Trafficking and persistence of fetal microchimeric cells (fMCs) and circulating extracellular vesicles (EVs) have been observed in animals and humans, but their consequences in the maternal body and their mechanistic contributions to maternal physiology and pathophysiology are not yet fully defined. Fetal cells and EVs may help remodel maternal organs after pregnancy‐associated changes, but the cell types and EV cargos reaching the mother in preterm pregnancies after exposure to various risk factors can be distinct from term pregnancies. As preterm (...) class='Hi'>delivery‐associated maternal complications are rising, revisiting this topic and formulating scientific questions for future research to reduce the risk of maternal morbidities are timely. Epidemiological studies report maternal cardiovascular risk as one of the major complications after preterm delivery. This paper suggests a potential link between fMCs and circulating EVs and adverse maternal cardiovascular outcomes post‐pregnancies, the underlying mechanisms, consequences, and methods for and how this link might be assessed. (shrink)

The demonstration that dendritic cell (DC)‐derived exosomes can be exploited for targeted RNAi delivery to the brain after systemic injection provides the first proof‐of‐concept for the potential of these naturally occurring vesicles as vehicles of drug delivery. As well as being amenable to existing in vivo targeting strategies already in use for viruses and liposomes, this novel approach offers the added advantages of in vivo safety and low immunogenicity. Fulfilment of the potential of exosome delivery methods warrants (...) a better understanding of their biology, as well as the development of novel production, characterisation, targeting and cargo‐loading nanotechnologies. Ultimately, exosome‐mediated drug delivery promises to overcome important challenges in the field of therapeutics, such as delivery of drugs across otherwise impermeable biological barriers, such as the blood brain barrier, and using patient‐derived tissue as a source of individualised and biocompatible therapeutic drug delivery vehicles. (shrink)

Ras homolog enriched in the striatum (Rhes) is a striatal enriched protein that promotes the formation of thin membranous tubes resembling tunneling nanotubes (TNT)—“Rhes tunnels”—that connect neighboring cell and transport cargoes: vesicles and proteins between the neuronal cells. Here the literature on TNT‐like structures is reviewed, and the implications of Rhes‐mediated TNT, the mechanisms of its formation, and its potential in novel cell‐to‐cell communication in regulating striatal biology and disease are emphasized. Thought‐provoking ideas regarding how Rhes‐mediated TNT, if it exists, (...) in vivo, would radically change the way neurons communicate in the brain are discussed. (shrink)

The generation of asymmetric cell shapes is a recurring theme in biology. In budding yeast, one form of cell asymmetry occurs for division and is generated by anisotropic growth of the mother cell to form a daughter cell bud. Previous genetic studies uncovered key roles for the small GTPase Cdc42 in organizing the actin cytoskeleton and vesicle delivery to the site of bud growth,1,2 but a recent paper has also raised questions about how control of Cdc42 activity is (...) integrated into a proposed hierarchical regulatory pathway that specifies a unique site of bud formation.3 BioEssays 25:833–836, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The exocyst is a conserved octameric complex that physically tethers a vesicle to the plasma membrane, prior to membrane fusion. It is important not only for secretion and membrane delivery but also, in mammalian cells, for cytokinesis, ciliogenesis, autophagy, tumorigenesis, and host defense. The combination of genome editing and advanced light microscopy of exocyst subunits in living cells has recently shown the complex to be much more dynamic than previously appreciated, and exposed how little we still know about (...) its function and regulation. (shrink)

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

Lysosomes are the site of degradation of obsolete intracellular material during autophagy and of extracellular macromolecules following endocytosis and phagocytosis. The membrane of lysosomes and late endosomes is enriched in highly glycosylated transmembrane proteins of largely unknown function. Significant progress has been made in recent years towards elucidating the pathways by which these lysosomal membrane proteins are delivered to late endosomes and lysosomes. While some lysosomal membrane proteins follow the constitutive secretory pathway and reach lysosomes indirectly via the cell surface (...) and endocytosis, others exit the trans‐Golgi network in clathrin‐coated vesicles for direct delivery to endosomes and lysosomes. Sorting from the Golgi or the plasma membrane into the endosomal system is mediated by signals encoded by the short cytosolic domain of these proteins. This review will discuss the role of lysosomal membrane proteins in the biogenesis of the late endosomal and lysosomal membranes, with particular emphasis on the structural features and molecular mechanisms underlying the intracellular trafficking of these proteins. (shrink)

