Éditeur(s) : Université des Antilles Le Carbet des Sciences
Extrait de : "Le théâtre des idées reçues" : conférence, le 17 novembre 2018. Palais des Congrès de Madiana
Description : Avec la prolifération sur les sites WEB, les blogs et les réseaux sociaux, comment Météo France et les autorités essaient de s'assurer que le citoyen a bien l'information officielle et pertinente en cas de menace météorologique pour lui permettre de gérer au mieux sa sécurité et/ou celle de ses proches ou de son entreprise ? L'objectif de cette intervention est de contrer les fake news dans la gestion des vigilances et des alertes météorologiques.

Droits : CC-BY-NC-ND - Attribution - Pas d'utilisation commerciale - Pas de modification
Permalien : http://www.manioc.org/fichiers/V19023
V19023

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Estrogen receptors (ER) α and β are found in both women and men in many tissues, where they have different functions, including having roles in cell proliferation and differentiation of the reproductive tract. In addition to estradiol (E2), a natural hormone, numerous compounds are able to bind ERs and modulate their activities. Among these compounds, phytoestrogens such as isoflavones, which are found in plants, are promising therapeutics for several pathologies. Glyceollins are second metabolites of isoflavones that are mainly produced in soybean in response to an elicitor. They have potentially therapeutic actions in breast cancer by reducing the proliferation of cancer cells. However, the molecular mechanisms driving these effects remain elusive. METHODS: First, to determine the proliferative or anti-proliferative effects of glyceollins, in vivo and in vitro approaches were used. The length of epithelial duct in mammary gland as well as uterotrophy after treatment by E2 and glyceollins and their effect on proliferation of different breast cell line were assessed. Secondly, the ability of glyceollin to activate ER was assessed by luciferase assay. Finally, to unravel molecular mechanisms involved by glyceollins, transcriptomic analysis was performed on MCF-7 breast cancer cells. RESULTS: In this study, we show that synthetic versions of glyceollin I and II exert anti-proliferative effects in vivo in mouse mammary glands and in vitro in different ER-positive and ER-negative breast cell lines. Using transcriptomic analysis, we produce for the first time an integrated view of gene regulation in response to glyceollins and reveal that these phytochemicals act through at least two major pathways. One pathway involving FOXM1 and ERα is directly linked to proliferation. The other involves the HIF family and reveals that stress is a potential factor in the anti-proliferative effects of glyceollins due to its role in increasing the expression of REDD1, an mTORC1 inhibitor. CONCLUSION: Overall, our study clearly shows that glyceollins exert anti-proliferative effects by reducing the expression of genes encoding cell cycle and mitosis-associated factors and biomarkers overexpressed in cancers and by increasing the expression of growth arrest-related genes. These results reinforce the therapeutic potential of glyceollins for breast cancer.
ISSN: 1478-811X

hal-01560288
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560288
DOI : 10.1186/s12964-017-0182-1
PUBMED : 28666461

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
Little is known about the impact of blood rheology on the occurrence of retinopathy in sickle cell disease (SCD). Fifty-nine adult SCD patients in steady-state condition participated to the study: 32 with homozygous SCD (sickle cell anemia; SCA) and 27 with sickle cell hemoglobin-C disease (SCC). The patients underwent retinal examination and were categorized according to the classification of Goldberg: 1) no retinopathy (group 1), 2) non-proliferative or proliferative stage I-II retinopathy (group 2) and 3) proliferative stage III-IV-V retinopathy (group 3). Hematological and hemorheological (whole blood viscosity, RBC deformability and aggregation properties) measurements were performed for each patient. In the whole SCD group (SCA + SCC patients) and in SCC patients, the group 3 had higher platelets count than group 2 but the difference between group 3 and group 1 did not reach statistical significance. No difference was observed for the other parameters between the three groups. SCC patients from the group 3 exhibited higher whole blood viscosity than SCC patients from the group 1. No significant difference was observed between the three groups in SCA patients. This study revealed that severe sickle proliferative retinopathy is associated with blood hyperviscosity in SCC patients but not in SCA patients.
ISSN: 1386-0291

inserm-00849032
http://www.hal.inserm.fr/inserm-00849032
http://www.hal.inserm.fr/inserm-00849032/document
http://www.hal.inserm.fr/inserm-00849032/file/inserm-00849032.pdf
DOI : 10.3233/CH-2012-1622

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.
ISSN: 0001-6322

hal-00875723
https://hal.archives-ouvertes.fr/hal-00875723
DOI : 10.1007/s00401-013-1084-y
PUBMED : 23400299

