A bi-directional dialog between vascular cells and monocytes/macrophages regulates tumor progression

Cancer progression largely depends on tumor blood vessels as well on immune cell infiltration. In various tumors, vascular cells, namely endothelial cells (ECs) and pericytes, strongly regulate leukocyte infiltration into tumors and immune cell activation, hence the immune response to cancers. Recently, a lot of compelling studies unraveled the molecular mechanisms by which tumor vascular cells regulate monocyte and tumor-associated macrophage (TAM) recruitment and phenotype, and consequently tumor progression. Reciprocally, TAMs and monocytes strongly modulate tumor blood vessel and tumor lymphatic vessel formation by exerting pro-angiogenic and lymphangiogenic effects, respectively. Finally, the interaction between monocytes/TAMs and vascular cells is also impacting several steps of the spread of cancer cells throughout the body, a process called metastasis. In this review, the impact of the bi-directional dialog between blood vascular cells and monocytes/TAMs in the regulation of tumor progression is discussed. All together, these data led to the design of combinations of anti-angiogenic and immunotherapy targeting TAMs/monocyte whose effects are briefly discussed in the last part of this review

Codage et classification non supervisée d'un corpus maya : extraire des contextes pour situer l'inconnu par rapport au connu

International audienceL'écriture logosyllabique des anciens Mayas comprend plus de 500 signes et est en bonne partie déchiffrée, avec des degrés de certitude divers. Nous avons appliqué au codex de Dresde, l'un des trois seuls manuscrits qui nous soient parvenus, codé sous LATEX avec le système mayaTEX, notre méthode de représentation graduée, par apprentissage non supervisé hybride entre clustering et analyse factorielle oblique, sous la métrique de Hellinger, afin d'obtenir une image nuancée des thèmes traités : les individus statistiques sont les 212 segments de folio du codex, et leurs attributs sont les 1687 bigrammes de signes extraits. Pour comparaison, nous avons introduit dans cette approche endogène un élément exogène, la décomposition en éléments des signes composites, pour préciser plus finement les contenus. La rétro-visualisation dans le texte original des résultats et expressions dégagées éclaire la signification de certains glyphes peu compris, en les situant dans des contextes clairement interprétables

Les protéines FXYD : nouveaux régulateurs de la Na,K-ATPase

Les protéines FXYD appartiennent à une famille de petites protéines membranaires. Des études récentes suggèrent que six des sept membres de cette famille, FXYD1 (phospholemman), FXYD2 (sous-unité γ de la Na,K-ATPase), FXYD3 (Mat-8), FXYD4 (CHIF), FXYD5 (Ric) et FXYD7, sont des sous-unités auxiliaires de la Na, K-ATPase régulant son activité de manière tissu et isoforme spécifique. Ces résultats soulignent la complexité de la régulation des ions Na+ et K+ par la Na,K-ATPase qui est nécessaire pour assurer les fonctions propres de différents tissus comme la réabsorption du Na+ par le rein, la contraction musculaire et l’excitabilité neuronale. De plus, une mutation dans FXYD2 a été liée à certains cas d’hypomagnésémie, suggérant que des perturbations de la régulation de la Na,K-ATPase par les protéines FXYD seraient impliquées dans des états physiopathologiques. Une meilleure compréhension de ce nouveau mécanisme de régulation de la Na,K-ATPase pourrait nous aider à mieux comprendre son rôle dans les états physiopathologiques. Dans cet article, nous discutons les données les plus récentes sur le rôle des protéines FXYD dans la modulation de la Na, K-ATPase.Members of the FXYD protein family are small membrane proteins which are characterized by an FXYD motif, two conserved glycines and a serine residue. FXYD proteins show a tissue-specific distribution. Recent evidence suggests that 6 out of 7 FXYD proteins, FXYD1 (phospholemman), FXYD2 (γ subunit of Na,K-ATPase), FXYD3 (Mat-8), FXYD4 (CHIF), FXYD5 (Ric) and FXYD7 associate with Na,K-ATPase and modulate its transport properties e.g. its Na+ and/or its K+ affinity in a distinct way. These results highlight the complex regulation of Na+ and K+ transport which is necessary to ensure proper tissue functions such as renal Na+-reabsorption, muscle contractility and neuronal excitability. Moreover, mutation of a conserved glycine residue into an arginine residue in FXYD2 has been linked to cases of human hypomagnesemia indicating that dysregulation of Na,K-ATPase by FXYD proteins may be implicated in pathophysiological states. A better characterization of this novel regulatory mechanism of Na,K-ATPase may help to better understand its role in physiological and pathophysiological conditions

A Divergent P Element and Its Associated MITE, BuT5, Generate Chromosomal Inversions and Are Widespread within the Drosophila repleta Species Group

