Protein‐carbohydrate interactions have been found to be important in many steps in lymphocyte recirculation and inflammatory responses. A family of carbohydrate‐binding proteins or lectins, termed selectins, has been discovered and shown to be involved directly in these processes. The three known selectins, termed L‐, E‐ and P‐selectins, have domains homologous to other Ca2+‐dependent (C‐type) lectins. L‐selectin is expressed constitutively on lymphocytes, E‐selectin is expressed by activated endothelial cells, and P‐selectin is expressed by activated platelets and endothelial cells. Here, we review (...) the nature of the carbohydrate determinants in tissues recognized by these selectins. The expression of specific sialylated, fucosylated and sulfated carbohydrates in activated endothelium and high endothelial venules promotes interactions with L‐selectin on leukocyte surfaces. In contrast, E‐ and P‐selectins recognize specific carbohydrate determinants related to sialyl Lex antigen on neutrophil and monocyte surfaces. The discovery of the selectins has generated excitemient among glycoconjugate researchers that other carbohydrate‐binding proteins and their cognate ligands will be found to function in regulating many types of cellular interactions. (shrink)

A large proportion of tumour‐associated antigens seem to be determined by carbohydrate structures. Advances in the study of the antigenicity of cell‐surface carbohydrates have been hampered by the absence of advanced monoclonal hybridoma technology comparable to that available for the study of protein antigens. Monoclonal antibodies have been raised against a carbohydrate epitope (43–9F) that is associated with the proliferative features of squamous lung carcinomas. These were used in turn to generate anti‐idiotype antibodies with homology to 43–9F. The method and (...) its possible applications are described, together with a procedure to detect rare cell membrane variants within large populations. (shrink)

One of the hardest tasks for a physician is to treat and take care of patients suffering from such chronic disease as diabetes. The difficulties arise mainly because the medical treatment and the necessary follow up demand that the physician interfere with, or at least influence, the whole lifestyle of the patient. The diabetic must pursue a distinct way of daily living: he must change his eating habits, go on a diet, create a healthy lifestyle and keep to it. Patients (...) may know about the necessity of being on a diet, but a great number of them don’t have any understanding of such basic terms as “protein”, “carbohydrate”, “lipid”, or even “calorie”, which are essential to an understanding matters to do with diet.1 While it is obvious that scientific and technical terms should be translated into everyday language, and acknowledging that providing patients with information is an essential part of care, it is not possible, and not even necessary to give every piece of information to every patient.Just as with any other chronic disease, a good outcome can only be achieved through a strong commitment to serving the interest of the patient. In order to accomplish this, physicians must be aware of the ethical implications raised by non-compliance. The authors are very much in agreement with the American sociologist, Peter Conrad, who stated that:"From a medical perspective, patients who do not comply with the doctor’s orders are usually seen as deviant, and deviance requires correction. But many chronically ill people view their behavior differently, as a matter of self regulation."He is also right when he states that “compliance” looks very different when seen from the patient’s perspective. As an example, patients might adjust their medication to meet their everyday social needs rather than complying exactly with …. (shrink)

Cells express many proteins that bind to laminin, the major adhesive component of basement membranes. Some of these, specifically integrins, function as transmembrane receptors that ‘signal’ the presence of laminin on the cell surface to the cytoplasm. Lectins constitute a second class of laminin binding proteins that may augment integrin function by interacting with laminin carbohydrate. Caution must be used in ascribing functions to other laminin binding proteins, especially cytosolic proteins.

Protein turnover (PT) has been formally defined only in equilibrium conditions, which is ill‐suited to quantify PT during dynamic processes that occur during embryogenesis or (extra) cellular signaling. In this Hypothesis, we propose a definition of PT in an out‐of‐equilibrium regime that allows the quantification of PT in virtually any biological context. We propose a simple mathematical and conceptual framework applicable to a broad range of available data, such as RNA sequencing coupled with pulsed‐SILAC datasets. We apply our framework to (...) a published dataset and show that stimulation of mouse dendritic cells with LPS leads to a proteome‐wide change in PT. This is the first quantification of PT out‐of‐equilibrium, paving the way for the analysis of biological systems in other contexts. (shrink)