Éditeur(s) : EDP Sciences
Résumé : A population of the invasive slipper limpet (Crepidula fornicata) has been spreading in the Bay of Mont-Saint-Michel (Western English Channel) for 40 years. Sidescan sonar, underwater video and quantitative sampling were conducted in 1996 and 2004 to document the widening geographic spread of the species over the bay. The limpet population grew by 50% during this period, to reach a fresh biomass of about 150 000 t. This local study analyses causes and effects of the spread and provides a typical example of the limpet spreading process. This population increase has significant effects on the environment in the most densely colonized area (modification to the sediment and biodiversity), leading to the emergence of a new benthic community. Anthropic dredging activities are among the causative factors of the spread but are also adversely affected by the invasion.
Depuis 40 ans, la population de crépidules (Crepidula fornicata) prolifère en baie du Mont Saint-Michel (Manche Ouest). Deux études réalisées en 1996 et 2004 ont permis de cartographier et d'estimer le stock de la population grâce à des moyens similaires : sonar à balayage latéral, vidéo sous-marine et prélèvements quantitatifs à la benne. Durant cet intervalle de temps, la biomasse a augmenté de 50 % pour atteindre 150 000 t dans la baie en 2004. Cette étude comparative a permis d'analyser les causes et les effets d'une telle prolifération et d'en montrer le processus général. Dans les secteurs fortement colonisés, les effets sur l'environnement sont particulièrement néfastes (modification du sédiment et de la biodiversité) et aboutissent à une nouvelle communauté benthique. Les activités de pêche aux engins traînants (dragues et chaluts) sont à la fois les principales responsables et les victimes de cette prolifération.
Aquatic Living Resources (0990-7440) (EDP Sciences), 2009 , Vol. 22 , N. 1 , P. 11-19

Droits : 2009 EDP Sciences
http://archimer.ifremer.fr/doc/2009/publication-6351.pdf
DOI:10.1051/alr/2009004
http://archimer.ifremer.fr/doc/00000/6351/

Éditeur(s) : HAL CCSD
Résumé : International audience
Studies report that foetal exposure to paracetamol by maternal consumption can interfere with male reproductive development. Moreover, recent biomonitoring data report widespread presence of paracetamol in German and Danish populations, suggesting exposure via secondary (non-pharmaceutical) sources such as metabolic conversion from the ubiquitous industrial compound aniline. In this study we investigated the extent to which paracetamol and aniline can interfere with female reproductive development. Intrauterine exposure to paracetamol by gavage of pregnant dams resulted in shortening of the anogenital distance in adult offspring, suggesting that foetal hormone signalling had been disturbed. Female offspring of paracetamol-exposed mothers had ovaries with diminished follicle reserve and reduced fertility. Foetal gonads of exposed animals had also reduced gonocyte numbers, suggesting that the reduced follicle count in adults could be due to early disruption of germ cell development. However, ex vivo cultures of ovaries from 12.5 days post coitum foetuses showed no decrease in proliferation or expression following exposure to paracetamol. This suggests that the effect of paracetamol occurs prior to this developmental stage. Accordingly, using embryonic stem cells as a proxy for primordial germ cells we show that paracetamol is an inhibitor of cellular proliferation, but without cytotoxic effects. Collectively, our data show that intrauterine exposure to paracetamol at levels commonly observed in pregnant women, as well as its precursor aniline, may block primordial germ cell proliferation, ultimately leading to reduced follicle reserves and compromised reproductive capacity later in life
Toxicological Sciences

hal-01259211
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259211
DOI : 10.1093/toxsci/kfv332
PUBMED : 26732887

Éditeur(s) : Gauthier-Villars
Résumé : This review addresses the problem of recently introduced plants in the Mediterranean in order to analyse their vectors, the dispersal processes and the possible ecological and economic consequences. Ninety-five cases (94 macroscopic algae and one seagrass) are listed and discussed. Three major routes of access into the Mediterranean are indicated: shipping, the Suez canal and aqua-culture. The recent introduction of Caulerpa taxifolia along our coasts has called attention to a new potential source: aquaria. Among the successful acclimatizations, cold-temperate Pacific and Atlantic species remain confined to the north of the Mediterranean (Gulf of Lions, Adriatic), whereas some tropical or sub-tropical plants colonize large areas. Some introduced algae proliferate to the detriment of the indigenous Mediterranean vegetation. In contrast with some terrestrial introductions, no population crash has been observed in the Mediterranean, although some notable fluctuations seem to occur in coastal lagoons. From an economic point of view, the two activities most affected by this phenomenon are aquaculture and fishing. With the gradual disappearance of European frontiers, the worldwide development of marine cultures and the multiplication of giant Seaworlds, the transfer of live marine organisms will become routine and the risk of new introductions will considerably increase in the Mediterranean. Only international legislation, established by the countries of the littoral, will be able to control these problems.
Oceanologica Acta (0399-1784) (Gauthier-Villars), 1994 , Vol. 17 , N. 1 , P. 1-23

