Oxidative Stress in Caenorhabditis elegans: Protective Effects of Spartin

Troyer syndrome is caused by a mutation in the SPG20 gene, which results in complete loss of expression of the protein spartin. We generated a genetic model of Troyer syndrome in worms to explore the locomotor consequences of a null mutation of the Caenorhabditis elegans SPG20 orthologue, F57B10.9, also known as spg-20. Spg-20 mutants showed decreased length, crawling speed, and thrashing frequency, and had a shorter lifespan than wild-type animals. These results suggest an age-dependent decline in motor function in mutant animals. The drug paraquat was used to induce oxidative stress for 4 days in the animals. We measured survival rate and examined locomotion by measuring crawling speed and thrashing frequency. After 4 days of paraquat exposure, 77% of wild-type animals survived, but only 38% of spg-20 mutant animals survived. Conversely, animals overexpressing spg-20 had a survival rate of 95%. We also tested lifespan after a 1 hour exposure to sodium azide. After a 24 hour recovery period, 87% of wild type animals survived, 57% of spg-20 mutant animals survived, and 82% of animals overexpressing spg-20 survived. In the behavioral assays, spg-20 mutant animals showed a significant decrease in both crawling speed and thrashing frequency compared with wild-type animals. Importantly, the locomotor phenotype for both crawling and thrashing was rescued in animals overexpressing spg-20. The animals overexpressing spg-20 had crawling speeds and thrashing frequencies similar to those of wild-type animals. These data suggest that the protein F57B10.9/SPG-20 might have a protective role against oxidative stress.     

The Harm of Bioethics: A Critique of Singer and Callahan on Obesity

Debate concerning the social impact of obesity has been ongoing since at least the 1980s. Bioethicists, however, have been relatively silent. If obesity is addressed it tends to be in the context of resource allocation or clinical procedures such as bariatric surgery. However, prominent bioethicists Peter Singer and Dan Callahan have recently entered the obesity debate to argue that obesity is not simply a clinical or personal issue but an ethical issue with social and political consequences. This article critically examines two problematic aspects of Singer and Callahan's respective approaches. First, there is an uncritical assumption that individuals are autonomous agents responsible for health‐related effects associated with food choices. In their view, individuals are obese because they choose certain foods or refrain from physical activity. However, this view alone does not justify intervention. Both Singer and Callahan recognize that individuals are free to make foolish choices so long as they do not harm others. It is at this point that the second problematic aspect arises. To interfere legitimately in the liberty of individuals, they invoke the harm principle. I contend, however, that in making this move both Singer and Callahan rely on superficial readings of public health research to amplify the harm caused by obese individuals and ignore pertinent epidemiological research on the social determinants of obesity. I argue that the mobilization of the harm principle and corresponding focus on individual behaviours without careful consideration of the empirical research is itself a form of harm that needs to be taken seriously.     

A Three-Dimensional Skeletal Reconstruction of the Stem Amniote Orobates pabsti (Diadectidae): Analyses of Body Mass,Centre of Mass Position,and Joint Mobility

Orobates pabsti, a basal diadectid from the lower Permian, is a key fossil for the understanding of early amniote evolution. Quantitative analysis of anatomical information suffers from fragmentation of fossil bones, plastic deformation due to diagenetic processes and fragile preservation within surrounding rock matrix, preventing further biomechanical investigation. Here we describe the steps taken to digitally reconstruct MNG 10181, the holotype specimen of Orobates pabsti, and subsequently use the digital reconstruction to assess body mass, position of the centre of mass in individual segments as well as the whole animal, and study joint mobility in the shoulder and hip joints. The shape of most fossil bone fragments could be recovered from micro-focus computed tomography scans. This also revealed structures that were hitherto hidden within the rock matrix. However, parts of the axial skeleton had to be modelled using relevant isolated bones from the same locality as templates. Based on the digital fossil, mass of MNG 10181 was estimated using a model of body shape that was varied within a plausible range to account for uncertainties of the dimension. In the mean estimate model the specimen had an estimated mass of circa 4 kg. Varying of the mass distribution amongst body segments further revealed that Orobates carried most of its weight on the hind limbs. Mostly unrestricted joint morphology further suggested that MNG 10181 was able to effectively generate propulsion with the pelvic limbs. The digital reconstruction is made available for future biomechanical studies.     

The ABC’s of Suicide Risk Assessment: Applying a Tripartite Approach to Individual Evaluations

There is considerable need for accurate suicide risk assessment for clinical, screening, and research purposes. This study applied the tripartite affect-behavior-cognition theory, the suicidal barometer model, classical test theory, and item response theory (IRT), to develop a brief self-report measure of suicide risk that is theoretically-grounded, reliable and valid. An initial survey (n = 359) employed an iterative process to an item pool, resulting in the six-item Suicidal Affect-Behavior-Cognition Scale (SABCS). Three additional studies tested the SABCS and a highly endorsed comparison measure. Studies included two online surveys (Ns = 1007, and 713), and one prospective clinical survey (n = 72; Time 2, n = 54). Factor analyses demonstrated SABCS construct validity through unidimensionality. Internal reliability was high (α = .86-.93, split-half = .90-.94)). The scale was predictive of future suicidal behaviors and suicidality (r = .68, .73, respectively), showed convergent validity, and the SABCS-4 demonstrated clinically relevant sensitivity to change. IRT analyses revealed the SABCS captured more information than the comparison measure, and better defined participants at low, moderate, and high risk. The SABCS is the first suicide risk measure to demonstrate no differential item functioning by sex, age, or ethnicity. In all comparisons, the SABCS showed incremental improvements over a highly endorsed scale through stronger predictive ability, reliability, and other properties. The SABCS is in the public domain, with this publication, and is suitable for clinical evaluations, public screening, and research.     

Conserved nonplanar heme distortions in cytochromesc

A nonplanar distortion of the heme ofc-type cytochromes is conserved in the proteins isolated from diverse species based upon a comprehensive analysis of available highresolution X-ray crystal structures. This distortion is induced through the cysteine thioether linkages between the porphyrin pyrrole groups and the polypeptide and results in an asymmetric pyrrole distortion. This asymmetry in the heme distortion is also conserved. For other heme proteins which lack these covalent bonds, nearly planar porphyrins are observed. Resonance Raman evidence indicates that nonplanar distortion of porphyrins containing metals, like iron, with large core sizes (?2.00 Å) is energetically unfavorable and can occur only in the presence of significant environmental perturbations. Further, energy minimization and dynamics calculations on the ferric form of yeast iso-1-cytochromec, starting from the crystallographic coordinates and using a molecular mechanics force field which accurately reproduces nonplanar distortions in metalloporphyrins, suggest that this distortion is indeed maintained by the protein tertiary structure. It is proposed that this protein-linked heme distortion modulates electron transfer function through modification of redox potentials of the porphyrin ring and the protein binding properties ofc-type cytochromes.