It is not clear why cancer cells choose to disrupt their circadian clock rhythms, and whether such disruption governs a selective fitness and a survival advantage. In this review, I focus on understanding the impacts of clock gene disruption on a simpler model, such as the unicellular cyanobacterium, in order to explain how cancer cells may alter the circadian rhythm to reprogram their metabolism based on their needs and status. It appears to be that the activation of the oxidative pentose (...) phosphate pathway (OPPP) and production of NADPH, the preferred molecule for detoxification of reactive oxygen species, is a critical process for night survival in unicellular organisms. The circadian clock acts as a gatekeeper that controls how the organism will utilize its sugar, shifting sugar influx between glycolysis and OPPP. The circadian clock can thus act as a gatekeeper between an anabolic, proliferative mode and a homeostatic, survival mode. (shrink)

O livro III da _Ética _de Espinosa se dedica a definição dos afetos. Dentro dessa definição o outro desempenha um papel importantíssimo, mesmo se, inicialmente, ele parece estar ausente. Espinosa começará sua definição falando de afetos direcionados a coisas e não necessariamente a outros sujeitos afetivos. Todavia, isso não significa que o outro não seja importante para a teoria de Espinosa, pelo contrário, a partir da proposição 21 desse livro ele faz sua aparição, trazendo novos elementos à teoria dos afetos (...) e, principalmente, apontando para uma via de mão dupla, mostrando-nos que, se por um lado, as relações interpessoais podem ser de amor, por outro, o ódio estará presente, ou seja, essa relação pode se revelar tanto harmoniosa quanto conflitante. É justamente esse o caminho que gostaríamos de iluminar neste artigo, explicitando assim como a entrada do outro na teoria dos afetos de Espinosa lhe confere novas nuances, novos caminhos, novas possibilidades. (shrink)

There is an urgent need for novel protection strategies to sustainably secure crop production under changing climates. Studying microbial effectors, defined as microbe‐derived proteins that alter signalling inside plant cells, has advanced our understanding of plant immunity and microbial plant colonisation strategies. Our understanding of effectors in the establishment and beneficial outcome of plant symbioses is less well known. Combining functional and comparative interaction assays uncovered specific symbiont effector targets in highly interconnected plant signalling networks and revealed the potential of (...) effectors in beneficially modulating plant traits. The diverse functionality of symbiont effectors differs from the paradigmatic immuno‐suppressive function of pathogen effectors. These effectors provide solutions for improving crop resilience against climate stress by their evolution‐driven specification in host protein targeting and modulation. Symbiont effectors represent stringent tools not only to identify genetic targets for crop breeding, but to serve as applicable agents in crop management strategies under changing environments. (shrink)

Darwinian evolution can be simply stated: natural selection of inherited variations increasing differential reproduction. However, formulated thus, links with biochemistry, cell biology, ecology, and population dynamics remain unclear. To understand interactive contributions of chance and selection, higher levels of biological organization (e.g., endosymbiosis), complexities of competing selection forces, and emerging biological novelties (such as eukaryotes or meiotic sex), we must analyze actual examples. Focusing on mitochondria, I will illuminate how biology makes sense of life's evolution, and the concepts involved. First, (...) looking at the bacterium – mitochondrion transition: merging with an archaeon, it lost its independence, but played a decisive role in eukaryogenesis, as an extremely efficient aerobic ATP generator and internal ROS source. Second, surveying later mitochondrion adaptations and diversifications illustrates concepts such as constructive neutral evolution, dynamic interactions between endosymbionts and hosts, the contingency of life histories, and metabolic reprogramming. Without oxygen, mitochondria disappear; with (intermittent) oxygen diversification occurs in highly complex ways, especially upon (temporary) phototrophic substrate supply. These expositions show the Darwinian model to be a highly fruitful paradigm. (shrink)

The reprogramming of metabolism has been identified as one of the hallmarks of cancer. It is becoming more and more frequent to connect other diseases with metabolic reprogramming. This article aims to argue that metabolic reprogramming is not driven by disease but instead is the main hallmark of metabolism, based on its dynamic behavior that allows it to continuously adapt to changes in the internal and external conditions.

The recent emergence of reprogramming technologies to convert brain cell types or epigenetically alter neurons and neural progenitors in vivo and in situ hold significant promises in brain repair and neuronal aging reversal. However, given the significant epigenetic and transcriptomic changes to components of the existing neuronal cells and network, we question if these reprogramming technology might inadvertently alter or erase memory engrams, conceivably resulting in changes in narrative identity or personality. We suggest that the nature of these (...) alterations might be less predictable compared to memory and personality changes known to be associated with diseases, drugs or brain stimulation therapies. While research in applying reprogramming technologies to neurological ailments and aging should continue, more targeted analyses should be put in place in animal experiments to gauge the severity and degree of memory alterations, and appropriate risk and benefit analyses should be conducted before these technologies move into human trials. (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)

Reprogramming technologies show that cellular identity can be reprogrammed, challenging the classical conception of cell differentiation as an irreversible process. If non-stem cells can be reprogrammed into stem cells, then what is it to be a stem cell, and what kind of property is stemness? This article addresses this question both philosophically and biologically, states the different possibilities, and illustrates their potential consequences for science with the example of anti-cancer therapies.