Increasing evidence indicates that extracellular vesicles (EVs) secreted from tumor cells play a key role in the overall progression of the disease state. EVs such as exosomes are secreted by a wide variety of cells and transport a varied population of proteins, lipids, DNA, and RNA species within the body. Gliomas constitute a significant proportion of all primary brain tumors and majority of brain malignancies. Glioblastoma multiforme (GBM) represents grade IV glioma and is associated with very poor prognosis despite the (...) cumulative advances in diagnostic procedures and treatment strategies. Here, the authors describe the progress in understanding the role of EVs, especially exosomes, in overall glioma progression, and how new research is unraveling the utilities of exosomes in glioma diagnostics and development of next‐generation therapeutic systems. Finally, based on an understanding of the latest scientific literature, a model for the possible working of therapeutic exosomes in glioma treatment is proposed. (shrink)

Once regarded as cellular ‘debris’ extracellular vesicles (EVs) emerge as one of the most intriguing entities in cancer pathogenesis. Intercellular trafficking of EVs challenges the notion of cancer cell autonomy, and highlights the multicellular nature of such fundamental processes as stem cell niche formation, tumour stroma generation, angiogenesis, inflammation or immunity. Recent studies reveal that intercellular exchange mediated by EVs runs deeper than expected, and includes molecules causative for cancer progression, such as oncogenes (epidermal growth factor receptor, Ras), and tumour (...) suppressors (PTEN). The uptake of oncogenic EVs (oncosomes) by various cells may profoundly change their biology, signalling patterns and gene expression, and in some cases cause their overt tumorigenic conversion. Moreover, EVs circulating in blood and present in body fluids provide an unprecedented access to the molecular circuitry driving cancer cells, and new technologies are being developed to exploit this property as a source of unique cancer biomarkers. (shrink)

No cure yet exists for devastating Alzheimer's disease (AD), despite many years and humongous efforts to find efficacious pharmacological treatments. So far, neither designing drugs to disaggregate amyloid plaques nor tackling solely inflammation turned out to be decisive. Mesenchymal stem cells (MSCs) and, in particular, extracellular vesicles (EVs) originating from them could be proposed as an alternative, strategic approach to attack the pathology. Indeed, MSC‐EVs—owing to their ability to deliver lipids/proteins/enzymes/microRNAs endowed with anti‐inflammatory, amyloid‐β degrading, and neurotrophic activities—may be exploited (...) as therapeutic tools to restore synaptic function, prevent neuronal death, and slow down memory impairment in AD. Herein the results presented in the most recently published studies on this topic are critically evaluated, providing a strong rationale for possible employment of MSC‐EVs in AD. (shrink)

Neurotransmitter release takes place by the exocytosis of loaded synaptic vesicles. The vesicles then fuse to the presynaptic membrane and are recycled by an endocytotic mechanism. A quantitative optical assay that detects uptake and release of a fluorescent dye during presynaptic activity was recently developed and used on the frog neauromuscular junction. I discuss a report(1) that demonstrates the effective application of this method to a Drosophila preparation. The authors use the shibire mutation and a spider venom to identify two (...) intermediates in vesicle recycling. Their report, along with other recent studies, demonstrates the power and promise of the genetic approach for the understanding of mechanisms of synapse function and development. (shrink)

As a result of the COVID-19 global pandemic, paramedics in the UK face unprecedented challenges in the care of acutely unwell patients and their family members. This article will describe and discuss a new ethical dilemma faced by clinicians in the out-of-hospital environment during this time, namely the delivery of bad news to family members who are required to remain at home and self-isolate while the critically unwell patient is transported to hospital. I will discuss some failings of current (...) practice and reflect on some of the ethical and practical challenges confronting paramedics in these circumstances. I conclude by making three recommendations: first, that dedicated pastoral outreach teams ought to be set up during pandemics to assist family members of patients transported to hospital; second, I offer a framework for how bad news can be delivered during a lockdown in a less damaging way; and finally, that a new model of bad news delivery more suited for unplanned, time-pressured care should be developed. (shrink)

The Alexandra District Ambulance Service is the only volunteer-based ambulance service in Victoria, Australia. It provides an opportunity to reflect on the ethical issues surrounding the delivery of ambulance service by volunteers, and its impact on the community.