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/00098/20879/18493.pdf
http://archimer.ifremer.fr/doc/00098/20879/

Résumé : En 1999, le risque écologique encouru par les écosystèmes côtiers soumis à la prolifération de la crépidule, Crepidula fornicata, a été pleinement reconnu par la communauté scientifique nationale et internationale. Au niveau national, le Programme National Environnement Côtier (PNEC) et le programme national LITEAU ont tous deux identifié des actions thématiques prioritaires sur la dynamique de prolifération de la crépidule et les interactions crépidule/bivalves exploités. Les actions du LEMAR (UMR 6539 CNRS) sur cette thématique s’inscrivent dans deux projets : 1 - La crépidule : identifier les mécanismes de sa prolifération et caractériser ses effets sur le milieu pour envisager sa gestion. » (LITEAU) 2 - Recrutement, milieu physique et interactions d'espèces en environnement côtier : cas des mollusques » (PNEC ART2) En rade de Brest, l’accent est mis sur l’interaction des cycles biologiques de la crépidule et de la coquille Saint-Jacques. Les objectifs poursuivis en rade de Brest s’articulent en 4 points, dans le cadre de LITEAU : 1- Dynamique de colonisation de la crépidule en rade de Brest : acquisition des paramètres de dynamique de population (caractéristiques du cycle reproducteur, déterminisme du recrutement, dispersion, croissance, sensibilité aux efflorescences toxiques...) ; 2- Impact de cette prolifération sur l’évolution de la nature sédimentaire des zones colonisées et l’enrichissement en matière organique (par le biais de l’activité alimentaire et de la production de biodépôts) ; 3- Modifications engendrées sur les peuplements benthiques dans leur globalité (sites ateliers). La strate à crépidules, au sens biosédimentaire et écologique, verra sa définition affinée et sa dynamique analysée en vue d'obtenir un modèle prévisionnel des évolutions possibles en matière de biodiversité ; 4- Rôle de la crépidule dans le contrôle de la production primaire phytoplanctonique (par le biais des activités de filtration et de production de biodépôts).

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/00032/14292/11570.pdf
http://archimer.ifremer.fr/doc/00032/14292/

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
In contrast to mammals that have limited proliferation and neurogenesis capacities, the Xenopus frog exhibit a great potential regarding proliferation and production of new cells in the adult brain. This ability makes Xenopus a useful model for understanding the molecular programs required for adult neurogenesis. Transcriptional factors that control adult neurogenesis in vertebrate species undergoing widespread neurogenesis are unknown. NeuroD1 is a member of the family of proneural genes, which function during embryonic neurogenesis as a potent neuronal differentiation factor. Here, we study in detail the expression of NeuroD1 gene in the juvenile and adult Xenopus brains by in situ hybridization combined with immunodetections for proliferation markers (PCNA, BrdU) or in situ hybridizations for cell type markers (Vimentin, Sox2). We found NeuroD1 gene activity in many brain regions, including olfactory bulbs, pallial regions of cerebral hemispheres, preoptic area, habenula, hypothalamus, cerebellum and medulla oblongata. We also demonstrated by double staining NeuroD1/BrdU experiments, after long post-BrdU administration survival times, that NeuroD1 gene activity was turned on in new born neurons during post-metamorphic neurogenesis. Importantly, we provided evidence that NeuroD1-expressing cells at this brain developmental stage were post-mitotic (PCNA-) cells and not radial glial (Vimentin+) or progenitors (Sox2+) cells.
ISSN: 1932-6203

hal-00877023
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00877023
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00877023/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00877023/file/The_Neurogenic_Factor-accepted.pdf
DOI : 10.1371/journal.pone.0066487

