Improved detection of biomarkers: scientists from Bremen discover new method with microcapsules

To investigate and cure diseases, researchers and doctors must be able to detect disease-related biological substances such as proteins and nucleic acids, so-called biomarkers, in small amounts and with a high precision in the blood or the urine of patients. Jacobs University researchers Dr. Sujit Kumar Verma and Prof. Dr. Sebastian Springer, in collaboration with the group of Prof. Dr. Gerd Klöck at the Bremen University of Applied Sciences (Hochschule Bremen), have developed a new highly sensitive detection method. Here, biomarkers are captured on microscopically small particles, so-called microcapsules, with the help of antibodies. (Mehr in: Pressemitteilungen – idw – Informationsdienst Wissenschaft)

A biological approach to precision medicine targets endless number of diseases

A new study proposes a novel approach to manipulate genes using a self-assembling platform that delivers nucleic acids to distinct subsets of cells. The new modular platform offers a robust biological approach — and may hold the key to the future of personalized medicine. (Mehr in: Cancer News — ScienceDaily)

Körpereigenes Protein macht Vernarbungen in Lunge rückgängig

Heidelberger Wissenschaftler entdecken neuen Mechanismus der Erbgut-Reparatur: Möglicher Therapieansatz zur Behandlung der Lungenfibrose / Im Tierversuch heilen Lungenschäden fast vollständig aus / Ergebnisse in „Nucleic Acids Research“ veröffentlicht (Mehr in: Pressemitteilungen – idw – Informationsdienst Wissenschaft)

Membrane vesicles released by bacteria may play different roles during infection

Bacteria release membrane-derived vesicles (MVs), which are small particles that can transport virulence factors to neighboring bacteria or to the cells of a mammalian host. This special MV-based system for delivering toxic proteins and nucleic acids in a protected manner to the target cells may have different specific functions depending on whether the bacterium acts as an extracellular or intracellular pathogen. (Mehr in: Cancer News — ScienceDaily)

Ultrafast detection of a cancer biomarker enabled by innovative nanobiodevice

Researchers have developed a nanobiodevice that can quickly and effectively separate microRNA, short lengths of ribonucleic acid present in bodily fluids, from mixtures of nucleic acids. The nanobiodevice contains a unique array of nanopillars that form a strong electric force under an applied electric field, allowing high-resolution separation of microRNA in less than 100 ms. Because microRNA is a biomarker for cancer, this technology may provide a simple, noninvasive approach for detecting cancer. (Mehr in: Cancer News — ScienceDaily)

A milestone in small RNA biology: piRNA biogenesis from start to finish

Organisms are in a constant battle against viruses, or transposable elements, which invade their genomes. Among their most effective weapons are silencing pathways that use small RNAs to selectively target invading nucleic acids for their destruction. The molecular understanding of these defense systems has revolutionized modern molecular biology, as they are the basis for powerful genome editing and gene silencing methods such as CRISPR/Cas9 or RNA interference. Scientists from the Institute of Molecular Biotechnology in Vienna (IMBA) have now unravelled the precise mechanisms by which germline cells produce a class of small RNAs, called piRNAs, that control transposon silencing in animals. (Mehr in: Pressemitteilungen – idw – Informationsdienst Wissenschaft)

Novel compounds could yield more effective, less toxic cancer chemotherapy

A novel class of compounds could yield more effective and less toxic chemotherapy drugs to treat cancer, say researchers. The approach offers advantages over existing chemotherapy drugs which target nucleic acids found in DNA. (Mehr in: Cancer News — ScienceDaily)

Forscher entwickeln Programm zur Vorhersage von Genen im Erbgut von Tieren und Pflanzen

Die Evolution hilft bei der Bestimmung von Genen in komplexen Organismen: Biologen und Bioinformatiker des Julius Kühn-Instituts (JKI) Quedlinburg und der Martin-Luther-Universität Halle-Wittenberg (MLU) haben ein neues Programm entwickelt, mit dem sich die Positionen von Genen im Erbgut von Tieren und Pflanzen besser vorhersagen lassen. Dazu nutzen sie Erkenntnisse über die Evolution von Genstrukturen. Die Ergebnisse der Studie wurden jetzt im renommierten Fachjournal „Nucleic Acids Research“ veröffentlicht. (Mehr in: Pressemitteilungen – idw – Informationsdienst Wissenschaft)

