New hippotragini (Bovidae, Mammalia) from the Late Miocene of Toros-Menalla (Chad)

International audienceUntil now, the pre-Pleistocene record of the bovid tribe Hippotragini was rather poor. We describe here two new taxa from the late Miocene of Toros-Menalla in northern Chad, which yielded the earliest known hominid, Sahelanthropus tchadensis. Tchadotragus sudrei n.gen. n.sp. is known by complete skulls and numerous horn-cores. It has typical hippotragine features such as long slender, curved horn-cores, weak cranial flexure, large frontal sinus, and hippotragine-like dentition, and is here taken as a basal member of the tribe, branching before the divergence between Oryx-Praedamalis and Hippotragus s.l. Saheloryx solidus n.gen. n.sp. is less well-known; it differs mainly by the lack of sinus in the frontal and horn-cores, shorter horn-cores, and rounded brain-case, but it shares with Tchadotragus a large number of features that prompt us to classify it also at the base of the hippotragine tree, perhaps as the sister-taxon of Tchadotragus. No other African taxon looks like Saheloryx, and the only one similar to Tchadotragus is from Sahabi, Libya. The abundance of hippotragines sharply distinguishes Toros-Menalla from the East African late Miocene bovid faunas

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Effect of Popcorn (Zea mays var. everta) Popping Mode (Microwave, Hot Oil, and Hot Air) on Fumonisins and Deoxynivalenol Contamination Levels

International audienceMycotoxins are secondary metabolites that are produced by molds during their development. According to fungal physiological particularities, mycotoxins can contaminate crops before harvest or during storage. Among toxins that represent a real public health issue, those produced by Fusarium genus in cereals before harvest are of great importance since they are the most frequent in European productions. Among them, deoxynivalenol (DON) and fumonisins (FUM) frequently contaminate maize. In recent years, numerous studies have investigated whether food processing techniques can be exploited to reduce the levels of these two mycotoxins, which would allow the identification and quantification of parameters affecting mycotoxin stability. The particularity of the popcorn process is that it associates heat treatment with a particular physical phenomenon (i.e., expansion). Three methods exist to implement the popcorn transformation process: hot air, hot oil, and microwaves, all of which are tested in this study. The results show that all popping modes significantly reduce FUM contents in both Mushroom and Butterfly types of popcorn. The mean initial contamination of 1351 _g/kg was reduced by 91% on average after popping. For DON, the reduction was less important despite a lower initial contamination than for FUM (560 _g/kg). Only the hot oil popping for the Mushroom type significantly reduced the contamination up to 78% compared to unpopped controls. Hot oil popping appears to provide the most important reduction for the two considered mycotoxins for both types of popcorn (-98% and- 58% average reduction for FUM and DON, respectively

Endometriosis and in vitro fertilisation: a review

This review aims to evaluate whether severe endometriosis has an impact on the outcome of in vitro fertilisation (IVF), whether IVF is associated with specific complications in this context, whether a specific ovarian stimulation protocol is most appropriate, whether the endometrial condition progresses following ovarian stimulation, and whether endometrial cysts pose a specific problem for IVF. In patients with severe endometriosis, IVF represents an effective treatment option for infertility, as a complement to surgery. The prognostic parameters of IVF are identical to those of other patients. However, the risks related to the severity of endometriosis, particularly the risk of ovarian deficiency, need to be considered. Because of this issue, to which endometriosis-related pain often adds, IVF treatment should be initiated as early as possible, using appropriate protocols and after having fully informed the patient about the specific oocytes retrieval-related risks

"Short agonist stop" protocol, an ovarian stimulation for poor responders in in vitro fertilization (IVF) : A pilot study