The relationship between law and a population’s health is complex and poorly understood. To the extent that scholarship exists on the subject, it has usually focused on epidemics that are concentrated in relatively vulnerable, marginalized communities. Often, individual behaviors are assumed to play a major role in the epidemiology of these diseases. Perhaps, as a result, these illnesses become stigmatized and the object of coercive laws, which in turn become the subject of litigation, legal debate, and ultimately scholarly analysis. Thus, (...) to the extent that U.S. legal scholars have thought about public health in the last 30 years, they have generally done so in the context of tuberculosis, intravenous drug abuse, and a handful of similar conditions. Likewise, Jonathan Mann’s own appreciation of the importance of human rights to public health emerged in the wake of his work with HIV, which is perhaps the prototypical stigmatized disease. (shrink)

The relationship between law and a population’s health is complex and poorly understood. To the extent that scholarship exists on the subject, it has usually focused on epidemics that are concentrated in relatively vulnerable, marginalized communities. Often, individual behaviors are assumed to play a major role in the epidemiology of these diseases. Perhaps, as a result, these illnesses become stigmatized and the object of coercive laws, which in turn become the subject of litigation, legal debate, and ultimately scholarly analysis. Thus, (...) to the extent that U.S. legal scholars have thought about public health in the last 30 years, they have generally done so in the context of tuberculosis, intravenous drug abuse, and a handful of similar conditions. Likewise, Jonathan Mann’s own appreciation of the importance of human rights to public health emerged in the wake of his work with HIV, which is perhaps the prototypical stigmatized disease. (shrink)

The accurate annotation of an unknown protein sequence depends on extant data of template sequences. This could be empirical or sets of reference sequences, and provides an exhaustive pool of probable functions. Individual methods of predicting dominant function possess shortcomings such as varying degrees of inter-sequence redundancy, arbitrary domain inclusion thresholds, heterogeneous parameterization protocols, and ill-conditioned input channels. Here, I present a rigorous theoretical derivation of various steps of a generic algorithm that integrates and utilizes several statistical methods to predict (...) the dominant function in unknown protein sequences. The accompanying mathematical proofs, interval definitions, analysis, and numerical computations presented are meant to offer insights not only into the specificity and accuracy of predictions, but also provide details of the operatic mechanisms involved in the integration and its ensuing rigor. The algorithm uses numerically modified raw hidden markov model scores of well defined sets of training sequences and clusters them on the basis of known function. The results are then fed into an artificial neural network, the predictions of which can be refined using the available data. This pipeline is trained recursively and can be used to discern the dominant principal function, and thereby, annotate an unknown protein sequence. Whilst, the approach is complex, the specificity of the final predictions can benefit laboratory workers design their experiments with greater confidence. -/- . (shrink)

Harm reduction initiatives such as the distribution of naloxone have been crucial in saving lives during the opioid crisis in North America. Despite these efforts, today’s drug supply contaminated...

This article examines the significance of Friedrich Nietzsche to Albert Camus’ concepts of absurdity and revolt. It rests on three related claims. First, that Nietzsche’s critique of metaphysics is the point of departure for Camus’ absurdist inquiries. Second, that Camus’ philosophy of revolt is informed in crucial ways by Nietzsche’s views on the sources of moral and intellectual authority in the modern world. Finally, that Camusian revolt is an attempt to deal with the political crisis of foundationalism in a way (...) that preserves Nietzsche’s anti-essentialism while also avoiding the excesses of absolutist politics. Ultimately, I suggest that the origins and implications of Camus’ project cannot be grasped apart from an account of its engagement with Nietzsche. (shrink)

From a twenty-first century partnership between bioethics and neuroscience, the modern field of neuroethics is emerging, and technologies enabling functional neuroimaging with unprecedented sensitivity have brought new ethical, social and legal issues to the forefront. Some issues, akin to those surrounding modern genetics, raise critical questions regarding prediction of disease, privacy and identity. However, with new and still-evolving insights into our neurobiology and previously unquantifiable features of profoundly personal behaviors such as social attitude, value and moral agency, the difficulty of (...) carefully and properly interpreting the relationship between brain findings and our own self-concept is unprecedented. Therefore, while the ethics of genetics provides a legitimate starting point - even a backbone - for tackling ethical issues in neuroimaging, they do not suffice. Drawing on recent neuroimaging findings and their plausible real-world applications, we argue that interpretation of neuroimaging data is a key epistemological and ethical challenge. This challenge is two-fold. First, at the scientific level, the sheer complexity of neuroscience research poses challenges for integration of knowledge and meaningful interpretation of data. Second, at the social and cultural level, we find that interpretations of imaging studies are bound by cultural and anthropological frameworks. In particular, the introduction of concepts of self and personhood in neuroimaging illustrates the interaction of interpretation levels and is a major reason why ethical reflection on genetics will only partially help settle neuroethical issues. Indeed, ethical interpretation of such findings will necessitate not only traditional bioethical input but also a wider perspective on the construction of scientific knowledge. (shrink)

Recent advances in the brain sciences have dramatically improved our understanding of brain function. As we find out more and more about what makes us tick, we must stop and consider the ethical implications of this new found knowledge. This ground-breaking book on the emerging field of neuroethics answers many pertinent questions, such as: What makes monitoring and manipulating the human brain so ethically challenging? Will having a new biology of the brain through imaging make us less responsible for our (...) behavior and lose our free will? Should certain brain scan studies be disallowed on the basis of moral grounds? A distinguished group of contributors from a wide range of fields make this an invaluable introduction to neuroethics. (shrink)

The handbook contains more than 50 chapters by leaders from around the world and a broad range of sectors of academia and clinical practice spanning the ...

Recent advances in the brain sciences have dramatically improved our understanding of brain function. As we find out more and more about what makes us tick, we must stop and consider the ethical implications of this new found knowledge. Will having a new biology of the brain through imaging make us less responsible for our behavior and lose our free will? Should certain brain scan studies be disallowed on the basis of moral grounds? Why is the media so interested in (...) reporting results of brain imaging studies? What ethical lessons from the past can best inform the future of brain imaging? These compelling questions and many more are tackled by a distinguished group of contributors to this volume on neuroethics. The wide range of disciplinary backgrounds that the authors represent, from neuroscience, bioethics and philosophy, to law, social and health care policy, education, religion and film, allow for profoundly insightful and provocative answers to these questions, and open up the door to a host of new ones. The contributions highlight the timeliness of modern neuroethics today, and assure the longevity and importance of neuroethics for generations to come. (shrink)

The application of neuroimaging technology to the study of the injured brain has transformed how neuroscientists understand disorders of consciousness, such as the vegetative and minimally conscious states, and deepened our understanding of mechanisms of recovery. This scientific progress, and its potential clinical translation, provides an opportunity for ethical reflection. It was against this scientific backdrop that we convened a conference of leading investigators in neuroimaging, disorders of consciousness and neuroethics. Our goal was to develop an ethical frame to move (...) these investigative techniques into mature clinical tools. This paper presents the recommendations and analysis of a Working Meeting on Ethics, Neuroimaging and Limited States of Consciousness held at Stanford University during June 2007. It represents an interdisciplinary approach to the challenges posed by the emerging use of neuroimaging technologies to describe and characterize disorders of consciousness. (shrink)

Neuroethics, in its modern form, investigates the impact of brain science in four basic dimensions: the self, social policy, practice and discourse. In this study, we analyzed a set of 461 peer-reviewed articles with neuroethics content, published by authors from 32 countries. We analyzed the data for: (1) trends in the development of international neuroethics over time, and (2) how challenges at the intersection of ethics and neuroscience are viewed in countries that are considered developed by International Monetary Fund (IMF) (...) standards, and in those that are developing. Our results demonstrate a steady increase in global participation in neuroethics from 1989 to 2005, characterized by an increase in numbers of articles published specifically on neuroethics, journals publishing these articles, and countries contributing to the literature. The focus from all countries was on the practice of brain science and the amelioration of neurological disease. Indicators of technology creation and diffusion in developing countries were specifically correlated with increases in publications concerning policy implications of brain science. Neuroethics is an international endeavor and, as such, should be sensitive to the impact that context has on acceptance and use of technological innovation. (shrink)

A landmark in the scientific literature, the Oxford Handbook of Neuroethics presents a pioneering review of a topic central to the biosciences. It breaks new ground in bringing together leading neuroscientists, philosophers, and lawyers to tackle some of the most significant ethical issues that face us now and will continue to do so.

In October 2022, I had the privilege of joining Hank Greely on the opening panel of the annual International Neuroethics Society (INS) meeting in Montréal, Tiohtiá:ke, situated on the traditional t...

In Phillip Kerr’s 1994 spellbinding novel A Philosophical Investigation, the medical test to which the protagonist refers is a functional brain scan based on positron emission tomography. It is used to run large studies of male and female brains and, following a lead suggested by animal studies, has been used to identify rare cases of human male subjects who lack the ventral medial nucleus. This nucleus, in the experiment, is hypothesized to inhibit the activity of the sexually dimorphic nucleus, a (...) preoptic area of the male brain believed to be a repository of male aggressive response. Prior research, we learn from the plot, shows that 3 in 100,000 human males are VMN-negative. Thirty percent of those affected are believed to be in prison or to have a criminal record; 70% are believed to stabilize levels of aggression by producing increased levels of estrogen. Identities of subjects participating in the brain scan studies are protected through the conversion of real names to those of famous figures of the past — Bertrand Russell, Charles Dickens. Those for whom results are unfavorable are recontacted, and they are offered counseling. (shrink)

As one of the most compelling technologies for imaging the brain, functional MRI (fMRI) produces measurements and persuasive pictures of research subjects making cognitive judgments and even reasoning through difficult moral decisions. Even after centuries of studying the link between brain and behavior, this capability presents a number of novel significant questions. For example, what are the implications of biologizing human experience? How might neuroimaging disrupt the mysteries of human nature, spirituality, and personal identity? Rather than waiting for an ethical (...) agenda to emerge from some unpredictable combination of the concerns of ethicists and researchers, the attention of journalists, or after controversy is sparked by research that cannot be retracted, we queried key figures in bioethics and the humanities, neuroscience, media, industry, and patient advocacy in focus groups and interviews. We identified specific ethical, legal and social issues (ELSI) that highlight researcher obligations and the nonclinical impact of the technology at this new frontier. (shrink)

Empirical studies and ethical-legal analyses have demonstrated that incidental fndings in the brain, most commonly vascular in origin, must be addressed in the current era of imaging research. The challenges, however, are substantial. The discovery and management of incidental fndings vary, at minimum, by institutional setting, professional background of investigators, and the inherent diferences between research and clinical protocols. In the context of human subjects protections, the challenges of disclosure of unexpected and potentially meaningful clinical information concern privacy and confdentiality, (...) communication, and responsibility for follow-up. Risks, including a blurring of boundaries between research and clinical practice, must be weighed against the possible beneft to subjects and a moral duty to inform. Identifcation and examination of these challenges have been met by scientifc interest and a robust, interdisciplinary response resulting in the pragmatic recommendations discussed here. (shrink)

Neuroethics, in its modern form, investigates the impact of brain science in four basic dimensions: the self, social policy, practice and discourse. In this study, we analyzed a set of 461 peer‐reviewed articles with neuroethics content, published by authors from 32 countries. We analyzed the data for: (1) trends in the development of international neuroethics over time, and (2) how challenges at the intersection of ethics and neuroscience are viewed in countries that are considered developed by International Monetary Fund (IMF) (...) standards, and in those that are developing. Our results demonstrate a steady increase in global participation in neuroethics from 1989 to 2005, characterized by an increase in numbers of articles published specifically on neuroethics, journals publishing these articles, and countries contributing to the literature. The focus from all countries was on the practice of brain science and the amelioration of neurological disease. Indicators of technology creation and diffusion in developing countries were specifically correlated with increases in publications concerning policy implications of brain science. Neuroethics is an international endeavor and, as such, should be sensitive to the impact that context has on acceptance and use of technological innovation. (shrink)

