Molecular mechanisms that distinguish TFIID housekeeping from regulatable SAGA promoters

An important distinction is frequently made between constitutively expressed housekeeping genes versus regulated genes. Although generally characterized by different DNA elements, chromatin architecture and cofactors, it is not known to what degree promoter classes strictly follow regulatability rules and which molecular mechanisms dictate such differences. We show that SAGA-dominated/wTATA-box promoters are more responsive to changes in the amount of activator, even compared to TFIID/TATA-like promoters that depend on the same activator Hsf1. Regulatability is therefore an inherent property of promoter class. Further analyses show that SAGA/TATA-box promoters are more dynamic because TATA-binding protein recruitment through SAGA is susceptible to removal by Mot1. In addition, the nucleosome configuration upon activator depletion shifts on SAGA/TATA-box promoters and seems less amenable to preinitiation complex formation. The results explain the fundamental difference between housekeeping and regulatable genes, revealing an additional facet of combinatorial control: an activator can elicit a different response dependent on core promoter class

Re-Printing Architectural Heritage: Exploring Current 3D Printing and Scanning Technologies

Additive Manufacturing (commonly known as 3D printing) technology has become a global phenomenon. In the domain of heritage, 3D printing is seen as a time and cost efficient method for restoring vulnerable architectural structures. The technology can also provide an opportunity to reproduce missing or destroyed cultural heritage, in the cases of conflicts or environmental threats. This project takes the Hippolytuskerk in the Dutch village of Middelstum, as a case study to explore the limits of the existing technology, and the challenges of 3D printing of cultural heritage. Architectural historians, modelling experts, and industrial scientists from the universities of Delft and Eindhoven have engaged with diverse aspects of 3D printing, to reproduce a selected part of the 15th century church. This experimental project has tested available technologies to reproduce a mural on a section of one of the church’s vault with maximum possible fidelity to material, colors and local microstructures. The project shows challenges and opportunities of today’s technology for 3D printing in heritage, varying from the incapability of the scanning technology to capture the existing cracks in the required resolution, to the high costs of speciality printing, and the limited possibilities for combining both printing techniques for such a complex structure. &nbsp

Re-Printing Architectural Heritage: Exploring Current 3D Printing and Scanning Technologies

Additive Manufacturing (commonly known as 3D printing) technology has become a global phenomenon. In the domain of heritage, 3D printing is seen as a time and cost efficient method for restoring vulnerable architectural structures. The technology can also provide an opportunity to reproduce missing or destroyed cultural heritage, in the cases of conflicts or environmental threats. This project takes the Hippolytuskerk in the Dutch village of Middelstum, as a case study to explore the limits of the existing technology, and the challenges of 3D printing of cultural heritage. Architectural historians, modelling experts, and industrial scientists from the universities of Delft and Eindhoven have engaged with diverse aspects of 3D printing, to reproduce a selected part of the 15th century church. This experimental project has tested available technologies to reproduce a mural on a section of one of the church’s vault with maximum possible fidelity to material, colors and local microstructures. The project shows challenges and opportunities of today’s technology for 3D printing in heritage, varying from the incapability of the scanning technology to capture the existing cracks in the required resolution, to the high costs of speciality printing, and the limited possibilities for combining both printing techniques for such a complex structure. &nbsp

Monocyte mitochondrial dysfunction, inflammaging, and inflammatory pyroptosis in major depression

BACKGROUND: The macrophage theory of depression states that macrophages play an important role in Major Depressive Disorder (MDD). METHODS: MDD patients (N = 140) and healthy controls (N = 120) participated in a cross-sectional study investigating the expression of apoptosis/growth and lipid/cholesterol pathway genes (BAX, BCL10, EGR1, EGR2, HB-EGF, NR1H3, ABCA1, ABCG1, MVK, CD163, HMOX1) in monocytes (macrophage/microglia precursors). Gene expressions were correlated to a set of previously determined and reported inflammation-regulating genes and analyzed with respect to various clinical parameters. RESULTS: MDD monocytes showed an overexpression of the apoptosis/growth/cholesterol and the TNF genes forming an inter-correlating gene cluster (cluster 3) separate from the previously described inflammation-related gene clusters (containing IL1 and IL6). While upregulation of monocyte gene cluster 3 was a hallmark of monocytes of all MDD patients, upregulation of the inflammation-related clusters was confirmed to be found only in the monocytes of patients with childhood adversity. The latter group also showed a downregulation of the cholesterol metabolism gene MVK, which is known to play an important role in trained immunity and proneness to inflammation. CONCLUSIONS: The upregulation of cluster 3 genes in monocytes of all MDD patients suggests a premature aging of the cells, i.e. mitochondrial apoptotic dysfunction and TNF "inflammaging", as a general feature of MDD. The overexpression of the IL-1/IL-6 containing inflammation clusters and the downregulation of MVK in monocytes of patients with childhood adversity indicates a shift in this condition to a more severe inflammation form (pyroptosis) of the cells, additional to the signs of premature aging and inflammaging

Multilaboratory Comparison of Pneumococcal Multiplex Immunoassays Used in lmmunosurveillance of Streptococcus pneumoniae across Europe

Surveillance studies are required to estimate the impact of pneumococcal vaccination in both children and the elderly across Europe. The World Health Organization (WHO) recommends use of enzyme immunoassays (EIAs) as standard methods for immune surveillance of pneumococcal antibodies. However, as levels of antibodies to multiple serotypes are monitored in thousands of samples, a need for a less laborious and more flexible method has evolved. Fluorescent-bead-based multiplex immunoassays (MIAs) are suitable for this purpose. An increasing number of public health and diagnostic laboratories use MIAs, although the method is not standardized and no international quality assessment scheme exists. The EU Pneumo Multiplex Assay Consortium was initiated in 2013 to advance harmonization of MIAs and to create an international quality assessment scheme. In a multilaboratory comparison organized by the consortium, agreement among nine laboratories that used their own optimized MIA was assessed on a panel of 15 reference sera for 13 pneumococcal serotypes with the new WHO standard 007sp. Agreement was assessed in terms of assay accuracy, reproducibility, repeatability, precision, and bias. The results indicate that the evaluated MIAs are robust and reproducible for measurement of vaccine-induced antibody responses. However, some serotype-specific variability in the results was observed in comparisons of polysaccharides from different sources and of different conjugation methods, especially for serotype 4. On the basis of the results, the consortium has contributed to the harmonization of MIA protocols to improve reliability of immune surveillance of Streptococcus pneumoniae