Measuring Gaussian rigidity using curved substrates

The Gaussian (saddle splay) rigidity of fluid membranes controls their equilibrium topology but is notoriously difficult to measure. In lipid mixtures, typical of living cells, linear interfaces separate liquid ordered (LO) from liquid disordered (LD) bilayer phases at subcritical temperatures. Here we consider such membranes supported by curved supports that thereby control the membrane curvatures. We show how spectral analysis of the fluctuations of the LO-LD interface provides a novel way of measuring the difference in Gaussian rigidity between the two phases. We provide a number of conditions for such interface fluctuations to be both experimentally measurable and sufficiently sensitive to the value of the Gaussian rigidity, whilst remaining in the perturbative regime of our analysis.Comment: 5 pages, 3 figures. v2: version accepted for publicatio

Occasional essay: upper motor neuron syndrome in amyotrophic lateral sclerosis

The diagnosis of amyotrophic lateral sclerosis (ALS) requires recognition of both lower (LMN) and upper motor neuron (UMN) dysfunction.1 However, classical UMN signs are frequently difficult to identify in ALS.2 LMN involvement is sensitively detected by electromyography (EMG)3 but, as yet, there are no generally accepted markers for monitoring UMN abnormalities,4 the neurobiology of ALS itself, and disease spread through the brain and spinal cord,.5 Full clinical assessment is therefore necessary to exclude other diagnoses and to monitor disease progression. In part, this difficulty regarding detection of UMN involvement in ALS derives from the definition of ‘the UMN syndrome’. Abnormalities of motor control in ALS require reformulation within an expanded concept of the UMN, together with the neuropathological, neuro-imaging and neurophysiological abnormalities in ALS. We review these issues here

Treatment of estrogen-induced dermatitis with omalizumab

In 1945, Drs Bernhard Zondek and Yehuda Bromberg demonstrated intradermal treatment with estrone and estradiol benzoate induced urticarial lesions in some patients.1 Fifty years later, Shelley et al,2 who introduced the concept of progesterone dermatitis several decades prior, defined estrogen dermatitis based on studies of 7 women with premenstrual flares of skin eruptions including papulovesicular, urticarial, or eczematous lesions or generalized pruritus. Previously described therapies for estrogen dermatitis include estrogen desensitization, tamoxifen, leuprolide, and oophorectomy.3 Here we report a case of estrogen-induced dermatitis successfully treated with omalizumab

Using GIS in a first national mapping of functional disability among older American Indians and Alaska natives from the 2000 census

BACKGROUND: Geographical information systems (GIS) have been used mainly in understanding infectious diseases and environmental threats in health research. Here, GIS was used to examine patterns of functional disability as one impact of chronic disease in American Indians and Alaska Natives. The study purpose was to create the first national mapping of functional disability for AIANs using the 2000 U.S. Census. RESULTS: American Indians and Alaska Natives over age 65 reported disability at a rate of 57.6% versus 41.9% for all people over 65 (P ≤ 0.0001). Regional differences in levels and type of disability were evident. CONCLUSION: Maps help visualize those who might otherwise be 'lost' from the data. The significance of this study is that gerontologic programs and policies are data-driven, yet there is a lack of reliable national level data from US health systems on functional disability among American Indians and Alaska Natives. One study limitation was that Census questions regarding disability differed from traditional measures of activities of daily living and instrumental activities of daily living. An immediate policy recommendation would be to incorporate standard activities of daily living and instrumental activities of daily living language into future Census for a comprehensive, linked database for the future

Non-equilibrium raft-like membrane domains under continuous recycling

We present a model for the kinetics of spontaneous membrane domain (raft) assembly that includes the effect of membrane recycling ubiquitous in living cells. We show that the domains have a broad power-law distribution with an average radius that scales with the 1/4 power of the domain lifetime when the line tension at the domain edges is large. For biologically reasonable recycling and diffusion rates the average domain radius is in the tens of nm range, consistent with observations. This represents one possible link between signaling (involving rafts) and traffic (recycling) in cells. Finally, we present evidence that suggests that the average raft size may be the same for all scale-free recycling schemes.Comment: 8 pages, 5 figure

Hydro-osmotic instabilities in active membrane tubes

We study a membrane tube with unidirectional ion pumps driving an osmotic pressure difference. A pressure driven peristaltic instability is identified, qualitatively distinct from similar tension-driven Rayleigh type instabilities on membrane tubes. We discuss how this instability could be related to the function and biogenesis of membrane bound organelles, in particular the contractile vacuole complex. The unusually long natural wavelength of this instability is in agreement with that observed in cells

Dynamics of passive and active membrane tubes

Utilising Onsager's variational formulation, we derive dynamical equations for the relaxation of a fluid membrane tube in the limit of small deformation, allowing for a contrast of solvent viscosity across the membrane and variations in surface tension due to membrane incompressibility. We compute the relaxation rates, recovering known results in the case of purely axis-symmetric perturbations and making new predictions for higher order (azimuthal) $m$-modes. We analyse the long and short wavelength limits of these modes by making use of various asymptotic arguments. We incorporate stochastic terms to our dynamical equations suitable to describe both passive thermal forces and non-equilibrium active forces. We derive expressions for the fluctuation amplitudes, an effective temperature associated with active fluctuations, and the power spectral density for both the thermal and active fluctuations. We discuss an experimental assay that might enable measurement of these fluctuations to infer the properties of the active noise. Finally we discuss our results in the context of active membranes more generally and give an overview of some open questions in the field.Comment: 14 pages, 9 figure

Three-Dimensional Structure of Conotoxin tx3a: A m-1 Branch Peptide of the M-Superfamily

The M-superfamily, one of eight major conotoxin superfamilies found in the venom of the cone snail, contains a Cys framework with disulfide-linked loops labeled 1, 2, and 3 (- CC1C2C3CC-). M-superfamily conotoxins can be divided into the m-1, -2, -3 and -4 branches, based upon the number of residues located in the third Cys loop between the fourth and fifth Cys residues. Here we provide a three-dimensional solution structure for the m-1 conotoxin tx3a found in the venom of Conus textile. The 15 amino acid peptide, CCSWDVCDHPSCTCC, has disulfide bonds between Cys1 and Cys14, Cys2 and Cys12, and Cys7 and Cys15 typical of the C1- C5, C2-C4, and C3-C6 connectivity pattern seen in m-1 branch peptides. The tertiary structure of tx3a was determined by 2D 1H NMR in combination with the combined assignment and dynamics algorithm for nuclear magnetic resonance (NMR) applications CYANA program. Input for structure calculations consisted of 62 inter- and intraproton, 5 phi angle, and 4 hydrogen bond constraints. The root-mean-square deviation values for the 20 final structures are 0.32 +/- 0.07 Å and 0.84 +/- 0.11 Å for the backbone and heavy atoms, respectively. Surprisingly, the structure of tx3a has a “triple-turn” motif seen in the m-2 branch conotoxin mr3a, which is absent in mr3e, the only other member of the m-1 branch of the M-superfamily whose structure is known. Interestingly, injection of tx3a into mice elicits an excitatory response similar to that of the m-2 branch peptide mr3a, even though the conotoxins have different disulfide connectivity patterns

Improved Constraints on the Acceleration History of the Universe and the Properties of the Dark Energy

We extend and apply a model-independent analysis method developed earlier by Daly & Djorgovski to new samples of supernova standard candles, radio galaxy and cluster standard rulers, and use it to constrain physical properties of the dark energy as functions of redshift. Similar results are obtained for the radio galaxy and supernova data sets. The first and second derivatives of the distance are compared directly with predictions in a standard model based on General Relativity. The good agreement indicates that General Relativity provides an accurate description of the data on look-back time scales of about ten billion years. The first and second derivatives are combined to obtain the acceleration parameter, assuming only the validity of the Robertson-Walker metric, independent of a theory of gravity and of the physical nature of the dark energy. The acceleration of the universe at the current epoch is indicated by the analysis. The effect of non-zero space curvature on q(z) is explored. We solve for the pressure, energy density, equation of state, and potential and kinetic energy of the dark energy as functions of redshift assuming that General Relativity is the correct theory of gravity, and the results indicate that a cosmological constant in a spatially flat universe provides a good description of each of these quantities over the redshift range from zero to about one. We define a new function, the dark energy indicator, in terms of the first and second derivatives of the coordinate distance and show how this can be used to measure deviations of w from -1 and to obtain a new and independent measure of Omega.Comment: 46 pages, submitted for publicatio