ATP-sensitive K channels in heart muscle Spare channels

AbstractWe show that ATP-sensitive K+ channels of excised inside-out membrane patches of rat ventricular myocytes show considerable variation in their sensitivity to ATP. In 102 different membrane patches IC50 values ranged from 9 to 580 μM ATP and Hill coefficient from 1% to 6.41% of patches showed openings of ATP-sensitive K+ channels in the presence of 1 mM ATP. These results considerably widen the range of internal ATP concentrations over which one might expect activation of the ATP-sensitive K+ current in cardiac myocytes

A study of autonomy in decapod crustacea

Autotomy is the process whereby an animal can discard a part of it's body from a preformed breakage plane. This study examines the natural occurrence of limb autotomy in the crab Carcinus maenas in the Yealm estuary, Devon; and the nervous control of limb autotomy in the hermit crab Pagurus bernhardus and the shore crab Carcinus maenas. Of the crabs caught in the Yealm estuary in monthly samples between February 1976 and January 1977, 13.2% had lost one or more limbs, with males showing a greater incidence of autotomy (14.5%) than females (12.2%). There is a significant positive relationship between crab's size and incidence of autotomy and seasonal changes in the incidence of autotomy can be explained in terms of alterations of the mean size of crabs caught in each monthly sample. Limb autotomy in Pagurus and Carcinus results from limb injury and coactivation of the two BI levator muscles. The smaller posterior levator muscle (PL) rotates to direct isometric force from the large anterior levator muscle (AL) onto a plug in the breakage plane which encircles the BI and cause autotomy. During normal locomotion, although the PL muscle is electrically active it's tendon does not rotate and AL force is directed away from the plug in the breakage plane. The nervous control of limb autotomy is a combination of injury induced central command and feedback from a peripheral sense organ. Injury causes high frequency excitation of AL motor neurones and inhibition of PL motor neurones. The PL muscle rotates, as during autotomy, when the sense organ CSD1 is stimulated by strong isometric contractions of the AL muscle. This investigation shows that PL rotation at autotomy results from such stimulation of CSD1 and not central nervous command. Accidental autotomy in inappropriate circumstances is prevented when CSD 1 inhibits AL contraction, inhibition which is avoided by injury induced excitation of AL motor neurones to cause autotomy.<p

Randomly Amplified DNA Fingerprinting: A Culmination of DNA Marker Technologies Based on Arbitrarily-Primed PCR Amplification

Arbitrarily-primed DNA markers can be very useful for genetic fingerprinting and for facilitating positional cloning of genes. This class of technologies is particularly important for less studied species, for which genome sequence information is generally not known. The technologies include Randomly Amplified Polymorphic DNA (RAPD), DNA Amplification Fingerprinting (DAF), and Amplified Fragment Length Polymorphism (AFLP). We have modified the DAF protocol to produce a robust PCR-based DNA marker technology called Randomly Amplified DNA Fingerprinting (RAF). While the protocol most closely resembles DAF, it is much more robust and sensitive because amplicons are labelled with either radioactive (33)P or fluorescence in a 30-cycle PCR, and then separated and detected on large polyacrylamide sequencing gels. Highly reproducible RAF markers were readily amplified from either purified DNA or alkali-treated intact leaf tissue. RAF markers typically display dominant inheritance. However, a small but significant portion of the RAF markers exhibit codominant inheritance and represent microsatellite loci. RAF compares favorably with AFLP for efficiency and reliability on many plant genomes, including the very large and complex genomes of sugarcane and wheat. While the two technologies detect about the same number of markers per large polyacrylamide gel, advantages of RAF over AFLP include: (i) no requirement for enzymatic template preparation, (ii) one instead of two PCRs, and (iii) overall cost. RAF and AFLP were shown to differ in the selective basis of amplification of markers from genomes and could therefore be used in complementary fashion for some genetic studies

Cost-effectiveness of donepezil and memantine in moderate to severe Alzheimer's disease (the DOMINO-AD trial).

OBJECTIVE: Most investigations of pharmacotherapy for treating Alzheimer's disease focus on patients with mild-to-moderate symptoms, with little evidence to guide clinical decisions when symptoms become severe. We examined whether continuing donepezil, or commencing memantine, is cost-effective for community-dwelling, moderate-to-severe Alzheimer's disease patients. METHODS: Cost-effectiveness analysis was based on a 52-week, multicentre, double-blind, placebo-controlled, factorial clinical trial. A total of 295 community-dwelling patients with moderate/severe Alzheimer's disease, already treated with donepezil, were randomised to: (i) continue donepezil; (ii) discontinue donepezil; (iii) discontinue donepezil and start memantine; or (iv) continue donepezil and start memantine. RESULTS: Continuing donepezil for 52 weeks was more cost-effective than discontinuation, considering cognition, activities of daily living and health-related quality of life. Starting memantine was more cost-effective than donepezil discontinuation. Donepezil-memantine combined is not more cost-effective than donepezil alone. CONCLUSIONS: Robust evidence is now available to inform clinical decisions and commissioning strategies so as to improve patients' lives whilst making efficient use of available resources. Clinical guidelines for treating moderate/severe Alzheimer's disease, such as those issued by NICE in England and Wales, should be revisited. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd

South African research in the Southern Ocean: New opportunities but serious challenges

South Africa has a long track record in Southern Ocean and Antarctic research and has recently invested considerable funds in acquiring new infrastructure for ongoing support of this research. This infrastructure includes a new base at Marion Island and a purpose-built ice capable research vessel, which greatly expand research opportunities. Despite this investment, South Africa's standing as a participant in this critical field is threatened by confusion, lack of funding, lack of consultation and lack of transparency. The research endeavour is presently bedevilled by political manoeuvring among groups with divergent interests that too often have little to do with science, while past and present contributors of research are excluded from discussions that aim to formulate research strategy. This state of affairs is detrimental to the country's aims of developing a leadership role in climate change and Antarctic research and squanders both financial and human capital