"The total amount of suffering per year in the natural world is beyond all decent contemplation. During the minute that it takes me to compose this sentence, thousands of animals are being eaten alive, others are running for their lives, whimpering with fear, others are being slowly devoured from within by rasping parasites, thousands of all k inds are dying of starvation, thirst and disease. It must be so." -/- —Richard Dawkins, River Out of Eden (1995).

Louise Brown's birth in 1978 heralded a new era not just in reproductive technology, but in the relationship between science, cells, and society. For the first time, human embryos could be created, selected, studied, manipulated, frozen, altered, or destroyed, outside the human body. But with this possibility came a plethora of ethical questions. Is it acceptable to destroy a human embryo for the purpose of research? Or to create an embryo with the specific purpose of destroying it for research? In (...) an attempt to construct ethical and legal frameworks for the new era of cellular reprogramming, legislators and ethicists have tried to distinguish between different kinds of biological entity. We treat cells differently depending on whether they are human or animal, somatic cells or gametes, and on whether they are embryos or not. But this approach to the ethics of cellular reprogramming is doomed to failure for the simple reason that cellular reprogramming in itself destroys the distinctions that the law requires to function. In this article, we explore the historical trajectory of cellular reprogramming and its relationship with ethics and society. We suggest that the early hype of embryo research has not obviously fulfilled expectations, but since new avenues of research are continuously opening, it is hard to say definitely that these promises have been broken. We explore the forthcoming challenges posed by the creation of DNA from scratch in the laboratory, and the implications of this for understandings of identity, privacy, and reproduction. We conclude that while ethics used to seek answers in biological facts, this is no longer possible, and a new approach is required. (shrink)

COVID-19 often manifests with different outcomes in different patients, highlighting the complexity of the host-pathogen interactions involved in manifestations of the disease at the molecular and cellular levels. In this paper, we propose a set of postulates and a framework for systematically understanding complex molecular host-pathogen interaction networks. Specifically, we first propose four host-pathogen interaction (HPI) postulates as the basis for understanding molecular and cellular host-pathogen interactions and their relations to disease outcomes. These four postulates cover (...) the evolutionary dispositions involved in HPIs, the dynamic nature of HPI outcomes, roles that HPI components may occupy leading to such outcomes, and HPI checkpoints that are critical for specific disease outcomes. Based on these postulates, an HPI Postulate and Ontology (HPIPO) framework is proposed to apply interoperable ontologies to systematically model and represent various granular details and knowledge within the scope of the HPI postulates, in a way that will support AI-ready data standardization, sharing, integration, and analysis. As a demonstration, the HPI postulates and the HPIPO framework were applied to study COVID-19 with the Coronavirus Infectious Disease Ontology (CIDO), leading to a novel approach to rational design of drug/vaccine cocktails aimed at interrupting processes occurring at critical host-coronavirus interaction checkpoints. Furthermore, the host-coronavirus protein-protein interactions (PPIs) relevant to COVID-19 were predicted and evaluated based on prior knowledge of curated PPIs and domain-domain interactions, and how such studies can be further explored with the HPI postulates and the HPIPO framework is discussed. (shrink)

The recent successful conversion of adult cells into induced pluripotent stem (iPS) cells through direct reprogramming opens a new chapter in the study of disease and the development of regenerative medicine. It also provides a historic opportunity to turn away from the ethically problematic use of embryonic stem cells isolated through the destruction of human embryos. Moreover, because iPS cells are patient specific, they render therapeutic cloning unnecessary. To maximize therapeutic benefit, adult stem cell research will need to be (...) pursued in parallel with studies using iPS cells. Among the four alternative methods presented by the President’s Council on Bioethics, direct reprogram- ming is the most ethically acceptable. Nonetheless, iPS cells are tainted by their association with the human embryonic stem cell lines, derived in the past, which will be required for their validation. This concern is one that can be resolved. Human iPS cells will serve to stem the tide of human embryonic stem cell research, changing it and diverting stem cell research in a more ethical direction. (shrink)

Reprogramming of somatic cells to a pluripotent state holds huge potentials for regenerative medicine. However, a debate over which method is better, somatic cell nuclear transfer (SCNT) or induced pluripotent stem (iPS) cells, still persists. Both approaches have the potential to generate patient‐specific pluripotent stem cells for replacement therapy. Yet, although SCNT has been successfully applied in various vertebrates, no human pluripotent stem cells have been generated by SCNT due to technical, legal and ethical difficulties. On the other hand, (...) human iPS cell lines have been reported from both healthy and diseased individuals. A recent study reported the generation of triploid human pluripotent stem cells by transferring somatic nuclei into oocytes, a variant form of SCNT. In this essay, we discuss this progress and the potentials of these two reprogramming approaches for regenerative medicine. (shrink)

