Description: The present paper reviews the literature related to the life cycle of the prymnesiophyte Phaeocystis and its controlling factors and proposes novel hypotheses based on unpublished observations in culture and in the field. We chiefly refer to P. globosa Scherffel as most of the observations concern this species. P. globosa exhibits a complex alternation between several types of free-living cells (non-motile, flagellates, microzoopores and possibly macrozoospores) and colonies for which neither forms nor pathways have been completely identified and described. The different types of Phaeocystis cells were reappraised on the basis of existing microscopic descriptions complemented by unpublished flow cytometric investigations. This analysis revealed the existence of at least three different types of free-living cells identified on the basis of a combination of size, motility and ploidy characteristics: non-motile cells, flagellates and microzoospores. Their respective function within Phaeocystis life cycle, and in particular their involvement in colony formation is not completely understood. Observational evidence shows that Phaeocystis colonies are initiated at the early stage of their bloom each by one free-living cell. The mechanisms controlling this cellular transformation are still uncertain due to the lack of information on the overwintering Phaeocystis fomms and on the cell type responsible for colony induction. The existence of haploid microzoospores released from senescent colonies gives however some support to sexuality involvement at some stages of colony formation. Once colonies are formed, at least two mechanisms were identified as responsible of the spreading of colony form: colony multiplication by colonial division or budding and induction of new colony from colonial cells released in the external medium after colony disruption. The latter mechanism was clearly identified, involving at least two successive cell differentiations in the following sequence: motility development, subsequent flagella loss and settlement to a surface, mucus secretion and colony formation, colonial cell division and colony growth. Aggregate formation, cell motility development and subsequent emigration from the colonies, release of non-motile cells after colony lysis on the other hand, were identified as characteristics for termination of Phaeocystis colony development. These pathways were shown to occur similarly in natural environments. In the early stages of the bloom however, many recently-formed colonies were found on the setae of Chaetoceros spp, suggesting this diatom could play a key-rôle in Phaeocystis bloom inception. Analysis of the possible environmental factors regulating the transition between the different phases of the life cycle, suggested that nutrient status and requirement of a substrate for attachment of free-living cells would be essential for initiation of the colonial form. Physical constraints obviously would be important in determining colony shape and fragmentation although autogenic factors cannot be excluded. Some evidence exists that nutrients regulate colony division, while temperature and nutrient stress would stimulate cell emigration from the colonies.

Description: The objective of COMWEB was to develop efficient analytical, numerical and experimental methods for assessing and predicting the effects of nutrient (N, P, Si) supply on the stability and persistence of pelagic food web structure and function in coastal waters. The experimental comparative work included a geographic gradient covering Baltic, Mediterranean, and NE Atlantic waters and a NE Atlantic gradient in state of eutrophication. COMWEB has been an experimental approach to coastal eutrophication, studying effects of enhanced nutrient supply on components and flows of the entire lower pelagic food web. Flow network representations of pelagic food webs has been a framework of data reduction and flows were established by sophisticated inverse modelling. Fundamental information on physiological properties of functional key species in the pelagic food web was used to constrain flow estimations. A main conclusion derived from the flow networks was that very little energy and materials were transferred from the microbial food web to the main food chain. The lower food web could therefore be described as two parallel food chains with relatively limited interaction between heterotrophic groups. Short-term effects of nutrient perturbations were examined in mesocosms along the geographic gradient. The response was comparable in all systems, with a stronger effect on the activity and biomass of autotrophic groups than those of heterotrophic ones. Mediterranean waters showed much lower autotrophic biomass response than Baltic and NE Atlantic waters, which responded almost equally. The response of primary production was, however, more comparable. High phytoplankton lysis rate explained this low accumulation of biomass in Mediterranean waters. The study of Atlantic coastal waters of different eutrophic states revealed that the ecological response was higher in the closed nutrient perturbed mesocosms than in open systems exposed for 〉4 summer months (summer/autumn season). The Atlantic lagoon evolved gradually from the natural oligotrophic situation towards the more eutrophicated North Sea during fertilisation. The responses observed on seasonal and long-term scale (〉10 years) may therefore be equal. The differences between short-term (weeks) and intermediate-term (seasonal) responses is most likely a result of the different time scales of perturbation and observation and the variable exchange rates with surrounding waters (water dilution rate). The analysis of pelagic flow networks provided a framework of diagnostic criteria for state and quality assessment of coastal waters. The nutrient loading rates related better to estimates of biotic fluxes than to concentrations of biotic compartments and total nutrients. On the contrary, the concentration of biotic compartments, or the biomasses, related better to total nutrient concentrations. Primary production, mesozooplankton grazing and growth, fraction of primary production consumed by grazers, bacterial production relative to primary production, cycling indices, and path lengths were all well related to nutrient loading rate. Autotrophic biomass, ratio of autotrophic to heterotrophic biomass, and fraction of pico-cyanobacteria of total autotrophic biomass were all related to total nutrients. Some of these variables, which responded equally in all systems, have the potential of becoming unified response functions in a management model for European coastal waters. COMWEB has provided further insight into the mechanisms behind coastal eutrophication. A main achievement is the conceptual framework for unified response functions, important components of management models for nutrient emission to coastal waters.

