Promotor and 5'splice site interactions in retroviruses and retroviral vectors

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Soziale Arbeit in Konfliktgebieten oder Eine Studienreise der anderen Art

Sozialarbeitende können in bewaffneten Konflikten eine wichtige Rolle spielen. Sie organisieren unter anderem Nothilfe, unterstützen Geflüchtete beim Bearbeiten von Traumata und helfen Gemeinschaften sich zu organisieren. Dies für Studierende erfahrbar zu machen, gelingt gut dank Studienreisen. Doch auch andere Formate eignen sich, wie die Winter School 2021 beweist

MCR XVII. Three Types of MCRs and the Libraries – Their Chemistry of Natural Events and Preparative Chemistry

The one-pot Multicomponent Reactions (MCRs)1 convert more than two different components into their products with at least two new chemical bonds, and the products contain all educts or at least some parts of them. Many chemical reactions have several, but not all, aspects of the MCRs. Three different basic types (I–III) and two subclasses (A and B) of MCRs can take place. Chemistry had started in the nature of our world roughly 4.6 billion years ago, including MCRs of the types I and II, forming libraries of many different products. A little later, the living cells came into existence, and their biochemical MCRs of all three types started. In their various local parts their biochemical products are selectively formed by their enzyme-assisted procedures, but many of their MCRs belong to type III. The preparative chemistry of MCRs started in the middle of the last century, when the first equilibrating but isolateable 3CR products of type IB were formed. The pre-final reactions of type I form compounds, which react further and form their final products irreversibly by MCRs of type II. The type IIA products are usually heterocycles, whereas those of type IIB are generally products of isocyanides. The U-4CR of type IIB was introduced and this led to a new preparative MCR chemistry. Their educts and intermediate products equilibrate (type IA) and undergo irreversible CII → CIV &alpha,-additions of the isocyanides, followed by a variety of rearrangements into their final products (type IIB). In recent years, unions of higher numbers of components were introduced, forming even more diverse types of products. The MCR libraries were proposed in 1961, and since 1995 this chemistry has become an essential part of the chemical research in industrial search for new desirable products. This methodology requires much less work than all previous methods and proceeds many orders of magnitude faster

MCR XVII. Three Types of MCRs and the Libraries – Their Chemistry of Natural Events and Preparative Chemistry

The one-pot Multicomponent Reactions (MCRs)1 convert more than two different components into their products with at least two new chemical bonds, and the products contain all educts or at least some parts of them. Many chemical reactions have several, but not all, aspects of the MCRs. Three different basic types (I–III) and two subclasses (A and B) of MCRs can take place. Chemistry had started in the nature of our world roughly 4.6 billion years ago, including MCRs of the types I and II, forming libraries of many different products. A little later, the living cells came into existence, and their biochemical MCRs of all three types started. In their various local parts their biochemical products are selectively formed by their enzyme-assisted procedures, but many of their MCRs belong to type III. The preparative chemistry of MCRs started in the middle of the last century, when the first equilibrating but isolateable 3CR products of type IB were formed. The pre-final reactions of type I form compounds, which react further and form their final products irreversibly by MCRs of type II. The type IIA products are usually heterocycles, whereas those of type IIB are generally products of isocyanides. The U-4CR of type IIB was introduced and this led to a new preparative MCR chemistry. Their educts and intermediate products equilibrate (type IA) and undergo irreversible CII → CIV &alpha,-additions of the isocyanides, followed by a variety of rearrangements into their final products (type IIB). In recent years, unions of higher numbers of components were introduced, forming even more diverse types of products. The MCR libraries were proposed in 1961, and since 1995 this chemistry has become an essential part of the chemical research in industrial search for new desirable products. This methodology requires much less work than all previous methods and proceeds many orders of magnitude faster

Alter und öffentlicher Raum in der Stadt Bern

Die Beziehung zwischen Raumbeschaffenheit und sozialer Partizipation am Beispiel der Stadt Bern – Kurzbericht eines Forschungsprojekts des Instituts Alter der Berner Fachhochschule in Zusammenarbeit mit dem Fachbereich Soziale Arbeit und dem Departement Architektur, Holz und Ba

Proteomic Analysis of Chloroplast-to-Chromoplast Transition in Tomato Reveals Metabolic Shifts Coupled with Disrupted Thylakoid Biogenesis Machinery and Elevated Energy-Production Components

