Fission of a multiphase membrane tube

A common mechanism for intracellular transport is the use of controlled deformations of the membrane to create spherical or tubular buds. While the basic physical properties of homogeneous membranes are relatively well-known, the effects of inhomogeneities within membranes are very much an active field of study. Membrane domains enriched in certain lipids in particular are attracting much attention, and in this Letter we investigate the effect of such domains on the shape and fate of membrane tubes. Recent experiments have demonstrated that forced lipid phase separation can trigger tube fission, and we demonstrate how this can be understood purely from the difference in elastic constants between the domains. Moreover, the proposed model predicts timescales for fission that agree well with experimental findings

Metastability, negative specific heat and weak mixing in classical long-range many-rotator system

We perform a molecular dynamical study of the isolated $d=1$ classical Hamiltonian ${\cal H} = {1/2} \sum_{i=1}^N L_i^2 + \sum_{i \ne j} \frac{1-cos(\theta_i-\theta_j)}{r_{ij}^\alpha} ;(\alpha \ge 0)$, known to exhibit a second order phase transition, being disordered for $u \equiv U/N{\tilde N} \ge u_c(\alpha,d)$ and ordered otherwise ($U\equiv$ total energy and ${\tilde N} \equiv \frac{N^{1-\alpha/d}-\alpha/d}{1-\alpha/d}$). We focus on the nonextensive case $\alpha/d \le 1$ and observe that, for $u<u_c$, a basin of attraction exists for the initial conditions for which the system quickly relaxes onto a longstanding metastable state (whose duration presumably diverges with $N$ like ${\tilde N}$) which eventually crosses over to the microcanonical Boltzmann-Gibbs stable state. The temperature associated with the (scaled) average kinetic energy per particle is lower in the metastable state than in the stable one. It is exhibited for the first time that the appropriately scaled maximal Lyapunov exponent $\lambda_{u<u_c}^{max}(metastable) \propto N^{-\kappa_{metastable}} ;(N \to \infty)$, where, for all values of $\alpha/d$, $\kappa_{metastable}$ numerically coincides with {\it one third} of its value for $u>u_c$, hence decreases from 1/9 to zero when $\alpha/d$ increases from zero to unity, remaining zero thereafter. This new and simple {\it connection between anomalies above and below the critical point} reinforces the nonextensive universality scenario.Comment: 9 pages and 4 PS figure

Limit distributions of scale-invariant probabilistic models of correlated random variables with the q-Gaussian as an explicit example

Extremization of the Boltzmann-Gibbs (BG) entropy under appropriate norm and width constraints yields the Gaussian distribution. Also, the basic solutions of the standard Fokker-Planck (FP) equation (related to the Langevin equation with additive noise), as well as the Central Limit Theorem attractors, are Gaussians. The simplest stochastic model with such features is N to infinity independent binary random variables, as first proved by de Moivre and Laplace. What happens for strongly correlated random variables? Such correlations are often present in physical situations as e.g. systems with long range interactions or memory. Frequently q-Gaussians become observed. This is typically so if the Langevin equation includes multiplicative noise, or the FP equation to be nonlinear. Scale-invariance, i.e. exchangeable binary stochastic processes, allow a systematical analysis of the relation between correlations and non-Gaussian distributions. In particular, a generalized stochastic model yielding q-Gaussians for all q (including q>1) was missing. This is achieved here by using the Laplace-de Finetti representation theorem, which embodies strict scale-invariance of interchangeable random variables. We demonstrate that strict scale invariance together with q-Gaussianity mandates the associated extensive entropy to be BG.Comment: 6 pages, 1 fig, to appear in EPJ

Membranes by the Numbers

Many of the most important processes in cells take place on and across membranes. With the rise of an impressive array of powerful quantitative methods for characterizing these membranes, it is an opportune time to reflect on the structure and function of membranes from the point of view of biological numeracy. To that end, in this article, I review the quantitative parameters that characterize the mechanical, electrical and transport properties of membranes and carry out a number of corresponding order of magnitude estimates that help us understand the values of those parameters.Comment: 27 pages, 12 figure

Vesicle-Like Biomechanics Governs Important Aspects of Nuclear Geometry in Fission Yeast

