Статті в журналах з теми "Boucle interactive"

Le passage de la forme non pathogène de la protéine prion normalement présente chez l’individu sain (PrPC) vers la forme pathogène (PrPSc) se traduit par une augmentation de la proportion de feuillet bêta dans la protéine, favorisant son agrégation, la formation de fibrilles et la résistance à la protéinase K. La structure tridimensionnelle de PrPC, déterminée pour quatre espèces, est extrêmement conservée. Elle comporte un segment désordonné et très flexible à l’extrémité N-terminale et une partie globulaire, constituée de deux brins bêta (S1, S2) et de trois hélices alpha (H1 à H3) associés par des boucles (L1 à L5). Le fragment de la protéine correspondant à l’hélice H1 se structure en hélice de façon autonome. En revanche, le peptide comportant la région H1-L3- S2 (PrPH1-L3-S2) montre, comme la protéine, une capacité à adopter différentes conformations. Ces résultats contribuent à proposer l’hélice H1 comme l’un des motifs structuraux de la protéine capables d’initier la transconformation, c’est-à-dire la transformation de la protéine prion normale en protéine prion pathogène. Le rôle clé de l’hélice H1 dans la transconformation a été étayé par une série d’études physicochimiques, détaillées dans l’article, réalisées à l’aide d’une série de peptides de tailles variées (9 à 33 résidus, séquence ovine) ciblés sur la région [133-165] qui comporte la succession des motifs structuraux L2-H1-L3-S2. Les principaux résultats de cette étude montrent la grande stabilité de l’hélice H1, en particulier en présence de la boucle L2 ou des deux boucles L2 et L3. L’absence de la boucle L2 et la présence du brin bêta S2 sont en revanche des facteurs de déstabilisation de l’hélice H1. La boucle L2 pourrait d’ailleurs jouer un rôle tout particulier comme le suggère l’observation d’une interaction entre cette boucle et la protéine PrPC. Une telle interaction pourrait être mise en jeu dans les mécanismes intervenant dans l’interaction protéine prion saine/protéine prion pathogène impliquée dans la propagation de la maladie. Ces résultats, qui devront être confirmés et développés, conduisent à proposer la boucle L2 et le feuillet S2 comme deux régions assurant la «régulation» de la stabilité de l’hélice H1, qui apparaît comme une région clef dans les processus de conversion pathogène.

Mutations in Deleted in Azoospermia (DAZ), a Y chromosome gene, are an important cause of human male infertility. DAZ is found exclusively in primates, limiting functional studies of this gene to its homologs: boule, required for meiotic progression of germ cells in invertebrate model systems, and Daz-like (Dazl), required for early germ cell maintenance in vertebrates. Dazl is believed to have acquired its premeiotic role in a vertebrate ancestor following the duplication and functional divergence of the single-copy gene boule. However, multiple homologs of boule have been identified in some invertebrates, raising the possibility that some of these genes may play other roles, including a premeiotic function. Here we identify two boule paralogs in the freshwater planarian Schmidtea mediterranea. Smed-boule1 is necessary for meiotic progression of male germ cells, similar to the known function of boule in invertebrates. By contrast, Smed-boule2 is required for the maintenance of early male germ cells, similar to vertebrate Dazl. To examine if Boule2 may be functionally similar to vertebrate Dazl, we identify and functionally characterize planarian homologs of human DAZL/DAZ-interacting partners and DAZ family mRNA targets. Finally, our phylogenetic analyses indicate that premeiotic functions of planarian boule2 and vertebrate Dazl evolved independently. Our study uncovers a premeiotic role for an invertebrate boule homolog and offers a tractable invertebrate model system for studying the premeiotic functions of the DAZ protein family.

Circular RNAs (circRNAs) are a large family of newly identified transcripts, and their physiological roles and evolutionary significance require further characterization. Here, we identify circRNAs generated from a conserved reproductive gene, Boule, in species from Drosophila to humans. Flies missing circular Boule (circBoule) RNAs display decreased male fertility, and sperm of circBoule knockout mice exhibit decreased fertilization capacity, when under heat stress conditions. During spermatogenesis, fly circBoule RNAs interact with heat shock proteins (HSPs) Hsc4 and Hsp60C, and mouse circBoule RNAs in sperm interact with HSPA2. circBoule RNAs regulate levels of HSPs by promoting their ubiquitination. The interaction between HSPA2 and circBoule RNAs is conserved in human sperm, and lower levels of the human circBoule RNAs circEx3-6 and circEx2-7 are found in asthenozoospermic sperm. Our findings reveal conserved physiological functions of circBoule RNAs in metazoans and suggest that specific circRNAs may be critical modulators of male reproductive function against stresses in animals.

We use thick, relatively high purity 4H SiC boule material to measure the wavelength modulated absorption spectrum with improved wavelength resolution and sensitivity with respect to previous work. We observe several small 0.6 ± 0.1 meV splittings, which we attribute to electron mass anisotropy and electron-hole exchange interaction. In addition, we identify several features in the absorption spectrum as signatures of nonparabolicity in the free exciton dispersion relations, the primary origin of which is likely the nonparabolic energy dispersion of the valence bands, as revealed by published band structure calculations based on density functional theory.

RaDMaX online is a major update to the previously published RaDMaX (radiation damage in materials analysed with X-ray diffraction) software [Souilah, Boulle & Debelle (2016). J. Appl. Cryst. 49, 311–316]. This program features a user-friendly interface that allows retrieval of strain and disorder depth profiles in irradiated crystals from the simulation of X-ray diffraction data recorded in symmetrical θ/2θ mode. As compared with its predecessor, RaDMaX online has been entirely rewritten in order to be able to run within a simple web browser, therefore avoiding the necessity to install any programming environment on the users' computers. The RaDMaX online web application is written in Python and developed within a Jupyter notebook implementing graphical widgets and interactive plots. RaDMaX online is free and open source and can be accessed on the internet at https://aboulle.github.io/RaDMaX-online/.

4H-SiC was grown on 4H-SiC (1100) substrates by sublimation boule growth, and transmission electron microscopic investigation was carried out. Two basal-plane-dislocations in the same basal plane (the BPD pair), whose dislocation line extend toward the [1100] growth direction, were observed as aligned along [0001]. The density of the BPD pairs along [0001] was in the same order with that of the stacking faults in the sample. A threading screw-dislocation was observed in between aligned BPD pairs. It is proposed that the interaction between stacking faults and threading screw-dislocations on the grown surface generates the BPD pairs. Since a high density of stacking faults is inherent to the growth on the substrates perpendicular to (0001), keeping an atomically flat grown surface is important to prevent the generation of the threading screw-dislocations, and thus to suppress the generation of the BPD pairs in case of the growth on (1100) and/or (11 2 0) substrates.

IntroductionLa question d’une transmission ou d’une influence des troubles mentaux des parents sur la santé mentale de leurs enfants, a pris un essor considérable en raison du développement de la génétique et des notions de vulnérabilité ou d’interactions gène–environnement. Les interactions précoces mère–enfant influencent de façon directe le développement psychoaffectif de l’enfant. Les troubles mentaux de l’enfant sont à leur tour générateur ou parfois révélateur d’une pathologie psychiatrique chez les parents, surtout la mère. Cette « boucle » dans laquelle la santé mentale de l’enfant et de la mère sont en perpétuelle interaction, nécessite une intervention spécialisée aussi bien sur l’un et l’autre mais aussi sur la dyade. Objectif.–Le but de ce travail est de faire le lien entre les troubles retrouvés des enfants suivis en pédopsychiatrie et leurs mères qui bénéficient d’une prise en charge en psychiatrie. Décrire le profil des mères dont les enfants sont suivis à la consultation de pédopsychiatrie de l’hôpital Razi et qui sont elles-mêmes suivies pour un trouble psychiatrique. Le recueil de données s’est fait à partir des dossiers médicaux des patientes.RésultatsNous avons recueilli dix dossiers de patientes suivies à la consultation de psychiatrie. Sur nos résultats préliminaires, la dépression maternelle est le trouble le plus fréquemment observé. Le travail est en cours de réalisation. Nous prévoyons d’élargir la population d’étude.ConclusionLa mise en place d’une guidance parentale repose sur le dépistage des troubles psychiatriques chez les parents et surtout la mère. Ce travail est une ébauche d’une perspective de collaboration entre psychiatres et pédopsychiatres.

Developing male germ cells are exquisitely sensitive to environmental insults such as heat and oxidative stress. An additional characteristic of these cells is their unique dependence on RNA-binding proteins for regulating posttranscriptional gene expression and translational control. Here we provide a mechanistic link unifying these two features. We show that the germ cell–specific RNA-binding protein deleted in azoospermia-like (Dazl) is phosphorylated by MAPKAP kinase 2 (MK2), a stress-induced protein kinase activated downstream of p38 MAPK. We demonstrate that phosphorylation of Dazl by MK2 on an evolutionarily conserved serine residue inhibits its interaction with poly(A)-binding protein, resulting in reduced translation of Dazl-regulated target RNAs. We further show that transgenic expression of wild-type human Dazl but not a phosphomimetic form in the Drosophila male germline can restore fertility to flies deficient in boule, the Drosophila orthologue of human Dazl. These results illuminate a novel role for MK2 in spermatogenesis, expand the repertoire of RNA-binding proteins phosphorylated by this kinase, and suggest that signaling by the p38-MK2 pathway is a negative regulator of spermatogenesis via phosphorylation of Dazl.

AbstractThe most convincing evidence to date of solar-type oscillations in other stars comes from recent observations of β Hydri (Bedding et al., 2001) and α Cen A (Bouchy & Carrier, 2001). It is the current belief that the convection dynamics in the outer layers of sun-like stars is the source for driving the intrinsically stable modes to the observed amplitudes. Comparing such observations with theoretical models will help us improve our understanding of the interaction between convection and pulsation.In this contribution I review the mechanisms responsible for mode damping in stars with convective envelopes, and the basic mechanism of stochastic driving by turbulent convection. The application of a stochastic excitation formalism to the Sun is discussed and compared with recent measurements and numerical simulations. Amplitude predictions for models of Procyon, α Cen A and β Hydri are compared with observations.

