Amphioxus functional genomics and the origins of vertebrate gene regulation.

Vertebrates have greatly elaborated the basic chordate body plan and evolved highly distinctive genomes that have been sculpted by two whole-genome duplications. Here we sequence the genome of the Mediterranean amphioxus (Branchiostoma lanceolatum) and characterize DNA methylation, chromatin accessibility, histone modifications and transcriptomes across multiple developmental stages and adult tissues to investigate the evolution of the regulation of the chordate genome. Comparisons with vertebrates identify an intermediate stage in the evolution of differentially methylated enhancers, and a high conservation of gene expression and its cis-regulatory logic between amphioxus and vertebrates that occurs maximally at an earlier mid-embryonic phylotypic period. We analyse regulatory evolution after whole-genome duplications, and find that-in vertebrates-over 80% of broadly expressed gene families with multiple paralogues derived from whole-genome duplications have members that restricted their ancestral expression, and underwent specialization rather than subfunctionalization. Counter-intuitively, paralogues that restricted their expression increased the complexity of their regulatory landscapes. These data pave the way for a better understanding of the regulatory principles that underlie key vertebrate innovations.

Gene Regulatory Networks of Epidermal and Neural Fate Choice in a Chordate.

Neurons are a highly specialized cell type only found in metazoans. They can be scattered throughout the body or grouped together, forming ganglia or nerve cords. During embryogenesis, centralized nervous systems develop from the ectoderm, which also forms the epidermis. How pluripotent ectodermal cells are directed toward neural or epidermal fates, and to which extent this process is shared among different animal lineages, are still open questions. Here, by using micromere explants, we were able to define in silico the putative gene regulatory networks (GRNs) underlying the first steps of the epidermis and the central nervous system formation in the cephalochordate amphioxus. We propose that although the signal triggering neural induction in amphioxus (i.e., Nodal) is different from vertebrates, the main transcription factors implicated in this process are conserved. Moreover, our data reveal that transcription factors of the neural program seem to not only activate neural genes but also to potentially have direct inputs into the epidermal GRN, suggesting that the Nodal signal might also contribute to neural fate commitment by repressing the epidermal program. Our functional data on whole embryos support this result and highlight the complex interactions among the transcription factors activated by the signaling pathways that drive ectodermal cell fate choice in chordates.

Number of opioid overdoses and depression as a predictor of suicidal thoughts.

BACKGROUND: Opioid use disorders are associated with increased risk of suicide thoughts, attempts, and death. We explored key variables from two theories of the development of suicidal thoughts and attempts (the interpersonal and three-step theories of suicide) to understand possible mechanisms underlying the association between opioid use and suicide risk. We hypothesized that interpersonal connections, variables reflecting psychological and physical pain, and variables that reduce fear of death (prior overdoses and risk-taking behaviors) would be associated with increased risk of thoughts of suicide. METHODS: Participants (N = 141) were opioid users recruited from an epicenter of the opioid crisis in Philadelphia using a mobile research center and completed an interview to assess substance use, depression, medical comorbidities, and suicidal thoughts among other variables. RESULTS: Univariate analyses showed that prior history of overdose, diagnosis of depression, older age, homelessness, and interpersonal connection were each associated with increased likelihood of endorsing thoughts of death/suicide. Multivariable analyses revealed prior history of overdose and depression were the variables most strongly associated with risk for thoughts of suicide. CONCLUSIONS: Consistent with two theories of the development of suicidal thoughts and attempts, exposure to variables that reduce fear of death (e.g., overdoses) were associated with suicidal thoughts. In contrast, other risk-taking behaviors, medical comorbidities, and substance use were not key predictors of suicidal thoughts in this sample. Implications for targeted risk assessment among clinicians are discussed.

[Performance criteria for the verification of IgE and tryptase assay methods: recommendations from the AllergoBioNet network]. / Critères de performance pour la vérification des méthodes de dosages des IgE et de la tryptase : recommandations du réseau AllergoBioNet.

Accreditation of an in vitro diagnostic assay according to the NF/EN/ISO 15189 standard requires to analyze its technical performance before implementation for routine use, and annually when reviewing effectiveness of quality controls. Performance is evaluated through repeatability, intermediate fidelity, accuracy and uncertainty of measurement. The coefficients of variation (CV) of the intra-assay and inter-assay precision tests must be compared with those of "peers" (results from laboratories employing the same method) and also with those obtained with "all methods", i.e., results from all laboratories performing the same assay, irrespective of the method. To our best knowledge, there is currently no French or international recommendation on what the acceptable limits of performance for specific IgE and tryptase assays should be. Therefore, the AllergoBioNet network of hospital allergy laboratories set out to characterize the performance of their current methods as a basis for the development of recommendations. The results provided by 24 centers were analyzed and led to consensus recommendations for specific IgE, total IgE and tryptase assays.

Nodal/Activin Pathway is a Conserved Neural Induction Signal in Chordates.

Neural induction is the process through which pluripotent cells are committed to a neural fate. This first step of Central Nervous System formation is triggered by the "Spemann organizer" in amphibians and by homologous embryonic regions in other vertebrates. Studies in classical vertebrate models have produced contrasting views about the molecular nature of neural inducers and no unifying scheme could be drawn. Moreover, how this process evolved in the chordate lineage remains an unresolved issue. In this work, by using graft and micromanipulation experiments, we definitively establish that the dorsal blastopore lip of the cephalochordate amphioxus is homologous to the vertebrate organizer and is able to trigger the formation of neural tissues in a host embryo. In addition, we demonstrate that Nodal/Activin is the main signal eliciting neural induction in amphioxus, and that it also functions as a bona fide neural inducer in the classical vertebrate model Xenopus. Altogether, our results allow us to propose that Nodal/Activin was a major player of neural induction in the ancestor of chordates. This study further reveals the diversity of neural inducers deployed during chordate evolution and advocates against a universally conserved molecular explanation for this process.

[Survey of professional practices within the framework of the Continuous professional development: an experience led on a national scale on the theme of macroenzymes]. / Enquête de pratiques professionnelles dans le cadre du DPC: une expérience menée à l'échelle nationale sur le thème des macroenzymes.

The recent HPST law (reform of the hospital and relative to the patients, to the health and to the territories) states that the formation of the healthcare professionals is now "independent" and "compulsory". This law introduces the term of "Continuous professional development". The "Continuous professional development" groups together the former systems of both Evaluation of the professional practices and in-services training. Indeed, our practice gave us an opportunity to evaluate the practices of the professional of the specialists in laboratory medicine. We had to deal with very unsual cases of interference with a medicine (tenofovir) during the dosage of creatines kinases induced by the presence of a macroenzyme. To achieve this goal, a situation scenario was constructed and sent to a sample of practitioners. The first part deals with a clinical case with an analytic interference provoked by a macroenzyme. The second part refers to the usual techniques employed to reveal the presence of macroenzymes. The results were returned as a document suggesting a way to behave "in front of a suspicion of macroenzymes". This study is an illustration of what can be realized to answer the obligations of continuous professional development.

Ethnic variation in symptoms and response to risperidone in youths with schizophrenia-spectrum disorders.

BACKGROUND: Evaluation of symptom presentation and antipsychotic response based on ethnicity in children and adolescents with schizophrenia is limited. The purpose of this naturalistic, retrospective database study was to compare symptom presentation of children and adolescents of different ethnicities with schizophrenia-spectrum disorders, and response to risperidone. METHOD: African-American (n = 38), Caucasian (n = 30), or Hispanic (n = 37) youths started on risperidone were eligible. Child Behavior Checklist (CBCL) total, internalizing, and externalizing scores were evaluated at baseline, 90 days, 1 year, and 2 year intervals. RESULTS: At baseline, Hispanic patients had lower CBCL externalizing scores than African-Americans or Caucasians. African-Americans showed significant differences in CBCL total, internalizing, and externalizing scores at 90 days compared to baseline. Hispanics showed improvement in CBCL internalizing scores over the 2 year period. No significant improvements were observed in Caucasians. African-American patients had significantly lower CBCL total at 90 days compared to Hispanic patients. No significant difference existed in 2 year hospitalization rates between groups. CONCLUSIONS: These findings suggest that ethnicity may play a role in symptom presentation and treatment response to risperidone for children and adolescents with schizophrenia-spectrum disorders. Future studies in children and adolescents are necessary to examine ethnospecific differences in antipsychotic use and treatment response.