There is substantial literature on fetal alcohol spectrum disorder research involving Aboriginal children, but little related literature on other common neurodevelopmental conditions such as autism spectrum disorder or cerebral palsy for this population. As part of our work in cross-cultural neuroethics, we examined this phenomenon as a case study in Canada. We conducted semi-structured interviews with health researchers working on the frontline with First Nation communities to obtain perspectives about: reasons for the lack of ASD and CP research within the (...) Aboriginal context, the potential ethical and social implications of this disparity, and recommendations for change. Participants reported that the major barriers to engage in ASD or CP research are under-reporting and under-diagnosis of these conditions in Aboriginal communities, difficulties in establishing trust between community members and researchers, challenges in accessing children living under the care of child welfare services, and lack of support from universities and funding agencies to encourage community partnerships. They further perceived threats to justice as the population is denied the benefits of ASD and CP research, and stigma related to the possible over-representation of FASD in the population. The adoption of strength- and community-based practices to improve engagement and address disparities, and to create health databases with prevalence rates that are representative of all forms of disability in both Aboriginal and non-Aboriginal populations are critical steps to close these gaps. (shrink)

Supply-side interventions such as prescription drug monitoring programs, “pill mill” laws, and dispensing limits have done little to quell the burgeoning opioid crisis. An increasingly popular demand-side alternative to these measures – now adopted by 38 jurisdictions in the USA and 7 provinces in Canada — is court-mandated involuntary commitment and treatment. In Massachusetts, for example, Part I, Chapter 123, Section 35 of the state's General Laws allows physicians, spouses, relatives, and police officers to petition a court to involuntarily commit (...) and treat a person whose alcohol or drug abuse poses a likelihood of serious harm. This paper explores the ethical underpinnings of this law as a case study for others. First, we highlight the procedural and substantive standards of Section 35 and evaluate the application of the law in practice, including the frequency with which it has been invoked and outcomes. We then use this background to inform an ethical critique of the law. Specifically, we argue that the infringement of autonomy and privacy associated with involuntary intervention under Section 35 is not currently justified on the grounds of a lack of evidenced benefits and a risk of significant of harm. Further ethical concerns also arise from a lack of standard of care provided under the Section 35 pathway. Based on this analysis, we advance four recommendations for change to mitigate these ethical shortcomings. (shrink)

Advances in neuroscience have enabled the transition of transcranial direct current stimulation (tDCS) from research and clinical settings to public use. For this primarily home-based context, tDCS has been popularized as a do-it-yourself (DIY) approach to improved cognition and wellness. The line between wellness and health is blurry, however, and little is known about how engagement with therapeutic tDCS impacts users’ interactions with other interventions such as clinical consultations, pharmacotherapy, complementary medicine, and even other neurotechnology. To close this gap, we (...) collected data from the online content aggregator Reddit and analyzed posts pertaining to tDCS. Findings indicate that most users turn to Reddit to request information about tDCS as an adjunct, but not as a bypass, to ongoing or prior approaches. Posts suggest that mainstream medical care is viewed as necessary but not sufficient to address conditions such as depression and anxiety. Users discuss a mix of benefits and harms. This discourse provides valuable insights into the health practices, concerns and priorities of users, and new knowledge for informing applications of neurotechnology both inside and outside the therapeutic setting. (shrink)

Abstract:Open neural tube defects or myelomeningoceles are a common congenital condition caused by failure of closure of the neural tube early in gestation, leading to a number of neurologic sequelae including paralysis, hindbrain herniation, hydrocephalus and neurogenic bowel and bladder dysfunction. Traditionally, the condition was treated by closure of the defect postnatally but a recently completed randomized controlled trial of prenatal versus postnatal closure demonstrated improved neurologic outcomes in the prenatal closure group. Fetal surgery, or more precisely maternal-fetal surgery, raises (...) a number of ethical issues that we address including who the patient is, informed consent, surgical innovation and equipoise as well maternal assumption of risk. As the procedure becomes more widely adopted into practice, we suggest close monitoring of new fetal surgery centers, in order to ensure that the positive results of the trial are maintained without increased risk to both the mother and fetus. (shrink)

Environmental ethicists and experts in human health have raised concerns about the effects of hydraulic fracking to access natural oil and gas resources found deep in shale rock formations on surrounding ecosystems and communities. In this study, we analyzed the prevalence of discourse on brain and mental health, and ethics, in the peer-reviewed and grey literature in the five-year period between 2016 and 2022. A total of 84 articles met inclusion criteria for analysis. Seventy-six percent (76%) mentioned impacts on brain (...) (e.g., neural tube defects, neurological symptoms), and mental health (e.g., negative psychological effects, stress, depression) briefly; 11 reports dedicated substantive discourse to either or both together. References to safety (77%) dominated the ethics context. Discussion of environmental injustices as fracking sites disproportionately affect vulnerable communities appeared in 38% of the papers. We examine the findings through the lens of environmental neuroethics that brings human-made changes to the environment, brain and mental health, and ethics together into three interwoven lines of inquiry. (shrink)

To date, ethics discussions about stem cell research overwhelmingly have centered on the morality and acceptability of using human embryonic stem cells. Governments in many jurisdictions have now answered these “first-level questions” and many have now begun to address ethical issues related to the donation of cells, gametes, or embryos for research. In this commentary, we move beyond these ethical concerns to discuss new themes that scientists on the forefront of NRM development anticipate, providing a preliminary framework for further discussion (...) between scientists and ethicists. Fostering strong partnerships between neuroscientists and ethicists that operate and collaborate within this evolving framework will maximize the translation of NRM discoveries on the brain into cures that are safe and address the needs of science and society. (shrink)

This article examines the significance of Friedrich Nietzsche to Albert Camus’ concepts of absurdity and revolt. It rests on three related claims. First, that Nietzsche’s critique of metaphysics is the point of departure for Camus’ absurdist inquiries. Second, that Camus’ philosophy of revolt is informed in crucial ways by Nietzsche’s views on the sources of moral and intellectual authority in the modern world. Finally, that Camusian revolt is an attempt to deal with the political crisis of foundationalism in a way (...) that preserves Nietzsche’s anti-essentialism while also avoiding the excesses of absolutist politics. Ultimately, I suggest that the origins and implications of Camus’ project cannot be grasped apart from an account of its engagement with Nietzsche. (shrink)

The momentum for global neuroscience that is geopolitically-free has never been greater, and neuroethics holds a unique place in this context both in its translational and transnational forms.In th...

ZusammenfassungMit den Fortschritten im Bereich der psychiatrisch-genetischen Forschung gehen auch intensive Diskussionen bezüglich der daraus erwachsenden Implikationen einher. Hoffnungen wie Befürchtungen gegenüber der neuen Technologie und deren Folgen werden gleichermaßen zum Ausdruck gebracht. Über die Einstellung der Bevölkerung und insbesondere der Patienten mit affektiven oder schizophrenen Erkrankungen und ihrer Angehörigen in Deutschland war bisher allerdings wenig bekannt. Daher führten wir im Rahmen des Deutschen Humangenomprojektes erstmals eine Studie durch, um die Einstellungen und ihre beeinflussenden Faktoren zu erfassen. Wir entwickelten einen (...) Fragebogen zur Erfassung der Erwartungen, Hoffnungen und Befürchtungen sowie der die Einstellung beeinflussenden Faktoren. Hiermit wurde eine repräsentative Stichprobe von 3077 Personen aus der Allgemeinbevölkerung am Telefon befragt. Weiterhin wurden mit 316 Patienten und 163 Angehörigen persönliche standardisierte Interviews anhand des Fragebogens durchgeführt. Die Mehrzahl der Befragten hatte eine positive Einstellung zu psychiatrisch-genetischer Forschung, äußerte jedoch gleichzeitig ethische Bedenken. Übereinstimmend waren die Befragten der Ansicht, dass Informationen aus genetischen Untersuchungen vertraulich behandelt werden sollten. Kleine, aber signifikante Unterschiede zwischen den Gruppen zeigten sich bezüglich der Einstellung zu präsymptomatischer genetischer Diagnostik. Unsere Ergebnisse weisen auf eine Ambivalenz der Befragten gegenüber der psychiatrisch-genetischen Forschung und Untersuchung hin: Neben einer überwiegend positiven Einstellung wurden auch moralische Bedenken geäußert. (shrink)