Tumor Necrosis Factors and Chemokines in Hair Development

Several embryonic organs, such as the hair follicle, develop as appendages of the ectoderm, the outermost layer of the embryo. These organs develop as a result of reciprocal tissue interactions between the surface epithelium and the underlying mesenchyme. The fi rst morphological sign of a developing hair follicle is a thickening of the epithelium called a placode. Several major signaling pathways are important for the development of hair and other ectodermal organs such as Wnts, fi broblast growth factors (Fgfs), Transforming growth factor-beta (TGF-beta), Hedgehogs (Hh) and tumor necrosis factors (TNFs). This thesis focuses on the role of TNFs in hair development and more particularly on one member of the TNF superfamily: Ectodysplasin (Eda). Mutations in Eda pathway components including the TNF ligand Eda, its receptor (Edar), and downstream effectors essential for activation of transcription factor NFbappaB in mouse or human give rise to a disease called hypohidrotic ectodermal dysplasia (HED). HED is an inherited disorder characterized by impaired development of ectodermal organs such as hair, teeth and several exocrine glands. A hallmark of mouse HED (Eda null mouse) is the absence of primary hair placodes that form at embryonic day 14 (E14). In order to identify the direct target genes of Eda, we have performed a microarray analysis on genes differentially expressed upon short exposure to recombinant Eda protein on Eda null skin at E14. Several of the genes identifi ed belong to the major signaling pathways mentioned above and interestingly, include also six chemokines that have not previously been associated with hair follicle morphogenesis. The purpose of this study was to validate whether the upregulated genes were truly transcriptional target genes of Eda/NFkappaB and to study their functional relevance in ectodermal organogenesis, in particular in hair follicle development. Based on these studies, we were able to confirm some Wnt pathway members, such as Dkk4 and Lrp4,TNF family member A20, and two chemokines, cxcl10 and cxcl11, as likely direct target genes of Eda. It is shown that whereas Dkk4 and Lrp4 are expressed in all ectodermal organs, A20 and the two chemokines seem to be hair follicle specific. Further study of Dkk4 and Lrp4 during development led us to conclude that Wnt and Eda pathways interact closely to fine tune the development of hair and other ectodermal organs. The role of A20 seems to be restricted to the termination of NFkappaB signaling induced by the Eda pathway in hair follicles. The lack of cxcl10 and cxcl11 signaling during hair follicle formation leads to more widely spaced hair placodes. This work has revealed an important role of Eda during hair placode induction as a modulator of inhibitors and activators of the major pathways in order to direct the patterning of hair placodes.Sikiönkehityksen aikana alkion pintakerroksesta, ektodermista, muodostuvat elimet, kuten karva, hammas, maito- ja hikirauhaset, saavat alkunsa pintakudoksen tihentymästä eli plakodista. Tämä kehityksen alkuvaihe on samankaltainen näillä elimillä ja sitä säätelevät samat tekijät. Tutkimukset ihmisessä ja hiirimalleilla ovat tuoneet tietoa näiden aineenvaihduntareittien toiminnasta normaalissa kehityksessä, sekä erilaisissa häiriöissä kuten perinnöllisessä kaljuuntumisessa ja hammasten kehityksen häiriöitä aiheuttavissa taudeissa. Säätelytekijöiden häiriöiden tiedetään myös aiheuttavan tiettyjä syöpätyyppejä. Tässä tutkimuksessa olemme selvittäneet TNF-tuumorinekroositekijäperheen jäsenen ektodysplasiinin (Eda) vaikutuskohteita karvan kehityksessä. Keskeisiä aineenvaihduntareittejä kehityksen säätelyssä ovat mm. Wnt, Fgf, TGF-beta, Hedgehog ja tuumorinekroositekijäperhe (TNF). Ektodysplasiini kuulu TNF-perheeseen. Tiedetään, että mutaatiot Eda-signaalinvälitysreitin eri osissa aiheuttavat muutoksia transkriptiotekijä NFkappaB:n aktivaatiossa. Tämä aiheuttaa ihmisillä sairauden, josta käytetään nimitystä HED (hypohidroottinen ektodermaalidysplasia). HED on perinnöllinen tauti, johon kuuluu useita ektodermaalisten elinten, mm. hampaiden, karvan ja hikirauhasten kehityshäiriöitä. Tässä tutkimuksessa olemme selvittäneet ektodysplasiinin kohdegeenejä HED-taudin hiirimallin ihoviljelmissä geenisiru-menetelmällä. Tunnettujen aineenvaihduntareittien lisäksi löysimme useita kemokiinejä, joiden ei ole aiemmin tiedetty säätelevän karvan kehitystä. Tutkimuksessa osoitimme, että Wnt-aineenvaihduntareitin geenit Dkk4, Lrp4, TNF-perheen A20 ja kemokiinit cxcl10 ja cxcl11 ovat Eda/NFkappaB-reitin suoria kohdegeenejä. Näistä nimenomaan kemokiinit cxcl10 ja -11 sekä A20- proteiini ovat karvaspesifisiä. Toiminnallisessa tutkimuksessa osoitimme, että Wnt- ja Eda- aineenvaihduntareitit hienosäätävät läheisessä vuorovaikutuksessa ektodermaalista kehitystä laajemmin. A20 sen sijaan pysäyttää Eda-välitteisen NFkappaB-signaloinnin kehittyvässä karvassa. Jos cxcl10 ja cxcl11 puuttuvat, karvaplakodit muodostuvat normaalia kauemmaksi toisistaan. Tämä työ osoittaa Eda-aineenvaihduntareitin keskeisen merkityksen karvaplakodien kehityksen säätelyssä: Se ohjaa muiden aineenvaihduntareittien säätelemää kaavoittumistapahtumaa niin, että karvat muodostuvat oikeisiin kohtiin. Tutkimuksen tulokset tuovat vastauksia perustavanlaatuisiin kehitysbiologisiin kysymyksiin. Lisäksi tulokset voivat auttaa löytämään uusia kohteita kudoksia uudistavien hoitojen kehittämiseksi ja selventää syövän syntyyn liittyviä prosesseja

