Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice

Duchenne muscular dystrophy (DMD) is characterized by progressive lethal muscle degeneration and chronic inflammatory response. The mdx mouse strain has served as the animal model for human DMD. However, while DMD patients undergo extensive necrosis, the affected muscles of adult mdx mice rapidly regenerates and regains structural and functional integrity. The basis for the mild effects observed in mice compared with the lethal consequences in humans remains unknown. In this study, we provide evidence that interleukin-6 (IL-6) is causally linked to the pathogenesis of muscular dystrophy. We report that forced expression of IL-6, in the adult mdx mice, recapitulates the severe phenotypic characteristics of DMD in humans. Increased levels of IL-6 exacerbate the dystrophic muscle phenotype, sustaining inflammatory response and repeated cycles of muscle degeneration and regeneration, leading to exhaustion of satellite cells. The mdx/IL6 mouse closely approximates the human disease and more faithfully recapitulates the disease progression in humans. This study promises to significantly advance our understanding of the pathogenic mechanisms that lead to DMD

Foxl2 functions in sex determination and histogenesis throughout mouse ovary development

Background. Partial loss of function of the transcription factor FOXL2 leads to premature ovarian failure in women. In animal models, Foxl2 is required for maintenance, and possibly induction, of female sex determination independently of other critical genes, e.g., Rspo1. Here we report expression profiling of mouse ovaries that lack Foxl2 alone or in combination with Wnt4 or Kit/c-Kit. Results. Following Foxl2 loss, early testis genes (including Inhbb, Dhh, and Sox9) and several novel ovarian genes were consistently dysregulated during embryonic development. In the absence of Foxl2, expression changes affecting a large fraction of pathways were opposite those observed in Wnt4-null ovaries, reinforcing the notion that these genes have complementary actions in ovary development. Loss of one copy of Foxl2 revealed strong gene dosage sensitivity, with molecular anomalies that were milder but resembled ovaries lacking both Foxl2 alleles. Furthermore, a Foxl2 transgene disrupted embryonic testis differentiation and increased the levels of key female markers. Conclusion. The results, including a comprehensive principal component analysis, 1) support the proposal of dose-dependent Foxl2 function and anti-testis action throughout ovary differentiation; and 2) identify candidate genes for roles in sex determination independent of FOXL2 (e.g., the transcription factors IRX3 and ZBTB7C) and in the generation of the ovarian reserve downstream of FOXL2 (e.g., the cadherin-domain protein CLSTN2 and the sphingomyelin synthase SGMS2). The gene inventory is a first step toward the identification of the full range of pathways with partly autonomous roles in ovary development, and thus provides a framework to analyze the genetic bases of female fertility

LIME -- a gas TPC prototype for directional Dark Matter search for the CYGNO experiment

The CYGNO experiment aims at the development of a large gaseous TPC with GEM-based amplification and an optical readout by means of PMTs and scientific CMOS cameras for 3D tracking down to O(keV) energies, for the directional detection of rare events such as low mass Dark Matter and solar neutrino interactions. The largest prototype built so far towards the realisation of the CYGNO experiment demonstrator is the 50 L active volume LIME, with 4 PMTs and a single sCMOS imaging a 33$\times$33 cm\textsuperscript{2} area for 50 cm drift, that has been installed in underground Laboratori Nazionali del Gran Sasso in February 2022. We will illustrate LIME performances as evaluated overground in Laboratori Nazionali di Frascati by means of radioactive X-ray sources, and in particular the detector stability, energy response and energy resolution. We will discuss the MC simulation developed to reproduce the detector response and show the comparison with actual data. We will furthermore examine the background simulation worked out for LIME underground data taking and illustrate the foreseen expected measurement and results in terms of natural and materials intrinsic radioactivity characterisation and measurement of the LNGS underground natural neutron flux. The results that will be obtained by underground LIME installation will be paramount in the optimisation of the CYGNO demonstrator, since this is foreseen to be composed by multiple modules with the same LIME dimensions and characteristics

