Functional studies of the deubiquitinating enzymes USP19, USP4 and UCH-L1

El marcaje de proteínas con ubiquitina, conocido como ubiquitinación, cumple diferentes funciones que incluyen la regulación de varios procesos celulares, tales como: la degradación de proteínas por medio del proteosoma, la reparación del ADN, la señalización mediada por receptores de membrana, y la endocitosis, entre otras (1). Las moléculas de ubiquitina pueden ser removidas de sus sustratos gracias a la acción de un gran grupo de proteasas, llamadas enzimas deubiquitinizantes (DUBs) (2). Las DUBs son esenciales para la manutención de la homeostasis de la ubiquitina y para la regulación del estado de ubiquitinación de diferentes sustratos. El gran número y la diversidad de DUBs descritas refleja tanto su especificidad como su utilización para regular un amplio espectro de sustratos y vías celulares. Aunque muchas DUBs han sido estudiadas a profundidad, actualmente se desconocen los sustratos y las funciones biológicas de la mayoría de ellas. En este trabajo se investigaron las funciones de las DUBs: USP19, USP4 y UCH-L1. Utilizando varias técnicas de biología molecular y celular se encontró que: i) USP19 es regulada por las ubiquitin ligasas SIAH1 y SIAH2 ii) USP19 es importante para regular HIF-1α, un factor de transcripción clave en la respuesta celular a hipoxia, iii) USP4 interactúa con el proteosoma, iv) La quimera mCherry-UCH-L1 reproduce parcialmente los fenotipos que nuestro grupo ha descrito previamente al usar otros constructos de la misma enzima, y v) UCH-L1 promueve la internalización de la bacteria Yersinia pseudotuberculosis.

Negative Fukui functions: new insights based on electronegativity equalization

The occurrence of negative values for Fukui functions was studied through the electronegativity equalization method. Using algebraic relations between Fukui functions and different other conceptual DFT quantities on the one hand and the hardness matrix on the other hand, expressions were obtained for Fukui functions for several archetypical small molecules. Based on EEM calculations for large molecular sets, no negative Fukui functions were found

Critical thoughts on computing atom condensed Fukui functions

Different procedures to obtain atom condensed Fukui functions are described. It is shown how the resulting values may differ depending on the exact approach to atom condensed Fukui functions. The condensed Fukui function can be computed using either the fragment of molecular response approach or the response of molecular fragment approach. The two approaches are nonequivalent; only the latter approach corresponds in general with a population difference expression. The Mulliken approach does not depend on the approach taken but has some computational drawbacks. The different resulting expressions are tested for a wide set of molecules. In practice one must make seemingly arbitrary choices about how to compute condensed Fukui functions, which suggests questioning the role of these indicators in conceptual density-functional theory

Linear response functions for a vibrational configuration interaction state

Linear response functions are implemented for a vibrational configuration interaction state allowing accurate analytical calculations of pure vibrational contributions to dynamical polarizabilities. Sample calculations are presented for the pure vibrational contributions to the polarizabilities of water and formaldehyde. We discuss the convergence of the results with respect to various details of the vibrational wave function description as well as the potential and property surfaces. We also analyze the frequency dependence of the linear response function and the effect of accounting phenomenologically for the finite lifetime of the excited vibrational states. Finally, we compare the analytical response approach to a sum-over-states approach

A Framework for Various Approaches under the UNFCCC: Necessity or luxury? CEPS Special Report No. 70, 20 November 2012

In recognition that the world is moving towards a new climate change regime that in many ways will be very different from the world in which the Kyoto Protocol has been operating, climate negotiators and other specialists have begun to focus their attention on developing a “framework for variable approaches” (FVA). It is hoped that this new framework will prove more adaptable to national circumstances and more capable of catalysing new ideas, at the regional, national or sub-national level. This paper examines the assumptions, objectives, scope, components and functions of an FVA, with a view to creating the right conditions in which a well-functioning global carbon market can emerge.

