Ki-67 is a PP1-interacting protein that organises the mitotic chromosome periphery

Copyright @ 2014 Booth et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.When the nucleolus disassembles during open mitosis, many nucleolar proteins and RNAs associate with chromosomes, establishing a perichromosomal compartment coating the chromosome periphery. At present nothing is known about the function of this poorly characterised compartment. In this study, we report that the nucleolar protein Ki-67 is required for the assembly of the perichromosomal compartment in human cells. Ki-67 is a cell-cycle regulated protein phosphatase 1-binding protein that is involved in phospho-regulation of the nucleolar protein B23/nucleophosmin. Following siRNA depletion of Ki-67, NIFK, B23, nucleolin, and four novel chromosome periphery proteins all fail to associate with the periphery of human chromosomes. Correlative light and electron microscopy (CLEM) images suggest a near-complete loss of the entire perichromosomal compartment. Mitotic chromosome condensation and intrinsic structure appear normal in the absence of the perichromosomal compartment but significant differences in nucleolar reassembly and nuclear organisation are observed in post-mitotic cells

Characterization of patients with bradyarrhythmias treated at the Cienfuegos Cardiology service (2018-2019)

Background: The creation of a bradyarrhythmias consultation in Cienfuegos, since 2017, has made possible the treatment and more specific follow-up of affected patients. Therefore, the study of its clinical and paraclinical characteristics is relevant.Objective: to characterize patients with non-reversible bradyarrhythmias from the clinical point of view.Methods: an observational, descriptive, cross-sectional study was carried out. All the patients seen by the Cardiology Service with a diagnosis of non-reversible bradyarrhythmia (N = 214) were taken into account to this work. Clinical, electrocardiographic, ergometric and echocardiographic variables were studied. Each one was given the statistical treatment according to its distribution, scale and type.Results: Male sex predominated. The median age was 74 years. Hypertension was the most frequent comorbidity. The echocardigraphic study showed some type of structural alteration in the 80% of the patients. The most common etiology was fibrosis of the excito-conductor system (77%), as well as third degree atrioventricular block was the most common electrocardiographic diagnosis among those who received temporary and permanent pacemaker implantation. There was a low rate of complications.Conclusion: the studied population was characterized as aged; with the presence of comorbidities; with some type of structural alteration in the majority, demonstrated through echocardiographic study. Fibrosis of the excito-conductive system and ischemic were the main causes of non-reversible bradyarrhythmia.</p

A Genetic Model of Constitutively Active Integrin CD11b/CD18

Pharmacological activation of integrin CD11b/CD18 (α β , Mac-1, and CR3) shows anti-inflammatory benefits in a variety of animal models of human disease, and it is a novel therapeutic strategy. Reasoning that genetic models can provide an orthogonal and direct system for the mechanistic study of CD11b agonism, we present in this study, to our knowledge, a novel knock-in model of constitutive active CD11b in mice. We genetically targeted the gene (which codes for CD11b) to introduce a point mutation that results in the I332G substitution in the protein. The I332G mutation in CD11b promotes an active, higher-affinity conformation of the ligand-binding I/A-domain (CD11b αA-domain). In vitro, this mutation increased adhesion of knock-in neutrophils to fibrinogen and decreased neutrophil chemotaxis to a formyl-Met-Leu-Phe gradient. In vivo, CD11b animals showed a reduction in recruitment of neutrophils and macrophages in a model of sterile peritonitis. This genetic activation of CD11b also protected against development of atherosclerosis in the setting of hyperlipidemia via reduction of macrophage recruitment into atherosclerotic lesions. Thus, our animal model of constitutive genetic activation of CD11b can be a useful tool for the study of integrin activation and its potential contribution to modulating leukocyte recruitment and alleviating different inflammatory diseases

Transcriptomics of Human Arteriovenous Fistula Failure: Genes Associated With Nonmaturation