Comparison of plasma exo-iohexol, endo-iohexol and creatinine clearances in cats with low, normal and high glomerular filtration rates

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Limited sampling strategies to estimate glomerular filtration rate in cats with low, normal and high glomerular filtration rates

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La gestion du manque d’eau structurel et des sécheresses en France

Cet article s’intéresse aux politiques et dispositifs de gestion du manque d’eau et des sécheresses en France. La première partie décrit les politiques et dispositifs existants, en distinguant la gestion quantitative des volumes d'eau et la gestion par les prix ainsi que les politiques structurelles et les politiques conjoncturelles. La seconde partie discute des politiques et dispositifs envisageables en France. Cela inclut des politiques incitant aux adaptations au niveau des exploitations, une réforme de la gestion de crise et des dispositifs de tarification et d’échange de droits qui pourraient être différenciés selon les utilisateurs, l’état de la ressource et la situation météorologique. Ces nouveaux dispositifs sont par ailleurs compatibles avec la réforme en cours et la mise en place des organismes uniques de gestion collective (OUGC) à l’échelle locale. / This article deals with policies and management measures addressing water scarcity and droughts in France. The first part describes existing practices, differentiating between quota and pricing instruments and between structural and temporary measures. The second part discusses policies and measures that could be applied in France. It includes policies providing incitation to support farm-level adaptations, a reform of current crisis management and pricing and market measures that could be differentiated depending on the end-user, the state of the resource and the weather conditions. Moreover, these measures fit in the current policy reform and the introduction of local institutions for collective water management, called OUGC

Belgique

Posidonia oceanica is a magniolophyte endemic to the Mediterranean Sea, in which flowering can vary depending on water temperature and nutrient concentration (C,N,P). Along corsican coast, in the Northwestern Mediterranean Sea, the flowering was unusual but in the last 20 years it flowered regularly. The aim of our study was to determine the effect of the frequency of flowering episode on the shoots by measuring the dynamics of elementary (C, N, P) and the trace element contents (TE) in different tissues (leaves, inflorescences and rhizomes) of flowering and non-flowering shoots. This study also focused on the biometry of these shoots. Keywords: Posidonia, North-Western Mediterranean, Trace elements, Monitoring, BiometricsThès

Deep-NFA: a Deep a contrario\textit{a contrario} Framework for Small Object Detection

The detection of small objects is a challenging task in computer vision. Conventional object detection methods have difficulty in finding the balance between high detection and low false alarm rates. In the literature, some methods have addressed this issue by enhancing the feature map responses, but without guaranteeing robustness with respect to the number of false alarms induced by background elements. To tackle this problem, we introduce an $\textit{a contrario}$ decision criterion into the learning process to take into account the unexpectedness of small objects. This statistic criterion enhances the feature map responses while controlling the number of false alarms (NFA) and can be integrated into any semantic segmentation neural network. Our add-on NFA module not only allows us to obtain competitive results for small target and crack detection tasks respectively, but also leads to more robust and interpretable results

A Contrario\textit{A Contrario} Paradigm for YOLO-based Infrared Small Target Detection