Résumé : Few years ago, proliferations of the green seaweed Enteromorpha have been noticed on sorne beaches of the southem coast of Martinique (American French Island). A study, in the year 1992, shows that Enteromorpha has a seasonal development, that nitrogen is the limiting factor, and that its principal feeding cornes from urban discharges thrown away directly into growing areas.
Certaines plages de la côte sud de Martinique voient apparaître depuis quelques années des échouages gênants de l'algue verte Enteromorpha. Une étude, réalisée en 1992, montre que le cycle de développement est saisonnier, que l'élément limitant est l'azote, et que la principale alimentation des proliférations d'algues vertes provient de rejets domestiques directs dans les zones de production.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/00132/24277/22275.pdf
http://archimer.ifremer.fr/doc/00132/24277/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Inorganic arsenic is a toxic environmental contaminant to which humans are mainly exposed through drinking water. This metalloid impairs functions of several key immune cells. Particularly, it reduces IL-2 secretion and proliferation of blood peripheral mononuclear cells stimulated by lectins that, however, do not mimic physiological T cell activation. The present study used isolated human T cells activated, in a more physiological manner, through stimulation with CD3/CD28 antibodies, to carefully analyze the impact of arsenic on T cell proliferation and cytokine expression. We demonstrate that non cytotoxic concentrations of sodium arsenite (As(III), 0.25-2μM) significantly reduce T cell proliferation by increasing the percentage of non dividing cells blocked in G1 phase and by preventing cyclin D3 and CDC25A expression. They also markedly, although not totally, reduces IL-2 expression at both mRNA and protein levels; however, metalloid-dependent inhibition of T cells could not be reversed by addition of recombinant IL-2. In addition, As(III) markedly reduces secretion of interferon-γ without impairing that of IL-4 and IL-13; it also decreases interferon-γ mRNA levels but increases those of IL-13. Finally, simultaneously to its immune effects, As(III) rapidly and potently increases expression of the redox-sensitive genes HMOX1, NQO1 and GCLM in activated T cells without altering the levels of reactive oxygen species. In conclusion, our results demonstrate that As(III) inhibits T cell proliferation, independently of IL-2, and alters the Th balance of cytokines secreted by co-stimulated T cells which thus constitute direct targets of this major environmental contaminant.
ISSN: 0300-483X

inserm-00872848
http://www.hal.inserm.fr/inserm-00872848
DOI : 10.1016/j.tox.2012.05.025
PUBMED : 22683347

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Estrogen receptors (ERs) α and β are distributed in most tissues of women and men. ERs are bound by estradiol (E2), a natural hormone, and mediate the pleiotropic and tissue-specific effects of E2, such as proliferation of breast epithelial cells or protection and differentiation of neuronal cells. Numerous environmental molecules, called endocrine disrupting compounds, also interact with ERs. Phytoestrogens belong to this large family and are considered potent therapeutic molecules that act through their selective estrogen receptor modulator (SERM) activity. Using breast cancer cell lines as a model of estrogen-dependent proliferation and a stably ER-expressing PC12 cell line as a model of neuronal differentiating cells, we studied the SERM activity of major dietary compounds, such as apigenin, liquiritigenin, daidzein, genistein, coumestrol, resveratrol and zearalenone. The ability of these compounds to induce ER-transactivation and breast cancer cell proliferation and enhance Nerve Growth Factor (NGF) -induced neuritogenesis was assessed. Surprisingly, although all compounds were able to activate the ER through an estrogen responsive element reporter gene, they showed differential activity toward proliferation or differentiation. Apigenin and resveratrol showed a partial or no proliferative effect on breast cancer cells but fully contributed to the neuritogenesis effect of NGF. However, daidzein and zearalenone showed full effects on cellular proliferation but did not induce cellular differentiation. In summary, our results suggest that the therapeutic potential of phytoestrogens can diverge depending on the molecule and the phenotype considered. Hence, apigenin and resveratrol might be used in the development of therapeutics for breast cancer and brain diseases.
ISSN: 0041-008X

hal-01558816
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01558816
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01558816/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01558816/file/Lecomte%20et%20al.%20-%20Assessment%20of%20the%20potential%20activity%20of%20major%20diet.pdf
DOI : 10.1016/j.taap.2017.04.005

Éditeur(s) : Springer
Résumé : The transforming growth factor (TGF)-beta superfamily is a group of important growth factors involved in multiple processes such as differentiation, cell proliferation, apoptosis and cellular growth. In the Pacific oyster Crassostrea gigas, the oyster gonadal (og) TGF-beta gene was recently characterized through genome-wide expression profiling of oyster lines selected to be resistant or susceptible to summer mortality. Og TGF-beta appeared specifically expressed in the gonad to reach a maximum when gonads are fully mature, which singularly contrasts with the pleiotropic roles commonly ascribed to most TGF-beta family members. The function of og TGF-beta protein in oysters is unknown, and defining its role remains challenging. In this study, we develop a rapid bacterial production system to obtain recombinant og TGF-beta protein, and we demonstrate that og TGF-beta is processed by furin to a mature form of the protein. This mature form can be detected in vivo in the gonad. Functional inhibition of mature og TGF-beta in the gonad was conducted by inactivation of the protein using injection of antibodies. We show that inhibition of og TGF-beta function tends to reduce gonadic area. We conclude that mature og TGF-beta probably functions as an activator of germ cells development in oyster.
Marine Biotechnology (1436-2228) (Springer), 2011-10 , Vol. 13 , N. 5 , P. 971-980

