Atmospheric X-ray emission experiment for shuttle

An experiment designed to measure the spatial, temporal, and energy distribution of X-ray aurorae produced by precipitating electrons, is presented. The experiment will provide vital data on solar-terrestrial relationships that may lead to defining the transfer mechanism that causes certain terrestrial weather events and climatological behavior. An instrument concept is discussed, and is based on a spatially sensitive multiwire proportional counter, combined with collimators to produce X-ray images of the aurorae. An instrument pointing system, on which the counter can be mounted, will provide the required altitude control, and can be operated by a Spacelab payload specialist for full control over its observing and data taking modes

Die Analyse des molekularen Mechanismus der Regulation der Zellmigration durch Pals1

Das kolorektale Karzinom ist eine prävalente Krebserkrankung, die jedes Jahr weltweit eine hohe Anzahl an Todesopfern fordert. Ein Attribut von Krebs, einschließlich Darmkrebs, ist der Verlust der Zellpolarität. Das tight junctions assoziierte Pals1- Protein ist ein elementarer Bestandteil des evolutionär konservierten Crb3-Pals1- PATJ-Komplexes und wesentlich an der Herstellung der apiko-basalen-Zellpolarität beteiligt. Eine Dysregulation von Polaritätsproteinen wird im Zusammenhang mit der dynamischen Protektion von GTPasen eine potentielle Bedeutung bei der Tumorgenese zugesprochen. Um den Stellenwert von Pals1 im Hinblick auf die Tumorentwicklung zu eruieren, wurden in dieser Arbeit verschiedene etablierte Kolonkarzinomzelllinien (DLD1, RKO, Caco-2) verwendet. Diese Krebszelllinien fungieren als Basis für die Generierung von Pals1-Knockout-Zelllinien, die bereits in Vorarbeiten durch das CRISPR/Cas9-System etabliert wurden. Im Rahmen von in- vitro Zellmigrations- und Zellinvasionsversuchen, Rac1 und Arf6 GST-Pulldown- Assays wurden die Pals1-Knockout-Zellen mit den Ursprungszelllinien umfassend charakterisiert. Die gewonnenen Ergebnisse der Assays zeigen eine kongruente Verhaltensweise der WT-Zelllinien und Pals1-Mutanten. Eine ausgiebige Literaturrecherche manifestiert eine potentielle Relevanz von SMAP1, eine spezifische Arf6-GAP. SMAP1 verfügt über einen 10-Adenin-Wiederholungstrakt, welcher prädisponiert für MSI-Mutationen ist. Eine Vielzahl von Kolonkarzinom- Zelllinien weisen SMAP1-Mutationen auf, allerdings verfügen die DLD1-, Caco-2- und RKO-Zelllinien über ein funktionsfähiges SMAP1-Protein. Eine Western Blot Analyse verifiziert, dass in den Pals1-Knockout-Zelllinien das SMAP1-Protein exorbitant hochreguliert ist. Mithilfe weiterer Kolonkarzinomzelllinien (SW48, LoVo) und der Etablierung zusätzlicher CRISPR/Cas9-Mutanten (DLD1 ΔPals1-SMAP1, SW48 ΔPals1, LoVo ΔPals1) konnte validiert werden, dass ein simultaner Pals1- und SMAP1-Verlust in der DLD1- und SW48-Zelllinie zu einer verstärkten Zellmotilität führt. Pals1 und SMAP1 induzieren komplementär die Inhibierung von Arf6, weshalb ein additionales Pals1-SMAP1-Defizit zu einer exzessiv aktiven Arf6-Hochregulation führt. Arf6-GTP interagiert wiederum mit Rac1-GDP, wodurch ein dynamisches Zusammenspiel dieser GTPasen in eine verstärkte Zellmigration reflektiert wird. Resümierend verdeutlichen die erzielten Ergebnisse, dass Pals1 und SMAP1 eine tumorsupprimierende Funktion zugesprochen werden kann und sie als mögliche onkogene Zielgene betrachtet werden können.Colorectal cancer is a prevalent disease that causes a large number of people worldwide every year. A hallmark of cancer, including colorectal cancer, is the loss of cell polarity. The tight junction associated Pals1 protein is an elementary component of the evolutionary conserved Crb3-Pals1-PATJ complex and is significantly involved in the establishment of apical–basal polarity in epithelial cells. Dysregulation of core polarity proteins is considered to play a crucial role in tumorigenesis in connection with the involvement of special GTPases. In order to determine the importance of Pals1 in tumor development, several established colon carcinoma cell lines (DLD1, RKO, Caco-2) were used in this work. These cancer cell lines were used for the generation of Pals1 knockout cell lines, which have already been established in preliminary work by the CRISPR/ Cas9 system. In the context of in-vitro cell migration and cell invasion experiments, Rac1 and Arf6 GST pulldown assays, the Pals1 knockout cells were sufficiently characterized in connection with the WT cell lines. The obtained results of the assays show a similar behaviour of WT cell lines and Pals1 mutants. An extensive literature search manifests a potential relevance of SMAP1, a specific Arf6-GAP. SMAP1 has a 10-adenine tract, which is predisposed to MSI mutations. A large number of colon cancer cell lines have SMAP1 mutations, but the DLD1, Caco- 2 and RKO cell lines have a functional SMAP1 protein. A Western blot analysis verifies that the SMAP1 protein is exorbitantly upregulated in the Pals1 knockout cell lines. Through further colon cancer cell lines (SW48, LoVo) and the establishment of additional CRISPR/Cas9 mutants (DLD1 ΔPals1-SMAP1, SW48 ΔPals1, LoVo ΔPals1) it could be validated that a simultaneous Pals1 and SMAP1 loss in the DLD1 and SW48 cell line leads to increased cell motility. Pals1 and SMAP1 complementarily induce the inhibition of Arf6-GTP, therefore an additional Pals1-SMAP1 deficit leads to excessive active Arf6 upregulation. Arf6-GTP interacts with Rac1-GDP, which is reflected in a Rac1-induced increased cell migration. In summary, the results show that Pals1 and SMAP1 can be assigned a tumor suppressing function and can be considered as possible oncogenic target genes

