25 research outputs found
Tumors escape immunosurveillance by overexpressing the proteasome activator PSME3
The success of CD8+ T cell-based cancer immunotherapy emphasizes the importance of understanding the mechanisms of generation of MHC-I peptide ligands and the possible pathways of tumor cell escape from immunosurveillance. Recently, we showed that peptides generated in the nucleus during a pioneer round of mRNA translation (pioneer translation products, or PTPs) are an important source of tumor specific peptides which correlates with the aberrant splicing and transcription events associated with oncogenesis. Here we show that up-regulation of PSME3 proteasome activator in cancer cells results in increased destruction of PTP-derived peptides in the nucleus thus enabling cancer cell to subvert immunosurveillance. These findings unveil a previously unexpected role for PSME3 in antigen processing and identify PSME3 as a druggable target to improve the efficacy of cancer immunotherapy
Fostering relations: first sex and marital timings for children raised by kin and non-kin carers
Kinship fostering is generally preferred to non-kin fostering by policy makers in the U.S. and elsewhere. Researchers and policy makers alike tend to provide several proximate reasons for why this may be, generally neglecting an ultimate evolutionary framework. However, kin selection theory predicts that in the absence of genetically related parents, care from kin will result in the most similar life history outcomes. In low-fertility settings, parents typically favour increased investment in embodied capital and thus delayed reproductive life history strategy. Using archival data from the original Kinsey survey, collected in the U.S. from 1938 to 1963, we used survival analyses to compare the effects of living with kin and non-kin fosterers in childhood on timings of first sex and marriage. Our results support a kin selection hypothesis showing that while fostered children have accelerated life histories compared to children from "intact families", kin fosterers buffer children from early sexual and reproductive behaviors, compared to children cared for by non-kin. © 2014 The Authors
Fetal growth restriction and intra-uterine growth restriction: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians
International audienc
Lâinterruption volontaire de grossesse : recommandations pour la pratique clinique â Texte des recommandations (texte court).
National audienceObjectif Ălaborer des recommandations pour la pratique des IVG. MatĂ©riel et mĂ©thodes Consultation de la base de donnĂ©es Medline, de la Cochrane Library et des recommandations des sociĂ©tĂ©s savantes françaises et Ă©trangĂšres. RĂ©sultats Le nombre dâIVG est stable depuis plusieurs dĂ©cennies. Il existe plusieurs Ă©lĂ©ments expliquant le choix de lâIVG lorsquâil existe une grossesse non prĂ©vue (GNP). Lâinitiation prĂ©coce de la contraception et le choix de la contraception en rapport avec la vie de la femme sont associĂ©s Ă une diminution des GNP. Les contraceptions rĂ©versibles de longue durĂ©e dâaction apparaissent comme une contraception Ă positionner en premiĂšre ligne pour lâadolescente du fait de son efficacitĂ© (grade C). LâĂ©chographie avant une IVG doit ĂȘtre encouragĂ©e mais nâest pas indispensable pour rĂ©aliser une IVG (accord professionnel). DĂšs lâapparition Ă©chographique de lâembryon, lâestimation de la datation de la grossesse se fait par la mesure de la longueur cranio-caudale (LCC) ou par la mesure du diamĂštre bipariĂ©tal (BIP) Ă partir de 11 SA (grade B). Les mesures Ă©tant fiables à ± 5 jours, lâIVG peut ĂȘtre rĂ©alisĂ©e lorsque les mesures de LCC et/ou de BIP sont respectivement infĂ©rieures Ă 90 mm et 30 mm (accord professionnel). LâIVG mĂ©dicamenteuse rĂ©alisĂ©e avec la dose de 200 mg de mifĂ©pristone associĂ© au misoprostol est efficace Ă tout Ăąge gestationnel (NP1). Avant 7 SA, la prise de mifĂ©pristone sera suivie entre 24 et 48 heures de la prise de misoprostol par voie orale, buccale, sublinguale voire vaginale Ă la dose de 400 ÎŒg Ă©ventuellement renouvelĂ© aprĂšs 3 heures (NP1, grade A). Au-delĂ de 7 SA, les modes dâadministration du misoprostol, par voie vaginale, sublinguale ou buccale, sont plus efficaces et mieux tolĂ©rĂ©s que la voie orale (NP1). Il est recommandĂ© dâutiliser systĂ©matiquement une prĂ©paration cervicale lors dâune IVG instrumentale (accord professionnel). Le misoprostol est un agent de premiĂšre intention pour la prĂ©paration cervicale Ă la dose de 400 ÎŒg (grade A). Lâaspiration Ă©vacuatrice est prĂ©fĂ©rable au curetage (grade B). Un utĂ©rus perforĂ© lors dâune aspiration instrumentale ne doit pas ĂȘtre considĂ©rĂ© en routine comme un utĂ©rus cicatriciel (accord professionnel). LâIVG instrumentale nâest pas associĂ©e Ă une augmentation du risque dâinfertilitĂ© ultĂ©rieure ou de GEU (NP2). Les consultations mĂ©dicales prĂ©-IVG nâinfluent pas sur la dĂ©cision dâinterrompre ou non la grossesse et une majoritĂ© de femmes est assez sĂ»re de son choix lors de ces consultations. LâacceptabilitĂ© de la mĂ©thode et la satisfaction des femmes semblent plus grandes lorsque celles-ci sont en mesure de choisir