Modulation of voltage-dependent sodium and potassium currents by charged amphiphiles in cardiac ventricular myocytes. Effects via modification of surface potential.

Modulation of voltage-dependent sodium and potassium currents by charged amphiphiles was investigated in cardiac ventricular myocytes using the patch-clamp technique. Negatively charged sodium dodecylsulfate (SDS) increased amplitude of INa, whereas positively charged dodecyltrimethylammonium (DDTMA) decreased INa. Furthermore, SDS shifted the steady-state activation and inactivation of INa in the negative direction, whereas DDTMA shifted the curves in the opposite direction. These shifts provided an explanation for the changes in current amplitude. Activation and inactivation kinetics of INa were accelerated by SDS but slowed by DDTMA. These changes in both steady-state gating and kinetics of INa are consistent with a decrease of the intramembrane field by SDS and an increase of the field by DDTMA due to an alteration of surface potential after their insertion into the outer monolayer of the sarcolemma. The effect of SDS on the steady-state inactivation of INa was concentration dependent and partially reversed by screening surface charges with increased extracellular [Ca2+]. These amphiphiles also altered the activation of the delayed rectifier K+ current (IK,del), producing a shift in the negative direction by SDS but in the positive direction by DDTMA. These results suggest that the insertion of charged amphiphiles into the cell membrane alters the behavior of voltage-dependent INa and IK,del by changing the surface charge density, and consequently the surface potential and implies, although indirectly, that the lipid surface charges are important to the voltage-dependent gating of these channels

Noncommutative geometry and stochastic processes

The recent analysis on noncommutative geometry, showing quantization of the volume for the Riemannian manifold entering the geometry, can support a view of quantum mechanics as arising by a stochastic process on it. A class of stochastic processes can be devised, arising as fractional powers of an ordinary Wiener process, that reproduce in a proper way a stochastic process on a noncommutative geometry. These processes are characterized by producing complex values and so, the corresponding Fokker-Planck equation resembles the Schroedinger equation. Indeed, by a direct numerical check, one can recover the kernel of the Schroedinger equation starting by an ordinary Brownian motion. This class of stochastic processes needs a Clifford algebra to exist. In four dimensions, the full set of Dirac matrices is needed and the corresponding stochastic process in a noncommutative geometry is easily recovered as is the Dirac equation in the Klein-Gordon form being it the Fokker--Planck equation of the process.Comment: 16 pages, 2 figures. Updated a reference. A version of this paper will appear in the proceedings of GSI2017, Geometric Science of Information, November 7th to 9th, Paris (France

Stellar Population Diagnostics of Elliptical Galaxy Formation

Major progress has been achieved in recent years in mapping the properties of passively-evolving, early-type galaxies (ETG) from the local universe all the way to redshift ~2. Here, age and metallicity estimates for local cluster and field ETGs are reviewed as based on color-magnitude, color-sigma, and fundamental plane relations, as well as on spectral-line indices diagnostics. The results of applying the same tools at high redshifts are then discussed, and their consistency with the low-redshift results is assessed. Most low- as well as high-redshift (z~1) observations consistently indicate 1) a formation redshift z>~3 for the bulk of stars in cluster ETGs, with their counterparts in low-density environments being on average ~1-2 Gyr younger, i.e., formed at z>~1.5-2, 2) the duration of the major star formation phase anticorrelates with galaxy mass, and the oldest stellar populations are found in the most massive galaxies. With increasing redshift there is evidence for a decrease in the number density of ETGs, especially of the less massive ones, whereas existing data appear to suggest that most of the most-massive ETGs were already fully assembled at z~1. Beyond this redshift, the space density of ETGs starts dropping significantly, and as ETGs disappear, a population of massive, strongly clustered, starburst galaxies progressively becomes more and more prominent, which makes them the likely progenitors to ETGs.Comment: To appear on Annual Review of Astronomy & Astrophysics, Vol. 44 (2006). 46 pages with 16 figures. Replaced version includes updated references, few typos less, and replaces Fig. 11 and Fig. 16 which had been skrewed u

Temperature effects on zoeal morphometric traits and intraspecific variability in the hairy crab Cancer setosus across latitude

International audiencePhenotypic plasticity is an important but often ignored ability that enables organisms, within species-specific physiological limits, to respond to gradual or sudden extrinsic changes in their environment. In the marine realm, the early ontogeny of decapod crustaceans is among the best known examples to demonstrate a temperature-dependent phenotypic response. Here, we present morphometric results of larvae of the hairy crab , the embryonic development of which took place at different temperatures at two different sites (Antofagasta, 23°45′ S; Puerto Montt, 41°44′ S) along the Chilean Coast. Zoea I larvae from Puerto Montt were significantly larger than those from Antofagasta, when considering embryonic development at the same temperature. Larvae from Puerto Montt reared at 12 and 16°C did not differ morphometrically, but sizes of larvae from Antofagasta kept at 16 and 20°C did, being larger at the colder temperature. Zoea II larvae reared in Antofagasta at three temperatures (16, 20, and 24°C) showed the same pattern, with larger larvae at colder temperatures. Furthermore, larvae reared at 24°C, showed deformations, suggesting that 24°C, which coincides with temperatures found during strong EL Niño events, is indicative of the upper larval thermal tolerance limit.   is exposed to a wide temperature range across its distribution range of about 40° of latitude. Phenotypic plasticity in larval offspring does furthermore enable this species to locally respond to the inter-decadal warming induced by El Niño. Morphological plasticity in this species does support previously reported energetic trade-offs with temperature throughout early ontogeny of this species, indicating that plasticity may be a key to a species' success to occupy a wide distribution range and/or to thrive under highly variable habitat conditions