The CYGNO Experiment

The search for a novel technology able to detect and reconstruct nuclear and electron recoil events with the energy of a few keV has become more and more important now that large regions of high-mass dark matter (DM) candidates have been excluded. Moreover, a detector sensitive to incoming particle direction will be crucial in the case of DM discovery to open the possibility of studying its properties. Gaseous time projection chambers (TPC) with optical readout are very promising detectors combining the detailed event information provided by the TPC technique with the high sensitivity and granularity of latest-generation scientific light sensors. The CYGNO experiment (a CYGNus module with Optical readout) aims to exploit the optical readout approach of multiple-GEM structures in large volume TPCs for the study of rare events as interactions of low-mass DM or solar neutrinos. The combined use of high-granularity sCMOS cameras and fast light sensors allows the reconstruction of the 3D direction of the tracks, offering good energy resolution and very high sensitivity in the few keV energy range, together with a very good particle identification useful for distinguishing nuclear recoils from electronic recoils. This experiment is part of the CYGNUS proto-collaboration, which aims at constructing a network of underground observatories for directional DM search. A one cubic meter demonstrator is expected to be built in 2022/23 aiming at a larger scale apparatus (30 m$^3$--100 m$^3$) at a later stage

Development of the testis

Compte-rendu  (publié dans Bryn Mawr Classical Review) de l'ouvrage de Laurent Dubois, Inscriptions Grecques Dialectales de Sicile. Tome II. Hautes Études du monde gréco-romain 40.   Genève:  Droz, 2008. Laurent Dubois, professeur à l'École Pratique des Hautes Études, propose dans ce recueil (par commodité IGDS II) un nouveau choix d'inscriptions découvertes en Sicile depuis la parution de son premier travail publié dans la collection de l'École Française de Rome en 1989. Comme l'auteur l'exp..

Genetics of the ovarian reserve

Primordial follicles or non-growing follicles (NGFs) are the functional unit of reproduction, each comprising a single germ cell surrounded by supporting somatic cells. NGFs constitute the ovarian reserve, prerequisite for germ cell ovulation and the continuation of the species. The dynamics of the reserve is determined by the number of NGFs formed and their complex subsequent fates. During the reproductive lifespan, the ovarian reserve progressively diminishes due to follicle atresia as well as recruitment, maturation, and ovulation. The depletion of the ovarian reserve is the major determining driver of menopause, which ensues when the number of primordial follicles falls below a threshold of ~1,000. Therefore, genes and processes involved in follicle dynamics are particularly important to understand the process of menopause, both in the typical reproductive lifespan and in conditions like primary ovarian insufficiency (POI), defined as menopause before age 40. Genes and their variants that affect the timing of menopause thereby provide candidates for diagnosis of and intervention in problems of reproductive lifespan. We review the current knowledge of processes and genes involved in the development of the ovarian reserve and in the dynamics of ovarian follicles

Germ cell formation from embryonic stem cells and the use of somatic cell nuclei in oocytes

Embryonic stem cells (ESCs) have remarkable properties of pluripotency and self-renewal, along with the retention of chromosomal integrity. Germ cells function as a kind of "transgenerational stem cells," transmitting genetic information from one generation to the next. The formation of putative primordial germ cells (PGCs) and germ cells from mouse and human ESCs (hESCs) has, in fact, been shown, and the apparent derivation of functional mouse male gametes has also been described. Additionally, investigators have successfully reprogrammed somatic nuclei into a pluripotent state by inserting them into ESCs or oocytes. This would enable the generation of ESCs genetically identical to the somatic cell donor and their use in cell therapy. However, these methodologies are still inefficient and their mechanisms poorly understood. Until full comprehension of these processes is obtained, clinical applications remain remote. Nevertheless, they represent promising tools in the future, enhancing methods of therapeutic cloning and infertility treatment