Cholesterol transport from late endosomes to the Golgi regulates t-SNARE trafficking, assembly, and function

Cholesterol regulates plasma membrane (PM) association and functioning of syntaxin-4 and soluble N-ethylmaleimide-sensitive fusion protein 23 (SNAP23) in the secretory pathway. However, the molecular mechanism and cellular cholesterol pools that determine the localization and assembly of these target membrane SNAP receptors (t-SNAREs) are largely unknown. We recently demonstrated that high levels of annexin A6 (AnxA6) induce accumulation of cholesterol in late endosomes, thereby reducing cholesterol in the Golgi and PM. This leads to an impaired supply of cholesterol needed for cytosolic phospholipase A2 (cPLA2) to drive Golgi vesiculation and caveolin transport to the cell surface. Using AnxA6-overexpressing cells as a model for cellular cholesterol imbalance, we identify impaired cholesterol egress from late endosomes and diminution of Golgi cholesterol as correlating with the sequestration of SNAP23/syntaxin-4 in Golgi membranes. Pharmacological accumulation of late endosomal cholesterol and cPLA2 inhibition induces a similar phenotype in control cells with low AnxA6 levels. Ectopic expression of Niemann-Pick C1 (NPC1) or exogenous cholesterol restores the location of SNAP23 and syntaxin-4 within the PM. Importantly, AnxA6-mediated mislocalization of these t-SNAREs correlates with reduced secretion of cargo via the SNAP23/syntaxin-4¿dependent constitutive exocytic pathway. We thus conclude that inhibition of late endosomal export and Golgi cholesterol depletion modulate t-SNARE localization and functioning along the exocytic pathway.

Colloidal assembly on magnetically vibrated stripes

We investigate the collective organization of paramagnetic colloidal particles externally driven above the periodic stripes of a uniaxial ferrimagnetic garnet film. An external field modulation induces vibration of the stripe walls and produces random motion of the particles. Defects in the stripe pattern break the symmetry of the potential and favor particle nucleation into large clusters above a critical density. Mismatch between particle size and pattern wavelength generates assemblies with different morphological order. At even higher field strengths, repulsive dipolar interactions between the particles induce cluster melting. We propose a novel approach to generate and externally control a variety of colloidal assemblies.

Self-organizing propagation patterns from dynamic self-assembly in monolayers

Propagation of localized orientational waves, as imaged by Brewster angle microscopy, is induced by low intensity linearly polarized light inside axisymmetric smectic-C confined domains in a photosensitive molecular thin film at the air/water interface (Langmuir monolayer). Results from numerical simulations of a model that couples photoreorientational effects and long-range elastic forces are presented. Differences are stressed between our scenario and the paradigmatic wave phenomena in excitable chemical media.

Self-organizing propagation patterns from dynamic self-assembly in monolayers

Propagation of localized orientational waves, as imaged by Brewster angle microscopy, is induced by low intensity linearly polarized light inside axisymmetric smectic-C confined domains in a photosensitive molecular thin film at the air/water interface (Langmuir monolayer). Results from numerical simulations of a model that couples photoreorientational effects and long-range elastic forces are presented. Differences are stressed between our scenario and the paradigmatic wave phenomena in excitable chemical media.

Eliciting preferences for collectively financed health programmes : the "willingness to assign" approach

Improving public involvement in health system decision making stands as a primary goal in health systems reform. However, still limited evidence is found on how best to elicit preferences for health care programs. This paper examines a contingent choice technique to elicit preferences among health programs so called, willingness to assign (WTAS): Moreover, we elicited contingents rankings as well as the willingness to pay extra taxes for comparative purposes. We argue that WTAS reveals relative ( monetary-based) values of a set of competing public programmes under a hypothetical healthcare budget assessment. Experimental evidence is reported from a delibertive empirical study valuing ten health programmes in the context of the Catalan Health Services. Evidence from a our experimental study reveals that perferences are internally more consistent and slightly less affected by "preference reversals" as compared to values revealed from the willingness to pay (WTP) extra taxes approach. Consistent with prior studies, we find that the deliberative approach helped to avoid possible misunderstandings. Interestingly, although programmes promoting health received the higher relative valuation, those promoting other health benefits also ranked highly

Model studies on the synthesis of madangamine alkaloids. Assembly of the macrocyclic rings

Using simplified model derivatives, the assembly of the macrocyclic rings of madangamines, including the 13- and 14-membered D rings of madangamines C-E, the all-cis-triunsaturated 15-membered D ring of madangamine A, and the (Z,Z)-unsaturated 11-membered E ring common to madangamines A-E, has been studied.