An improved parameter estimation and comparison for soft tissue constitutive models containing an exponential function

Motivated by the well-known result that stiffness of soft tissue is proportional to the stress, many of the constitutive laws for soft tissues contain an exponential function. In this work, we analyze properties of the exponential function and how it affects the estimation and comparison of elastic parameters for soft tissues. In particular, we find that as a consequence of the exponential function there are lines of high covariance in the elastic parameter space. As a result, one can have widely varying mechanical parameters defining the tissue stiffness but similar effective stress–strain responses. Drawing from elementary algebra, we propose simple changes in the norm and the parameter space, which significantly improve the convergence of parameter estimation and robustness in the presence of noise. More importantly, we demonstrate that these changes improve the conditioning of the problem and provide a more robust solution in the case of heterogeneous material by reducing the chances of getting trapped in a local minima. Based upon the new insight, we also propose a transformed parameter space which will allow for rational parameter comparison and avoid misleading conclusions regarding soft tissue mechanics

Effects of Thyroxine Exposure on Osteogenesis in Mouse Calvarial Pre-Osteoblasts

The incidence of craniosynostosis is one in every 1,800-2500 births. The gene-environment model proposes that if a genetic predisposition is coupled with environmental exposures, the effects can be multiplicative resulting in severely abnormal phenotypes. At present, very little is known about the role of gene-environment interactions in modulating craniosynostosis phenotypes, but prior evidence suggests a role for endocrine factors. Here we provide a report of the effects of thyroid hormone exposure on murine calvaria cells. Murine derived calvaria cells were exposed to critical doses of pharmaceutical thyroxine and analyzed after 3 and 7 days of treatment. Endpoint assays were designed to determine the effects of the hormone exposure on markers of osteogenesis and included, proliferation assay, quantitative ALP activity assay, targeted qPCR for mRNA expression of Runx2, Alp, Ocn, and Twist1, genechip array for 28,853 targets, and targeted osteogenic microarray with qPCR confirmations. Exposure to thyroxine stimulated the cells to express ALP in a dose dependent manner. There were no patterns of difference observed for proliferation. Targeted RNA expression data confirmed expression increases for Alp and Ocn at 7 days in culture. The genechip array suggests substantive expression differences for 46 gene targets and the targeted osteogenesis microarray indicated 23 targets with substantive differences. 11 gene targets were chosen for qPCR confirmation because of their known association with bone or craniosynostosis (Col2a1, Dmp1, Fgf1, 2, Igf1, Mmp9, Phex, Tnf, Htra1, Por, and Dcn). We confirmed substantive increases in mRNA for Phex, FGF1, 2, Tnf, Dmp1, Htra1, Por, Igf1 and Mmp9, and substantive decreases for Dcn. It appears thyroid hormone may exert its effects through increasing osteogenesis. Targets isolated suggest a possible interaction for those gene products associated with calvarial suture growth and homeostasis as well as craniosynostosis. © 2013 Cray et al

Diabetes status and post-load plasma glucose concentration in relation to site-specific cancer mortality: findings from the original Whitehall study

ObjectiveWhile several studies have reported on the relation of diabetes status with pancreatic cancer risk, the predictive value of this disorder for other malignancies is unclear. Methods: The Whitehall study, a 25year follow-up for mortality experience of 18,006 men with data on post-challenge blood glucose and self-reported diabetes, allowed us to address these issues. Results: There were 2158 cancer deaths at follow-up. Of the 15 cancer outcomes, diabetes status was positively associated with mortality from carcinoma of the pancreas and liver, while the relationship with lung cancer was inverse, after controlling for a range of potential covariates and mediators which included obesity and socioeconomic position. After excluding deaths occurring in the first 10years of follow-up to examine the effect of reverse causality, the magnitude of the relationships for carcinoma of the pancreas and lung was little altered, while for liver cancer it was markedly attenuated. Conclusions: In the present study, diabetes status was related to pancreatic, liver, and lung cancer risk. Cohorts with serially collected data on blood glucose and covariates are required to further examine this area

Effects of an exercise programme with people living with HIV: Research in a disadvantaged setting

This study aimed to analyse the physical health effects of a community based 10-week physical activity programme with people living with HIV. It was developed, implemented and evaluated in a disadvantaged community in South Africa. A pre-post research design was chosen. Major recruitment and adherence challenges resulted in a small sample. Among the 23 participants who took part in both baseline and final testing, compliant participants (n = 12) were compared to non-compliant participants (n = 11). Immunological (CD4, viral load), anthropometric (height, weight, skinfolds and waist to hip ratio), muscular strength (h1RM) and cardiopulmonary fitness (time on treadmill) parameters were measured. The compliant and non-compliant groups were not different at baseline. Muscular strength was the parameter most influenced by compliance with the physical activity programme (F = 4.516, p = 0.047). Weight loss and improvement in cardiopulmonary fitness were restricted by the duration of the programme, compliance and influencing factors (e.g. nutrition, medication). The increase in strength is significant and meaningful in the context, as the participants goals were to look healthy and strong to avoid HIV related stigma. The improvements in appearance were a motivational factor, especially since the changes were made visible in a short time. Practical implications for health promotion are described. More research contextualised in disadvantaged settings is needed.DHE