Tracking the big ones : novel dynamics of organelles and macromolecular complexes during cell division and aging

In this Thesis we address two important aspects of protein dynamics: protein synthesis and distribution upon cell division and dynamics of the protein degradation machinery. In Chapter 2, we present novel technology (Recombination-Induced Tag Exchange)to distinguish and simultaneously track old and new proteins. In Chapter 3 we usedthis technology to make a comprehensive analysis of the inheritance and synthesis of organelles and macromolecular complexes in budding yeast. Thereby we resolved outstanding issues in organelle synthesis and uncovered symmetrical and asymmetrical patterns of inheritance. Asymmetrical inheritance of organelles and macromolecular complexes may induce lineage differences and could be involved in cell differentiation. Next, we address two aspects of the dynamics of the protein degradation machinery that may be relevant for cellular aging: proteasome localization and degradation of the proteasome. In Chapter 4 we show that the localization of the proteasome, like its activity, may be a relevant factor in cellular aging and identify genetic factors affecting proteasome localization and longevity in budding yeast. In Chapter 5 we present data that is consistent with lysosomal degradation of damaged proteasomes, which may represent the first sketches of a quality control mechanism for the proteasome.Netherlands Proteomics CentreUBL - phd migration 201

Impact of water content on the performance of alkali-activated slag concretes

In this study, we report the effect of varying the water/binder (w/b) ratio on the performance of sodium silicate activated concretes. Compressive strength development and water transport properties of these concretes were assessed, along with their resistance to carbonation. The results demonstrate that varying the water content within a reasonable range induced negligible changes in the compressive strengths of these concretes, when a constant paste content was used. A direct correlation between the w/b ratio and the amount of permeable voids in the concretes was not identified. The carbonation behaviour of these concretes changes prominently depending on the CO2 concentration of exposure, meaning that comparable accelerated carbonation rates were observed at varying w/b ratios, conversely to observations under natural carbonation conditions where w/b was significant in defining the carbonation rate

The Effect of Aggregate Particle Size on Formation of Geopolymeric Gel

Due to enhanced mechanical and chemical properties, geopolymeric materials are a potential alternative to ordinary Portland cement and high-strength cement for the construction industry. The effects of aggregate particle size on the formation and the mechanical properties of geopolymeric materials are investigated in the current work. The addition of soluble silicates to the alkaline activator was found to increase the dissolution of silicate ions from the aggregate into the geopolymer binder phase. The results indicate that the surface area of aggregate influences the strength development of a geopolymer

High frequency of inactivating tetraspanin CD37 mutations in diffuse large B-cell lymphoma at immune-privileged sites

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PhP.B enhanced adeno-associated virus mediated-expression following systemic delivery or direct brain administration

Of the adeno-associated viruses (AAVs), AAV9 is known for its capability to cross the blood-brain barrier (BBB) and can, therefore, be used as a noninvasive method to target the central nervous system. Furthermore, the addition of the peptide PhP.B to AAV9 increases its transduction across the BBB by 40-fold. Another neurotropic serotype, AAV5, has been shown as a gene therapeutic delivery vehicle to ameliorate several neurodegenerative diseases in preclinical models, but its administration requires invasive surgery. In this study, AAV9-PhP.B and AAV5-PhP.B were designed and produced in an insect cell-based system. To AAV9, the PhP.B peptide TLAVPFK was added, whereas in AAV5-PhP.B (AQTLAVPFKAQAQ), with AQ-AQAQ sequences used to swap with the corresponding sequence of AAV5. The addition of PhP.B to AAV5 did not affect its capacity to cross the mouse BBB, while increased transduction of liver tissue was observed. Then, intravenous (IV) and intrastriatal (IStr) delivery of AAV9-PhP.B and AAV5 were compared. For AAV9-PhP.B, similar transduction and expression levels were achieved in the striatum and cortex, irrespective of the delivery method used. IStr administration of AAV5 resulted in significantly higher amounts of vector DNA and therapeutic miRNA in the target regions such as striatum and cortex when compared with an IV administration of AAV9-PhP.B. These results illustrate the challenge in developing a vector that can be delivered noninvasively while achieving a transduction level similar to that of direct administration of AAV5. Thus, for therapeutic miRNA delivery with high local expression requirements, intraparenchymal delivery of AAV5 is preferred, whereas a humanized AAV9-PhP.B may be useful when widespread brain (and peripheral) transduction is needed.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Effects of the cholesteryl ester transfer protein inhibitor, TA-8995, on cholesterol efflux capacity and high-density lipoprotein particle subclasses

CONCLUSION: TA-8995 dose dependently increased not only total and non-ABCAl-specific CEC but also ABCAl-specific CEC and preBeta-1 HDL particle levels. These findings suggest that TA-8995 not only increases HDL-C levels but also promotes functional properties of HDL particles. This CETP inhibitor driven preBeta-1 HDL increase is an important predictor of both ABCA1 and total CEC increase, independent of HDL-C increase. Whether these changes in HDL particle composition and functionality have a beneficial effect on cardiovascular outcome requires formal testing in a cardiovascular outcome trial. (C) 2016 National Lipid Association. All rights reserved.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Obituary J. W. ten Cate

Thrombosis and Hemostasi

Phase evolution of C-(N)-A-S-H/N-A-S-H gel blends investigated via alkali-activation of synthetic calcium aluminosilicate precursors

Stoichiometrically-controlled alkali-activated pastes containing calcium-(sodium) aluminosilicate hydrate (C-(N)-A-S-H) and sodium aluminosilicate hydrate (N-A-S-H) gels are produced by alkali-activation of high-purity synthetic calcium aluminosilicate powders. These powders are chemically comparable to the glass in granulated blast furnace slag, but without interference from minor constituents. The physiochemical characteristics of these gels depend on precursor chemical composition. Increased Ca content of the precursor promotes formation of low-Al, high-Ca C-(N)-A-S-H with lower mean chain length as determined by quantification of solid state nuclear magnetic resonance spectra, and less formation of calcium carboaluminate ‘Alumino-ferrite mono’ (AFm) phases. Increased Al content promotes Al inclusion and reduced crosslinking within C-(N)-A-S-H, increased formation of calcium carboaluminate AFm phases, and formation of an additional N-A-S-H gel. Small changes in precursor composition can induce significant changes in phase evolution, nanostructure and physical properties, providing a novel route to understand microstructural development in alkali-activated binders and address key related durability issues

Synthesis of stoichiometrically controlled reactive aluminosilicate and calcium-aluminosilicate powders

Aluminosilicate and calcium-aluminosilicate powders are synthesised via an organic steric entrapment route under conditions permitting strict stoichiometric control, utilising polyvinyl alcohol and polyethylene glycol as polymeric carriers. Polyethylene glycol is superior to polyvinyl alcohol for synthesis of calcium-aluminosilicate powders via this method, producing a more controllable product which generated less fine ash during calcination. This paper presents detailed description of synthesis and characterisation of the powders produced through this approach, including new insight into the nanostructures within the calcined powders. Aluminium environments are a mixture of 4-, 5- and 6-coordinated, while silicon is tetrahedral and shows a broad range of connectivity states. The powders are X-ray amorphous, display a high degree of homogeneity, and thus offer potential for utilisation as precursors for synthesis of hydrous aluminosilicates in the quaternary CaO-Na2O-Al2O3-SiO2 system

N-terminal acetylation and replicative age affect proteasome localization and cell fitness during aging

Contains fulltext : 152512.pdf (publisher's version ) (Open Access)Specific degradation of proteins is essential for virtually all cellular processes and is carried out predominantly by the proteasome. The proteasome is important for clearance of damaged cellular proteins. Damaged proteins accumulate over time and excess damaged proteins can aggregate and induce the death of old cells. In yeast, the localization of the proteasome changes dramatically during aging, possibly in response to altered proteasome activity requirements. We followed two key parameters of this process: the distribution of proteasomes in nuclear and cytosolic compartments, and the formation of cytoplasmic aggregate-like structures called proteasome storage granules (PSGs). Whereas replicative young cells efficiently relocalized proteasomes from the nucleus to the cytoplasm and formed PSGs, replicative old cells were less efficient in relocalizing the proteasome and had less PSGs. By using a microscopy-based genome-wide screen, we identified genetic factors involved in these processes. Both relocalization of the proteasome and PSG formation were affected by two of the three N-acetylation complexes. These N-acetylation complexes also had different effects on the longevity of cells, indicating that each N-acetylation complex has different roles in proteasome location and aging