The Expanded mtDNA Phylogeny of the Franco-Cantabrian Region Upholds the Pre-Neolithic Genetic Substrate of Basques

The European genetic landscape has been shaped by several human migrations occurred since Paleolithic times. The accumulation of archaeological records and the concordance of different lines of genetic evidence during the last two decades have triggered an interesting debate concerning the role of ancient settlers from the Franco-Cantabrian region in the postglacial resettlement of Europe. Among the Franco-Cantabrian populations, Basques are regarded as one of the oldest and more intriguing human groups of Europe. Recent data on complete mitochondrial DNA genomes focused on macrohaplogroup R0 revealed that Basques harbor some autochthonous lineages, suggesting a genetic continuity since pre-Neolithic times. However, excluding haplogroup H, the most representative lineage of macrohaplogroup R0, the majority of maternal lineages of this area remains virtually unexplored, so that further refinement of the mtDNA phylogeny based on analyses at the highest level of resolution is crucial for a better understanding of the European prehistory. We thus explored the maternal ancestry of 548 autochthonous individuals from various Franco-Cantabrian populations and sequenced 76 mitogenomes of the most representative lineages. Interestingly, we identified three mtDNA haplogroups, U5b1f, J1c5c1 and V22, that proved to be representative of Franco-Cantabria, notably of the Basque population. The seclusion and diversity of these female genetic lineages support a local origin in the Franco-Cantabrian area during the Mesolithic of southwestern Europe, ∼10,000 years before present (YBP), with signals of expansions at ∼3,500 YBP. These findings provide robust evidence of a partial genetic continuity between contemporary autochthonous populations from the Franco-Cantabrian region, specifically the Basques, and Paleolithic/Mesolithic hunter-gatherer groups. Furthermore, our results raise the current proportion (≈15%) of the Franco-Cantabrian maternal gene pool with a putative pre-Neolithic origin to ≈35%, further supporting the notion of a predominant Paleolithic genetic substrate in extant European populations.     

PHENOTYPIC PLASTICITY INDUCED IN TRANSPLANT EXPERIMENTS IN A MUTUALISTIC ASSOCIATION BETWEEN THE RED ALGA JANIA ADHAERENS (RHODOPHYTA,CORALLINALES) AND THE SPONGE HALICLONA CAERULEA (PORIFERA: HAPLOSCLERIDA): MORPHOLOGICAL RESPONSES OF THE ALGA1

The association between the red macroalga Jania adhaerens J. V. Lamour. and the sponge Haliclona caerulea is the most successful life‐form between 2 and 4 m depth in Mazatlán Bay (Mexican Pacific). J. adhaerens colonizes the rocky intertidal area and penetrates into deeper areas only when it lives in association with H. caerulea. The aposymbiotic form of the sponge has not been reported in the bay. To understand the ecological success of this association, we examined the capacity of J. adhaerens to acclimate in Mazatlán Bay using transplant experiments. The transplanted aposymbiotic J. adhaerens did not survive the first 2 weeks; however, J. adhaerens when living in association with H. caerulea, acclimated easily to depth, showing no sign of mortality during the 103 d of the experiment. We conclude that the ability of J. adhaerens to colonize in deeper areas in this hydrodynamic environment may in part rely on the protection provided by the sponge to the algal canopy. Both species contribute to the shape of the associated form. Nevertheless, the morphological variation in the association appears to be dominated by the variation in J. adhaerens canopy to regulate pigment self‐shading under light‐limited conditions and/or tissue resistance under high hydrodynamics. Consequently, our results are consistent with light as the abiotic controlling factor, which regulates the lower depth distribution of the association in Mazatlán Bay, through limiting the growth rate of J. adhaerens. Hydrodynamics may determine the upper limit of the association by imposing high mass losses.     

The role of arctic zooplankton in biogeochemical cycles: respiration and excretion of ammonia and phosphate during summer

The study of the structural and functional properties of key components of polar marine ecosystems has received increased attention in order to better understand the ecological consequences of future sea temperature rise and seasonal ice retraction. Owing to this purpose, during the ATOS-Arctic cruise, held in July 2007 in the framework of the 2007–2008 International Polar Year, we studied the respiratory carbon demand of mesozooplankton as well as their contribution to the regeneration of inorganic nitrogen and phosphorus (NH₄-N and PO₄-P) via excretion. The studied area comprised several stations along a latitudinal gradient in the East Greenland current, plus a network of stations NW of the Svalbard islands. The specific respiratory carbon losses and phosphorus (PO₄-P) excretion rates were similar or slightly higher than some reports for Arctic mesozooplankton, but the nitrogen (NH₄-N) excretion rates were higher by a factor of 3 when compared with previous data sets. The mesozooplankton respiratory losses were equivalent to 23% of primary production, and at turn zooplankton contributed by excretion to more than 50% of the N and P required by phytoplankton. Although C:N, C:P and N:P metabolic atomic quotients almost coincided with the average Redfield’s stoichiometric ratios, the low C:N values when compared to previous reports suggested a predominance of protein-related metabolic substrates. The potential consequences of changes observed in the C:N, N:P and C:P metabolic ratios of mesozooplankton for Arctic marine ecosystems are discussed.     

Plasma Biomarkers Discriminate Clinical Forms of Multiple Sclerosis

Multiple sclerosis, the most common cause of neurological disability in young population after trauma, represents a significant public health burden. Current challenges associated with management of multiple sclerosis (MS) patients stem from the lack of biomarkers that might enable stratification of the different clinical forms of MS and thus prompt treatment for those patients with progressive MS, for whom there is currently no therapy available. In the present work we analyzed a set of thirty different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive and primary progressive MS) and 53 healthy controls, across two independent cohorts. The set of plasma analytes was quantified with Luminex xMAP technology and their predictive power regarding clinical outcome was evaluated both individually using ROC curves and in combination using logistic regression analysis. Our results from two independent cohorts of MS patients demonstrate that the divergent clinical and histology-based MS forms are associated with distinct profiles of circulating plasma protein biomarkers, with distinct signatures being composed of chemokines and growth/angiogenic factors. With this work, we propose that an evaluation of a set of 4 circulating biomarkers (HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4) in MS patients might serve as an effective tool in the diagnosis and more personalized therapeutic targeting of MS patients.     

Nitric oxide decreases superoxide anion generation by microsomes from soybean embryonic axes

Experiments were carried out to evaluate the effects of exposure to nitric oxide on the ability by NADPH‐dependent microsomal electron transfer to generate oxygen radicals. Such interactions could play a role in the potential antioxidant action of nitric oxide (NO). Isolated microsomes from soybean ( Glycine max [L.] Merr. cv. Hood) embryonic axes were exposed to an exogenously added source of nitric oxide (NO) (S‐nitrosoglutathione + dithiothreitol). The O₂⁻ generation rate by microsomes exposed to NO decreased significantly as compared to the rate measured in microsomes incubated in the absence of NO. The exposure of the microsomes to the NO donor did not alter the microsomal rate of hydroxyl radical generation. Preincubation of the microsomes with the NO donor affected neither iron reduction rate nor activity of cytochrome c reductase. However, cytochrome P₄₅₀ activity was significantly inhibited after exposure to NO. This inhibition was completely prevented by hemoglobin. The data are consistent with the hypothesis that NO exhibits a potential antioxidant role in the plant cell by decreasing the rate of generation of superoxide anion. Since endogenous NO was detected in homogenates of soybean embryonic axes by EPR studies, this interaction between NO and cytochrome P₄₅₀ in soybean embryonic axes could be a factor of relevance for the control of oxidative stress in vivo.     

Host Cell Poly(ADP-Ribose) Glycohydrolase Is Crucial for Trypanosoma cruzi Infection Cycle

Trypanosoma cruzi, etiological agent of Chagas’ disease, has a complex life cycle which involves the invasion of mammalian host cells, differentiation and intracellular replication. Here we report the first insights into the biological role of a poly(ADP-ribose) glycohydrolase in a trypanosomatid (TcPARG). In silico analysis of the TcPARG gene pointed out the conservation of key residues involved in the catalytic process and, by Western blot, we demonstrated that it is expressed in a life stage-dependant manner. Indirect immunofluorescence assays and electron microscopy using an anti-TcPARG antibody showed that this enzyme is localized in the nucleus independently of the presence of DNA damage or cell cycle stage. The addition of poly(ADP-ribose) glycohydrolase inhibitors ADP-HPD (adenosine diphosphate (hydroxymethyl) pyrrolidinediol) or DEA (6,9-diamino-2-ethoxyacridine lactate monohydrate) to the culture media, both at a 1 µM concentration, reduced in vitro epimastigote growth by 35% and 37% respectively, when compared to control cultures. We also showed that ADP-HPD 1 µM can lead to an alteration in the progression of the cell cycle in hydroxyurea synchronized cultures of T. cruzi epimastigotes. Outstandingly, here we demonstrate that the lack of poly(ADP-ribose) glycohydrolase activity in Vero and A549 host cells, achieved by chemical inhibition or iRNA, produces the reduction of the percentage of infected cells as well as the number of amastigotes per cell and trypomastigotes released, leading to a nearly complete abrogation of the infection process. We conclude that both, T. cruzi and the host, poly(ADP-ribose) glycohydrolase activities are important players in the life cycle of Trypanosoma cruzi, emerging as a promising therapeutic target for the treatment of Chagas’ disease.     

Sex differences in antipredator tail-waving displays of the diurnal yellow-headed gecko Gonatodes albogularis from tropical forests of Colombia

Many vertebrate species show display behaviors when predators are in their vicinity. Some of these displays may inform the predator of the improbability of capturing the prey (i.e., pursuit-deterrent displays) and are potentially advantageous to both predator and prey. Here we present data on a tail display performed by Gonatodes albogularis, a diurnal tropical gecko. We performed transect surveys in three habitats near Bogotá in Colombia. Geckos detected during transects were approached by the observer in a standardized way, and details of their tail-waving displays were recorded. In control recordings animals were watched from a distant site without approaching them. Results showed sexual differences in tail-waving display: when approached by the observer, males performed this behavior more frequently than females. We found no significant differences between males and females in flight-initiation distances and height above the substratum when they were initially located. Results also showed that males displayed more frequently when approached than when the simulated predator remained stationary. We interpret these results as evidence that the display functions as a pursuit-deterrent signal to potential predators. However, as some tail displays were performed in the presence of conspecifics, the display may also have a social function.     

Synthesis and structure-activity relationship of 2-(aminoalkyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives: a novel series of 5-HT(2A/2C) receptor antagonists. Part 2.

Following the programme started at Janssen Research Foundation searching for 5-HT(2A/2C) antagonists, we now report on the synthesis of a series of substituted 2-(Dimethylaminomethyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives. The 5-HT(2A), 5-HT(2C) and H(1) receptor affinities as well as the mCPP antagonistic activity of the compounds synthesised is described.