From non-symmetric particle systems to non-linear PDEs on fractals

We present new results and challenges in obtaining hydrodynamic limits for non-symmetric (weakly asymmetric) particle systems (exclusion processes on pre-fractal graphs) converging to a non-linear heat equation. We discuss a joint density-current law of large numbers and a corresponding large deviations principle.Comment: v2: 10 pages, 1 figure. To appear in the proceedings for the 2016 conference "Stochastic Partial Differential Equations & Related Fields" in honor of Michael R\"ockner's 60th birthday, Bielefel

Use of aequorin-based indicators for monitoring Ca2+ in acidic organelles

Over the last years, there is accumulating evidence that acidic organelles can accumulate and release Ca2+ upon cell activation. Hence, reliable recording of Ca2+ dynamics in these compartments is essential for understanding the physiopathological aspects of acidic organelles. Genetically encoded Ca2+ indicators (GECIs) are valuable tools to monitor Ca2+ in specific locations, although their use in acidic compartments is challenging due to the pH sensitivity of most available fluorescent GECIs. By contrast, bioluminescent GECIs have a combination of features (marginal pH sensitivity, low background, no phototoxicity, no photobleaching, high dynamic range and tunable affinity) that render them advantageous to achieve an enhanced signal-to-noise ratio in acidic compartments. This article reviews the use of bioluminescent aequorin-based GECIs targeted to acidic compartments. A need for more measurements in highly acidic compartments is identified

Revision of the Late Jurassic teleosaurid genus Machimosaurus (Crocodylomorpha, Thalattosuchia)

© 2014 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. The attached file is the published version of the article

Predicting the onset and persistence of episodes of depression in primary health care. The predictD-Spain study: Methodology

Background: The effects of putative risk factors on the onset and/or persistence of depression remain unclear. We aim to develop comprehensive models to predict the onset and persistence of episodes of depression in primary care. Here we explain the general methodology of the predictD-Spain study and evaluate the reliability of the questionnaires used. Methods: This is a prospective cohort study. A systematic random sample of general practice attendees aged 18 to 75 has been recruited in seven Spanish provinces. Depression is being measured with the CIDI at baseline, and at 6, 12, 24 and 36 months. A set of individual, environmental, genetic, professional and organizational risk factors are to be assessed at each follow-up point. In a separate reliability study, a proportional random sample of 401 participants completed the test-retest (251 researcher-administered and 150 self-administered) between October 2005 and February 2006. We have also checked 118,398 items for data entry from a random sample of 480 patients stratified by province. Results: All items and questionnaires had good test-retest reliability for both methods of administration, except for the use of recreational drugs over the previous six months. Cronbach's alphas were good and their factorial analyses coherent for the three scales evaluated (social support from family and friends, dissatisfaction with paid work, and dissatisfaction with unpaid work). There were 191 (0.16%) data entry errors. Conclusion: The items and questionnaires were reliable and data quality control was excellent. When we eventually obtain our risk index for the onset and persistence of depression, we will be able to determine the individual risk of each patient evaluated in primary health car

Non-human TRIM5 variants enhance recognition of HIV-1-infected cells by CD8+ T cells

Tripartite motif-containing protein 5 (TRIM5) restricts human immunodeficiency virus type-1 (HIV-1) in a species-specific manner by uncoating viral particles while activating early innate responses. Although the contribution of TRIM5 proteins to cellular immunity has not yet been studied, their interactions with the incoming viral capsid and the cellular proteasome led us to hypothesize a role for them. Here, we investigate whether the expression of two non-human TRIM5 orthologs, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), both of which are potent restrictors of HIV-1, could enhance immune recognition of infected cells by CD8+ T cells. We illustrate how TRIM5 restriction improves CD8+ T cell-mediated HIV-1 inhibition. Moreover, when TRIM5 activity was blocked by the non-immunosuppressive analog of cyclosporin A, SmBz-CsA, we found a significant reduction in CD107a/MIP1β expression in HIV-1-specific CD8+ T cells. This finding underscores the direct link between TRIM5 restriction and activation of CD8+ T-cell responses. Interestingly, cells expressing RhT5 induced stronger CD8+ T-cell responses through the specific recognition of the HIV-1 capsid by the immune system. The underlying mechanism of this process may involve TRIM5-specific capsid recruitment to cellular proteasomes and increase peptide availability for loading and presentation of HLA class I antigens. In summary, we identified a novel function for non-human TRIM5 variants in cellular immunity. We hypothesise that TRIM5 can couple innate viral sensing and CD8+ T-cell activation to increase species barriers against retrovirus infection. IMPORTANCE: New therapeutics to tackle HIV-1 infection should aim to combine rapid innate viral sensing and cellular immune recognition. Such strategies could prevent seeding of the viral reservoir and the immune damage that occurs during acute infection. The non-human TRIM5 variants, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), are attractive candidates owing to their potency in sensing HIV-1 and blocking its activity. Here, we show that expression of RhT5 and TCyp in HIV-1-infected cells improves CD8+ T cell-mediated inhibition through the direct activation of HIV-1-specific CD8+ T-cell responses. We found that the potency in CD8+ activation was stronger for RhT5 variants and capsid-specific CD8+ T-cells in a mechanism that relies on TRIM5-dependent particle recruitment to cellular proteasomes. This novel mechanism couples innate viral sensing with cellular immunity in a single protein and could be exploited to develop innovative therapeutics for control of HIV-1 infection