The transposon BuT5 caused two chromosomal inversions fixed in two Drosophila species of the repleta group, D. mojavensis and D. uniseta. BuT5 copies are approximately 1-kb long, lack any coding capacity, and do not resemble any other transposable element (TE). Because of its elusive features, BuT5 has remained unclassified to date. To fully characterize BuT5, we carried out bioinformatic similarity searches in available sequenced genomes, including 21 Drosophila species. Significant hits were only recovered for D. mojavensis genome, where 48 copies were retrieved, 22 of them approximately 1-kb long. Polymerase chain reaction (PCR) and dot blot analyses on 54 Drosophila species showed that BuT5 is homogeneous in size and has a widespread distribution within the repleta group. Thus, BuT5 can be considered as a miniature inverted-repeat TE. A detailed analysis of the BuT5 hits in D. mojavensis revealed three partial copies of a transposon with ends very similar to BuT5 and a P -element-like transposase-encoding region in between. A putatively autonomous copy of this P element was isolated by PCR from D. buzzatii. This copy is 3,386-bp long and possesses a seven-exon gene coding for an 822-aa transposase. Exon-intron boundaries were confirmed by reverse transcriptase-PCR experiments. A phylogenetic tree built with insect P superfamily transposases showed that the D. buzzatii P element belongs to an early diverging lineage within the P -element family. This divergent P element is likely the master transposon mobilizing BuT5. The BuT5 / P element partnership probably dates back approximately 16 Ma and is the ultimate responsible for the generation of the two chromosomal inversions in the Drosophila repleta species group

Processing a Mayan Corpus for Enhancing our Knowledge of Ancient Scripts

International audienceThe ancient Maya writing comprises more than 500 signs, either syllabic or semantic, and is largely deciphered, with a variable degree of reliability. We applied to the Dresden Codex, one of the only three manuscripts that reached us, encoded for LATEX with the mayaTEX package, our graded representation method of hybrid non-supervised learning, intermediate between clustering and oblique factor analysis, and following Hellinger metrics, in order to obtain a nuanced image of themes dealt with: the statistical entities are the 214 codex segments, and their attributes are the 1687 extracted bigrams of signs. For comparison, we introduced in this approach an exogenous element, i.e. the splitting of the composed signs into their elements, for a finer elicitation of the contents. The results are visualized as a set of "thematic concordances": for each homogeneous semantic context, the most salient bigrams or sequences of bigrams are displayed in their textual environment, which sheds a new light on the meaning of some little understood glyphs, placing them in clearly understandable contexts

The Transposon Galileo Generates Natural Chromosomal Inversions in Drosophila by Ectopic Recombination

Background: transposable elements (TEs) are responsible for the generation of chromosomal inversions in several groups of organisms. However, in Drosophila and other Dipterans, where inversions are abundant both as intraspecific polymorphisms and interspecific fixed differences, the evidence for a role of TEs is scarce. Previous work revealed that the transposon Galileo was involved in the generation of two polymorphic inversions of Drosophila buzzatii. Methodology/Principal Findings: to assess the impact of TEs in Drosophila chromosomal evolution and shed light on the mechanism involved, we isolated and sequenced the two breakpoints of another widespread polymorphic inversion from D. buzzatii, 2z3. In the non inverted chromosome, the 2z3 distal breakpoint was located between genes CG2046 and CG10326 whereas the proximal breakpoint lies between two novel genes that we have named Dlh and Mdp. In the inverted chromosome, the analysis of the breakpoint sequences revealed relatively large insertions (2,870-bp and 4,786-bp long) including two copies of the transposon Galileo (subfamily Newton), one at each breakpoint, plus several other TEs. The two Galileo copies: (i) are inserted in opposite orientation; (ii) present exchanged target site duplications; and (iii) are both chimeric. Conclusions/Significance: our observations provide the best evidence gathered so far for the role of TEs in the generation of Drosophila inversions. In addition, they show unequivocally that ectopic recombination is the causative mechanism. The fact that the three polymorphic D. buzzatii inversions investigated so far were generated by the same transposon family is remarkable and is conceivably due to Galileo's unusual structure and current (or recent) transpositional activity

Evidence on individual preferences for longevity risk

The standard model of intertemporal choice assumes risk neutrality toward the length of life: due to additivity, agents are not sensitive to a mean preserving spread in the length of life. Using a survey fielded in the RAND American Life Panel (ALP), this paper provides empirical evidence on possible deviation from risk neutrality with respect to longevity in the U.S. population. The questions we ask allow to find the distribution as well as to quantify the degree of risk aversion with respect to the length of life in the population. We find evidence that roughly 75% of respondents were not neutral with respect to longevity risk. Higher income households are more likely to be risk averse. We do not find evidence that the degree of risk aversion varies with age or education

Officiers et seigneurs

Le magistrat du parlement de Toulouse Bernard de La Roche-Flavin (1552-1627) a connu une carrière professionnelle marquée par l'ascension puis par la chute. Conseiller et magistrat présidial en la sénéchaussée de Toulouse en 1575, il appartient d'abord au groupe des officiers « moyens ». En obtenant en 1584 une charge de président aux requêtes du parlement, il gagne l'élite des cours souveraines. À partir de 1614, il se voue à l'écriture dans le but de transmettre ses années d'expériences pro..