Partially because of the high cost of developing and maintaining cold chains, systems needed to keep heat-labile vaccines under adequate refrigeration from their points of manufacture to their administration in the field, the Joint WHO/FAO Expert Committee on Zoonoses (i.e., the approximately four fifths of all described human infections that people share with other vertebrate animals) recommended in 1982 operation of common cold chains by health and veterinary services in rural areas. Following this recommendation, a 1984 pilot level initiative in (...) medical-veterinary intersectoral cooperation should be regarded as a practical way to deliver human primary health care to currently neglected African pastoralists, and as a potential core program for development efforts overall within arid and semiarid areas of the African continent. (shrink)

James Walsh and Moira McQueen accurately conclude that the early delivery of anencephalic fetuses is morally acceptable, but the reasoning they use to reach that conclusion is flawed. First, the principle of double effect does not require a weighing of good and evil, but rather seeks a sufficient reason for tolerating the physical evil indirectly intended. Second, the principle of double effect requires a clear distinction between physical and moral causality. Third, the Catholic moral tradition will not admit direct (...) and intended killing of the innocent. Rather, early delivery of anencephalic fetuses is permissible because of the pathology associated with delivery of anencephalic fetuses at full term. Thus, the early delivery of an anencephalic infant is acceptable if the purpose of the moral act is avoiding a pathological condition on the part of the mother. (shrink)

In this article, we use the principlist approach to identify, analyse and attempt to solve the ethical problem raised by a pregnant woman's request for cesarean delivery in absence of medical indications.We use two different types of premises: factual (facts about cesarean delivery and specifically attitudes of obstetricians as derived from the EUROBS European study) and value premises (principles of beneficence and non-maleficence, respect for autonomy and justice).Beneficence/non-maleficence entails physicians' responsibility to minimise harms and maximise benefits. Avoiding its (...) inherent risks makes a prima facie case against cesarean section without medical indication. However, as vaginal delivery can have unintended consequences, there is a need to balance the somewhat dissimilar risks and benefits. The principle of autonomy poses a challenge in case of disagreement between the pregnant woman and the physician. Improved communication aimed to enable better informed choice may overcome some instances of disagreement. The principle of justice prohibits unfair discrimination, and broadly favours optimising resource utilisation.Available evidence supports vaginal birth in uncomplicated term pregnancies as the standard of care. The principlist approach offered a useful framework for ethical analysis of cesarean delivery on maternal request, identified the rights and duties of those involved, and helped reach a conclusion, although conflict at the individual level may remain challenging. (shrink)

My paper aims to find potential elements of comparison between ancient oratoria popularis and modern populist oratory. I will consider case studies drawn from Gracchan speech style and from the oratory of Donald Trump.

In this article, I will argue that the delivery of healthcare could be an act of resistance, that is, day‐to‐day, routine and perhaps mundane acts, undertaken in the course of the delivery of health services, which for many could also be considered otherwise routine care. I first consider how resistance has been conceptualised. How we understand resistance will determine if we believe healthcare could be conceptualised this way. I will show how resistance has been applied to day‐to‐day struggles (...) elsewhere and argue that it can clearly encompass open, collective dissent and more subtle, day‐to‐day action that does not necessarily make clear political demands. I go on to introduce some examples, where the delivery of health services could be conceptualised as resistance. While I advocate for a broad understanding of resistance, clearly not every act could be considered resistance; I will consider some points of tension and contention in utilising resistance to describe the delivery of health services, in particular discussing the issue of intent and opposition as they relate to resistance. Finally, while I hope that I make a convincing case, one final issue remains, namely, why turn to resistance at all, when many of the examples that I provide could be labelled using concepts that are more widely utilised. I will offer some general reflections on this point, speaking to the benefits and potential of resistance. (shrink)

