Adenosine Deaminase Enhances the Immunogenicity of Human Dendritic Cells from Healthy and HIV-Infected Individuals

ADA is an enzyme implicated in purine metabolism, and is critical to ensure normal immune function. Its congenital deficit leads to severe combined immunodeficiency (SCID). ADA binding to adenosine receptors on dendritic cell surface enables T-cell costimulation through CD26 crosslinking, which enhances T-cell activation and proliferation. Despite a large body of work on the actions of the ecto-enzyme ADA on T-cell activation, questions arise on whether ADA can also modulate dendritic cell maturation. To this end we investigated the effects of ADA on human monocyte derived dendritic cell biology. Our results show that both the enzymatic and non-enzymatic activities of ADA are implicated in the enhancement of CD80, CD83, CD86, CD40 and CCR7 expression on immature dendritic cells from healthy and HIV-infected individuals. These ADA-mediated increases in CD83 and costimulatory molecule expression is concomitant to an enhanced IL-12, IL-6, TNF-α, CXCL8(IL-8), CCL3(MIP1-α), CCL4(MIP-1β) and CCL5(RANTES) cytokine/chemokine secretion both in healthy and HIV-infected individuals and to an altered apoptotic death in cells from HIV-infected individuals. Consistently, ADA-mediated actions on iDCs are able to enhance allogeneic CD4 and CD8-T-cell proliferation, globally yielding increased iDC immunogenicity. Taken together, these findings suggest that ADA would promote enhanced and correctly polarized T-cell responses in strategies targeting asymptomatic HIV-infected individuals.     

The MAPK1/3 pathway is essential for the deregulation of autophagy observed in G2019S LRRK2 mutant fibroblasts

The link between the deregulation of autophagy and cell death processes can be essential in the development of several neurodegenerative diseases, such as Parkinson disease (PD). However, the molecular mechanism of deregulation of this degradative process in PD patients is unknown. The leucine-rich repeat kinase 2 (LRRK2) gene is related to PD and its implication in autophagy regulation has been described. Our recent work shows that the presence of the G2019S LRRK2 mutation, one of the most prevalent in LRRK2, is accompanied by a deregulation of autophagy basal levels dependent on the MAPK1/3 (ERK2/1) pathway.     

Fire adaptations in the Canary Islands pine (Pinus canariensis)

A wide set of phenotypic characteristics related to life history were studied in mature stands of Pinus canariensis throughout its natural range of distribution in the Canary archipelago. Natural forests ranging from those located in xeric areas through to the sub-tropical cloud forests and high mountain stands were classified into eight ecological regions according to their main climatic features. The recent history of forest fires (covering the last 30 years) was taken into account using a categorical factor with three levels. The phenotypic variables studied included those related to seed dispersal (cone size, number of seed scales, seed and wing size and percentage of serotinous trees) and stem growth both on the breast height section (bark thickness, radial growth at various ages and sapwood and heartwood sizes) and on the entire stem (height growth related to age). The average percentage of serotinous trees present in the ecological regions studied varied from 3 to 35%. Average bark thickness in adult trees ranged from 22 to 49 mm and was found to be unrelated to age or diameter. Growth both in height and diameter was found to decline after an average of 25 years, although clear trends in relation to this could not be established across the ecological regions. A high correlation was found to exist between annual rainfall, fire frequency, serotiny and bark thickness at a regional level. Sapwood area per hectare proved to be a valuable indirect site-quality index for the objectives of this paper. Favourable sites (characterised by a high sapwood area per hectare) displayed the highest levels of both bark thickness and serotiny. These particular areas are those, which have suffered more frequent and intense fires over the last decades. The evolutionary implications of this trend and of other general traits of the species, such as vegetative resprouting, are discussed here in relation to the role of understorey vegetation in fire regimes, competition and volcanic history of the islands.     

Genetic characterization of the Klebsiella pneumoniae waa gene cluster, involved in core lipopolysaccharide biosynthesis

A recombinant cosmid containing genes involved in Klebsiella pneumoniae C3 core lipopolysaccharide biosynthesis was identified by its ability to confer bacteriocin 28b resistance to Escherichia coli K-12. The recombinant cosmid contains 12 genes, the whole waa gene cluster, flanked by kbl and coaD genes, as was found in E. coli K-12. PCR amplification analysis showed that this cluster is conserved in representative K. pneumoniae strains. Partial nucleotide sequence determination showed that the same genes and gene order are found in K. pneumoniae subsp. ozaenae, for which the core chemical structure is known. Complementation analysis of known waa mutants from E. coli K-12 and/or Salmonella enterica led to the identification of genes involved in biosynthesis of the inner core backbone that are shared by these three members of the Enterobacteriaceae. K. pneumoniae orf10 mutants showed a two-log-fold reduction in a mice virulence assay and a strong decrease in capsule amount. Analysis of a constructed K. pneumoniae waaE deletion mutant suggests that the WaaE protein is involved in the transfer of the branch beta-D-Glc to the O-4 position of L-glycero-D-manno-heptose I, a feature shared by K. pneumoniae, Proteus mirabilis, and Yersinia enterocolitica.     

To grow or to seed: ecotypic variation in reproductive allocation and cone production by young female Aleppo pine (Pinus halepensis, Pinaceae)

Age and size at the first reproduction and the reproductive allocation of plants are linked to different life history strategies. Aleppo pine only reproduces through seed, and, as such, early female reproduction confers high fitness in its infertile highly fire-prone habitats along the Mediterranean coast because life expectancy is short. We investigated the extent of ecotypic differentiation in female reproductive allocation and examined the relation between early female reproduction and vegetative growth. In a common-garden experiment, the threshold age and size at first female reproduction and female reproductive allocation at age seven differed significantly among Aleppo pine provenances of ecologically distinct origin. Significant correlations among reproductive features of the provenances and the ecological traits of origin were found using different analytical tools. In nonlinear models of cone counts vs. stem volume, medium-sized trees (not the largest trees) produced the highest cone yield, confirming that, at the individual level, early female reproduction is incompatible with fast vegetative growth. The contribution of founder effects and adaptation to contrasting fire regimes may be confounding factors. But considering all traits analyzed, the geographical patterns of resource allocation by Aleppo pine suggest ecotypic specialization for either resource-poor (favoring early reproduction) or resource-rich (favoring vegetative growth) habitats.     

Sequence of rat skeletal muscle phosphoglycerate mutase cDNA

A cDNA clone coding rat skeletal muscle phosphoglycerate mutase was isolated from a rat muscle lambda gt10 cDNA library and its sequence was determined. The deduced protein possesses 252 amino acids and is 94% homologous with respect to human muscle phosphoglycerate mutase. No amino acids changes occur at the active site and structural predictions suggest strong conformational homologies with other enzymes of the mutase family.