Current methods of reprogramming differentiated cells into induced pluripotent stem cells remain slow and inefficient. In a recent report published online in Nature, Bhutani et al.1 developed a cell fusion strategy, achieving quick and efficient reprogramming toward pluripotency. Using this assay, they identified an immune system protein called activation‐induced cytidine deaminase, or AID, which unexpectedly is actually able to “aid” in reprogramming due to its involvement in DNA demethylation that is required for induction of the two key (...) pluripotency genes, Oct4 and Nanog. More recently, Popp et al. 2 also reported online in Nature that AID is important for complete cell reprogramming in mammals. Together, these findings provide new insights into how cells are reprogrammed, identify the specific role of AID in cell fate reversal, and advance the field of regenerative medicine. (shrink)

Rejuvenation of cells by reprogramming toward the pluripotent state raises increasing attention. In fact, generation of induced pluripotent stem cells (iPSCs) completely reverses age‐associated molecular features, including elongation of telomeres, resetting of epigenetic clocks and age‐associated transcriptomic changes, and even evasion of replicative senescence. However, reprogramming into iPSCs also entails complete de‐differentiation with loss of cellular identity, as well as the risk of teratoma formation in anti‐ageing treatment paradigms. Recent studies indicate that partial reprogramming by limited exposure (...) to reprogramming factors can reset epigenetic ageing clocks while maintaining cellular identity. So far, there is no commonly accepted definition of partial reprogramming, which is alternatively called interrupted reprogramming, and it remains to be elucidated how the process can be controlled and if it resembles a stable intermediate state. In this review, we discuss if the rejuvenation program can be uncoupled from the pluripotency program or if ageing and cell fate determination are inextricably linked. Alternative rejuvenation approaches with reprogramming into a pluripotent state, partial reprogramming, transdifferentiation, and the possibility of selective resetting of cellular clocks are also discussed. (shrink)

What makes something an embryo—as opposed to what is actually, and not just in biotech parlance, a collection of cells? This question has come to the fore in recent years with proposals for producing embryonic stem cells for research. While some of those opposed to use of standard embryonic stem cells emphasise that adult cells have a clinical track record, others argue that there may be further benefits obtainable from cells very like those of embryos, provided such cells can be (...) derived in new ways. Rather than deriving them in ways that kill or otherwise endanger a living human embryo, they could be obtained from an entity that merely resembles a human embryo sufficiently closely for its cells to be of use. Such an entity might be created after introducing genetic changes to an ovum before it is activated by, for example, a cloning-type procedure, such that a gene essential to embryogenesis will be either absent, blocked in its expression, or overexpressed.1,2 The claim is that the ovum could be made to give rise to embryonic stem cells—mere living parts—without ever giving rise to a whole embryo, who is killed to obtain them. Whereas cloning “proper” winds back the specialisation of the cell nucleus to a point where a whole embryo is formed who has not yet specialised its cells, oocyte-assisted reprogramming , it is claimed, would wind back the specialisation merely to an intermediate point at which no embryo is created. Other methods proposed for deriving pseudoembryonic cells include parthenogenesis, in which an ovum is activated without a sperm, or even the insertion of an adult cell nucleus.1MORAL STATUS OF THE EMBRYOIn this paper, I assume that a genuine …. (shrink)

DNA methylation is a repressive epigenetic mark vital for normal development. Recent studies have uncovered an unexpected role for the DNA methylome in ensuring the correct targeting of the Polycomb repressive complexes throughout the genome. Here, we discuss the implications of these findings for cancer, where DNA methylation patterns are widely reprogrammed. We speculate that cancer‐associated reprogramming of the DNA methylome leads to an altered Polycomb binding landscape, influencing gene expression by multiple modes. As the Polycomb system is responsible (...) for the regulation of genes with key roles in cell fate decisions and cell cycle regulation, DNA methylation induced Polycomb mis‐targeting could directly drive carcinogenesis and disease progression.Editor's suggested further reading in BioEssays Unmasking risk loci: DNA methylation illuminates the biology of cancer predisposition Abstract. (shrink)

This paper makes use of an example of Williams’s, an example involving so-called psychological deprogramming–reprogramming, in arguing that procedures such as Teletransportation would not provide what matters to us in our self-interested concern for the future. This is so because the beliefs and other psychological states of a resultant person would not be appropriately causally dependent on any beliefs or other psychological states of the original person.