Inside and outside of a Christian worldview, bioethicists have discussed ectopic pregnancy at some length as a maternal-fetal vital conflict. Most bioethicists agree that methotrexate and salpingostomy are low-risk, successful interventions for this life-threatening pathology, and are thus beneficent, just, and wholly acceptable. A small cohort of Christian, largely Catholic, bioethicists have reservations about methotrexate and salpingostomy, but cannot resolve their internal disputes about these because of flawed casuistry. This paper aims to settle the issue about whether methotrexate and salpingostomy (...) are acceptable within a Catholic worldview: despite the best arguments in favor of methotrexate as a moral option, it is morally unacceptable, and despite hesitation about salpingostomy related to analogies with previable delivery, it is the optimal procedure for ectopic pregnancy. (shrink)

필자는 본 논문을 통해 서구 형이상학이 제시하는 몸의 위상을 분석한 뒤 새로운 몸 개념을 통해 기존의 몸의 도식의 전복 가능성을 고찰해 보고자 한다. 데카르트에 의해 수립된 몸의 도식은 몸-자동기계(body-mecanic)와 의식조정-자동기계라는 이중의 층위로 분절화되어 있는데 우리는 논증을 통해 이것을 비판적으로 분석하도록 할 것이다. 기존의 몸 도식이 ‘메카닉(mecanic)’이라는 정합적이고 기능주의적인 유기체 논리에서 벗어나지 못하고 있다는 점에 주목하여, 필자는 들뢰즈와 가따리의 “기관 없는 신체(Corps sans organes)” 개념의 프리즘을 통해 “장기-몸(intestins-corps)”이라는 새로운 몸 개념을 제시하고자 한다. 장기-몸(intestins-corps)은 일련의 정합적이고 유기체적인 질서로부터 적출되어 나와 카오스적인 에너지로 (...) 들끓으며 이질적 요소들과의 무한연접으로 열려있는, 새로운 차원의 몸이다. 이러한 장기-몸의 봉기를 가장 잘 나타내주는 사태는 다름 아닌 극한고통이 도래하는 출산이라고 본다. 필자는 출산이 어떤 의미에서 ‘장기-몸’이 실질적으로 가동되는 상태인지를 지젝의 논의의 분석을 통해 심도 있게 고찰할 것이다. 또한 출산을 거친 자들이 상징질서로 편입되지 않고 금기를 깨고 되돌아오는, 살아있는 망자(the living dead)임을 지젝의 논의로부터 분석해 보겠다. 이로서 출산과 같은 극한고통의 체험이 갖는 카오스적 파괴의 힘이 어떤 측면에서 상징적 질서에 균열을 가할 수 있는지도 발터 벤야민의 ‘신적 폭력’ 개념을 착안해 고찰할 것이다. (shrink)

In the discipline of practical theology, one finds a long history of linking the name of the field to diaconiology, in which you find the Greek word diaconia, directly translated as 'service'. For good and scientific reasons, the field changed its name to practical theology in some Faculties of Theology but that does not take away the fact that this field of research is still very much engaged in the broad area of 'service of all kinds'. The purpose of this (...) article was to do a descriptive investigation into the problems and challenges of service delivery in the suburb of Belhar (Cape Town), specifically looking at the role of leadership during a (new) time of struggle. As part of the normative task, the researcher took a closer look at the Belhar Confession as a prophetic stance in this regard. In an ironic twist, we see in these events the struggle between the real and the ideal that is typical of many places in the country facing problems with service delivery. The Church often thinks it knows what the world wants from it - inspiration, 'leadership,' clear teaching. But surely what the world is most hungry for is the simple knowledge that healing is possible - not by forgetting or minimizing outrages and sufferings but by sheer, obstinate, costly commitment to work with the grain of grace. (Rowan Williams, Archbishop of Canterbury, in Lapsley 2012:i). (shrink)

Cochran has argued that Catholic health care occupies a “unique place on the border of public and private life”. Catholic health care is accountable to both its religious and sacramental traditions and its public responsibilities. It is inevitable that “border skirmishes” will arise. Yet there is no single formula for suggesting what public-private collaboration should comprise or how conflicts between values ought to be resolved. It may be, as Cochran suggests, that increasingly bitter conflicts over widely valued services such as (...) sterilization, combined with market pressures to conform to for-profit trends in health care, will make divestiture of faith-based hospitals in favor of other types of church-community partnerships the best course for the future. (shrink)

Lipid vesicles are often used as compartment structures for preparing cell‐like systems and models of protocells, the hypothetical precursor structures of the first cells at the origin of life. Although the various artificially made vesicle systems are already remarkably complex, they are still very different from and much simpler than any known living cell. Nevertheless, the preparation and study of the structure and the dynamics of functionalized vesicle systems may contribute to a better understanding of biological cells, in (...) particular of the essential features of a living cell that are not found in the non‐living form of matter. The study of protocell models may possibly lead to a better understanding of the origin of the first cells. To avoid misunderstanding in this field of research, it would be useful if generally accepted definitions of terms like “artificial cells,” “synthetic cells,” “minimal cells,” “protocells,” and “primitive cells” exist. Editor's suggested further reading in BioEssaysSynthetic cells and organelles: compartmentalization strategies Abstract. (shrink)

Thinkers from a variety of fields analyze the roles of imaging technologies in science and consider their implications for many issues, from our conception of selfhood to the authority of science. In what follows, I encourage scholars to develop an applied philosophy of imaging, that is, to collect these analyses of scientific imaging and to reflect on how they can be made useful for ongoing scientific work. As an example of this effort, I review concepts developed in Don Ihde’s phenomenology (...) of technology and refigure them for use in the analysis of scientific practice. These concepts are useful for drawing out the details of the interpretive frameworks scientists bring to laboratory images. Next, I apply these ideas to a contemporary debate in neurobiology over the interpretation of images of neurons which have been frozen at the moment of transmitter release. This reveals directions for further thought for the study of neurotransmission. (shrink)

Herpes simplex virus (HSV)‐derived vectors are currently being developed for the introduction of foreign DNA into neurons. HSV vectors can facilitate a range of molecular studies on postmitotic neurons and may ultimately be used for somatic cell gene therapy for certain neurologic diseases. In this article, the salient features of the pathogenesis and molecular biology of HSV relevant to its use as a vector are described, along with an overview of the methods used to derive these vectors. The accomplishments which (...) have been made to date using the HSV vector system are discussed, with emphasis on the issues of this technology which remain to be addressed. HSV has the potential to be a most useful tool for neuronal cell transgenesis and it is likely that important neurobiological questions will be answered using this vector system. (shrink)

Microfluidic technology – the manipulation of fluids at micrometer scales – has revolutionized many areas of synthetic biology. The bottom‐up synthesis of “minimal” cell models has traditionally suffered from poor control of assembly conditions. Giant unilamellar vesicles (GUVs) are good models of living cells on account of their size and unilamellar membrane structure. In recent years, a number of microfluidic approaches for constructing GUVs has emerged. These provide control over traditionally elusive parameters of vesicular structure, such as size, lamellarity, membrane (...) composition, and internal contents. They also address sophisticated cellular functions such as division and protein synthesis. Microfluidic techniques for GUV synthesis can broadly be categorized as continuous‐flow based approaches and droplet‐based approaches. This review presents the state‐of‐the‐art of microfluidic technology, a robust platform for recapitulating complex cellular structure and function in synthetic models of biological cells. (shrink)

