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TRPM8 represents an ion channel activated by cold temperatures and cooling agents, such as menthol, that underlies the cold-induced excitation of sensory neurons. Interestingly, the only human tissue outside the peripheral nervous system, in which the expression of TRPM8 transcripts has been detected at high levels, is the prostate, a tissue not exposed to any essential temperature variations. Here we show that the TRPM8 cloned from human prostate and heterologously expressed in HEK-293 cells is regulated by the Ca(2+)-independent phospholipase A(2) (iPLA(2)) signaling pathway with its end products, lysophospholipids (LPLs), acting as its endogenous ligands. LPLs induce prominent prolongation of TRPM8 channel openings that are hardly detectable with other stimuli (e.g. cold, menthol, and depolarization) and that account for more than 90% of the total channel open time. Down-regulation of iPLA(2) resulted in a strong inhibition of TRPM8-mediated functional responses and abolished channel activation. The action of LPLs on TRPM8 channels involved either changes in the local lipid bilayer tension or interaction with the critical determinant(s) in the transmembrane channel core. Based on this, we propose a novel concept of TRPM8 regulation with the involvement of iPLA(2) stimulation. This mechanism employs chemical rather than physical (temperature change) signaling and thus may be the main regulator of TRPM8 activation in organs not exposed to any essential temperature variations, as in the prostate gland.

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This text presents an analysis of aggregated membership’s dynamics for Spanish trade unions, using ECVT data, as well as union memberships’ trajectories, or members’ decisions about joining the organization, permanency and responsibilities, and subsequent attrition. For the analysis of trajectories we make use of information of the records of actual memberships and the record of quitting of CCOO, and of a survey-questionnaire to a sample of leavers of the same union. This study allows us to confirm a linkage between the decision and motivations to become union member, to participate in union activities, the time of permanency, and the motives to quit the organization. We also identify five types of union members’ trajectories, indicating that, far from views that assert a monolithic structure, unions are complex organizations.

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In electromigration (EM) experiments on metallic wires, a flux of atoms can lead to motion of the centre of mass (COM) of the wire. Hence, it may be tempting to assume that the flow of current produces a net force on the wire as a whole. We point out, on the basis of known momentum-balance arguments, that the net force on a metallic wire due to a passing steady-state current is zero. This is possible, because in addition to EM driving forces, acting on scattering centres, there are counterbalancing forces, acting on the rest of the system. Drift of the COM in EM experiments occurs inevitably because the substrate keeps the crystal lattice of the wire fixed, while allowing diffusion of defects in the bulk of the wire. This drift is not evidence for a net force on the wire.

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Control of ocular blood flow occurs predominantly at the level of the retinal and choroidal arterioles. The present article provides an overview of the Ca2 + handling mechanisms and plasmalemmal ion channels involved in the regulation of retinal and choroidal arteriolar smooth muscle tone. Increases in global intracellular free Ca2 + ([Ca2 +]i) involve multiple mechanisms, including agonist-dependent release of Ca2 + from intracellular stores through activation of the inositol trisphosphate (IP3) pathway. Ca2 + enters by voltage-dependent L-type Ca2 + channels and novel dihydropyridine-sensitive store-operated nonselective cation channels. Ca2 + extrusion is mediated by plasmalemmal Ca2 +-ATPases and through Na+/Ca2+ exchange. Local Ca2 + transients (Ca2 + sparks) play an important excitatory role, acting as the building blocks for more global Ca2 + signals that can initiate vasoconstriction. K+ and Cl- channels may also affect cell function by modulating membrane potential. The precise contribution of each of these mechanisms to the regulation of retinal and choroidal perfusion in vivo warrants future investigation.

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The somatic JAK2 valine-to-phenylalanine (V617F) mutation has been detected in up to 90% of patients with polycythemia and in a sizeable proportion of patients with other myeloproliferative disorders such as essential thrombocythemia and idiopathic myelofibrosis. Suppressor of cytokine signaling 3 (SOCS3) is known to be a strong negative regulator of erythropoietin (EPO) signaling through interaction with both the EPO receptor (EPOR) and JAK2. We report here that JAK2 V617F cannot be regulated and that its activation is actually potentiated in the presence of SOCS3. Instead of acting as a suppressor, SOCS3 enhanced the proliferation of cells expressing both JAK2 V617F and EPOR. Additionally, although SOCS1 and SOCS2 are degraded in the presence of JAK2 V617F, turnover of SOCS3 is inhibited by the JAK2 mutant kinase and this correlated with marked tyrosine phosphorylation of SOCS3 protein. We also observed constitutive tyrosine phosphorylation of SOCS3 in peripheral blood mononuclear cells (PBMCs) derived from patients homozygous for the JAK2 V617F mutant. These findings suggest that the JAK2 V617F has overcome normal SOCS regulation by hyperphosphorylating SOCS3, rendering it unable to inhibit the mutant kinase. Thus, JAK2 V617F may even exploit SOCS3 to potentiate its myeloproliferative capacity.

