The role of fatty aldehyde dehydrogenase in epidermal structure and function

The epidermal water barrier resides in the stratum corneum (SC) and is dependent on a highly organized network of multi-lamellar membranes comprised of a critical lipid composition. The SC membranes are formed from precursor membranes packaged in cytoplasmic lamellar bodies in the stratum granulosum and delivered to the SC by exocytosis. An abnormal lipid composition of the SC membranes often results in a disrupted water barrier and the clinical appearance of ichthyosis. This cutaneous feature is characteristic of Sjögren-Larsson syndrome (SLS), an inborn error of lipid metabolism caused by deficiency of fatty aldehyde dehydrogenase (FALDH). The contribution of FALDH to normal epidermal function has become increasingly evident with the recognition that this enzyme has an essential role in metabolism of several lipids, including fatty aldehydes and alcohols, ether glycerolipids, isoprenoid alcohols and certain lipids that undergo ω-oxidation, such as leukotriene B4 and very long-chain fatty acids. In the absence of FALDH, the skin produces lamellar bodies that are empty, lack their surrounding vesicle membranes or contain granular contents rather then the usual cargo membranes. These defective organelles also have impaired exocytosis, which results in structurally abnormal, deficient multi-lamellar membranes in the SC and a leaky water barrier. Although the exact biochemical mechanism for the cutaneous pathology is still unclear, studies in SLS demonstrate the critical importance of FALDH for normal epidermal structure and function

Green and hawksbill turtles in the Lesser Antilles demonstrate behavioural plasticity in inter-nesting behaviour and post-nesting migration

Satellite transmitters were deployed on three green turtles, Chelonia mydas, and two hawksbill turtles, Eretmochelys imbricata, nesting in the Lesser Antilles islands, Caribbean, between 2005-2007 to obtain preliminary information about the inter-nesting, migratory and foraging habitats in the region. Despite the extremely small dataset, both year-round residents and migrants were identified; specifically (1) two green turtles used local shallow coastal sites within 50 km of the nesting beach during all of their inter-nesting periods and then settled at these sites on completion of their breeding seasons, (2) one hawksbill turtle travelled 200 km westward before reversing direction and settling within 50 km of the original nesting beach and (3) one green and one hawksbill turtle initially nested at the proximate site, before permanently relocating to an alternative nesting site over 190 km distant. A lack of nesting beach fidelity was supported by flipper tag datasets for the region. Tagging datasets from 2002-2012 supported that some green and hawksbill individuals exhibit low fidelity to nesting beaches, whereas other females exhibited a high degree of fidelity (26 turtles tagged, 40.0km maximum distance recorded from original nesting beach). Individual turtles nesting on St Eustatius and St Maarten appear to exhibit behavioural plasticity in their inter-nesting behaviour and post-nesting migration routes in the Eastern Caribbean. The tracking and tagging data combined indicate that some of the green and hawksbill females that nest in the Lesser Antilles Islands are year-round residents, while others may nest and forage at alternative sites. Thus, continued year-round protection of these islands and implementation of protection programmes in nearby islands could contribute towards safeguarding the green and hawksbill populations of the region

The kinetics of antibody binding to Plasmodium falciparum VAR2CSA PfEMP1 antigen and modelling of PfEMP1 antigen packing on the membrane knobs

<p>Abstract</p> <p>Background</p> <p>Infected humans make protective antibody responses to the PfEMP1 adhesion antigens exported by <it>Plasmodium falciparum </it>parasites to the erythrocyte membrane, but little is known about the kinetics of this antibody-receptor binding reaction or how the topology of PfEMP1 on the parasitized erythrocyte membrane influences antibody association with, and dissociation from, its antigenic target.</p> <p>Methods</p> <p>A Quartz Crystal Microbalance biosensor was used to measure the association and dissociation kinetics of VAR2CSA PfEMP1 binding to human monoclonal antibodies. Immuno-fluorescence microscopy was used to visualize antibody-mediated adhesion between the surfaces of live infected erythrocytes and atomic force microscopy was used to obtain higher resolution images of the membrane knobs on the infected erythrocyte to estimate knob surface areas and model VAR2CSA packing density on the knob.</p> <p>Results</p> <p>Kinetic analysis indicates that antibody dissociation from the VAR2CSA PfEMP1 antigen is extremely slow when there is a high avidity interaction. High avidity binding to PfEMP1 antigens on the surface of <it>P. falciparum</it>-infected erythrocytes in turn requires bivalent cross-linking of epitopes positioned within the distance that can be bridged by antibody. Calculations of the surface area of the knobs and the possible densities of PfEMP1 packing on the knobs indicate that high-avidity cross-linking antibody reactions are constrained by the architecture of the knobs and the large size of PfEMP1 molecules.</p> <p>Conclusions</p> <p>High avidity is required to achieve the strongest binding to VAR2CSA PfEMP1, but the structures that display PfEMP1 also tend to inhibit cross-linking between PfEMP1 antigens, by holding many binding epitopes at distances beyond the 15-18 nm sweep radius of an antibody. The large size of PfEMP1 will also constrain intra-knob cross-linking interactions. This analysis indicates that effective vaccines targeting the parasite's vulnerable adhesion receptors should primarily induce strongly adhering, high avidity antibodies whose association rate constant is less important than their dissociation rate constant.</p

The photodissociation dynamics of ozone at 193 nm: an O(1D2) angular momentum polarization study.

