Neuroimaging and Responsibility Assessments

Could neuroimaging evidence help us to assess the degree of a person’s responsibility for a crime which we know that they committed? This essay defends an affirmative answer to this question. A range of standard objections to this high-tech approach to assessing people’s responsibility is considered and then set aside, but I also bring to light and then reject a novel objection—an objection which is only encountered when functional (rather than structural) neuroimaging is used to assess people’s responsibility

Effect of Maternal Exercise on Adverse Cardio-Pulmonary Responses in Offspring Exposed to Post-Natal Chronic Hypoxia

Emerging evidence shows exercise by women throughout pregnancy (i.e., maternal exercise) endows the offspring with positive health benefits and resistance to many diseases later in life. PURPOSE: To determine if maternal exercise reduces unfavorable cardiopulmonary development and improves exercise capacity in offspring after chronic hypoxic exposure throughout early life. METHODS: Female adult C57BL/6J mice were randomly assigned to one of the following groups: high altitude, sedentary (HS), high altitude, active (HE), or the respective, low-altitude conditions (LS or LE). Pregnant females in the exercise groups performed voluntary wheel running during mating and the perinatal period (about 4 weeks). Three days after birth, the pups in the high-altitude groups were exposed to chronic hypobaric hypoxia (450mmHg). When pups were eight weeks old, body size (weight and tail length) was measured and exercise capacity was assessed via a Rotarod test. Terminal procedures were performed to measure right ventricular systolic pressure (RVSP), hematocrit, and heart remodeling (Fulton’s Index: right ventricular weight ratio to bodyweight (RV/BW) and to the left ventricle plus septum (RV/LV+S)). RESULTS: All variables measured had a main effect for altitude (pCONCLUSION: Chronic hypoxia decreases exercise capacity and attenuates growth. This stress also induces potentially harmful cardiovascular changes, such as high blood viscosity, RVSP, and right ventricular hypertrophy. Our results indicate that maternal exercise may attenuate some of the negative effects of chronic hypoxia in the offspring, but does not prevent significant development impairments

Moral enhancement: do means matter morally?

One of the reasons why moral enhancement may be controversial, is because the advantages of moral enhancement may fall upon society rather than on those who are enhanced. If directed at individuals with certain counter-moral traits it may have direct societal benefits by lowering immoral behavior and increasing public safety, but it is not directly clear if this also benefits the individual in question. In this paper, we will discuss what we consider to be moral enhancement, how different means may be used to achieve it and whether the means we employ to reach moral enhancement matter morally. Are certain means to achieve moral enhancement wrong in themselves? Are certain means to achieve moral enhancement better than others, and if so, why? More specifically, we will investigate whether the difference between direct and indirect moral enhancement matters morally. Is it the case that indirect means are morally preferable to direct means of moral enhancement and can we indeed pinpoint relevant intrinsic, moral differences between both? We argue that the distinction between direct and indirect means is indeed morally relevant, but only insofar as it tracks an underlying distinction between active and passive interventions. Although passive interventions can be ethical provided specific safeguards are put in place, these interventions exhibit a greater potential to compromise autonomy and disrupt identity

IUPHAR-DB: new receptors and tools for easy searching and visualization of pharmacological data

The IUPHAR database is an established online reference resource for several important classes of human drug targets and related proteins. As well as providing recommended nomenclature, the database integrates information on the chemical, genetic, functional and pathophysiological properties of receptors and ion channels, curated and peer-reviewed from the biomedical literature by a network of experts. The database now includes information on 616 gene products from four superfamilies in human and rodent model organisms: G protein-coupled receptors, voltage- and ligand-gated ion channels and, in a recent update, 49 nuclear hormone receptors (NHRs). New data types for NHRs include details on co-regulators, DNA binding motifs, target genes and 3D structures. Other recent developments include curation of the chemical structures of approximately 2000 ligand molecules, providing electronic descriptors, identifiers, link-outs and calculated molecular properties, all available via enhanced ligand pages. The interface now provides intelligent tools for the visualization and exploration of ligand structure-activity relationships and the structural diversity of compounds active at each target. The database is freely available at http://www.iuphar-db.org

A COL17A1 Splice-Altering Mutation Is Prevalent in Inherited Recurrent Corneal Erosions

