Entamoeba lysyl-tRNA synthetase contains a cytokine-like fomain with chemokine activity towards human endothelial cells

Immunological pressure encountered by protozoan parasites drives the selection of strategies to modulate or avoid the immune responses of their hosts. Here we show that the parasite Entamoeba histolytica has evolved a chemokine that mimics the sequence, structure, and function of the human cytokine HsEMAPII (Homo sapiens endothelial monocyte activating polypeptide II). This Entamoeba EMAPII-like polypeptide (EELP) is translated as a domain attached to two different aminoacyl-tRNA synthetases (aaRS) that are overexpressed when parasites are exposed to inflammatory signals. EELP is dispensable for the tRNA aminoacylation activity of the enzymes that harbor it, and it is cleaved from them by Entamoeba proteases to generate a standalone cytokine. Isolated EELP acts as a chemoattractant for human cells, but its cell specificity is different from that of HsEMAPII. We show that cell specificity differences between HsEMAPII and EELP can be swapped by site directed mutagenesis of only two residues in the cytokines' signal sequence. Thus, Entamoeba has evolved a functional mimic of an aaRS-associated human cytokine with modified cell specificity.

Jugar : un deure sagrat. Activitat lúdica i trascendència

Si alguna obra és de citació gairebé obligatòria quan es parla del joc, és Homo ludens, de Johan Huizinga (Huizinga, 2000). El llibre, publicat originàriament a Leiden el 1938, és la plasmació final de les reflexions dutes a terme per Huizinga des de 1903. Com fa notar el mateix autor, el seu objectiu és presentar el joc com un element omnipresent en la realitat. Tanmateix, sense compartir necessàriament la tesi del llibre (segons la qual no es pot afirmar que el joc sigui un element cultural sinó que ha d’afirmar-se que la cultura humana brolla tota ella del joc, és a dir, que la cultura mateixa ofereix el caràcter de joc i no que el joc sigui una manifestació cultural), el fet inqüestionable és que Huizinga escriu contínuament sobre les connexions entre jugar i accés a la transcendència. Aquesta correspondència serà el nostre fil conductor a fi d’establir alguns dels elements que intervenen en les complexes relacions entre autoconeixement i autotranscendència.

Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation

Asparagine N-Glycosylation is one of the most important forms of protein post-translational modification in eukaryotes. This metabolic pathway can be subdivided into two parts: an upstream sub-pathway required for achieving proper folding for most of the proteins synthesized in the secretory pathway, and a downstream sub-pathway required to give variability to trans-membrane proteins, and involved in adaptation to the environment and innate immunity. Here we analyze the nucleotide variability of the genes of this pathway in human populations, identifying which genes show greater population differentiation and which genes show signatures of recent positive selection. We also compare how these signals are distributed between the upstream and the downstream parts of the pathway, with the aim of exploring how forces of population differentiation and positive selection vary among genes involved in the same metabolic pathway but subject to different functional constraints. Our results show that genes in the downstream part of the pathway are more likely to show a signature of population differentiation, while events of positive selection are equally distributed among the two parts of the pathway. Moreover, events of positive selection are frequent on genes that are known to be at bifurcation points, and that are identified as being in key position by a network-level analysis such as MGAT3 and GCS1. These findings indicate that the upstream part of the Asparagine N-Glycosylation pathway has lower diversity among populations, while the downstream part is freer to tolerate diversity among populations. Moreover, the distribution of signatures of population differentiation and positive selection can change between parts of a pathway, especially between parts that are exposed to different functional constraints. Our results support the hypothesis that genes involved in constitutive processes can be expected to show lower population differentiation, while genes involved in traits related to the environment should show higher variability. Taken together, this work broadens our knowledge on how events of population differentiation and of positive selection are distributed among different parts of a metabolic pathway.

Saccharomyces cerevisiae as a model organism: a comparative study

Background: Model organisms are used for research because they provide a framework on which to develop and optimize methods that facilitate and standardize analysis. Such organisms should be representative of the living beings for which they are to serve as proxy. However, in practice, a model organism is often selected ad hoc, and without considering its representativeness, because a systematic and rational method to include this consideration in the selection process is still lacking. Methodology/Principal Findings: In this work we propose such a method and apply it in a pilot study of strengths and limitations of Saccharomyces cerevisiae as a model organism. The method relies on the functional classification of proteins into different biological pathways and processes and on full proteome comparisons between the putative model organism and other organisms for which we would like to extrapolate results. Here we compare S. cerevisiae to 704 other organisms from various phyla. For each organism, our results identify the pathways and processes for which S. cerevisiae is predicted to be a good model to extrapolate from. We find that animals in general and Homo sapiens in particular are some of the non-fungal organisms for which S. cerevisiae is likely to be a good model in which to study a significant fraction of common biological processes. We validate our approach by correctly predicting which organisms are phenotypically more distant from S. cerevisiae with respect to several different biological processes. Conclusions/Significance: The method we propose could be used to choose appropriate substitute model organisms for the study of biological processes in other species that are harder to study. For example, one could identify appropriate models to study either pathologies in humans or specific biological processes in species with a long development time, such as plants.