Description: Author(s): C. Beaufils, W. Redjem, E. Rousseau, V. Jacques, A. Yu. Kuznetsov, C. Raynaud, C. Voisin, A. Benali, T. Herzig, S. Pezzagna, J. Meijer, M. Abbarchi, and G. Cassabois We addressed the carrier dynamics in so-called G-centers in silicon (consisting of substitutional-interstitial carbon pairs interacting with interstitial silicons) obtained via ion implantation into a silicon-on-insulator wafer. We performed detailed photoluminescence experiments as a function of ex... [Phys. Rev. B 97, 035303] Published Tue Jan 09, 2018

Description: Pulmonary fibrosis is a progressive disease with unknown etiology that is characterized by extensive remodeling of the lung parenchyma, ultimately resulting in respiratory failure. Lymphatic vessels have been implicated with the development of pulmonary fibrosis, but the role of the lymphatic vasculature in the pathogenesis of pulmonary fibrosis remains enigmatic. Here we show in a murine model of pulmonary fibrosis that lymphatic vessels exhibit ectopic mural coverage and that this occurs early during the disease. The abnormal lymphatic vascular patterning in fibrotic lungs was driven by expression of platelet-derived growth factor B (PDGF-B) in lymphatic endothelial cells and signaling through platelet-derived growth factor receptor (PDGFR)–β in associated mural cells. Because of impaired lymphatic drainage, aberrant mural cell coverage fostered the accumulation of fibrogenic molecules and the attraction of fibroblasts to the perilymphatic space. Pharmacologic inhibition of the PDGF-B/PDGFR-β signaling axis disrupted the association of mural cells and lymphatic vessels, improved lymphatic drainage of the lung, and prevented the attraction of fibroblasts to the perilymphatic space. Our results implicate aberrant mural cell recruitment to lymphatic vessels in the pathogenesis of pulmonary fibrosis and that the drainage capacity of pulmonary lymphatics is a critical mediator of fibroproliferative changes.

Description: Background Most non-small-cell lung cancer (NSCLC) patients receive cisplatin-based chemotherapy though clinical response is restricted to a subset of patients. DNA repair protein levels are possible surrogates for cisplatin-induced DNA adduct (and subsequent cell death) repair efficiency and thus molecular determinants of therapeutic efficacy. The International Adjuvant Lung Trial (IALT)-Bio study previously suggested ERCC1 and MSH2 as predictive of cisplatin-based therapeutic benefit. Patients and methods DNA repair protein expression (XPF, BRCA1, ERCC1, MSH2, p53, PARP1, and ATM) was assessed by immunohistochemistry on a large subset of patients ( N  = 769) from the IALT trial. Tissue Microarray slides were digitally scanned and signal quantified by user-defined macros. Statistical analyses (univariate and multivariate) of 5-year disease-free survival (DFS) and 5-year overall survival used binary cut-offs ( H score low/high expression). Results In patients with squamous cell carcinoma (SCC), ATM, p53, PARP1, ERCC1, and MSH2 displayed significant (borderline) predictive values, mainly on DFS with chemotherapy efficacy limited to low marker levels. Adenocarcinoma (ADC) results were not significant. BRCA1 and XPF were not significant for predictive modeling in either SCC or ADCs. Conclusion Here predictive utility of DNA repair enzymes co-segregates with SCC histology, focusing their predictive value to this histological subclass of NSCLC. Distinct mechanisms of chemotherapeutic response or resistance might exist among histological subclasses of solid tumors.

Description: p21-activated kinase 1 (PAK1) and PAK3 belong to group I of the PAK family and control cell movement and division. They also regulate dendritic spine formation and maturation in the brain, and play a role in synaptic transmission and synaptic plasticity. PAK3, in particular, is known for its implication in X-linked intellectual disability. The pak3 gene is expressed in neurons as a GTPase-regulated PAK3a protein and also as three splice variants which display constitutive kinase activity. PAK1 regulation is based on its homodimerization, forming an inactive complex. Here, we analyze the PAK3 capacity to dimerize and show that although PAK3a is able to homodimerize, it is more likely to form heterodimeric complexes with PAK1. We further show that two intellectual disability mutations impair dimerization with PAK1. The b and c inserts present in the regulatory domain of PAK3 splice variants decrease the dimerization but retain the capacity to form heterodimers with PAK1. PAK1 and PAK3 are co-expressed in neurons, are colocalized within dendritic spines, co-purify with post-synaptic densities, and co-immunoprecipitate in brain lysates. Using kinase assays, we demonstrate that PAK1 inhibits the activity of PAK3a but not of the splice variant PAK3b in a trans-regulatory manner. Altogether, these results show that PAK3 and PAK1 signaling may be coordinated by heterodimerization.

Description: Chronic lymphocytic leukemia (CLL) outgrowth depends on signals from the microenvironment. We have previously found that in vitro reconstitution of this microenvironment induces specific variant isoforms of the adhesion molecule CD44, which confer human CLL with high affinity to hyaluronan (HA). Here, we determined the in vivo contribution of standard CD44 and its variants to leukemic B-cell homing and proliferation in Tcl1 transgenic mice with a B-cell–specific CD44 deficiency. In these mice, leukemia onset was delayed and leukemic infiltration of spleen, liver, and lungs, but not of bone marrow, was decreased. Competitive transplantation revealed that CLL homing to spleen and bone marrow required functional CD44. Notably, enrichment of CD44v6 variants particularly in spleen enhanced CLL engraftment and proliferation, along with increased HA binding. We recapitulated CD44v6 induction in the human disease and revealed the involvement of MAPK and NF-B signaling upon CD40 ligand and B-cell receptor stimulation by in vitro inhibition experiments and chromatin immunoprecipitation assays. The investigation of downstream signaling after CD44v6-HA engagement uncovered the activation of extracellular signal-regulated kinase and p65. Consequently, anti-CD44v6 treatment reduced leukemic cell proliferation in vitro in human and mouse, confirming the general nature of the findings. In summary, we propose a CD44-NF-B-CD44v6 circuit in CLL, allowing tumor cells to gain HA binding capacity and supporting their proliferation.