A comparative proteomic approach was performed to identify differentially expressed proteins in plastids at three stages of tomato(Solanum lycopersicum) fruit ripening (mature-green, breaker, red). Stringent curation and processing of the data from three independent replicates identified 1,932 proteins among which 1,529 were quantified by spectral counting. The quantification procedures have been subsequently validated by immunoblot analysis of six proteins representative of distinct metabolic or regulatory pathways. Among the main features of the chloroplast-to-chromoplast transition revealed by the study, chromoplastogenesis appears to be associated with major metabolic shifts: (1) strong decrease in abundance of proteins of light reactions (photosynthesis, Calvin cycle, photorespiration)and carbohydrate metabolism (starch synthesis/degradation), mostly between breaker and red stages and (2) increase in terpenoid biosynthesis (including carotenoids) and stress-response proteins (ascorbate-glutathione cycle, abiotic stress, redox, heat shock). These metabolic shifts are preceded by the accumulation of plastid-encoded acetyl Coenzyme A carboxylase D proteins accounting for the generation of a storage matrix that will accumulate carotenoids. Of particular note is the high abundance of proteins involved in providing energy and in metabolites import. Structural differentiation of the chromoplast is characterized by a sharp and continuous decrease of thylakoid proteins whereas envelope and stroma proteins remain remarkably stable. This is coincident with the disruption of the machinery for thylakoids and photosystem biogenesis (vesicular trafficking, provision of material for thylakoid biosynthesis, photosystems assembly) and the loss of the plastid division machinery. Altogether, the data provide new insights on the chromoplast differentiation process while enriching our knowledge of the plant plastid proteome

Inhibition of metal dusting using thermal spray coatings and laser treatment

Alloy 600 and Alloy 800H are susceptible to metal dusting. Both alloys were thermally sprayed with two different corrosion resistant coatings: Ni50Cr and Ni31Cr11Al0.6Y. Laser remelting was used to enhance further the effectiveness of these coatings to resist metal dusting by eliminating interconnected porosity and improving coating adhesion. Uncoated, coated and laser-treated coated samples of Alloy 600 and Alloy 800H were exposed to a mixed gas atmosphere (20% H2, 80% CO at 650°C). Samples were examined in plan and cross-section using optical and scanning electron microscopy, electron probe microanalysis and X-ray diffraction. The extent of carbon deposition was tracked by mass difference measurements at intervals during exposure. The thermally sprayed coatings enhanced metal dusting resistance by acting as physical barriers to carbon ingress. The NiCrAlY coating performed well on both substrates. The NiCr coating itself underwent metal dusting and spalled from Alloy 800H due partly to CTE mis-match stresses. Laser treatment of both coatings successfully eliminated interconnected porosity and hence enhanced metal dusting resistance

Preclinical Development of a Lentiviral Vector for Gene Therapy of X-Linked Severe Combined Immunodeficiency

X-linked severe combined immunodeficiency (SCID-X1) is caused by mutations in the interleukin-2 receptor \u3b3 chain gene (IL2RG), and it is characterized by profound defects in T, B, and natural killer (NK) cell functions. Transplantation of hematopoietic stem/progenitor cells (HSPCs) genetically corrected with early murine leukemia retrovirus (MLV)-derived gammaretroviral vectors showed restoration of T cell immunity in patients, but it resulted in vector-induced insertional oncogenesis. We developed a self-inactivating (SIN) lentiviral vector carrying a codon-optimized human IL2RG cDNA driven by the EF1\u3b1 short promoter (EFS-IL2RG), and we tested its efficacy and safety in vivo by transplanting transduced Il2rg-deficient Lin 12 HSPCs in an Il2rg 12/ 12/Rag2 12/ 12 mouse model. The study showed restoration of T, B, and NK cell counts in bone marrow and peripheral blood and normalization of thymus and spleen cellularity and architecture. High-definition insertion site analysis defined the EFS-IL2RG genomic integration profile, and it showed no sign of vector-induced clonal selection or skewing in primarily and secondarily transplanted animals. The study enables a phase I/II clinical trial aimed at restoring both T and B cell immunity in SCID-X1 children upon non-myeloablative conditioning

Decavanadate effects in biological systems

Vanadium biological studies often disregarded the formation of decameric vanadate species known to interact, in vitro, with high-affinity with many proteins such as myosin and sarcoplasmic reticulum calcium pump and also to inhibit these biochemical systems involved in energy transduction. Moreover, very few in vivo animal studies involving vanadium consider the contribution of decavanadate to vanadium biological effects. Recently, it has been shown that an acute exposure to decavanadate but not to other vanadate oligomers induced oxidative stress and a different fate in vanadium intracellular accumulation. Several markers of oxidative stress analyzed on hepatic and cardiac tissue were monitored after in vivo effect of an acute exposure (12, 24 h and 7 days), to a sub-lethal concentration (5 mM; 1 mg/kg) of two vanadium solutions (‘‘metavanadate’’ and ‘‘decavanadate’’). It was observed that ‘‘decavanadate’’ promote different effects than other vanadate oligomers in catalase activity, glutathione content, lipid peroxidation, mitochondrial superoxide anion production and vanadium accumulation, whereas both solutions seem to equally depress reactive oxygen species (ROS) production as well as total intracellular reducing power. Vanadium is accumulated in mitochondria in particular when ‘‘decavanadate’’ is administered. These recent findings, that are now summarized, point out the decameric vanadate species contributions to in vivo and in vitro effects induced by vanadium in biological systems