HES cell research to investigate this method. (shrink)

Stem cell biology is driven by experiment. Its major achievements are striking experimental productions: "immortal" human cell lines from spare embryos (Thomson et al. 1998); embryo-like cells from "reprogrammed" adult skin cells (Takahashi and Yamanaka 2006); muscle, blood and nerve tissue generated from stem cells in culture (Lanza et al. 2009, and references therein). Well-confirmed theories are not so prominent, though stem cell biologists do propose and test hypotheses at a profligate rate. 1 This paper aims to (...) characterize the role of experiment in stem cell biology, so as to answer the following question: how do experiments contribute to our knowledge of stem cells and related phenomena? The .. (shrink)

Cell biologists, including those seeking molecular mechanistic explanations of cellular phenomena, frequently rely on experimental strategies focused on identifying the cellular context relevant to their investigations. We suggest that such practices can be understood as a guided decomposition strategy, where molecular explanations of phenomena are defined in relation to natural contextual (cell) boundaries. This “top-down” strategy contrasts with “bottom-up” reductionist approaches where well-defined molecular structures and activities are orphaned by their displacement from actual biological functions. We focus on (...) the central role of microscopic imaging in cell biology to uncover possible constraints on the system. We show how identified constraints are used heuristically to limit possible mechanistic explanations to those that are biologically meaningful. Historical examples of this process described here include discovery of the mechanism of oxidative phosphorylation in mitochondria, molecular explanation of the first steps in protein secretion, and identification of molecular motors. We suggest that these instances are examples of a form of downward causation or, more specifically, constraining relations, where higher-level structures and variables delimit and enable lower-level system states. The guided decomposition strategy in our historical cases illustrates the irreducibility of experimentally identified constraints in explaining biological activities of cells. Rather than viewing decomposition and recomposition as separate epistemic activities, we contend that they need to be iteratively integrated to account for the ontological complexity of multi-level systems. (shrink)

Gene therapies to treat sickle cell disease are in development and are expected to have high costs. The large eligible population size — by far, the largest for a gene therapy — poses daunting budget challenges and threatens to exacerbate health disparities for Black patients, who make up the vast majority of American sickle cell patients.

I argue that campus closures and shifts to online instruction in the early stages of the COVID-19 pandemic created an obligation to offer courses asynchronously. This is because some students could not have reasonably foreseen circumstances making continued synchronous participation impossible. Offering synchronous participation options to students who could continue to participate thusly would have been unfair to students who could not participate synchronously. I also discuss why ex post facto consideration of this decision is warranted, noting that similar actions (...) may be necessary in the future and that other tough pedagogical cases share important similarities with this case. (shrink)

In Islam, the acquisition of knowledge is a form of worship. But human achievement must be exercised in conformity with God's will. Warnings against feelings of superiority often are coupled with the command to remain within the confines of God's laws and limits. Because of the fear of arrogance and disregard of the balance created by God, any new knowledge or discovery must be applied with careful consideration to maintaining balance in the creation. Knowledge must be applied to ascertain equity (...) and justice for all of humanity. Research in Islam must be linked to the broad ethical base set forth in the Qur'an and the Sunnah. Whether embryonic stem cell research or cloning is ethically acceptable in Islam depends on the benefits derived from such applications. What is most important for the scholars is to adhere to the concepts of compassion, mercy, and benefit to everyone. (shrink)

Ubiquitination plays a central role in the regulation of stem cell self‐renewal, propagation, and differentiation. In this review, the functions of ubiquitin dynamics in a myriad of cellular processes, acting along side the pluripotency network, to regulate embryonic stem cell identity are highlighted. The implication of deubiquitinases (DUBs) and E3 Ubiquitin (Ub) ligases in cellular functions beyond protein degradation is reported, including key functions in the regulation of mRNA stability, protein translation, and intra‐cellular trafficking; and how it affects (...) cell metabolism, the micro‐environment, and chromatin organization is discussed. Finally, unsolved issues in the field are emphasized and will need to be tackled in order to fully understand the contribution of ubiquitin dynamics to stem cell self‐renewal and differentiation. (shrink)

We report on the deliberations of an interdisciplinary group of experts in science, law, and philosophy who convened to discuss novel ethical and policy challenges in stem cell research. In this report we discuss the ethical and policy implications of safety concerns in the transition from basic laboratory research to clinical applications of cell-based therapies derived from stem cells. Although many features of this transition from lab to clinic are common to other therapies, three aspects of stem (...) class='Hi'>cell biology pose unique challenges. First, tension regarding the use of human embryos may complicate the scientific development of safe and effective cell lines. Second, because human stem cells were not developed in the laboratory until 1998, few safety questions relating to human applications have been addressed in animal research. Third, preclinical and clinical testing of biologic agents, particularly those as inherently complex as mammalian cells, present formidable challenges, such as the need to develop suitable standardized assays and the difficulty of selecting appropriate patient populations for early phase trials. We recommend that scientists, policy makers, and the public discuss these issues responsibly, and further, that a national advisory committee to oversee human trials of cell therapies be established. **NB we did not reccommend a NAC, we think it might be appropriate**. (shrink)

