A role for TASK-1 (KCNK3) channels in the chemosensory control of breathing

Acid-sensitive K+ channels of the tandem P-domain K+-channel family (TASK-1 and TASK-3) have been implicated in peripheral and central respiratory chemosensitivity; however, because of the lack of decisive pharmacological agents, the final proof of the role of the TASK channel in the chemosensory control of breathing has been missing. In the mouse, TASK-1 and TASK-3 channels are dispensable for central respiratory chemosensitivity (Mulkey et al., 2007Go). Here, we have used knock-out animals to determine whether TASK-1 and TASK-3 channels play a role in the carotid body function and chemosensory control of breathing exerted by the carotid body chemoreceptors. Ventilatory responses to hypoxia (10% O2 in inspired air) and moderate normoxic hypercapnia (3–6% CO2 in inspired air) were significantly reduced in TASK-1 knock-out mice. In contrast, TASK-3-deficient mice showed responses to both stimuli that were similar to those developed by their wild-type counterparts. TASK-1 channel deficiency resulted in a marked reduction of the hypoxia (by 49%)- and CO2 (by 68%)-evoked increases in the carotid sinus nerve chemoafferent discharge recorded in the in vitro superfused carotid body/carotid sinus nerve preparations. Deficiency in both TASK-1 and TASK-3 channels increased baseline chemoafferent activity but did not cause a further reduction of the carotid body chemosensory responses. These observations provide direct evidence that TASK-1 channels contribute significantly to the increases in the carotid body chemoafferent discharge in response to a decrease in arterial PO2 or an increase in PCO2/[H+]. TASK-1 channels therefore play a key role in the control of ventilation by peripheral chemoreceptors

Crystal structure of the N-benzyloxycarbonyl-Alanyl-Phenylalanyl-methyl ester: the importance of the H-bonding pattern

Large crystals of the methyl ester of the N-a-benzyloxycarbonyl protected Ala-Phe dipeptide (Z-AF-OMe) were obtained after the very slow evaporation of a solution of the corresponding carboxylic acid (Z-AF-OH) in methanol containing an excess of HCl. The structure was confirmed by single crystal X-ray diffraction data. It crystallizes in the orthorhombic space group P212121 with unit cell dimensions a = 5.0655(6) Å, b = 8.4614(8) Å, c = 46.856(5) Å, V = 2008.3(4) Å3, Z = 4. In the crystal, the molecules form hydrogen bonded chains running along the a axis of the unit cell. Other secondary interactions are also discussed

Rigid systems of second-order linear differential equations

We say that a system of differential equations d^2x(t)/dt^2=Adx(t)/dt+Bx(t)+Cu(t), in which A and B are m-by-m complex matrices and C is an m-by-n complex matrix, is rigid if it can be reduced by substitutions x(t)=Sy(t), u(t)=Udy(t)/dt+Vy(t)+Pv(t) with nonsingular S and P to each system obtained from it by a small enough perturbation of its matrices A,B,C. We prove that there exists a rigid system if and only if m<n(1+square_root{5})/2, and describe all rigid systems.Comment: 22 page

Liderazgo de ambientes seguros que ayudan a crecer : directivos

El terremoto ocurrido en el norte de Chile provocó un estado de emergencia que afectó de manera integral nuestra existencia como personas y como comunidad. En una primera instancia, dicha situación requirió ser abordada con apoyos y acciones de resguardo de la integridad vital, atención de necesidades de alimentación, seguridad, vivienda, de salud física y mental, de conectividad y comunicaciones. El material fue preparado para el desarrollo de espacios de contención y apoyo emocional y la creación de ambientes de respeto, confianza, prevención y autocuidado, tanto dentro como fuera del aula. También busca estimular y motivar la realización de actividades de auto conocimiento, reflexión y expresión de las emociones, de las propias ideas y de las maneras diferentes que tenemos todos y todas de reaccionar

Biophysical characterization of the outer membrane polysaccharide export protein and the polysaccharide co-polymerase protein from Xanthomonas campestris

This study investigated the structural and biophysical characteristics of GumB and GumC, two Xanthomonas campestris membrane proteins that are involved in xanthan biosynthesis. Xanthan is an exopolysaccharide that is thought to be a virulence factor that contributes to bacterial in planta growth. It also is one of the most important industrial biopolymers. The first steps of xanthan biosynthesis are well understood, but the polymerization and export mechanisms remain unclear. For this reason, the key proteins must be characterized to better understand these processes. Here we characterized, by biochemical and biophysical techniques, GumB, the outer membrane polysaccharide export protein, and GumC, the polysaccharide co-polymerase protein of the xanthan biosynthesis system. Our results suggested that recombinant GumB is a tetrameric protein in solution. On the other hand, we observed that both native and recombinant GumC present oligomeric conformation consistent with dimers and higher-order oligomers. The transmembrane segments of GumC are required for GumC expression and/or stability. These initial results provide a starting point for additional studies that will clarify the roles of GumB and GumC in the xanthan polymerization and export processes and further elucidate their functions and mechanisms of action.Fil: Bianco, María Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Jacobs, Melisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Salinas, Silvina Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Salvay, Andrés Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Ielmini, M. V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ielpi, Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Cooperative Education in Green Chemistry: The Spanish Experience