Similar to parasites, cancer cells depend on their hosts for sustenance, proliferation and reproduction, exploiting the hosts for energy and resources, and thereby impairing their health and fitness. Because of this lifestyle similarity, it is predicted that cancer cells could, like numerous parasitic organisms, evolve the capacity to manipulate the phenotype of their hosts to increase their own fitness. We claim that the extent of this phenomenon and its therapeutic implications are, however, underappreciated. Here, we review and discuss what can (...) be regarded as cases of host manipulation in the context of cancer development and progression. We elaborate on how acknowledging the applicability of these principles can offer novel therapeutic and preventive strategies. The manipulation of host phenotype by cancer cells is one more reason to adopt a Darwinian approach in cancer research. -/- . (shrink)

Resident microorganisms, known as the microbiota, are essential for many physiological functions including protection against pathogens. Microbiota is indeed required for proper immune system development and function, and can also host-independently protect against infections. Thus, a co-constructed view of host protection involving both host and microbiota, named ’co-immunity,’ has been proposed, and the idea of an ’immunological holobiont’ has been suggested. Yet this view of co-immunity might be too limited, as experimental work has shown that the immune (...) system is involved in functions other than protection, essentially development and repair. Microbiota, through co-immunity, is thereby most likely involved in these functions, although strong evidence is currently lacking. Moreover, as our point of view is mainly host-centered, we may miss the implications of co-immunity at broader scales, including cellular and population levels. Intriguingly, co-immunity effects could be beneficial for one function and/or one level, while being detrimental for others. All these elements should be taken into consideration for microbiota manipulation, in order to avoid potentially harmful side effects. (shrink)

Within medical education, there is an increasing need to provide ethics education for learners embarking on service learning. The concept of hospitality, as illustrated in Homer’s classic epic the Odyssey, has the potential to underpin such ethics education. This paper describes the implementation and evaluation of an ethics education session for medical students, built on the concept of hospitality, before they embark on a three-year longitudinal service-learning home visit program. In preparation for their household visits, second-year students at a medical (...) school in Miami, Florida, participate in weekly didactic sessions. One of these classes consisted of a two-hour ethics session, involving a brief introductory large-group lecture, followed by self-administered small-group discussions of a series of case scenarios. An innovative web-based platform called Rise allowed the students to run their own small group activities. To assess the impact on the students’ ability to identify, and on their confidence in handling, ethical dilemmas, we administered pre- and post-session surveys. Students indicated statistically significant improvement in median responses to all questions, for two consecutive years. Students also listed three adjectives, both before and after the session, that they associated with good and bad hosts and guests. The consistency of the terms listed suggests that hospitality is a robust concept for the learners. In our experience, the concept of hospitality provides a robust framework for the students, and the mixed large-group and self-facilitated small-group format offers a valuable tool for ethics education related to service learning in medicine. Our study supports the utility of the concept as a teaching tool, and the format facilitates a session using minimal faculty. The notion of hospitality seems particularly fruitful for various ethical considerations in medicine, even beyond those that involve home visits. (shrink)

Within medical education, there is an increasing need to provide ethics education for learners embarking on service learning. The concept of hospitality, as illustrated in Homer’s classic epic the Odyssey, has the potential to underpin such ethics education. This paper describes the implementation and evaluation of an ethics education session for medical students, built on the concept of hospitality, before they embark on a three-year longitudinal service-learning home visit program. In preparation for their household visits, second-year students at a medical (...) school in Miami, Florida, participate in weekly didactic sessions. One of these classes consisted of a two-hour ethics session, involving a brief introductory large-group lecture, followed by self-administered small-group discussions of a series of case scenarios. An innovative web-based platform called Rise allowed the students to run their own small group activities. To assess the impact on the students’ ability to identify, and on their confidence in handling, ethical dilemmas, we administered pre- and post-session surveys. Students indicated statistically significant improvement in median responses to all questions, for two consecutive years. Students also listed three adjectives, both before and after the session, that they associated with good and bad hosts and guests. The consistency of the terms listed suggests that hospitality is a robust concept for the learners. In our experience, the concept of hospitality provides a robust framework for the students, and the mixed large-group and self-facilitated small-group format offers a valuable tool for ethics education related to service learning in medicine. Our study supports the utility of the concept as a teaching tool, and the format facilitates a session using minimal faculty. The notion of hospitality seems particularly fruitful for various ethical considerations in medicine, even beyond those that involve home visits. (shrink)

