EVALUATION OF LIPID-BASED DELIVERY SYSTEMS FOR INDUCTION OF MUCOSAL AND SYSTEMIC IMMUNE RESPONSES: EFFECT OF CpG MOTIFS

CpG oligodeoxynucleotides (ODNs) are potent adjuvants that significantly enhance cellular and humoral responses to coadministered antigens when given parenterally or by mucosal routes. However, in vivo degradation of ODNs limits their uptake and their effectiveness as adjuvants. The purpose of these studies was to investigate the ability of biphasic lipid vesicles (VTA) to enhance the adjuvant activity of CpG ODNs following systemic administration and to evaluate the feasibility of non-invasive methods for vaccine delivery such as mucosal and transcutaneous immunization. Results showed that formulation of CpG ODN in VTA significantly enhanced its adjuvanticity and protected pigs against infection with Actinobacillus pleuropneumoniae without induction of the severe tissue damage seen with the commercial adjuvant VSA. The dose of CpG ODN required to induce protective immune responses in pigs when formulated in VTA was also established. The present studies also showed that administration of antigen and CpG ODN in biphasic lipid vesicles resulted in induction of systemic and local antibody responses after immunization with a combined mucosal/systemic approach, while the protein either alone or with CpG ODN did not induce mucosal immune responses. The mechanism by which these biphasic lipid vesicles may enhance the adjuvant effect of CpG ODN include: 1) increasing its availability by preventing dilution and degradation in vivo, 2) improving its uptake by antigen presenting cells (APCs) due to the particulate nature of lipid-based formulations. The least effective combinations induced mild or no inflammation, while formulations--- containing both the antigen and CpG ODN induced cell infiltration 24 and 48 h after administration, suggesting that cellular infiltration may be essential for the induction of immune responses. The ability of microneedles to facilitate the delivery of antigens after topical administration was also evaluated in these studies and the data presented clearly showed that only with previous application of microneedles, topical administration of CT induces systemic and mucosal immunity in pigs

On the bend number of circular-arc graphs as edge intersection graphs of paths on a grid

Golumbic, Lipshteyn and Stern \cite{Golumbic-epg} proved that every graph can be represented as the edge intersection graph of paths on a grid (EPG graph), i.e., one can associate with each vertex of the graph a nontrivial path on a rectangular grid such that two vertices are adjacent if and only if the corresponding paths share at least one edge of the grid. For a nonnegative integer $k$, $B_k$-EPG graphs are defined as EPG graphs admitting a model in which each path has at most $k$ bends. Circular-arc graphs are intersection graphs of open arcs of a circle. It is easy to see that every circular-arc graph is a $B_4$-EPG graph, by embedding the circle into a rectangle of the grid. In this paper, we prove that every circular-arc graph is $B_3$-EPG, and that there exist circular-arc graphs which are not $B_2$-EPG. If we restrict ourselves to rectangular representations (i.e., the union of the paths used in the model is contained in a rectangle of the grid), we obtain EPR (edge intersection of path in a rectangle) representations. We may define $B_k$-EPR graphs, $k\geq 0$, the same way as $B_k$-EPG graphs. Circular-arc graphs are clearly $B_4$-EPR graphs and we will show that there exist circular-arc graphs that are not $B_3$-EPR graphs. We also show that normal circular-arc graphs are $B_2$-EPR graphs and that there exist normal circular-arc graphs that are not $B_1$-EPR graphs. Finally, we characterize $B_1$-EPR graphs by a family of minimal forbidden induced subgraphs, and show that they form a subclass of normal Helly circular-arc graphs

On maximizing clique, clique-Helly and hereditary clique-Helly induced subgraphs

Clique-Helly and hereditary clique-Helly graphs are polynomial-time recognizable. Recently, we presented a proof that the clique graph recognition problem is NP-complete [L. Alcón, L. Faria, C.M.H. de Figueiredo, M. Gutierrez, Clique graph recognition is NP-complete, in: Proc. WG 2006, in: Lecture Notes in Comput. Sci., vol. 4271, Springer, 2006, pp. 269-277]. In this work, we consider the decision problems: given a graph G = (V, E) and an integer k ≥ 0, we ask whether there exists a subset V ′ ⊆ V with | V ′ | ≥ k such that the induced subgraph G [V ′ ] of G is, variously, a clique, clique-Helly or hereditary clique-Helly graph. The first problem is clearly NP-complete, from the above reference; we prove that the other two decision problems mentioned are NP-complete, even for maximum degree 6 planar graphs. We consider the corresponding maximization problems of finding a maximum induced subgraph that is, respectively, clique, clique-Helly or hereditary clique-Helly. We show that these problems are Max SNP-hard, even for maximum degree 6 graphs. We show a general polynomial-time frac(1, Δ + 1)-approximation algorithm for these problems when restricted to graphs with fixed maximum degree Δ. We generalize these results to other graph classes. We exhibit a polynomial 6-approximation algorithm to minimize the number of vertices to be removed in order to obtain a hereditary clique-Helly subgraph.Facultad de Ciencias Exacta