la mĂ©thode dâIVG (grade B). Il nây a pas de relation entre une augmentation des troubles psychiatriques et le recours Ă lâIVG (NP2). Les femmes ayant des antĂ©cĂ©dents psychiatriques sont Ă risque accru de troubles psychiques aprĂšs la survenue dâune grossesse non prĂ©vue (NP2). En cas dâIVG instrumentale, la contraception estro-progestative orale et le patch devraient ĂȘtre dĂ©butĂ©s dĂšs le jour de lâIVG, lâanneau vaginal insĂ©rĂ© dans les 5 jours suivant lâIVG (grade B). En cas dâIVG mĂ©dicamenteuse, lâanneau vaginal devrait ĂȘtre insĂ©rĂ© dans la semaine suivant la prise de mifĂ©pristone, la contraception estro-progestative orale et le patch devraient ĂȘtre dĂ©butĂ©s le jour mĂȘme ou le lendemain de la prise des prostaglandines (grade C). En cas dâIVG instrumentale, lâimplant devrait ĂȘtre insĂ©rĂ© le jour de lâIVG (grade B). En cas dâIVG mĂ©dicamenteuse, lâimplant peut ĂȘtre insĂ©rĂ© Ă partir du jour de la prise de mifĂ©pristone (grade C). Le DIU au cuivre et au lĂ©vonorgestrel doit ĂȘtre insĂ©rĂ© prĂ©fĂ©rentiellement le jour de lâIVG instrumentale (grade A). En cas dâIVG mĂ©dicamenteuse, un DIU peut ĂȘtre insĂ©rĂ© dans les 10 jours suivant la prise de mifĂ©pristone aprĂšs sâĂȘtre assurĂ© par Ă©chographie de lâabsence de grossesse intra-utĂ©rine (grade C). Conclusion Lâapplication de ces recommandations devrait favoriser une prise en charge plus homogĂšne et amĂ©liorĂ©e des femmes dĂ©sirant une IVG. Summary Objective Develop recommendations for the practice of induced abortion. Materials and methods The Pubmed database, the Cochrane Library and the recommendations from the French and foreign Gyn-Obs societies or colleges have been consulted. Results The number of induced abortions (IA) has been stable for several decades. There are a lot of factors explaining the choice of abortion when there is an unplanned pregnancy (UPP). Early initiation and choice of contraception in connection to the woman's life are associated with lower NSP. Reversible contraceptives of long duration of action should be positioned fist in line for the teenager because of its efficiency (grade C). Ultrasound before induced abortion must be encouraged but should not be obligatory before performing IA (Professional consensus). As soon as the sonographic apparition of the embryo, the estimated date of pregnancy is done by measuring the crown-rump length (CRL) or by measuring the biparietal diameter (BIP) from 11 weeks on (grade B). Reliability of these parameters being ± 5 days, IA could be done if measurements are respectively less than 90 mm for CRL and less than 30 mm for BIP (Professional consensus). A medical IA performed with a dose of 200 mg mifepristone combined with misoprostol is effective at any gestational age (EL1). Before 7 weeks, mifepristone followed between 24 and 48 hours by taking misoprostol orally, buccally sublingually or eventually vaginally at a dose of 400 ug possibly renewed after 3 hours (EL1, grade A). Beyond 7 weeks, misoprostol given vaginally, sublingually or buccally are better tolerated with fewer side effects than oral route (EL1). It is recommended to always use a cervical preparation during an instrumental abortion (Professional consensus). Misoprostol is a first-line agent for cervical preparation at a dose of 400 mcg (grade A). Aspiration evacuation is preferable to curettage (grade B). A perforated uterus during an instrumental suction should not be considered as a scarred uterus (Professional consensus). IA is not associated with increased subsequent risk of infertility or ectopic pregnancy (EL2). The pre-abortion medical consultations does not affect, most of the time, the decision to request an IA. Indeed, a majority of women is quite sure of her choice during these consultations. Acceptability of the method of IA and satisfaction appears to be larger when they are able to choose the abortion method (grade B). There is no relationship between an increase in psychiatric disorders and IA (EL2). Women with psychiatric histories are at increased risk of mental disorders after the occurrence of an UPP (EL2). In case of instrumental abortion, oral estrogen-progestogen contraceptives and the patch should be started from the day of the abortion, the vaginal ring inserted within 5 days of IA (grade B). In case of medical abortion, the vaginal ring should be inserted within a week of taking mifepristone, oral estrogen-progestogen contraceptives and the patch should be initiated on the same day or the day after taking prostaglandins (grade C). In case of instrumental abortion, the contraceptive implant may be inserted on the day of the abortion (grade B). In case of medical abortion, the implant can be inserted on the day of mifepristone (grade C). The copper Intrauterine Device (IUD) and levonorgestrel should be inserted preferably on the day of instrumental abortion (grade A). In case of medical abortion, an IUD can be inserted within 10 days following mifepristone after ensuring by ultrasound of the absence of intrauterine pregnancy (grade C). Conclusion The implementation of these guidelines may promote a better and more homogenous care for women requesting IA in our country