Recently, Gao et al. and Chappie et al. elucidated the crystal structures of the polytetrameric stalk domain of the dynamin‐like virus resistance protein, MxA, and of the G‐domain dimer of the large, membrane‐deforming GTPase, dynamin, respectively. Combined, they provide a hypothetical oligomeric structure for the complete dynamin protein. Here, it is discussed how the oligomers are expected to form and how they participate in dynamin mediated vesicle fission during the process of endocytosis. The proposed oligomeric structure is compared with (...) the novel mechanochemical model of dynamin function recently proposed by Bashkirov et al. and Pucadyil and Schmid. In conclusion, the new model of the dynamin oligomer has the potential to explain how short self‐limiting fissogenic dynamin assemblies are formed and how concerted GTP hydrolysis is achieved. The oligomerisation of two other dynamin superfamily proteins, the guanylate binding proteins (GBPs) and the immunity‐related GTPases (IRGs), is addressed briefly. (shrink)

Interest in home birth appears to be growing among American women, and most obstetricians can expect to encounter patients who are considering home birth. In 2011, the American College of Obstetricians and Gynecologists (ACOG) issued an opinion statement intended to guide obstetricians in responding to such patients.In this article, I examine the ACOG statement in light of the historical and contemporary clinical realities surrounding home birth in the United States, an examination guided in part by my own experiences as an (...) obstetrician in home-birth-friendly and homebirth-unfriendly medical milieus. Comparison with other guidelines indicates that ACOG treats home birth as an ethical exception: comparable evidence leads to strikingly different recommendations in the case of home birth and the case of trial of labor following a prior cesarean; and ACOG treats other controversial issues that involve similar ethical questions quite differently.By casting the provision of information as not just the primary but the sole ethical responsibility of the obstetrician, ACOG statement obviates obstetricians’ responsibilities to provide appropriate clinical care and to make the safest possible clinical environment for those mothers who choose home birth and for their newborns. What, on its face, seems to be a statement of respect for women’s autonomy, implicitly authorizes behaviors that unethically restrain truly autonomous choices. Obstetricians need not attend home births, I argue. Our ethical duties do, however, oblige us (1) to refer clients to skilled clinicians who will attend home birth, (2) to continue respectful antenatal care for those women choosing home birth, (3) to provide appropriate consultation to home birth attendants, and (4) to ensure that transfers of care are smooth and nonpunitive. (shrink)

Hydroxycamptothecin is a potent antineoplastic agent that has shown efficacy against multiple tumor lines in vitro. eww140918dxn This is the first study to investigate the release, distribution, and efficacy of hydroxycamptothecin which was incorporated into the biodegradable polymer Polylactic Acid (PLA), and implant into brain directly. In vitro release curve generated showed that a large initial release occurred over the first three days and was followed by a steady, but considerably slower rate of release over the next 25 days. After (...) implanting the discs into 40 male SD rats, the animals were followed up to 28 days, where the concentration in brain tissue was far higher than that in peripheral blood at the each of the eight time-points evaluated, and it was also within the therapeutic range for C6 cells tested in vitro. The in vivoefficacy of the discs was evaluated with rats inoculated intracranially with C6 glioma and treated with hydroxycamptothecin polymer compared to intravenous as well as intratumoral injections; the median survival is 21.1, 13.9, 14.9 days, respectively. Given these data, we conclude that the biodegradable polymer PLA releases hydroxycamptothecin, producing tumoricidal levels in brain tissues and prolonging survival in a rat glioma model. (shrink)

The radical transformations caused by the rapid development of information and communication technologies in the mid-1990s prompted the transition to the knowledge society which identified the key role of knowledge as the most important and valuable capital of organizations and had a decisive impact on the development of corporate training. In our study, we aimed to analyze the training methods used in American companies in the knowledge society, particularly, their feasibility, features, benefits and possible limitations. The results of our study (...) show that, at present, e-learning is considerably more widely used in American companies than instructor-led classroom training. Most organizations use blended learning which implies the combination of e-learning methods and instructor-led learning methods. A powerful stimulus for the wide implementation of e-learning methods was produced by the COVID-19 pandemic when the use of educational technologies made it possible for the companies not only to continue training and development of their employees but also to implement tactical and strategic practices which will have long-term implications for the future of the training industry. The most widely used e-learning methods in American companies are virtual classroom/webcast, online or computer-based methods, social learning, augmented reality, virtual reality, and artificial intelligence. In spite of certain limitations of e-learning methods, they have a number of important benefits which allow companies to expand access to training, save costs, increase adaptability and flexibility of learning programs, etc., and thus satisfy their needs in qualified employees. (shrink)