Stem cell scientists and ethicists have focused intently on questions relevant to the developmental stage and developmental capacities of stem cells. Comparably less attention has been paid to an equally important set of questions about the nature of stem cells, their common characteristics, their non‐negligible differences and their possible developmental species specificity. Answers to these questions are essential to the project of justly inferring anything about human stem cell biology from studies in non‐human model systems—and so to the (...) possibility of eventually developing human therapies based on stem cell biology. After introducing and discussing these questions, I conclude with a brief discussion of the creation of novel model systems in stem cell biology: human‐to‐animal embryonic chimeras. Such novel model systems may help to overcome obstacles to extrapolation, but they are also scientifically and ethically contentious. BioEssays 26:1005‐1012, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Mechanical forces provide essential cues for morphogenetic processes during embryonic development. Coordinated orientation of cells in the plane of epithelia, that is known as planar cell polarity (PCP), is also required for morphogenesis. How PCP is established and what role PCP signaling plays in tissue rearrangements remains poorly understood. Here, we review the evidence for a positive regulatory loop that connects PCP to mechanotransduction, the process by which cells convert mechanical stimuli, such as pressure or tension, into biochemical signals. (...) Accumulating data strongly support a hypothesis that a PCP axis can form in response to intrinsic or extrinsic mechanical stresses. Moreover, we suggest that PCP signaling functions to control physical force production in the tissue. This mechanochemical feedback regulation is proposed to be a fundamental mechanism that ensures proper tissue shape and positioning during morphogenesis. (shrink)

Host‐pathogen arms race is a universal, central aspect of the evolution of life. Most organisms evolved several distinct yet interacting strategies of anti‐pathogen defense including resistance to parasite invasion, innate and adaptive immunity, and programmed cell death (PCD). The PCD is the means of last resort, a suicidal response to infection that is activated when resistance and immunity fail. An infected cell faces a decision between active defense and altruistic suicide or dormancy induction, depending on whether immunity is (...) “deemed” capable of preventing parasite reproduction and consequent infection of other cells. In bacteria and archaea, immunity genes typically colocalize with PCD modules, such as toxins‐antitoxins, suggestive of immunity‐PCD coupling, likely mediated by shared proteins that sense damage and “predict” the outcome of infections. In type VI CRISPR‐Cas systems, the same enzyme that inactivates the target RNA might execute cell suicide, in a case of ultimate integration of immunity and PCD. (shrink)

In textbook illustrations of migrating cells, actomyosin contractility is typically depicted as the contraction force necessary for cell body retraction. This dogma has been transformed by the molecular clutch model, which acknowledges that actomyosin traction forces also generate and transmit biomechanical signals at the leading edge, enabling cells to sense and shape their migratory path in mechanically complex environments. To fulfill these complementary functions, the actomyosin system assembles a gradient of contractile energy along the front‐rear axis of migratory cells. (...) Here, we highlight the hierarchic assembly and self‐regulatory network structure of the actomyosin system and explain how the kinetics of different nonmuscle myosin II (NM II) paralogs synergize during contractile force generation. Our aim is to emphasize how protrusion formation, cell adhesion, contraction, and retraction are spatiotemporally integrated during different modes of migration, including chemotaxis and durotaxis. Finally, we hypothesize how different NM II paralogs might tune aspects of migration in vivo, highlighting future research directions. (shrink)

The cell theory—the thesis that all life is made up of one or more cells, the fundamental structural and physiological unit—is one of the most celebrated achievements of modern biological science. And yet from its very inception in the nineteenth century it has faced repeated criticism from some biologists. Why do some continue to criticize the cell theory, and how has it managed nevertheless to keep burying its undertakers? The answers to these questions reveal the complex nature of (...) the cell theory and the cell concept on which it is based. Like other scientific ‘laws’, the assertion that all living things are made of cells purchases its universality at the expense of abstraction. If, however, this law is regarded merely as a widely applicable empirical generalization with notable exceptions, it still remains too important to discard. Debate about whether the cell or the organism standpoint provides the more correct account of anatomical, physiological, and developmental facts illustrates the tension between our attempts to express the truth about reality in conceptual terms conducive to a unified human understanding. (shrink)