Cluster glasses of ultrasoft particles

We present molecular dynamics (MD) simulations results for dense fluids of ultrasoft, fully penetrable particles. These are a binary mixture and a polydisperse system of particles interacting via the generalized exponential model, which is known to yield cluster crystal phases for the corresponding monodisperse systems. Because of the dispersity in the particle size, the systems investigated in this work do not crystallize and form disordered cluster phases. The clusteringtransition appears as a smooth crossover to a regime in which particles are mostly located in clusters, isolated particles being infrequent. The analysis of the internal cluster structure reveals microsegregation of the big and small particles, with a strong homo-coordination in the binary mixture. Upon further lowering the temperature below the clusteringtransition, the motion of the clusters" centers-of-mass slows down dramatically, giving way to a cluster glass transition. In the cluster glass, the diffusivities remain finite and display an activated temperature dependence, indicating that relaxation in the cluster glass occurs via particle hopping in a nearly arrested matrix of clusters. Finally we discuss the influence of the microscopic dynamics on the transport properties by comparing the MD results with Monte Carlo simulations.

Morfología comparada de la escápula de primates humanos y no humanos mediante morfometría geométrica. Estudio preliminar.

Este trabajo estudia la morfología comparada de la escápula de primates humanos y no humanos mediante morfometría geométrica. Se han utilizado 62 omóplatos de individuos adultos de sexo desconocido (22 humanos actuales, 1 Neandertal y 39 primates no humanos), procedentes de las colecciones de las Universidades UAB, UB y del Museo de Ciencias Naturales de Barcelona. Cada escápula se fotografió ortogonalmente y se cuantificó su morfología mediante el uso de puntos anatómicos de referencia (12 para la cara posterior y 13 para la anterior). Después de evaluar la fiabilidad de las mediciones mediante un test de distancias euclídeas, se analizó la diversidad de este hueso en las diferentes especies de primates mediante un Análisis de Componentes Principales (ACP). Los resultados mostraron clara separación morfológica entre primates cuadrúpedos y no cuadrúpedos (suspensores, saltadores y bípedos). En este último conjunto los humanos se separan netamente del resto. En los primates cuadrúpedos predomina la dimensión horizontal (mayor anchura y menor altura), mientras que en los no cuadrúpedos se da la tendencia contraria (menor anchura y mayor altura). La espina escapular queda situada en posición más horizontal enprimates cuadrúpedos respecto a los no cuadrúpedos, aunque en el género Homo, esta inclinación está atenuada. La escápula analizada de Neandertal, si bien es más robusta y con menor inclinación de la espina escapular que la de los humanos actuales, se agrupa bien con éstos. Nuestros resultados muestran el potencial de la metodología utilizada para el estudio de la morfología escapular de Homo y demás géneros de primates.

Building complexity in O2-binding copper complexes : site-selective metalation and intermolecular O2-binding at dicopper and heterometallic complexes derived from an unsymmetric ligand

A novel unsymmetric dinucleating ligand (LN3N4) combining a tridentate and a tetradentate binding sites linked through a m-xylyl spacer was synthesized as ligand scaffold for preparing homo- and dimetallic complexes, where the two metal ions are bound in two different coordination environments. Site-selective binding of different metal ions is demonstrated. LN3N4 is able to discriminate between CuI and a complementary metal (M′ = CuI, ZnII, FeII, CuII, or GaIII) so that pure heterodimetallic complexes with a general formula [CuIM′(LN3N4)]n+ are synthesized. Reaction of the dicopper(I) complex [CuI 2(LN3N4)]2+ with O2 leads to the formation of two different copper-dioxygen (Cu2O2) intermolecular species (O and TP) between two copper atoms located in the same site from different complex molecules. Taking advantage of this feature, reaction of the heterodimetallic complexes [CuM′(LN3N4)]n+ with O2 at low temperature is used as a tool to determine the final position of the CuI center in the system because only one of the two Cu2O2 species is formed