Galectin-3, histone deacetylases, and Hedgehog signaling:Possible convergent targets in schistosomiasis-induced liver fibrosis

Schistosomiasis affects approximately 240 million people in the world. Schistosoma mansoni eggs in the liver induce periportal fibrosis and hepatic failure driven by monocyte recruitment and macrophage activation, resulting in robust Th2 response. Here, we suggested a possible involvement of Galectin-3 (Gal-3), histone deacetylases (HDACs), and Hedgehog (Hh) signaling with macrophage activation during Th1/Th2 immune responses, fibrogranuloma reaction, and tissue repair during schistosomiasis. Gal-3 is highly expressed by liver macrophages (Kupffer cells) around Schistosoma eggs. HDACs and Hh regulate macrophage polarization and hepatic stellate cell activation during schistosomiasis-associated fibrogenesis. Previously, we demonstrated an abnormal extracellular matrix distribution in the liver that correlated with atypical monocyte-macrophage differentiation in S. mansoni-infected, Gal-3-deficient (Lgals3-/-) mice. New findings explored in this review focus on the chronic phase, when wild-type (Lgals3+/+) and Lgals3-/- mice were analyzed 90 days after cercariae infection. In Lgals3-/- infected mice, there was significant inflammatory infiltration with myeloid cells associated with egg destruction (hematoxylin and eosin staining), phagocytes (specifically Kupffer cells), numerically reduced and diffuse matrix extracellular deposition in fibrotic areas (Gomori trichrome staining), and severe disorganization of collagen fibers surrounding the S. mansoni eggs (reticulin staining). Granuloma-derived stromal cells (GR cells) of Lgals3-/- infected mice expressed lower levels of alpha smooth muscle actin (α-SMA) and eotaxin and higher levels of IL-4 than Lgals3+/+ mice (real-time PCR). The relevant participation of macrophages in these events led us to suggest distinct mechanisms of activation that culminate in defective fibrosis in the liver of Lgals3-/- infected mice. These aspects were discussed in this review, as well as the possible interference between Gal-3, HDACs, and Hh signaling during progressive liver fibrosis in S. mansoni-infected mice. Further studies focused on macrophage roles could elucidate these questions and clear the potential utility of these molecules as antifibrotic targets

Human plague: An old scourge that needs new answers

Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague’s resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a “One Health” approach

ELECTRICAL ACTIVITY OF GRAIN BOUNDARIES IN SILICON BY THE S.T.E.B.I.C. METHOD

In order to be able to analyse in TEM-STEM the crystallochemistry of recombining defects in p-type polysilicon (L = 100 µm), we have developed the scanning transmission electron beam induced current technique (STEBIC) originally proposed by Sparrow and Valdre. The key point is the making of a thin Schottky diode which must be transparent to electrons. This is realized by means of an Al-Ga ohmic contact, ion milling and an Al or Ag Schottky junction. Under such conditions an optimum lateral resolution of 100 nm is obtained and transmission imaging as well as diffraction , microdiffraction, X-ray microanalysis and EELS can be carried out concurrenty

Impurity-induced microstructure of grain boundaries in cast silicon. Incidence on electrical properties

The role of impurities in polysilicon for photocell has been investigated. Aluminium and carbon residual impurities in the Bridgman and HEM materials were particularly considered. The combination of local electrical, chemical and structural information with high spatial resolution, specifically in transmission electron microscopy, allowed to correlate the crystallography and chemistry with the electrical activity and barriers at grain boundaries. For aluminium it was shown that GB electrical property depends on the localization and environment of this dopant. The different ways for carbon to impair electrical properties are described. The correlation with other impurities and specially oxygen are considered and finally the predominant role of impurities is pointed out.Le rôle des impuretés dans le silicium polycristallin pour photopile est analysé et tout particulièrement pour 1'aluminium et le carbone, impuretés résiduelles des méthodes Bridgman et HEM. Par combinaison des informations locales, électriques, chimiques et structurales, essentiellement en microscopie électronique en transmission, il est possible de relier l'activité et les barrières électriques à la cristallochimie du joint. Dans le cas de l'aluminium, il est montré que l'activité électrique du joint dépend de la localisation et de l'environnement du dopant. Par ailleurs, les différentes façons dont le carbone dégrade les propriétés électriques sont décrites. On considère les corrélations avec les autres impuretés dont l'oxygène et finalement le rôle prédominant des impuretés est souligné

ORIENTATION RELATIONSHIPS, MICROSTRUCTURE AND ELECTRICAL BEHAVIOUR OF GRAIN BOUNDARIES IN CERAMIC SUPERCONDUCTORS

The relationships between the crystallochemistry and the local electrical behaviour of grain boundaries in cuprate superconductors are considered. It is shown that the number of GBs with low electrical barriers should be drastically enhanced in order to increase the critical current. This could be reached by specific treatments to favour distributions of GBs including in particular low-energy coincidence [001] tilt boundaries.On considère les relations entre la cristallochimie et le comportement électrique local des joints de grains dans les cuprates supraconducteurs. On montre qu'afin d'augmenter le courant critique la proportion de joints présentant des barrières électriques faibles doit être nettement augmentée. Il convient de favoriser une distribution de joints contenant en particulier des joints de flexion [001] de faible énergie grâce à des traitements spécifiques

STRUCTURE AND LOCAL ELECTRICAL PROPERTIES OF GRAIN BOUNDARIES IN POLYCRYSTALLINE SEMICONDUCTORS

The electrical properties of polycrystalline semiconductors are strongly related to their intergranular microstructures. It is first shown how the electrical behaviour of carriers can be basically deduced from the electronic structure of simple interfaces. Experimentally, bulk methods do not have usually a sufficient spatial resolution and do not permit a direct correlation between the local structure and the electrical properties. Local investigations, especially by in situ techniques in transmission electron microscopy are reported. Finally the key role of the distribution of the different types of boundaries to relate the local properties to the bulk behaviour is underlined.Les propriétés électriques des semiconducteurs polycristallins dépendent largement de la microstructure intergranulaire. Le comportement des porteurs peut être déduit de la structure électronique des interfaces simples. Les méthodes expérimentales globales n'ont pas, en général, une résolution spatiale suffisante et elles ne donnent pas une corrélation directe entre la structure locale et les propriétés électriques. Nous considérons les différentes informations locales obtenues principalement en microscopie électronique en transmission. Enfin, nous montrons que pour remonter des propriétés locales au comportement du matériau massif la distribution des différents types de joints est un paramètre essentiel

Low temperature semi-quantitative analysis of local electrical field in silicon diode by transmission electron microscopy

The local electric behaviour of IMPATT diodes was studied by scanning transmission electron beam induced current in cross-section method (X-STEBIC). This technique of induced current measurement makes it possible to probe the depletion zone of a junction with the beam of a transmission electron microscope. Two series of experiments were carried out. The X-STEBIC signal was analyzed according to the sample thickness and under different electrical polarizations. Moreover, these measurements were done and compared at room and low temperature (≅110 K). From these data, simulations of X-STEBIC profile allowed us to determine the main physical parameters brought into play in the signal formation. We have shown that, in the vicinity of the junction, the intensity of the induced current partly depends on the avalanche effect. The kinetic energy of the minority carriers generated by the electron beam is sufficient to induce collisions in cascade, even when the junction is not polarized. At low temperature, surface recombination has an essential role on the lateral resolution of the X-STEBIC method. By choosing carefully the range of sample thickness and by positioning the probe in the field of the diode, it is possible to optimize the resolution. Surface recombination annihilates the diffusion of the carriers so that the STEBIC image becomes a true image of the electric field. Consequently, semi-quantitative physical data can be obtained on the junction field

ELECTRICAL ACTIVITY OF GRAIN BOUNDARIES IN SILICON GROWN WITH AN ALUMINIUM CONTENT GRADIENT

In order to discriminate between the role of the structure and chemistry on the electrical activity of boundaries, p-type silicon bicrystals, characterized by a chemical gradient in aluminium from bottom to top of the ingot, were grown by a directional solidification method. The crystallographical and chemical analysis of symmetrical tilt boundaries namely Σ9, 13 and 25 was carried out by TEM and STEM X-ray spectroscopy. The electrical activity was studied by the scanning transmission electron beam induced current technique (STEBIC) which allowed the direct correlation with the microstructure to be achieved. It is shown that these coincidence tilt boundaries do not show intrinsic activity and that their behaviour is related to chemical decoration. The specific electrical activity of each type of decoration is considered.Afin de déterminer l'importance relative de la structure et de la chimie des joints sur leur activité électrique, nous avons élaboré par solidification directionnelle des bicristaux de silicium de type p dotés d'un gradient de composition en aluminium le long du lingot. La cristallochimie des joints symétriques de flexion Σ9, 13 et 25 a été étudiée par TEM et microanalyse STEM. L'activité électrique a été observée par la technique du courant induit sur lame mince, en microscopie électronique en transmission à balayage (STEBIC), qui permet la corrélation directe avec la microstructure. On montre que les joints symétriques de flexion ne présentent pas d'activité électrique intrinsèque et qu'ils ne sont recombinants que lorsqu'ils sont décorés. On décrit le comportement spécifique de chaque type de décoration

The electrical activity of IMPATT diodes on a nanometric scale by X-STEBIC method

The Scanning Transmission Electron Beam Induced Current Technique (STEBIC) was adapted to allow the analysis of local electrical activity in semiconductor diodes. This technique enabled us to analyse the in situ properties of IMPATT junctions (IMPact Avalanche Transit Time: which are Si doped $p^+/p/n/n^+$ multijunctions). The samples were thinned down as cross-sections, to be observed and analysed in transmission electron microscopy. The current induced by the electron beam was collected by the depleted zone. By synchronising measurements with each scan of the electron beam, the electrical activity can be viewed at a very local scale. The STEBIC signal was simulated by using a model of drift- diffusion. The prevailing role of the recombination rate on the form of the STEBIC profile was evidenced. We found that the spatial resolution of this method depends on the thickness of the sample and on the zone where the measurement is taken. We show that the spatial resolution of this method is optimal when the electron beam is localised in the p/n depleted zone. In thin areas, the maximum spatial resolution is calculated to be $\le 20$ nm. Outside the electric field the transport phenomena are governed by the diffusion of carriers and the signal width is widened