Physical forces regulate numerous biological processes during development, physiology, and pathology. Forces between the external environment and intracellular actin cytoskeleton are primarily transmitted through integrin‐containing focal adhesions and cadherin‐containing adherens junctions. Crosstalk between these complexes is well established and modulates the mechanical landscape of the cell. However, integrins and cadherins constitute large families of adhesion receptors and form multiple complexes by interacting with different ligands, adaptor proteins, and cytoskeletal filaments. Recent findings indicate that integrin‐containing hemidesmosomes oppose force transduction and (...) traction force generation by focal adhesions. The cytolinker plectin mediates this crosstalk by coupling intermediate filaments to the actin cytoskeleton. Similarly, cadherins in desmosomes might modulate force generation by adherens junctions. Moreover, mechanotransduction can be influenced by podosomes, clathrin lattices, and tetraspanin‐enriched microdomains. This review discusses mechanotransduction by multiple integrin‐ and cadherin‐based cell adhesion complexes, which together with the associated cytoskeleton form an integrated network that allows cells to sense, process, and respond to their physical environment. (shrink)

Adult stem cell populations must coordinate their own maintenance with the generation of differentiated cell types to sustain organ physiology, in a spatially controlled manner and over long periods. Quantitative analyses of clonal dynamics have revealed that, in epithelia, homeostasis is achieved at the population rather than at the single stem cell level, suggesting that feedback mechanisms coordinate stem cell maintenance and progeny generation. In the central nervous system, however, little is known of the possible community (...) processes underlying neural stem cell maintenance. Recent work, in part based on intravital imaging made possible in the adult zebrafish, conclusively highlights that homeostasis in neural stem cell pools may rely on population asymmetry and long‐term spatiotemporal coordination of neural stem cell states and fates. These results suggest that neural stem cell assemblies in the vertebrate brain behave as self‐organized systems, such that the stem cells themselves generate their own intrinsic niche. (shrink)

A new theory of the neuropsychological underpinnings of phenomenal consciousness, “asynchronous introspection theory,” is proposed that emphasizes asynchrony between different neurocognitive processes. We provide a detailed explanation of how a mind might arrive at a cognitive structure isomorphic to the cognitive structure that would emerge from experiential qualia. The theory suggests that a temporal illusion is created because of the mismatch between the real physical timeline and the neurally constructed timeline composed inside a person’s brain. This temporal illusion leads (...) to the origination of a thought that one has had a certain experience wherein the thought and the feeling seem synchronous to the person but, in fact, are not. This leads to the thought, “I had a feeling.” The theory is elaborated via a metaphorical “robot supervisor model” and is shown to explain many current problems of phenomenal consciousness. (shrink)

Nijhawan argues that neural compensation is necessary to account for couplings of perception and action. Although perhaps true in some cases, computational tolerance for asynchronously arriving continuous information is of more importance. Moreover, some of the everyday venues Nijhawan uses to argue for the relevance of prediction and compensation can be better ascribed to skill.

Interleukin‐1 receptor‐associated kinase‐1 (IRAK1) is linked to the pathogenesis of atherosclerosis; however, its role in macrophage foam cell formation is not known. Therefore, the present study investigated the role of IRAK1 in lipid uptake, biosynthesis, and efflux in THP‐1 derived macrophages and human monocyte‐derived macrophages (HMDMs). Ox‐LDL (40 μg/mL, 15 minutes–48 hours) treatment induced time‐dependent increase in IRAK1, IRAK4, and Stat1 activation in THP‐1 derived macrophages. IRAK1/4 inhibitor (INH) or IRAK1 siRNA significantly attenuated cholesterol accumulation, DiI‐Ox‐LDL binding, and uptake (...) while cholesterol efflux to apoAI and HDL was enhanced in THP‐1 derived macrophages and HMDMs. Ox‐LDL treatment significantly increased the mRNA expression of CD36, LOX‐1, SR‐A, ABCA1, ABCG1, Caveolin‐1, CYP27A1 while that of SR‐BI was decreased. IRAK1/4 inhibition or IRAK1 knockdown, however, attenuated Ox‐LDL‐induced CD36 expression; augmented ABCA1 and ABCG1 expression while expression of others was unaffected in THP‐1 derived macrophages and HMDMs. Moreover, IRAK1/4 inhibition had no significant effect on genes involved in lipid biosynthesis. In IRAK1/4 INH pre‐treated THP‐1 derived macrophages Ox‐LDL‐induced Stat1 phosphorylation and its binding to CD36 promoter was significantly attenuated while LXRα expression and its binding to the ABCA1/ABCG1 locus, NFATc2 activation and its binding to ABCA1 locus was enhanced. The present study thus demonstrates that IRAK regulates lipid accumulation by modulating CD36‐mediated uptake and ABCA1‐, ABCG1‐dependent cholesterol efflux. Therefore, IRAK1 can be a potential target for preventing macrophage foam cell formation. (shrink)

Studies on the development of cell populations are often based on results of the theory of stochastic birth- and death-processes (continuous or discrete (seee.g. references inVogel, Niewisch &Matioli (1969), in some cases, death may be interpreted not as actual death of the cell bute.g. as a recruitment of the cell considered into another cell compartment, etc.). It is usually assumed that the conditions for the development are homogeneous,i.e. that the probabilities of births and deaths are independent (...) on the time. However, in most situations, this assumption is not fulfilled (owing to the maturation and differentiation of cells, changes of the microenvironment, inducing factors, etc.). Then it is necessary to study the development of cell populations under non-homogeneous conditions. In this paper, some properties of appropriate birth- and death-processes under nonhomogeneous conditions are studied; formulae given in section 4 permit calculation of some characteristics describing the cell population size distribution at individual discrete epochs (at individual generations) during the development of the cell population considered. (shrink)

Abstractp53 has a determinant role in cancer prevention and is among the most studied proteins in the world. The majority of studies devoted to this protein are carried out in cell lines because they are easy to use and have naturally emerged as the main research tool in laboratories. However, the p53 pathway is commonly deregulated in cancer cells, from which the experimental cell lines are generally derived. The fact that the pathway is deregulated challenges the relevance of (...) using cancer‐derived cell lines to study wild‐type p53 activities, or, in a broader sense, to study any normal cellular process. In the present article, we identify and discuss a number of limitations of cell lines using examples related to p53. Finally, we point out the general limitations of cell lines and propose solutions as alternatives to these cells. (shrink)

An elementary semistochastic model for cell cycle analysis is presented. Various independently generated experimental data sets are compared with the theory in which for the first time, a consistent consideration of non-proliferating cells has also been taken into account.

Collective cell migration is fundamental to developmental processes and disease progression. Despite extensive study, the field lacks a unifying framework for how collective cells initiate and terminate their migration. While these processes have traditionally been explained for individual cell migration by epithelial‒mesenchymal transition (EMT) and mesenchymal‒epithelial transition (MET), these models do not fully recapitulate the complex features of collective cell migration. In this review, I explore the distinct mechanisms by which groups of cells initiate and terminate collective (...) migration, highlighting in vivo examples such as gastrulation and neural crest formation in vertebrates, lateral line migration in zebrafish, and tracheal branch and border cell migration in Drosophila. I also discuss collective cell migration in cancer metastasis. I focus on how the initiation and termination of collective migration are regulated, emphasizing the regulatory pathways and unique features. Clarifying these mechanisms will guide hypothesis‐driven discovery and inform strategies to modulate collective cell behaviors in development, regeneration, and metastasis. (shrink)

In the last decade it has become en vogue for cognitive comparative psychologists to study animal behavior in an ‘integrated’ fashion to account for both the ‘innate’ and the ‘acquired’. We will argue that these studies, instead of really integrating the concepts of ‘nature’ and ‘nurture’, rather cement this old dichotomy. They combine empty nativist interpretation of behavior systems with blatantly environmentalist explanations of learning. We identify the main culprit as the failure to take development seriously. While in some areas (...) of biology interest in the relationship between behavior and development has surged through topics such as extragenetic inheritance, niche construction, and phenotypic plasticity, this has gone almost completely unnoticed in the study of animal behavior in comparative psychology, and is frequently ignored in ethology too. The main aims of this paper are to clarify the relationship between the concepts of learning, experience, and development, and to investigate whether and how all three concepts can be usefully deployed in the study of animal behavior. This will require the full integration of the psychological study of behavior into biology, and of the idea of learning into a wider concept of experience. We lay out how, in a systems view of development, learning may just appear as one among many processes in which experience influences behavior. This new synthesis should help to overcome the age-old dualism between innate and acquired. It thereby opens up the possibility of developing scientifically more fruitful distinctions. (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.

Now that stem cell scientists are clamouring for human eggs for cloning-based stem cell research, there is vigorous debate about the ethics of paying women for their eggs. Generally speaking, some claim that women should be paid a fair wage for their reproductive labour or tissues, while others argue against the further commodification of reproductive labour or tissues and worry about voluntariness among potential egg providers. Siding mainly with those who believe that women should be financially compensated for (...) providing eggs for research, the new stem cell guidelines of the International Society for Stem Cell Research (ISSCR) legitimise both reimbursement of direct expenses and financial compensation for many women who supply eggs for research. In this paper, the authors do not attempt to resolve the thorny issue of whether payment for eggs used in human embryonic stem cell research is ethically legitimate. Rather, they want to show specifically that the ISSCR recommended payment practices are deeply flawed and, more generally, that all payment schemes that aim to avoid undue inducement of women risk the global exploitation of economically disadvantaged women. (shrink)