Structural studies provide new insights into the role of lysine acetylation on substrate recognition by CARM1 and inform the design of potent peptidomimetic inhibitors

Microbial Biotechnolog

Soil-landscape and climatic relationships in the middle Miocene of the Madrid Basin

The Miocene alluvial-lacustrine sequences of the Madrid Basin, Spain, formed in highly varied landscapes. The presence of various types of palaeosols allows assessment of the effects of local and external factors onsedimentation, pedogenesis and geomorphological development. In the northern, more arid, tectonicallyactive arca, soils were weakly developed in aggrading alluvial fans, dominated by mass flows. reflecting high sedimentation rates. In more distal parts of the fans and in playa lakes calcretes and dolocretes developed: the former were associated with Mg-poor fan sediments whitc: the latter formed on Mg-rich lake clays exposed during minar lake lowstands. The nonh-east part of the basin had a less arid climate. Alluvial fans in this area were dominated by stream Aood deposits, sourced by carbonate terrains. Floodplain and freshwater lakc deposits formed in distal areas. The high local supply of calcium carbonate may have contributed to the preferential developmenl on calcretes on the fans. Both the fan and floodplain palaeosols exhibit pedofacies relationships and more mature soils developed in settings more distant from the sediment sources. Palaeosols also developed on pond and lake margin carbonates, and led to the formation of palustrine limestones. The spatial distributions and stratigraphies of palaeosols in the Madrid Basin alluvial fans suggest that soil formation was controlled by local factors. These palaeosols differ from those seen in Quatemary fans. Which are characterized by climatically induced periods of stability and instability

A direct assay for measuring the activity and inhibition of coactivator-associated arginine methyltransferase 1

Coactivator-associated arginine methyltransferase 1 (CARM1) is a member of the family of protein arginine methyltransferases. CARM1 catalyzes methyl group transfer from the cofactor S-adenosyl-L-methionine (AdoMet) to both histone and nonhistone protein substrates. CARM1 is involved in a range of cellular processes, mainly involving RNA transcription and gene regulation. As the aberrant expression of CARM1 has been linked to tumorigenesis, the enzyme is a potential therapeutic target, leading to the development of inhibitors and tool compounds engaging with CARM1. To evaluate the effects of these compounds on the activity of CARM1, sensitive and specific analytical methods are needed. While different methods are currently available to assess the activity of methyltransferases, these assays mainly focus on either the measurement of the cofactor product S-adenosyl-L-homocysteine (AdoHcy) or employ radioactive or expensive reagents, each with their own advantages and limitations. To complement the tools currently available for the analysis of CARM1 activity, we here describe the development of a convenient assay employing peptide substrates derived from poly(A)-binding protein 1 (PABP1). This operationally straightforward liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based approach allows for the direct detection of substrate methylation with minimal workup. The method was validated, and its value in characterizing CARM1 activity and inhibition was demonstrated through a comparative analysis involving a set of established small molecules and peptide-based CARM1 inhibitors

Functional insights from structural studies of protein arginine methyltransferase 2

FWN – Publicaties zonder aanstelling Universiteit Leide

Artificial weathering of Spanish granites subjected to salt crystallization tests: Surface roughness quantification

For hundreds of years, two types of granite (Zarzalejo and Alpedrete) from the Madrid region, Spain, have been extensively used as building stones. Fresh specimens of both stone types have been sampled from their respective quarries and subjected to sodium sulphate salt crystallization test (SCT). The resulting physical and chemical weathering patterns have been characterized by polarized light optical and environmental scanning electron microscopy. Water absorption under vacuum conditions and mercury intrusion porosimetry techniques were used to determine the pre- and post-SCT porosity and pore size distribution. The following non-destructive techniques were performed to assess stone durability and decay: ultrasound velocity (US) and surface roughness determination (SR) of intra- and inter-granular quartz, feldspar and biotite minerals at the centre as well as at the corners and edges of specimen surfaces. Before the SCT, US values were lower and SR values higher in Zarzalejo (ZAR) than Alpedrete (ALP) granite. After SCT, the US values declined while SR rose in both types of granites, with greater average differences in ZAR than ALP for both parameters. Feldspar and biotite and their inter-granular contacts were found to be the weakest and therefore the most decay-prone areas of the stone. The initial SR parameters were generally higher and rose more steeply after SCT at the corners and around the edges of the specimens. While behaviour was found to be similar in the two types of granite, variations were greater in ZAR, the less durable and more decay-prone of the two. Surface roughness measurement of mineral grains in granite stones is a very useful, in situ, non-destructive technique for quantifying salt crystallization-mediated physical and chemical weathering. The resulting quantification of decay and of related durability provides insight into the future behaviour of this type of stone, commonly used in historic buildings