A two-step transport pathway allows the mother cell to nurture the developing spore in Bacillus subtilis

© 2017 Ramírez-Guadiana et al. One of the hallmarks of bacterial endospore formation is the accumulation of high concentrations of pyridine-2,6-dicarboxylic acid (dipicolinic acid or DPA) in the developing spore. This small molecule comprises 5–15% of the dry weight of dormant spores and plays a central role in resistance to both wet heat and desiccation. DPA is synthesized in the mother cell at a late stage in sporulation and must be translocated across two membranes (the inner and outer forespore membranes) that separate the mother cell and forespore. The enzymes that synthesize DPA and the proteins required to translocate it across the inner forespore membrane were identified over two decades ago but the factors that transport DPA across the outer forespore membrane have remained mysterious. Here, we report that SpoVV (formerly YlbJ) is the missing DPA transporter. SpoVV is produced in the mother cell during the morphological process of engulfment and specifically localizes in the outer forespore membrane. Sporulating cells lacking SpoVV produce spores with low levels of DPA and cells engineered to express SpoVV and the DPA synthase during vegetative growth accumulate high levels of DPA in the culture medium. SpoVV resembles concentrative nucleoside transporters and mutagenesis of residues predicted to form the substrate-binding pocket supports the idea that SpoVV has a similar structure and could therefore function similarly. These findings provide a simple two-step transport mechanism by which the mother cell nurtures the developing spore. DPA produced in the mother cell is first translocated into the intermembrane space by SpoVV and is then imported into the forespore by the SpoVA complex. This pathway is likely to be broadly conserved as DPA synthase, SpoVV, and SpoVA proteins can be found in virtually all endospore forming bacteria

Photodynamic therapy of cutaneous T-cell lymphoma cell lines mediated by 5-aminolevulinic acid and derivatives

The delta-amino acid 5-aminolevulinic acid (ALA), is the precursor of the endogenous photosensitiser Protoporphyrin IX (PpIX), and is currently approved for Photodynamic Therapy (PDT) of certain superficial cancers. However, ALA-PDT is not very effective in diseases in which T-cells play a significant role. Cutaneous T-cell lymphomas (CTCL) is a group of non-Hodgkin malignant diseases, which includes mycosis fungoides (MF) and Sézary syndrome (SS). In previous work, we have designed new ALA esters synthesised by three-component Passerini reactions, and some of them showed higher performance as compared to ALA. This work aimed to determine the efficacy as pro-photosensitisers of five new ALA esters of 2-hydroxy-N-arylacetamides (1f, 1 g, 1 h, 1i and 1 k) of higher lipophilicity than ALA in Myla cells of MF and HuT-78 cells of SS. We have also tested its effectiveness against ALA and the already marketed ALA methyl ester (Me-ALA) and ALA hexyl ester (He-ALA). Both cell Myla and SS cells were effectively and equally photoinactivated by ALA-PDT. Besides, the concentration of ALA required to induce half the maximal porphyrin synthesis was 209 μM for Myla and 169 μM for HuT-78 cells. As a criterion of efficacy, we calculated the concentration of the ALA derivatives necessary to induce half the plateau porphyrin values obtained from ALA. These values were achieved at concentrations 4 and 12 times lower compared to ALA, according to the derivative used. For He-ALA, concentrations were 24 to 25 times lower than required for ALA for inducing comparable porphyrin synthesis in both CTCL cells. The light doses for inducing 50% of cell death (LD50) for He-ALA, 1f, 1 g, 1 h and 1i were around 18 and 25 J/cm2 for Myla and HuT-78 cells respectively, after exposure to 0.05 mM concentrations of the compounds. On the other hand, the LD50s for the compound 1 k were 40 and 57 J/cm2 for Myla and HuT-78, respectively. In contrast, 0.05 mM of ALA and Me-ALA did not provoke photokilling since the concentration employed was far below the porphyrin saturation point for these compounds. Our results suggest the potential use of ALA derivatives for topical application in PDT treatment of MF and extracorporeal PDT for the depletion of activated T-cells in SS

