The conducting form of gramicidin A is a right-handed double-stranded double helix

The linear pentadecapeptide antibiotic, gramicidin D, is a naturally occurring product of Bacillus brevis known to form ion channels in synthetic and natural membranes. The x-ray crystal structures of the right-handed double-stranded double-helical dimers (DSDHℛ) reported here agree with 15N-NMR and CD data on the functional gramicidin D channel in lipid bilayers. These structures demonstrate single-file ion transfer through the channels. The results also indicate that previous crystal structure reports of a left-handed double-stranded double-helical dimer in complex with Cs+ and K+ salts may be in error and that our evidence points to the DSDHℛ as the major conformer responsible for ion transport in membranes.

Polaris, a Protein Involved in Left-Right Axis Patterning, Localizes to Basal Bodies and Cilia

Mutations in Tg737 cause a wide spectrum of phenotypes, including random left-right axis specification, polycystic kidney disease, liver and pancreatic defects, hydrocephalus, and skeletal patterning abnormalities. To further assess the biological function of Tg737 and its role in the mutant pathology, we identified the cell population expressing Tg737 and determined the subcellular localization of its protein product called Polaris. Tg737 expression is associated with cells possessing either motile or immotile cilia and sperm. Similarly, Polaris concentrated just below the apical membrane in the region of the basal bodies and within the cilia or flagellar axoneme. The data suggest that Polaris functions in a ciliogenic pathway or in cilia maintenance, a role supported by the loss of cilia on the ependymal cell layer in ventricles of Tg737orpk brains and by the lack of node cilia in Tg737Δ2-3βGal mutants.

Interaction of the histone (H3-H4)2 tetramer of the nucleosome with positively supercoiled DNA minicircles: Potential flipping of the protein from a left- to a right-handed superhelical form.

We have studied the ability of the histone (H3-H4)2 tetramer, the central part of the nucleosome of eukaryotic chromatin, to form particles on DNA minicircles of negative and positive superhelicities, and the effect of relaxing these particles with topoisomerase I. The results show that even modest positive torsional stress from the DNA, and in particular that generated by DNA thermal fluctuations, can trigger a major, reversible change in the conformation of the particle. Neither a large excess of naked DNA, nor a crosslink between the two H3s prevented the transition from one form to the other. This suggested that during the transition, the histones neither dissociated from the DNA nor were even significantly reshuffled. Moreover, the particles reconstituted on negatively and positively supercoiled minicircles look similar under electron microscopy. These data agree best with a transition involving a switch of the wrapped DNA from a left- to a right-handed superhelix. It is further proposed, based on the left-handed overall superhelical conformation of the tetramer within the octamer [Arents, G., Burlingame, R. W., Wang, B. C., Love, W. E. & Moudrianakis, E. N. (1991) Proc. Natl.Acad. Sci. USA 88, 10148-10152] that this change in DNA topology is mediated by a similar change in the topology of the tetramer itself, which may occur through a rotation (or a localized deformation) of the two H3-H4 dimers about their H3-H3 interface. Potential implications of this model for nucleosome dynamics in vivo are discussed.

The First Century of Right to Arms Litigation

This Article examines state court cases involving the right to arms, during the first century following ratification of the Amendment in 1791. This is not the first article to survey some of those cases. This Article includes additional cases, and details the procedural postures and facts, not only the holdings. The Article closely examines how the Supreme Court integrated the nineteenth century arms cases into Heller and McDonald to shape modern Second Amendment law. Part I briefly explains two English cases which greatly influenced American legal understandings. Semayne’s Case is the foundation of “castle doctrine” — the right to home security which includes the right of armed self-defense in the home. Sir John Knight’s Case fortified the tradition of the right to bear arms, providing that the person must bear arms in a non-terrifying manner. Part II examines American antebellum cases; these are the cases to which Heller looked for guidance on the meaning of the Second Amendment. Part III looks at cases from Reconstruction and the early years of Jim Crow, through 1891. As with the antebellum cases, the large majority of post-war cases are from the Southeast, which during the nineteenth century was the region most ardent for gun control. The heart of gun control country was Tennessee and Arkansas; courts there resisted some infringements of the right to arms, but eventually gave up. Heller and McDonald did not look to the Jim Crow cases as constructive precedents on the Second Amendment.

Is health a right for all? An umbrella review of the barriers to health care access faced by migrants

Objective. To synthesise the scientific evidence concerning barriers to health care access faced by migrants. We sought to critically analyse this evidence with a view to guiding policies. Design. A systematic review methodology was used to identify systematic and scoping reviews which quantitatively or qualitatively analysed data from primary studies. The main variables analysed were structural and contextual barriers (health system organisation) as well as individual (patients and providers). The quality of evidence from the systematic reviews was critically appraised. From 2674 reviews, 79 were retained for further scrutiny, and finally 9 met the inclusion criteria. Results. The structural barriers identified were the lack of health insurance and the high cost of drugs (non-universal health system) and organisational aspects of health system (social insurance system and national health system). The individual barriers were linguistic and cultural. None of the reviews provided a quality appraisal of the studies. Conclusions. Barriers to health care for migrants range from entitlement in non-universal health systems to accessibility in universal ones, and determinants of access to the respective health services should be analysed within the corresponding national context. Generate social and institutional changes that eliminate barriers to access to health services is essential to ensure health for all.

Making it easy to do the right thing in healthcare: Advancing improvement science education through accredited pan European higher education modules

Background: Numerous international policy drivers espouse the need to improve healthcare. The application of Improvement Science has the potential to restore the balance of healthcare and transform it to a more person-centred and quality improvement focussed system. However there is currently no accredited Improvement Science education offered routinely to healthcare students. This means that there are a huge number of healthcare professionals who do not have the conceptual or experiential skills to apply Improvement Science in everyday practise. Methods: This article describes how seven European Higher Education Institutions (HEIs) worked together to develop four evidence informed accredited inter-professional Improvement Science modules for under and postgraduate healthcare students. It outlines the way in which a Policy Delphi, a narrative literature review, a review of the competency and capability requirements for healthcare professionals to practise Improvement Science, and a mapping of current Improvement Science education informed the content of the modules. Results: A contemporary consensus definition of Healthcare Improvement Science was developed. The four Improvement Science modules that have been designed are outlined. A framework to evaluate the impact modules have in practise has been developed and piloted. Conclusion: The authors argue that there is a clear need to advance healthcare Improvement Science education through incorporating evidence based accredited modules into healthcare professional education. They suggest that if Improvement Science education, that incorporates work based learning, becomes a staple part of the curricula in inter-professional education then it has real promise to improve the delivery, quality and design of healthcare.