Founder effects drive the genetic structure of passively dispersed aquatic invertebrates

Populations of passively dispersed organisms in continental aquatic habitats typically show high levels of neutral genetic differentiation despite their high dispersal capabilities. Several evolutionary factors, including founder events, local adaptation, and life cycle features such as high population growth rates and the presence of propagule banks, have been proposed to be responsible for this paradox. Here, we have modeled the colonization process to assess the impact of migration rate, population growth rate, population size, local adaptation and life-cycle features on the population genetic structure in these organisms. Our simulations show that the strongest effect on population structure are persistent founder effects, resulting from the interaction of a few population founders, high population growth rates, large population sizes and the presence of diapausing egg banks. In contrast, the role of local adaptation, genetic hitchhiking and migration is limited to small populations in these organisms. Our results indicate that local adaptation could have different impact on genetic structure in different groups of zooplankters

Diapause as escape strategy to exposure to toxicants: response of Brachionus calyciforus to arsenic

Invertebrate organisms commonly respond to environmental fluctuation by entering diapause. Production of diapause in monogonont rotifers involves a previous switch from asexual to partial sexual reproduction. Although zooplankton have been used in ecotoxicological assays, often their true vulnerability to toxicants is underestimated by not incorporating the sexual phase. We experimentally analyzed traits involved in sexual reproduction and diapause in the cyclically parthenogenetic freshwater rotifer, Brachionus calyciflorus, exposed to arsenic, a metalloid naturally found in high concentrations in desert zones, focusing on the effectiveness of diapause as an escape response in the face of an adverse condition. Addition of sublethal concentrations of arsenic modified the pattern of diapause observed in the rotifer: investment in diapause with arsenic addition peaked earlier and higher than in non-toxicant conditions, which suggests that sexual investment could be enhanced in highly stressed environmental conditions by increased responsiveness to stimulation. Nevertheless, eggs produced in large amount with arsenic, were mostly low quality, and healthy-looking eggs had lower hatching success, therefore it is unclear whether this pattern is optimum in an environment with arsenic, or if rather arsenic presence in water bodies disturbs the optimal allocation of offspring entering diapause. We observed high accumulation of arsenic in organisms exposed to constant concentration after several generations, which suggests that arsenic may be accumulated transgenerationally. The sexual phase in rotifers may be more sensitive to environmental conditions than the asexual one, therefore diapause attributes should be considered in ecotoxicological assessment because of its ecological and evolutionary implications on lakes biodiversity

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Mycorhization précoce et croissance de deux types de matériel végétal de plantain (Musa AAB)

Les bananes et plantains constituent une source de devises et fournissent des aliments de base pour les populations du Cameroun, avec une production annuelle de 1 000 000 de tonnes de plantains et près de 700 000 tonnes de bananes dessert [1]. Cette culture, bien qu'en nette expansion, est soumise à de nombreuses contraintes abiotiques et biotiques qui peuvent, par ailleurs, être exacerbées par le manque de matériel de plantation de qualité. Des techniques de multiplication de bananiers in vitro et in planta ont été développées dans le but de mettre à la disposition des planteurs du matériel végétal homogène indemne de parasites et ravageurs. Ces vitroplants ou plants issus de fragments de tige (PIF) sont dépourvus des symbiotes naturels que sont les champignons mycorhiziens à arbuscules (MA). Ces micro-organismes forment à l'état naturel une association symbiotique avec les racines des végétaux. Dans cette symbiose, qui se traduit par l'apparition d'organes mixtes mycélium-racine appelés mycorhize, le champignon MA permet à la plante de mieux assimiler le phosphore et d'autres éléments nutritifs [2]. Il en résulte des gains de biomasse souvent importants. Les plants produits in vitro à partir de cultures de méristèmes ou in planta à partir des fragments de tige sont dépourvus de ces symbiotes qui peuvent cependant être réintroduits pendant la phase de sevrage avant la transplantation au champ [3], augmentant de la sorte leur croissance [4] ainsi que leur tolérance aux stress biotiques [5] et abiotiques [6]. Ce travail évalue la possibilité d'une mycorhization précoce de PIF et de vitroplants de plantain c.v. Bâtard (AAB, sous-groupe plantain) et mesure l'effet de cette mycorhization sur la croissance des plants

Hormonal control of plasminogen activator inhibitor-1 gene expression and production in human adipose tissue: stimulation by glucocorticoids and inhibition by catecholamines.

Plasma levels of type 1 plasminogen activator inhibitor (PAI-1), a risk factor for cardiovascular disease, are elevated in obese subjects, especially those with omental fat accumulation. We investigated the hormonal control of PAI-1 gene expression and secretion in cultured human adipose tissue. We more particularly focused on the effects of glucocorticoids, insulin, cAMP, and catecholamines in explants from the omental region. The addition of dexamethasone to the culture medium increased PAI-1 secretion in a time-dependent manner for up to 24 h. The stimulation by the glucocorticoid was preceded by a 2-fold rise in PAI-1 messenger ribonucleic acid levels between 4-8 h of culture. The effectiveness of the glucocorticoid was concentration dependent, with a half-maximal effect within a physiological range. This stimulation was also observed in sc fat, but dexamethasone-stimulated as well as basal PAI-1 secretion rates were always higher in omental fat. Unlike dexamethasone, 24-h insulin did not modify PAI-1 secretion while accelerating glucose consumption. In contrast, 24-h cAMP inhibited PAI-1 gene expression and protein production under basal conditions and in the presence of dexamethasone. This inhibition was already detectable after 1 h and was maximal after 4 h at the level of gene expression. It occurred in both omental and sc adipose tissues. Importantly, epinephrine dose dependently inhibited PAI-1 parameters, an effect that was reproduced by isoproterenol. Dexamethasone- and cAMP-induced changes in PAI-1 messenger ribonucleic acid abundance were similar in explants and isolated fat cells. In isolated stromal-vascular cells, only dexamethasone was effective. In conclusion, we provide evidence for a reciprocal regulation of PAI-1 by dexamethasone (positive effector) and cAMP/catecholamines (negative effectors) in cultured human adipose tissue. The stimulation by glucocorticoids could contribute to enhanced production of PAI-1 by adipose tissue and high plasma levels of PAI-1 associated with central obesity and thereby be a link between this disorder and cardiovascular disease. Impaired inhibition by catecholamines could also contribute, as in vivo adipose tissue responses to these hormones are usually blunted in obese individuals

Dietary fructans, but not cellulose, decrease triglyceride accumulation in the liver of obese Zucker fa/fa rats

This study was designed to compare the effects of dietary supplementation with nondigestible carbohydrates, differing in fermentability by colonic bacteria, on hepatic steatosis in growing obese Zucker rats. Male Zucker fa/fa rats were divided into three groups: a control group that received the basal diet, a fructan group that received 10 g highly fermented Synergy 1/100 g diet and a cellulose group that received 10 g poorly fermented Vivapur Microcrystalline cellulose/100 g diet. Rats consuming fructan had a lower energy intake, a lower body weight and less triacylglycerol accumulation in the liver as assessed in vivo by nuclear magnetic resonance (NMR) spectroscopy, and ex vivo by biochemical and histochemical analysis compared with the control and/or cellulose groups. The high fermentation of fructans compared with cellulose was reflected by greater cecal contents and by a twofold greater propionate concentration in the portal vein of rats fed fructan compared with those fed cellulose. By measuring the capacity of hepatocytes isolated from liver of Zucker rats to synthesize triglycerides or total lipids from different precursors, we showed that propionate, at the concentrations measured in the portal vein of rats treated with fructan, selectively decreased the incorporation of acetate into total lipids, a phenomenon that could contribute, along with the lower energy intake, to less triglyceride accumulation in the liver of obese Zucker rats fed dietary fructans