Intestinal Cell Tight Junctions Limit Invasion of Candida albicans through Active Penetration and Endocytosis in the Early Stages of the Interaction of the Fungus with the Intestinal Barrier

C. albicans is a commensal yeast of the mucous membranes in healthy humans that can also cause disseminated candidiasis, mainly originating from the digestive tract, in vulnerable patients. It is necessary to understand the cellular and molecular mechanisms of the interaction of C. albicans with enterocytes to better understand the basis of commensalism and pathogenicity of the yeast and to improve the management of disseminated candidiasis. In this study, we investigated the kinetics of tight junction (TJ) formation in parallel with the invasion of C. albicans into the Caco-2 intestinal cell line. Using invasiveness assays on Caco-2 cells displaying pharmacologically altered TJ (i.e. differentiated epithelial cells treated with EGTA or patulin), we were able to demonstrate that TJ protect enterocytes against invasion of C. albicans. Moreover, treatment with a pharmacological inhibitor of endocytosis decreased invasion of the fungus into Caco-2 cells displaying altered TJ, suggesting that facilitating access of the yeast to the basolateral side of intestinal cells promotes endocytosis of C. albicans in its hyphal form. These data were supported by SEM observations of differentiated Caco-2 cells displaying altered TJ, which highlighted membrane protrusions engulfing C. albicans hyphae. We furthermore demonstrated that Als3, a hypha-specific C. albicans invasin, facilitates internalization of the fungus by active penetration and induced endocytosis by differentiated Caco-2 cells displaying altered TJ. However, our observations failed to demonstrate binding of Als3 to E-cadherin as the trigger mechanism of endocytosis of C. albicans into differentiated Caco-2 cells displaying altered TJ.     

Recessive Mutations in COL25A1 Are a Cause of Congenital Cranial Dysinnervation Disorder

Abnormal ocular motility is a common clinical feature in congenital cranial dysinnervation disorder (CCDD). To date, eight genes related to neuronal development have been associated with different CCDD phenotypes. By using linkage analysis, candidate gene screening, and exome sequencing, we identified three mutations in collagen, type XXV, alpha 1 (COL25A1) in individuals with autosomal-recessive inheritance of CCDD ophthalmic phenotypes. These mutations affected either stability or levels of the protein. We further detected altered levels of sAPP (neuronal protein involved in axon guidance and synaptogenesis) and TUBB3 (encoded by TUBB3, which is mutated in CFEOM3) as a result of null mutations in COL25A1. Our data suggest that lack of COL25A1 might interfere with molecular pathways involved in oculomotor neuron development, leading to CCDD phenotypes.     

Childhood environmental harshness predicts coordinated health and reproductive strategies: A cross-sectional study of a nationally representative sample from France

There is considerable variation in health and reproductive behaviours within and across human populations. Drawing on principles from Life History Theory, psychosocial acceleration theory predicts that individuals developing in harsh environments decrease their level of somatic investment and accelerate their reproductive schedule. Although there is consistent empirical support for this general prediction, most studies have focused on a few isolated life history traits and few have investigated the way in which individuals apply life strategies across reproductive and somatic domains to produce coordinated behavioural responses to their environment. In our study, we thus investigate the impact of childhood environmental harshness on both reproductive strategies and somatic investment by applying structural equation modeling (SEM) to cross-sectional survey data obtained in a representative sample of the French population (n = 1015, age: 19–87 years old, both genders). This data allowed us to demonstrate that (i) inter-individual variation in somatic investment (e.g. effort in looking after health) and reproductive timing (e.g. age at first birth) can be captured by a latent fast-slow continuum, and (ii) faster strategies along this continuum are predicted by higher childhood harshness. Overall, our results support the existence of a fast-slow continuum and highlight the relevance of the life history approach for understanding variations in reproductive and health related behaviours.     

Treatment of Chronic Experimental Autoimmune Encephalomyelitis with Epigallocatechin-3-Gallate and Glatiramer Acetate Alters Expression of Heme-Oxygenase-1

We previously demonstrated that epigallocatechin-3-gallate (EGCG) synergizes with the immunomodulatory agent glatiramer acetate (GA) in eliciting anti-inflammatory and neuroprotective effects in the relapsing-remitting EAE model. Thus, we hypothesized that mice with chronic EAE may also benefit from this combination therapy. We first assessed how a treatment with a single dose of GA together with daily application of EGCG may modulate EAE. Although single therapies with a suboptimal dose of GA or EGCG led to disease amelioration and reduced CNS inflammation, the combination therapy had no effects. While EGCG appeared to preserve axons and myelin, the single GA dose did not improve axonal damage or demyelination. Interestingly, the neuroprotective effect of EGCG was abolished when GA was applied in combination. To elucidate how a single dose of GA may interfere with EGCG, we focused on the anti-inflammatory, iron chelating and anti-oxidant properties of EGCG. Surprisingly, we observed that while EGCG induced a downregulation of the gene expression of heme oxygenase-1 (HO-1) in affected CNS areas, the combined therapy of GA+EGCG seems to promote an increased HO-1 expression. These data suggest that upregulation of HO-1 may contribute to diminish the neuroprotective benefits of EGCG alone in this EAE model. Altogether, our data indicate that neuroprotection by EGCG in chronic EAE may involve regulation of oxidative processes, including downmodulation of HO-1. Further investigation of the re-dox balance in chronic neuroinflammation and in particular functional studies on HO-1 are warranted to understand its role in disease progression.     

Biologie des Eleonorenfalken (Falco eleonorae) 3. Parasitenbefall w?hrend der Brutzeit und Jugendentwicklung

Summary Adult falcons were found to be parasitized byLeucocytozoon toddi and a microfilaria (19%). The hippoboscid fly,Ornithophila gestroi is found in 74%, the Mallophaga,Laemobothrion tinnunculi andDegeeriella rufa in 84% rsp. 77% and the tick,Haemaphysalis numidiana in 62% of adult falcons. The fluctuation of parasitaemia within the breeding season and during growth of the nestlings is described for adult and juvenile falcons respectively.     

Sphagnum physiological responses to elevated temperature,nitrogen, CO2 and low moisture in laboratory and in situ microhabitats: a review

Aquatic Ecology - Sphagnum mosses are considered peatland engineers because of their ability to create conditions inducing carbon accumulation. Here, we report on a review of the effects of four...     

Centrosomes promote timely mitotic entry in C. elegans embryos

Several mitotic regulators, including Cyclin B1/Cdk1, are present at centrosomes prior to mitosis onset, but it is unclear whether centrosomes promote mitotic entry in vivo. Here we developed a sensitive assay in C. elegans embryos for the temporal analysis of mitotic entry, in which the male and female pronuclei undergo asynchronous entry into mitosis when separated from one another. Using this assay, we found that centrosome integrity is necessary for timing mitotic entry. Centrosomes do not function in this instance through their ability to nucleate microtubules. Instead, centrosomes serve to focus the Aurora A kinase AIR-1, which is essential for timely mitotic entry. Furthermore, analysis of embryos in which centrosomes and pronuclei are detached from one another demonstrates that centrosomes are sufficient to promote mitosis onset. Together, our findings support a model in which centrosomes serve as integrative centers for mitotic regulators and thus trigger mitotic entry in a timely fashion.