Droits : Springer Science+Business Media, LLC 2011
http://archimer.ifremer.fr/doc/00042/15371/13438.pdf
DOI:10.1007/s10126-010-9361-4
http://archimer.ifremer.fr/doc/00042/15371/

Éditeur(s) : HAL CCSD
Résumé : International audience
STUDY QUESTION: Do freezing and in vitro culture procedures enhance the expression of proteins involved in apoptotic or autophagic pathways in murine pre-pubertal testicular tissue? SUMMARY ANSWER: IVM strongly modified apoptosis- and autophagy-related relative protein levels in mice testicular tissue whereas the impact of cryopreservation procedures was minimal at the end of the culture. WHAT IS KNOWN ALREADY: In vitro spermatogenesis remains a challenging technical issue as it imposes to find a very close balance between survival and death of germ cell natural precursors (i.e. gonocytes and spermatogonia), which will eventually undergo a complete spermatogenesis close to in vivo conditions. The establishment of efficient culture conditions coupled with suitable cryopreservation procedures (e.g. controlled slow freezing [CSF] and solid surface vitrification [SSV]) of pre-pubertal testicular tissue is a crucial step in the fields of fertility preservation and restoration to improve the spermatic yield obtained in vitro. STUDY DESIGN, SIZE, DURATION: Here, we study cryopreservation procedures (i.e. CSF or SSV) and the impact of culture media compositions. A first set of 66 mouse pre-pubertal testes were directly cultured during 30, 36, 38 and 60 days (D) from 2.5 to 6.5-day-old CD-1 mice to evaluate the impact of time-aspect of culture and to endorse the reverse phase protein microarrays (RPPM) technique as an adapted experimental tool for the field of in vitro spermatogenesis. Ninety others fresh, slow-frozen and vitrified pre-pubertal testes were cultured during 30 days for the principal study to evaluate the impact of cryopreservation procedures before and after culture. Thirty-four testes dissected from 2.5, 6.5, 36.5, 40.5, 42.5 and 62.5 days postpartum (dpp) mice, corresponding to the time frames of spermatogenesis orchestrated in vitro, were used as in vivo controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: After in vitro culture, testicular tissue samples originated from 2.5 or 6.5-day-old CD-1 male mice were analyzed using RPPM. This targeted proteomic technique allowed us to assess the expression level of 29 apoptosis- and autophagy-related factors by normalizing blank-corrected signal values. In addition, morphological analyses (e.g. HES, PAS, TRA98 and CREM) and DNA fragmentation in intra-tubular cells (i.e. terminal deoxynucleotidyl transferase dUTP nick end labeling; TUNEL) were assessed for the distinct experimental conditions tested as well as for in vivo control mouse testes. MAIN RESULTS AND THE ROLE OF CHANCE: A validation of the RPPM procedure in the field of in vitro spermatogenesis was completed with assay and array robustness before a principal study concerning the evaluation of the impact of in vitro culture and cryopreservation procedures. The proportion of elongated spermatids and the total cell number per seminiferous tubule tended to be very different between the in vivo and in vitro conditions (P < 0.05), suggesting the presence of a beneficial regulation on the first spermatogenesis wave by intrinsic apoptosis (Caspase₉) and autophagy (Atg5) factors (P < 0.0003 and r2 = 0.74). Concerning the impact of culture media compositions, a basic medium (BM) composed of αMEM plus 10% KnockOut™ serum replacement and gentamicin supplemented with retinol (Rol) and vitamin E (Vit. E) was selected as the best culture medium for fresh 6.5 dpp tissue cultured during 30D with 27.7 ± 8.10% of seminiferous tubules containing elongated spermatids. Concerning the impact of cryopreservation procedures, SSV did not have any impact on the morphological parameters evaluated after culture in comparison to fresh tissue (FT) controls. The proportion of tubules with elongated spermatids on testicular explants cultured with BMRol+Vit. E was not different between SSV (6.6 ± 1.6%) and CSF (5.3 ± 1.9%); however, round spermatids were observed more frequently for SSV (19 ± 6.2%) than CSF (3.3 ± 1.9%, P = 0.0317). Even if the proportion of TUNEL-positive cells for BMRol+Vit. E was higher at D30 after SSV (4.12 ± 0.26%) than CSF (1.86 ± 0.12%, P = 0.0022) and FT (2.69 ± 0.33%, P = 0.0108), the DNA damages observed at the end of the culture (i.e. D30) were similar to respective 6.5 dpp controls. In addition, the relative protein level expression ratio of an apoptotic factor, the phosphorylated FADD on Fas, was reduced by 64-fold in vitrified testes cultured with BMRol+Vit. E. Furthermore, we found in this study that the StemPro®-34 SFM culture medium supplemented with growth factors (e.g. EGF, bFGF, GDNF and LIF) prevented the differentiation of spermatogonial stem cells in favor of a significant proliferation with a better architectural pattern than in vivo 6.5 dpp controls with an increase of seminiferous tubules area for FT (P = 0.0357) and CSF (P = 0.0317). LIMITATIONS REASONS FOR CAUTION: Despite our promising results, the evaluation of apoptotic- and autophagic-related proteins was studied for a limited amount of proteins and on global testicular tissue. WIDER IMPLICATIONS OF THE FINDINGS: The data presented herein will help to improve apoptotic and autophagic understanding during the first spermatogenic wave. Moreover, our findings illustrate for the first time that, using finely-tuned experimental conditions, a testicular in vitro culture combined with proteomic technologies may significantly facilitate the study of cryopreservation procedures and in vitro culture evaluations. This study may also contribute to improve work on testicular tissues from pre-pubertal and adolescent cancer survivors. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a Ph.D. grant from the Rouen Normandie Université and a financial support from 'la Ligue nationale contre le cancer' (both awarded to L.D.), funding from Institute for Research and Innovation in Biomedicine (IRIB), Agence de la Biomédecine, and co-supported by European Union and Région Normandie. Europe gets involved in Normandie with European Regional Development Fund (ERDF). The authors declare that there is no conflict of interest.
Molecular Human Reproduction

