Spindle Assembly Checkpoint Protein Dynamics Reveal Conserved and Unsuspected Roles in Plant Cell Division

Background: In eukaryotes, the spindle assembly checkpoint (SAC) ensures that chromosomes undergoing mitosis do not segregate until they are properly attached to the microtubules of the spindle. Methodology/Principal Findings: We investigated the mechanism underlying this surveillance mechanism in plants, by characterising the orthogolous SAC proteins BUBR1, BUB3 and MAD2 from Arabidopsis. We showed that the cell cycle-regulated BUBR1, BUB3.1 and MAD2 proteins interacted physically with each other. Furthermore, BUBR1 and MAD2 interacted specifically at chromocenters. Following SAC activation by global defects in spindle assembly, these three interacting partners localised to unattached kinetochores. In addition, in cases of 'wait anaphase', plant SAC proteins were associated with both kinetochores and kinetochore microtubules. Unexpectedly, BUB3.1 was also found in the phragmoplast midline during the final step of cell division in plants. Conclusions/Significance: We conclude that plant BUBR1, BUB3.1 and MAD2 proteins may have the SAC protein functions conserved from yeast to humans. The association of BUB3.1 with both unattached kinetochore and phragmoplast suggests that in plant, BUB3.1 may have other roles beyond the spindle assembly checkpoint itself. Finally, this study of the SAC dynamics pinpoints uncharacterised roles of this surveillance mechanism in plant cell division

Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

[Excerpt] Multiple myeloma (MM) is the third most common hematological malignancy, after Non-Hodgkin Lymphoma and Leukemia. MM is generally preceded by Monoclonal Gammopathy of Undetermined Significance (MGUS) [1], and epidemiological studies have identified older age, male gender, family history, and MGUS as risk factors for developing MM [2]. The somatic mutational landscape of sporadic MM has been increasingly investigated, aiming to identify recurrent genetic events involved in myelomagenesis. Whole exome and whole genome sequencing studies have shown that MM is a genetically heterogeneous disease that evolves through accumulation of both clonal and subclonal driver mutations [3] and identified recurrently somatically mutated genes, including KRAS, NRAS, FAM46C, TP53, DIS3, BRAF, TRAF3, CYLD, RB1 and PRDM1 [3,4,5]. Despite the fact that family-based studies have provided data consistent with an inherited genetic susceptibility to MM compatible with Mendelian transmission [6], the molecular basis of inherited MM predisposition is only partly understood. Genome-Wide Association (GWAS) studies have identified and validated 23 loci significantly associated with an increased risk of developing MM that explain ~16% of heritability [7] and only a subset of familial cases are thought to have a polygenic background [8]. Recent studies have identified rare germline variants predisposing to MM in KDM1A [9], ARID1A and USP45 [10], and the implementation of next-generation sequencing technology will allow the characterization of more such rare variants. [...]French National Cancer Institute (INCA) and the Fondation Française pour la Recherche contre le Myélome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myélome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myélome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organizatio

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Oceans and Coastal Ecosystems and Their Services

Ocean and coastal ecosystems support life on Earth and many aspects of human well-being. Covering two-thirds of the planet, the ocean hosts vast biodiversity and modulates the global climate system by regulating cycles of heat, water and elements, including carbon. Marine systems are central to many cultures, and they also provide food, minerals, energy and employment to people. Since previous assessments1 , new laboratory studies, field observations and process studies, a wider range of model simulations, Indigenous knowledge, and local knowledge have provided increasing evidence on the impacts of climate change on ocean and coastal systems, how human communities are experiencing these impacts, and the potential solutions for ecological and human adaptation.Peer reviewe

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Problématique d'une étude de caractérisation d'un sol contaminé non excavé

L'étude de caractérisation d'un sol contaminé a pour but d'évaluer aussi précisément que possible l'étendue de la contamination. Pour ce faire, elle est effectuée en deux principales étapes: l'investigation préliminaire et la caractérisation détaillée. Cette dernière complète et précise l'information recueillie lors de l'investigation préliminaire. Selon le site, les deux peuvent être réalisées simultanément ou séparément. Aussi bien dans l'investigation préliminaire que dans la caractérisation détaillée, un échantillonnage du terrain est effectué. Il est donc important que le patron d'échantillonnage corresponde aux objectifs de l'étude. Les trois principales approches permettant d'élaborer un tel patron sont la méthode par jugement, la méthode aléatoire et la méthode systématique. Une fois l'échantillonnage effectué, les données recueillies sont analysées. Tout dépendant des objectifs de l'étude et de la méthode d'échantillonnage choisie, les statistiques classiques et/ou la géostatistique sont employées. Dans tous les cas un statistique expérimenté en patron d'échantillonnage devrait être consulté avant et pendant les procédures d'analyse des données. Ce document examine la méthodologie et les principales techniques impliquées dans l'élaboration d'une étude de caractérisation d'un sol non excavé

Problématique d'une étude de caractérisation d'un sol contaminé non excavé

L'étude de caractérisation d'un sol contaminé a pour but d'évaluer aussi précisément que possible l'étendue de la contamination. Pour ce faire, elle est effectuée en deux principales étapes: l'investigation préliminaire et la caractérisation détaillée. Cette dernière complète et précise l'information recueillie lors de l'investigation préliminaire. Selon le site, les deux peuvent être réalisées simultanément ou séparément. Aussi bien dans l'investigation préliminaire que dans la caractérisation détaillée, un échantillonnage du terrain est effectué. Il est donc important que le patron d'échantillonnage corresponde aux objectifs de l'étude. Les trois principales approches permettant d'élaborer un tel patron sont la méthode par jugement, la méthode aléatoire et la méthode systématique. Une fois l'échantillonnage effectué, les données recueillies sont analysées. Tout dépendant des objectifs de l'étude et de la méthode d'échantillonnage choisie, les statistiques classiques et/ou la géostatistique sont employées. Dans tous les cas un statistique expérimenté en patron d'échantillonnage devrait être consulté avant et pendant les procédures d'analyse des données. Ce document examine la méthodologie et les principales techniques impliquées dans l'élaboration d'une étude de caractérisation d'un sol non excavé

Stratégies d hybridation entre rosiers sauvages et cultivés : approches génétique, cytologique et moléculaire

Les flux de gènes entre espèces sauvages et cultivées nécessitent chez le rosier le contournement des différences de niveaux de ploïdie. L utilisation d un intermédiaire triploïde fertile en tant que pont génétique semble prometteuse. Ces individus présentent une méiose particulière (production de gamètes haploïdes et diploïdes simultanément), et le transfert de gènes issus du parent sauvage via des gamètes diploïdes a été prouvé. Le doublement chromosomique in vitro d espèces sauvages diploïdes, ainsi que l haploïdisation de cultivars tétraploïdes sont génotypes-dépendants, les taux de réussite restant faibles. L utilisation de gamètes non réduits semble être une voie intéressante, malgré la complexité et la variabilité du caractère. Des gènes de cyclines, RhCYCB1;1 et RhCYCB2;1, potentiellement impliqués dans la régulation de mécanismes méiotiques, ont été isolés. Ils pourraient être de bons marqueurs pour étudier l effet des conditions environnementales sur la microsporogénèse.AIX-MARSEILLE3-BU Sc.St Jérô (130552102) / SudocSudocFranceF