The Cas9 endonuclease is the central component of the Type II CRISPR/Cas system, a prokaryotic adaptive restriction system against invading nucleic acids, such as those originating from bacteriophages and plasmids. Recently, this RNA‐directed DNA endonuclease has been harnessed to target DNA sequences of interest. Here, we review the development of Cas9 as an important tool to not only edit the genomes of a number of different prokaryotic and eukaryotic species, but also as an efficient system for site‐specific transcriptional repression or (...) activation. Additionally, a specific Cas9 protein has been observed to target an RNA substrate, suggesting that Cas9 may have the ability to be programmed to target RNA as well. Cas proteins from other CRISPR/Cas subtypes may also be exploited in this regard. Thus, CRISPR/Cas systems represent an effective and versatile biotechnological tool, which will have significant impact on future advancements in genome engineering. (shrink)

Objectives—To assess the process involved in obtaining ethical approval for a single-centre study involving geographically dispersed subjects with an uncommon genetic disorder. Design—Observational data of the application process to 53 local research ethics committees (LRECs) throughout Wales, England and Scotland. The Multicentre Research Ethics Committee (MREC) for Wales had already granted approval. Results—Application to the 53 LRECs required 24,552 sheets of paper and took two months of the researcher's time. The median time taken for approval was 39 days with only (...) seven (13%) of committees responding within the recommended 21 days. In at least nineteen cases (36%) a subcommittee considered the application. Thirty-three committees (62%) accepted the proposal without amendments but, of the remainder, four (8%) requested changes outside of the remit of LRECs. Discussion—Difficulties still exist with the system for obtaining ethical approval for studies involving a single centre but with patients at multiple sites, as is often required for genetic observational research. As such studies differ from true multicentre studies, it may be advantageous to develop a separate and specific process of application to ensure that resources are not unnecessarily expended in the quest for ethical approval. (shrink)

We can gain fresh insights into aspects of criminal liability by focusing first on the prior topic of criminal responsibility, and on the relational dimensions of responsibility: responsibility is responsibility for something, to someone. We are criminally responsible as citizens, to our fellow citizens, for committing 'public' wrongs: I discuss the difficulty of giving determinate content to this idea of public wrongs, and the way in which, whereas moral responsibility is typically strict, criminal responsibility is not. Finally, I explore the (...) grounds on which defendants might deny that they are criminally responsible before the courts that seek to try them. (shrink)

The larval arms of echinoid plutei are used for locomotion and feeding. They are composed of internal calcite skeletal rods covered by an ectoderm layer bearing a ciliary band. Skeletogenesis includes an autonomous molecular differentiation program in primary mesenchyme cells (PMCs), initiated when PMCs leave the vegetal plate for the blastocoel, and a patterning of the differentiated skeletal units that requires molecular cues from the overlaying ectoderm. The arms represent a larval feature that arose in the echinoid lineage during the (...) Paleozoic and offers a subject for the study of gene co-option in the evolution of novel larval features. We isolated new molecular markers in two closely related but differently developing species, Heliocidaris tuberculata and Heliocidaris erythrogramma. We report the expression of a larval arm-associated ectoderm gene tetraspanin, as well as two new PMC markers, advillin and carbonic anhydrase. Tetraspanin localizes to the animal half of blastula stage H. tuberculata and then undergoes a restriction into the putative oral ectoderm and future location of the postoral arms, where it continues to be expressed at the leading edge of both the postoral and anterolateral arms. In H. erythrogramma, its expression initiates in the animal half of blastulae and expands over the entire ectoderm from gastrulation onward. Advillin and carbonic anhydrase are upregulated in the PMCs postgastrulation and localized to the leading edge of the growing larval arms of H. tuberculata but do not exhibit coordinated expression in H. erythrogramma larvae. The tight spatiotemporal regulation of these genes in H. tuberculata along with other ontogenetic and phylogenetic evidence suggest that pluteus arms are novel larval organs, distinguishable from the processes of skeletogenesis per se. The dissociation of expression control in H. erythrogramma suggest that coordinate gene expression in H. tuberculata evolved as part of the evolution of pluteus arms, and is not required for larval or adult development. (shrink)

Careful reading of imaginative literature teaches an attentiveness fundamental to the care of the sick.

Teaching medical ethics by the case method may be enriched by adding to the principles-and-rules approach to practical reasoning modes of inquiry and interpretation that engage the moral imagination.

The origin of marine invertebrate larvae has been an area of controversy in developmental evolution for over a century. Here, we address the question of whether a pelagic “larval” or benthic “adult” morphology originated first in metazoan lineages by testing the hypothesis that particular gene co-option patterns will be associated with the origin of feeding, indirect developing larval forms. Empirical evidence bearing on this hypothesis is derivable from gene expression studies of the sea urchin larval gut of two closely related (...) but differently developing congenerics, Heliocidaris tuberculata (feeding indirect-developing larva) and H. erythrogramma (nonfeeding direct developer), given two subsidiary hypotheses. (1) If larval gut gene expression in H. tuberculata was co-opted from an ancestral adult expression pattern, then the gut expression pattern will remain in adult H. erythrogramma despite its direct development. (2) Genes expressed in the larval gut of H. tuberculata will not have a coordinated expression pattern in H. erythrogramma larvae due to loss of a functional gut. Five structural genes expressed in the invaginating archenteron of H. tuberculata during gastrulation exhibit substantially different expression patterns in H. erythrogramma with only one remaining endoderm specific. Expression of these genes in the adult of H. erythrogramma and larval gut of H. tuberculata, but not in H. erythrogramma larval endoderm, supports the hypothesis that they first played roles in the formation of adult structures and were subsequently recruited into larval ontogeny during the origin and evolution of feeding planktotrophic deuterostome larvae. (shrink)

The study of law and politics is one of the foundation stones of the discipline of political science, and it has been one of the productive areas of cross-fertilization between the various subfields of political science and between political science and other cognate disciplines. This Handbook provides a comprehensive survey of the field of law and politics in all its diversity, ranging from such traditional subjects as theories of jurisprudence, constitutionalism, judicial politics and law-and-society to such re-emerging subjects as comparative (...) judicial politics, international law, and democratization. The Oxford Handbook of Law and Politics gathers together leading scholars in the field to assess key literatures shaping the discipline today and to help set the direction of research in the decade ahead. (shrink)

Jeffrie G Murphy & Jean Hampton, Forgiveness and Mercy Cambridge and New York: Cambridge University Press, 1988, 194 pp. Kathleen Dean Moore, Pardons: Justice, Mercy, and the Public Interest New York and Oxford: Oxford University Press, 1989, 271 pp.

Cassirer, E. Antropología filosófica.--Vecchio, G. del. El hombre y la naturaleza.--Jaspers, K. La pregunta acerca del hombre.--Marx, K. Existencia y conciencia.--Mounier, E. Las estructuras del universo personal.--Ortega y Gasset, J. Pasado y porvenir para el hombre actual.--Platón. Fedón.--Santayana, G. El nacimiento de la razón. Schaff, A. El marxismo y la filosofía del hombre.--Shorojova, E. V. Lo general humano y lo clasista en la concienia del hombre.--Spear, O. Animal rationale.--Spengler, O. El advenimiento del hombre. Wahl, J. Algunas observaciones acerca del hombre.

Reviewed work: The Eighteenth Century Confronts the Gods by Frank E. Manuel Historical Pessimism in the French Enlightenment by Henry Vyverberg.