Proteomics of plaques and novel sources of potential biomarkers for atherosclerosis

Cardiovascular disease (CVD) is the leading cause of death and loss of productive life years in the world. The underlying syndrome of CVD, atherosclerosis, is a complex disease process, which involves lipid metabolism, inflammation, innate and adaptive immunity, and many other pathophysiological aspects. Furthermore, CVD is influenced by genetic as well as environmental factors. Early detection of CVD and identification of patients at risk are crucial to reduce the burden of disease and to allow personalized treatment. As established risk factors fail to accurately predict which part of the population is likely to suffer from the disease, novel biomarkers are urgently needed. Proteomics can play a significant role in identifying these biomarkers. In this review, we describe the progress made in proteome profiling of the atherosclerotic plaque and several novel sources of potential biomarkers, including circulating cells and plasma extracellular vesicles. The importance of longitudinal biobanking in biomarker discovery is highlighted and exemplified by several plaque proteins identified in the biobank study Athero-Express. Finally, we discuss the PTMs of proteins that are involved in atherosclerosis, which may become one of the foci in the ongoing quest for biomarkers through proteomics of plaque and other matrices relevant to the progression of atherosclerosis.     

Viscosity measurements of liquids under pressure by using the quartz crystal resonators

A quartz crystal viscometer has been developed for measuring viscosity in liquids under pressure. It employs an AT-cut quartz crystal resonator of fundamental frequency 3 MHz inserted in a variable-volume vessel designed for working up to 80 MPa. Viscosity is determined by two methods from resonance frequency and bandwidth measurements along up to eight different overtones. The resonance frequency allows an absolute measurement of the viscosity but leads to an accuracy limited to 5% whereas the bandwidth technique which works in a relative way provides an accuracy of 2%. The techniques were tested by carrying out measurements in two pure compounds: heptane and toluene. Measurement results demonstrate the feasibility of the technique in this viscosity range. The apparatus was also used to determine the viscosity of n-decane with dissolved methane. The results obtained with these mixtures reveal the applicability of the apparatus for reservoir fluids study.     

Overactuation: A solution for the accuracy-throughput speed contradiction in parallel axis positioning systems

In parallel axis positioning systems an accuracy-throughput speed contradiction is present. The configuration is often such that the minimum number of actuators from kinematic point of view is used. The mechanical system should possess sufficient stiffness but also low mass. Structural stiffness, and hence accuracy, is obtained at the cost of mass. In intermittent motion systems the moving mass should be minimized, because it limits the attainable acceleration and thus the throughput speed. This dynamic performance barrier can be shifted with additional parallel actuators. To enhance prudence in the initial design phase, knowledge about the opportunities and limitations of parallel axis systems is required. The basic dynamical aspects of parallel axis positioning systems, with a minimum and additional number of parallel actuators, are examined for beam and plate systems. The results of the numerical models are verified with an experimental plate system.     

Atom probe tomography and transmission electron microscopy characterisation of precipitation in an Al-Cu-Li-Mg-Ag alloy

State-of-the art atom probe tomography (APT) combined with transmission electron microscopy (TEM) were used to investigate the microstructure at different stages of the ageing process of an alloy of composition (at%) Al-1.68%Cu-4.62%Li-0.33%Mg-0.1%Ag. These alloys were shown to exhibit a complex microstructure of T₁ plates and several metastable phases, including θ′ and S. We will highlight the early stages of clustering, precipitate interactions and possible solute segregation at the matrix/precipitate interfaces and detail the chemical composition of the different phases.     

Linking the proteins--elucidation of proteome-scale networks using mass spectrometry

Proteomes are intricate. Typically, thousands of proteins interact through physical association and post-translational modifications (PTMs) to give rise to the emergent functions of cells. Understanding these functions requires one to study proteomes as "systems" rather than collections of individual protein molecules. The abstraction of the interacting proteome to "protein networks" has recently gained much attention, as networks are effective representations, that lose specific molecular details, but provide the ability to see the proteome as a whole. Mostly two aspects of the proteome have been represented by network models: proteome-wide physical protein-protein-binding interactions organized into Protein Interaction Networks (PINs), and proteome-wide PTM relations organized into Protein Signaling Networks (PSNs). Mass spectrometry (MS) techniques have been shown to be essential to reveal both of these aspects on a proteome-wide scale. Techniques such as affinity purification followed by MS have been used to elucidate protein-protein interactions, and MS-based quantitative phosphoproteomics is critical to understand the structure and dynamics of signaling through the proteome. We here review the current state-of-the-art MS-based analytical pipelines for the purpose to characterize proteome-scale networks.