Detecting small to tiny targets in infrared images is a challenging task in computer vision, especially when it comes to differentiating these targets from noisy or textured backgrounds. Traditional object detection methods such as YOLO struggle to detect tiny objects compared to segmentation neural networks, resulting in weaker performance when detecting small targets. To reduce the number of false alarms while maintaining a high detection rate, we introduce an $\textit{a contrario}$ decision criterion into the training of a YOLO detector. The latter takes advantage of the $\textit{unexpectedness}$ of small targets to discriminate them from complex backgrounds. Adding this statistical criterion to a YOLOv7-tiny bridges the performance gap between state-of-the-art segmentation methods for infrared small target detection and object detection networks. It also significantly increases the robustness of YOLO towards few-shot settings.Comment: Accepted to ICASSP 202

Influence of water on the circulation of the West Nile Virus in horses in Southern France

International audienc

Plasma symmetric dimethylarginine and creatinine concentrations and glomerular filtration rate in cats with normal and decreased renal function

Background Glomerular filtration rate (GFR) is the gold standard in assessing renal function but is impractical. Serum creatinine (sCr) has limited sensitivity in identifying early chronic kidney disease (CKD), whereas symmetric dimethylarginine (SDMA) has been commercialized as more accurate biomarker. Studies comparing SDMA and sCr with GFR in cats are limited. Objectives To further investigate the diagnostic performance of SDMA in nonazotemic and azotemic cats. Animals Forty-nine client-owned cats: 17 cats with CKD, 15 cats with diabetes mellitus (DM), and 17 healthy cats. Methods Retrospective study using spare blood samples from cats with documented sCr and GFR results for SDMA analysis. Diagnostic performances of SDMA and sCr were evaluated using correlation coefficients, sensitivities, specificities, and receiver operator characteristic curves. Results Compared to healthy cats and cats with DM, CKD cats had significantly higher SDMA(plasma) (26.7 +/- 9.9 mu g/dL) and sCr (249.7 +/- 71.6 mu mol/L [2.8 +/- 0.8 mg/dL]; both P < .001) values. SDMA(plasma) (tau(B) = -0.57; P < .001) and sCr (tau(B) = -0.56; P < .001) were significantly correlated with GFR. SDMA(plasma) (tau(B) = 0.52; P < .001) had a significant relationship with sCr. SDMA(plasma) and sCr had similar sensitivity (76%-94% and 71%-88%, respectively) in detecting reduced renal function. Creatinine had higher specificity (94%-96%) than SDMA(plasma) (75%-76%) (P < .05). Conclusion and Clinical Importance In this study of azotemic and nonazotemic cats, SDMA was a reliable marker to identify decreased GFR. However, superiority of SDMA over sCr could not be confirmed

The carbon fraction in biomass and organic matter in boreal open woodlands of Eastern Canada

In Canada, boreal open woodlands (OWs) show interesting afforestation potential, but no detailed study is available regarding the carbon fraction (CF) of dry matter in biomass and litter reservoirs (tonne C/tonne dry mass). This study aimed at providing the very first specific CF values of C reservoirs and compartments in OWs, with the main hypothesis that given the particular stand characteristics of OWs, more precise CF values than IPCC’s default values would significantly change the calculation of C stocks in OWs. Results indicate that even though the CF values measured in this study were significantly different among the different C reservoirs and compartments in OWs, they matched the IPCC default CF values for the biomass (0.50) and humus (0.37) reservoirs. Therefore, the main hypothesis of this study – that more precise CF values than IPCC’s default values would significantly change the calculation of C stocks in OWs – was not supported by the results. Consequently, the IPCC default values of the CF in the biomass and litter (humus) reservoirs can be used to estimate C stocks in boreal OWs, for example when using OWs as the baseline scenario in afforestation projects. Les terrains dénudés secs (DS) boréaux du Canada montrent un potentiel de boisement intéressant, sauf qu’aucune étude détaillée n’est disponible à propos de la fraction carbonique (FC) de la matière sèche dans les réservoirs de la biomasse et de la litière (tonne de C par tonne de masse sèche). La présente étude visait à fournir les toutes premières valeurs spécifiques de FC des réservoirs et compartiments de C des DS, avec l’hypothèse principale que vu les caractéristiques particulières des DS, des valeurs de FC plus précises que les valeurs par défaut du GIEC changeraient significativement le calcul des stocks de C dans les DS. Les résultats indiquent que bien que les valeurs de FC étaient significativement différentes entre les réservoirs et compartiments des DS, elles étaient similaires aux valeurs par défaut du GIEC, tant pour les réservoirs de la biomasse (0.50) que de la litière (0.37). Ainsi, l’hypothèse principale de l’étude – que des valeurs de FC plus précises que les valeurs par défaut du GIEC changeraient significativement le calcul des stocks de C dans les DS – n’est pas soutenue par les résultats. Par conséquent, les valeurs de FC par défaut du GIEC pour les réservoirs de la biomasse et de la litière (humus) peuvent être utilisées pour estimer les stocks de C des DS boréaux, par exemple lorsque les DS font office de scénario de référence dans des projets de boisement