hal-01647081
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647081
DOI : 10.1093/molehr/gax054
PUBMED : 29040674

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Cell proliferation is a hallmark of cancer and depends on complex signaling networks that are chiefly supported by protein kinase activities. Therapeutic strategies have been used to target specific kinases but new methods are required to identify combined targets and improve treatment. Here, we propose a small interfering RNA genetic screen and an integrative approach to identify kinase networks involved in the proliferation of cancer cells. The functional siRNA screen of 714 kinases in HeLa cells identified 91 kinases implicated in the regulation of cell growth, most of them never being reported in previous whole-genome siRNA screens. Based on gene ontology annotations, we have further discriminated between two classes of kinases that, when suppressed, result in alterations of the mitotic index and provoke cell-cycle arrest. Extinguished kinases that lead to a low mitotic index mostly include kinases implicated in cytosolic signaling. In contrast, extinguished kinases that result in a high mitotic index mostly include kinases implicated in cell division. By mapping hit kinases in the PhosphPOINT phosphoprotein database, we generated scale-free networks consisting of 449 and 661 protein-protein interactions for kinases from low MI and high MI groups, respectively. Further analyses of the kinase interactomes revealed specific modules such as FER- and CRKL-containing modules that connect three members of the epidermal growth factor receptor (EGFR) family, suggesting a tight control of the mitogenic EGF-dependent pathway. Based on experimental studies, we confirm the involvement of these two kinases in the regulation of tumor cell growth. Based on a combined approach of large kinome-wide siRNA screens and ontology annotations, our study identifies for the first time two kinase groups differentially implicated in the control of cell proliferation. We further demonstrate that integrative analysis of the kinase interactome provides key information which can be used to facilitate or optimize target design for new therapeutic strategies. The complete list of protein-protein interactions from the two functional kinase groups will provide a useful database for future investigations.
ISSN: 1471-2164

hal-01118475
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118475
DOI : 10.1186/1471-2164-15-1169
PUBMED : 25540073

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
: In non-mammalian vertebrates, serotonin (5-HT)-producing neurons exist in the paraventricular organ (PVO), a diencephalic structure containing cerebrospinal fluid (CSF)-contacting neurons exhibiting 5-HT or dopamine (DA) immunoreactivity. Because the brain of the adult teleost is known for its neurogenic activity supported, for a large part, by radial glial progenitors, this study addresses the origin of newborn 5-HT neurons in the hypothalamus of adult zebrafish. In this species, the PVO exhibits numerous radial glial cells (RGCs) whose somata are located at a certain distance from the ventricle. To study relationships between RGCs and 5-HT CSF-contacting neurons, we performed 5-HT immunohistochemistry in transgenic tg(cyp19a1b-GFP) zebrafish in which RGCs are labelled with GFP under the control of the cyp19a1b promoter. We show that the somata of the 5-HT neurons are located closer to the ventricle than those of RGCs. RGCs extend towards the ventricle cytoplasmic processes that form a continuous barrier along the ventricular surface. In turn, 5-HT neurons contact the CSF via processes that cross this barrier through small pores. Further experiments using proliferating cell nuclear antigen or 5-bromo-2'-deoxyuridine indicate that RGCs proliferate and give birth to 5-HT neurons migrating centripetally instead of centrifugally as in other brain regions. Furthermore, treatment of adult zebrafish with tryptophan hydroxylase inhibitor causes a significant decrease in the number of proliferating cells in the PVO, but not in the mediobasal hypothalamus. These data point to the PVO as an intriguing region in which 5-HT appears to promote genesis of 5-HT neurons that accumulate along the brain ventricles and contact the CSF.
ISSN: 0953-816X