Within medical education, there is an increasing need to provide ethics education for learners embarking on service learning. The concept of hospitality, as illustrated in Homer’s classic epic the Odyssey, has the potential to underpin such ethics education. This paper describes the implementation and evaluation of an ethics education session for medical students, built on the concept of hospitality, before they embark on a three-year longitudinal service-learning home visit program. In preparation for their household visits, second-year students at a medical (...) school in Miami, Florida, participate in weekly didactic sessions. One of these classes consisted of a two-hour ethics session, involving a brief introductory large-group lecture, followed by self-administered small-group discussions of a series of case scenarios. An innovative web-based platform called Rise allowed the students to run their own small group activities. To assess the impact on the students’ ability to identify, and on their confidence in handling, ethical dilemmas, we administered pre- and post-session surveys. Students indicated statistically significant improvement in median responses to all questions, for two consecutive years. Students also listed three adjectives, both before and after the session, that they associated with good and bad hosts and guests. The consistency of the terms listed suggests that hospitality is a robust concept for the learners. In our experience, the concept of hospitality provides a robust framework for the students, and the mixed large-group and self-facilitated small-group format offers a valuable tool for ethics education related to service learning in medicine. Our study supports the utility of the concept as a teaching tool, and the format facilitates a session using minimal faculty. The notion of hospitality seems particularly fruitful for various ethical considerations in medicine, even beyond those that involve home visits. (shrink)

Within medical education, there is an increasing need to provide ethics education for learners embarking on service learning. The concept of hospitality, as illustrated in Homer’s classic epic the Odyssey, has the potential to underpin such ethics education. This paper describes the implementation and evaluation of an ethics education session for medical students, built on the concept of hospitality, before they embark on a three-year longitudinal service-learning home visit program. In preparation for their household visits, second-year students at a medical (...) school in Miami, Florida, participate in weekly didactic sessions. One of these classes consisted of a two-hour ethics session, involving a brief introductory large-group lecture, followed by self-administered small-group discussions of a series of case scenarios. An innovative web-based platform called Rise allowed the students to run their own small group activities. To assess the impact on the students’ ability to identify, and on their confidence in handling, ethical dilemmas, we administered pre- and post-session surveys. Students indicated statistically significant improvement in median responses to all questions, for two consecutive years. Students also listed three adjectives, both before and after the session, that they associated with good and bad hosts and guests. The consistency of the terms listed suggests that hospitality is a robust concept for the learners. In our experience, the concept of hospitality provides a robust framework for the students, and the mixed large-group and self-facilitated small-group format offers a valuable tool for ethics education related to service learning in medicine. Our study supports the utility of the concept as a teaching tool, and the format facilitates a session using minimal faculty. The notion of hospitality seems particularly fruitful for various ethical considerations in medicine, even beyond those that involve home visits. (shrink)

In recent years the notion of biological specificity has attracted significant philosophical attention. This paper focuses on host specificity, a kind of biological specificity that has not yet been discussed by philosophers, and which concerns the extent to which a species is selective in the range of other species it exploits for feeding and/or reproduction. Host specificity is an important notion in ecology, where it plays a variety of theoretical roles. Here I focus on the role of (...) class='Hi'>host specificity in biological control, a field of applied ecology that deals with the suppression of pests through the use of living organisms. Examining host specificity and its role in biological control yields several valuable contributions to our understanding of biological specificity. In particular, I argue that host specificity cannot be fully understood in terms of Woodward’s well-known account of causal specificity. To adequately account for host specificity, we need a notion of causal specificity that takes into consideration the extent to which a variable’s effects are similar to one another – a dimension not captured in Woodward’s account. In addition, the literature on host specificity in biological control highlights certain aspects in which causally specific relationships can be practically valuable that have not yet been addressed in philosophical discussions of specificity. That literature also reveals that in certain contexts specificity can hinder rather than foster effective control, thus leading to a nuanced assessment of the practical value of specific causes. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Direct Nuclear Reprogramming: Response to Condic, Lee, and GeorgeGerard Magill, Ph.D. and William B. NeavesWe read with great interest the response of Maureen Condic, Patrick Lee, and Robert George (2009) to our essay, “Ontological and Ethical Implications of Direct Nuclear Reprogramming” in the March 2009 issue of the Kennedy Institute of Ethics Journal (Magill and Neaves 2009). Much of their response addressed issues that are not in (...) dispute: somatic cells are not zygotes, neurons and hepatocytes are different, growth-factor signals from the trophoblast influence development of the inner cell mass, membranes derived from the trophectoderm are critically required for embryonic survival, and stem cells cannot produce a fetus “on their own.”The crucial point of disagreement deals with the fact that iPS cells are not totipotent but zygotes are. Zygotes can generate their own placental structures while iPS cells must be given them through tetraploid complementation. Condic, Lee, and George consider totipotency to be crucial to natural potentiality. We present an alternative view in our essay (Magill and Neaves 2009, pp. 28–29). Placental structures make no lasting contribution to the postnatal organism, and the equivalency of iPS cells with the inner cell mass of the blastocyst is apparent from tetraploid complementation experiments.The respondents acknowledge the following:... somatic cells can be “converted” into zygotes by the process of somatic cell nuclear transfer (SCNT) or direct reprogramming in combination with tetraploid complementation—just as sperm and egg cells can be “converted” into a zygote by the process of natural fertilization—....(Condic, Lee, and George 2009, p. 35)As the respondents recognize, different ways of manipulating cells can lead to embryogenesis: sperm and egg cells in the process of natural fertilization, the enucleated egg and an ordinary body cell in the process of somatic cell nuclear transfer, and reprogrammed skin cells and a tetraploid blastocyst in the case of induced pluripotent stem (iPS) cells. In each case, different cells are manipulated—or “converted” in the respondents’ terminology—in a process that alters their biological fate within a supportive environment facilitating embryogenesis.The developmental potential that resides in the human genome does not unfold in isolation, not even in a zygote. In all cases, whether involving a zygote or an iPS cell, interaction with a supportive environment is required to express the developmental program residing in the genome. [End Page 201]This biological reality supports what we have described as “early cellular development along the continuum of natural potentiality that can result in the formation of a fetus” (Magill and Neaves 2009, p. 30), and it presents a significant challenge to the natural potentiality argument.Gerard MagillVernon F. Gallagher Chair for the Integration of Science, Theology, Philosophy, and Law, and Professor, Center for Healthcare Ethics Duquesne University Pittsburgh, PA.William B. NeavesPresident and CEO Stowers Institute for Medical Research and Professor of Basic Medical Science University of Missouri at Kansas City School of Medicine Kansas City, MOReferencesCondic, Maureen L.; Lee, Patrick; and George, Robert P. 2008. Ontological and Ethical Implications of Direct Nuclear Reprogramming: Response to Magill and Neaves. Kennedy Institute of Ethics Journal 19: 33–40. Google ScholarMagill, Gerard, and Neaves William B. 2009. Ontological and Ethical Implications of Direct Nuclear Reprogramming. Kennedy Institute of Ethics Journal 19: 23–32. Google ScholarCopyright © 2009 The Johns Hopkins University Press... (shrink)