International audienceIntroduction Poor responder patients remain a challenge in assisted reproductive technologies. The “short agonist stop” (SAS) stimulation protocol uses a double stimulation (flare up effect with the gonadotropin-releasing hormone (GnRH) agonist (GnRH-a) then gonadotropins) associated with a less strenuous blockage (discontinuation of GnRH-a) to favor follicular recruitment in order to obtain a better ovarian response. This study aims to compare the number of oocytes obtained after a SAS stimulation protocol with those obtained after the previous stimulation protocol, in the same women, with poor ovarian response (POR) diagnosed according to the POSEIDON criteria. Design This therapeutic observational retrospective cohort from 2018 to 2022, with a case-control evaluation compared with the same patients’ previous performance, included women with POR undergoing IVF with SAS stimulation protocol. The primary outcome was the number of total oocytes recovered and secondary outcomes were the numbers of mature oocytes, total embryos observed at day 2 and usable cleaved embryos and blastocysts (day 5/6). Results 63 patients with SAS and previous cycles were included. In the SAS group, the mean number of oocytes was significantly higher: 7.3 vs 5.7, p=0.018 in comparison with the previous attempt. So was the number of mature oocytes (5.8 vs 4.1, p=0.032) and the total mean number of embryos obtained at day 2 (4.1 versus 2.7, p=0.016). The SAS stimulation generated 84 usable embryos: 57 cleaved embryos and 27 blastocysts. The mean number of usable embryos was similar in both groups (1.64 vs 1.31, respectively, p=0.178). In total, out of 63 patients, after the SAS protocol, and subsequent embryo transfers (fresh and frozen, n=54), 9 patients had ongoing pregnancies and no miscarriage occurred. The cumulative ongoing pregnancy rate (cOPR) after the SAS protocol was 14.3% (9/63) per oocyte pick-up and 16.7% (9/54) per transfer. Conclusion SAS stimulation is a short and original protocol strengthening the therapeutic arsenal of poor responders, that may offer promising results for those patients with low prognosis and previous failed IVF. Results must be confirmed with a randomized controlled trial

Chromosomal Translocation Formation Is Sufficient to Produce Fusion Circular RNAs Specific to Patient Tumor Cells

Summary: Circular RNAs constitute a unique class of RNAs whose precise functions remain to be elucidated. In particular, cancer-associated chromosomal translocations can give rise to fusion circular RNAs that play a role in leukemia progression. However, how and when fusion circular RNAs are formed and whether they are being selected in cancer cells remains unknown. Here, we used CRISPR/Cas9 to generate physiological translocation models of NPM1-ALK fusion gene. We showed that, in addition to generating fusion proteins and activating specific oncogenic pathways, chromosomal translocation induced by CRISPR/Cas9 led to the formation of de novo fusion circular RNAs. Specifically, we could recover different classes of circular RNAs composed of different circularization junctions, mainly back-spliced species. In addition, we identified fusion circular RNAs identical to those found in related patient tumor cells providing evidence that fusion circular RNAs arise early after chromosomal formation and are not just a consequence of the oncogenesis process. : Molecular Biology; Molecular Genetics; Cancer Subject Areas: Molecular Biology, Molecular Genetics, Cance

Spatiotemporal Trends and Prognosis of End-Stage Renal Disease Patients with Biopsy-Proven Immunoglobulin A Nephropathy in France from 2010 to 2014

Abstract Background Although end-stage renal disease (ESRD) is frequently used as an outcome marker for primary immunoglobulin A nephropathy (IgAN), the clinical course after reaching ESRD is not well documented. This study examined patients' characteristics and survival in ESRD-related biopsy-proven IgAN in France. Methods French Renal Epidemiology and Information Network Registry data from 2010 to 2014 were used to analyse patients' survival and outcome in incident ESRD patients &gt;16\,years of age with biopsy-proven primary IgAN, in comparison with other primary and secondary glomerulonephritis (GN), adult polycystic kidney disease (ADPKD) or diabetes. Multivariable survival analysis was adjusted for age, sex, time on dialysis and comorbidities. Results Among 17\,138 incident dialysis patients with ESRD, IgAN (242.8/10\,000 dialysis initiation) represents the most common GN related to ESRD during 2010. IgAN patients were the youngest, and had the fewest comorbidities and the highest use of peritoneal dialysis (PD) (17%). In comparison with the haemodialysis group, hazard ratios for death were not different in the preemptive transplantation group [0.46, 95% confidence interval (CI) 0.17\textendash 1.28] and in the PD group (0.77, 95% CI 0.44\textendash 1.33). Mortality rates in IgAN patients with preemptive transplantation and in those receiving dialysis waiting for transplantation were 2.9% (95% CI 0.0\textendash 5.6) and 6.7% (95% CI 0.9\textendash 12.3). Mortality rates of ADPKD patients receiving dialysis waiting for transplantation were higher (18%, 95% CI 3.1\textendash 30.6). Conclusion IgAN has the best prognosis among primary and secondary GN. IgAN patients receiving dialysis waiting transplantation seem to have a more favourable prognosis than ADPKD patients, who usually comprise the reference population. The underlying reasons for the difference in access treatment modalities should be investigated to improve survival with respect to renal disease