We present the case of a 36-year-old woman who has experienced three lost pregnancies; during the most recent loss, a full term pregnancy, she almost died from complications of placental abruption. She is now completing the 34th week of gestation and is experiencing symptoms similar to those under which she lost the previous pregnancy. Despite a lack of specific medical indications, the patient and her husband firmly but politely request that the attending obstetrician/perinatologist perform an immediate cesarean section in order (...) to alleviate the couple’s anxiety about possibly never having a family. Discussing the case are an experienced perinatologist, a neonatologist, a regional perinatal center coordinator, and a clinical ethicist. (shrink)

The cilium/flagellum is a sensory-motile organelle ancestrally present in eukaryotic cells. For assembly cilia universally rely on intraflagellar transport (IFT), a specialised bidirectional transport process mediated by the ancestral and conserved IFT complex. Based on the homology of IFT complex proteins to components of coat protein I (COPI) and clathrin-coated vesicles, we propose that the non- vesicular, membrane-bound IFT evolved as a specialised form of coated vesicle transport from a protocoatomer complex. IFT thus shares common ancestry with all protocoatomer (...) derivatives, including all vesicle coats and the nuclear pore complex (NPC). This has major implications for the evolutionary origin of the cilium. First, it reinforces the tenet that duplication and divergence of pre-existing structures, rather than symbiosis, were the major themes during cilium evolution. Second, it suggests that the initial step in the autogenous origin of the cilium was the establishment of a membrane patch with transmembrane proteins transported by the ancestral vesicle-coating IFT complex. We propose a scenario for how the initial membrane patch gradually protruded to enhance exposure to the environment, then started to move, and finally compartmentalised to render receptor signalling and ciliary beating more efficient. BioEssays 28: 191–198, 2006. © 2006 Wiley periodicals, Inc. (shrink)

Joining an antagonistic phosphoinositide (PtdInsP) kinase and phosphatase into a single protein complex may regulate rapid and local PtdInsP changes. This may be important for processes such as membrane fission that require a specific PtdInsP and that are innately local and rapid. Such a complex could couple vesicle formation, with erasing of the identity of the donor organelle from the vesicle prior to its fusion with target organelles, thus preventing organelle identity intermixing. Coordinating signals are postulated to switch (...) the relative activities of the kinase and phosphatase in a spatio‐temporal manner that matches membrane fission events. The discovery of two such complexes supports this hypothesis. One regulates the interconversion of phosphatidylinositol and PtdIns(3)P by joining the Vps34 PtdIns 3‐kinase and the myotubularin 3‐phosphatases. The other regulates the interconversion between PtdIns(3)P and PtdIns(3,5)P2 through the Fab1/PIKfyve kinase and the Fig4/mFig4 phosphatase. These lipids are essential components of the endosomal identity code. (shrink)

In “Practical Knowledge of Language”, C.-h. Tsai criticizes the arguments in “Swimming and Speaking Spanish” (this issue, pp. 331–341), on the grounds that its account of knowledge of language as knowledge-how is mistaken. In its place, he proposes an alternative account in terms of Russell’s concept “knowledge-by-acquaintance”. In this paper, I show that this account succeeds neither in displacing the account in Swimming and Speaking Spanish nor in addressing Tsai’s main concern: solving the “delivery problem”.

