14 research outputs found
Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci
Background: A Xist RNA decorated Barr body is the structural hallmark of the compacted inactive X territory in female mammals. Using super resolution three-dimensional structured illumination microscopy (3D-SIM) and quantitative image analysis, we compared its ultrastructure with active chromosome territories (CTs) in human and mouse somatic cells, and explored the spatio-temporal process of Barr body formation at onset of inactivation in early differentiating mouse embryonic stem cells (ESCs). Results: We demonstrate that all CTs are composed of structurally linked chromatin domain clusters (CDCs). In active CTs the periphery of CDCs harbors low-density chromatin enriched with transcriptionally competent markers, called the perichromatin region (PR). The PR borders on a contiguous channel system, the interchromatin compartment (IC), which starts at nuclear pores and pervades CTs. We propose that the PR and macromolecular complexes in IC channels together form the transcriptionally permissive active nuclear compartment (ANC). The Barr body differs from active CTs by a partially collapsed ANC with CDCs coming significantly closer together, although a rudimentary IC channel system connected to nuclear pores is maintained. Distinct Xist RNA foci, closely adjacent to the nuclear matrix scaffold attachment factor-A (SAF-A) localize throughout Xi along the rudimentary ANC. In early differentiating ESCs initial Xist RNA spreading precedes Barr body formation, which occurs concurrent with the subsequent exclusion of RNA polymerase II (RNAP II). Induction of a transgenic autosomal Xist RNA in a male ESC triggers the formation of an `autosomal Barr body' with less compacted chromatin and incomplete RNAP II exclusion. Conclusions: 3D-SIM provides experimental evidence for profound differences between the functional architecture of transcriptionally active CTs and the Barr body. Basic structural features of CT organization such as CDCs and IC channels are however still recognized, arguing against a uniform compaction of the Barr body at the nucleosome level. The localization of distinct Xist RNA foci at boundaries of the rudimentary ANC may be considered as snap-shots of a dynamic interaction with silenced genes. Enrichment of SAF-A within Xi territories and its close spatial association with Xist RNA suggests their cooperative function for structural organization of Xi
Identification of rare germline copy number variations over-represented in five human cancer types
Intracameral Interleukin 1尾, 6, 8, 10, 12p, Tumor Necrosis Factor 伪 and Vascular Endothelial Growth Factor and Axial Length in Patients with Cataract
Comparative effectiveness of three-dimensional scaffold, differentiation media and co-culture with native cardiomyocytes to trigger in vitro cardiogenic differentiation of menstrual blood and bone marrow stem cells
mRECIST criteria to assess recurrent thyroid carcinoma treatment response after radiofrequency ablation: a prospective study
Clinicopathologic features and genetic characteristics of the BRCA1/2 mutation in Turkish breast cancer patients
Transcription factors regulate GPR91-mediated expression of VEGF in hypoxia-induced retinopathy
Vascular Alterations in Mental Disorders: Focus in Angiotensin II Role
Mental disorders have high prevalence and long duration, affecting the quality of life and generating elevated economic costs in public health. Approximately 25% of population worldwide will develop any mental illness at some moment of its lifetime. These disorders are the result of complex processes involving the interaction of many pathological changes. Although, each psychiatric disease has well-defined characteristics, some of their neurobiological processes, like inflammation and vascular alterations, seem to be common. Since microvasculature is involved in essential functions as oxygen delivery, waste product removal, and transvascular exchange, any brain vessel alteration could promote a pathological state. In this sense, capillary ultrastructural abnormalities, deficient perfusion, and blood-brain barrier disruption have been described in schizophrenia, depression, and Parkinson?s and Alzheimer?s diseases. These vascular dysfunctions could be related to angiogenic factor deregulations. The abovementioned evidences point out to evaluate the vasculature as a future pharmacological target for the treatment of mental disorders. Among the several factors involved in the regulation of angiogenesis, this chapter will focus on the upstream angiogenic mediator Angiotensin II. This peptide is produced at peripheral and brain level and exerts its principal effects acting through AT1 receptors. Considering that the available treatments for mental illnesses have low efficacy and high incidence of side effects, new pharmacological tools become necessary. The present chapter will be focused in the evidences that support Angiotensin II as a key factor in the understanding and therapy of these pathologies.Fil: Delgado Mar铆n, Leticia Ester. Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas. Centro Cient铆fico Tecnol贸gico Conicet - C贸rdoba. Instituto de Investigaciones Biol贸gicas y Tecnol贸gicas. Universidad Nacional de C贸rdoba. Facultad de Ciencias Exactas, F铆sicas y Naturales. Instituto de Investigaciones Biol贸gicas y Tecnol贸gicas; ArgentinaFil: Basmadjian, Osvaldo Martin. Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas. Centro Cient铆fico Tecnol贸gico Conicet - C贸rdoba. Instituto de Farmacolog铆a Experimental de C贸rdoba. Universidad Nacional de C贸rdoba. Facultad de Ciencias Qu铆micas. Instituto de Farmacolog铆a Experimental de C贸rdoba; ArgentinaFil: Occhieppo, Victoria Belen. Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas. Centro Cient铆fico Tecnol贸gico Conicet - C贸rdoba. Instituto de Farmacolog铆a Experimental de C贸rdoba. Universidad Nacional de C贸rdoba. Facultad de Ciencias Qu铆micas. Instituto de Farmacolog铆a Experimental de C贸rdoba; ArgentinaFil: Marchese, Natalia Andrea. Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas. Centro Cient铆fico Tecnol贸gico Conicet - C贸rdoba. Instituto de Farmacolog铆a Experimental de C贸rdoba. Universidad Nacional de C贸rdoba. Facultad de Ciencias Qu铆micas. Instituto de Farmacolog铆a Experimental de C贸rdoba; ArgentinaFil: Bregonzio Diaz, Claudia. Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas. Centro Cient铆fico Tecnol贸gico Conicet - C贸rdoba. Instituto de Farmacolog铆a Experimental de C贸rdoba. Universidad Nacional de C贸rdoba. Facultad de Ciencias Qu铆micas. Instituto de Farmacolog铆a Experimental de C贸rdoba; ArgentinaFil: Baiardi, Gustavo Carlos. Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas. Centro Cient铆fico Tecnol贸gico Conicet - C贸rdoba. Instituto de Investigaciones Biol贸gicas y Tecnol贸gicas. Universidad Nacional de C贸rdoba. Facultad de Ciencias Exactas, F铆sicas y Naturales. Instituto de Investigaciones Biol贸gicas y Tecnol贸gicas; Argentin