Dual enzyme-triggered controlled release on capped nanometric silica mesoporous supports

We thank the Spanish Government (project MAT2009-14564-C04 and CTQ2007-64735-AR07) the Generalitat Valencia (project PROMETEO/2009/016) for support. A.A. and L.M. thank the Generalitat Valenciana for their Santiago Grisolia Fellowship and VALI+D postdoctoral contract, respectively. We thank the confocal microscopy service from CIPF for technical support.Agostini, A.; Mondragón Martínez, L.; Coll Merino, MC.; Aznar Gimeno, E.; Marcos Martínez, MD.; Martínez Mañez, R.; Sancenón Galarza, F.... (2012). Dual enzyme-triggered controlled release on capped nanometric silica mesoporous supports. ChemistryOpen. 1:17-20. https://doi.org/10.1002/open.201200003S17201Saha, S., Leung, K. C.-F., Nguyen, T. D., Stoddart, J. F., & Zink, J. I. (2007). Nanovalves. Advanced Functional Materials, 17(5), 685-693. doi:10.1002/adfm.200600989Trewyn, B. G., Slowing, I. I., Giri, S., Chen, H.-T., & Lin, V. S.-Y. (2007). 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Business Ownership and Self-Employment in Developing Economies: The Colombian Case

We characterize entrepreneurship in developing economies through a case study for Colombia. We document self-employment and business ownership since the 1980s; while the relative size of these groups within the labor force is stable across time, they differ significantly in important observable dimensions such as education and business sector. We then study the motivations to become an entrepreneur. First, we analyze the transition into and out of potential forms of entrepreneurship by measuring the flows across occupations, and study the determinants of entry and exit into and out of self-employment and business ownership; there is surprisingly little transition between self-employment and business ownership. Second, we focus on the financial motivations by measuring the differences in earnings of self-employment and businessownership relative to salaried work, at the mean and along the distribution. There is a substantial earnings premium to become a business owner, but it is not financially attractive to become self-employed. The results of this paper suggest that while business ownership is what the literature associates with entrepreneurship, self-employment is basically a subsistence activity.Entrepreneurship, self-employment, business ownership, transition prob-ability, earnings premium

Antibody-Capped Mesoporous Nanoscopic Materials:Design of a Probe for the Selective Chromo-FluorogenicDetection of Finasteride

[EN] The synthesis of capped mesoporous silica nanoparticles (MSN) conjugated with an antibody (AB) as a gatekeeper has been carried out in order to obtain a delivery system able to release an entrapped cargo (dye) in the presence of a target molecule (antigen) to which the conjugated antibody binds selectively. In particular, MSN loaded with rhodamine B and functionalized on the external surface with a suitable derivative of N-(t-butyl)- 3-oxo-(5a,17b)-4-aza-androst-1-ene-17-carboxamide (finasteride) have been prepared (S1). The addition of polyclonal antibodies against finasteride induced capping of the pores due to the interaction with the anchored hapten-like finasteride derivative to give a MSN¿hapten¿AB nanoparticle S1-AB. It was found that the addition of capped material S1-AB to water solutions containing finasteride resulted in displacement of the antibody, pore uncapping and entrapped-dye release. The response of the gated material is highly selective, and only finasteride, among other steroids, was able to induce a significant uncapping process. Compared with finasteride, the finasteride metabolite was able to release 17% of the dye, whereas the exogen steroids testosterone, metenolone and 16-b-hydroxystanozolol only induced very little release of rhodamine B (lower than 10%) from aqueous suspensions containing sensing solid S1-AB. A detection limit as low as 20 ppb was found for the fluorimetric detection of finasteride. In order to evaluate a possible application of the material for label-free detection of finasteride, the capped material was isolated and stored to give final sensing solid S1-AB-i. It was found to display a similar behavior towards finasteride as to that shown by freshly prepared S1-AB; even after a period of two months, no significant loss of selectivity or sensitivity was noted. Moreover, to study the application for the detection of finasteride in biological samples, this ¿aged¿ material, S1-AB-i, was tested using commercially available blank urine as matrix. Samples containing 70 and 90% blank urine were spiked with a defined amount of finasteride, and the concentration was determined using capped S1-AB-i. Recovery ranges from 94% to 118% were reached.Financial support from the Spanish Government (project MAT2009-14564-C04-01) and the Generalitat Valenciana (Spain) (projects PROMETEO/2009/016 and PROMETEO/2010/008) is gratefully acknowledged. E. C. thanks the Minesterio de Ciencia e Innovacion (MICINN, Spain) for her fellowship.Climent Terol, E.; Martínez Mañez, R.; Maquieira Catala, Á.; Sancenón Galarza, F.; Marcos Martínez, MD.; Brun Sánchez, EM.; Soto Camino, J.... (2012). Antibody-Capped Mesoporous Nanoscopic Materials:Design of a Probe for the Selective Chromo-FluorogenicDetection of Finasteride. ChemistryOpen. 1:251-259. https://doi.org/10.1002/open.201100008S251259