New nanotechnology detects biomarkers of cancer

Researchers have developed a new technology to detect disease biomarkers in the form of nucleic acids, the building blocks of all living organisms. (Mehr in: Cancer News — ScienceDaily)

New nanotechnology detects biomarkers of cancer

Researchers have developed a new technology to detect disease biomarkers in the form of nucleic acids, the building blocks of all living organisms. (Mehr in: Cancer News — ScienceDaily)

Den Ursachen für Herzmuskelverdickung auf der Spur

Molekularer Signalweg entschlüsselt
Für das Wachstum und die Entwicklung des Herzens in frühen Entwicklungsphasen sind bestimmte Gene verantwortlich. Werden diese im späteren Leben reaktiviert, kommt es zu einer krankhaften Verdickung des Herzmuskels. Den verantwortlichen molekularen Mechanismus haben jetzt Wissenschaftler der Charité – Universitätsmedizin Berlin unter der Leitung von Prof. Dr. Rickert-Sperling entschlüsselt. Die Studie, publiziert im Fachjournal Nucleic Acids Research*, ist die erste, die die Rolle eines bestimmten Schlüsselproteins bei dieser weit verbreiteten Form von Herzerkrankungen zeigt. (Mehr in: Pressemitteilungen – idw – Informationsdienst Wissenschaft)

A global assessment of cancer genomic alterations in epigenetic mechanisms

Muhammad A Shah, Emily L Denton, Cheryl H Arrowsmith, Mathieu Lupien and Matthieu Schapira

Abstract

Background

The notion that epigenetic mechanisms may be central to cancer initiation and progression is supported by recent next-generation sequencing efforts revealing that genes involved in chromatin-mediated signaling are recurrently mutated in cancer patients.

Results

Here, we analyze mutational and transcriptional profiles from TCGA and the ICGC across a collection 441 chromatin factors and histones. Chromatin factors essential for rapid replication are frequently overexpressed, and those that maintain genome stability frequently mutated. We identify novel mutation hotspots such as K36M in histone H3.1, and uncover a general trend in which transcriptional profiles and somatic mutations in tumor samples favor increased transcriptionally repressive histone methylation, and defective chromatin remodeling.

Conclusions

This unbiased approach confirms previously published data, uncovers novel cancer-associated aberrations targeting epigenetic mechanisms, and justifies continued monitoring of chromatin-related alterations as a class, as more cancer types and distinct cancer stages are represented in cancer genomics data repositories.

Continue reading „A global assessment of cancer genomic alterations in epigenetic mechanisms“

Quantum entanglement between the electron clouds of nucleic acids in DNA

Rieper, Anders and Vedral modelled the electron clouds of nucleic acids in a single strand of DNA as a chain of coupled quantum harmonic oscillators with dipole-dipole interaction between nearest neighbours. As a main result, the entanglement contained in the chain coincides with the binding energy of the molecule. Derived in the limit of long distances and periodic potentials analytic expressions linking the entanglement witnesses to the energy reduction due to the quantum entanglement in the electron clouds.

Rieper E, Anders J, Vedral V (2011) Quantum entanglement between the electron clouds of nucleic acids in DNA. arxiv.org/abs/1006.4053

 

Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci

3D-SIM-based DAPI intensity classification in the Barr body versus the entire nucleus of C2C12 cells. (A) Mid z-section of a DAPI-stained nucleus. The area below the dashed line illustrates the resolution level obtained by wide-field deconvolution microscopy, for comparison. Inset magnifications show the non-uniformly compacted structure of the Barr body resolvable with 3D-SIM (1) and an arbitrary autosomal region with CDCs (2). Scale bars: 5 μm, insets 1 μm. (B) X chromosome-specific painting (green) of Xi (left) and Xa territories (right) of the same nucleus in different z-sections. Note the high convergence between the painted Xi and the DAPI visualized Barr body (arrowheads). Scale bars: 2 μm, insets 1 μm. (C) 3D DAPI intensity classification exemplified for the nucleus shown in (A). Seven DAPI intensity classes displayed in false-color code ranging from class 1 (blue) representing pixels close to background intensity, largely representing the IC, up to class 7 (white) representing pixels with highest density, mainly associated with chromocenters. Framed areas of the Barr body (inset 1) and a representative autosomal region (inset 2) are shown on the right at resolution levels of 3D-SIM, deconvolution and conventional wide-field microscopy. The Xi territory pervaded by lower DAPI intensities becomes evident only at 3D-SIM resolution, whereas both wide-field and deconvolution microscopy imply a concentric increase of density in the Barr body. In the autosomal region, chromatin assigned to classes 2 to 3 lines compacted CDCs, represented by classes 4 to 6. (D) Left: average DAPI intensity classification profiles with standard deviations evaluated for entire nuclear volumes or the Barr body region only (dark grey bars). Right: over/underrepresentation of the average DAPI intensity class fraction sizes in the Barr body versus entire nuclear volumes (n = 12). Distribution differences on classes between Xi and entire nucleus P <0.001. 3D-SIM, three-dimensional structured illumination microscopy; CDC, chromatin domain cluster; DAPI, 4',6-diamidino-2-phenylindole; FISH, fluorescence in situ hybridization; IC, interchromatin compartment; Xa, active X chromosome; Xi, inactive X chromosome. Smeets et al. Epigenetics & Chromatin 2014 7:8   doi:10.1186/1756-8935-7-8
3D-SIM-based DAPI intensity classification in the Barr body versus the entire nucleus of C2C12 cells. (A) Mid z-section of a DAPI-stained nucleus. The area below the dashed line illustrates the resolution level obtained by wide-field deconvolution microscopy, for comparison. Inset magnifications show the non-uniformly compacted structure of the Barr body resolvable with 3D-SIM (1) and an arbitrary autosomal region with CDCs (2). Scale bars: 5 μm, insets 1 μm. (B) X chromosome-specific painting (green) of Xi (left) and Xa territories (right) of the same nucleus in different z-sections. Note the high convergence between the painted Xi and the DAPI visualized Barr body (arrowheads). Scale bars: 2 μm, insets 1 μm. (C) 3D DAPI intensity classification exemplified for the nucleus shown in (A). Seven DAPI intensity classes displayed in false-color code ranging from class 1 (blue) representing pixels close to background intensity, largely representing the IC, up to class 7 (white) representing pixels with highest density, mainly associated with chromocenters. Framed areas of the Barr body (inset 1) and a representative autosomal region (inset 2) are shown on the right at resolution levels of 3D-SIM, deconvolution and conventional wide-field microscopy. The Xi territory pervaded by lower DAPI intensities becomes evident only at 3D-SIM resolution, whereas both wide-field and deconvolution microscopy imply a concentric increase of density in the Barr body. In the autosomal region, chromatin assigned to classes 2 to 3 lines compacted CDCs, represented by classes 4 to 6. (D) Left: average DAPI intensity classification profiles with standard deviations evaluated for entire nuclear volumes or the Barr body region only (dark grey bars). Right: over/underrepresentation of the average DAPI intensity class fraction sizes in the Barr body versus entire nuclear volumes (n = 12). Distribution differences on classes between Xi and entire nucleus P Smeets et al. Epigenetics & Chromatin 2014 7:8 doi:10.1186/1756-8935-7-8

Daniel Smeets, Yolanda Markaki, Volker J Schmid, Felix Kraus, Anna Tattermusch, Andrea Cerase, Michael Sterr, Susanne Fiedler, Justin Demmerle, Jens Popken, Heinrich Leonhardt, Neil Brockdorff, Thomas Cremer1, Lothar Schermelleh and Marion Cremer

Abstract

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.

Continue reading „Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci“