The reversible polydisperse Parking Lot Model

We use a new version of the reversible Parking Lot Model to study the compaction of vibrated polydisperse media. The particle sizes are distributed according to a truncated power law. We introduce a self-consistent desorption mechanism with a hierarchical initialization of the system. In this way, we approach densities close to unity. The final density depends on the polydispersity of the system as well as on the initialization and will reach a maximum value for a certain exponent in the power law.Comment: 7 pages, Latex, 12 figure

On the evaluation of global sea-salt aerosol models at coastal/orographic sites

Sea-salt aerosol global models are typically evaluated against concentration observations at coastal stations that are unaffected by local surf conditions and thus considered representative of open ocean conditions. Despite recent improvements in sea-salt source functions, studies still show significant model errors in specific regions. Using a multiscale model, we investigated the effect of high model resolution (0.1 degrees x 0.1 degrees vs. 1 degrees x 1.4 degrees) upon sea-salt patterns in four stations from the University of Miami Network: Baring Head, Chatam Island, and Invercargill in New Zealand, and Marion Island in the sub-antarctic Indian Ocean. Normalized biases improved from +63.7% to +3.3% and correlation increased from 0.52 to 0.84. The representation of sea/land interfaces, mesoscale circulations, and precipitation with the higher resolution model played a major role in the simulation of annual concentration trends. Our results recommend caution when comparing or constraining global models using surface concentration observations from coastal stations. (C) 2014 The Authors. Published by Elsevier Ltd.Postprint (published version

Interface localisation-delocalisation transition in a symmetric polymer blend: a finite-size scaling Monte Carlo study

Using extensive Monte Carlo simulations we study the phase diagram of a symmetric binary (AB) polymer blend confined into a thin film as a function of the film thickness D. The monomer-wall interactions are short ranged and antisymmetric, i.e, the left wall attracts the A-component of the mixture with the same strength as the right wall the B-component, and give rise to a first order wetting transition in a semi-infinite geometry. The phase diagram and the crossover between different critical behaviors is explored. For large film thicknesses we find a first order interface localisation/delocalisation transition and the phase diagram comprises two critical points, which are the finite film width analogies of the prewetting critical point. Using finite size scaling techniques we locate these critical points and present evidence of 2D Ising critical behavior. When we reduce the film width the two critical points approach the symmetry axis $\phi=1/2$ of the phase diagram and for $D \approx 2 R_g$ we encounter a tricritical point. For even smaller film thickness the interface localisation/delocalisation transition is second order and we find a single critical point at $\phi=1/2$. Measuring the probability distribution of the interface position we determine the effective interaction between the wall and the interface. This effective interface potential depends on the lateral system size even away from the critical points. Its system size dependence stems from the large but finite correlation length of capillary waves. This finding gives direct evidence for a renormalization of the interface potential by capillary waves in the framework of a microscopic model.Comment: Phys.Rev.

Exact Three Dimensional Casimir Force Amplitude, CC-function and Binder's Cumulant Ratio: Spherical Model Results

The three dimensional mean spherical model on a hypercubic lattice with a film geometry $L\times \infty ^2$ under periodic boundary conditions is considered in the presence of an external magnetic field $H$. The universal Casimir amplitude $\Delta$ and the Binder's cumulant ratio $B$ are calculated exactly and found to be $\Delta =-2\zeta (3)/(5\pi)\approx -0.153051$ and $B=2\pi /(\sqrt{5}\ln ^3[(1+\sqrt{5})/2]).$ A discussion on the relations between the finite temperature $C$-function, usually defined for quantum systems, and the excess free energy (due to the finite-size contributions to the free energy of the system) scaling function is presented. It is demonstrated that the $C$-function of the model equals 4/5 at the bulk critical temperature $T_c$. It is analytically shown that the excess free energy is a monotonically increasing function of the temperature $T$ and of the magnetic field $|H|$ in the vicinity of $T_c.$ This property is supposed to hold for any classical $d$-dimensional $O(n),n>2,$ model with a film geometry under periodic boundary conditions when $d\leq 3$. An analytical evidence is also presented to confirm that the Casimir force in the system is negative both below and in the vicinity of the bulk critical temperature $T_c.$Comment: 12 pages revtex, one eps figure, submitted to Phys. Rev E A set of references added with the text needed to incorporate them. Small changes in the title and in the abstrac

Human Iron−Sulfur Cluster Assembly, Cellular Iron Homeostasis, and Disease†

ABSTRACT: Iron-sulfur (Fe-S) proteins contain prosthetic groups consisting of two or more iron atoms bridged by sulfur ligands, which facilitate multiple functions, including redox activity, enzymatic function, and maintenance of structural integrity. More than 20 proteins are involved in the biosynthesis of iron-sulfur clusters in eukaryotes. Defective Fe-S cluster synthesis not only affects activities of many iron-sulfur enzymes, such as aconitase and succinate dehydrogenase, but also alters the regulation of cellular iron homeostasis, causing both mitochondrial iron overload and cytosolic iron deficiency. In this work, we review human Fe-S cluster biogenesis and human diseases that are caused by defective Fe-S cluster biogenesis. Fe-S cluster biogenesis takes place essentially in every tissue of humans, and products of human disease genes, including frataxin, GLRX5, ISCU, and ABCB7, have important roles in the process. However, the human diseases, Friedreich ataxia, glutaredoxin 5-deficient sideroblastic anemia, ISCU myopathy, and ABCB7 sideroblastic anemia/ataxia syndrome, affect specific tissues, while sparing others. Here we discuss the phenotypes caused by mutations in these different disease genes, and we compare the underlying pathophysiology and discuss the possible explanations for tissue-specific pathology in these diseases caused by defective Fe-S cluster biogenesis. HUMAN CELLULAR IRON HOMEOSTASI

Expression of Human Frataxin Is Regulated by Transcription Factors SRF and TFAP2

Friedreich ataxia is an autosomal recessive neurodegenerative disease caused by reduced expression levels of the frataxin gene (FXN) due to expansion of triplet nucleotide GAA repeats in the first intron of FXN. Augmentation of frataxin expression levels in affected Friedreich ataxia patient tissues might substantially slow disease progression.We utilized bioinformatic tools in conjunction with chromatin immunoprecipitation and electrophoretic mobility shift assays to identify transcription factors that influence transcription of the FXN gene. We found that the transcription factors SRF and TFAP2 bind directly to FXN promoter sequences. SRF and TFAP2 binding sequences in the FXN promoter enhanced transcription from luciferase constructs, while mutagenesis of the predicted SRF or TFAP2 binding sites significantly decreased FXN promoter activity. Further analysis demonstrated that robust SRF- and TFAP2-mediated transcriptional activity was dependent on a regulatory element, located immediately downstream of the first FXN exon. Finally, over-expression of either SRF or TFAP2 significantly increased frataxin mRNA and protein levels in HEK293 cells, and frataxin mRNA levels were also elevated in SH-SY5Y cells and in Friedreich ataxia patient lymphoblasts transfected with SRF or TFAP2.We identified two transcription factors, SRF and TFAP2, as well as an intronic element encompassing EGR3-like sequence, that work together to regulate expression of the FXN gene. By providing new mechanistic insights into the molecular factors influencing frataxin expression, our results should aid in the discovery of new therapeutic targets for the treatment of Friedreich ataxia

Bioavailable Trace Metals in Neurological Diseases

Medical treatment in Wilson’s disease includes chelators (d-penicillamine and trientine) or zinc salts that have to be maintain all the lifelong. This pharmacological treatment is categorised into two phases; the first being a de-coppering phase and the second a maintenance one. The best therapeutic approach remains controversial, as only a few non-controlled trials have compared these treatments. During the initial phase, progressive increase of chelators’ doses adjusted to exchangeable copper and urinary copper might help to avoid neurological deterioration. Liver transplantation is indicated in acute fulminant liver failure and decompensated cirrhosis; in cases of neurologic deterioration, it must be individually discussed. During the maintenance phase, the most important challenge is to obtain a good adherence to lifelong medical therapy. Neurodegenerative diseases that lead to a mislocalisation of iron can be caused by a culmination of localised overload (pro-oxidant siderosis) and localised deficiency (metabolic distress). A new therapeutic concept with conservative iron chelation rescues iron-overloaded neurons by scavenging labile iron and, by delivering this chelated metal to endogenous apo-transferrin, allows iron redistribution to avoid systemic loss of iron

Iron Storage within Dopamine Neurovesicles Revealed by Chemical Nano-Imaging

Altered homeostasis of metal ions is suspected to play a critical role in neurodegeneration. However, the lack of analytical technique with sufficient spatial resolution prevents the investigation of metals distribution in neurons. An original experimental setup was developed to perform chemical element imaging with a 90 nm spatial resolution using synchrotron-based X-ray fluorescence. This unique spatial resolution, combined to a high brightness, enables chemical element imaging in subcellular compartments. We investigated the distribution of iron in dopamine producing neurons because iron-dopamine compounds are suspected to be formed but have yet never been observed in cells. The study shows that iron accumulates into dopamine neurovesicles. In addition, the inhibition of dopamine synthesis results in a decreased vesicular storage of iron. These results indicate a new physiological role for dopamine in iron buffering within normal dopamine producing cells. This system could be at fault in Parkinson's disease which is characterized by an increased level of iron in the substancia nigra pars compacta and an impaired storage of dopamine due to the disruption of vesicular trafficking. The re-distribution of highly reactive dopamine-iron complexes outside neurovesicles would result in an enhanced death of dopaminergic neurons

A Novel Role for the SMG-1 Kinase in Lifespan and Oxidative Stress Resistance in Caenorhabditis elegans

The PTEN tumour suppressor encodes a phosphatase, and its daf-18 orthologue in Caenorhabditis elegans negatively regulates the insulin/IGF-1 DAF-2 receptor pathway that influences lifespan in worms and other species. In order to identify new DAF-18 regulated pathways involved in aging, we initiated a candidate RNAi feeding screen for clones that lengthen lifespan. Here, we report that smg-1 inactivation increases average lifespan in a daf-18 dependent manner. Genetic analysis is consistent with SMG-1 acting at least in part in parallel to the canonical DAF-2 receptor pathway, but converging on the transcription factor DAF-16/FOXO. SMG-1 is a serine-threonine kinase which plays a conserved role in nonsense-mediated mRNA decay (NMD) in worms and mammals. In addition, human SMG-1 has also been implicated in the p53-mediated response to genotoxic stress. The effect of smg-1 inactivation on lifespan appears to be unrelated to its NMD function, but requires the p53 tumour suppressor orthologue cep-1. Furthermore, smg-1 inactivation confers a resistance to oxidative stress in a daf-18-, daf-16- and cep-1-dependent manner. We propose that the role of SMG-1 in lifespan regulation is at least partly dependent on its function in oxidative stress resistance. Taken together, our results unveil a novel role for SMG-1 in lifespan regulation

Developing a community-based genetic nomenclature for anole lizards

Background: Comparative studies of amniotes have been hindered by a dearth of reptilian molecular sequences. With the genomic assembly of the green anole, Anolis carolinensis available, non-avian reptilian genes can now be compared to mammalian, avian, and amphibian homologs. Furthermore, with more than 350 extant species in the genus Anolis, anoles are an unparalleled example of tetrapod genetic diversity and divergence. As an important ecological, genetic and now genomic reference, it is imperative to develop a standardized Anolis gene nomenclature alongside associated vocabularies and other useful metrics. Results: Here we report the formation of the Anolis Gene Nomenclature Committee (AGNC) and propose a standardized evolutionary characterization code that will help researchers to define gene orthology and paralogy with tetrapod homologs, provide a system for naming novel genes in Anolis and other reptiles, furnish abbreviations to facilitate comparative studies among the Anolis species and related iguanid squamates, and classify the geographical origins of Anolis subpopulations. Conclusions: This report has been generated in close consultation with members of the Anolis and genomic research communities, and using public database resources including NCBI and Ensembl. Updates will continue to be regularly posted to new research community websites such as lizardbase. We anticipate that this standardized gene nomenclature will facilitate the accessibility of reptilian sequences for comparative studies among tetrapods and will further serve as a template for other communities in their sequencing and annotation initiatives.Organismic and Evolutionary BiologyOther Research Uni