Amyloid Beta and Tau Proteins as Therapeutic Targets for Alzheimer's Disease Treatment: Rethinking the Current Strategy

Alzheimer's disease (AD) is defined by the concurrence of accumulation of abnormal aggregates composed of two proteins: Amyloid beta (Aβ) and tau, and of cellular changes including neurite degeneration and loss of neurons and cognitive functions. Based on their strong association with disease, genetically and pathologically, it is not surprising that there has been a focus towards developing therapies against the aggregated structures. Unfortunately, current therapies have but mild benefit. With this in mind we will focus on the relationship of synaptic plasticity with Aβ and tau protein and their role as potential targets for the development of therapeutic drugs. Finally, we will provide perspectives in developing a multifactorial strategy for AD treatment

BMC Biology BMC Biology The toxoplasma-host cell junction is anchored to the cell cortex to sustain parasite invasive force

International audienceBackgroundThe public health threats imposed by toxoplasmosis worldwide and by malaria in sub-Saharan countries are directly associated with the capacity of their closely related causative agents Toxoplasma and Plasmodium, respectively to colonize and expand inside host cells. Therefore, deciphering how these two Apicomplexan protozoan parasites access their hosting cells has been highlighted as a high priority research with the relevant perspective of designing anti-invasive molecules to prevent diseases. Central to the mechanistic base of invasion for both genera is mechanical force, which is thought to be applied by the parasite at the interface between the two cells following assembly of a unique cell junction but this model lacks direct evidence and has been challenged by recent genetic and cell biology studies. In this work, using parasites expressing the fluorescent core component of this junction, we analyse characteristic features of the kinematics of penetration of more than 1000 invasion events.ResultsThe majority of invasion events occur with a typical forward rotational progression of the parasite through a static junction into a vacuole formed from the invaginating host cell plasma membrane, in which the parasite subsequently replicates. However, if parasites encounter resistance and if the junction is not strongly anchored to the host cell cortex, as when parasites do not secrete the toxofilin protein and therefore are unable to locally remodel the cortical actin cytoskeleton, the junction is capped backwards and travels retrogradely with the host cell membrane along the parasite surface as it is enclosed within a functional vacuole. Kinetic measurements of the invasive trajectories strongly support a similar parasite driven force in both static and capped junctions, both of which lead to successful invasion. However about 20% of toxofilin mutants fail to enter and eventually disengage from the host cell membrane while the secreted RON2 molecules are capped at the posterior pole before being cleaved and released in the medium. By contrast in cells characterized by low cortex tension and high cortical actin dynamics, junction capping and entry failure are drastically reduced.ConclusionThis kinematic analysis of pre-invasive and invasive T. gondii tachyzoite behaviors newly highlights that to invade cells, parasites need to engage their motor with the junction molecular complex where force is efficiently applied only upon proper anchorage to the host cell membrane and cortex

Free L\'evy Processes on Dual Groups

We give a short introduction to the theory of L\'evy processes on dual groups. As examples we consider L\'evy processes with additive increments and L\'evy processes on the dual affine group.Comment: 12 pages, Extended abstract to be published in Mini-proceedings: Second MaPhySto Conference on ``L\'evy Processes - Theory and Applications,'' January 2002, Aarhus, Denmar

Contribution of the Residual Body in the Spatial Organization of Toxoplasma gondii Tachyzoites within the Parasitophorous Vacuole

Toxoplasma gondii proliferates and organizes within a parasitophorous vacuole in rosettes around a residual body and is surrounded by a membranous nanotubular network whose function remains unclear. Here, we characterized structure and function of the residual body in intracellular tachyzoites of the RH strain. Our data showed the residual body as a body limited by a membrane formed during proliferation of tachyzoites probably through the secretion of components and a pinching event of the membrane at the posterior end. It contributes in the intravacuolar parasite organization by the membrane connection between the tachyzoites posterior end and the residual body membrane to give place to the rosette conformation. Radial distribution of parasites in rosettes favors an efficient exteriorization. Absence of the network and presence of atypical residual bodies in a ΔGRA2-HXGPRT knock-out mutant affected the intravacuolar organization of tachyzoites and their exteriorization