inserm-00866212
http://www.hal.inserm.fr/inserm-00866212
DOI : 10.1111/ejn.12348
PUBMED : 23981075

Éditeur(s) : Université Montpellier 2 - Sciences et Techniques du Languedoc
Résumé : The work reported here was motivated by the economical importance of the pacific blue shrimp Litopenaeus stylirostris farming where high mortality rates are due to bacterial and viral diseases. It consists in the characterisation of two original peptides, the first members of a new multifunctional family of peptides from peneide shrimps, the stylicines. Those two peptides, named stylicines 1 and 2, are negatively charged (pI < 6.0), and characterised by a proline-rich N-terminal region and a C-terminal region containing 13 cysteine residues. Stylicines are synthesized by heamocytes where they are stored within small cytoplasmic granules. To understand the role of these peptides in the immune response of shrimps to a vibrio infection, their recombinant forms were produced in E. coli BL21 (DE3) plysS, purified and characterised. The two rstylicines display biological anti-proliferative and blood clotting activities. Only rstylicine 1 displays antimicrobial activities: antifungal against Fusarium oxysporum (MIC<2.5μM) and bacteriostatic against Gram (−) bacteria, Vibrio sp. (MIC<80μM). Moreover this peptide displays an LPS-binding activity (dissociation constant (Kd) of 9.6×10−8 M) and agglutinate Vibrio. penaeicida "in vitro". Finally, the presence of sequences coding for modified forms of stylicine 1 in some shrimp’s genome may be in relation with their lower ability to survive infections.
Les travaux présentés dans ce mémoire ont été motivés par l’importance économique de l’élevage de la crevette bleue du pacifique Litopenaeus stylirostris dont les fortes mortalités sont principalement dues au développement de maladies bactériennes et virales. Ils ont consisté en la caractérisation des deux premiers membres d’une famille originale de peptides multifonctionnels présents chez les crevettes pénéides, les stylicines. Ces peptides, nommés stylicines 1 et 2, sont des peptides anioniques (pI < 6.0), formés d’une région amino-terminale riche en résidus de type proline et d’une région carboxyterminale riche de treize résidus cystéines. Ces molécules sont synthétisées et stockées dans de petits granules présents dans le cytoplasme des hémocytes. Pour mieux appréhender leurs rôles dans la réponse immunitaire des crevettes à une infection par des Vibrio, leurs formes recombinantes ont été produites dans E. coli BL21 (DE3) plysS, purifiées et caractérisées. Les deux rstylicines présentent des activités antiproliférative et anticoagulante. Seule la rstylicine1 présente des activités antimicrobiennes : antifongique sur Fusarium oxysporum (CMI<2.5 μM), et antibactérienne (bactériostatique) sur Vibrio sp (CMI<80 μM). Ce peptide est également capable de se lier aux LPS des bactéries à Gram (-) (Kd= 9.6x10-8 M) et d’agglutiner V. penaeicida "in vitro". Enfin, l’existence de gènes codant des formes modifiées de la stylicine1, chez certaines crevettes, pourrait être en relation avec une diminution de la résistante des individus aux infections.

Droits : 2010 The Author, Univ Montpellier 2
http://archimer.ifremer.fr/doc/00024/13558/10612.pdf
http://archimer.ifremer.fr/doc/00024/13558/