Viral self-assembly as a thermodynamic process

The protein shells, or capsids, of nearly all spherelike viruses adopt icosahedral symmetry. In the present Letter, we propose a statistical thermodynamic model for viral self-assembly. We find that icosahedral symmetry is not expected for viral capsids constructed from structurally identical protein subunits and that this symmetry requires (at least) two internal switching configurations of the protein. Our results indicate that icosahedral symmetry is not a generic consequence of free energy minimization but requires optimization of internal structural parameters of the capsid proteins

Heuristic procedures for solving the General Assembly Line Balancing Problem with Setups (GALBPS)

The General Assembly Line Balancing Problem with Setups (GALBPS) was recently defined in the literature. It adds sequence-dependent setup time considerations to the classical Simple Assembly Line Balancing Problem (SALBP) as follows: whenever a task is assigned next to another at the same workstation, a setup time must be added to compute the global workstation time, thereby providing the task sequence inside each workstation. This paper proposes over 50 priority-rule-based heuristic procedures to solve GALBPS, many of which are an improvement upon heuristic procedures published to date.

World Library and Information Congress: 75th IFLA General Conference and Assembly.

L"edició del 2009 de la trobada de l"IFLA s"ha celebrat a Milà. La maquinària de l"organització va funcionar amb precisió per a aquest esdeveniment. Després d"anys de regularitat en les trobades per tot el món, l"IFLA funciona com un autòmat, una d"aquestes màquines perfectes, tant que podria continuar uncionant en les formes amb exemplar artifici. És un trobada singular, que aplega, a la vegada, la reunió de l"organització, un congrés mundial i una fira comercial; tot això amanit amb una ciutat diferent cada any i un finançament que depèn de la bona marxa de tot l"esdeveniment. En certa mesura, l"IFLA és un aparador de la professió, al qual assisteixen bibliotecaris de tot el món i de centenars d"institucions, amb tot el que suposa d"artificiositat en la representació d"entitats i promoció; un espai de reflexió, amb ponències i debats de molt variat interès que poden trobar-se, generalment, en altres esdeveniments; i una posada a punt dels treballs de tots els comitès, que tenen un complex desenvolupament previ i una àrdua tasca desenvolupada amb generositat per tots els participants.

Evolution and cellular function of monothiol glutaredoxins: involvement in iron-sulphur cluster assembly

A number of bacterial species, mostly proteobacteria, possess monothiol glutaredoxins homologous to the Saccharomyces cerevisiae mitochondrial protein Grx5, which is involved in iron–sulphur cluster synthesis. Phylogenetic profiling is used to predict that bacterial monothiol glutaredoxins also participate in the iron–sulphur cluster (ISC) assembly machinery, because their phylogenetic profiles are similar to the profiles of the bacterial homologues of yeast ISC proteins. High evolutionary cooccurrence is observed between the Grx5 homologues and the homologues of the Yah1 ferredoxin, the scaffold proteins Isa1 and Isa2, the frataxin protein Yfh1 and the Nfu1 protein. This suggests that a specific functional interaction exists between these ISC machinery proteins. Physical interaction analyses using low-definition protein docking predict the formation of strong and specific complexes between Grx5 and several components of the yeast ISC machinery. Two-hybrid analysis has confirmed the in vivo interaction between Grx5 and Isa1. Sequence comparison techniques and cladistics indicate that the other two monothiol glutaredoxins of S. cerevisiae, Grx3 and Grx4, have evolved from the fusion of a thioredoxin gene with a monothiol glutaredoxin gene early in the eukaryotic lineage, leading to differential functional specialization. While bacteria do not contain these chimaeric glutaredoxins, in many eukaryotic species Grx5 and Grx3/4-type monothiol glutaredoxins coexist in the cell.

Signaling across the synapse: a role for Wnt and Dishevelled in presynaptic assembly and neurotransmitter release

Proper dialogue between presynaptic neurons and their targets is essential for correct synaptic assembly and function. At central synapses, Wnt proteins function as retrograde signals to regulate axon remodeling and the accumulation of presynaptic proteins. Loss of Wnt7a function leads to defects in the localization of presynaptic markers and in the morphology of the presynaptic axons. We show that loss of function of Dishevelled-1 (Dvl1) mimics and enhances the Wnt7a phenotype in the cerebellum. Although active zones appear normal, electrophysiological recordings in cerebellar slices from Wnt7a/Dvl1 double mutant mice reveal a defect in neurotransmitter release at mossy fi ber–granule cell synapses. Deficiency in Dvl1 decreases, whereas exposure to Wnt increases, synaptic vesicle recycling in mossy fi bers. Dvl increases the number of Bassoon clusters, and like other components of the Wnt pathway, it localizes to synaptic sites. These fi ndings demonstrate that Wnts signal across the synapse on Dvl-expressing presynaptic terminals to regulate synaptic assembly and suggest a potential novel function for Wnts in neurotransmitter release.