Parameter sensitivity and predictive uncertainty in a new water quality model, Q(2)

A new dynamic model of water quality, Q(2), has recently been developed, capable of simulating large branched river systems. This paper describes the application of a generalized sensitivity analysis (GSA) to Q(2) for single reaches of the River Thames in southern England. Focusing on the simulation of dissolved oxygen (DO) (since this may be regarded as a proxy for the overall health of a river); the GSA is used to identify key parameters controlling model behavior and provide a probabilistic procedure for model calibration. It is shown that, in the River Thames at least, it is more important to obtain high quality forcing functions than to obtain improved parameter estimates once approximate values have been estimated. Furthermore, there is a need to ensure reasonable simulation of a range of water quality determinands, since a focus only on DO increases predictive uncertainty in the DO simulations. The Q(2) model has been applied here to the River Thames, but it has a broad utility for evaluating other systems in Europe and around the world.

Good practice in reviewing and publishing studies on herbal medicine, with special emphasis on traditional Chinese medicine and Chinese materia medica

Ethnopharmacological relevance: Studies on traditional Chinese medicine (TCM), like those of other systems of traditional medicine (TM), are very variable in their quality, content and focus, resulting in issues around their acceptability to the global scientific community. In an attempt to address these issues, an European Union funded FP7 consortium, composed of both Chinese and European scientists and named “Good practice in traditional Chinese medicine” (GP-TCM), has devised a series of guidelines and technical notes to facilitate good practice in collecting, assessing and publishing TCM literature as well as highlighting the scope of information that should be in future publications on TMs. This paper summarises these guidelines, together with what has been learned through GP-TCM collaborations, focusing on some common problems and proposing solutions. The recommendations also provide a template for the evaluation of other types of traditional medicine such as Ayurveda, Kampo and Unani. Materials and methods: GP-TCM provided a means by which experts in different areas relating to TCM were able to collaborate in forming a literature review good practice panel which operated through e-mail exchanges, teleconferences and focused discussions at annual meetings. The panel involved coordinators and representatives of each GP-TCM work package (WP) with the latter managing the testing and refining of such guidelines within the context of their respective WPs and providing feedback. Results: A Good Practice Handbook for Scientific Publications on TCM was drafted during the three years of the consortium, showing the value of such networks. A “deliverable – central questions – labour division” model had been established to guide the literature evaluation studies of each WP. The model investigated various scoring systems and their ability to provide consistent and reliable semi-quantitative assessments of the literature, notably in respect of the botanical ingredients involved and the scientific quality of the work described. This resulted in the compilation of (i) a robust scoring system and (ii) a set of minimum standards for publishing in the herbal medicines field, based on an analysis of the main problems identified in published TCM literature.

Spectral gap for Glauber type dynamics for a special class of potentials

We consider an equilibrium birth and death type process for a particle system in infinite volume, the latter is described by the space of all locally finite point configurations on Rd. These Glauber type dynamics are Markov processes constructed for pre-given reversible measures. A representation for the ``carré du champ'' and ``second carré du champ'' for the associate infinitesimal generators L are calculated in infinite volume and for a large class of functions in a generalized sense. The corresponding coercivity identity is derived and explicit sufficient conditions for the appearance and bounds for the size of the spectral gap of L are given. These techniques are applied to Glauber dynamics associated to Gibbs measure and conditions are derived extending all previous known results and, in particular, potentials with negative parts can now be treated. The high temperature regime is extended essentially and potentials with non-trivial negative part can be included. Furthermore, a special class of potentials is defined for which the size of the spectral gap is as least as large as for the free system and, surprisingly, the spectral gap is independent of the activity. This type of potentials should not show any phase transition for a given temperature at any activity.

