HOXA1 binds RBCK1/HOIL-1 and TRAF2 and modulates the TNF/NF-κB pathway in a transcription-independent manner

HOX proteins define a family of key transcription factors regulating animal embryogenesis. HOX genes have also been linked to oncogenesis and HOXA1 has been described to be active in several cancers, including breast cancer. Through a proteome-wide interaction screening, we previously identified the TNFR-associated proteins RBCK1/HOIL-1 and TRAF2 as HOXA1 interactors suggesting that HOXA1 is functionally linked to the TNF/NF-κB signaling pathway. Here, we reveal a strong positive correlation between expression of HOXA1 and of members of the TNF/NF-κB pathway in breast tumor datasets. Functionally, we demonstrate that HOXA1 can activate NF-κB and operates upstream of the NF-κB inhibitor IκB. Consistently, we next demonstrate that the HOXA1-mediated activation of NF-κB is non-transcriptional and that RBCK1 and TRAF2 influences on NF-κB are epistatic to HOXA1. We also identify an 11 Histidine repeat and the homeodomain of HOXA1 to be required both for RBCK1 and TRAF2 interaction and NF-κB stimulation. Finally, we highlight that activation of NF-κB is crucial for HOXA1 oncogenic activity

In a marine teleost, the significance of oxygen supply for acute thermal tolerance depends upon the context and the endpoint used

Eight juvenile European seabass were exposed to two thermal ramping protocols with different levels of aerobic activity and tolerance endpoint: the critical thermal maximum for swimming (CTSmax) while exercising aerobically until fatigue, and the critical thermal maximum (CTmax) under static conditions until loss of equilibrium (LOE). In the CTSmax, warming caused a profound increase in oxygen uptake rate (M˙O2) culminating in a gait transition, from steady aerobic towards unsteady anaerobic swimming, then fatigue at 30.3±0.4°C (mean±SE). Gait transition and fatigue presumably indicate an oxygen limitation, an inability to meet the combined demands of swimming plus warming. The CTmax also elicited an increase in M˙O2, culminating in LOE at 34.0±0.4°C, significantly warmer than fatigue at CTSmax. The maximum M˙O2 achieved in the CTmax was, however, less than 30% of that achieved in the CTSmax. Therefore, the static CTmax did not exploit full cardiorespiratory capacity for oxygen supply, indicating that LOE was not caused by systemic oxygen limitation. Consequently, systemic oxygen supply can be significant for tolerance of acute warming in seabass but this depends upon the physiological context and the endpoint used

Effects of pre‐operative isolation on postoperative pulmonary complications after elective surgery : an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care

A SNP map of the European sea bass genome based on a meiotic gynogenetic family

International audienc

Search for Charged Higgs Bosons in e+e- Collisions at sqrt(s)= 189 GeV

Background  Fully isogenic lines in fish can be developed using “mitotic” gynogenesis (suppression of first zygotic mitosis following inactivation of the sperm genome). However, genome-wide verification of the steps in this process has seldom been applied. We used ddRADseq to generate SNP markers in a meiotic gynogenetic family of European seabass (Dicentrarchus labrax): (i) to verify the lack of paternal contribution in a meiotic gynogenetic family; (ii) to generate a gene-centromere map from this family; (iii) to identify telomeric markers that could distinguish mitotic gynogenetics from meiotic gynogenetics, which sometimes arise spontaneously in mitotic gynogenetic families.  Results  From a single meiotic gynogenetic family consisting of 79 progeny, 42 million sequencing reads (Illumina, trimmed to 148 bases) resolved 6866 unique RAD-tags. The 340 male-informative SNP markers that were identified confirmed the lack of paternal contribution. A gene-centromere map was constructed based on 804 female-informative SNPs in 24 linkage groups (2n=48) with a total length of 1251.02cM (initial LG assignment was based on the seabass genome assembly, dicLab v1). Chromosome arm structure could be clearly discerned from the pattern of heterozygosity in each linkage group in 18 out of 24 LGs: the other six showed anomalies that appeared to be related to issues in the genome assembly.  Conclusion  Genome-wide screening enabled substantive verification of the production of the gynogenetic family used in this study. The large number of telomeric and subtelomeric markers with high heterozygosity values in the meiotic gynogenetic family indicate that such markers could be used to clearly distinguish between meiotic and mitotic gynogenetics

Genetic Inactivation of European Sea Bass (Dicentrarchus labrax L.) Eggs Using UV-Irradiation: Observations and Perspectives

International audienceAndrogenesis is a form of uniparental reproduction leading to progenies inheriting only the paternal set of chromosomes. Ithas been achieved with variable success in a number of freshwater species and can be attained by artificial fertilization ofgenetically inactivated eggs following exposure to gamma (c), X-ray or UV irradiation (haploid androgenesis) and byrestoration of diploidy by suppression of mitosis using a pressure or thermal shock. The conditions for the geneticinactivation of the maternal genome in the European sea bass (Dicentrarchus labraxL.) were explored using differentcombinations of UV irradiation levels and durations. UV treatments significantly affected embryo survival and generated awide range of developmental abnormalities. Despite the wide range of UV doses tested (from 7.2 to 720 mJ.cm22), only onedose (60 mJ.cm22.min21with 1 min irradiation) resulted in a small percentage (14%) of haploid larvae at hatching in theinitial trials as verified by flow cytometry. Microsatellite marker analyses of three further batches of larvae produced by usingthis UV treatment showed a majority of larvae with variable levels of paternal and maternal contributions and only one larvadisplaying pure paternal inheritance. The results are discussed also in the context of an assessment of the UV-absorbancecharacteristics of egg extracts in this species that revealed the presence of gadusol, a compound structurally related tomycosporine-like amino acids (MAAs) with known UV-screening properties