Analysis of the P. lividus sea urchin genome highlights contrasting trends of genomic and regulatory evolution in deuterostomes

Sea urchins are emblematic models in developmental biology and display several characteristics that set them apart from other deuterostomes. To uncover the genomic cues that may underlie these specificities, we generated a chromosome-scale genome assembly for the sea urchin Paracentrotus lividus and an extensive gene expression and epigenetic profiles of its embryonic development. We found that, unlike vertebrates, sea urchins retained ancestral chromosomal linkages but underwent very fast intrachromosomal gene order mixing. We identified a burst of gene duplication in the echinoid lineage and showed that some of these expanded genes have been recruited in novel structures (water vascular system, Aristotle's lantern, and skeletogenic micromere lineage). Finally, we identified gene-regulatory modules conserved between sea urchins and chordates. Our results suggest that gene-regulatory networks controlling development can be conserved despite extensive gene order rearrangement

Defensome against Toxic Diatom Aldehydes in the Sea Urchin Paracentrotus lividus

Many diatom species produce polyunsaturated aldehydes, such as decadienal, which compromise embryonic and larval development in benthic organisms. Here newly fertilized Paracentrotus lividus sea urchins were exposed to low concentration of decadienal and the expression levels of sixteen genes, implicated in a broad range of functional responses, were followed by Real Time qPCR in order to identify potential decadienal targets. We show that at low decadienal concentrations the sea urchin Paracentrotus lividus places in motion different classes of genes to defend itself against this toxic aldehyde, activating hsp60 and two proteases, hat and BP10, at the blastula stage and hsp56 and several other genes (14-3-3ε, p38 MAPK, MTase, and GS) at the prism stage. At this latter stage all genes involved in skeletogenesis (Nec, uni, SM50 and SM30) were also down-expressed, following developmental abnormalities that mainly affected skeleton morphogenesis. Moreover, sea urchin embryos treated with increasing concentrations of decadienal revealed a dose-dependent response of activated target genes. Finally, we suggest that this orchestrated defense system against decadienal represents part of the chemical defensome of P. lividus affording protection from environmental toxicants

Epitome historiae sacrae

156 p

Conceptualization and measurement of homosexuality in sex surveys: a critical review Modos de conceitualizar e medir homossexualidade em pesquisas sobre sexualidade: uma revisão crítica

This article reviews major national population sex surveys that have asked questions about homosexuality focusing on conceptual and methodological issues, including the definitions of sex, the measured aspects of homosexuality, sampling and interviewing technique, and questionnaire design. Reported rates of major measures of same-sex attraction, behavior, partners, and sexual identity from surveys are also presented and compared. The study of homosexuality in surveys has been shaped by the research traditions and questions ranging from sexology to the epidemiology of HIV/AIDS. Sexual behavior has been a central topic at least since Kinsey. Issues of sexual attraction and/or orientation and sexual identity have emerged more recently. Differences in the treatment of men and women in the design and analysis of surveys as well as in the reported rates in different surveys, in different countries and time periods are also presented and discussed. We point out the importance of the consideration of both methodological and social change issues in assessing such differences.<br>O artigo traz uma revisão das principais pesquisas nacionais sobre sexualidade que apresentam perguntas sobre homossexualidade, com foco nas questões conceituais e metodológicas sobre as definições de sexo, os aspectos de medição da homossexualidade, as técnicas de amostragem e de entrevistas e o formato do questionário. As taxas de declaração sobre atração pelo mesmo sexo, comportamento, parceiros e identidade também são apresentadas e comparadas. O estudo da homossexualidade em inquéritos populacionais foi moldado com base em tradições de investigação e questões provenientes desde a sexologia até a epidemiologia do HIV/AIDS. O comportamento sexual é assunto central nas pesquisas sobre sexualidade desde Kinsey. Os temas sobre atração sexual, identidade e/ou orientação sexual surgem mais recentemente. São abordadas e discutidas as diferenças no tratamento de homens e mulheres na formulação e análise das pesquisas, assim como as taxas de respostas em diferentes pesquisas, em distintos países e momentos históricos. Ressaltamos a relevância de que sejam consideradas tanto mudanças metodológicas quanto sociais para interpretar as diferenças constatadas

IRE1-MEDIATED IMMUNOMODULATION IN GLIOBLASTOMA

International audienceConference: 12th Meeting of the European-Association-of-Neuro-Oncology Location: GERMANY Date: OCT 12-16, 2016 - Meeting Abstract: OS1.

Posttranscriptional Regulation of PER1 Underlies the Oncogenic Function of IRE

International audienceGrowing evidence supports a role for the unfolded protein response (UPR) in carcinogenesis; however, the precise molecular mechanisms underlying this phenomenon remain elusive. Herein, we identified the circadian clock PER1 mRNA as a novel substrate of the endoribonuclease activity of the UPR sensor IRE1α. Analysis of the mechanism shows that IRE1α endoribonuclease activity decreased PER1 mRNA in tumor cells without affecting PER1 gene transcription. Inhibition of IRE1α signaling using either siRNA-mediated silencing or a dominant-negative strategy prevented PER1 mRNA decay, reduced tumorigenesis, and increased survival, features that were reversed upon PER1 silencing. Clinically, patients showing reduced survival have lower levels of PER1 mRNA expression and increased splicing of XBP1, a known IRE-α substrate, thereby pointing toward an increased IRE1α activity in these patients. Hence, we describe a novel mechanism connecting the UPR and circadian clock components in tumor cells, thereby highlighting the importance of this interplay in tumor development

Local intracerebral inhibition of IRE1 by MKC8866 sensitizes glioblastoma to irradiation/chemotherapy in vivo

Glioblastoma multiforme (GBM) is the most severe primary brain cancer. Despite an aggressive treatment comprising surgical resection and radio/chemotherapy, patient's survival post diagnosis remains short. A limitation for success in finding novel improved therapeutic options for such dismal disease partly lies in the lack of a relevant animal model that accurately recapitulates patient disease and standard of care. In the present study, we have developed an immunocompetent GBM model that includes tumor surgery and a radio/chemotherapy regimen resembling the Stupp protocol and we have used this model to test the impact of the pharmacological inhibition of the endoplasmic reticulum (ER) stress sensor IRE1, on treatment efficacy. © 2020 Elsevier B.V