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: The Hippo pathway regulates growth rate and organ size in fly and mouse, notably through control of cell proliferation. Molecular interactions at the heart of this pathway are known to have originated in the unicellular ancestry of metazoans. They notably involve a cascade of phosphorylations triggered by the kinase Hippo, with sub‑ sequent nuclear to cytoplasmic shift of Yorkie localisation, preventing its binding to the transcription factor Scalloped, thereby silencing proliferation genes. There are few comparative expression data of Hippo pathway genes in non‑ model animal species and notably none in non‑bilaterian phyla.Results: All core Hippo pathway genes could be retrieved from the ctenophore Pleurobrachia pileus and the hydro‑ zoan cnidarian Clytia hemisphaerica, with the important exception of Yorkie in ctenophore. Expression study of the Hippo, Salvador and Scalloped genes in tentacle " cellular conveyor belts " of these two organisms revealed striking differences. In P. pileus, their transcripts were detected in areas where undifferentiated progenitors intensely prolifer‑ ate and where expression of cyclins B and D was also seen. In C. hemisphaerica, these three genes and Yorkie are expressed not only in the proliferating but also in the differentiation zone of the tentacle bulb and in mature tentacle cells. However, using an antibody designed against the C. hemiphaerica Yorkie protein, we show in two distinct cell lineages of the medusa that Yorkie localisation is predominantly nuclear in areas of active cell proliferation and mainly cytoplasmic elsewhere.Conclusions: This is the first evidence of nucleocytoplasmic Yorkie shift in association with the arrest of cell prolifera‑ tion in a cnidarian, strongly evoking the cell division‑promoting role of this protein and its inhibition by the activated Hippo pathway in bilaterian models. Our results furthermore highlight important differences in terms of deployment and regulation of Hippo pathway genes between cnidarians and ctenophores.
ISSN: 2041-9139

Droits : http://creativecommons.org/licenses/by/
hal-01286578
http://hal.upmc.fr/hal-01286578
http://hal.upmc.fr/hal-01286578/document
http://hal.upmc.fr/hal-01286578/file/comparative.pdf
DOI : 10.1186/s13227-016-0041-y

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The brain of the adult teleost fish exhibits intense neurogenic activity and an outstanding capability for brain repair. Remarkably, the brain estrogen-synthesizing enzyme, aromatase B, is strongly expressed, particularly in adult fishes, in radial glial cells, which act as progenitors. Using zebrafish, we tested the hypothesis that estrogens affect adult neurogenesis and brain regeneration by modulating the neurogenic activity of radial glial cells. To investigate this, the estrogenic environment was modified through inhibition of aromatase activity, blockade of nuclear estrogen receptors, or estrogenic treatments. Estrogens significantly decreased cell proliferation and migration at the olfactory bulbs/telencephalon junction and in the mediobasal hypothalamus. It also appears that cell survival is reduced at the olfactory bulbs/telencephalon junction. We also developed a model of telencephalic lesion to assess the role of aromatase and estrogens in brain repair. Proliferation increased rapidly immediately after the lesion in the parenchyma of the injured telencephalon, while proliferation at the ventricular surface appeared after 48 h and peaked at 7 days. At this time, most proliferative cells express Sox2, however, none of these Sox2 positive cells correspond to aromatase B-positive radial glial cells. Interestingly, aromatase B expression was significantly reduced 48 h and 7 days after the injury, but surprisingly, at 72 h after lesion, aromatase B expression appeared de novo expressed in parenchyma cells, suggesting a role for this ectopic expression of aromatase in brain repair mechanisms. Altogether these data suggest that estrogens modulate adult, but not reparative neurogenesis, in zebrafish.
ISSN: 0018-506X

inserm-00831715
http://www.hal.inserm.fr/inserm-00831715
DOI : 10.1016/j.yhbeh.2012.04.003
PUBMED : 22521210

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Adult fish exhibit a strong neurogenic capacity due to the persistence of radial glial progenitor cells. In zebrafish, radial glial cells display well-established markers such as the estrogen-synthesizing enzyme (AroB) and the brain lipid binding protein (Blbp), which is known to strongly bind omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA). While Blpb is mainly described in the telencephalon of adult zebrafish, its expression in the remaining regions of the brain is poorly documented. The present study was designed to further investigate Blbp expression in the brain, its co-expression with AroB, and its link with radial glial cells proliferation in zebrafish. We generated a complete and detailed mapping of Blbp expression in the whole brain and show its complete co-expression with AroB, except in some tectal and hypothalamic regions. By performing PCNA and Blbp immunohistochemistry on cyp19a1b-GFP (AroB-GFP) fish, we also demonstrated preferential Blbp expression in proliferative radial glial cells in almost all regions studied. To our knowledge, this is the first complete and detailed mapping of Blbp-expressing cells showing strong association between Blbp and radial glial cell proliferation in the adult brain of fish. Given that zebrafish is now recognized models for studying neurogenesis and brain repair, our data provide detailed characterization of Blbp in the entire brain and open up a broad field of research investigating the role of omega-3 polyunsaturated fatty acids in neural stem cell activity in fish
ISSN: 1567-133X

hal-01237088
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237088
DOI : 10.1016/j.gep.2015.11.003
PUBMED : 26611722