I hypothesize here that the ability of probiotics to synthesize neuroactive compounds provides a unifying microbial endocrinology‐based mechanism to explain the hitherto incompletely understood action of commensal microbiota that affect the host's gastrointestinal and psychological health. Once ingested, probiotics enter an interactive environment encompassing microbiological, immunological, and neurophysiological components. By utilizing a trans‐disciplinary framework known as microbial endocrinology, mechanisms that would otherwise not be considered become apparent since any candidate would need to be shared among all three components. The range (...) of neurochemicals produced by probiotics includes neurochemicals for which receptor‐based targets on immune and neuronal elements (intestinal and extra‐intestinal) have been well characterized. Production of neurochemicals by probiotics therefore allows for their consideration as delivery vehicles for neuroactive compounds. This unifying microbial endocrinology‐based hypothesis, which may facilitate the selection and design of probiotics for clinical use, also highlights the largely unrecognized role of neuroscience in understanding how microbes may influence health.Editor's suggested further reading in BioEssays Harvesting the biological potential of the human gut microbiome Abstract. (shrink)

Fast delivery to customers required Amazon fulfillment center employees to meet high daily productivity quotas. In some of the centers, robots and people worked together. The efficiency of the robots and the company’s productivity standards, made it challenging for workers to avoid injury. Candace accepted a position in a center utilizing robots and was injured on the job, just like hundreds of others. Her injuries and lack of workplace accommodations prevented her from meeting productivity quotas and consequently jeopardized her (...) job. She wondered if customers understood the human cost incurred to achieve such fast delivery and if it was ethical to subject employees to such work environments. Students are asked to analyze the situation from various ethical perspectives and offer their opinions to Candace. During their analysis they will learn about ethics, ethical standards, stakeholders, and corporate social responsibility. (shrink)

The Arf family proteins are best known for their roles in the vesicle biogenesis. However, they also play fundamental roles in a wide range of cellular regulation besides vesicular trafficking, such as modulation of lipid metabolic enzymes, cytoskeleton remodeling, ciliogenesis, lysosomal, and mitochondrial morphology and functions. Growing studies continue to expand the downstream effector landscape of Arf proteins, especially for the less‐studied members, revealing new biological functions, such as amino acid sensing. Experiments with cutting‐edge technologies and in vivo functional (...) studies in the last decade help to provide a more comprehensive view of Arf family functions. In this review, we summarize the cellular functions that are regulated by at least two different Arf members with an emphasis on those beyond vesicle biogenesis. (shrink)

Definition of the problem: The rapid pace of medical progress has drawn renewed attention to the various possible ways of treating dead or brain-dead pregnant women since the 1980's. The discussion today revolves around medical, social, legal and economic aspects. The historical areas of conflict which surrounded deliveries carried out on dead mothers (usually by means of a Sectio in mortua, nowadays known as a perimortem Caesarean section) and their significance in today's debate are, for the most part, regarded as (...) being of little relevance.Arguments: The history of the Sectio in mortua was, for a long time, influenced by the difficulty in establishing whether the mother and foetus were actually dead, by the degree of autonomy of the foetus in the womb, by religious issues, by the lack of acceptance among the people because of their irrational fears concerning the operation and by legal regulations and constraints especially in relation to operations carried out on the dying. Each of these areas shows remarkable parallels to the present-day medical and ethical discussion.Conclusion: The value of such considerations does not lie in the uncritical application of experience gained in the past, but rather in a growing awareness of the wide spectrum of parameters and in a deeper understanding of the various possible approaches to a given situation. The tradition in the Western world of carrying out a delivery on a dead mother, in spite of the conflict of interests between the mother and the foetus, is of particular importance. In practice, the many non-medical factors should be taken more into consideration, with special emphasis being placed on the informed consent of the relatives. (shrink)

ABSTRACT Although dominant discourses of various kinds are frequently reproduced on talk radio, the fundamentally collaborative nature of the medium also means that it is able to serve as a channel through which to challenge these discourses. Using Critical Discourse Analysis, this article examines how neoliberal ideology structures discussions around ‘service delivery protest’ on South African talk radio, and explores some of the roles that talk radio is, and is not, able to play in constructing resistance to neoliberal ideology. (...) Our analysis yielded two discourses, namely: naturalisation of the commodification of everyday life, and market over welfare – both of which seemed to cohere with neoliberal frameworks and rationalities in different ways. We conclude by suggesting how radio can be used to denaturalise neoliberalism’s impulse towards making common sense conditions that enable economic oppression and exploitation. (shrink)