Interplay between surface anisotropy and dipolar interactions in an assembly of nanomagnets

We study the interplay between the effects of surface anisotropy and dipolar interactions in monodisperse assemblies of nanomagnets with oriented anisotropy. We derive asymptotic formulas for the assembly magnetization, taking into account temperature, applied field, core and surface anisotropy, and dipolar interparticle interactions. We find that the interplay between surface anisotropy and dipolar interactions is well described by the analytical expression of the assembly magnetization derived here: the overall sign of the product of the two parameters governing the surface and the dipolar contributions determines whether intrinsic and collective terms compete or have synergistic effects on the magnetization. This is illustrated by the magnetization curves of γ-Fe2O3 nanoparticle assemblies in the low concentration limit.

Substrate and depth preferences of macroinvertebrates along a transect in a Pyrenean high mountain lake (Estanh Redo, NE Spain)

Se estudia la composiciÛn y estructura de la comunidad de macroinvertebrados a lo largo de un transecto en profundidad en el lago Redó (Pirineos). Este estudio se enmarca dentro del proyecto de ámbito europeo MOLAR (Mountain Lake Research). Un equipo de buceadores muestreo dos tipos de substrato, piedras y fondos blandos, cada 2 m desde los 2 a los 20 m de profundidad. En la parte m·s profunda del lago las muestras se tomaron con draga Ekman (tres rÈplicas). Todas las muestras se tomaron el mismo día, el 15 de Julio de 1997. Los resultados, mediante un análisis de autocorrelación de Mantel, muestran que no existe un gradiente continuo en la sustituciÛn de unas especies por otras en la comunidad sobre substrato rocoso, sino que se distinguen dos discontinuidades claras, una a los 4 metros y otra a los 14 metros. La primera separa las especies propias de la zona litoral respecto a las de la zona sublitoral, mientras que la segunda coincide con la parte inferior de la termoclina, una zona siempre mas frÌa, con menos luz y con mayor acumulación de material fino sobre los sustratos duros a la vez que desaparece la cobertura algal que cubrÌa las piedras hasta esta profundidad. Respecto al sustrato existen especies que claramente prefieren el sustrato blando (oligoquetos, o los quironÛmidos Micropsectra radialis y Pseudodiamesa nivosa), mientras que otras eran más abundantes o exclusivas de los sustratos duros (Radix peregra, Plectrocnemia laetabilis, Psectrocladius octomaculatus). Estos resultados seran muy útiles para la interpretaciÛn de los datos paleolimnolÛgicos de los cores que actualmente se est·n estudiando en el lago.

Social Preferences and Transport Policy: The case of US speed limits

This article, in reviewing the longrunning US debate on speed limits, illustrates how a different valuation of the trade-off between private mobility needs and safety concerns can shape transport policies. It is argued that the regulatory decentralization debate, together with the speed limit in force in each state, obey the social preferences and valuation given to this tradeoff. Such a view is consistent with evidence that higher speed limits are to be found in states with greater private mobility needs, even though their fatality rates might be among the highest in the country. By contrast, lower speed limits and supporters of a low national speed limit are to be found in states that show a greater concern for safety outcomes and which are less dependent on private mobility. By reviewing these events and examining the role played by the main actors and analyzing their motivations, the article identifies important lessons for similar future discussions on transport policy.

Anisotropic surface properties of micro/nanostructured a-C:H:F thin films with self-assembly applications

The singular properties of hydrogenated amorphous carbon (a-C:H) thin filmsdeposited by pulsed DC plasma enhanced chemical vapor deposition (PECVD), such as hardness and wear resistance, make it suitable as protective coating with low surface energy for self-assembly applications. In this paper, we designed fluorine-containing a-C:H (a-C:H:F) nanostructured surfaces and we characterized them for self-assembly applications. Sub-micron patterns were generated on silicon through laser lithography while contact angle measurements, nanotribometer, atomic force microscopy (AFM), and scanning electron microscopy (SEM) were used to characterize the surface. a-C:H:F properties on lithographied surfaces such as hydrophobicity and friction were improved with the proper relative quantity of CH4 and CHF3 during deposition, resulting in ultrahydrophobic samples and low friction coefficients. Furthermore, these properties were enhanced along the direction of the lithographypatterns (in-plane anisotropy). Finally, self-assembly properties were tested with silicananoparticles, which were successfully assembled in linear arrays following the generated patterns. Among the main applications, these surfaces could be suitable as particle filter selector and cell colony substrate.