On maximizing clique, clique-Helly and hereditary clique-Helly induced subgraphs

Clique-Helly and hereditary clique-Helly graphs are polynomial-time recognizable. Recently, we presented a proof that the clique graph recognition problem is NP-complete [L. Alcón, L. Faria, C.M.H. de Figueiredo, M. Gutierrez, Clique graph recognition is NP-complete, in: Proc. WG 2006, in: Lecture Notes in Comput. Sci., vol. 4271, Springer, 2006, pp. 269-277]. In this work, we consider the decision problems: given a graph G = (V, E) and an integer k ≥ 0, we ask whether there exists a subset V ′ ⊆ V with | V ′ | ≥ k such that the induced subgraph G [V ′ ] of G is, variously, a clique, clique-Helly or hereditary clique-Helly graph. The first problem is clearly NP-complete, from the above reference; we prove that the other two decision problems mentioned are NP-complete, even for maximum degree 6 planar graphs. We consider the corresponding maximization problems of finding a maximum induced subgraph that is, respectively, clique, clique-Helly or hereditary clique-Helly. We show that these problems are Max SNP-hard, even for maximum degree 6 graphs. We show a general polynomial-time frac(1, Δ + 1)-approximation algorithm for these problems when restricted to graphs with fixed maximum degree Δ. We generalize these results to other graph classes. We exhibit a polynomial 6-approximation algorithm to minimize the number of vertices to be removed in order to obtain a hereditary clique-Helly subgraph.Facultad de Ciencias Exacta

Adapting Mediterranean forests to the effects of climate change by modifying management

It is forecast that climate change will affect Mediterranean forests and woodlands in many ways. Consequently, the managers of these areas are faced with the need to take decisions aimed at enhancing the areas’ capacity to adapt to such changes. This is the context which gave rise to the For Climadapt project (within the European MED programme). This article presents as examples two trials in the Lower Pyrenees of Catalonia with the double aim of reducing the vulnerability of forest stands to massive wildfire and enhancing the adaptability and resilience of forests by establishing an ensemble of enrichment stands within sub-Mediterranean single-species pine forests to improve their characteristics

Des mesures de gestion pour adapter les espaces forestiers méditerranéens aux effets des changements climatiques

Il est prévu que les changements climatiques auront de nombreux impacts sur les peuplements forestiers méditerranéens. Les gestionnaires de ces espaces sont donc confrontés au besoin de prendre des décisions orientées pour améliorer leur capacité d’adaptation face à ces changements. C’est dans ce contexte que le projet ForClimadapt est né. L’article présente deux actions démonstratives conduites dans les Pré-Pyrénées catalanes visant d’une part la réduction de la vulnérabilité des peuplements forestiers face aux grands feux de forêt et, d’autre part, l’augmentation de l’adaptabilité et de la résilience des forêts par la réalisation d’un ensemble de plantations d’enrichissement en pinèdes sous-méditerranéennes monospécifiques

On maximizing clique, clique-Helly and hereditary clique-Helly induced subgraphs

Clique-Helly and hereditary clique-Helly graphs are polynomial-time recognizable. Recently, we presented a proof that the clique graph recognition problem is NP-complete [L. Alcón, L. Faria, C.M.H. de Figueiredo, M. Gutierrez, Clique graph recognition is NP-complete, in: Proc. WG 2006, in: Lecture Notes in Comput. Sci., vol. 4271, Springer, 2006, pp. 269-277]. In this work, we consider the decision problems: given a graph G = (V, E) and an integer k ≥ 0, we ask whether there exists a subset V ′ ⊆ V with | V ′ | ≥ k such that the induced subgraph G [V ′ ] of G is, variously, a clique, clique-Helly or hereditary clique-Helly graph. The first problem is clearly NP-complete, from the above reference; we prove that the other two decision problems mentioned are NP-complete, even for maximum degree 6 planar graphs. We consider the corresponding maximization problems of finding a maximum induced subgraph that is, respectively, clique, clique-Helly or hereditary clique-Helly. We show that these problems are Max SNP-hard, even for maximum degree 6 graphs. We show a general polynomial-time frac(1, Δ + 1)-approximation algorithm for these problems when restricted to graphs with fixed maximum degree Δ. We generalize these results to other graph classes. We exhibit a polynomial 6-approximation algorithm to minimize the number of vertices to be removed in order to obtain a hereditary clique-Helly subgraph.Facultad de Ciencias Exacta

The histone binding capacity of SPT2 controls chromatin structure and function in Metazoa

Histone chaperones control nucleosome density and chromatin structure. In yeast, the H3-H4 chaperone Spt2 controls histone deposition at active genes but its roles in metazoan chromatin structure and organismal physiology are not known. Here we identify the Caenorhabditis elegans ortholog of SPT2 (CeSPT-2) and show that its ability to bind histones H3-H4 is important for germline development and transgenerational epigenetic gene silencing, and that spt-2 null mutants display signatures of a global stress response. Genome-wide profiling showed that CeSPT-2 binds to a range of highly expressed genes, and we find that spt-2 mutants have increased chromatin accessibility at a subset of these loci. We also show that SPT2 influences chromatin structure and controls the levels of soluble and chromatin-bound H3.3 in human cells. Our work reveals roles for SPT2 in controlling chromatin structure and function in Metazoa.</p