Detection of Salinity by the Lobster, Homarus americanus

Changes in the heart rates of lobsters (Homarus americanus) were used as an indicator that the animals were capable of sensing a reduction in the salinity of the ambient seawater. The typical response to a gradual (1 to 2 ppt/min) reduction in salinity consisted of a rapid increase in heart rate at a mean threshold of 26.6 ± 0.7 ppt, followed by a reduction in heart rate when the salinity reached 22.1 ± 0.5 ppt. Animals with lesioned cardioregulatory nerves did not exhibit a cardiac response to changes in salinity. A cardiac response was elicited from lobsters exposed to isotonic chloride-free salines but not to isotonic sodium-, magnesium- or calcium-free salines. There was little change in the blood osmolarity of lobsters when bradycardia occurred, suggesting that the receptors involved are external. Furthermore, lobsters without antennae, antennules, or legs showed typical cardiac responses to low salinity, indicating the receptors are not located in these areas. Lobsters exposed to reductions in the salinity of the ambient seawater while both branchial chambers were perfused with full-strength seawater did not display a cardiac response until the external salinity reached 21.6 ± 1.8 ppt. In contrast, when their branchial chambers were exposed to reductions in salinity while the external salinity was maintained at normal levels, changes in heart rate were rapidly elicited in response to very small reductions in salinity (down to 29.5 ± 0.9 ppt in the branchial chamber and 31.5 ± 0.3 ppt externally). We conclude that the primary receptors responsible for detecting reductions in salinity in H. americanus are located within or near the branchial chambers and are primarily sensitive to chloride ions

The reduced cost of providing a nationally recognised service for familial hypercholesterolaemia

OBJECTIVE: Familial hypercholesterolaemia (FH) affects 1 in 500 people in the UK population and is associated with premature morbidity and mortality from coronary heart disease. In 2008, National Institute for Health and Care Excellence (NICE) recommended genetic testing of potential FH index cases and cascade testing of their relatives. Commissioners have been slow to respond although there is strong evidence of cost and clinical effectiveness. Our study quantifies the recent reduced cost of providing a FH service using generic atorvastatin and compares NICE costing estimates with three suggested alternative models of care (a specialist-led service, a dual model service where general practitioners (GPs) can access specialist advice, and a GP-led service).METHODS: Revision of existing 3?year costing template provided by NICE for FH services, and prediction of costs for running a programme over 10?years. Costs were modelled for the first population-based FH service in England which covers Southampton, Hampshire, Isle of Wight and Portsmouth (SHIP). Population 1.95 million.RESULTS: With expiry of the Lipitor (Pfizer atorvastatin) patent the cost of providing a 10-year FH service in SHIP reduces by 42.5% (£4.88 million on patent vs £2.80 million off patent). Further cost reductions are possible as a result of the reduced cost of DNA testing, more management in general practice, and lower referral rates to specialists. For instance a dual-care model with GP management of patients supported by specialist advice when required, costs £1.89 million.CONCLUSIONS: The three alternative models of care are now <50% of the cost of the original estimates undertaken by NICE

Fibrillin-Rich Microfibrils are Reduced in Photoaged Skin. Distribution at the Dermal–Epidermal Junction

Chronic sun exposure results in photoaged skin with deep coarse wrinkles and loss of elasticity. We have examined the distribution and abundance of fibrillin-rich microfibrils, key structural components of the elastic fiber network, in photoaged and photoprotected skin. Punch biopsies taken from photoaged forearm and from photoprotected hip and upper inner arm of 16 subjects with a clinical range of photoaging were examined for fibrillin-1 and fibrillin-2 expression and microfibril distribution. In situ hybridization revealed decreased fibrillin-1 mRNA but unchanged fibrillin-2 mRNA levels in severely photoaged forearm biopsies relative to photoprotected dermal sites. An immunohistochemical approach demonstrated that microfibrils at the dermal–epidermal junction were significantly reduced in moderate to severely photoaged forearm skin. Confocal microscopy revealed that the papillary dermal microfibrillar network was truncated and depleted in photoaged skin. These studies highlight that the fibrillin-rich microfibrillar network associated with the upper dermis undergoes extensive remodeling following solar irradiation. These changes may contribute to the clinical features of photoaging, such as wrinkle formation and loss of elasticity