Epigenetics of T lymphocytes in health and disease

The risk of developing autoimmune diseases depends on both genetic and environmental factors, with epigenetic mechanisms of regulation potentially translating environmental cues into stable modifications in gene expression. Such stable memory of a functional state has been deciphered into a number of molecular mechanisms that collectively define the epigenetic status of a cell. In recent years, it has become increasingly clear that epigenetic modifications are highly dynamic and are able to adapt to the changing environment, with important impact on the onset and development of a number of diseases. Here, we describe some of the epigenetic mechanisms of regulation of cellular functional states in T lymphocytes, with a particular focus on DNA methylation. We will also discuss current knowledge on the role of epigenetics in autoimmunity and consider open questions in the field

Operating SIRTF for maximum lifetime

The instruments of the Space Infrared Telescope Facility (SIRTF) are cooled directly by liquid helium, while the optical system is cooled by helium vapor. The greater the power dissipation into the liquid helium, the more vapor is produced, and the colder the telescope. Observations at shorter wavelengths do not require telescope temperatures as low as those required at shorter wavelengths. By taking advantage of this, it may be possible to extend the helium and mission lifetime by 10% or even 20%

TET2 regulates mast cell differentiation and proliferation through catalytic and non-catalytic activities

Dioxygenases of the TET family impact genome functions by converting 5-methylcytosine (5mC) in DNA to 5-hydroxymethylcytosine (5hmC). Here, we identified TET2 as a crucial regulator of mast cell differentiation and proliferation. In the absence of TET2, mast cells showed disrupted gene expression and altered genome-wide 5hmC deposition, especially at enhancers and in the proximity of downregulated genes. Impaired differentiation of Tet2- ablated cells could be relieved or further exacerbated by modulating the activity of other TET family members, and mechanistically it could be linked to the dysregulated expression of C/EBP family transcription factors. Conversely, the marked increase in proliferation induced by the loss of TET2 could be rescued exclusively by re-expression of wild-type or catalytically inactive TET2. Our data indicate that, in the absence of TET2, mast cell differentiation is under the control of compensatory mechanisms mediated by other TET family members, while proliferation is strictly dependent on TET2 expression

Operating SIRTF for maximum lifetime

The instruments of the Space Infrared Telescope Facility (SIRTF) are cooled directly by liquid helium, while the optical system is cooled by helium vapor. The greater the power dissipation into the liquid helium, the more vapor is produced, and the colder the telescope. Observations at shorter wavelengths do not require telescope temperatures as low as those required at shorter wavelengths. By taking advantage of this, it may be possible to extend the helium and mission lifetime by 10% or even 20%

Photorheologische Effekte und ihr Einfluss auf die Struktur micellarer Loesungen

SIGLEAvailable from TIB Hannover: DW 3872 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman