The Streptococcus pyogenes CRISPR‐Cas system has gained widespread application as a genome editing and gene regulation tool as simultaneous cellular delivery of the Cas9 protein and guide RNAs enables recognition of specific DNA sequences. The recent discovery that Cas9 can also bind and cleave RNA in an RNA‐programmable manner indicates the potential utility of this system as a universal nucleic acid‐recognition technology. RNA‐targeted Cas9 (RCas9) could allow identification and manipulation of RNA substrates in live cells, empowering the study of (...) cellular gene expression, and could ultimately spawn patient‐ and disease‐specific diagnostic and therapeutic tools. Here we describe the development of RCas9 and compare it to previous methods for RNA targeting, including engineered RNA‐binding proteins and other types of CRISPR‐Cas systems. We discuss potential uses ranging from live imaging of transcriptional dynamics to patient‐specific therapies and applications in synthetic biology. (shrink)

Presented in six principal analytic chapters with supporting appendices, this book explores the role of Islam in precipitating Europe's twelfth century commercial renaissance. Employing the classic analytic techniques of economics, Gene Heck determines that medieval Europe's feudal interregnum was largely caused by indigenous governmental business regulation and not by shifts in international trade patterns. He then proceeds by demonstrating how Islamic economic precepts provided the ideological rationales that empowered medieval Europe to escape its three-centuries-long experiment in "Dark Age economics" (...) ― in the process, providing the West with its archetypic tools of capitalism. While treatises such as Maxime Rodinson's excellent book, Islam and Capitalism, document the capitalistic nature of the Islamic economic system, in applying modern economic method to medieval orientalist historiography, this work is unique in capturing both the evolution and the impact of the system's role in forging medieval history. (shrink)

Restructured health care reimbursement systems and new requirements for nonprofit hospitals are transforming the U.S. health system, creating opportunities for enhanced integration of public health and health care goals. This article explores the role of public health practitioners and lawyers in this moment of transformation. We argue that the population perspective and structural strategies that characterize public health can add value to the health care system but could get lost in translation as changes to tax requirements and payment systems are (...) rapidly implemented. We urge public health leaders to take a more active role in hospital assessments of community health needs and evaluation of the patient outcomes for which providers are accountable. (shrink)

Before September 11, 2001, a mass-casualty terrorist attack on American soil was generally considered a remote possibility. Similarly, before October 4, 2001—the first confirmed case of anthrax caused by intentional release — widespread bioterrorism seemed implausible. Among the arguments that such a biological artack was unlikely included: the lack of a historical precedent; the technological and organizational challenges to acquiring and weaponizing a biological agent; and the almost universal moral opprobrium that would certainly accompany the use by terrorists of such (...) a weapon. In the wake of September 11th and October 4th, however, many are reconsidering the likelihood of a large-scale bioterrorist attack against civilians.The Centers for Disease Control and Prevention defines bioterrorism as the intentional release of viruses, bacteria, or toxins for the purpose of harming or killing civilian. One measurement of the public health system's level of bioterrorism preparedness is the quality and distribution of laws mandating the reporting of diseases caused by certain biological agents. (shrink)

Before September 11, 2001, a mass-casualty terrorist attack on American soil was generally considered a remote possibility. Similarly, before October 4, 2001—the first confirmed case of anthrax caused by intentional release — widespread bioterrorism seemed implausible. Among the arguments that such a biological artack was unlikely included: the lack of a historical precedent; the technological and organizational challenges to acquiring and weaponizing a biological agent; and the almost universal moral opprobrium that would certainly accompany the use by terrorists of such (...) a weapon. In the wake of September 11th and October 4th, however, many are reconsidering the likelihood of a large-scale bioterrorist attack against civilians.The Centers for Disease Control and Prevention defines bioterrorism as the intentional release of viruses, bacteria, or toxins for the purpose of harming or killing civilian. One measurement of the public health system's level of bioterrorism preparedness is the quality and distribution of laws mandating the reporting of diseases caused by certain biological agents. (shrink)

We address two points. First, one must explain how different, rare mutations ultimately lead to common psychopathological conditions. The developmental instability model offers one solution. Second, Keller & Miller perhaps miss the major processes other than variation fueled by rare deleterious mutations that account for interesting genetic variation in psychopathology, particularly when single alleles have non-negligible effects: Red Queen processes.

