Influenza A viruses alter the stability and antiviral contribution of host E3-ubiquitin ligase Mdm2 during the time-course of infection

International audienceThe interplay between influenza A viruses (IAV) and the p53 pathway has been reported in several studies, highlighting the antiviral contribution of p53. Here, we investigated the impact of IAV on the E3-ubiquitin ligase Mdm2, a major regulator of p53, and observed that IAV targets Mdm2, notably via its non-structural protein (NS1), therefore altering Mdm2 stability, p53/Mdm2 interaction and regulatory loop during the time-course of infection. This study also highlights a new antiviral facet of Mdm2 possibly increasing the list of its many p53-independent functions. Altogether, our work contributes to better understand the mechanisms underlining the complex interactions between IAV and the p53 pathway, for which both NS1 and Mdm2 arise as key players

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams

Analysis of width/height ratio and gingival zenith in patients with bilateral agenesis of maxillary lateral incisor

OBJECTIVE: The purpose of this study was to evaluate the width/length ratio and the gingival zenith (GZ), by means of dental casts and digital caliper, in patients with missing maxillary lateral incisors after treatment. METHODS: The sample was composed of 52 subjects divided into 3 groups: BRG (n = 18), patients with bilateral agenesis treated with tooth re-contouring; BIG (n = 10) patients with agenesis treated with implants and CG (n = 24), control group. The data were analyzed using Shapiro-Wilk, Spearman correlation, Wilcoxon, Kruskal-Wallis, t test and ANOVA tests (p < 0.05). RESULTS: For the width/length ratio of the lateral incisors, BIG presented the lowest mean values (0.72 right and left), when compared with other groups. However, comparison between groups presented statistically significant differences for the right lateral incisor (BIG x CG) and for the canine (BRG x CG). GZ data evaluation showed the greatest difference for BRG (0.5 right and 0.48 left). BIG (0.95 right and 0.98 left) and CG (0.98 right and 0.8 left) presented more similar values, nevertheless, without statistical difference (p > 0.05). GZ data for the right and left sides of the smile were not considered statistically different. CONCLUSION: Although no statistical difference was found in the comparison between the groups, analysis of the descriptive values showed that group BIG showed the greatest difference in values with regard to width/length ratio. Regarding gingival zenith, BRG showed the greatest difference.<br>OBJETIVO: o propósito desse estudo foi analisar, por meio de modelos de estudo e paquímetro digital, a proporção largura/altura e o zênite gengival (ZG) em pacientes com agenesia bilateral do incisivo lateral superior após o tratamento. MÉTODOS: a amostra consistiu de 52 voluntários divididos em 3 grupos: GBR (n=18), pacientes com agenesia bilateral tratados com reanatomizações dentárias; GBI (n=10), pacientes com agenesia bilateral tratados com implantes; e GC (n=24), grupo controle. Os dados foram avaliados por meio dos testes de Shapiro-Wilk, Wilcoxon, Kruskal-Wallis, teste t, ANOVA (p<0,05) e correlação de Spearman. RESULTADOS: para a proporção largura/altura dos incisivos laterais, o GBI apresentou menores valores (0,72 direito e esquerdo), quando comparado aos demais. Porém, a comparação intergrupos revelou diferenças estatisticamente significativas para o incisivo lateral direito (GBI x GC) e para o canino (GBR x GC). A avaliação das medianas obtidas para o ZG demonstrou que o GBR foi o mais destoante (0,5 direito e 0,48 esquerdo), e que o GBI (0,95 direito e 0,98 esquerdo) e o GC (0,98 direito e 0,8 esquerdo) apresentaram valores semelhantes, sem diferença estatisticamente significativa (p>0,05). Os valores obtidos para os lados direito e esquerdo foram considerados iguais dentro de cada grupo. CONCLUSÃO: embora não tenham sido encontradas diferenças estatísticas na comparação entre os grupos, pela análise descritiva dos dados, o GBI foi o grupo que apresentou as medidas mais destoantes dos demais em relação à proporção largura/altura, sendo que, para o zênite gengival, a maior diferença observada foi no GBR

Behavior of Lactobacilli isolated from fermented slurry (ben-saalga) in gnotobiotic rats

Most bacterial strains, which have been studied so far for their probiotic functions, are extensively used by manufacturers in developed countries. In our work, we sought to study a mix (called BSL) comprising three strains belonging to Lactobacillus fermentum, L. paraplantarum and L. salivarius, that were isolated from a traditional African pearl millet based fermented slurry. Our objective was to study this BSL cocktail in gnotobiotic rats, to evaluate their survival and their behavior in the digestive tract conditions. After a single oral inoculation of germfree rats with BSL, the species established stably in the digestive tract with the following hierarchy of abundance: L. salivarius> L. plantarum> L. fermentum. BSL cocktail was metabolically active since it produced 50 mM lactate and it expressed genes involved in binding mechanism in the caecum. Furthermore, the global morphology of the colon epithelium was not disturbed by the BSL cocktail. BSL cocktail did not modify mucus content and host mucus-related genes (MUC1, MUC2, MUC3 or resistin-like molecule beta). The cocktail of lactobacilli enhanced the proliferating cell nuclear antigen (PCNA) at a level comparable to what was observed in conventional rats. PCNA was involved in proliferation and DNA repair, but the presence of the cocktail did not provoke proliferative events (with Ki67 as indicator), so we suppose BSL may help gut preservation. This work is the first step towards the selection of strains that are derived from traditional fermented food to formulate new probiotic mixture