It has long been known that during the closed mitosis of many unicellular eukaryotes, including the fission yeast (Schizosaccharomyces pombe), the nuclear envelope remains intact while the nucleus undergoes a remarkable sequence of shape transformations driven by elongation of an intranuclear mitotic spindle whose ends are capped by spindle pole bodies embedded in the nuclear envelope. However, the mechanical basis of these normal cell cycle transformations, and abnormal nuclear shapes caused by intranuclear elongation of microtubules lacking spindle pole bodies, remain unknown. Although there are models describing the shapes of lipid vesicles deformed by elongation of microtubule bundles, there are no models describing normal or abnormal shape changes in the nucleus. We describe here a novel biophysical model of interphase nuclear geometry in fission yeast that accounts for critical aspects of the mechanics of the fission yeast nucleus, including the biophysical properties of lipid bilayers, forces exerted on the nuclear envelope by elongating microtubules, and access to a lipid reservoir, essential for the large increase in nuclear surface area during the cell cycle. We present experimental confirmation of the novel and non-trivial geometries predicted by our model, which has no free parameters. We also use the model to provide insight into the mechanical basis of previously described defects in nuclear division, including abnormal nuclear shapes and loss of nuclear envelope integrity. The model predicts that (i) despite differences in structure and composition, fission yeast nuclei and vesicles with fluid lipid bilayers have common mechanical properties; (ii) the S. pombe nucleus is not lined with any structure with shear resistance, comparable to the nuclear lamina of higher eukaryotes. We validate the model and its predictions by analyzing wild type cells in which ned1 gene overexpression causes elongation of an intranuclear microtubule bundle that deforms the nucleus of interphase cells

Polymorphisms in regulatory regions of Cyclooxygenase-2 gene and breast cancer risk in Brazilians: a case-control study

<p>Abstract</p> <p>Background</p> <p>Cyclooxygenase-2 (COX-2) is up-regulated in several types of cancer, and it is hypothesized that COX-2 expression may be genetically influenced. Here, we evaluate the association between single-nucleotide polymorphisms (SNPs) in the COX-2 gene (<it>PTGS2</it>) and the occurrence of breast cancer among Brazilian women.</p> <p>Methods</p> <p>The study was conducted prospectively in two steps: First, we screened the promoter region and three fragments of the 3'-untranslated region of <it>PTGS2 </it>from 67 healthy Brazilians to identify SNPs and to select those with a minor allele frequency (MAF) of at least 0.10. The MAF of these selected SNPs was further characterized in 402 healthy volunteers to evaluate potential differences related to heterogeneous racial admixture and to estimate the existence of linkage disequilibrium among the SNPs. The second step was a case-control study with 318 patients and 273 controls designed to evaluate <it>PTGS2 </it>genotype- or haplotype-associated risk of breast cancer.</p> <p>Results</p> <p>The screening analysis indicated nine SNPs with the following MAFs: rs689465 (0.22), rs689466 (0.15), rs20415 (0.007), rs20417 (0.32), rs20419 (0.015), rs5270 (0.02), rs20424 (0.007), rs5275 (0.22) and rs4648298 (0.01). The SNPs rs689465, rs689466, rs20417 and rs5275 were further studied: Their genotypic distributions followed Hardy-Weinberg equilibrium and the MAFs were not affected by gender or skin color. Strong linkage disequilibrium was detected for rs689465, rs20417 and rs5275 in the three possible pairwise combinations. In the case-control study, there was a significant increase of rs5275TC heterozygotes in cases compared to controls (OR = 1.44, 95% CI = 1.01-2.06; P = 0.043), and the haplotype formed by rs689465G, rs689466A, rs20417G and rs5275C was only detected in cases. The apparent association with breast cancer was not confirmed for rs5275CC homozygotes or for the most frequent rs5275C-containing haplotypes.</p> <p>Conclusions</p> <p>Our results indicate no strong association between the four most frequent <it>PTGS2 </it>SNPs and the risk of breast cancer.</p

Genetics, genomics and breeding of groundnut (Arachis hypogaea L.)

Groundnut is an important food and oil crop in the semiarid tropics, contributing to household food consumption and cash income. In Asia and Africa, yields are low attributed to various production constraints. This review paper highlights advances in genetics, genomics and breeding to improve the productivity of groundnut. Genetic studies concerning inheritance, genetic variability and heritability, combining ability and trait correlations have provided a better understanding of the crop's genetics to develop appropriate breeding strategies for target traits. Several improved lines and sources of variability have been identified or developed for various economically important traits through conventional breeding. Significant advances have also been made in groundnut genomics including genome sequencing, marker development and genetic and trait mapping. These advances have led to a better understanding of the groundnut genome, discovery of genes/variants for traits of interest and integration of marker‐assisted breeding for selected traits. The integration of genomic tools into the breeding process accompanied with increased precision of yield trialing and phenotyping will increase the efficiency and enhance the genetic gain for release of improved groundnut varieties

The Dopamine Augmenter L-DOPA Does Not Affect Positive Mood in Healthy Human Volunteers

Dopamine neurotransmission influences approach toward rewards and reward-related cues. The best cited interpretation of this effect proposes that dopamine mediates the pleasure that commonly accompanies reward. This hypothesis has received support in some animal models and a few studies in humans. However, direct assessments of the effect of transiently increasing dopamine neurotransmission have been largely limited to the use of psychostimulant drugs, which elevate brain levels of multiple neurotransmitters in addition to dopamine. In the present study we tested the effect of more selectively elevating dopamine neurotransmission, as produced by administration of the immediate dopamine precursor, L-DOPA (0, 100/25, 200/50 mg, Sinemet), in healthy human volunteers. Neither dose altered positive mood. The results suggest that dopamine neurotransmission does not directly influence positive mood in humans

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially