A coordinated phosphorylation cascade initiated by MSK1 directs RAR alpha recruitment to target gene promoters

The nuclear retinoic acid (RA) receptor alpha (RARα) is a transcriptional transregulator that controls the expression of specific gene subsets through binding at response elements and dynamic interactions with coregulators, which are coordinated by the ligand. Here, we highlighted a novel paradigm in which the transcription of RARα-target genes is controlled by phosphorylation cascades initiated by the rapid RA activation of the p38MAPK/MSK1 pathway. We demonstrate that MSK1 phosphorylates RARα at S369 located in the Ligand Binding Domain, allowing the binding of TFIIH and thereby phosphorylation of the N-terminal domain at S77 by cdk7/cyclin H. MSK1 also phosphorylates Histone H3 at S10. Finally, the phosphorylation cascade initiated by MSK1 is required for the recruitment of RARα/TFIIH complexes to response elements and subsequently for RARα target genes activation. Cancer cells characterized by a deregulated p38MAPK/MSK1 pathway, do not respond to RA, outlining the essential contribution of the RA-triggered phosphorylation cascade in RA signaling

Extreme climate variability should be considered in forestry-assisted migration

International audienceRecently, Pedlar et al. (2012) stated that assisted migration in forestry (forestry AM) differs from species-rescue-assisted migration (species rescue AM) because the risks of invasiveness, hybridization with local species, and spread of diseases are minimized in managed forests. The rationale behind this assertion for forestry AM is that it involves the translocation of populations within the existing geographic range of the species, whereas species rescue AM involves the introduction of exotic species. However, while we agree that forestry AM is less risky than species rescue AM for the recipient ecosystem, forestry AM can not only fail but can also incur enormous financial costs. The failure of efforts that involved planting maritime pine (Pinus pinaster Aït) trees in Southwest France (Aquitaine) with seeds from more southerly populations from Portugal for production purposes is a textbook case. The climate variability in Aquitaine includes periods of intense frost that are sufficiently rare (every 10 to 20 years) to be overlooked when establishing tree populations. The frost of the winter of 1985, the most intense frost event since records began with temperatures dropping as low as -22 °C (Boisseaux, 1986), affecting about 350 km2 of tree plantations in the region (Doré & Varoquaux, 2006). The highest mortality related to frost was observed in populations harvested from Leiria in Portugal, for which nearby records show that the absolute minimum temperature was only -7.8 °C in the last 60 years. Climate averages over the last 30 years differ only slightly between Leiria and Aquitaine, which would erroneously suggest that samples from Portugal would have survived in the Aquitaine region. Newly emerging climates (Williams et al. 2007) and the uncertainty related to climate change extreme events (Easterling, 2000) will make the search for southern locations with climatic conditions similar to those of northern populations of trees extremely difficult. Policies of forest adaptation to climate change should account for extreme cold events in the target populations even if climate change will likely decrease the number of extreme cold events (Easterling, 2000), that remain in our opinion, the hidden element behind the maladaptation of southern populations to northern locations

ÉLABORATION ET ÉVALUATION DES RAPPORTS DIAGNOSTIQUES DES DONNÉES DU PIRLS 2011: PERCEPTIONS DES ENSEIGNANTS AU PRIMAIRE, DES CONSEILLERS PÉDAGOGIQUES ET DES ORTHOPÉDAGOGUES

La demande croissante pour des évaluations à grande échelle s’accompagne d’une forte pression pour rendre ces évaluations plus informatives sur l’apprentissage des élèves. Or, ces évaluations fournissent les résultats des élèves sous forme de scores globaux et de sous-scores, ce qui renseigne peu sur leurs forces et faiblesses. Par ailleurs, les recherches en approche diagnostique cognitive suggèrent qu’il est possible de décomposer la lecture en connaissances et habiletés possibles à diagnostiquer grâce à des modélisations psychométriques. Des épreuves à grande échelle ont donc le potentiel de fournir aux enseignants des rapports diagnostiques contenant des rétroactions détaillées sur les forces et les faiblesses des élèves. Cet article décrit l'élaboration de rapports diagnostiques à partir des données du PIRLS 2011 avec un panel d'experts et rapporte les résultats de l’évaluation de ces rapports auprès d’enseignants au primaire, de conseillers pédagogiques et d’orthopédagogues

Consensus-based care recommendations for congenital and childhood-onset myotonic dystrophy type 1

Purpose of reviewMyotonic dystrophy type 1 is a multisystemic disorder caused by a noncoding triplet repeat. The age of onset is variable across the lifespan, but in its most severe form, the symptoms appear at birth (congenital myotonic dystrophy) or in the pediatric age range (childhood-onset myotonic dystrophy). These children have a range of disabilities that reduce the lifespan and cause significant morbidity. Currently, there are no agreed upon recommendations for caring for these children.Recent findingsThe Myotonic Dystrophy Foundation recruited 11 international clinicians who are experienced with congenital and childhood-onset myotonic dystrophy to create consensus-based care recommendations. The experts used a 2-step methodology using elements of the single text procedure and nominal group technique. Completion of this process has led to the development of clinical care recommendations for this population.SummaryChildren with myotonic dystrophy often require monitoring and interventions to improve the lifespan and quality of life. The resulting recommendations are intended to standardize and improve the care of children with myotonic dystrophy

MycoBank gearing up for new horizons.

MycoBank, a registration system for fungi established in 2004 to capture all taxonomic novelties, acts as a coordination hub between repositories such as Index Fungorum and Fungal Names. Since January 2013, registration of fungal names is a mandatory requirement for valid publication under the International Code of Nomenclature for algae, fungi and plants (ICN). This review explains the database innovations that have been implemented over the past few years, and discusses new features such as advanced queries, registration of typification events (MBT numbers for lecto, epi- and neotypes), the multi-lingual database interface, the nomenclature discussion forum, annotation system, and web services with links to third parties. MycoBank has also introduced novel identification services, linking DNA sequence data to numerous related databases to enable intelligent search queries. Although MycoBank fills an important void for taxon registration, challenges for the future remain to improve links between taxonomic names and DNA data, and to also introduce a formal system for naming fungi known from DNA sequence data only. To further improve the quality of MycoBank data, remote access will now allow registered mycologists to act as MycoBank curators, using Citrix software

SARS-CoV-2 can infect human embryos

The spread of SARS-CoV-2 has led to a devastating pandemic, with infections resulting in a range of symptoms collectively known as COVID-19. The full repertoire of human tissues and organs susceptible to infection is an area of active investigation, and some studies have implicated the reproductive system. The effects of COVID-19 on human reproduction remain poorly understood, and particularly the impact on early embryogenesis and establishment of a pregnancy are not known. In this work, we explore the susceptibility of early human embryos to SARS-CoV-2 infection. By using RNA-seq and immunofluorescence, we note that ACE2 and TMPRSS2, two canonical cell entry factors for SARS-CoV-2, are co-expressed in cells of the trophectoderm in blastocyst-stage preimplantation embryos. For the purpose of viral entry studies, we used fluorescent reporter virions pseudotyped with Spike (S) glycoprotein from SARS-CoV-2, and we observe robust infection of trophectoderm cells. This permissiveness could be attenuated with blocking antibodies targeting S or ACE2. When exposing human blastocysts to the live, fully infectious SARS-CoV-2, we detected cases of infection that compromised embryo health. Therefore, we identify a new human target tissue for SARS-CoV-2 with potential medical implications for reproductive health during the COVID-19 pandemic and its aftermath

Biomedicines

Antibody-mediated rejection (ABMR) is the leading cause of allograft failure in kidney transplantation. Its histological hallmark is represented by lesions of glomerulitis i.e., inflammatory cells within glomeruli. Current therapies for ABMR fail to prevent chronic allograft damage i.e., transplant glomerulopathy, leading to allograft loss. We used laser microdissection of glomeruli from formalin-fixed allograft biopsies combined with mass spectrometry-based proteomics to describe the proteome modification of 11 active and 10 chronic active ABMR cases compared to 8 stable graft controls. Of 1335 detected proteins, 77 were deregulated in glomerulitis compared to stable grafts, particularly involved in cellular stress mediated by interferons type I and II, leukocyte activation and microcirculation remodeling. Three proteins extracted from this protein profile, TYMP, WARS1 and GBP1, showed a consistent overexpression by immunohistochemistry in glomerular endothelial cells that may represent relevant markers of endothelial stress during active ABMR. In transplant glomerulopathy, 137 proteins were deregulated, which favor a complement-mediated mechanism, wound healing processes through coagulation activation and ultimately a remodeling of the glomerular extracellular matrix, as observed by light microscopy. This study brings novel information on glomerular proteomics of ABMR in kidney transplantation, and highlights potential targets of diagnostic and therapeutic interest