An anthology of contemporary readings in analytic aesthetics, this reference reflects the relationships among the central aesthetic concerns of recent years. Providing a new perspective on the contemporary philosophy of art, this volume examines the challenge of Postmodernism and how it may or may not affect the future of analytic aesthetics... offers a case study of the progress that has been made in handling the problem of expression in the arts... reconceptualizes the concepts of the art work, its properties, and (...) our experience and evaluation of it -- to take into account an expanding cultural, sociological contextualization, i.e., art as a culturally emergent product of social institutions and conventions... features several readings organized around clusters of writers discussing each other's ideas and proposals, including: Beardsley, Dickie, and Blizek -- Wolterstorff, Levinson, and Bender -- Stolnitz and Dickie -- Beardsley, Margolis, and Novitz -- and Sibley and Dickie. Suitable for professionals in the art industry and anyone interested in the philosophy or aesthetics of art. (shrink)

Bertolt Brecht and Theodor W. Adorno stand for opposing modes and stances within an artistic modernism oriented toward radical social transformation. In his 1962 essay ‘Commitment’, Adorno advanced a biting critique of Brecht’s work and artistic position. Adorno’s arguments have often been dismissed but, surprisingly, are seldom closely engaged with. This paper assesses these two approaches that have been so central to twentieth-century debates in aesthetics: Brecht’s dialectical realism and Adorno’s sublime or dissonant modernism. It provides what still has been (...) missing: a close reading and immanent critique of Adorno’s case against Brecht. And it clarifies one methodological blind spot of Adorno’s formalist conceptualisation of autonomy: he fails to provide the detailed analysis of context that his own dialectical method immanently calls for. The paper shows how and why Brecht’s dialectical realism holds up under Adorno’s attack, and draws conclusions for contemporary artistic practice. (shrink)

Joseph Beuys’ installation Plight forcefully avows of the Nazi genocide by means of negative presentation. The work culminates a collective artistic investigation of negative sculptural strategies for representing traumatic history, opened by the Nouveaux Réalistes under the impact of Alain Resnais’ documentary film Nuit et Brouillard. This article outlines this history and analyzes Plight in the context of the ‘after Auschwitz’ crisis of representation and traditional culture theorized by Theodor W. Adorno. For Adorno, Auschwitz demonstrated threats to autonomous subjectivity posed (...) by tendencies unfolding within the global social process of modernity itself. Reflecting on the fate of music, poetry and literature under these conditions, Adorno advocated a hermetic art of silence and dissonance, as exemplified by Paul Celan and above all Samuel Beckett. This article shows that in the visual arts, too, the genocidal violence of World War II was confronted with analogous strategies of indirection. In Plight, Beuys would successfully synthesize John Cage’s symbolic demolitions of traditional music and the investigations of negative presentation carried out in sculpture by Arman and Daniel Spoerri. (shrink)

Paul W. Taylor has proposed a foundational structure for developing a respect for nature. This structure appears to go weIl beyond what is needed to justify such respect. The intricacies and nuances of life on Earth can gain our respect without attempting the impossible task of abandoning our human perspective or a particular interest in our own species.

Despite widespread agreement that it would be ethical to use somatic cell gene therapy to correct serious diseases, there is still uneasiness on the part of the public about this procedure. The basis for this concern lies less with the procedure's clinical risks than with fear that genetic engineering could lead to changes in human nature. Legitimate concerns about the potential for misuse of gene transfer technology justify drawing a moral line that includes corrective germline therapy but excludes (...) enhancement interventions in both somatic and germline contexts. Keywords: somatic cell, germ line, genetic diseases, genetic engineering, humanness, enhancement, eugenics CiteULike Connotea Del.icio.us What's this? (shrink)