I argue that David Oelhoffen's 2014 film Far From Men, while departing from the letter of Camus' 1957 story, “The Guest/Host”, does remarkable cinematic justice to its spirit. Oelhoffen's Daru and the Arab character Mohamed, it is suggested, represent embodiments of Camus’ idealised Algerian “first men”, in the vision Camus was developing in Le Premier Homme at the time of his death in January 1960. Part 1 frames the film in light of Camus’ “The Guest/Host”, and Part 2 (...) frames Camus’ story in light of Camus’ agnonised struggle to come to terms with the Algerian situation. Part 3 makes the case that Oelhoffen's departures from Camus’ original story present in cinematic form Camus’ ideal of a post-colonial, post-ethnic solidarity between people, predicated on the overcoming of all arche-ideological fantasies of untained prelapsarian community. (shrink)

Despite the progress achieved over the last decade after the birth of the first cloned mammal, the efficiency of reproductive cloning remains invariably low. However, research aiming at the use of nuclear transfer for the production of patient‐tailored stem cells for cell/tissue therapy is progressing rapidly. Yet, reproductive cloning has many potential implications for animal breeding, transgenic research and the conservation of endangered species. In this article we suggest that the changes in the epi‐/genotype observed in cloned embryos arise from (...) unbalanced nuclear reprogramming between parental chromosomes. It is probable that the oocyte reprogramming machinery, devised for resident chromosomes, cannot target the paternal alleles of somatic cells. We, therefore, suggest that a reasonable approach to balance this asymmetry in nuclear reprogramming might involve the transient expression in donor cells of chromatin remodelling proteins, which are physiologically expressed during spermatogenesis, in order to induce a male‐specific chromatin organisation in the somatic cells before nuclear transfer. BioEssays 30:66–74, 2008. © 2007 Wiley Periodicals, Inc. (shrink)

Investigation into the impact of the stages of a radio call on host–caller interaction has traditionally been conducted in single host scenarios, whereby one host interacts with one caller. Further, this analysis has often been done in the context of talk radio that is designed to promote a sense of conflict in order to entertain its audience. However, what of dual or multi-host scenarios, where a number of hosts are co-participants when interacting with callers? This article (...) considers a talkback segment within a chat-based program in which two studio-based hosts are involved in conversation with callers. It considers previous research into call sequence as applied to this scenario and reveals that rather than working to challenge the caller, the hosts work together to enable the callers to challenge the hosts but in a way that orients to sociability rather than conflict. (shrink)

Emerging evidence suggests that microRNA (miRNA)‐mediated post‐transcriptional gene regulation plays an essential role in modulating embryonic stem (ES) cell pluripotency maintenance, differentiation, and reprogramming of somatic cells to an ES cell‐like state. Investigations from ES cell‐enriched miRNAs, such as mouse miR‐290 cluster and human miR‐302 cluster, and ES cell‐depleted miRNAs such as let‐7 family miRNAs, revealed a common theme that miRNAs target diverse cellular processes including cell cycle regulators, signaling pathway effectors, transcription factors, and epigenetic modifiers and shape their (...) protein output. The combinatorial effects downstream of miRNA action allow miRNAs to modulate cell‐fate decisions effectively. Furthermore, the transcription and biogenesis of miRNAs are also tightly regulated. Thus, elucidating the interplay between miRNAs and other modes of gene regulation will shed new light on the biology of pluripotent stem cells and somatic cell reprogramming. (shrink)