Background: In the males, Spermatogonial Stem Cells (SSCs) contribute to the production of sex cells and fertility. In vitro SSCs culture can operate as an effective strategy for studies on spermatogenesis and male infertility treatment. Cell culture in a three-dimensional (3D) substrate, relative to a two-dimensional substrate (2D), creates better conditions for cell interaction and is closer to in vivo conditions. In the present study, in order to create a 3D matrix substrate, decellularized testicular matrix (DTM) was used to engender optimal conditions for SSCs culture and differentiation. Materials and Methods: After, testicular cells enzymatic extraction from testes of brain-dead donors, the SSCs were proliferated in a specific culture medium for four weeks, and after confirming the identity of the colonies derived from the growth of these cells, they were cultured on a layer of DTM as well as in 2D condition with a differentiated culture medium. In the Sixth week since the initiation of the differentiation culture, the expression of pre meiotic (OCT4 & PLZF), meiotic (SCP3 & BOULE) and post meiotic (CREM & Protamine-2) genes were measured in both groups. Results: The results indicated that the expression of pre meiotic, meiotic and post meiotic genes was significantly higher in the cells cultured on DTM (P ≤ 0.001). Conclusion: SSCs culture in DTM with the creation of ECM and similar conditions with in vivo can be regarded as a way of demonstrating spermatogenesis in vitro, which can be adopted as a treatment modality for male infertility. [GMJ.2019;8:e1565]

AbstractThe paper presents the results of direct numerical simulations of the fall of a single freely moving sphere in a vertical circular tube. Most results are obtained for the solid–fluid density ratio ${\rho }_{s} / \rho = 2$. The parametric investigation is carried out depending on the Galileo number defined in Jenny, Dušek & Bouchet J. Fluid Mech., vol. 508, 2004, pp. 201–239. A qualitatively new scenario is found, as compared to that of an unconfined sphere. The primary bifurcation making the sphere deviate from a vertical fall along the tube axis at a constant velocity is of Hopf type. It sets in at a Galileo number (between 155 and 160) similar to that for an unconfined sphere. We find evidence for two stages of the primary regime: a planar trajectory at $G= 160$ and a helical one (at $G= 165$ and 170). At these Galileo numbers, the regime is perfectly periodic, with a slow period corresponding to a Strouhal number only slightly above 0.01. The dynamics is identified as a periodic wake–wall interaction. The helical regime is found to give way directly to chaos between $G= 170$ and $G= 180$. This transition is associated with the onset of vortex shedding in the wake of the falling sphere and with a complex interaction between the unsteady wake and the wall marked by intermittent wake extinction. The effect of density ratio is partly investigated at $G= 250$ by considering three density ratios: 2, 3 and 5. A significant change of behaviour is found between the ratios 3 and 5.

BACKGROUND: Interstitial cystitis (IC) is a prevalent and debilitating chronic inflammatory disease of the urinary bladder. Currently there are no fully effective therapeutic agents available, in part due to the still obscure pathogenesis of IC. Lipopolysaccharide (LPS) also known as endotoxin from Gram negative bacteria elicits IC in mice and has formed the basis of model systems for investigation. Excess free iron plays an important role in inflammation through generation of reactive oxygen species (ROS). The novel iron chelator DIBI has been shown to sequester excess free iron and dampen excess inflammatory responses to systemic LPS administration and also to Gram negative bacterial infections. OBJECTIVE: The overall objective of this study was to evaluate the effects of DIBI on LPS induced IC in mice. Leukocyte activation, endothelial adhesion and functional capillary density were assessed by intravital microscopy of the bladder microcirculation following a single intravesical LPS administration with or without intravesical DIBI treatment. Clinical IC symptoms were also assessed through behavioral and pain threshold force measurements. METHODS: Four groups of female BALB/c mice (n = 5–6/group) were randomized in this study: control group, IC group without therapy, IC group with DIBI therapy and control group with DIBI therapy. The groups were examined using intravital microscopy (IVM) of the bladder for leukocyte-endothelial interactions (adherent leukocytes, temporarily interacting leukocytes) and functional capillary density (FCD). A modified behavioral score by Boucher et al. and Von-Frey-Aesthesiometry were used to evaluate key behavioral indices related to pain and visceral pain perception. RESULTS: LPS introduced intravesically induced an early (≤2h) inflammation of the bladder evidenced by leukocyte activation and adhesion to bladder capillary walls. Intravesical DIBI therapy of mice 30min following LPS administration and assessed after 1.5h treatment showed a significant decrease in the number of adherent leukocytes compared to IC animals without DIBI treatment. DIBI treated mice showed a significantly lowered increase in behavioral distress scores compared to IC mice without therapy. Untreated IC mice exhibited a significantly decreased threshold force value for evoked pain response and DIBI treatment improved the threshold pain response. A significant inverse correlation was found for the two pain and suffering evaluation methods results. CONCLUSION: DIBI reduced inflammatory endothelial leukocyte adhesion and key indices related to pain and suffering over those observed in untreated IC mice. Our findings suggest a potential therapeutic role for DIBI for IC treatment.

Abstract Introduction: Basal-like breast cancer (BLBC; TNBC) cells use aerobic glycolysis at a higher rate than Luminal A (LumA) cells. Metabolic reprogramming using aerobic glycolysis (Warburg effect), is correlated with increased aggressiveness of cancer cells and poor outcome in patients. Therefore, genes involved in this pathway are promising targets for developing cancer therapeutics. Method: MIMs has developed a unique platform of augmented intelligence that combines bioinformatics, systems biology and artificial intelligence. It integrates multi-layered omics data with a knowledge-base that aggregates structured data from more than 140 databases as well as unstructured data from the scientific literature. Using this approach a genetic interaction graph (GI-Graph) is inferred per patient, capturing functional relationships between genes in the specific context of the tumor. The GI-Graphs are subsequently used to train supervised machine learning algorithms for predicting gene functionality and potential as a target. Preliminary analysis was performed on transcriptomic data from 321 LumA and 162 TNBC samples, from the TCGA Data Portal and a predictive model was developed using two GI-Graphs from the two subgroups. Briefly, subgraphs, containing genes with functional interactions with the known genes in OXPHOS and glycolysis pathways, were used to extract gene attributes, and to build an algorithm that predicts involvement of a gene in the Warburg effect. Using a testing gene set extracted from the literature the performance of the model was assessed, which showed a true positive rate of 18% and a false positive rate of 0.36%, and outperformed 5-times the classical bioinformatics tools. Results: This model predicted 108 genes as the top 1% genes being involved in the metabolic reprogramming of TNBC. Additional information from MIMs’ platform, including differential gene expression between LumA and TNBC, gene pleiotropy and essentiality and the topological metrics, enabled the life scientists to further refine the gene lists, based on the expected characteristics of a good target in oncology. Following this process, 30 genes were selected as potential targets controlling the metabolic reprogramming of TNBC, among which 4 genes were already evaluated in TNBC clinical trials. Conclusion: Our preliminary data strongly supports that the predictive model based on the GI-Graphs has the potential to identify promising therapeutic targets for TNBC. Citation Format: Sarah Jenna, Benjamin Boucher, Liebaut Dudragne, Abdoulaye Baniré Diallo. Augmented intelligence to define drug targets associated with triple negative breast cancer (TNBC) metabolic reprogramming [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6375.

The Core Zone, a broad region located between the Superior and North Atlantic cratons and predominantly underlain by Archean gneiss and granitoid rocks, remained until recently one of the less well known parts of the Canadian Shield. Previously thought to form part of the Archean Rae Craton, and later referred to as the Southeastern Churchill Province, it has been regarded as an ancient continental block trapped between the Paleoproterozoic Torngat and New Quebec orogens, with its relationships to the adjacent Superior and North Atlantic cratons remaining unresolved. The geochronological data presented herein suggest that the Archean evolution of the Core Zone was distinct from that in both the Superior and North Atlantic (Nain) cratons. Moreover, the Core Zone itself consists of at least three distinct lithotectonic entities with different evolutions, referred to herein as the George River, Mistinibi-Raude and Falcoz River blocks, that are separated by steeply-dipping, crustal-scale shear zones interpreted as paleosutures. Specifically, the George River Block consists of ca. 2.70 Ga supracrustal rocks and associated ca. 2.70–2.57 Ga intrusions. The Mistinibi-Raude Block consists of remnants of a ca. 2.37 Ga volcanic arc intruded by a ca. 2.32 Ga arc plutonic suite (Pallatin) and penecontemporaneous alkali plutons (Pelland and Nekuashu suites). It also hosts a coarse clastic cover sequence (the Hutte Sauvage Group) which contains detrital zircons provided from locally-derived, ca. 2.57–2.50 Ga, 2.37–2.32 Ga, and 2.10–2.08 Ga sources, with the youngest concordant grain dated at 1987 ± 7 Ma. The Falcoz River Block consists of ca. 2.89–2.80 Ga orthogneiss intruded by ca. 2.74–2.70 granite, tonalite, and granodiorite. At the western margin of the Core Zone, the George River Block and Kuujjuaq Domain may have been proximal by ca. 1.84 Ga as both appear to have been sutured by the 1.84–1.82 Ga De Pas Batholith, whereas at its eastern margin, the determination of metamorphic ages of ca. 1.85 to 1.80 Ga in the Falcoz River Block suggests protracted interaction with the adjacent Lac Lomier Complex during their amalgamation and suturing, but with a younger, ‘New Quebec’ overprint as well. The three crustal blocks forming the Core Zone add to a growing list of ‘exotic’ Archean to earliest Paleoproterozoic microcontinents and crustal slices that extend around the Superior Craton from the Grenville Front through Hudson Strait, across Hudson Bay and into Manitoba and Saskatchewan, in what was the Manikewan Ocean realm, which closed between ca. 1.83–1.80 Ga during the formation of supercontinent Nuna.RÉSUMÉLa Zone noyau, une vaste région située entre les cratons du Supérieur et de l’Atlantique Nord et reposant principalement sur des gneiss archéens et des roches granitiques, est demeurée jusqu’à récemment l’une des parties les moins bien connues du Bouclier canadien. Considérée auparavant comme faisant partie du craton archéen de Rae, puis comme la portion sud-est de la Province de Churchill, on l’a perçue comme un ancien bloc continental piégé entre les orogènes paléoprotérozoïques des Torngat et du Nouveau-Québec, ses relations avec les cratons supérieurs adjacents et de l’Atlantique Nord demeurant nébuleuses. Les données géochronologiques présentées ici permettent de penser que l’évolution archéenne de la Zone noyau a été différente de celle des cratons du Supérieur et de l’Atlantique Nord (Nain). De plus, la Zone noyau elle-même se compose d’au moins trois entités lithotectoniques distinctes avec des évolutions différentes, appelées ici les blocs de la rivière George, de Mistinibi-Raude et de la rivière Falcoz, lesquels sont séparées par des zones de cisaillement crustales à forte inclinaison, conçues comme des paléosutures. Plus précisément, le bloc de la rivière George est constitué de roches supracrustales d'env. 2,70 Ga, et d’intrusions connexes d'env. 2,70–2,57 Ga. Le bloc Mistinibi-Raude est constitué de vestiges d’un arc volcanique d'env. 2,37 Ga, recoupé par une suite plutonique d’arc d'env. 2,32 Ga (Pallatin) et de plutons alcalins péné-contemporains (suites Pelland et Nekuashu). Il contient également une séquence de couverture clastique grossière (le groupe Hutte Sauvage) renfermant des zircons détritiques de sources locales, âgés d'env. 2,57–2,50 Ga, 2,37–2,32 Ga et 2,10–2,08 Ga, le grain concordant le plus jeune étant âgé de 1987 ± 7 Ma. Le bloc de la rivière Falcoz est formé d’un orthogneiss âgé d'env. 2,89–2,80 Ga, recoupé par des intrusions de granite, tonalite et granodiorite âgées d'env. 2,74–2,70 Ga. À la marge ouest de la Zone noyau, le bloc de la rivière George et du domaine de Kuujjuaq peuvent avoir été proximaux il y a 1,84 Ga env., car les deux semblent avoir été suturés par le batholithe De Pas il y a environ 1,84–1,82 Ga, alors qu’à sa marge est, la détermination des datations métamorphiques de 1,85 à 1,80 Ga dans le bloc de la rivière Falcoz suggère une interaction prolongée avec le complexe adjacent du lac Lomier durant leur amalgamation et leur suture, mais affecté aussi d’une surimpression « Nouveau Québec » plus jeune. Les trois blocs crustaux formant la Zone noyau s’ajoutent à une liste croissante de micro-continents et d’écailles crustales « exotiques » archéennes à paléoprotérozoïques très précoces qui s’étalent autour du craton Supérieur depuis le front de Grenville jusqu’au Manitoba, à travers le détroit d’Hudson, la baie d’Hudson jusque dans le Manitoba et la Saskatchewan, là où s’étendait l’océan Manikewan, lequel s’est refermé il y a environ 1,83–1,80 Ga, pendant la formation du supercontinent Nuna.