That holobionts are units of selection squares poorly with the observation that microbes are often recruited from the environment, not passed down vertically from parent to offspring, as required for collective reproduction. The taxonomic makeup of a holobiont’s microbial community may vary over its lifetime and differ from that of conspecifics. In contrast, biochemical functions of the microbiota and contributions to host biology are more conserved, with taxonomically variable but functionally similar microbes recurring across generations and hosts. To save what (...) is of interest in holobiont thinking, we propose casting metabolic and developmental interaction patterns, rather than the taxa responsible for them, as units of selection. Such units need not directly reproduce or form parent-offspring lineages: their prior existence has created the conditions under which taxa with the genes necessary to carry out their steps have evolved in large numbers. These taxa or genes will reconstruct the original interaction patterns when favorable conditions occur. Interaction patterns will vary in ways that affect the likelihood of and circumstances under which such reconstruction occurs. Thus, they vary in fitness, and evolution by natural selection will occur at this level. It is on the persistence, reconstruction, and spread of such interaction patterns that students of holobiosis should concentrate, we suggest. This model also addresses other multi-species collectively beneficial interactions, such as biofilms or biogeochemical cycles maintaining all life. (shrink)

types of application of genetic engineering for the insertion of genes into humans. The scientific requirements and the ethical issues associated with each type are discussed. Somatic cell gene therapy is technically the simplest and ethically the least controversial. The first clinical trials will probably be undertaken within the next year. Germ line gene therapy will require major advances in our present knowledge and it raises ethical issues that are now being debated. In order to provide guidelines for (...) determining when germ line gene therapy would be ethical, the author presents three criteria which should be satisfied prior to the time that a clinical protocol is attempted in humans. Enhancement genetic engineering presents significant, and troubling, ethical concerns. Except where this type of therapy can be justified on the grounds of preventive medicine, enhancement engineering should not be performed. The fourth type, eugenic genetic engineering, is impossible at present and will probably remain so for the foreseeable future, despite the widespread media attention it has received. Keywords: genetic engineering, somatic cells, germ cells, enhancement, eugenics, humanhood CiteULike Connotea Del.icio.us What's this? (shrink)

Our understanding of what microbes are and how they evolve has undergone many radical shifts since the late nineteenth century, when many still believed that bacteria could be spontaneously generated and most thought microbial “species” (if any) to be unstable and interchangeable in form and function (pleomorphic). By the late twentieth century, an ontology based on single cells and definable species with predictable properties, evolving like species of animals or plants, was widely accepted. Now, however, genomic and metagenomic data show (...) that lateral gene transfer compromises this picture of stability and predictability, and refocuses our attention on multilineage communities. Treating such communities as unstable but identifiable evolving “individuals” makes us again pleomorphists, of a sort. (shrink)

Lateral gene transfer, the exchange of genetic information between lineages, not only makes construction of a universal Tree of Life difficult to achieve, but calls into question the utility and meaning of any result. Here I review the science of prokaryotic LGT, the philosophy of the TOL as it figured in Darwin’s formulation of the Theory of Evolution, and the politics of the current debate within the discipline over how threats to the TOL should be represented outside it. We (...) could encourage a more realistic and supportive public understanding of evolution by admitting that what we believe in is not a unified meta-theory but a versatile and well-stocked explanatory toolkit. (shrink)

The causal theory, by J. Locke.--Phenomenalism, by G. Berkeley.--Skepticism, by D. Hume.--Traditional rationalism, by G. W. Leibniz.--Critical rationalism, by I. Kant.--Empiricism, by C. I. Lewis.--The quest for certainty, by R. Descartes.--Knowing and believing, by H. A. Prichard.--The right to be sure, by A. J. Ayer.

In fact, nearly every scientist who has written on the general subject of evolution has felt compelled to show how deftly he can skate toward the abyss of teleology without falling in.J.H. Campbell, 163Molecular biology has as its primary objective the elucidation of the coupling between genotype and phenotype. This goal has so far been pursued within a neoDarwinian theoretical framework which is relatively limited. Within this framework we can indeed understand remarkably well the mechanisms of replication and expression of (...) genes and the means by which replication and expression are regulated in cells; we know how genotype determines phenotype at the molecular level, in single cells. We are also close to an understanding of the relationship between genes and development in muticellular animals and plants. (shrink)

In fact, nearly every scientist who has written on the general subject of evolution has felt compelled to show how deftly he can skate toward the abyss of teleology without falling in.J.H. Campbell, 163Molecular biology has as its primary objective the elucidation of the coupling between genotype and phenotype. This goal has so far been pursued within a neoDarwinian theoretical framework which is relatively limited. Within this framework we can indeed understand remarkably well the mechanisms of replication and expression of (...) genes and the means by which replication and expression are regulated in cells; we know how genotype determines phenotype at the molecular level, in single cells. We are also close to an understanding of the relationship between genes and development in muticellular animals and plants. (shrink)

I distinguish two versions of kin selection theory—a purely genetic version and a version that also appeals to cultural forms of cooperation —and present an argument in favor of using the former when it comes to accounting for the evolution of cooperation in non-human organisms. Specifically, I first show that both GKST and WKST are equally mathematically coherent—they can both be derived from the Price equation—but not necessarily equally empirically plausible, as they are based on different assumptions about the inheritance (...) system underlying the cooperative phenotype. Given this, I then, second, present a model selection theoretic argument in favor of GKST over WKST. This argument is based on the fact that, in non-human cases, the former theory is likely to be as empirically successful as WKST, while containing fewer degrees of freedom. I end by defending both the intrinsic importance of this argument and its relevance to the discussion surrounding the “gene’s eye view of evolution.”. (shrink)

In this paper, rather than focusing on genes as an organising concept around which historical considerations of theory and practice in genetics are elucidated, we place genetic markers at the heart of our analysis. This reflects their central role in the subject of our account, livestock genetics concerning the domesticated pig, Sus scrofa. We define a genetic marker as a element existing in different forms in the genome, that can be identified and mapped using a variety of quantitative, classical and (...) molecular genetic techniques. The conjugation of pig genome researchers around the common object of the marker from the early-1990s allowed the distinctive theories and approaches of quantitative and molecular genetics concerning the size and distribution of gene effects to align in projects to populate genome maps. Critical to this was the nature of markers as ontologically inert, internally heterogeneous and relational. Though genes as an organising and categorising principle remained important, the particular concatenation of limitations, opportunities, and intended research goals of the pig genetics community, meant that a progressively stronger focus on the identification and mapping of markers rather than genes per se became a hallmark of the community. We therefore detail a different way of doing genetics to more gene-centred accounts. By doing so, we reveal the presence of practices, concepts and communities that would otherwise be hidden. (shrink)

In this paper, rather than focusing on genes as an organising concept around which historical considerations of theory and practice in genetics are elucidated, we place genetic markers at the heart of our analysis. This reflects their central role in the subject of our account, livestock genetics concerning the domesticated pig, Sus scrofa. We define a genetic marker as a element existing in different forms in the genome, that can be identified and mapped using a variety of quantitative, classical and (...) molecular genetic techniques. The conjugation of pig genome researchers around the common object of the marker from the early-1990s allowed the distinctive theories and approaches of quantitative and molecular genetics concerning the size and distribution of gene effects to align in projects to populate genome maps. Critical to this was the nature of markers as ontologically inert, internally heterogeneous and relational. Though genes as an organising and categorising principle remained important, the particular concatenation of limitations, opportunities, and intended research goals of the pig genetics community, meant that a progressively stronger focus on the identification and mapping of markers rather than genes per se became a hallmark of the community. We therefore detail a different way of doing genetics to more gene-centred accounts. By doing so, we reveal the presence of practices, concepts and communities that would otherwise be hidden. (shrink)

Interspecific comparisons reveal remarkable diversity in patterns of gene expression, even among closely related species. Combinatorial regulatory mechanisms could facilitate the evolution of this diversity. However, the high degree of interdependence characteristic of combinatorial networks would represent a major constraint on evolution and might generate many features that have no direct adaptive value.