Dual Action of BPC194: A Membrane Active Peptide Killing Bacterial Cells

Membrane active peptides can perturb the lipid bilayer in several ways, such as poration and fusion of the target cell membrane, and thereby efficiently kill bacterial cells. We probe here the mechanistic basis of membrane poration and fusion caused by membrane-active, antimicrobial peptides. We show that the cyclic antimicrobial peptide, BPC194, inhibits growth of Gram-negative bacteria and ruptures the outer and inner membrane at the onset of killing, suggesting that not just poration is taking place at the cell envelope. To simplify the system and to better understand the mechanism of action, we performed Förster resonance energy transfer and cryogenic transmission electron microscopy studies in model membranes and show that the BPC194 causes fusion of vesicles. The fusogenic action is accompanied by leakage as probed by dual-color fluorescence burst analysis at a single liposome level. Atomistic molecular dynamics simulations reveal how the peptides are able to simultaneously perturb the membrane towards porated and fused states. We show that the cyclic antimicrobial peptides trigger both fusion and pore formation and that such large membrane perturbations have a similar mechanistic basis

Avantatges i inconvenients de la metodologia INE per a elaborar indicadors de la producció industrial per a les regions espanyoles

Conèixer l'evolució conjuntural del sector industrial, tant a nivell nacional com regional, és de gran importància. En aquest sentit, el retard en la publicació de les xifres de les Comptabilitats Nacionals/Regionals, fa necessària l'elaboració d'indicadors que permetin dur a terme un seguiment a curt termini de l'activitat industrial. Així, l'INE elabora un IPI mensual obtingut pel mètode directe pel conjunt de l'Estat. D'altra banda, al llarg dels darrers anys, a algunes comunitats autònomes espanyoles, s'han engegat projectes centrats en l'elaboració d'indicadors de l'activitat industrial regional, tot i que a partir de metodologies no homogènies. Per corregir aquesta situació, d'un temps ençà, a diferents fòrums s'ha proposat emprar la metodologia emprada per l'IDESCAT per elaborar l'indicador de la comunitat catalana com a alternativa per construir indicadors de l'activitat industrial regional, atès el seu bon comportament per Catalunya. Així, l'INE recentment ha publicat uns IPIs per les CA espanyoles d'acord amb dita metodologia. A aquest treball s'estudia la idoneïtat d'estendre l'esmentada metodologia a totes les regions espanyoles. Per això, es duu a terme una anàlisi comparativa centrada en (tres de) les quatre regions que disposen d'un IPI elaborat pel mètode directe: Andalusia, Astúries i el País Basc.

Cooking and Active Leisure TAS Program, Spain: A Program Impact Pathways (PIP) analysis

Background. The “Cooking and Active Leisure” Tu y Alícia por la Salud (CAL-TAS) Program is a schoolbased pilot that addresses healthy lifestyle needs of Spanish secondary school students with initiatives that research has proven to improve dietary and physical activity behaviors. Objective. The objectives were to perform a Program Impact Pathways (PIP) analysis to describe key activities and processes of the CAL-TAS Program, identify Critical Quality Control Points (CCPs), and identify a suite of common indicators of healthy lifestyles to be applied across participant schools. Methods. The CAL-TAS Program designers and implementation team developed this PIP analysis through an iterative process and presented the results for feedback at the seven-country Healthy Lifestyles Program Evaluation Workshop held in Granada, Spain, 13–14 September 2013, under the auspices of the Mondelēz International Foundation. Results. The team identified three PIP CCPs: teachers’ motivation and training, changes in students’ knowledge of healthy lifestyles, and changes in students’ healthy lifestyle behavior. The selected indicators of the program’s impact on healthy lifestyles are adequacy of food intake, level of knowledge of healthy lifestyles gained, and adequacy of physical activity level according to World Health Organization recommendations. A clear definition of impact indicators, as well as collection of accurate data on healthy lifestyle behaviors and knowledge, is essential to understanding the effectiveness of this program before it can be scaled up. Conclusions. CAL-TAS is an effective secondary school-based program encouraging healthy lifestyles. The PIP analysis was instrumental in identifying CCPs to sustain and improve the quality of the program. The team hopes to sustain and improve the program through these program evaluation recommendations.

Local human capital and productivity: An analysis for Spanish regions

In this paper, we examine the relationship between the stock of human capital and productivity in the Spanish regions (NUTS III), and assess whether the transmission channel involves external economies. The empirical evidence points to a positive relationship between the two variables, although it cannot be explained in terms of the impact of exogenous local human capital external economies, but rather in terms of other demand factors.

Probing quantum gravity using photons from a flare of the active galactic nucleus Markarian 501 observed by the MAGIC telescope

We analyze the timing of photons observed by the MAGIC telescope during a flare of the active galactic nucleus Mkn 501 for a possible correlation with energy, as suggested by some models of quantum gravity (QG), which predict a vacuum refractive index similar or equal to 1 + (E/M-QGn)(n), n = 1, 2. Parametrizing the delay between gamma-rays of different energies as Delta t = +/-tau E-1 or Delta t = +/-tau E-q(2), we find tau(1) = (0.030 +/- 0.012) s/GeV at the 2.5-sigma level, and tau(q) = (3.71 +/- 2.57) x 10(-6) s/GeV2, respectively. We use these results to establish lower limits M-QG1 > 0.21 X 10(18) GeV and M-QG2 > 0.26 x 10(11) GeV at the 95% C.L. Monte Carlo studies confirm the MAGIC sensitivity to propagation effects at these levels. Thermal plasma effects in the source are negligible, but we cannot exclude the importance of some other source effect.

Factors associated with active aging in Finland, Poland, and Spain

BACKGROUND: Continuous population aging has raised international policy interest in promoting active aging (AA). AA theoretical models have been defined from a biomedical or a psychosocial perspective. These models may be expanded including components suggested by lay individuals. This paper aims to study the correlates of AA in three European countries, namely, Spain, Poland, and Finland using four different definitions of AA. METHODS: The EU COURAGE in Europe project was a cross-sectional general adult population survey conducted in a representative sample of the noninstitutionalized population of Finland, Poland, and Spain. Participants (10,800) lived in the community. This analysis focuses on individuals aged 50 years old and over (7,987). Four definitions (two biomedical, one psychosocial, and a complete definition including biomedical, psychosocial, and external variables) of AA were analyzed. RESULTS: Differences in AA were found for country, age, education, and occupation. Finland scored consistently the highest in AA followed by Spain and Poland. Younger age was associated with higher AA. Higher education and occupation was associated with AA. Being married or cohabiting was associated with better AA compared to being widowed or separated in most definitions. Gender and urbanicity were not associated with AA, with few exceptions. Men scored higher in AA only in Spain, whereas there was no gender association in the other two countries. Being widowed was only associated with lower AA in Poland and not being married was associated with lower AA in Poland and Finland but not Spain. CONCLUSIONS: Associations with education, marital status, and occupation suggest that these factors are the most important components of AA. These association patterns, however, seem to vary across the three countries. Actions to promote AA in these countries may be addressed at reducing inequalities in occupation and education or directly tackling the components of AA lacking in each country.

Leaving the Dark ages with AMIGA

We present an Analytic Model of Intergalactic-medium and GAlaxy (AMIGA) evolution since the dark ages. AMIGA is in the spirit of the popular semi-analytic models of galaxy formation, although it does not use halo merger trees but interpolates halo properties in grids that are progressively built. This strategy is less memory-demanding and allows one to start modeling at sufficiently high redshifts and low halo masses to have trivial boundary conditions. The number of free parameters is minimized by making a causal connection between physical processes usually treated as independent of each other, which leads to more reliable predictions. However, the strongest points of AMIGA are the following: (1) the inclusion of molecular cooling and metal-poor, population III (Pop III) stars with the most dramatic feedback and (2) accurate follow up of the temperature and volume filling factor of neutral, singly ionized, and doubly ionized regions, taking into account the distinct halo mass functions in those environments. We find the following general results. Massive Pop III stars determine the intergalactic medium metallicity and temperature, and the growth of spheroids and disks is self-regulated by that of massive black holes (MBHs) developed from the remnants of those stars. However, the properties of normal galaxies and active galactic nuclei appear to be quite insensitive to Pop III star properties due to the much higher yield of ordinary stars compared to Pop III stars and the dramatic growth of MBHs when normal galaxies begin to develop, which cause the memory loss of the initial conditions.

A monolithic glass chip for active single-cell sorting based on mechanical phenotyping

The mechanical properties of biological cells have long been considered as inherent markers of biological function and disease. However, the screening and active sorting of heterogeneous populations based on serial single-cell mechanical measurements has not been demonstrated. Here we present a novel monolithic glass chip for combined fluorescence detection and mechanical phenotyping using an optical stretcher. A new design and manufacturing process, involving the bonding of two asymmetrically etched glass plates, combines exact optical fiber alignment, low laser damage threshold and high imaging quality with the possibility of several microfluidic inlet and outlet channels. We show the utility of such a custombuilt optical stretcher glass chip by measuring and sorting single cells in a heterogeneous population based on their different mechanical properties and verify sorting accuracy by simultaneous fluorescence detection. This offers new possibilities of exact characterization and sorting of small populations based on rheological properties for biological and biomedical applications.