A common postgraduate training in Green Chemistry is currently being carried out by several Spanish universities. This initiative considers the corresponding Máster and PhD programs in Sustainable Chemistry and has been successfully achieved with the participation of experts from different Universities and Research Institutions grouped within the coverage of the Spanish Network on Sustainable Chemistry (REDQS). A cooperative effort and a modular design are the key elements that have allowed maintaining the Spanish Interuniversity Máster and PhD programs for more than a decade, providing a high level of quality and a unique possibility, for many students, of being trained at an advanced level in Green Chemistry

Simplest miniversal deformations of matrices, matrix pencils, and contragredient matrix pencils

V. I. Arnold [Russian Math. Surveys 26 (2) (1971) 29-43] constructed a simple normal form for a family of complex n-by-n matrices that smoothly depend on parameters with respect to similarity transformations that smoothly depend on the same parameters. We construct analogous normal forms for a family of real matrices and a family of matrix pencils that smoothly depend on parameters, simplifying their normal forms by D. M. Galin [Uspehi Mat. Nauk 27 (1) (1972) 241-242] and by A. Edelman, E. Elmroth, B. Kagstrom [Siam J. Matrix Anal. Appl. 18 (3) (1997) 653-692].Comment: 20 page

Macrocycle Synthesis by Chloride-Templated Amide Bond Formation

A new family of pseudopeptidic macrocyclic compounds has been prepared involving an anion-templated amide bond formation reaction at the macrocyclization step. Chloride anion was found to be the most efficient template in the macrocyclization process, producing improved macrocyclization yields with regard to the nontemplated reaction. The data suggest a kinetic effect of the chloride template, providing an appropriate folded conformation of the openchain precursor and reducing the energy barrier for the formation of the macrocyclic product.This work was supported by the Spanish Ministry of Science and Innovation (CTQ2012-38543-C03) and Generalitat Valenciana (PROMETEO/2012/020). V.M.-C. thanks Generalitat Valenciana for a postdoctoral fellowship (APOSTD/ 2013/041)

Kinetic Analysis for Macrocyclizations Involving Anionic Template at the Transition State

Several kinetic models for the macrocyclization of a C2 pseudopeptide with a dihalide through a SN2 reaction have been developed. These models not only focus on the kinetic analysis of the main macrocyclization reaction, but also consider the competitive oligomerization/polymerization processes yielding undesired oligomeric/polymeric byproducts. The effect of anions has also been included in the kinetic models, as they can act as catalytic templates in the transition state reducing and stabilizing the transition state. The corresponding differential equation systems for each kinetic model can be solved numerically. Through a comprehensive analysis of these results, it is possible to obtain a better understanding of the different parameters that are involved in the macrocyclization reaction mechanism and to develop strategies for the optimization of the desired processes

Caffeine affects the biological responses of human hematopoietic cells of myeloid lineage via downregulation of the mTOR pathway and xanthine oxidase activity

Correction of human myeloid cell function is crucial for the prevention of inflammatory and allergic reactions as well as leukaemia progression. Caffeine, a naturally occurring food component, is known to display anti-inflammatory effects which have previously been ascribed largely to its inhibitory actions on phosphodiesterase. However, more recent studies suggest an additional role in affecting the activity of the mammalian target of rapamycin (mTOR), a master regulator of myeloid cell translational pathways, although detailed molecular events underlying its mode of action have not been elucidated. Here, we report the cellular uptake of caffeine, without metabolisation, by healthy and malignant hematopoietic myeloid cells including monocytes, basophils and primary acute myeloid leukaemia mononuclear blasts. Unmodified caffeine downregulated mTOR signalling, which affected glycolysis and the release of pro-inflammatory/pro-angiogenic cytokines as well as other inflammatory mediators. In monocytes, the effects of caffeine were potentiated by its ability to inhibit xanthine oxidase, an enzyme which plays a central role in human purine catabolism by generating uric acid. In basophils, caffeine also increased intracellular cyclic adenosine monophosphate (cAMP) levels which further enhanced its inhibitory action on mTOR. These results demonstrate an important mode of pharmacological action of caffeine with potentially wide-ranging therapeutic impact for treating non-infectious disorders of the human immune system, where it could be applied directly to inflammatory cells