3D virtual histology of murine kidneys-high resolution visualization of pathological alterations by micro computed tomography

The increasing number of patients with end stage chronic kidney disease not only calls for novel therapeutics but also for pioneering research using convincing preclinical disease models and innovative analytical techniques. The aim of this study was to introduce a virtual histology approach using micro computed tomography (mu CT) for the entire murine kidney in order to close the gap between single slice planar histology and a 3D high resolution dataset. An ex vivo staining protocol based on phosphotungstic acid diffusion was adapted to enhance renal soft tissue x-ray attenuation. Subsequent CT scans allowed (i) the detection of the renal cortex, medulla and pelvis in greater detail, (ii) the analysis of morphological alterations, (iii) the quantification of the volume as well as the radio-opacity of these portions and (iv) the quantification of renal fibrotic remodeling based on altered radio-opacity using the unilateral ureteral obstruction model. Thus, virtual histology based on PTA contrast enhanced CT will in future help to refine the outcome of preclinical research on kidney associated murine disease models

Orthorexic tendencies are linked with difficulties with emotion identification and regulation.

Background: Orthorexia nervosa (ON) is characterised by an unhealthy obsession with healthy eating and while it is not recognised as an eating disorder (or any disorder), current research is exploring similarities and differences with such disorders. The literature has shown that individuals with eating disorders have difficulties identifying and describing emotions (known as alexithymia) as well as regulating them. However no research to date has looked at whether people with orthorexic tendencies also suffer from difficulties with emotions. In this paper, we refer to people with orthorexic tendencies but do not assume that their healthy eating is at a pathological level needing clinical attention. Methods: The current study examined this by asking 196 healthy adults with an interest in healthy eating to complete four questionnaires to measure ON (ORTO-15 - reduced to ORTO-7CS), eating psychopathology (EAT-26), alexithymia (TAS-20) and emotion dysregulation (DERS-16). Results: We found that difficulties identifying and regulating emotions was associated with symptoms of ON, similar to what is found in other eating disorders. We suggest that ON behaviours may be used as a coping strategy in order to feel in control in these participants who have poor emotion regulation abilities. Conclusions: Our results show that individuals with ON tendencies may share similar difficulties with emotions compared to other eating disorders. While important, our results are limited by the way we measured ON behaviours and we recommend that further research replicate our findings once a better and more specific tool is developed and validated to screen for ON characteristics more accurately

The Politics of Exhaustion and the Externalization of British Border Control. An Articulation of a Strategy Designed to Deter, Control and Exclude

In response to contemporary forms of human mobility, there has been a continued hardening of borders seeking to deter, control and exclude certain groups of people from entering nation states in Europe, North America and Australasia. Within this context, a disconcerting evolution of new and increasingly sophisticated forms of border control measures have emerged, which often play out within bilateral arrangements of “externalised” or “offshore” border controls. Drawing on extensive first‐hand field research among displaced people in Calais, Paris and Brussels in 2016–2019, this paper argues that the externalization of the British border to France is contingent upon a harmful strategy, which can be understood as the “politics of exhaustion.” This is a raft of (micro) practices and methods strategically aimed to deter, control and exclude certain groups of people on the move who have been profiled as “undesirable,” with a detrimental (un)intended impact on human lives

Discovery of a new class of inhibitors for the protein arginine deiminase type 4 (PAD4) by structure-based virtual screening

<p>Abstract</p> <p>Background</p> <p>Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology. Anticitrullinated protein autoantibody has been documented as a highly specific autoantibody associated with RA. Protein arginine deiminase type 4 (PAD4) is the enzyme responsible for catalyzing the conversion of peptidylarginine into peptidylcitrulline. PAD4 is a new therapeutic target for RA treatment. In order to search for inhibitors of PAD4, structure-based virtual screening was performed using LIDAEUS (Ligand discovery at Edinburgh university). Potential inhibitors were screened experimentally by inhibition assays.</p> <p>Results</p> <p>Twenty two of the top-ranked water-soluble compounds were selected for inhibitory screening against PAD4. Three compounds showed significant inhibition of PAD4 and their IC₅₀values were investigated. The structures of the three compounds show no resemblance with previously discovered PAD4 inhibitors, nor with existing drugs for RA treatment.</p> <p>Conclusion</p> <p>Three compounds were discovered as potential inhibitors of PAD4 by virtual screening. The compounds are commercially available and can be used as scaffolds to design more potent inhibitors against PAD4.</p

New insights into an ancient insect nose: the olfactory pathway of Lepismachilis y-signata (Archaeognatha: Machilidae)

Hexapods most likely derived from an aquatic ancestor, which they shared with crustaceans. During the transition from water to land, their sensory systems had to face the new physiological demands that terrestrial conditions impose. This process also concerns the sense of smell and, more specifically, detection of volatile, air-borne chemicals. In insects, olfaction plays an important role in orientation, mating choice, and food and host finding behavior. The first integration center of odor information in the insect brain is the antennal lobe, which is targeted by the afferents from olfactory sensory neurons on the antennae. Within the antennal lobe of most pterygote insects, spherical substructures called olfactory glomeruli are present. In order to gain insights into the evolution of the structure of the central olfactory pathway in insects, we analyzed a representative of the wingless Archaeognatha or jumping bristletails, using immunocytochemistry, antennal backfills and histological section series combined with 3D reconstruction. In the deutocerebrum of Lepismachilis y-signata, we found three different neuropil regions. Two of them show a glomerular organization, but these glomeruli differ in their shape from those in all other insect groups. The connection of the glomerular neuropils to higher brain centers remains unclear and mushroom bodies are absent as reported from other archaeognathan species. We discuss the evolutionary implications of these findings

Towards Automated Business Process Deduction through a Social and Collaborative Platform

Part 12: Collaboration PlatformsInternational audienceThe French project OpenPaaS aims at providing a social and collaborative platform that supports inter-organizational collaborations. This platform is a social network in which subscribing organizations are defined by their profiles (i.e. their capabilities). In response to a collaboration opportunity suggested by an organization, the IT system intends to automatically deduce a corresponding inter-organizational process, meaning that it enables simultaneously (i) the discovery of the collaborative partners and (ii) the building of a collective business process model. This paper aims at describing the interactions that take place first, between the system and the users and second, within the system between the IT components. It also provides an overview of two specific reconciliations in the context of such a design of emerging networks: (i) functional versus non-functional and (ii) business versus technical