Film-thickness-dependent conduction in ordered Si quantum dot arrays.

In recent years, silicon nanostructures have been investigated extensively for their potential use in photonic and photovoltaic applications. So far, for silicon quantum dots embedded in SiO(2), control over inter-dot distance and size has only been observed in multiple bilayer stacks of silicon-rich oxides and silicon dioxide. In this work, for the first time the fabrication of spatially well-ordered Si quantum dots (QDs) in SiO(2) is demonstrated, without using the multilayer approach. This ordered formation, confirmed with TEM micrographs, depends on the thickness of the initially deposited sub-stoichiometric silicon oxide film. Grazing incidence x-ray diffraction confirms the crystallinity of the 5 nm QDs while photoluminescence shows augmented bandgap values. Low-temperature current-voltage measurements demonstrate film thickness and order-dependent conduction mechanisms, showing the transition from temperature-dependent conduction in randomly placed dots to temperature-independent tunnelling for geometrically ordered nanocrystals. Contrary to expectations from dielectric materials, significant conduction and photocarrier generation have been observed in our Si QDs embedded in SiO(2) demonstrating the possibility of forming initial film-thickness-controlled conductive films. This conduction via the silicon quantum dots in thick single layers is a promising result for integration into photovoltaic devices.

A Chiral fNIRS Spotlight on Cerebellar Activation in a Finger Tapping Task.

Functional Magnetic Resonance Imaging (fMRI) has been so far the golden standard to study the functional aspects of the cerebellum. In this paper, a low-cost alternative imaging, i.e. functional Near-Infrared Spectroscopy (fNIRS) is demonstrated to achieve successful measurements of the cerebellar hemodynamics towards the challenging observation of motor and cognitive processes at the cerebellar level. The excitation and reception optodes need to be properly placed to circumvent a major hindering from the shielding by the neck muscles. A simple experimental protocol, i.e. finger tapping task, was implemented to observe the subject's engagement and the presence of functional asymmetries. Marked differences among subjects with different levels of lateralization were clearly noticed in terms of activation and latencies, together with peaks in the hemodynamic response following neural activation. These preliminary results suggest also differences in the hemodynamic behavior between the brain and the cerebellum and encourage future and extended analysis in this direction.Clinical Relevance-This establishes the possibility to use a novel technique (fNIRS) to study cerebellar hemodynamics instead of fMRI.

Single-Trial Detection of Event-Related Potentials with Integral Shape Averaging: An Application to the Elusive N400.

The estimation of Event-Related Potentials (ERPs) from the ambient EEG is a difficult task, usually achieved through the synchronous averaging of an extensive series of trials. However, this technique has some caveats: the ERPs have to be strictly time-locked with similar shape, i.e. emitted with the same latency and the same profile, with minor fluctuations of their amplitudes. Also, the method requires a huge number of valid trials (~100) to efficiently raise the ERPs from the EEG trials. In the case of cognitive ERPs, as with the N400, the delivered stimulus has to be different for each trial, the latencies are varying, and the number of available trials is usually low. In this paper, an alternative method, coined Integral Shape Averaging (ISA) and its derivatives are detailed. ISA is robust to varying latencies and affine transforms of shape. Furthermore, a new method coined ISAD can be derived to extract ERPs even from a single trial experiment. The aim here is to illustrate the potential of ISAD for N400 component extraction on real EEG data, with emphasis on its general applicability for ERPs computation and its major assets like reduced experimental protocol. Some insights are also given on its potential use to study ERP variability, through shape and latency.Clinical Relevance- The proposed algorithm aims to be a helpful tool in clinical practice to analyze and interpret evoked responses in real experimental settings, especially for particularities in neurology.

Behavioural and biochemical alterations in gammarids as induced by chronic metallic exposures (Cd, Cu and Pb): Implications for freshwater biomonitoring.

In freshwater species, metal toxicity is usually assessed through short-term exposures, hence limiting the practical usefulness of biomarkers for monitoring long-term impacts on wildlife populations. This study investigates the biological alterations elicited by chronic metallic exposures in Gammarus fossarum using multi-level biomarkers. In aquaria, gammarids were exposed for 10 weeks to field-realistic concentrations of Cd, Cu or Pb (0.25, 1.5 or 5.0 µg/L). At the individual level, behavioural traits (respiration, locomotion and feeding) were compared between naive and chronically-exposed gammarids. At the cellular level, enzymatic activities involved in digestion, moult and cell stress were monitored after 2, 6 and 10 weeks of exposure in males and females to consider the temporal feature of their responses. Results showed that the inhibitory effects of Cd and Pb on respiration and locomotion disappeared in chronically-exposed gammarids, reflecting acclimation to maintain these processes, unlike Cu. Chronic Cu- and Pb-elicited feeding inhibition was associated with the inhibitions of digestion enzymes. Chitobiase was inhibited by Cu in males and, by Cd and Pb in females, suggesting gender-dependent disturbances in moulting. In both genders, Cd generated cellular stress by stimulating acidic phosphatase and peroxidase activities. To conclude, such cellular impairments and alterations in individual performances are likely to disturb individual growth, population dynamics and litter decomposition in the long-term. Besides, obtaining biological responses, common to metals or specific to a metal or a gender, supports the development of biomarkers highlighting long-term impacts of metals on the health of organisms and their associated ecological functions in natural environments.

Effects of marine noise pollution on Mediterranean fishes and invertebrates: A review.

Marine noise pollution (MNP) can cause a multitude of impacts on many organisms, but information is often scattered and general outcomes difficult to assess. We have reviewed the literature on MNP impacts on Mediterranean fish and invertebrates. Both chronic and acute MNP produced by various human activities - e.g. maritime traffic, pile driving, air guns - were found to cause detectable effects on intra-specific communication, vital processes, physiology, behavioral patterns, health status and survival. These effects on individuals can extend to inducing population- and ecosystem-wide alterations, especially when MNP impacts functionally important species, such as keystone predators and habitat forming species. Curbing the threats of MNP in the Mediterranean Sea is a challenging task, but a variety of measures could be adopted to mitigate MNP impacts. Successful measures will require more accurate information on impacts and that effective management of MNP really becomes a priority in the policy makers' agenda.

Endotoxin-induced myeloid-derived suppressor cells inhibit alloimmune responses via heme oxygenase-1.

Inflammation and cancer are associated with impairment of T-cell responses by a heterogeneous population of myeloid-derived suppressor cells (MDSCs) coexpressing CD11b and GR-1 antigens. MDSCs have been recently implicated in costimulation blockade-induced transplantation tolerance in rats, which was under the control of inducible NO synthase (iNOS). Herein, we describe CD11b+GR-1+MDSC-compatible cells appearing after repetitive injections of lipopolysaccharide (LPS) using a unique mechanism of suppression. These cells suppressed T-cell proliferation and Th1 and Th2 cytokine production in both mixed lymphocyte reaction and polyclonal stimulation assays. Transfer of CD11b+ cells from LPS-treated mice in untreated recipients significantly prolonged skin allograft survival. They produced large amounts of IL-10 and expressed heme oxygenase-1 (HO-1), a stress-responsive enzyme endowed with immunoregulatory and cytoprotective properties not previously associated with MDSC activity. HO-1 inhibition by the specific inhibitor, SnPP, completely abolished T-cell suppression and IL-10 production. In contrast, neither iNOS nor arginase 1 inhibition did affect suppression. Importantly, HO-1 inhibition before CD11b+ cell transfer prevented the delay of allograft rejection revealing a new MDSC-associated suppressor mechanism relevant for transplantation.

[Sentinel node and breast cancer: A state-of-the-art in 2019]. / Ganglion sentinelle et cancer du sein : où en est-on en 2019 ?

Since 1994 and Giuliano's description of sentinel lymph node technique, this procedure has considerably improved and is nowadays, one of the essential pillars in the management of breast cancer. Neoadjuvant chemotherapy (NAC) is effective on regional control, especially on axillary lymph node. Various learned societies recommend that the initial proved GS can be realized before (CNGOF 2010, Saint-Paul de Vence 2013, ESMO 2015, St-Gallen 2015, NCCN 2016) or after (ASCO 2014, ESMO 2015, Saint-Gallen 2015) CNA when the patient is considered like N0. In patients with initial lymph node involvement, GS searching it is not yet recommended. SLN detection before NAC remains an important prognostic factor especially in N+ patients before surgery. The purpose of this article was a reviewing of medical literature regarding possible indications for SLN detection and axillary dissection in patients with NAC according to sentinel lymph node status. The secondary objective was to put forward different perspectives and studies dealing with this subject. The complete pathological response appears to be an important selection criterion for proposing SLN to these patients and avoiding a "useless" AD. It is important to include patients in the trials to make recommendations progress on SLN after NAC and avoid a rate of uninjured AD.

Calnexin-dependent regulation of tunicamycin-induced apoptosis in breast carcinoma MCF-7 cells.

The endoplasmic reticulum (ER) has evolved specific mechanisms to ensure protein folding as well as the maintenance of its own homeostasis. When these functions are not achieved, specific ER stress signals are triggered to activate either adaptive or apoptotic responses. Here, we demonstrate that MCF-7 cells are resistant to tunicamycin-induced apoptosis. We show that the expression level of the ER chaperone calnexin can directly influence tunicamycin sensitivity in this cell line. Interestingly, the expression of a calnexin lacking the chaperone domain (DeltaE) partially restores their sensitivity to tunicamycin-induced apoptosis. Indeed, we show that DeltaE acts as a scaffold molecule to allow the cleavage of Bap31 and thus generate the proapoptotic p20 fragment. Utilizing the ability of MCF-7 cells to resist tunicamycin-induced apoptosis, we have characterized a molecular mechanism by which calnexin regulates ER-stress-mediated apoptosis in a manner independent of its chaperone functions but dependent of its binding to Bap31.

Activin and inhibin have antagonistic effects on ligand-dependent heteromerization of the type I and type II activin receptors and human erythroid differentiation.

Activins and inhibins belong to the transforming growth factor beta (TGF-beta)-like superfamily and exert their effects on a broad range of cellular targets by modulating cell differentiation and proliferation. Members of this family interact with two structurally related classes of receptors (type I and type II), both containing a serine/threonine kinase domain. When expressed alone, the type II but not the type I activin receptor can bind activin. However, the presence of a type I receptor is required for signaling. For TGF-beta1, ligand binding to the type II receptor results in the recruitment and transphosphorylation of the type I receptor. Transient overexpression of the two types of activin receptor results in ligand-independent receptor heteromerization and activation. Nevertheless, activin addition to the transfected cells increased complex formation between the two receptors, suggesting a mechanism of action similar to that observed for the TGF-beta receptor. In the present study, we generated a stable cell line, overexpressing the two types of activin receptor upon induction, in the human erythroleukemia cell line K562. We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. Using this stable line, we analyzed the effects of activin and inhibin on human erythroid differentiation. Our results indicate that activin signal transduction mediated through its type I and type II receptors results in an increase in the hemoglobin content of the cells and limits their proliferation. Finally, using cell lines that can be induced to overexpress ActRII and ActRIB or ActRIB only, we show that the inhibin antagonistic effects on activin-induced biological responses are mediated through a competition for the type II activin receptor but also require the presence of an inhibin-specific binding component.

Comparison in waterborne Cu, Ni and Pb bioaccumulation kinetics between different gammarid species and populations: Natural variability and influence of metal exposure history.

Kinetic parameters (uptake from solution and elimination rate constants) of Cu, Ni and Pb bioaccumulation were determined from two Gammarus pulex and three Gammarus fossrum wild populations collected from reference sites throughout France in order to assess the inter-species and the natural inter-population variability of metal bioaccumulation kinetics in that sentinel organism. For that, each population was independently exposed for seven days to either 2.5µgL-1 Cu (39.3nM), 40µgL-1 Ni (681nM) or 10µgL-1 Pb (48.3nM) in laboratory controlled conditions, and then placed in unexposed microcosms for a 7-day depuration period. In the same way, the possible influence of metal exposure history on subsequent metal bioaccumulation kinetics was addressed by collecting wild gammarids from three populations inhabiting stations contaminated either by Cd, Pb or both Pb and Ni (named pre-exposed thereafter). In these pre-exposed organisms, assessment of any changes in metal bioaccumulation kinetics was achieved by comparison with the natural variability of kinetic parameters defined from reference populations. Results showed that in all studied populations (reference and pre-exposed) no significant Cu bioaccumulation was observed at the exposure concentration of 2.5µgL-1. Concerning the reference populations, no significant differences in Ni and Pb bioaccumulation kinetics between the two species (G. pulex and G. fossarum) was observed allowing us to consider all the five reference populations to determine the inter-population natural variability, which was found to be relatively low (kinetic parameters determined for each population remained within a factor of 2 of the minimum and maximum values). Organisms from the population exhibiting a Pb exposure history presented reduced Ni uptake and elimination rate constants, whereas no influence on Ni kinetic parameters was observed in organisms from the population exhibiting an exposure history to both Ni and Pb. Furthermore Pb bioaccumulation kinetics were unaffected whatever the condition of pre-exposure in natural environment. Finally, these results highlight the complexity of confounding factors, such as metal exposure history, that influence metal bioaccumulation processes and showed that pre-exposure to one metal can cause changes in the bioaccumulation kinetics of other metals. These results also address the question of the underlying mechanisms developed by organisms to cope with metal contamination.

Ecotoxicoproteomic assessment of the functional alterations caused by chronic metallic exposures in gammarids.

Very few ecotoxicological studies have been performed on long-term exposure under controlled conditions, hence limiting the assessment of the impact of chronic and diffuse chemical pressures on the health of aquatic organisms. In this study, an ecotoxicoproteomic approach was used to assess the integrated response and possible acclimation mechanisms in Gammarus fossarum following chronic exposures to Cd, Cu or Pb, at environmentally realistic concentrations (i.e. 0.25, 1.5 and 5 µg/L respectively). After 10-week exposure, changes in protein expression were investigated in caeca of control and exposed males. Gel-free proteomic analyses allowed for the identification of 35 proteins involved in various biological functions, for which 23 were significantly deregulated by metal exposures. The protein deregulation profiles were specific to each metal, providing evidence for metal-specific action sites and responses of gammarids. Among the tested metals, Cu was the most toxic in terms of mortality, probably linked with persistent oxidative stress. Moulting and osmoregulation were the major biological functions affected by Cu in the long-term. In Pb-exposed gammarids, significant deregulations of proteins involved in immune response and cytoskeleton were observed. Reproduction appears to be strongly affected in gammarids chronically exposed to Cd or Pb. Besides, modified expressions of several proteins involved in energy transfer and metabolism highlighted important energetic reshuffling to cope with chronic metal exposures. These results support the fact that metallic pressures induce a functional and energetic cost for individuals of G. fossarum with potential repercussions on population dynamics. Furthermore, this ecotoxicoproteomic study offers promising lines of enquiry in the development of new biomarkers that could make evidence of long-term impacts of metals on the health of organisms.

Environmental relevance of laboratory-derived kinetic models to predict trace metal bioaccumulation in gammarids: Field experimentation at a large spatial scale (France).

Kinetic models have become established tools for describing trace metal bioaccumulation in aquatic organisms and offer a promising approach for linking water contamination to trace metal bioaccumulation in biota. Nevertheless, models are based on laboratory-derived kinetic parameters, and the question of their relevance to predict trace metal bioaccumulation in the field is poorly addressed. In the present study, we propose to assess the capacity of kinetic models to predict trace metal bioaccumulation in gammarids in the field at a wide spatial scale. The field validation consisted of measuring dissolved Cd, Cu, Ni and Pb concentrations in the water column at 141 sites in France, running the models with laboratory-derived kinetic parameters, and comparing model predictions and measurements of trace metal concentrations in gammarids caged for 7 days to the same sites. We observed that gammarids poorly accumulated Cu showing the limited relevance of that species to monitor Cu contamination. Therefore, Cu was not considered for model predictions. In contrast, gammarids significantly accumulated Pb, Cd, and Ni over a wide range of exposure concentrations. These results highlight the relevance of using gammarids for active biomonitoring to detect spatial trends of bioavailable Pb, Cd, and Ni contamination in freshwaters. The best agreements between model predictions and field measurements were observed for Cd with 71% of good estimations (i.e. field measurements were predicted within a factor of two), which highlighted the potential for kinetic models to link Cd contamination to bioaccumulation in the field. The poorest agreements were observed for Ni and Pb (39% and 48% of good estimations, respectively). However, models developed for Ni, Pb, and to a lesser extent for Cd, globally underestimated bioaccumulation in caged gammarids. These results showed that the link between trace metal concentration in water and in biota remains complex, and underlined the limits of these models, in their present form, to assess trace metal bioavailability in the field. We suggest that to improve model predictions, kinetic models need to be complemented, particularly by further assessing the influence of abiotic factors on trace metal uptake, and the relative contribution of the trophic route in the contamination of gammarids.

Expression of prolactin and its receptor in human lymphoid cells.

We have investigated whether human lymphoid cells are able to synthesize and secrete human PRL (hPRL) and to express PRL receptors. Metabolic labeling with [35S]methionine and immunoprecipitation of cell extracts from human mononuclear cells (MNC) and a human T lymphocyte cell line with an antiserum against hPRL revealed protein of M(r) 23,000, identical in size to pituitary hPRL. Dilution curves of lymphocyte immunoreactive hPRL were parallel to those obtained with pituitary hPRL in an immunoradiometric assay using two monoclonal antibodies against hPRL. Polymerase chain reaction experiments with primers located in the coding sequence of hPRL showed that the hPRL gene was expressed in MNC. Furthermore, cDNA cloning and sequence analysis indicated the presence of an extra 5' noncoding exon previously described for decidual hPRL. When MNCs were further separated into B cells, T cells, and monocytes, the expression of hPRL appeared to be mainly associated with the T lymphocyte fraction. The hPRL transcript was also detected in thymocytes and in a set of human lymphoid cell lines. Finally, polymerase chain reaction experiments revealed a ubiquitous distribution of PRL receptor gene expression in B cells, T cells, and monocytes. The presence of the receptor for PRL and production of PRL by T lymphocytes suggest a possible autocrine or paracrine effect of PRL in immune cell function.

Roles of pathway-specific and inhibitory Smads in activin receptor signaling.

Activins and other members of the transforming growth factor-beta-like superfamily of growth factors transduce their signals by interacting with two types of receptor serine/threonine kinases. The Smad proteins, a new family of intracellular mediators are involved in the signaling pathways of these receptors, but the initial stages of their activation as well as their specific functions remain to be defined. We report here that the pathway-specific Smad2 and 3 can form a complex with the activin receptor in a ligand-dependent manner. This complex formation is rapid but also transient. Indeed, soon after their association with the activin receptor, Smad2 and Smad3 are released into the cytoplasm where they interact with the common partner Smad4. These Smad complexes then mediate activin-induced transcription. Finally, we show that the inhibitory Smad7 can prevent the association of the two pathway-specific Smads with the activin receptor complex, thereby blocking the activin signal.

A biodynamic model predicting waterborne lead bioaccumulation in Gammarus pulex: Influence of water chemistry and in situ validation.

Metals bioaccumulated in aquatic organisms are considered to be a good indicator of bioavailable metal contamination levels in freshwaters. However, bioaccumulation depends on the metal, the species, and the water chemistry that influences metal bioavailability. In the laboratory, a kinetic model was used to describe waterborne Pb bioaccumulated in Gammarus pulex. Uptake and elimination rate constants were successfully determined and the effect of Ca(2+) on Pb uptake was integrated into the model. Thereafter, accumulated Pb concentrations in organisms were predicted with the model and compared with those measured in native populations from the Seine watershed (France). The predictions had a good agreement with the bioaccumulation levels observed in native gammarids and particularly when the effect of calcium was considered. To conclude, kinetic parameters experimentally derived for Pb in G. pulex are applicable in environmental conditions. Moreover, the consideration of the water's chemistry is crucial for a reliable interpretation of bioaccumulation.

Effect of experimental dermatophyte infection on cutaneous flora.

The cutaneous aerobic bacterial flora was monitored during the course of experimental dermatiphyte (ringworm) infections on the forearms of 9 volunteers. Micrococcaceae were identified by the new Baird-Parker classification with the aid of a replica-plating technique. There were significant differences in total populations but not in kinds of flora compared with control (opposite) forearms. The proportion of penicillin-resistant microorganisms, however increased the infection, to a degree which varied as to individual. All coccal groups were affected; resistant flora diminished when the fungus was no longer DETECTED. Staphylococci were more frequently isolated than micrococci on the infected areas, but Staphylococcus aureus was not found. Trends toward hierarchies in persistance and quantities IV were observed among the flora, with Staphylococcus subgroups II and dominating the infected sites. On both areas almost all diphtheroids were nonfluorescent, lipophilic, and lipolytic. One subject consistently carried Bacillus firmus; another's normal microbiota contained Alcaligenes faecalis.

JAK2 activation and cell proliferation induced by antibody-mediated prolactin receptor dimerization.

Cytokines that interact with receptors of the hematopoietin super-family have recently been reported to stimulate receptor-associated JAK tyrosine kinases, including PRL activation of JAK2. Unlike other tyrosine kinases, none of the JAK kinases has thus far been implicated in oncogenesis, and their involvement in growth signaling has not been established. Using the PRL-dependent pre-T-cell line Nb2, the present study provided a link between bivalent dimerization of a hematopoietin receptor and activation of its associated JAK kinase, and demonstrated a strong positive correlation between the mitogenic potency of a series of bivalent anti-PRL receptor antibodies and the degree of induced tyrosine phosphorylation of JAK2. Antibody bivalency was required for JAK2 phosphorylation. Monovalent anti-PRL receptor Fab fragments alone were inactive, but their activity could be partially restored by cross-linking with bivalent anti-Fab antibodies. Additional evidence for antibody-induced receptor dimerization was provided by a bell-shaped dose-response curve for the most potent receptor agonist, monoclonal antibody T6. This phenomenon is typically seen at pharmacological concentrations of bivalent ligands, when bound ligand molecules fail to adjoin a second receptor due to occupancy. The present study provided functional support for a model of PRL receptor triggering by ligand-induced receptor homodimerization and subsequent activation of the associated tyrosine kinase JAK2.

Use of heterologous DNA-based gene transfer to follow physiological, T3-dependent regulation of myosin heavy chain genes in Xenopus tadpoles.

In vivo gene transfer and RNase protection assay were used to follow thyroid hormone (T3)-dependent regulation of myosin heavy chain (myHC) genes in Xenopus tadpole dorsal muscle. One embryonic and one adult myHC form were measured by each approach. RNase protection assay showed that T3 decreased expression of endogenous embryonic mRNA (E3), but increased adult (A7) transcripts. Gene transfer showed that T3 exerted transcriptional effects on mammalian embryonic and adult myHc promoters injected into the same muscle. The kinetics and profiles of the transcriptional responses were superimposable on endogenous responses. The results strengthen the use of in vivo approaches for determining the roles of transcription factors and cis-regulatory sequences in integrated contexts.

Interruption of activin A autocrine regulation by antisense oligodeoxynucleotides accelerates liver tumor cell proliferation.

Administration of activin A, a member of the transforming growth factor-beta superfamily inhibits hepatocyte proliferation in vitro and reduces liver mass in vivo. However, a role of endogenous activin A in local growth modulation has not been established in any system. The aim of this study was to examine the production of activin A in the human hepatoma cell line HLF and to explore a possible autocrine role of activin as a cell growth inhibitor by blocking production of endogenous activin using antisense oligodeoxynucleotides. Administration of exogenous activin A suppressed HLF cell growth, and immunoreactive activin A was shown to be produced in the cells at confluency by Western blotting analysis. Cells were exposed to phosphorothioate-modified oligodeoxynucleotides, synthesized with antisense or randomly shuffled base sequences of activin betaA subunit messenger RNA, under serum-free conditions. Uptake of the oligodeoxynucleotides into the cells was confirmed by use of fluorescein isothiocyanate-labeled oligodeoxynucleotides. Administration of antisense oligodeoxynucleotides reduced activin A production as confirmed by both competitive PCR and Western blotting. Activin betaA antisense oligodeoxynucleotides significantly increased cell proliferation compared with controls. These findings are consistent with the existence of an autocrine role of activin A as an inhibitor of hepatocyte proliferation.