Improving arteriovenous fistula (AVF) outcomes requires better understanding of the biology underlying maturation or failure. Our current knowledge of maturation relies on extrapolation from other vascular pathologies, which does not incorporate unique aspects of AVF remodeling. This study compares the RNA expression of pre-access (native) veins and AVFs with distinct maturation outcomes. Case-control study. 64 patients undergoing 2-stage AVF surgeries at a single center. 19 native veins and 19 AVF samples were analyzed using RNA sequencing (RNA-seq). 58 native veins were studied using real-time polymerase chain reaction; 45, using immunohistochemistry; and 19, using Western blot analysis. RNA expression in native veins and AVFs. Anatomic nonmaturation, defined as an AVF that never achieved an internal diameter ≥ 6mm. Pre-access native veins and AVF samples were obtained from patients undergoing 2-stage AVF creation. Veins that subsequently matured or failed after access creation were analyzed using RNA-seq to search for genes associated with maturation failure. Genes associated with nonmaturation were confirmed using real-time polymerase chain reaction, immunohistochemistry, and Western blot analysis. In addition, the association between pre-access gene expression and postoperative morphology was evaluated. RNA-seq was also performed on AVFs to search for transcriptional differences between AVFs that matured and those that failed at the time of transposition. Pro-inflammatory genes (CSF3R, FPR1, S100A8, S100A9, and VNN2) were upregulated in pre-access veins that failed (false discovery rate < 0.05), and their expression colocalized to smooth muscle cells. Expression of S100A8 and S100A9 correlated with postoperative intimal hyperplasia and the product of medial fibrosis and intimal hyperplasia (r=0.32-0.38; P < 0.05). AVFs that matured or failed were transcriptionally similar at the time of transposition. Small sample size, analysis of only upper-arm veins and transposed fistulas. Increased expression of proinflammatory genes in pre-access veins appears to be associated with greater risk for AVF nonmaturation

Dysregulation of RNA polymerase I transcription during disease

Transcription of the ribosomal RNA genes by the dedicated RNA polymerase I enzyme and subsequent processing of the ribosomal RNA are fundamental control steps in the synthesis of functional ribosomes.Dysregulation of Pol I transcription and ribosome biogenesis is linked to the etiology of a broad range of human diseases. Diseases caused by loss of function mutations in the molecular constituents of the ribosome, or factors intimately associated with RNA polymerase I transcription and processing are collectively termed ribosomopathies. Ribosomopathies are generally rare and treatment options are extremely limited tending to be more palliative than curative. Other more common diseases are associated with profound changes in cellular growth such as cardiac hypertrophy, atrophy or cancer. In contrast to ribosomopathies, altered RNA polymerase I transcriptional activity in these diseases largely results from dysregulated upstream oncogenic pathways or by direct modulation by oncogenes or tumor suppressors at the level of the RNA polymerase I transcription apparatus itself. Ribosomopathies associated with mutations in ribosomal proteins and ribosomal RNA processing or assembly factors have been covered by recent excellent reviews. In contrast, here we review our current knowledge of human diseases specifically associated with dysregulation of RNA polymerase I transcription and its associated regulatory apparatus, including some cases where this dysregulation is directly causative in disease. We will also provide insight into and discussion of possible therapeutic approaches to treat patients with dysregulated RNA polymerase I transcription. This article is part of a Special Issue entitled: Transcription by Odd Pols

Cultural Identity, Religion, and Globalization in Latin America. Our Lady of Guadalupe and Saint Martin de Porres as Clear Examples of Interculturalism and Instruments of Mediation among Different Weltanschauungen

Latin America is a part of that Global village where—according to Marc Augé—places, time, and space exist in abundance and where the presumed unique nature of the Western model clashes with the image of the “other”. (Augé (2009); Salgues (2016), p. 114) Thus, while the formation of a multiethnic and multicultural society—one based on the principle of tolerance, in which diversity and homologation should coexist without conflict—is hoped for, the spread of such categories as ethnicity and minority underscores the dissimilarities of our time. Starting from such basic concepts as, for example, religion, culture, otherness, and identity, and with the analysis of two case studies—Our Lady of Guadalupe and Saint Martín de Porres—the aim is to raise a problem: does a Latin American cultural identity exist? And how can it be identified