Nitrogen is a paramount important essential element for all living organisms. It has been found to bea crucial structural component of proteins, nucleic acids, enzymes and other cellular constituents which are inevitable for all forms of life. In the atmosphere, the percentage of nitrogen is very high (N2, 78%) compared to other inorganic gases. However, most organisms have practically no direct access to this nitrogen. While plants can not directly uptake nitrogen from atmosphere, they are capable of assimilating other forms of nitrogen, for example ammonium (NH4+) and nitrate (NO3-). For agricultural crop production, artificial fixation of nitrogen is heavily utilized and it is an expensive process that requires high temperatures (at least 400 °C) and pressures (around 200 atm). It has been conspicuously demonstrated that indiscriminate use of fertilizer hampers soil physical, chemical and micro biological properties and also a potential risk to environment e.g. water quality. Besides, chemically manufactured fertilizers are depleted from soils in various ways, for instance; denitrifying bacteria, volatilization, and leaching. Consequently, it results relatively poor availability of nitrogen to get into plants. On the flipside, only 1-2% of the nitrogen fixation in the world occurs through the natural process of lightening. Notably, microbial fixation is well characterized in diazotrophs for example; Rhizobia and Frankia, and blue-green algae. Against the backdrop, we are accentuated on an environmentally friendlyand themost sustainable approach to increase productivity for legume and non-legume crops. Till today, the term biological nitrogen fixation (BNF) has received much attention as a sustainable alternative; this process facilitates atmospheric nitrogen to convert into ammonia by rhizobia in specialized plan organs termed “root nodules”. This review article seeks to better understand plant mechanisms involved in the development of root nodules in soybean. Soybean (Glycine max) is one of the most important oil crops and a source of animal feed protein in the world. It has a salient feature to fix atmospheric nitrogen through symbioses with compatible rhizobia that yields to determinate type nodule (Oldroyd, Murray et al. 2011). Biological nitrogen fixation in soybean nodules reduces the use of chemical nitrogen fertilizers resulting in cost-savings to producers and minimizes environmental damage due to nitrogen run-off. A better understanding of how nodules form and function is important for selection or generation of soybean genotypes with better nitrogen fixation capacity. Soybean nodules originate from root cortex via de novo cell differentiation (Oldroyd 2013). Consequently, two major nodule development zones are formed for instance; the nodule primordium (Npr) in the middle and it is encircled by nodule parenchyma (Npa). At later time point, the Npr gives rise to N-fixation zone and the Npa holds vascular bundles. It is not clear what early signaling pathways driving the conspicuous development of the nodule zones. My research is aimed at filling this knowledge gap by illustrating the molecular signatures that paves the way to cellular differentiation in root nodule development in soybean. Based on initial evidence obtained by the Subramanian lab, we hypothesize that microRNAs (miRNAs) play important regulatory roles in spatio-temporal expression of their target genes during nodule developmental in soybean. For instance, the regulation of auxin sensitivity by miR160 has been found to be crucial for formation of nodule primordia and vasculature in the parenchyma (Marie Turner 2013). Against this backdrop, this review article focused on nuclear and cytoplasmic transcriptome as well as miRNA profiles of parenchyma and primordial tissues and determine the relative abundance and differentially expressed mRNAs and regulatory role of miRNAs in cell differentiation and nodule development. Root nodule a sustainable alternative to fix atmospheric nitrogen Atmospheric nitrogen percentage is very high (N2, 78%) compared to other inorganic gases (Mary Elvira 1932). However, most of the organisms have practically no direct access to this nitrogen. Nevertheless, plants can not directly uptake nitrogen from atmosphere but they are capable of assimilating only very specific forms of nitrogen, for example ammonium (NH4+) and nitrate (NO3-) (Bytnerowicz and Fenn 1996, Peter M. Vitousek 1997) (Sponseller, Gundale et al. 2016). Virtually, nitrogen has been found to be a crucial structural component of proteins, nucleic acids, enzymes, and other cellular constituents which are inevitable for all forms of life (O'Brien, Vega et al. 2016). For agricultural crop production, artificial fixation of nitrogen is heavily utilized. It is an expensive process that requires high temperatures (approx. 400 °C) and pressures (approx. 200 atm) (Witschi 2000). It has been conspicuously demonstrated that indiscriminate use of N fertilizer hampers the diversity of the bacterial community and decreases soil C and N concentrations (Verzeaux, Alahmad et al. 2016). Notably, it has been demonstrated as a potential risk to environment e.g. water quality (Zhao, Sha et al. 2016) (Sponseller, Gundale et al. 2016). Besides, chemically manufactured fertilizers are depleted from soils in various ways, for instance; denitrifying bacteria, volatilization, and leaching (Johnson 1996, Peter M. Vitousek 1997). Consequently, it results relatively poor availability of nitrogen to get into plants. On the flipside, over 90 % of the nitrogen fixation in the world occurs through the natural process of lightening and microorganisms. Furthermore, microbial fixation is well characterized in diazotrophs for example; Rhizobia and Frankia, and blue-green algae (Cheng 2008). It has been demonstrated that Bradyrhizobium strains substantially escalated soybean grain yield, and protein content up to 57% and 26%, respectively (Zimmer, Messmer et al. 2016). Against the backdrop, we are accentuated on an environmentally friendly and a sustainable approach to increase the productivity for legume and non-legume crops. Literature mining depicted that biological nitrogen fixation in soybean nodules reduces the use of chemical nitrogen fertilizers resulting in cost-savings to producers and minimizes environmental damage due to nitrogen run-off. Rhizobia infection leads to the root nodule development In the natural environment, plants are continuously confronted with pathogenic and symbiotic microbes. Symbioses involves mutual exchange of diffusible signal molecules, first endophytic bacteria (rhizobia) are attracted by the plant root exudates flavonoids which are perceived and triggered the bacterial nodulation (nod) genes. Consequently, the bacteria synthesize specific lipochito-oligosaccharides, called nodulation (Nod) factors. This signal is perceived by the LysM receptor like kinase of host plant, it induces the root hair curling, and bacteria get access into the host epidermis through infection threads (ITs) and initiate cell division within the root cortex, leading to the progression of the root nodule meristem. In later stages of the interaction, bacteria are released from the infection threads into the plant cells, surrounded by membrane of plant origin. These bacteria multiply within the host cells and differentiate into the nitrogen fixing bacteroids (Udvardi and Day 1997) (Oldroyd 2013). Till now, integration of genetic and genomic approaches has revealed twenty-six genes to be involved in nodule development of Medicago truncatualaand Lotus japonicum (Kouchi, Imaizumi-Anraku et al. 2010). In addition, deep sequencing of the Medicago truncatularoot transcriptome has uncovered thousands of genes to be induced during Nod factor signaling and its resulting ethylene (ET) biosynthesis throughout the multiple development stages of indeterminate nodule (Larrainzar, Riely et al. 2015). Albeit the molecular mechanism of such regulation is not well understood. There has been a large-scale transcriptome analysis of B. japonicum-inoculated and mock-inoculated soybean root hairs. It has showed that a total of 1,973 soybean genes differentially expressed during root hair infection, particularly NFR5 and NIN genes (Libault, Farmer et al. 2010). Nevertheless, the signaling mechanisms directing the cellular differentiation of nodule are not known. Soybean root nodule organogenesis Soybean (Glycine max) has a genome size of 1.1 to1.5 Gb, it is partially diploidized tetraploid. It is one of the most important oil crops and a source of animal feed protein in the world (soybase.org/sb_about.php). It has a salient feature to fix atmospheric nitrogen through symbioses with compatible rhizobia that yields to determinate type nodule (Udvardi and Day 1997) (Oldroyd, Murray et al. 2011). Notwithstanding of the economic and environmental importance, there has been very few studies about quantitative trait loci (QTL) that controlling BNF traits, for instance nodule number, ration of nodule dry weight with nodule number, and shoot dry weight (SDW). It has been reported via composite interval mapping that approximately six QTLs bears very small effect on BNF traits (Santos, Geraldi et al. 2013). Besides, it has been demonstrated in earlier studies that nodules originate from root cortex via de novo cell differentiation into two different cell types, parenchymal and primordium (Celine Charon 1997) (Oldroyd&Downie 2008; Oldroyd 2013). In addition, early nodulin genes in legume for instance; Enod 40 gene reported to be expressed in root pericycle during the rhizobia infection and later it occupied in the dividing cortical cells (H. Kouchi and S. Hata 1993). Among the two major nodule development zones, the nodule primordium (Npr) in the middle which is encircled by nodule parenchyma (Npa). At later time point, the Npr gives rise to N-fixation zone and the Npa holds vascular bundles. Lately, a β- expansin gene, GmEXPB2 fused with GUS reporter gene which was observed to be preferentially expressed in nodule vascular trace and nodule vascular bundles. It indicated that GmEXPB2 might be crucial for nodule organogenesis. Over expression of GmEXPB2 contrast to suppressed GmEXPB2 transgenic lines found to be escalated nodule number, nodule mass and nitrogenase activity. It further suggested that GmEXPB2 might have influenced over root architecture, nodule formation and development, and profoundly yielding to biological N2 fixation (Li, Zhao et al. 2015). Even though, it is not clear what early signaling pathways driving the conspicuous development of the nodule zones. Against the back drop, to understand the regulation of auxin sensitivity by miR160 which is believed to be crucial for the formation of nodule primordia (Marie Turner 2013). Figure 1 a. Illustrating the progression of root nodule development through Rhizobial bacterial infection in the plant root leading to the determinate nodule (Oldroyd 2013). b. Nodule development zones A. Nodule primordial zone (Enod 40 gene) in the middle B. surrounding parenchyma (Enod 2 gene), differentiated from cortex (collected from Sen Subramanian lab). Regulatory small RNAs biogenesis and its molecular functions Regulatory small RNAs are ranged between 20 to 24 nucleotides which are ubiquitous elements of endogenous plant transcriptomics, a common response to exogenous viral infections and introduced double-stranded RNA (Axtell 2013). Three core enzymes families, for instance; RNAdependent RNA polymerase (RDR), Dicer like (DCL), and Argonaute (AGO) proteins paves the way of small RNA biogenesis and function in plants. Firstly, ribonuclease type III or DICERLIKE1 involves in the yield of a fold-back precursor RNA or primary miRNA (primiRNA) transcripts using an RNA templates in the nuclei. Later, the resulting miRNA-miRNA duplex which is originated in nucleus then translocated into cytoplasm. The guided miRNAmolecule is incorporated into ARGONAUTE (AGO) to form an active RISC complex to specific target RNAs that are complementary to the miRNA, and this process eventually follows up mRNA cleavage, represses the translation of the mRNAs or Chromatin modification. This phenomenon accentuated as an inhibition or silencing of the gene expression, which play a crucial role in the developmental process in plant and animal (Chapman and Carrington 2007) (Axtell 2013). Fig. 2 Regulation of gene expression events via RISC complex (modified from https://www.google.com/?gws_rd=ssl#q=mirna+picture+in+plants accessed on 7th February, 2016) Fig. 3 Gene expression events occurring in typical plant cell (modified https://www.google.com/search?q=transcription+and+translation accessed on 7th February, 2016) It has been found in several studies that most plant miRNAs are non-coding RNA, and small 21-24 nucleotide long (Cuperus, Fahlgren et al. 2011). It requires DCL1-clade DCL for their biogenesis and AGO1-clade AGO for their function (Wu, Zhou et al. 2010, Manavella, Koenig et al. 2012). In rice (Oryza sativa), DCL3 has been reported in the biogenesis of 24nt long miRNA that incorporated in AGO4 to regulate the target gene expression primarily through mRNA cleavage (Wu, Zhou et al. 2010). Argonaute proteins (AGO) form RNA inducing silencing complexes (RISC) with small RNAswhich is known as post-transcriptional gene silencing. It has typically four domains, for instance:N-terminal, PAZ, MID and PIWI domains. The MID-PIWI lobes are belongs to the C-terminus. It has been studied that MID-domains contains the specificity loop to recognize and bind to the 5’-phosphate of smRNAs. The PIWI domains contained the catalytic active site D-E-D-H/D. PAZ domain anchored the 2-nt overhang at the 3’ end of miRNAs. The N-terminal domain involved in the separation of miRNA-miRNA duplex and the slicer activity of the mRNA (Song, Smith et al.2004). There has been an expansion and duplications of AGO family members during plantevolution (Singh, Gase et al. 2015). The functional diversification of AGOs is indicating sRNAdirected regulatory pathways. The binding preference of AGO and sRNA is mainly assigned by the sequence of sRNA. In Arabidopsis, 10 AGO have been extensively studied (Liu et al. 2014). It has been demonstrated that AtAGO10 like AtAGO1, it recognized distinct structural features in miR165/miR166 duplex than involved by AtGO1. AtAGO10 found to regulate shoot apical meristem by decoying miR165/miR166 and subsequent repression of homeodomain-leucinezipper (HD-ZIP) gene expression (Zhu, Hu et al. 2011). Notably, 22 AGO proteins have been reported in Soybean (Glycine max). It has been found that genome duplication in Soybean resulted such a proliferation of AGOs. For example: its genome encodes two copies of AGO1, AGO2, AGO5, AGO4/9, AGO6 and AGO7 (Xiang Liu 2014). However, the molecular function of the plant AGO genes yet not very clear. There are several miRNA families that are conserved across the vast evolutionary distances from flowering plants to mosses (Cuperus, Fahlgren et al. 2011). It has been observed in another study that miRNA, and its target pairing found to be stable for a prolonged periods of plant evolution. On the flip side, another group demonstrated that conserved plant miRNAs and their targets are to somehow flexible. For instance; miR159 is a highly conserved miRNA that targets not only a subset of MYB mRNAs but also observed to target a non MYB mRNA, SGN-U567133 (Buxdorf, Hendelman et al. 2010). A mutant tomato transgenic line (miR159-resistant line) showed higher level of the SGN-U567133 transcript and exhibited defects in leaf and flower development. This result suggests that miR159 involves in a post-transcriptional regulation. Additionally, it is found to be crucial for the normal tomato development. Recently, the identification of miRNAs in the regulation of photoperiodic pathways in soybean have been reported through high throughput sequencing and qRT-PCR. Six libraries were constructed using Illumina Solexa, for instance; 0, 8, and 16 h under short day treatment, similar time points considered for the long the long day treatment. A total of 163 miRNAs families were reported which covered 318 plant miRNAs, and unclassified 81 novel predicted miRNAs. As expected, significant differences in abundance between short day and long day treatment was observed (Wenbin Li 2015). These findings provided evidence of miRNA in the regulation of flowering time that ultimately affects the seed yield and quality of soybean. The complex regulatory network of miRNA-mRNA interactions during viral infection has been revealed via small RNA seq (sRNA), degradome seq, and genome-wide transcriptome analysis. There has been a total of 253 soybean miRNAs found to be two-folds abundance compared with mock-inoculated control demonstrated through sRNA seq analysis. Among them 105 miRNAs were identified as potential targets of 125 transcripts that has been validated by degradome seq analyses. In addition, 2679 genes were detected via genome wide transcriptomic analysis. These genes have been differentially expressed during infection of soybean mosaic virus and among them 71 genes projected to induce in defense response (Hui Chen 2016). These findings suggested the regulatory role miRNA that governed the target gene expression during viral infection. Furthermore, the regulatory role of microRNAs (miRNAs) during Soybean- Bradyrhizobium japonicum mutualistic association was studied first by Subramanian et al. 2008. They sequenced approximately 350000 small RNAs of soybean root sample which were inoculated with B. japonicum. It helps to detect 20 conserved miRNAs loci based on the similarity to miRNAs in another plant species. In addition, 35 novel miRNAs were identified based on potential hairpin forming precursors in Soybean EST as well as shotgun genomic sequences (Subramanian, Fu et al. 2008). These findings advocated the potential role of miRNAs in the regulation of legumerhizobiumsymbiosis. In another study, 120 hairpin-forming precursor genes have been identified in soybean by Turner et al. In addition, they reported three novel miRNAs for instance; miR160, miR164 and miR393 found to be involved in auxin signaling (Turner, Yu et al. 2012). Moreover, the plant hormone auxin is thought to have a pivotal role in nodule organogenesis in determinate and indeterminate type of nodule. It indicates a redundancy and diversity of miRNAs family members that governs the formation of root nodule. It has been illustrated that auxin receptor gene family hushed by over expressed microRNA393. These plant roots found to be hypersensitive to auxin and yielded normal nodule. This observation advocated that only minimal/reduced auxin signaling is required for determinate nodule development. Likewise, overexpressed microRNA160 hushed a set of repressor auxin response transcription factor. These plant roots were hypersensitive to auxin and observed not to be reluctant in epidermal responses to rhizobia. Notably, it yielded to lower sized nodule primordium (Marie Turner 2013). This observation indicated that auxin hypersensitivity inhibits nodule organogenesis Organ specific expression of profile of miRNA and the potential targets were also studied. Two genes (Glyma10g10240 and Glyma17g05920) which were the target of miR169 but detected to be highly expressed in soybean nodule. Likewise, three potential targets of gma-new-miR13587 demonstrated to be highly expressed in the nodules than in the roots. As expected, gma-newmiR13587 found to be poorly expressed in the nodules than in the roots (Turner, Yu et al. 2012). There was an inverse expression pattern observed in between roots and nodules. Li et al., studied the transgene expression of three novel miRNAs namely, miR482, miR1512, and miR1515 in Soybean. They noticed a significant increase of nodule numbers while root length and later root density were normal in all tested miRNA lines. As expected, there were differential expression of these miRNAs in supernodulating and nonnodulating soybean mutants. They reported that 6 novel miRNAs decoyed 22 predicted target genes. And it was estimated via real time polymerase chain reaction and qRT-PCR (Li, Deng et al. 2010). It advocates that miRNAs have the signatory roles in soybean nodule development. Sequencing of small RNAs and Parallel analysis of RNA ends (PARE) libraries revealed to identify 284 nodule miRNAs, more than 500 target genes, and including 178 novel soybean miRNAs. It has been reported that ENOD93 only found to be expressed in nodule tissue not in other plant parts of Soybean. Ectopic expression of miR393j-3p and RNAi silencing approach to ENOD93 expression showed a significant reduction in nodule formation (Zhe Yan 2015). Therefore, this study showed a list of miRNAs and their potential target of nodulation genes. In the model legume (Medicago truncatula), 25 conserved miRNA families and 100 novel miRNA reads were detected by high-throughput sequencing. The expression of MtHAP2-1 (encodes a CCAAT binding transcription factor) to meristematic zones was restricted by miR169a which is found to be critical for the development of indeterminate type of nodule (Combier, Frugier et al. 2006). In another study, HDZIPIII transcripts were inhibited by overexpression of miR166, it dropped the number of symbiotic nodule and lateral root (Boualem, Laporte et al. 2008). To get insights into key genes of nodule zones, transcript profiles of specific cells/tissues were investigated at different time points from indeterminate nodules of M. truncatulausing laser capture micro dissection. It has been demonstrated from the comprehensive gene expression map that selected genes enriched in different cell/tissue types (Limpens, Moling et al. 2013). These findings indicated that organ specific gene expression could be controlled by the presence or absence of miRNAs. Recently, Agrobacterium rhizogenesmediated hairy root transformation has been applied as tool for exploring cell type specific gene expression in tomato. Cell type or tissue specific promoter introduced into INTACT and TRAP constructs via gateway cloning technology to develop binary vectors. INTACT method used to capture biotin tagged nuceli from specific cell types and TRAP method used for profiling of mRNAs or foot printing of individual ribosomes (Ron 2014). TRAP methodology is not required tissue fixation or single cell suspension. It has been successfully used to date in organisms ranging from D. melanogaster to mice and human cultured cells. Multiple ribosomes or Polyribosomes (polysomes) are engaged in translation on a single mRNA. To evaluate the translation state of an mRNA, ribosomal subunits, ribosomes, and polysomes can be isolated from detergent-treated cell extracts (Heiman, Kulicke et al. 2014). In this study, we would perform polysome isolation deploying gene cassettes ENOD40p:HF-GFP-RPL18 for primordial tissues, and ENOD2p:HF-GFP-RPL18 for parenchymal tissues in Glycine max root nodules that express an epitope tagged version of ribosomal protein L18. Over the last one decade, there has been several microarrays-based studies which characterized transcriptional variations deployed in nodule formation. It has been embedded with couple of shortcomings, for instance; relative late time points study, incomplete representation of plant genes,discrimination of close paralogs, and reduced sensitivity. Lately, next generation sequencingtechnology have widened the horizon of transcription analyses in different legume species to detectsymbiosis induced changes in late nodule developmental stages. Against this backdrop, we areaccentuated to reveal early transcriptional changes induced in determinate type of soybean noduleby Bradyrhizobium japonicum. In determinate type of nodule, two major nodule development zones are formed for instance, the nodule primordium (Npr) in the middle and it is encircled by nodule parenchyma (Npa). At later time point, the Npr converted to N-fixation zone and the Npa contained vascular bundles. Of these facts, it is not clear what early signaling pathways driving the conspicuous development of thenodule zones. In this context, mechanisms regulate the distinct gene expression profiles in Npr andNpa cell types has not understood clearly. The proposed research study is aimed at filling this knowledge gap byillustrating the molecular signatures that paves the way to cellular differentiation in root noduledevelopment in soybean considering four different time points (5 dai, 7 dai, 10 dai& 14 dai). The hypothesisis microRNAs(miRNAs) play important regulatory roles in spatio-temporal expression of their target genesduring nodule developmental in soybean. For example, a gradient of microRNA localizationbetween nodule primordium and parenchyma cells could result in distinct differentiation of thesecell types. To test this hypothesis, one has to obtain both cell type-specific miRNA andtranscriptome (miRNA target) profiles. Since, the majority of miRNA regulation occurs in thecytoplasm, we reasoned that comparison of nuclear and ribosomal transcriptome profiles wouldreveal genes whose expression is potentially regulated by post transcriptional mechanisms such asmiRNA cleavage. Combining this information with cell type-specific miRNA profiles, andto test the above hypothesis and identify key miRNA-target pairs important for nodule celldifferentiation. The use of translating ribosome affinity purification (TRAP) of nodule zonecells, namely from parenchyma and primordial tissues, to obtain cytoplasmic transcriptomes data. Techniques to determine cell type specific expression profiles: TRAP methods TRAP is termed translating ribosome affinity purification, combines cell-type-specific transgene expression with affinity purification of translating ribosomes. It supersedes the need for tissue fixation, and facilitates to study the cell type-specific mRNA profiles of any genetically defined cell type. It has been successfully used to date in organisms ranging from D. melanogaster to mice, and human cultured cells. Multiple ribosomes or Polyribosomes (polysomes) are engaged in translation on a single mRNA. To evaluate the translation state of an mRNA, ribosomal subunits, ribosomes, and polysomes can be isolated from detergent-treated cell extracts. In this study, the polysome isolation using gene cassettes ENOD40p:HF-GFP-RPL18 for primordial tissues, and ENOD2p:HF-GFP-RPL18 for parenchymal tissues in Glycine max root nodules that express an epitope tagged version of ribosomal protein L18 RPL18(Heiman, Kulicke et al. 2014, Ron 2014). Relative abundance and differentially expressed mRNAs profile in two different tissue specific zones would help to understand the effect of regulatory role of miRNAs in cell differentiation and nodule development. References: Axtell, M. J. (2013). "Classification and comparison of small RNAs from plants." Annu Rev PlantBiol 64: 137-159. Boualem, A., et al. (2008). "MicroRNA166 controls root and nodule development in Medicago truncatula." Plant J 54(5): 876-887. Buxdorf, K., et al. (2010). "Identification and characterization of a novel miR159 target not relatedto MYB in tomato." Planta 232(5): 1009-1022. Celine Charon, C. J., Eva Kondorosi, Adam Kondorosi and Martin Crespi (1997). "enod40 inducesdedifferentiation and division of root cortical cells in legumes." Proc. Natl Acad. Sci. USA. 94:8901-8906. Chapman, E. J. and J. C. Carrington (2007). "Specialization and evolution of endogenous small RNA pathways." Nat Rev Genet 8(11): 884-896. Cheng, Q. (2008). "Perspectives in biological nitrogen fixation research." J Integr Plant Biol 50(7):786-798. Combier, J. P., et al. (2006). "MtHAP2-1 is a key transcriptional regulator of symbiotic nodule development regulated by microRNA169 in Medicago truncatula." Genes Dev 20(22): 3084-3088. Cuperus, J. T., et al. (2011). "Evolution and functional diversification of MIRNA genes." Plant Cell 23(2): 431-442. Hiroshi Kouchi1, K.-i. T., Rollando B. So2, Jagdish K. Ladha2 and Pallavolu M. Reddy2 (1999). "Rice ENOD40: isolation and expression analysis in rice and transgenic soybean root nodules." The Plant Journal 18(2): 121-129. Johnson, D. S. O. a. G. V. (1996). "Fertilizer Nutrient Leaching and Nutrient Mobility: A Simple Laboratory Exercise." Nat. Resour. L. ife Sci. Educ 25(2): 128-131. Kouchi, H. and Hata, S. (1993) Isolation and characterization of novel nodulin cDNAs representing genes expressed at early stages of soybean nodule development. Gen. Genet. 238, 106–119. Li, H., et al. (2010). "Misexpression of miR482, miR1512, and miR1515 increases soybean nodulation." Plant Physiol 153(4): 1759-1770. Manavella, P. A., et al. (2012). "Plant secondary siRNA production determined by microRNAduplexstructure." Proc Natl Acad Sci U S A 109(7): 2461-2466. Marie Turner, e. a. (2013). "Ectopic Expression of miR160 Results in Auxin Hypersensitivity, Cytokinin Hyposensitivity, and Inhibition of Symbiotic Nodule Development in Soybean." Plant Physiology 162(2013): 2042–2055. Oldroyd GE, Downie JA. (2008). “Coordinating nodule morphogenesis with rhizobial infection inlegume. Annual Review of Plant Biology 59:519-546. Singh, R. K., et al. (2015). "Molecular evolution and diversification of the Argonaute family of proteins in plants." BMC Plant Biol 15: 23. Song, J. J., et al. (2004). "Crystal structure of Argonaute and its implications for RISC slicer activity." Science 305(5689): 1434-1437. Sponseller, R. A., et al. (2016). "Nitrogen dynamics in managed boreal forests: Recent advances and future research directions." Ambio 45 Suppl 2: 175-187. Subramanian, S., et al. (2008). "Novel and nodulation-regulated (2012). microRNAs in soybean roots." BMC Genomics 9: 160. Turner, M., et al. "Genome organization and characteristics of soybean microRNAs." BMCGenomics 13: 169. Udvardi and Day (1997). "Metabolite transport across symbiotic membranes of legume nodules." Annual Review of Plant Physiology and Plant Molecular Biology 48: 493-523. Weeks, Marry Elvira (1932). “The discovery of the elements. IV. Three impotant gases”. Journal of Chemical Education. 9 (2): 215 Wu, L., et al. (2010). "DNA methylation mediated by a microRNA pathway." Mol Cell 38(3): 465-475. Xiang Liu, T. L., Yongchao Dou, Bin Yu, and Chi Zhang (2014). "Identification of RNA silencingcomponents in soybean and sorghum." BMC Bioinform 15: 4. Zhe Yan, M. S. H., SiwaretArikit, Oswaldo Valdes-Lopez, JixianZhai, Jun Wang1,Marc Libault1, Tieming Ji, LijuanQiu, Blake C. Meyers and Gary Stacey (2015). "Identification of microRNAs and their mRNA targets during soybean nodule development: functional analysis of the role of miR393j-3p in soybean nodulation." New Phytologist 207: 748–759. Zhu, H., et al. (2011). "Arabidopsis Argonaute10 specifically sequesters miR166/165 to regulate shoot apical meristem development." Cell 145(2): 242-256.

