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Partially, these complications can be explained by the most frequently used transcatheter heart valves, which are balloon-expanding bioprostheses intended for transcatheter aortic valve implantation that cannot be repositioned. Currently, frequently used approaches for transcatheter mitral valve replacement include retrograde transapical and antegrade transseptal techniques, most often with the use of transcatheter heart valves from the Sapien family (Edwards Lifesciences Inc., Irvine, CA, USA) followed by the mechanical expandable Lotus valve (Boston Scientific, Marlborough, MS, USA). Anecdotal reports have described the application of self-expandable transcatheter heart valves (Centera; Edwards) or dedicated transcatheter mitral valve replacement devices. In this report, we give an overview of current interventional techniques, available evidence and reported outcomes for transcatheter mitral valve replacement for degenerated bioprosthetic valves and failed annuloplasty rings.Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that plays a crucial role in the development of the nervous system while supporting the survival of existing neurons and instigating neurogenesis. Altered levels of BDNF, both in the circulation and in the central nervous system (CNS), have been reported to be involved in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), multiple sclerosis (MS), and ischemic stroke. MicroRNAs (miRNAs) are a class of non-coding RNAs found in body fluids such as peripheral blood and cerebrospinal fluid. Several different miRNAs, and their target genes, are recognized to be involved in the pathophysiology of neurodegenerative and neurovascular diseases. Thus, they present as promising biomarkers and a novel treatment approach for CNS disorders. Currently, limited studies provide viable evidence of miRNA-mediated post-transcriptional regulation of BDNF. The aim of this review is to provide a comprehensive assessment of the current knowledge regarding the potential diagnostic and prognostic values of miRNAs affecting BDNF expression and its role as a CNS disorders and neurovascular disease biomarker. Moreover, a novel therapeutic approach in neurodegenerative diseases and ischemic stroke targeting miRNAs associated with BDNF will be discussed.The adaptation of Hi-C protocols to enable the investigation of chromosome organization in single cells opens new avenues to study the dynamics of this process during embryogenesis. However, the analysis of single-cell Hi-C data is not yet standardized and raises novel bioinformatic challenges. Here we describe a complete workflow for the analysis of single-cell Hi-C data, with a main focus on allele-specific analysis based on data obtained from hybrid embryos.Over the past two decades, the development of chromosome conformation capture technologies has allowed to intensively probe the properties of genome folding in various cell types. High-throughput versions of these C-based assays (named Hi-C) have released the mapping of 3D chromosome folding for the entire genomes. Applied to mammalian preimplantation embryos, it has revealed a unique chromosome organization after fertilization when a new individual is being formed. However, the questions of whether specific structures could arise depending on their parental origins or of their transcriptional status remain open. Our method chapter is dedicated to the technical description on how applying scHi-C to mouse embryos at different stages of preimplantation development. This approach capitalized with the limited amount of material available at these developmental stages. It also provides new research avenues, such as the study of mutant embryos for further functional studies.Investigating the chromatin landscape of the early mammalian embryo is essential to understand how epigenetic mechanisms may direct reprogramming and cell fate allocation. #link# Genome-wide analyses of the epigenome in preimplantation mouse embryos have recently become available, thanks to the development of low-input protocols. DNA adenine methyltransferase identification (DamID) enables the investigation of genome-wide protein-DNA interactions without the requirement of specific antibodies. Most importantly, DamID can be robustly applied to single cells. Here we describe the protocol for performing DamID in single oocytes and mouse preimplantation embryos, as well as single blastomeres, using a Dam-LaminB1 fusion to generate high-resolution lamina-associated domain (LAD) maps. This low-input method can be adapted for other proteins of interest to faithfully profile their genomic interaction, allowing us to interrogate the chromatin dynamics and nuclear organization during the early mammalian development.Cleavage under targets and release using nuclease (CUT&RUN) allows the chromatin profiling of proteins of interest for which specific antibodies are available. Because it is performed on intact chromatin in situ, CUT&RUN provides exceptional signal over background, making it an ideal choice for chromatin profiling on primary cells available at limited numbers. Here, we describe its application to the profiling of histone post-translational modifications in germ cells isolated from mouse embryos from 12.5 up to 18.5 days postfertilization. This approach can be applied to as low as 100 isolated germ cells, allowing the generation of multiple genome-wide profiles from the cells obtained from a single embryo.ChIP-seq is a powerful technique that allows the detection of chromatin localization for proteins and epigenetic modifications. However, conventional ChIP-seq usually requires millions of cells. This becomes a daunting task for applications in which only limited experimental materials are available. For example, during mammalian embryo development, the epigenomes undergo drastic reprogramming which endows a fertilized egg with the potential to develop into the whole body. Low-input ChIP-seq methods would be instrumental to help decipher molecular mechanisms underlying such epigenetic reprogramming. Here we describe an optimized ChIP-seq method-STAR (Small-scale TELP-Assisted Rapid) ChIP-seq-that allows the detection of histone modifications using only a few hundred cells. Tolinapant is proven to be robust in epigenomic profiling in both embryos and cultured cells.

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