In this paper, we revisit a host–parasite system with multiple parasite strains and superinfection proposed by Nowak and May :81–89, 1994), and study its global dynamics when we relax the two strict conditions assumed therein. As for system with two parasite strains, we derive that the basic reproduction number $$R_0$$ is the threshold condition for parasite extinction and the invasion reproduction number $$R_i^j\ $$ is the subthreshold condition for coexistence of two parasite strains. As for system with three parasite (...) strains, we are surprised to discover the global stability of parasite-free and coexistence equilibrium, which is distinct from the previous result. Furthermore, for system with n strains, we obtain the global asymptotical stability of the parasite-free equilibrium, conjecture a general result on the global stability of coexistence equilibrium and provide two numerical examples to testify our conjecture. (shrink)

This study explores positive migrant storytelling in non-governmental organizations’ advocacy campaigns. We focus on the practices and implications of leveraging storytelling towards charity organizations’ institutional goals. Drawing upon critical discourse studies and narrative studies, we propose a critical storytelling approach that pays attention to the specific nature of storytelling as a discourse practice in itself. We focus on a UNHCR human-interest story of refugee displacement and subsequent integration into the UK. We employ the heuristic concept of positioning that calls for (...) analysis at different, though interrelated levels of narrative activity, to explore how affect is mobilized and the specific identity categories and affect types that are created for migrants and their hosts. We then situate these identity positions in wider dominant discourses of migrant integration. We show that the story foregrounds emblematic refugees, worthy of hosts’ support as well as relationships of dependence between migrants and the host society as requisites to successful integration. We argue that the ways in which an individual refugee story gets mobilized as an exemplary story reveals canonized forms of positive migrant storytelling emerging in the UK context that end up invoking dominant power asymmetries in relation to migration and British integration. (shrink)

Through corporate social responsibility activities, a firm can develop the capability for managing and benefiting from stakeholder relationships. This study refers to such a capability as stakeholder influence capacity. In a host country, locally sourcing parts and/or materials can generate economic value and improve social welfare. Moreover, local sourcing provides opportunities for a foreign firm to apply and advance SIC while closely interacting with host-country stakeholders. Accordingly, we expect that a firm, having gained SIC through CSR activities in (...) its home country, will be more likely to source parts and/or materials in the host country. We also expect that the relationship between SIC and host-country sourcing is conditional upon a foreign firm’s intangible resources and liabilities of foreignness. Our empirical analysis, using Korean datasets, supports the positive relationship between CSR and local sourcing. We find that this positive relationship is more pronounced either when the firm is committed to technology development or when its home and host countries are geographically or culturally distant. (shrink)

The metaphor of host and guest has value for exploring the practice and role identity of nurses on inpatient mental health units. Two complementary texts, one from the ancient Zen record of Lin‐chi, and the other from the contemporary hermeneutic philosopher Richard Kearney, are used to elaborate meanings of host and guest that can be applied to the situation of mental health nurses. In a doctoral study with a hermeneutic design, I addressed the topic of nurse–patient relationship using (...) an interpretive framework that included sources from Buddhist thought. The positions of host and guest emerged from interviews with nurses as one interpretive theme to open up new understanding of the topic. The two texts, originally distant in era and culture, both employ the host and guest metaphor. They are applied to extracts from interviews to open up discussions of hierarchy, status, patients' perspectives, otherness and resistances as features of nurses' complex experience. These provide insights into understanding practice and suggest implications for how institutional environments shape practice. An intercultural reading of texts can provide a source of new understanding of nurse–patient relationships. (shrink)

Studies on surrogate motherhood have mostly explored paid arrangements through the lens of a contract model, as clinical work or as a maternal identity-building project. Turning to the under-examined case of unpaid, so-called altruistic surrogate motherhood and based on an analysis of interviews with women who had been unpaid surrogate mothers in a full gestational surrogacy with a friend or relative in Canada, the United States or Australia, this article explores altruistic surrogate motherhood as relational work. It argues that this (...) form of surrogate motherhood within close interpersonal relations can be conceptualised through the relational work involved in hosting a child for the intended parents. The article explores how relational work in this context implies an embodied, asymmetrical and far-reaching sense of responsibility that surrogate mothers describe as characteristic of their surrogacy experience. In this way, the article sheds light on feminist concerns about surrogacy as an embodied and objectifying work of women while at the same time illuminating how surrogate mothers respond to the intended parents in light of their pre-surrogacy relationship, how meanings are negotiated by them and how relationships are managed during the pregnancy. (shrink)

Viruses are the simplest of pathogens, but possess sophisticated molecular mechanisms to manipulate host behavior, frequently utilizing molecular mimicry. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to bind to the host receptor neuropilin-1 in order to gain entry into the cell. To do this, the virus utilizes its spike protein polybasic cleavage site (PCS), which mimics the CendR motif of neuropilin-1’s endogenous ligands. In addition to facilitating cell entry, binding to neuropilin-1 has analgesic effects. We (...) discuss the potential impact of neuropilin-1 binding by SARS-CoV-2 in ameliorating sickness behavior of the host, and identify a convergent evolutionary strategy of PCS cleavage and subsequent neuropilin binding in other human viruses. In addition, we discuss the evolutionary leap of the ancestor of SARS-COV-2, which involved acquisition of the PCS thus faciliting binding to the neuropilin-1 receptor. Acquisition of the PCS by the ancestor of SARS-CoV-2 appears to have led to pleiotropic beneficial effects including enhancement of cell entry via binding to ACE2, facilitation of cell entry via binding to neuropilin-1, promotion of analgesia, and potentially the formation of decoy epitopes via enhanced shedding of the S1 subunit. Lastly, other potential neuromanipulation strategies employed by SARS-CoV-2 are discussed, including interferon suppression and the resulting reduction in sickness behavior, enhanced transmission through neurally mediated cough induction, and reduction in sense of smell. (shrink)

The paper by Magill and Neaves in this issue of the Journal attempts to rebut the "natural potency" position, based on recent advances in direct reprogramming of somatic cells to yield "induced pluripotent stem" (iPS) cells. As stated by the authors, the natural potency position holds that because "a human embryo directs its own integral organismic function from its beginning . . . there is a whole, albeit immature, and distinct human organism that is intrinsically valuable with the status (...) of inviolability and deserving full moral respect" (p. 26). The authors boldly assert that "The recent production of iPS . . . highlights a prima facie absurdity for the natural potentiality argument" (p. 29). Yet the argument against natural potency is both logically flawed and based on a characterization of the scientific evidence that is factually inaccurate. (shrink)

A better understanding of how schistosomes exploit host nutrients, neuro‐endocrine hormones and signalling pathways for growth, development and maturation may provide new insights for improved interventions in the control of schistosomiasis. This paper describes recent advances in the identification and characterisation of schistosome tyrosine kinase and signalling pathways. It discusses the potential intervention value of insulin signalling, which may play an important role in glucose uptake and carbohydrate metabolism in schistosomes, providing the nutrients essential for parasite growth, development and, (...) notably, female fecundity. Significant progress has also been made in the characterisation of other schistosome growth factor receptors, such as transforming growth factor beta receptor and epidermal growth factor receptor, and in our understanding of their roles in the host‐parasite molecular dialogue and parasite development. The use of parasite signal transduction components as novel vaccine or drug targets may prove invaluable in prevention, treatment and control strategies to combat schistosomiasis. (shrink)

Sharing economy platforms mediate exchanges between service providers and consumers. The experiences of service providers in the sharing economy have been extensively studied. Nevertheless, our knowledge in regard to the extent to which providers’ participation influences their wellbeing remains incomplete. This study focuses on the peer-to-peer accommodation platform Airbnb and explores why and how different aspects involved in hosting can contribute to or hinder hosts’ hedonic and eudaimonic wellbeing. To that end, I conducted a netnography and depth interviews with Airbnb (...) hosts. Based on a qualitative analysis of the overall dataset, I identify three sources of positive affect associated with hosting, namely, the sociability involved in the host-guest interaction, the act of providing hospitality, and positive feedback from guests. However, I also identify four conditions, which can turn hosting into a source of negative affect, namely, customer misbehavior, high volumes of guests, negative reviews, and income dependency. In addition, I elaborate on the relationship between hosting and life satisfaction in regard to the income that hosts generate through hosting and the working conditions of Airbnb hosts. Last but not least, I show that being a provider on Airbnb can contribute to eudaimonic wellbeing, focusing on four dimensions of eudaimonia, namely, self-realization, personal growth, a sense of purpose and meaning, and relationships. Theoretical and managerial implications for service providers and sharing economy platforms are discussed. (shrink)

People's attitude to animals is similar to the attitude Westworld has people adopt vis‐a‐vis the hosts: People often deem animal suffering acceptable because it improves their well‐being but still feel upset when an animal is mistreated just for the sake of it. Speciesism is the view that human well‐being matters more than that of other creatures. One justification for this view attempts to ground human beings’ special moral status in their membership in the human species itself. Some of Westworld's characters (...) are visibly tempted by this kind of justification. Logan is a prime example. One common argument in defense of speciesism is that non‐human animals are far less intelligent than human beings. Westworld's characters have interesting discussions about free will. In Westworld, all dialogues about free will focus on whether the hosts are determined or whether they could act otherwise. (shrink)