AbstractAn analytical study of the dependence of shear and von-Mises stress distributions, which develop during PVT (Physical Vapor Transport) growth of 4H-SiC, has been executed. The key parameters investigated include thermal conditions of the crystal growth and parameters of the growing boule geometry. The evaluation was conducted via a 24 full factorial DOE (Design of Experiments). Parameters of the growing boule geometry, i.e. seed diameter, growth front height, inclination angle and height of the side surface were set as the DOE factors, while responses were calculated using numerical simulations. It is found that unique SiC boule growth conditions, which simultaneously minimize both the shear stress and von Mises stress magnitudes, cannot be achieved. Optimization of the shear stress distribution favors longer SiC boules with small seed diameters, small expansion angles and flat growth fronts. Alternatively, optimization of von-Mises stress favors short crystals with small seed diameters and small expansion angles but with curved growth fronts. Consequently, optimization of stress components in SiC crystals involves careful investigation of the interaction and compromise of the reaction cell geometry and growth conditions.

The COVID-19 pandemic has had profound implications for continuing medical education. Travel restrictions, lockdowns and social distancing in an effort to curb spread have meant that medical conferences have been postponed or cancelled. When the Australian and New Zealand College of Anaesthetists made the decision to commit to a fully virtual 2021 Annual Scientific Meeting, the organising committee investigated the viability of presenting a virtual ‘Can’t intubate, can’t oxygenate’ workshop. A workshop was designed comprising a lecture, case scenario discussion and demonstration of emergency front-of-neck access techniques broadcast from a central hub before participants separated into Zoom® (Zoom Video Communications, San Jose, CA, USA) breakout rooms for hands-on practice, guided by facilitators working virtually from their own home studios. Kits containing equipment including a 3D printed larynx, cannula, scalpel and bougie were sent to workshop participants in the weeks before the meeting. Participants were asked to complete pre- and post-workshop surveys. Of 42 participants, 32 responded, with the majority rating the workshop ‘better than expected’. All except two respondents felt the workshop met learning objectives. Themes of positive feedback included being impressed with the airway model, the small group size, content and delivery. Feedback focused on previously unperceived advantages of virtual technical skills workshops, including convenience, equitable access and the reusable airway model. Disadvantages noted by respondents included lack of social interaction, inability to trial more expensive airway equipment, and some limitations of the ability of facilitators to review participants’ technique. Despite limitations, in our experience, virtual workshops can be planned with innovative solutions to deliver technical skills education successfully.