Estudio descriptivo sobre heridas incisas por accidente laboral

Bearing in mind the number of wounds to workers affiliated to Mutual Universal in the whole national territory, we have that 8 % of simple wounds and 4.4 % of complex wounds were attended to in the welfare centers of Mutual Universal in the province of Las Palmas.In a previous analysis performed at the centers taking part in the study, it was determined that the scrappy wounds were the most frequent, so we focus our study on this type of wounds. From September, 2006 to September, 2007, there was gathered a whole of 289 cases that fulfilled the criteria of incorporation. Knowledge of the characteristics of this type of injuries, always related to the labour activity, will allow us to increase the quality of the sanitary assistance given and to have first-hand knowledge of the average durations of Temporary Invalidity for the suitable and ideal reincorporation of the worker in the work place.The study that we have carried out has as its principal aim to describe the characteristics of the scrappy wounds for accidents at work of the users who come to the centers of primary assistance of Mutual Universal in the Province of Las PalmasLa patología traumática y especialmente las heridas, son uno de los principales motivos de consulta de los usuarios que acuden a nuestros centros asistenciales. El conocimiento de las características, tanto de las heridas como de los trabajadores que las padecen, nos permitirá mejorar la calidad de la asistencia sanitaria prestada y conocer con detalle las duraciones medias de Incapacidad Temporal (IT) para la adecuada y óptima reincorporación del paciente a su puesto de trabajo.Como objetivos, nos plantemos describir las características de las heridas incisas por accidente laboral, así como también analizar la duración de la IT de las mismas, en los usuarios que acuden a los centros de asistencia primaria de Mutua Universal en la Provincia de Las Palmas.La investigación que realizamos fue de carácter no experimental, de tipo descriptivo, prospectivo y con diseño transversal. Mediante un cuestionario elaborado específicamente para este estudio, examinamos las características de las heridas incisas de los pacientes que acudieron a nuestros centros de asistencia primaria desde septiembre de 2006 a septiembre de 2007. Tras la recogida de la información se realizó un análisis descriptivo de los datos mediante el paquete estadístico SPSS 12.0.Como conclusión observamos que la mayoría de los trabajadores que acudieron a nuestros centros de asistencia sanitaria por presentar una herida incisa fue de sexo masculino, diestro, fundamentalmente entre 21 a 40 años de edad, perteneciente al rubro de la construcción, el miembro superior fue el más afectado y las heridas en su gran mayoría tuvieron menos de 6,01 cm de longitud. La cura aplicada más habitual fue mediante sutura y el tratamiento médico coadyuvante analgesia y/o AINE. El proceso cursó sin complicación y precisó, en términos medios, de 5 a 6 días de IT y de 8 a 10 días para la curación

On Poincare and logarithmic Sobolev inequalities for a class of singular Gibbs measures

This note, mostly expository, is devoted to Poincar{\'e} and log-Sobolev inequalities for a class of Boltzmann-Gibbs measures with singular interaction. Such measures allow to model one-dimensional particles with confinement and singular pair interaction. The functional inequalities come from convexity. We prove and characterize optimality in the case of quadratic confinement via a factorization of the measure. This optimality phenomenon holds for all beta Hermite ensembles including the Gaussian unitary ensemble, a famous exactly solvable model of random matrix theory. We further explore exact solvability by reviewing the relation to Dyson-Ornstein-Uhlenbeck diffusion dynamics admitting the Hermite-Lassalle orthogonal polynomials as a complete set of eigenfunctions. We also discuss the consequence of the log-Sobolev inequality in terms of concentration of measure for Lipschitz functions such as maxima and linear statistics.Comment: Minor improvements. To appear in Geometric Aspects of Functional Analysis -- Israel Seminar (GAFA) 2017-2019", Lecture Notes in Mathematics 225

Structure Sensitivity and Evolution of Nickel-Bearing Nitrogen-Doped Carbons in the Electrochemical Reduction of CO2

The emergence of nickel single atoms on nitrogen-doped carbons as high-performance catalysts amenable to rationalization due to their well-defined structure could lead to applicable technologies for the electrocatalytic CO2 reduction reaction (eCO2RR). However, real materials are unlikely to display a uniform site structure, which limits the scope of current efforts focused on idealized models for future implementation. Here, we prepare distinct nickel entities (single atoms or nanoparticles) on nitrogen-doped carbons and evaluate them in eCO2RR. Single atoms demonstrate a characteristic high selectivity to CO. However, this is not altered by the presence of metal nanoparticles formed upon reducing the nitrogen content of the carrier. In contrast, nanoparticles incorporated via a colloidal route promote the parasitic hydrogen evolution reaction. In these systems, the CO selectivity evolves upon repeated exposure to potential, reaching values comparable to single atoms. By introducing CO stripping voltammetry as a characterization tool for this class of materials, we identify a decreased metallic surface, suggesting that the nanoparticle surface is altered by CO. The findings highlight the critical role of dynamic effects in catalyst design for eCO2RR

Structure of the TPR Domain of AIP: Lack of Client Protein Interaction with the C-Terminal alpha-7 Helix of the TPR Domain of AIP Is Sufficient for Pituitary Adenoma Predisposition

PMCID: PMC3534021This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited