Importance of molecular cell biology investigations in human medicine in the story of the Hutchinson-Gilford progeria syndrome

Ranged among laminopathies, Hutchinson–Gilford progeria syndrome is a syndrome that involves premature aging, leading usually to death at the age between 10 to 14 years predominatly due to a myocardial infarction or a stroke. In the lecture I shall overview the importance of molecular cell biology investigations that led to the discovery of the basic mechanism standing behind this rare syndrome. The genetic basis in most cases is a mutation at the nucleotide position 1824 of the lamin A gene. At this position, cytosine is substituted for thymine so that a cryptic splice site within the precursor mRNA for lamin A is generated. This results in a production of abnormal lamin A, termed progerin, its presence in cells having a deleterious dominant effect. Depending on the cell type and tissue, progerin induces a pleiotropy of defects that vary in different tissues. The present endeavour how to challenge this terrible disease will be also mentioned

Function and Assembly of a Chromatin-Associated RNase P that Is Required for Efficient Transcription by RNA Polymerase I

Background: Human RNase P has been initially described as a tRNA processing enzyme, consisting of H1 RNA and at least ten distinct protein subunits. Recent findings, however, indicate that this catalytic ribonucleoprotein is also required for transcription of small noncoding RNA genes by RNA polymerase III (Pol III). Notably, subunits of human RNase P are localized in the nucleolus, thus raising the possibility that this ribonucleoprotein complex is implicated in transcription of rRNA genes by Pol I. Methodology/Principal Findings: By using biochemical and reverse genetic means we show here that human RNase P is required for efficient transcription of rDNA by Pol I. Thus, inactivation of RNase P by targeting its protein subunits for destruction by RNA interference or its H1 RNA moiety for specific cleavage causes marked reduction in transcription of rDNA by Pol I. However, RNase P restores Pol I transcription in a defined reconstitution system. Nuclear run on assays reveal that inactivation of RNase P reduces the level of nascent transcription by Pol I, and more considerably that of Pol III. Moreover, RNase P copurifies and associates with components of Pol I and its transcription factors and binds to chromatin of the promoter and coding region of rDNA. Strikingly, RNase P detaches from transcriptionally inactive rDNA in mitosis and reassociates with it at G1 phase through a dynamic and stepwise assembly process that is correlated with renewal of transcription

Function and Assembly of a Chromatin-Associated RNase P that Is Required for Efficient Transcription by RNA Polymerase I

Human RNase P has been initially described as a tRNA processing enzyme, consisting of H1 RNA and at least ten distinct protein subunits. Recent findings, however, indicate that this catalytic ribonucleoprotein is also required for transcription of small noncoding RNA genes by RNA polymerase III (Pol III). Notably, subunits of human RNase P are localized in the nucleolus, thus raising the possibility that this ribonucleoprotein complex is implicated in transcription of rRNA genes by Pol I.By using biochemical and reverse genetic means we show here that human RNase P is required for efficient transcription of rDNA by Pol I. Thus, inactivation of RNase P by targeting its protein subunits for destruction by RNA interference or its H1 RNA moiety for specific cleavage causes marked reduction in transcription of rDNA by Pol I. However, RNase P restores Pol I transcription in a defined reconstitution system. Nuclear run on assays reveal that inactivation of RNase P reduces the level of nascent transcription by Pol I, and more considerably that of Pol III. Moreover, RNase P copurifies and associates with components of Pol I and its transcription factors and binds to chromatin of the promoter and coding region of rDNA. Strikingly, RNase P detaches from transcriptionally inactive rDNA in mitosis and reassociates with it at G1 phase through a dynamic and stepwise assembly process that is correlated with renewal of transcription.Our findings reveal that RNase P activates transcription of rDNA by Pol I through a novel assembly process and that this catalytic ribonucleoprotein determines the transcription output of Pol I and Pol III, two functionally coordinated transcription machineries

Basaltic Dyke with Specific Volcanogenic Structures and its geomorphic evolution: Unique Geoheritage of the Faroe Islands (North Atlantic Ocean)

Volcanic landforms resulting from Cenozoic volcanism represent the most peculiar features of global geodiversity and provide eminent narratives for geoeducation. Among them, however, relict volcanic forms and site-specific landforms in remote areas have received less attention. In this paper, we provide the first description of unique volcanogenic features (hereinafter referred to as pseudo-hieroglyphs) developed on a summit rock wall at the Sandfelli ridge near the village of Gjógv in the N Eysturoy Island (Faroe Islands). The geomorphic evolution of the ridge and rock wall during the Quaternary is described and detailed petrographic analyses of the volcanogenic features are provided. Based on observed petrographical features, we interpret the pseudo-hieroglyphs to probably represent unique examples of chaotic horizontal columnar jointing. Following the geomorphological and petrographic examination of the study site, we analyse current Faroese legislation aiming at nature conservation and use this case to discuss broader implications of geoheritage conservation and geotourism in distant regions.Vulkanická krajina vzniklá kenozoickým vulkanismem představuje nejpodivnější rysy globální geodiversity a poskytuje vynikající příběhy pro geovzdělávání. Méně pozornosti se však dostává reliktním vulkanickým formám a lokálním tvarům reliéfu v odlehlých oblastech. V tomto článku přinášíme první popis unikátních vulkanogenních tvarů (dále jen "pseudo-hieroglyfy"), které se vyvíjely na skalní stěně vrcholu na hřbetě Sandfelli u vesnice Gjógv v severní části ostrova Eysturoy (Faerské ostrovy). Je popsán geomorfologický vývoj hřbetu a skalní stěny během kvartéru a jsou uvedeny podrobné petrografické analýzy vulkanogenních vlastností. Na základě pozorovaných petrografických rysů interpretujeme pseudo-hieroglyfy, které pravděpodobně představují jedinečné příklady chaotické horizontální sloupcovité odlučnosti. Po geomorfologickém a petrografickém studiu zájmové lokality analyzujeme současnou faerskou legislativu zaměřenou na ochranu přírody a užíváme tohoto příkladu k diskusi širších důsledků zachování a geoturistiky geografického dědictví ve vzdálených regionech

Nucleologenesis in the Caenorhabditis elegans Embryo

In the Caenorhabditis elegans nematode, the oocyte nucleolus disappears prior to fertilization. We have now investigated the re-formation of the nucleolus in the early embryo of this model organism by immunostaining for fibrillarin and DAO-5, a putative NOLC1/Nopp140 homolog involved in ribosome assembly. We find that labeled nucleoli first appear in somatic cells at around the 8-cell stage, at a time when transcription of the embryonic genome begins. Quantitative analysis of radial positioning showed the nucleolus to be localized at the nuclear periphery in a majority of early embryonic nuclei. At the ultrastructural level, the embryonic nucleolus appears to be composed of a relatively homogenous core surrounded by a crescent-shaped granular structure. Prior to embryonic genome activation, fibrillarin and DAO-5 staining is seen in numerous small nucleoplasmic foci. This staining pattern persists in the germline up to the ∼100-cell stage, until the P4 germ cell divides to give rise to the Z2/Z3 primordial germ cells and embryonic transcription is activated in this lineage. In the ncl-1 mutant, which is characterized by increased transcription of rDNA, DAO-5-labeled nucleoli are already present at the 2-cell stage. Our results suggest a link between the activation of transcription and the initial formation of nucleoli in the C. elegans embryo

Dynamics of Rising Bubbles

Dynamics of a rising bubble suspended in a downstream was investigated. Visualization data of the bubble trajectory displayed certain periodic patterns

Win–win for everyone? Reflecting on nature-based solutions for flood risk management from an environmental justice perspective

Nature-based solutions (NbS) are often framed positively in terms of win–win options or no-regret measures. However, are NbS equally beneficial for everyone? Are burdens and benefits of NbS really equally distributed and projects embraced by everyone? Is the process leading to the implementation of NbS always fair and inclusive? This chapter provides a broad overview of different environmental justice issues, critically reflecting on NbS through recognition justice, procedural justice, and distributive justice. Whereas the current critical literature focuses particularly on urban NbS, this chapter focuses on the wider translocal consequences of NbS projects. The theoretical reflections are illustrated with case studies of NbS from various countries: the recognition of marginalised women in Vietnam in mangrove restoration projects, the challenges when introducing procedural justice in implementing NbS in Serbia, the legal injustices locals are faced in the Czech Republic when they want to implement NbS, the trade-off between public collective and individual economic interest when implementing a sand nourishment project in the Netherlands, and the development of a beneficiary-pays based upstream–downstream compensation scheme in Austria