Morning report (MR) is a valued educational experience in internal medicine training programs. Many senior residents and faculty have not received formal training in how to effectively facilitate MR. Faculty at the University of Toronto were surveyed to provide insights into what they felt were key elements for the successful facilitation of MR. These insights fell within 5 major categories: planning and preparation, the case, running the show, wrapping up and closing the loop.Résumé Le rapport du matin (RM) est un outil pédagogique précieux dans les programmes de formation en médecine interne. Nombre de résidents séniors et de membres du corps enseignant n’ont toutefois jamais reçu de formation officielle sur la façon de faciliter l’élaboration du RM. Nous avons sondé les membres du corps enseignant de l’université de Toronto pour avoir un aperçu de ce qu’ils percevaient comme étant des éléments-clés susceptibles d’améliorer grandement l’élaboration du RM. Les réponses reçues se répartissent en cinq principales catégories: la planification et la préparation du RM, les caractéristiques du cas évalué, l’importance et la façon de prendre en main le processus, le résumé des informations et l’art de « boucler la boucle». Morning report (MR) has long been an integral and valued part of Internal Medicine training programs in North America.1,2 Some residents recognize MR as the most important educational activity during their training.3 Medical students, residents and faculty typically attend MR. Although the structure and function of MR can vary across institutions, it usually involves a case-based discussion facilitated by a faculty member, chief medical resident (CMR), or other senior resident. The facilitator discusses pertinent aspects of one or more clinical cases to teach medical knowledge, clinical reasoning and other important aspects of physician competencies, such as communication and collaboration skills. 4 Residents have expressed a preference for an interactive teaching session led by an individual with extensive medical knowledge and excellent clinical acumen.5Despite trainees’ perceptions about the core educational function of MR and their preference for skilled facilitators, most residents and many faculty have never received any formal training on how to conduct an effective MR. This, coupled with a lack of resources in the literature, may contribute to feelings of trepidation about assuming the role of facilitator.6 Based on this need, we were invited by the organizing group of residents at the 2015 Canadian CMR Conference, held in Toronto, Canada, to lead a seminar to introduce CMRs to the principles of effective MR facilitation. The conference was attended by over 70 current and future CMRs. In preparation for this seminar, we reviewed available literature and found that practical guidelines on how to facilitate a successful MR were generally lacking. To help us to provide guidance and to capture broad opinions and experiences, we recruited a sample of 24 faculty at the University of Toronto, including many award-winning teachers whose experience in leading MR ranges from 3 to over 30 years. We asked them to provide insights into what they felt were key elements of facilitating a successful MR. While not a systematic collection of data, their insights taken together represent a broad experience base. Given the relative lack of evidence-based literature describing how to facilitate MR, we decided to disseminate a refined summary of the shared wisdom we uncovered in hopes that it would benefit other CMRs and junior faculty as they take on this challenging role.The insights provided fall within 5 main themes (Table 1) which are discussed below, followed by a brief discussion about future directions for MR:1) Planning and preparation2) The case3) Running the show4) Wrapping up5) Closing the LoopTable 1. Experience-Based Tips to Running an Effective Morning ReportPLANNING AND PREPARATION:1) Ensure audiovisual aids are present and working before starting. 2) Start and end on time. 3) Encourage all faculty to attend and participate. 4) Know the audience (including names).THE CASE:5) The case can be undifferentiated or one for which the diagnosis and even response to treatment is known. 6) There are pros and cons to the facilitator knowing details of the case in advance. 7) If details of the case are not known to the facilitator, determine with the person presenting if the discussion should be focused on diagnosis, management or other pertinent issues. 8) Cases need not be limited to inpatients and can include ambulatory cases and case simulations.RUNNING THE SHOW:9) Establish a respectful learning climate. 10) Personal anecdotes and reflections on past cases can engage the audience. 11) Ensure time is spent discuss learning issues valuable to all present. 12) Facilitate and engage in discussion rather than deliver a lecture. 13) Use a mix of pattern recognition (heuristics) and analytical reasoning strategies. 14) Start with a question that has an obvious answer if dealing with a quiet audience. 15) Promote volunteerism for answers as much as possible, but direct a question to a specific person if no one volunteers. 16) Begin by engaging the most junior learners and advance to involve senior learners. 17) Encourage resource stewardship and evidence-based medicine. 18) Acknowledge areas of uncertainty and don’t be afraid to say “I don’t know”. 19) Teaching “scripts” or the use of a systematic approach to developing a differential diagnosis can be used when discussing less familiar topics. 20) Highlight the variability in clinical approach amongst "the experts" in the room.WRAPPING-UP:21) Ensure there is time to summarize “take home points”. 22) Provide learners with the opportunity to summarize what they have learned.CLOSING THE LOOP23) Reinforcement of learning can include a distribution of a relevant paper or providing a summary of learning points via email or blog. 24) Maintain a case log to ensure a balanced curriculum. 25) Provide feedback to the case presenter and facilitator.Planning and Preparation It is important for the organizer and facilitator (these may or may not be the same person) to be diligent when preparing for MR. The person in charge of organizing MR should ensure that all necessary audiovisual equipment is in working order, which may be as simple as ensuring there is a whiteboard and working marker. To optimize housestaff attendance, the sessions and facilitators should be scheduled in a regular and predictable way. The lure of a light breakfast should not be underestimated and may add to the social aspect of this event. Sessions should begin and finish on time (or even slightly early). Ideally, deferring pages for all but critical clinical issues should occur. Having faculty regularly attend MR as audience participants, and not just as facilitators, improves the attendance of learners who see through role-modelling the importance of continuing medical education and lifelong learning. Faculty presence also raises the level of discussion around grey areas of diagnosis and management, providing trainees with a spectrum of opinions and approaches to clinical medicine, specifically role-modelling how faculty approach clinical uncertainty. The organizer must also ensure that someone, usually a trainee, is responsible for bringing the details of one or more clinical cases to be discussed.The facilitator should ensure they know the names and year of training of the housestaff in attendance. It is helpful if the organizer can provide a list (ideally with pictures) of those who will be in attendance for the facilitator to reference. Over time, this helps to develop a sense of community within the group. It also allows the facilitator to engage all participants and with the goals of first posing level-specific questions to the more junior learners and ending with the most senior learners.The Case The selected clinical case can be either a new patient seen in consultation in the past 24 hours or a patient that has been in hospital for some time and for whom results of investigations and response to treatment are known. Ideally, the majority of the cases selected should not involve particularly rare medical issues and should mirror the clinical case mix of patients being cared for by the trainees. Trainees will benefit more from discussions about common clinical problems rather. However, to highlight issues of diagnostic reasoning, it can be beneficial to occasionally discussing uncommon case including typical presentations of rare diseases or unusual presentations of common problems.The faculty surveyed expressed differing opinions when asked if they thought the details of the case should be known to the facilitator in advance. Knowing the details of the case in advance can ensure the facilitator is comfortable with the content area and allows them to focus on aspects of the case that they think will have the highest learning impact for trainees. However, when the case is not known to the facilitator, the audience will be more likely to garner insight into the clinical reasoning process of the facilitator. The opportunity to learn about the cognitive process that an “expert” uses when generating a differential diagnosis and formulating plans for investigation and management is potentially much more valuable than the discussion of content that could be read in a textbook or electronically. When the details of a case are not known, the discussion is more spontaneous and the lines of discussion are more reflective of the thoughts of the trainees, rather than the facilitator. The discussion can be guided by the case itself and the trainees’ questions and answers. A mixed approach to case discussion will provide the variety that the participants value.Although traditionally MR has focused on the diagnosis or management of one or more clinical cases from the inpatient service, its format is flexible enough to provide opportunity for discussion or for other important aspects of patient care. MR can also address ambulatory cases,7 include the presence of a real patient for the purposes of highlighting history-taking and clinical findings and also incorporate discussion of simulated cases, such as code blue scenarios. The discussion can also be enriched by the health professionals from other disciplines including, pharmacists, physical therapists, occupational therapists, nurses, and social workers. The case can also be selected to allow the discussion to be focused on other specific elements of management, such as resource utilization and “choosing wisely,”8 quality and safety, bioethics, and evidence-based medicine.9Running the Show In developing their skills in facilitation, many of the faculty surveyed discussed that they continuously build on the facilitation skills that they have learned over time, the basic principles of which are described elsewhere.10,11 Through feedback and reflection, they adapt to a style that reflects how they believe the MR should be conducted.The facilitator must establish a respectful climate at MR that is conducive to learning. He or she must ensure that the session is collegial and enforce that the