The population of close double white dwarfs in the Galaxy

We present a new model for the Galactic population of close double white dwarfs. The model accounts for the suggestion of the avoidance of a substantial spiral-in during mass transfer between a giant and a main-sequence star of comparable mass and for detailed cooling models. It agrees well with the observations of the local sample of white dwarfs if the initial binary fraction is close to 50% and an ad hoc assumption is made that white dwarfs with mass less than about 0.3 solar mass cool faster than the models suggest. About 1000 white dwarfs brighter than V=15 have to be surveyed for detection of a pair which has total mass greater than the Chandrasekhar mass and will merge within 10 Gyr.Comment: 15 pages, 7 figures, to appear in Proc. ``The influence of binaries on stellar population studies'', Brussels, August 2000 (Kluwer, D. Vanbeveren ed.

Tratamiento antifúngico con posaconazol y anfotericina B en paciente con mucormicosis rinosinusal

Introducción: La mucormicosis es una infección fúngica con elevada morbilidad y mortalidad. Se requiere tanto tratamiento quirúrgico como antifúngico, siendo el antimicótico de elección anfotericina B. Posaconazol es un antimicótico derivado de triazol que presenta actividad in vitro e in vivo frente a zygomicetes y que se ha usado en pacientes refractarios o intolerantes a anfotericina B. Descripción del caso: Varón de 70 años con recidiva de mucormicosis rinosinusal ocular izquierda. Había recibido anfotericina B liposomal asociada a posaconazol 8 semanas; tras este primer ingreso fue dado de alta con dosis infraterapéuticas de posaconazol. Volvió a ingresar por recidiva de la enfermedad, se practicó cirugía y recibió anfotericina B liposomal asociada a posaconazol 5 semanas. Siete meses después del alta, el paciente estaba clínicamente estable y continuaba tratamiento con posaconazol. Discusión/Conclusiones: Anfotericina B es el tratamiento de elección en la mucormicosis. Posaconazol es una alternativa aceptable en pacientes refractarios o intolerantes, presentando un perfil de seguridad favorable

Tratamiento antifúngico con posaconazol y anfotericina B en paciente con mucormicosis rinosinusal

Introducción: La mucormicosis es una infección fúngica con elevada morbilidad y mortalidad. Se requiere tanto tratamiento quirúrgico como antifúngico, siendo el antimicótico de elección anfotericina B. Posaconazol es un antimicótico derivado de triazol que presenta actividad in vitro e in vivo frente a zygomicetes y que se ha usado en pacientes refractarios o intolerantes a anfotericina B. Descripción del caso: Varón de 70 años con recidiva de mucormicosis rinosinusal ocular izquierda. Había recibido anfotericina B liposomal asociada a posaconazol 8 semanas; tras este primer ingreso fue dado de alta con dosis infraterapéuticas de posaconazol. Volvió a ingresar por recidiva de la enfermedad, se practicó cirugía y recibió anfotericina B liposomal asociada a posaconazol 5 semanas. Siete meses después del alta, el paciente estaba clínicamente estable y continuaba tratamiento con posaconazol. Discusión/Conclusiones: Anfotericina B es el tratamiento de elección en la mucormicosis. Posaconazol es una alternativa aceptable en pacientes refractarios o intolerantes, presentando un perfil de seguridad favorable