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El estudio de la satisfacción de los estudiantes es fundamental para conocer los errores y aciertos de una institución educativa superior con el fin de poner en práctica estrategias que conduzcan a una mejora en la calidad de su enseñanza. Con este fin, en este artículo hemos evaluado el grado de satisfacción de los estudiantes de Interpretación Textual de la Escuela Superior de Arte Dramático de Córdoba “Miguel Salcedo Hierro”. Alejándonos de los modelos habituales de medir la satisfacción, principalmente de carácter cuantitativo, hemos utilizado como eje metodológico la Teoría Fundamentada en Datos, y como técnicas, la entrevista comprehensiva de Kaufmann y los grupos de discusión. Los resultados han sido muy positivos, pues han mostrado que estos estudiantes tienen un alto nivel de satisfacción, lo que resulta muy valioso para conocer la calidad de esta enseñanza en el momento presente, así como para desarrollar planes específicos que conduzcan a su mejora en el futuro cercano.

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Volume III of the new eleven-volume edition of Milton's Complete Works provides a definitive scholarly edition of all of Milton's shorter poems in English, Latin, Italian, and Greek, as well as his Mask, taken from both published and manuscript sources. It includes his 1645 Poems complete with all prefatory materials, thus illuminating the ways in which author, publisher, and print shop shaped this volume. It then presents all the new poems added in the 1673 edition (with the new Table of Contents), as well as the poems omitted from both editions. A careful collation of textual variants among these sources as well as the 1637 anonymous publication of Milton's Mask is provided. The Bridgewater manuscript of Milton's Mask (probably close to the acting version) and his working copy from the Trinity Manuscript, with its many alterations and additions, are transcribed in their entirety, so that the various versions may be compared and studied. 

A special feature of this edition is a new translation of Milton's many Latin and Greek poems that is both accurate and attentive to their literary qualities. This is augmented by a detailed and comprehensive commentary that highlights classical, vernacular, and neo-Latin parallels. A poetic translation of Milton's six Italian sonnets and Canzone is also supplied. In addition, the Appendices contain all the versions of Milton's shorter poems in all the contemporary manuscript and printed sources, so they may be examined in relation to their specific contexts. The transcription of all the versions of Milton's poems in the Trinity Manuscript allows in several cases, notably 'Lycidas' and 'At a Solemn Music,' for examination of the evolution of these poems as Milton weighed choiced of diction and sound qualities, enabling further understanding of his poetic practices. 

Barbara Lewalski is responsible for text, textual apparatus, and commentary pertaining to the vernacular poems in all sections of this edition including the appendices, and manuscript transcriptions (with the exception of A Maske), as well as the Occasions, Vernacular Poems,and Textual Introductions. Estelle Haan is responsible for text, textual apparatus, and commentary for the Poemata in all sections of this edition,and for the Poemata Introduction. She has also provided all translations from Latin, Italian, and Greek in the Testimonia, Poemata, and associated commentary, and transcriptions of the BL Damon, the Bodleian AdJoannem Rousium, and A Maske from the Trinity and Bridgewater manuscripts. Andrew McNeillie has provided poetic translations for Milton’s Italian sonnets, and Jason Rosenblatt has provided some Hebrew text and commentary pertaining to Milton’s Psalm translations.John Cunningham has transcribed Henry Lawes’ music for Milton’s masque, with commentary (Appendix E). Biblical references are taken from the King James (Authorized) Version.

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The 67LR (67 kDa laminin receptor) is a cell-surface receptor with high affinity for its primary ligand. Its role as a laminin receptor makes it an important molecule both in cell adhesion to the basement membrane and in signalling transduction following this binding event. The protein also plays critical roles in the metastasis of tumour cells. Isolation of the protein from either normal or cancerous cells results in a product with an approx. molecular mass of 67 kDa. This protein is believed to be derived from a smaller precursor, the 37LRP (37 kDa laminin receptor precursor). However, the precise mechanism by which cytoplasmic 37LRP becomes cell-membrane-embedded 67LR is unclear. The process may involve post-translational fatty acylation of the protein combined with either homo- or hetero-dimerization, possibly with a galectin-3-epitope-containing partner. Furthermore, it has become clear that acting as a receptor for laminin is not the only function of this protein. 67LR also acts as a receptor for viruses, such as Sindbis virus and dengue virus, and is involved with internalization of the prion protein. Interestingly, unmodified 37LRP is a ribosomal component and homologues of this protein are found in all five kingdoms. In addition, it appears to be strongly associated with histones in the eukaryotic cell nucleus, although the precise role of these interactions is not clear. Here we review the current understanding of the structure and function of this molecule, as well as highlighting areas requiring further research.

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Asymptotic estimates of the norms of orbits of certain operators that commute with the classical Volterra operator V acting on L-P[0,1], with 1 0, but also to operators of the form phi (V), where phi is a holomorphic function at zero. The method to obtain the estimates is based on the fact that the Riemann-Liouville operator as well as the Volterra operator can be related to the Levin-Pfluger theory of holomorphic functions of completely regular growth. Different methods, such as the Denjoy-Carleman theorem, are needed to analyze the behavior of the orbits of I - cV, where c > 0. The results are applied to the study of cyclic properties of phi (V), where phi is a holomorphic function at 0.

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It is shown, for a bounded weighted bilateral shift T acting on l(p)(Z), and for 1

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We prove that under certain topological conditions on the set of universal elements of a continuous map T acting on a topological space X, that the direct sum T and M_g is universal, where M_g is multiplication by a generating element of a compact topological group. We use this result to characterize R_+-supercyclic operators and to show that whenever T is a supercyclic operator and z_1,...,z_n are pairwise different non-zero complex numbers, then the operator z_1T\oplus ... \oplus z_n T is cyclic. The latter answers affirmatively a question of Bayart and Matheron.

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A complex number lambda is called an extended eigenvalue of a bounded linear operator T on a Banach space B if there exists a non-zero bounded linear operator X acting on B such that XT = lambda TX. We show that there are compact quasinilpotent operators on a separable Hilbert space, for which the set of extended eigenvalues is the one-point set {1}.

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It is remarkable how the classical Volterra integral operator, which was one of the first operators which attracted mathematicians' attention, is still worth of being studied. In this essentially survey work, by collecting some of the very recent results related to the Volterra operator, we show that there are new (and not so new) concepts that are becoming known only at the present days. Discovering whether the Volterra operator satisfies or not a given operator property leads to new methods and ideas that are useful in the setting of Concrete Operator Theory as well as the one of General Operator Theory. In particular, a wide variety of techniques like summability kernels, theory of entire functions, Gaussian cylindrical measures, approximation theory, Laguerre and Legendre polynomials are needed to analyze different properties of the Volterra operator. We also include a characterization of the commutator of the Volterra operator acting on L-P[0, 1], 1

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We provide a sufficient condition of analyticity of infinitely differentiable eigenfunctions of operators of the form Uf(x) = integral a(x, y) f(b( x, y)) mu(dy) acting on functions f: [u, v] --> C ( evolution operators of one-dimensional dynamical systems and Markov processes have this form). We estimate from below the region of analyticity of the eigenfunctions and apply these results for studying the spectral properties of the Frobenius-Perron operator of the continuous fraction Gauss map. We prove that any infinitely differentiable eigenfunction f of this Frobenius-Perron operator, corresponding to a non-zero eigenvalue admits a (unique) analytic extension to the set C\(-infinity, 1]. Analyzing the spectrum of the Frobenius Perron operator in spaces of smooth functions, we extend significantly the domain of validity of the Mayer and Ropstorff asymptotic formula for the decay of correlations of the Gauss map.

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In the mate-guarding amphipod, Gammarus pulex, the enlarged male posterior gnathopods have been variously suggested to function to grasp and subdue the female, to be used as weapons in fights between males, to signal to the female the male presence and stimulate moult accelaration, egg development or egg extrusion. These hypotheses were tested in a series of experiments, the results of which reveal an unexpected function. Ablation of the posterior gnathopods of males showed that they were neither necessary for, nor advantageous in, establishment and/ or maintenance of precopula mate guarding, with or without competition with intact males. Furthermore, these appendages do not function to advance female moult, or stimulate egg development or extrusion. However, only males with intact posterior gnathopods were able to copulate. We also show that females require a full copulation of several bouts to extrude eggs. We conclude that the function of the posterior gnathopods is to facilitate copulation and suggest future studies focus on the selective pressures acting on copulating males.