goal of the session is learning, rather than showmanship. The environment should encourage interaction and permit people to ask questions. Trainees should feel comfortable enough to answer questions and test hypotheses, even if answers are incorrect. However, the facilitator must ensure that the correct information is conveyed to the group and that incorrect answers are explored as key teaching points. Humour can put people at ease. Self-deprecating humour can be non-threatening and freely employed if it is within the facilitator’s comfort zone. However, humour should never come at the expense of a trainee. Personal anecdotes and reflections on past cases can engage the audience, relax the atmosphere and vividly impart key facts and clinical wisdom.It is important for the facilitator to be respectful of time. Trainees often report that too much time is spent on reviewing the history and physical examination and on the development of an exhaustive differential diagnosis while less time is spent on investigation and management issues, which senior trainees find most valuable. There need not be a fixed formula related to how much time to spend on specific components of the case. A skilled facilitator will expand and abbreviate aspects of the case discussion based on the specific case presented. Some cases represent excellent opportunities to review evidence-based physical examination, some may highlight issues of resource stewardship related to investigation and some are particularly well-suited to discussion of evidence-based management.The facilitator should facilitate a clinical discussion, rather than deliver a didactic talk. He or she should coach the audience to identify key historical facts or findings on physical examination to allow everyone to fully participate in the case formulation and clinical reasoning that will follow. Demonstrating a mix of pattern recognition and heuristics (e.g., “Quick – what do you think the diagnosis is?”) and analytical reasoning strategies will help trainees learn to employ and recognize the strengths and limitations of each.In the face of a quiet audience, questions that have obvious answers should be posed first. The facilitator should promote volunteerism as much as possible; however, addressing specific members of the audience prevents silence and can help ensure everyone is engaged in the discussion. Sensitivity to the level of trainee is important. A facilitator should avoid potential embarrassment of a trainee by allowing a more junior learner to come up with the answer to a question that the more senior trainee could not answer. In other words, there should be an inviolate sequence wherein, for any given topic, the facilitator starts with trainees at an appropriate level for the questions and moves upward sequentially by level of training. This allows participants to relax and set their focus on learning, rather than avoiding eye contact and fearing embarrassment.A skilled facilitator should not allow any one person to dominate the discussion and should also refrain from asking multiple questions to the same participant. However, it can be valuable to challenge a respondent or the group to elaborate on their answers, as this can uncover gaps in knowledge and understanding and provide additional opportunities for learning.It is important to ensure that the discussion is of interest to trainees at all levels. If faculty are present, their opinions should be sought throughout the case. It is helpful to highlight the variability in approach amongst “the experts” in the room. Judicious use and justification of investigations should be encouraged to promote learning about resource stewardship and evidence-based medicine principles should be incorporated, when relevant.Many facilitators are anxious about how to handle situations where they don’t know the answer to a particular clinical problem. In these cases, a demonstration of the clinical reasoning process and a focus on an approach to clinical problems can be helpful. Some of the most useful discussions centre on how to deal with uncertainty and on how to find answers to clinical questions in real-time using available resources. The facilitator should not hesitate to say “I don’t know,” as this demonstrates that nobody has infinite knowledge and role-models the necessity of recognizing one’s limitations. Teaching scripts relating to specific topics or the use of an etiologic or body systems-based approach to developing a differential diagnosis are helpful teaching approaches6.Wrapping Up Sufficient time should be dedicated to recapitulation and repetition of one to 3 key take home messages. This serves to reinforce the important points that were discussed and to ensure that participants walk away with key messages to facilitate learning. Having a few members of the audience identify what they have learned is often beneficial as the facilitator may not identify the same issues as the trainees.Closing the Loop Further reinforcement can occur if a summary of the take home points, or a relevant paper, is circulated by email or posted to a blog.12 This must be done in a manner that protects patient confidentiality. Updates on previously presented diagnostic dilemmas will enhance learning. Finally, the organizer of MR can keep a log of cases that have been presented to avoid excessive repetition of topics and ensure a balanced curriculum.A process for the person presenting the case to be provided with feedback about their presentation skills by the facilitator or peers should be implemented. It is also important for the facilitator to receive feedback about their teaching and the session overall. Feedback will help faculty refine their facilitation skills, especially if coupled with faculty development initiatives to improve teaching skills.13 It may also be important for novice clinician teachers who need to build a teaching portfolio as part of their academic review and promotion process. 14 If it is clear the faculty utilize the feedback, it serves to role-model self-reflection and promote a culture of frequent formative feedback.The Future of MR MR has a long tradition and can be an evolving teaching format capable of meeting current educational needs. For example, with the implementation of competency-based medical education (CBME) into residency training programs, the competencies being developed for Internal Medicine trainees can provide a framework to organize aspects of learning experiences, including MR. 15 Issues of advocacy and stewardship may be highlighted as explicit learning points of cases, as MR allows for discussion of authentic core clinical tasks and problems, avoiding the reduction of competencies to endless lists taught without the necessary context needed for deeper learning.16 There are also challenges to implementing and sustaining a successful MR in today's current training climate. Issues such as duty-hour restrictions, increased volume and acuity of patients, and pressure to discharge patients early in the day17–19 have prompted some to modify the traditional MR. An “afternoon report” allows for attention to clinical duties early in the day and preserves teaching for later in the day. MR should continue to evolve to meet current education and healthcare delivery needs, and these innovations should be described in the literature and studied.Although these tips have been generated from shared experiences at a single centre, we believe they will be useful to facilitators in many other settings, as they represent the experiences of many facilitators with many cumulative years of experience. This article is intended to stimulate others to reflect upon and discuss what they have found to be the key elements to facilitating a successful MR.Acknowledgements We would like to thank our colleagues who contributed tips and whose teaching has influenced the careers of countless trainees: Dr. Ahmed Bayoumi, Dr. Isaac Bogoch, Dr. Mark Cheung, Dr. Allan Detsky, Dr. Irfan Dhalla, Dr. Vera Dounaevskaia, Dr. Trevor Jamieson, Dr. Lauren Lapointe Shaw, Dr. Jerome A. Leis, Dr. Don Livingstone, Dr. Julia Lowe, Dr. Ophyr Mourad, Dr. Valerie Palda, Dr. Joel Ray, Dr. Donald Redelmeier, Dr. Steve Shadowitz, Dr. Rob Sargeant.References1. Parrino TA, Villanueva AG. The principles and practice of MR. JAMA 1986;256(6):730–33.2. Amin Z, Guajardo J, Wisniewski W, Bordage G, Tekian A, Niederman LG. MR: focus and methods over the past three decades. Acad Med 2000;75(10):S1–S5.3. Gross CP, Donnelly GB, Reisman AB, Sepkowitz KA, Callahan MA. Resident expectations of MR: a multi-institutional study. Arch Int Med 1999;159(16):1910–14.4. McNeill M, Ali SK, Banks DE, Mansi IA. MR: can an established medical education tradition be validated? J Grad Med Educ 2013;5(3):374–84.5. Ways M, Kroenke K, Umali J, Buchwald D. MR: A survey of resident attitudes. Arch Int Med 1995;155(13):1433–37.6. Sacher AG, Detsky AS. Taking the stress out of MR: an analytic approach to the differential diagnosis. J Gen Intern Med 2009;24(6):747–51.7. Wenderoth S, Pelzman F, Demopoulos B. Ambulatory MR. J Grad Med Educ 2002;17(3):207–209.8. Kane GC, Holumzer C, Sorokin R. Utilization management MR: Purpose, planning and early experience in a university hospital residency program. Sem Med Pract 2001;4(1):27–36.9. Banks DE, Runhua Shi M. Decreased hospital length of stay associated with presentation of cases at MR with librarian support. J Med Libr Assoc 2007;95(4):381–87.10. Azer SA. Challenges facing PBL tutors: 12 tips for successful group facilitation. Med Teach 2005;27(8):676–81.11. Skeff KM. Enhancing teaching effectiveness and vitality in the ambulatory setting. J Gen Intern Med 1988;3(1):S26–S33.12. Bogoch II, Frost DW, Bridge S, Lee TC, Gold WL, Pansiko DM, Cavalcanti R. MR blog: a web-based tool to enhance case-based learning. Teach Learn Med 2012;24(3):238–41.13. Boerboom TB, Stalmeijer RE, Dolmans DH, Jaarsma DA. How feedback can foster professional growth of teachers in the clinical workplace: A review of the literature. Stud Educ Eval 2015;46:47–52.14. Fleming VM, Schindler N, Martin GJ, DaRosa DA. Separate and equitable promotion tracks for clinician-educators. JAMA 2005;294(9):1101–1104.15. Frank JR, Snell LS, Ten Cate O, Holmboe ES, Carraccio C, Swing SR, Harris, KA. Competency-based medical education: theory to practice. Med Teach, 2010;32(8):638–45.16. Hawkins RE, Welcher CM, Holmboe ES, Kirk LM, Norcini JJ, Simons KB, Skochelak SE. Implementation of competency‐based medical education: are we addressing the concerns and challenges? Med Educ. 2015;49(11):1086–1102.17. Arora VM, Georgitis E, Siddique J, Vekhter B, Woodruff JN, Humphrey HJ, Meltzer DO. Association of workload of on-call medical interns with on-call sleep duration, shift duration, and participation in educational activities. JAMA 2008;300(10):1146–53.18. Horwitz LI, Krumholz HM, Huot SJ, Green ML. Internal medicine residents' clinical and didactic experiences after work hour regulation: a survey of chief residents. J Gen Int Med 2006;21(9):961–65.19. Khanna S, Sier D, Boyle J, Zeitz K. Discharge timeliness and its impact on hospital crowding and emergency department flow performance. Emerg Med Aus 2016;28(2):164–70.