Developing a quick, cost-effective genetic screen for enamel disease

Amelogenesis imperfecta (AI) refers to a group of rare, inherited disorders characterised by abnormal enamel formation. According to the AI Leiden Open Variant Database (LOVD) hosted by Leeds University (http://dna2.leeds.ac.uk/LOVD/), there are 19 genes involved in non-syndromic AI that account for >90% of the known AI-causing mutations. Conventionally the identification of inherited gene mutations in a family would be done through family studies. However, with technological improvements and decreasing costs, next generation sequencing (NGS) technology has become the gold standard in the genetic research. Single molecule molecular inversion probe (smMIP) is an NGS based DNA sequencing approach that can selectively target and analyse thousands of genomic positions in a single reaction. It is superior in terms of cost, throughput, scalability, sensitivity, and specificity and can process hundreds of patients simultaneously. To identify mutations in AI patients, an smMIP method was adapted and validated that can be used as a first point of screening for all the future patients. The aim is to make diagnosis quicker for patients with known mutations and to provide extra resources to focus on the discovery of novel gene mutations

A search for radioactive 26Al in the nova-like variable V4332 Sagittarii

We have searched for the important radioactive isotope 26Al in the nova-like source V4332 Sgr. Recent results from gamma ray astronomy show that there is pervasive emission of the 1.809 MeV gamma ray photon, arising from the decay of 26Al to 26Mg, from all over the galactic plane. Though the sites from where this emission originates are not clearly established, novae are believed to be an important contributing source. In this context, V4332 Sgr presented a rare opportunity to observationally investigate whether novae or novae-like sources synthesize 26Al and to what extent. Strong AlO bands in the near-IR have been reported in this object recently. As molecular bands of different isotopic compositions are readily resolved spectroscopically (e.g. 12CO and 13CO), it was thought that the components of AlO associated with 26Al and stable 27Al could be detected as separate bands. Our spectra indicate that there is no strong presence of 26Al in V4332 Sgr. A reliable upper limit of 0.10 for the 26Al/27Al ratio is determined which constitutes the first observational constraint for this ratio in a potential 26Al producing source. While V4332 Sgr is not a typical nova, its outburst amplitude and light-curve behaviour bear close similarity to that of novae. Hence, although the results from V4332 Sgr cannot be directly extended to novae in general, the limit on the observed 26Al/27Al ratio could be a useful input in constraining rather uncertain nucleosynthesis models for the production of 26Al in novae/novae-like sources. By comparing the observed 26Al/27Al ratio in V4332 Sgr with that expected in classical novae it appears unlikely that the progenitor of V4332 Sgr is an Oxygen-Neon-Magnesium white dwarf.Comment: 9 pages, 2 figures, to appear in Ap.J(L) July 200

Representational precision in visual cortex reveals outcome encoding and reward modulation during action preparation

According to ideomotor theory, goal-directed action involves the active perceptual anticipation of actions and their associated effects. We used multivariate analysis of fMRI data to test if preparation of an action promotes precision in the perceptual representation of the action. In addition, we tested how reward magnitude modulates this effect. Finally, we examined how expectation and uncertainty impact neural precision in the motor cortex. In line with our predictions, preparation of a hand or face action increased the precision of neural activation patterns in the extrastriate body area (EBA) and fusiform face area (FFA), respectively. The size of this effect of anticipation predicted individuals\u27 efficiency at performing the prepared action. In addition, increasing reward magnitude increased the precision of perceptual representations in both EBA and FFA although this effect was limited to the group of participants that learned to associate face actions with high reward. Surprisingly, examination of representations in the hand motor cortex and face motor cortex yielded effects in the opposite direction. Our findings demonstrate that the precision of representations in visual and motor areas provides an important neural signature of the sensorimotor representations involved in goal-directed action