An optimization problem concerning multiplicative functions

In this paper we study the problem of maximizing a quadratic form 〈Ax,x〉 subject to ‖x‖q=1, where A has matrix entries View the MathML source with i,j|k and q≥1. We investigate when the optimum is achieved at a ‘multiplicative’ point; i.e. where x1xmn=xmxn. This turns out to depend on both f and q, with a marked difference appearing as q varies between 1 and 2. We prove some partial results and conjecture that for f multiplicative such that 0

ALGEBRAIC AND GEOMETRIC THEORY OF THE TOPOLOGICAL RING OF COLOMBEAU GENERALIZED FUNCTIONS

We continue the investigation of the algebraic and topological structure of the algebra of Colombeau generalized functions with the aim of building up the algebraic basis for the theory of these functions. This was started in a previous work of Aragona and Juriaans, where the algebraic and topological structure of the Colombeau generalized numbers were studied. Here, among other important things, we determine completely the minimal primes of (K) over bar and introduce several invariants of the ideals of 9(Q). The main tools we use are the algebraic results obtained by Aragona and Juriaans and the theory of differential calculus on generalized manifolds developed by Aragona and co-workers. The main achievement of the differential calculus is that all classical objects, such as distributions, become Cl-functions. Our purpose is to build an independent and intrinsic theory for Colombeau generalized functions and place them in a wider context.

Bloch-Kohn and Wannier-Kohn functions in one dimension

Bloch and Wannier functions of the Kohn type for a quite general one-dimensional Hamiltonian with inversion symmetry are studied. Important clarifications on null minigaps and the symmetry of those functions are given, with emphasis on the Kronig-Penney model. The lack of a general selection rule on the miniband index for optical transitions between edge states in semiconductor superlattices is discussed. A direct method for the calculation of Wannier-Kohn functions is presented.

Distinct mitochondrial HSP70 homologues conserved in various Leishmania species suggest novel biological functions

We report the identification of two distinct homologues of the 70-kDa mitochondrial heat shock protein (mtHSP70) from Leishmania chagasi/Leishmania infantum (Lc2.1 and Lc2.2). in Leishmania species, multiple genes encoding Lc2.2 are present whilst single genes encode Lc2.1. Strikingly, genes encoding Lc2.1-like proteins are absent from Trypanosoma species. Lc2.2 is characterized by a poly-glutamine rich C-terminus, absent from Lc2.1 or mtHSP70 homologues outside the trypanosomatids. Lc2.1 displays unique substitutions within its peptide-binding domain which modify amino acids strictly conserved in cytoplasmic and mitochondrial HSP70 proteins alike. Affinity purified antibodies recognize mainly a single protein in extracts from promastigotes/epimastigotes of various Leishmania/Trypanosoma species. Upon differentiation of Leishmania amazonensis into amastigotes a second protein (presumably Lc2.1) is induced and becomes the predominant mtHSP70 homologue expressed. Subcellular localization of these proteins was investigated and ratified a distribution throughout the mitochondrial matrix. Our results imply novel mtHSP70 functions which evolved within the genus Leishmania. (C) 2008 Elsevier B.V. All rights reserved.

Zeros of Jacobi functions of second kind

The number of zeros in (- 1, 1) of the Jacobi function of second kind Q(n)((alpha, beta)) (x), alpha, beta > - 1, i.e. The second solution of the differential equation(1 - x(2))y (x) + (beta - alpha - (alpha + beta + 2)x)y' (x) + n(n + alpha + beta + 1)y(x) = 0,is determined for every n is an element of N and for all values of the parameters alpha > - 1 and beta > - 1. It turns out that this number depends essentially on alpha and beta as well as on the specific normalization of the function Q(n)((alpha, beta)) (x). Interlacing properties of the zeros are also obtained. As a consequence of the main result, we determine the number of zeros of Laguerre's and Hermite's functions of second kind. (c) 2005 Elsevier B.V. All rights reserved.

Schur-SzegA composition of entire functions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Measurement of jet fragmentation into charged particles in pp and PbPb collisions at root s(NN)=2.76 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)