The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Facteurs prédictifs de succès du sevrage tabagique (étude prospective à propos de 874 fumeurs)

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Titre : La place controversée de la gestation pour autrui en 2021 : des repères éthiques (in)discutables ?

International audienceAt the time of the revision of French bioethics law and of the disruption of the access to assisted reproductive technology, surrogacy challenges the ethical benchmarks of French legislators. Surrogacy is at the intersection of numerous issues, whether they are medical, social, psychological, legal, political or feminist, and thus it questions the motto of the French Republic « Liberty, Equality, Fraternity ». At the center of many debates, the access to parenthood gives rise to passions when it is enabled by surrogacy. So, it leads to consider other alternatives as uterus transplant or even adoption. This article debates, through the subject of surrogacy, the symbolic value of motherhood and the place of child desire in the French society. This article aims to survey the potential feminine and child vulnerability to which surrogacy could expose. In the light of collected and discussed data, we advocate for a legal framework of surrogacy in order to avoid a hypocrisy of recognition in which the French system is currently positioned and to avoid the drifts indirectly accepted by France outside of its borders. The analysis is simple and clear: refusing to regulate, it's choosing not to protect anyone.À l’heure de la révision de la loi de bioéthique française et du bouleversement de l’accès à la procréation médicalement assistée, la gestation pour autrui vient questionner les repères éthiques auxquels se rattachent les législateurs français. Au carrefour de nombreuses problématiques médicales, sociales, psychologiques, légales, politiques ou encore féministes, la gestation pour autrui interroge la devise française « liberté, égalité, fraternité ». Au cœur de nombreux débats, l’accès à la parentalité soulève les passions quand elle est permise par la gestation pour autrui, ce qui induit d’envisager d’autres alternatives comme la greffe d’utérus ou encore l’adoption. Cet article discute, à travers la gestation pour autrui, la valeur symbolique de la maternité et la place du désir d’enfant dans la société française. Il a également pour objet de sonder la vulnérabilité féminine et infantile à laquelle cette pratique pourrait exposer. Au regard des données collectées et discutées, nous plaidons pour un encadrement légal de la gestation pour autrui afin d’éviter une hypocrisie de reconnaissance dans laquelle se place actuellement le système français et d’empêcher les dérives que la France tolère tacitement en dehors de ses frontières. Le constat est simple : refuser d’encadrer, c’est choisir de ne protéger personne

Diversity of Extracellular Vesicles in Human Follicular Fluid: Morphological Analysis and Quantification

International audienceThe oocyte microenvironment constituted by the follicular fluid (FF) is a key for the optimal development of female gametes. Its composition reflects the physiological state of the ovarian follicle. The particularity of FF is to contain a huge diversity of extracellular vesicles specific to women, in the same way as seminal plasma in men. Here, we described and compared morphological aspects of broad subcategories of human FF-related Extracellular Vesicles (EVs). EVs participate in physiological and pathological processes and have potential applications in diagnostics or therapeutics. EVs isolated from FF are involved in different biological functions related to follicular growth, oocyte maturation, and embryo development. However, knowledge on the morphology of FF-derived EVs is limited, mainly due to their sub-micrometer size and to intrinsic limitations in methods applied for their characterization. The aim of this study was to provide a comprehensive morphological description of EVs from FF of healthy subjects and quantification. EVs separation was realized by centrifugation, with comparison of the EV yield obtained from differential centrifugation and one-step ultracentrifugation. Cryo-Transmission Electron Microscopy was used to reveal the morphology, size, and phenotype of EVs. Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA) were used to quantify and analyze the size distribution for each centrifugation step. We performed a comprehensive inventory of human follicular fluid EVs. We show that human FF contains a huge diversity of EVs. This study brings novel insights on EVs from normal FF and provides a reference for further studies of EVs in ovarian diseases

Livre blanc -Octobre 2022 Protéines végétales pour une santé globale : identification des connaissances, verrous et leviers pour leur développement dans l'alimentation humaine Auteurs

Son périmètre concerne la biologie végétale, l'agronomie, la transformation et la nutrition humaine

Pseudodicentric Chromosome Originating from Autosomes 9 and 21 in a Male Patient with Oligozoospermia

International audienceGenetic factors are responsible for 15% of male infertility conditions. Numerical and structural chromosomal anomalies (related to the Y chromosome or to the autosomes) are validated genetic factors leading to spermatogenic quantitative defects with a frequency depending on the severity of the phenotype. The most frequent structural chromosomal rearrangements of autosomes are translocations and inversions, whereas dicentric chromosomes involving autosomes are rare. We report a man bearing a pseudodicentric chromosome (9;21) and presenting with oligozoospermia. Extensive cytogenetic analyses were necessary to determine the precise nature of the derivative chromosome and to discount the presence of interstitial telomeric sequences. Defects in spermatogenesis and abnormal segregation at meiosis for existing spermatozoa are proposed and are the likely cause of the reproductive phenotype of the patient

The genome sequence of Bacillus cereus ATCC 10987 reveals metabolic adaptations and a large plasmid related to Bacillus anthracis pXO1

We sequenced the complete genome of Bacillus cereus ATCC 10987, a non-lethal dairy isolate in the same genetic subgroup as Bacillus anthracis. Comparison of the chromosomes demonstrated that B.cereus ATCC 10987 was more similar to B.anthracis Ames than B.cereus ATCC 14579, while containing a number of unique metabolic capabilities such as urease and xylose utilization and lacking the ability to utilize nitrate and nitrite. Additionally, genetic mechanisms for variation of capsule carbohydrate and flagella surface structures were identified. Bacillus cereus ATCC 10987 contains a single large plasmid (pBc10987), of ∼208 kb, that is similar in gene content and organization to B.anthracis pXO1 but is lacking the pathogenicity-associated island containing the anthrax lethal and edema toxin complex genes. The chromosomal similarity of B.cereus ATCC 10987 to B.anthracis Ames, as well as the fact that it contains a large pXO1-like plasmid, may make it a possible model for studying B.anthracis plasmid biology and regulatory cross-talk

Lung cancer in combined pulmonary fibrosis and emphysema: A series of 47 western patients

Introduction: The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is characterized by imaging features consisting of the association of centrilobular and/or paraseptal emphysema and pulmonary fibrosis. Virtually all patients are smokers and thus at high risk of developing lung cancer. Methods: This retrospective multicentre study was conducted by the Groupe d'Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P). Results: A total of 47 patients presenting with lung cancer and CPFE syndrome were identified. All patients were smokers, with a mean of 47 pack-years. A pathological diagnosis of lung cancer was obtained for 38 (81%) patients. Histological type was squamous cell carcinoma in 17 (36%) patients, adenocarcinoma in 14 (30%), non- small-cell lung cancer not otherwise specified in three (6%), smallcell lung cancer in three (6%), and sarcomatoid carcinoma in one (2%). Overall, 20 of the 47 patients could not receive standard-ofcare treatment for lung cancer, as per international recommendations or guidelines; this limitation was considered to be directly related to the CPFE syndrome in eight (40%) cases. Conclusion: Lung cancer in patients with CPFE syndrome represents a specific entity with a poor prognosis, that further represents the most characteristic and severe model of tobacco-related disease. Copyright © 2014 by the International Association for the Study of Lung