Handicap : nom commun d’origine anglo-saxonne dont l’étymologie proviendrait de Hand in Cap, une pratique populaire pour fixer la valeur d'échange d’un bien. Dans le domaine des courses de chevaux, le handicap vise à ajouter du poids aux concurrents les plus puissants pour égaliser les chances de gagner la course pour tous les participants. Il apparait dans le dictionnaire de l’Académie française dans les années 1920 dans le sens de mettre en état d’infériorité. Son utilisation pour désigner les infirmes et invalides est tardive, après les années 1950 et se généralise au début des années 1970. Par un glissement de sens, le terme devient un substantif qualifiant l’infériorité intrinsèque des corps différentiés par leurs atteintes anatomiques, fonctionnelles, comportementales et leur inaptitude au travail. Les handicapés constituent une catégorisation sociale administrative aux frontières floues créée pour désigner la population-cible de traitements socio-politiques visant l’égalisation des chances non plus en intervenant sur les plus forts mais bien sur les plus faibles, par des mesures de réadaptation, de compensation, de normalisation visant l’intégration sociale des handicapés physiques et mentaux. Ceci rejoint les infirmes moteurs, les amputés, les sourds, les aveugles, les malades mentaux, les déficients mentaux, les invalides de guerre, les accidentés du travail, de la route, domestiques et par extension tous ceux que le destin a doté d’un corps différent de la normalité instituée socio-culturellement dans un contexte donné, ce que les francophones européens nomment les valides. Dans une perspective anthropologique, l’existence de corps différents est une composante de toute société humaine (Stiker 2005; Fougeyrollas 2010; Gardou 2010). Toutefois l’identification de ce qu’est une différence signifiante pour le groupe culturel est extrêmement variée et analogue aux modèles d’interprétation proposés par François Laplantine (1993) dans son anthropologie de la maladie. Ainsi le handicap peut être conçu comme altération, lésion ou comme relationnel, fonctionnel, en déséquilibre. Le plus souvent le corps différent est un corps mauvais, marqueur symbolique culturel du malheur lié à la transgression d’interdits visant à maintenir l’équilibre vital de la collectivité. La responsabilité de la transgression peut être endogène, héréditaire, intrinsèque aux actes de la personne, de ses parents, de ses ancêtres, ou exogène, due aux attaques de microbes, de virus, de puissances malveillantes, génies, sorts, divinités, destin. Plus rarement, le handicap peut être un marqueur symbolique de l’élection, comme porteur d’un pouvoir bénéfique singulier ou d’un truchement avec des entités ambiantes. Toutefois être handicapé, au-delà du corps porteur de différences signifiantes, n’implique pas que l’on soit malade. Avec la médicalisation des sociétés développées, une fragmentation extrême du handicap est liée au pouvoir biomédical d’attribuer des diagnostics attestant du handicap, comme garde-barrière de l’accès aux traitements médicaux, aux technologies, à la réadaptation, aux programmes sociaux, de compensation ou d’indemnisation, à l’éducation et au travail protégé ou spécial. Les avancées thérapeutiques et de santé publique diminuent la mortalité et entrainent une croissance continue de la morbidité depuis la Deuxième Guerre mondiale. Les populations vivant avec des conséquences chroniques de maladies, de traumatismes ou d’atteintes à l’intégrité du développement humain augmentent sans cesse. Ceci amène l’Organisation mondiale de la santé (OMS) à s’intéresser non plus aux diagnostics du langage international médical, la Classification internationale des maladies, mais au développement d’une nosologie de la chronicité : la Classification internationale des déficiences, des incapacités et des handicaps qui officialise une perspective tridimensionnelle du handicap (WHO 1980). Cette conceptualisation biomédicale positiviste situe le handicap comme une caractéristique intrinsèque, endogène à l’individu, soit une déficience anatomique ou physiologique entrainant des incapacités dans les activités humaines normales et en conséquence des désavantages sociaux par rapport aux individus ne présentant pas de déficiences. Le modèle biomédical ou individuel définit le handicap comme un manque, un dysfonctionnement appelant à intervenir sur la personne pour l’éduquer, la réparer, l’appareiller par des orthèses, des prothèses, la rétablir par des médicaments, lui enseigner des techniques, des savoirs pratiques pour compenser ses limitations et éventuellement lui donner accès à des subsides ou services visant à minimiser les désavantages sociaux, principalement la désaffiliation sociale et économique inhérente au statut de citoyen non performant ( Castel 1991; Foucault 1972). À la fin des années 1970 se produit une transformation radicale de la conception du handicap. Elle est étroitement associée à la prise de parole des personnes concernées elles-mêmes, dénonçant l’oppression et l’exclusion sociale dues aux institutions spéciales caritatives, privées ou publiques, aux administrateurs et professionnels qui gèrent leur vie. C’est l’émergence du modèle social du handicap. Dans sa tendance sociopolitique néomarxiste radicale, il fait rupture avec le modèle individuel en situant la production structurelle du handicap dans l’environnement socio-économique, idéologique et matériel (Oliver 1990). La société est désignée responsable des déficiences de son organisation conçue sur la performance, la norme et la productivité entrainant un traitement social discriminatoire des personnes ayant des déficiences et l’impossibilité d’exercer leurs droits humains. Handicaper signifie opprimer, minoriser, infantiliser, discriminer, dévaloriser, exclure sur la base de la différence corporelle, fonctionnelle ou comportementale au même titre que d’autres différences comme le genre, l’orientation sexuelle, l’appartenance raciale, ethnique ou religieuse. Selon le modèle social, ce sont les acteurs sociaux détenant le pouvoir dans l’environnement social, économique, culturel, technologique qui sont responsables des handicaps vécus par les corps différents. Les années 1990 et 2000 ont été marquées par un mouvement de rééquilibrage dans la construction du sens du handicap. Réintroduisant le corps sur la base de la valorisation de ses différences sur les plans expérientiels, identitaires et de la créativité, revendiquant des modes singuliers d’être humain parmi la diversité des êtres humains (Shakespeare et Watson 2002; French et Swain 2004), les modèles interactionnistes : personne, environnement, agir, invalident les relations de cause à effet unidirectionnelles propres aux modèles individuels et sociaux. Épousant la mouvance de la temporalité, la conception du handicap est une variation historiquement et spatialement située du développement humain comme phénomène de construction culturelle. Une construction bio-socio-culturelle ouverte des possibilités de participation sociale ou d’exercice effectif des droits humains sur la base de la Déclaration des droits de l’Homme, des Conventions internationales de l’Organisation des Nations-Unies (femmes, enfants, torture et maltraitance) et en l’occurrence de la Convention relative aux droits des personnes handicapées (CDPH) (ONU 2006; Quinn et Degener 2002; Saillant 2007). Par personnes handicapées, on entend des personnes qui présentent des incapacités physiques, mentales, intellectuelles ou sensorielles dont l’interaction avec diverses barrières peut faire obstacle à leur pleine et effective participation à la société sur la base de l’égalité avec les autres. (CDPH, Art 1, P.4). Fruit de plusieurs décennies de luttes et de transformations de la conception du handicap, cette définition représente une avancée historique remarquable autant au sein du dernier des mouvements sociaux des droits civiques, le mouvement international de défense des droits des personnes handicapées, que de la part des États qui l’ont ratifiée. Malgré le fait que l’on utilise encore le terme personne handicapée, le handicap ne peut plus être considéré comme une caractéristique de la personne ni comme un statut figé dans le temps ni comme un contexte oppressif. Il est le résultat d’une relation dont il est nécessaire de décrire les trois composantes anthropologiques de l’être incarné : soi, les autres et l’action ou l’habitus pour en comprendre le processus de construction singulier. Le handicap est situationnel et relatif , sujet à changement, puisqu’il s’inscrit dans une dynamique interactive temporelle entre les facteurs organiques, fonctionnels, identitaires d’une part et les facteurs contextuels sociaux, technologiques et physiques d’autre part, déterminant ce que les personnes ont la possibilité de réaliser dans les habitudes de vie de leurs choix ou culturellement attendues dans leurs collectivités. Les situations de handicap ne peuvent être prédites à l’avance sur la base d’une évaluation organique, fonctionnelle, comportementale, identitaire ou de la connaissance de paramètres environnementaux pris séparément sans réintroduire leurs relations complexes avec l’action d’un sujet définissant le sens ou mieux incarnant la conscience vécue de cette situation de vie. Suite au succès de l’expression personne en situation du handicap en francophonie, on remarque une tendance à voir cette nouvelle appellation remplacer celle de personne handicapée. Ceci est généralement interprété comme une pénétration de la compréhension du modèle interactionniste et socio constructiviste. Toutefois il est inquiétant de voir poindre des dénominations comme personnes en situation de handicap physique, mental, visuel, auditif, intellectuel, moteur. Cette dérive démontre un profond enracinement ontologique du modèle individuel. Il est également le signe d’une tendance à recréer un statut de personne en situation de handicap pour remplacer celui de personne handicapée. Ceci nécessite une explication de la notion de situation de handicap en lien avec le concept de participation sociale. Une personne peut vivre à la fois des situations de handicap et des situations de participation sociale selon les activités qu’elle désire réaliser, ses habitudes de vie. Par exemple une personne ayant des limitations intellectuelles peut vivre une situation de handicap en classe régulière et avoir besoin du soutien d’un éducateur spécialisé mais elle ne sera pas en situation de handicap pour prendre l’autobus scolaire pour se rendre à ses cours. L’expression personne vivant des situations de handicap semble moins propice à la dérive essentialiste que personne en situation de handicap. Le phénomène du handicap est un domaine encore largement négligé mais en visibilité croissante en anthropologie. Au-delà des transformations de sens donné au terme de handicap comme catégorie sociale, utile à la définition de cibles d’intervention, de traitements sociaux, de problématiques sociales pour l’élaboration de politiques et de programmes, les définitions et les modèles présentés permettent de décrire le phénomène, de mieux le comprendre mais plus rarement de formuler des explications éclairantes sur le statut du handicap d’un point de vue anthropologique. Henri-Jacques Stiker identifie, en synthèse, cinq théories du handicap co-existantes dans le champ contemporain des sciences sociales (2005). La théorie du stigmate (Goffman 1975). Le fait du marquage sur le corps pour indiquer une défaveur, une disgrâce, un discrédit profond, constitue une manière de voir comment une infirmité donne lieu à l’attribution d’une identité sociale virtuelle, en décalage complet avec l’identité sociale réelle. Le handicap ne peut être pensé en dehors de la sphère psychique, car il renvoie toujours à l’image de soi, chez celui qui en souffre comme celui qui le regarde. Le regard d’autrui construit le regard que l’on porte sur soi mais en résulte également (Stiker 2005 :200). La théorie culturaliste qui met en exergue la spécificité des personnes handicapées, tout en récusant radicalement la notion même de handicap, est enracinée dans le multiculturalisme américain. Les personnes handicapées se constituent en groupes culturels avec leurs traits singuliers, à partir de conditions de vie, d’une histoire (Stiker 2005). Par exemple au sein des Disability Studies ou Études sur le handicap, il est fréquent de penser que seuls les corps différents concernés peuvent véritablement les pratiquer et en comprendre les fondements identitaires et expérientiels. L’exemple le plus probant est celui de la culture sourde qui se définit comme minorité ethno-linguistique autour de la langue des signes et de la figure identitaire du Sourd. On fera référence ici au Deaf Studies (Gaucher 2009). La théorie de l’oppression (Oliver 1990). Elle affirme que le handicap est produit par les barrières sociales en termes de déterminants sociologiques et politiques inhérents au système capitaliste ou productiviste. Les personnes sont handicapées non par leurs déficiences mais par l’oppression de l’idéologie biomédicale, essentialiste, individualiste construite pour empêcher l’intégration et l’égalité. Ce courant des Disability Studies s’inscrit dans une mouvance de luttes émancipatoires des personnes opprimées elles-mêmes (Stiker 2005 : 210; Boucher 2003) La théorie de la liminalité (Murphy 1990). Par cette différence dont ils sont les porteurs, les corps s’écartent de la normalité attendue par la collectivité et sont placés dans une situation liminale, un entre-deux qu’aucun rite de passage ne semble en mesure d’effacer, de métamorphoser pour accéder au monde des corps normaux. Cette théorie attribue un statut anthropologique spécifique au corps handicapé sans faire référence obligatoire à l’oppression, à l’exclusion, à la faute, ou au pouvoir. Marqués de façon indélébile, ils demeurent sur le seuil de la validité, de l’égalité, des droits, de l’humanité. La théorie de l’infirmité comme double, la liminalité récurrente de Stiker (2005). L’infirmité ne déclenche pas seulement la liminalité mais en référant à la psychanalyse, elle est un véritable double. La déficience est là, nous rappelant ce que nous n’aimons pas et ne voulons pas être, mais elle est notre ombre. Nous avons besoin de l’infirmité, comme de ceux qui la portent pour nous consoler d’être vulnérable et mortel tout autant que nous ne devons pas être confondus avec elle et eux pour continuer à nous estimer. Ils sont, devant nous, notre normalité, mais aussi notre espoir d’immortalité (Stiker 2005 : 223)