Knockdown of embryonic myosin heavy chain reveals an essential role in the morphology and function of the developing heart

The expression and function of embryonic myosin heavy chain (eMYH) has not been investigated within the early developing heart. This is despite the knowledge that other structural proteins, such as alpha and beta myosin heavy chains and cardiac alpha actin, play crucial roles in atrial septal development and cardiac function. Most cases of atrial septal defects and cardiomyopathy are not associated with a known causative gene, suggesting that further analysis into candidate genes is required. Expression studies localised eMYH in the developing chick heart. eMYH knockdown was achieved using morpholinos in a temporal manner and functional studies were carried out using electrical and calcium signalling methodologies. Knockdown in the early embryo led to abnormal atrial septal development and heart enlargement. Intriguingly, action potentials of the eMYH knockdown hearts were abnormal in comparison with the alpha and beta myosin heavy chain knockdowns and controls. Although myofibrillogenesis appeared normal, in knockdown hearts the tissue integrity was affected owing to apparent focal points of myocyte loss and an increase in cell death. An expression profile of human skeletal myosin heavy chain genes suggests that human myosin heavy chain 3 is the functional homologue of the chick eMYH gene. These data provide compelling evidence that eMYH plays a crucial role in important processes in the early developing heart and, hence, is a candidate causative gene for atrial septal defects and cardiomyopathy

Molecular characterisation of canine osteosarcoma in high risk breeds

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Dogs develop osteosarcoma (OSA) and the disease process closely resembles that of human OSA. OSA has a poor prognosis in both species and disease-free intervals and cure rates have not improved in recent years. Gene expression in canine OSAs was compared with non-tumor tissue utilising RNA sequencing, validated by qRT-PCR and immunohistochemistry (n = 16). Polymorphic polyglutamine (polyQ) tracts in the androgen receptor (AR/NR3C4) and nuclear receptor coactivator 3 (NCOA3) genes were investigated in control and OSA patients using polymerase chain reaction (PCR), Sanger sequencing and fragment analysis (n = 1019 Rottweilers, 379 Irish Wolfhounds). Our analysis identified 1281 significantly differentially expressed genes (>2 fold change, p < 0.05), specifically 839 lower and 442 elevated gene expression in osteosarcoma (n = 3) samples relative to non-malignant (n = 4) bone. Enriched pathways and gene ontologies were identified, which provide insight into the molecular pathways implicated in canine OSA. Expression of a subset of these genes (SLC2A1, DKK3, MMP3, POSTN, RBP4, ASPN) was validated by qRTPCR and immunohistochemistry (MMP3, DKK3, SLC2A1) respectively. While little variation was found in the NCOA3 polyQ tract, greater variation was present in both polyQ tracts in the AR, but no significant associations in length were made with OSA. The data provides novel insights into the molecular mechanisms of OSA in high risk breeds. This knowledge may inform development of new prevention strategies and treatments for OSA in dogs and supports utilising spontaneous OSA in dogs to improve understanding of the disease in people

Effect of Endocrine Disruptor Pesticides: A Review

Endocrine disrupting chemicals (EDC) are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air). For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Détection des récidives locales des sarcomes des parties molles des membres (évaluation rétrospective du suivi par IRM de 124 patients pris en charge à l'Institut Claudius Regaud)

L'intérêt de la réalisation systématique d'Imagerie par Résonnance Magnétique (IRM) dans la surveillance post-opératoire des sarcomes des parties molles des membres n'a pas été prouvé. Le but de notre étude est d'évaluer rétrospectivement l'efficacité d'un programme de surveillance par IRM réalisé chez 124 adultes traités entre 1996 et 2006 pour un sarcome des parties molles de membre non métastatique à l'Institut Claudius Regaud ; 86 patients (70%) avaient des marges de résection saines (R0) et 111 patients (90%) ont reçu une radiothérapie adjuvante. Sur les 11 récidives locales observées (9%), l'IRM n'a été capable de détecter que 2 récidives asymptomatiques, 1 avec et 1 sans métastases synchrones, les 2 avaient initialement des marges contaminées sur le plan microscopique (R1). Par ailleurs, il y a eu 11 faux positifs de l'IRM. La valeur prédictive positive de l'IRM a donc été calculée à 42%, la surveillance clinique seule semble plus efficace. Nos résultats ne permettent pas de conclure à l'efficacité de l'IRM dans la surveillance postopératoire de tous les sarcomes des parties molles des membres. Une étude prospective pourrait être effectuée pour l'évaluer chez les patients à haut risque de récidive locale.TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

IRM du cancer prostatique localisé (étude prospective sur 5 ans )

TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Implementation and Validation of an LTE D2D Model for ns-3

International audienceThe ability to perform device-to-device (D2D) communication in Long Term Evolution (LTE)-based cellular networks became possible with the introduction of Proximity Services (ProSe) functionalities in the 3rd Generation Partnership Program (3GPP) specifications. In this paper, we provide a description of the ProSe implementation that extends the LTE model already available in ns-3. Our model contains key features defined in LTE Release 12 and further enhanced in LTE Release 13 related to synchronization, discovery, and communication. We also provide validation of each feature by comparing simulation results with analytical models developed as part of our work on D2D communication

A Long Term Evolution (LTE) Device-to-Device module for ns-3

International audienceIn this paper, we provide an overview of our ongoing implementation of a 3 rd Generation Partnership Program (3GPP) Proximity Services (ProSe) module in ns-3 to enable the performance evaluation of device-to-device (D2D) discovery and communication in Long Term Evolution (LTE) networks

La Maison du triomphe de Neptune à Acholla (Botria, Tunisie). I. Les mosaïques

Les fouilles du port antique d'Acholla, commencées en 1947, poursuivies depuis 1979 par une équipe franco-tunisienne, ont mis au jour, outre deux établissements thermaux, trois habitations privées qui conservent de riches pavements en mosaïque. La maison du Triomphe de Neptune - la première entièrement publiée - tire son nom de la mosaïque de l'œcus dont le centre représente le dieu en char, entouré de son cortège de Néréides et d'Ichtyocentaures. L'ensemble pavimental, en excellent état lors de la découverte, recouvrait le péristyle et toutes les pièces d'habitation, à l'exception des pièces de service, soit 1175 m2 environ, composant cinquante-six décors différents. Très homogène, sûrement d'une seule venue, il a été daté de la fin du règne d'Antonin le Pieux ou du début du règne de Marc-Aurèle (env. 150-170). La plupart des tapis présentent de beaux décors ornementaux : géométriques ou végétalisants. Cinq contiennent des sujets figurés : xenia, scènes marines et dionysiaques. Leur analyse minutieuse et les rapprochements faits avec la production de la province conduisent à discerner des habitudes de travail ou des manières d'atelier, et à identifier un répertoire et une facture typiques de la région thysdritaine. Ils permettent aussi d'apprécier la beauté de ces pavements, due à la qualité de l'exécution, et les caractéristiques d'un style qui combine harmonieusement, d'une part, la sobriété des canevas et la rigueur de leur mise en place, d'autre part, la finesse et la grâce des tracés qui les réalisent. La décoration de cette demeure aristocratique témoigne en somme du goût d'une province et d'une époque, et en est une des plus belles expressions.Gozlan Suzanne. La Maison du triomphe de Neptune à Acholla (Botria, Tunisie). I. Les mosaïques. Rome : École Française de Rome, 1992. 428 p. (Publications de l'École française de Rome, 160