PurposeCorneal dystrophies are a genetically heterogeneous group of disorders. We previously described a family with an autosomal dominant epithelial recurrent erosion dystrophy (ERED). We aimed to identify the underlying genetic cause of ERED in this family and 3 additional ERED families. We sought to characterize the potential function of the candidate genes using the human and zebrafish cornea.DesignCase series study of 4 white families with a similar ERED. An experimental study was performed on human and zebrafish tissue to examine the putative biological function of candidate genes.ParticipantsFour ERED families, including 28 affected and 17 unaffected individuals.MethodsHumanLinkage-12 arrays (Illumina, San Diego, CA) were used to genotype 17 family members. Next-generation exome sequencing was performed on an uncle–niece pair. Segregation of potential causative mutations was confirmed using Sanger sequencing. Protein expression was determined using immunohistochemistry in human and zebrafish cornea. Gene expression in zebrafish was assessed using whole-mount in situ hybridization. Morpholino-induced transient gene knockdown was performed in zebrafish embryos.Main Outcome MeasuresLinkage microarray, exome analysis, DNA sequence analysis, immunohistochemistry, in situ hybridization, and morpholino-induced genetic knockdown results.ResultsLinkage microarray analysis identified a candidate region on chromosome chr10:12,576,562–112,763,135, and exploration of exome sequencing data identified 8 putative pathogenic variants in this linkage region. Two variants segregated in 06NZ–TRB1 with ERED: COL17A1 c.3156C→T and DNAJC9 c.334G→A. The COL17A1 c.3156C→T variant segregated in all 4 ERED families. We showed biologically relevant expression of these proteins in human cornea. Both proteins are expressed in the cornea of zebrafish embryos and adults. Zebrafish lacking Col17a1a and Dnajc9 during development show no gross corneal phenotype.ConclusionsThe COL17A1 c.3156C→T variant is the likely causative mutation in our recurrent corneal erosion families, and its presence in 4 independent families suggests that it is prevalent in ERED. This same COL17A1 c.3156C→T variant recently was identified in a separate pedigree with ERED. Our study expands the phenotypic spectrum of COL17A1 disease from autosomal recessive epidermolysis bullosa to autosomal dominant ERED and identifies COL17A1 as a key protein in maintaining integrity of the corneal epithelium

The Physics of the Colloidal Glass Transition

As one increases the concentration of a colloidal suspension, the system exhibits a dramatic increase in viscosity. Structurally, the system resembles a liquid, yet motions within the suspension are slow enough that it can be considered essentially frozen. This kinetic arrest is the colloidal glass transition. For several decades, colloids have served as a valuable model system for understanding the glass transition in molecular systems. The spatial and temporal scales involved allow these systems to be studied by a wide variety of experimental techniques. The focus of this review is the current state of understanding of the colloidal glass transition. A brief introduction is given to important experimental techniques used to study the glass transition in colloids. We describe features of colloidal systems near and in glassy states, including tremendous increases in viscosity and relaxation times, dynamical heterogeneity, and ageing, among others. We also compare and contrast the glass transition in colloids to that in molecular liquids. Other glassy systems are briefly discussed, as well as recently developed synthesis techniques that will keep these systems rich with interesting physics for years to come.Comment: 56 pages, 18 figures, Revie

Free will, punishment and criminal responsibility

Retributive attitudes are deeply held and widespread in the general population and most legal systems incorporate retributive elements. It is probably also the dominant theory of punishment among contemporary philosophers of criminal justice. However, retributivism relies on conceptions of free will and responsibility that have, for millennia, fundamentally divided those who have thought seriously about the subject. Our legal system upholds the principle that the responsibility of the offender has to be proven beyond reasonable doubt, before the accused can be punished. In view of the intractable doubts surrounding the soundness of retributivism’s very conception of responsibility, my thesis argues that it is ethically dubious to punish individuals for solely retributive reasons. Instead, my thesis proposes that a person should only be punished if the main theories of punishment agree that punishing that person is appropriate – I call this ‘the convergence requirement’. This approach, I argue, is in accordance with the considerations underlying the beyond reasonable doubt standard. In addition to considering the question of ‘whom to punish’ my thesis considers what methods of responding to criminal behaviour are acceptable. In particular, it attempts to explain, without appealing to the contested notions of free will or retributive desert, what is problematic about ‘manipulative’ methods of dealing with criminal offenders (focussing in particular on the possibility of modifying their behaviour through neurological interventions). The final part of this thesis also gives an overview of some of the practical implications for Scots criminal law of taking doubts about free will and retributivism seriously. Given the severe treatment that offenders undergo within the Scottish penal system (e.g. deprivation of liberty, stigma) and the high rate of recidivism, it is important to consider whether our current penal practices are justified, what alternatives are available and what goals and values should guide attempts at reforming the system

Soluble proteins of chemical communication: an overview across arthropods

Detection of chemical signals both in insects and in vertebrates is mediated by soluble proteins, highly concentrated in olfactory organs, which bind semiochemicals and activate, with still largely unknown mechanisms, specific chemoreceptors. The same proteins are often found in structures where pheromones are synthesised and released, where they likely perform a second role in solubilising and delivering chemical messengers in the environment.A single class of soluble polypeptides, called Odorant-Binding Proteins (OBPs) is known in vertebrates, while two have been identified in insects, OBPs and CSPs (Chemosensory Proteins). Despite their common name, OBPs of vertebrates bear no structural similarity with those of insects. We observed that in arthropods OBPs are strictly limited to insects, while a few members of the CSP family have been found in crustacean and other arthropods, where however, based on their very limited numbers, a function in chemical communication seems unlikely.The question we address in this review is whether another class of soluble proteins may have been adopted by other arthropods to perform the role of OBPs and CSPs in insects. We propose that lipid-transporter proteins of the Niemann-Pick type C2 family could represent likely candidates and report the results of an analysis of their sequences in representative species of different arthropods