STIM1/Orai1-mediated store-operated Ca2+ entry: the tip of the iceberg

Highly efficient mechanisms regulate intracellular calcium (Ca2+) levels. The recent discovery of new components linking intracellular Ca2+ stores to plasma membrane Ca2+ entry channels has brought new insight into the understanding of Ca2+ homeostasis. Stromal interaction molecule 1 (STIM1) was identified as a Ca2+ sensor essential for Ca2+ store depletion-triggered Ca2+ influx. Orai1 was recognized as being an essential component for the Ca2+ release-activated Ca2+ (CRAC) channel. Together, these proteins participate in store-operated Ca2+ channel function. Defective regulation of intracellular Ca2+ is a hallmark of several diseases. In this review, we focus on Ca2+ regulation by the STIM1/Orai1 pathway and review evidence that implicates STIM1/Orai1 in several pathological conditions including cardiovascular and pulmonary diseases, among others

Vascular reactivity in hypertension: Altered effect of ouabain

Ouabain inhibits the relaxing effect of Ca 2+ (but not of Mn 2+ ) on contractile responses in tail artery strips isolated from spontaneously hypertensive and normotensive rats. The magnitude of ouabain inhibition was greater in vascular strips from hypertensive rats suggesting a significant difference in basic membrane function in hypertensive vascular smooth muscle.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42713/1/18_2005_Article_BF01953743.pd

Mandai mangrove, Singapore: Lessons for the conservation of Southeast Asia's mangroves

Raffles Bulletin of ZoologySUPPL.2555-6

Law, politics and the governance of English and Scottish joint-stock companies 1600-1850

This article examines the impact of law on corporate governance by means of a case study of joint-stock enterprise in England and Scotland before 1850. Based on a dataset of over 450 company constitutions together with qualitative information on governance practice, it finds little evidence to support the hypothesis that common-law regimes such as England were more supportive of economic growth than civil-law jurisdictions such as Scotland: indeed, levels of shareholder protection were slightly stronger in the civil-law zone. Other factors, such as local political institutions, played a bigger role in shaping organisational forms and business practice

Observable Effects of Scalar Fields and Varying Constants

We show by using the method of matched asymptotic expansions that a sufficient condition can be derived which determines when a local experiment will detect the cosmological variation of a scalar field which is driving the spacetime variation of a supposed constant of Nature. We extend our earlier analyses of this problem by including the possibility that the local region is undergoing collapse inside a virialised structure, like a galaxy or galaxy cluster. We show by direct calculation that the sufficient condition is met to high precision in our own local region and we can therefore legitimately use local observations to place constraints upon the variation of "constants" of Nature on cosmological scales.Comment: Invited Festscrift Articl

Spreading Dynamics of Polymer Nanodroplets

The spreading of polymer droplets is studied using molecular dynamics simulations. To study the dynamics of both the precursor foot and the bulk droplet, large drops of ~200,000 monomers are simulated using a bead-spring model for polymers of chain length 10, 20, and 40 monomers per chain. We compare spreading on flat and atomistic surfaces, chain length effects, and different applications of the Langevin and dissipative particle dynamics thermostats. We find diffusive behavior for the precursor foot and good agreement with the molecular kinetic model of droplet spreading using both flat and atomistic surfaces. Despite the large system size and long simulation time relative to previous simulations, we find no evidence of hydrodynamic behavior in the spreading droplet.Comment: Physical Review E 11 pages 10 figure

'Education, education, education' : legal, moral and clinical

This article brings together Professor Donald Nicolson's intellectual interest in professional legal ethics and his long-standing involvement with law clinics both as an advisor at the University of Cape Town and Director of the University of Bristol Law Clinic and the University of Strathclyde Law Clinic. In this article he looks at how legal education may help start this process of character development, arguing that the best means is through student involvement in voluntary law clinics. And here he builds upon his recent article which argues for voluntary, community service oriented law clinics over those which emphasise the education of students

Svestka's Research: Then and Now

Zdenek Svestka's research work influenced many fields of solar physics, especially in the area of flare research. In this article I take five of the areas that particularly interested him and assess them in a "then and now" style. His insights in each case were quite sound, although of course in the modern era we have learned things that he could not readily have envisioned. His own views about his research life have been published recently in this journal, to which he contributed so much, and his memoir contains much additional scientific and personal information (Svestka, 2010).Comment: Invited review for "Solar and Stellar Flares," a conference in honour of Prof. Zden\v{e}k \v{S}vestka, Prague, June 23-27, 2014. This is a contribution to a Topical Issue in Solar Physics, based on the presentations at this meeting (Editors Lyndsay Fletcher and Petr Heinzel

A comparative and regional study of potassium induced relaxation of vascular smooth muscle

The current study was undertaken to assess species and regional variations in the relaxation of vascular smooth muscle in response to potassium and in the ouabain sensitivity of this relaxation. The effect of species variation was investigated through the use of tail arteries from rats, dogs, cats, monkeys, and pigs; the effect of regional variation was studied in tail, middle cerebral, femoral, and posterior coronary arteries from baboons. Helical strips from all of these vessels were made to contract with norepinephrine or serotonin in a potassium-free solution. The vessels relaxed when potassium was added back to the solution. Strips of tail artery from rats, dogs, and monkeys showed greater relaxation in response to potassium than did strips from pigs and cats. Helical strips from tail, cerebral, and coronary arteries of the baboon relaxed to a greater degree in response to potassium than did strips from the femoral artery. Ouabain produced a concentration-dependent decrease in the magnitude of potassium relaxation in all vessel types. Half-maximal inhibition occurred at approximately 10 −8 to 10 −7 M in all arterial strips except those obtained from rat tail artery (5×10 −5 M). The inhibition of potassium relaxation by ouabain was fully reversed by 30 min exposure to a ouabain-free solution in only the rat tail artery strips. A component of potassium-induced relaxation in tail artery strips from monkeys and baboons was not inhibited by ouabain. The results show that the magnitude of response, potassium and ouabain sensitivity, and recovery from ouabain treatment of potassium relaxation are species related. The regional bed from which the vascular smooth muscle is derived also determines the magnitude and potassium sensitivity of the relaxation. These parameters of potassium-dependent relaxation may reflect corresponding differences in the electrogenic pumping of sodium and potassium among various animal species and various regional vascular beds.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47086/1/359_2004_Article_BF00657652.pd

Further evidence for a variable fine-structure constant from Keck/HIRES QSO absorption spectra

[Abridged] We previously presented evidence for a varying fine-structure constant, alpha, in two independent samples of Keck/HIRES QSO spectra. Here we present a detailed many-multiplet analysis of a third Keck/HIRES sample containing 78 absorption systems. We also re-analyse the previous samples, providing a total of 128 absorption systems over the redshift range 0.2<z_abs<3.7. All three samples separately yield consistent, significant values of da/a. The analyses of low- and high-z systems rely on different ions/transitions with very different dependencies on alpha, yet they also give consistent results. We identify additional random errors in 22 high-z systems characterized by transitions with a large dynamic range in apparent optical depth. Increasing the statistical errors on da/a for these systems gives our fiducial result, a weighted mean da/a=(-0.543+/-0.116)x10^-5, representing 4.7-sigma evidence for a smaller weighted mean alpha in the absorption clouds. Assuming that da/a=0 at z_abs=0, the data marginally prefer a linear increase in alpha with time: dota/a=(6.40+/-1.35)x10^-16 yr^-1. The two-point correlation function for alpha is consistent with zero over 0.2-13 Gpc comoving scales and the angular distribution of da/a shows no significant dipolar anisotropy. We therefore have no evidence for spatial variations in da/a. We extend our previous searches for possible systematic errors, identifying atmospheric dispersion and isotopic structure effects as potentially the most significant. However, overall, known systematic errors do not explain the results. Future many-multiplet analyses of QSO spectra from different telescopes and spectrographs will provide a now crucial check on our Keck/HIRES results.Comment: 31 pages, 25 figures (29 EPS files), 8 tables. Accepted by MNRAS. Colour versions of Figs. 6, 8 & 10 and text version of Table 3 available at http://www.ast.cam.ac.uk/~mim/pub.htm