Polarized laser photolysis, coupled with resonantly enhanced multiphoton ionization detection of O(1D2) and velocity-map ion imaging, has been used to investigate the photodissociation dynamics of ozone at 193 nm. The use of multiple pump and probe laser polarization geometries and probe transitions has enabled a comprehensive characterization of the angular momentum polarization of the O(1D2) photofragments, in addition to providing high-resolution information about their speed and angular distributions. Images obtained at the probe laser wavelength of around 205 nm indicate dissociation primarily via the Hartley band, involving absorption to, and diabatic dissociation on, the B 1B2(3 1A1) potential energy surface. Rather different O(1D2) speed and electronic angular momentum spatial distributions are observed at 193 nm, suggesting that the dominant excitation at these photon energies is to a state of different symmetry from that giving rise to the Hartley band and also indicating the participation of at least one other state in the dissociation process. Evidence for a contribution from absorption into the tail of the Hartley band at 193 nm is also presented. A particularly surprising result is the observation of nonzero, albeit small values for all three rank K = 1 orientation moments of the angular momentum distribution. The polarization results obtained at 193 and 205 nm, together with those observed previously at longer wavelengths, are interpreted using an analysis of the long range quadrupole-quadrupole interaction between the O(1D2) and O2(1Deltag) species

Current practice of carotid endarterectomy in the UK

Background: Carotid endarterectomy (CEA) reduces the risk of stroke in patients with internal carotid stenosis of 50-99 per cent. This study assessed national surgical practice through audit of CEA procedures and outcomes. Methods: This was a prospective cohort study of UK surgeons performing CEA, using clinical audit data collected continuously and reported in two rounds, covering operations from December 2005 to December 2007, and January 2008 to September 2009. Results: Some 352 (92·6 per cent) of 380 eligible surgeons contributed data. Of 19 935 CEAs recorded by Hospital Episode Statistics, 12 496 (62·7 per cent) were submitted to the audit. A total of 10 452 operations (83·6 per cent) were performed for symptomatic carotid stenosis; among these patients, the presenting symptoms were transient ischaemic attack in 4507 (43·1 per cent), stroke in 3572 (34·2 per cent) and amaurosis fugax in 1965 (18·8 per cent). The 30-day mortality rate was 1·0 per cent (48 of 4944) in round 1 and 0·8 per cent (50 of 6151) in round 2; the most common cause of death was stroke, followed by myocardial infarction. The rate of death or stroke within 30 days of surgery was 2·5 per cent (124 of 4918) in round 1 and 1·8 per cent (112 of 6135) in round 2. Conclusion: CEA is performed less commonly in the UK than in other European countries and probably remains underutilized in the prevention of stroke. Increasing the number of CEAs done in the UK, together with reducing surgical waiting times, could prevent more strokes

Current practice of carotid endarterectomy in the UK.

BACKGROUND: Carotid endarterectomy (CEA) reduces the risk of stroke in patients with internal carotid stenosis of 50-99 per cent. This study assessed national surgical practice through audit of CEA procedures and outcomes. METHODS: This was a prospective cohort study of UK surgeons performing CEA, using clinical audit data collected continuously and reported in two rounds, covering operations from December 2005 to December 2007, and January 2008 to September 2009. RESULTS: Some 352 (92·6 per cent) of 380 eligible surgeons contributed data. Of 19,935 CEAs recorded by Hospital Episode Statistics, 12,496 (62·7 per cent) were submitted to the audit. A total of 10,452 operations (83·6 per cent) were performed for symptomatic carotid stenosis; among these patients, the presenting symptoms were transient ischaemic attack in 4507 (43·1 per cent), stroke in 3572 (34·2 per cent) and amaurosis fugax in 1965 (18·8 per cent). The 30-day mortality rate was 1·0 per cent (48 of 4944) in round 1 and 0·8 per cent (50 of 6151) in round 2; the most common cause of death was stroke, followed by myocardial infarction. The rate of death or stroke within 30 days of surgery was 2·5 per cent (124 of 4918) in round 1 and 1·8 per cent (112 of 6135) in round 2. CONCLUSION: CEA is performed less commonly in the UK than in other European countries and probably remains underutilized in the prevention of stroke. Increasing the number of CEAs done in the UK, together with reducing surgical waiting times, could prevent more strokes