Different Expression of Mitochondrial and Endoplasmic Reticulum Stress Genes in Epicardial Adipose Tissue Depends on Coronary Atherosclerosis

The aim of our study was to analyze mitochondrial and endoplasmic reticulum (ER) gene expression profiles in subcutaneous (SAT) and epicardial (EAT) adipose tissue, skeletal muscle, and myocardium in patients with and without CAD undergoing elective cardiac surgery. Thirty-eight patients, 27 with (CAD group) and 11 without CAD (noCAD group), undergoing coronary artery bypass grafting and/or valvular surgery were included in the study. EAT, SAT, intercostal skeletal muscle, and right atrium tissue and blood samples were collected at the start and end of surgery; mRNA expression of selected mitochondrial and ER stress genes was assessed using qRT-PCR. The presence of CAD was associated with decreased mRNA expression of most of the investigated mitochondrial respiratory chain genes in EAT, while no such changes were seen in SAT or other tissues. In contrast, the expression of ER stress genes did not differ between the CAD and noCAD groups in almost any tissue. Cardiac surgery further augmented mitochondrial dysfunction in EAT. In our study, CAD was associated with decreased expression of mitochondrial, but not endoplasmic reticulum stress genes in EAT. These changes may contribute to the acceleration of coronary atherosclerosis.     

State of the Art of Molecular Visualization in Immersive Virtual Environments

Visualization plays a crucial role in molecular and structural biology. It has been successfully applied to a variety of tasks, including structural analysis and interactive drug design. While some of the challenges in this area can be overcome with more advanced visualization and interaction techniques, others are challenging primarily due to the limitations of the hardware devices used to interact with the visualized content. Consequently, visualization researchers are increasingly trying to take advantage of new technologies to facilitate the work of domain scientists. Some typical problems associated with classic 2D interfaces, such as regular desktop computers, are a lack of natural spatial understanding and interaction, and a limited field of view. These problems could be solved by immersive virtual environments and corresponding hardware, such as virtual reality head-mounted displays. Thus, researchers are investigating the potential of immersive virtual environments in the field of molecular visualization. There is already a body of work ranging from educational approaches to protein visualization to applications for collaborative drug design. This review focuses on molecular visualization in immersive virtual environments as a whole, aiming to cover this area comprehensively. We divide the existing papers into different groups based on their application areas, and types of tasks performed. Furthermore, we also include a list of available software tools. We conclude the report with a discussion of potential future research on molecular visualization in immersive environments.     

The Impact of the Microbiome on Resistance to Cancer Treatment with Chemotherapeutic Agents and Immunotherapy

Understanding the mechanisms of resistance to therapy in human cancer cells has become a multifaceted limiting factor to achieving optimal cures in cancer patients. Besides genetic and epigenetic alterations, enhanced DNA damage repair activity, deregulation of cell death, overexpression of transmembrane transporters, and complex interactions within the tumor microenvironment, other mechanisms of cancer treatment resistance have been recently proposed. In this review, we will summarize the preclinical and clinical studies highlighting the critical role of the microbiome in the efficacy of cancer treatment, concerning mainly chemotherapy and immunotherapy with immune checkpoint inhibitors. In addition to involvement in drug metabolism and immune surveillance, the production of microbiota-derived metabolites might represent the link between gut/intratumoral bacteria and response to anticancer therapies. Importantly, an emerging trend of using microbiota modulation by probiotics and fecal microbiota transplantation (FMT) to overcome cancer treatment resistance will be also discussed.     

Mitochondrial Processing Peptidases—Structure,Function and the Role in Human Diseases

Mitochondrial proteins are encoded by both nuclear and mitochondrial DNA. While some of the essential subunits of the oxidative phosphorylation (OXPHOS) complexes responsible for cellular ATP production are synthesized directly in the mitochondria, most mitochondrial proteins are first translated in the cytosol and then imported into the organelle using a sophisticated transport system. These proteins are directed mainly by targeting presequences at their N-termini. These presequences need to be cleaved to allow the proper folding and assembly of the pre-proteins into functional protein complexes. In the mitochondria, the presequences are removed by several processing peptidases, including the mitochondrial processing peptidase (MPP), the inner membrane processing peptidase (IMP), the inter-membrane processing peptidase (MIP), and the mitochondrial rhomboid protease (Pcp1/PARL). Their proper functioning is essential for mitochondrial homeostasis as the disruption of any of them is lethal in yeast and severely impacts the lifespan and survival in humans. In this review, we focus on characterizing the structure, function, and substrate specificities of mitochondrial processing peptidases, as well as the connection of their malfunctions to severe human diseases.     

Arsenic in atmospheric deposition at the Czech-Polish border: two sampling campaigns 20 years apart

Arsenic (As) occurs in atmospheric deposition both in soluble and insoluble forms, mainly bound to fine aerosol particles (less than 2.5 microm). Interception deposition (i.e. fog, dew and ice accretion) represents a specific type of atmospheric deposition, which has been much more contaminated with As than bulk deposition. This study compares the As amount and its binding forms in bulk and interception deposition in the winters of 1984-1986 and 2003-2005 in the Orlické hory mountains (Adlergebirge) near the Czech-Polish border; sampled and analysed by the same methodology. The As concentrations in ice accretions decreased 16 times over the twenty year period (from 50 microg L(-1) to 3 microg L(-1)), while the pH values increased by 0.8 units. As concentrations in snow decreased from 15 microg L(-1) in 1984-1986 to <2 microg L(-1) in 2003-2005. This decline mirrored the considerable decrease in industrial emissions in Central Europe. Higher acidity of interception deposition (about 1 pH unit) in comparison with the bulk deposition was observed in both sampling periods. The quantity of bulk deposition (snowfall) also influenced the As concentration in interception deposition. Dry periods resulted in higher As-amounts in interception deposition due to limited washing of atmospheric aerosol particles by wet deposition. The As concentration and stability in atmospheric deposition are important for the study of subsequent As-migration and/or accumulation in soil -- groundwater -- surface water.     

Hierarchically Structured Surfaces Prepared by Phase Separation: Tissue Mimicking Culture Substrate

The pseudo 3D hierarchical structure mimicking in vivo microenvironment was prepared by phase separation on tissue culture plastic. For surface treatment, time-sequenced dosing of the solvent mixture with various concentrations of polymer component was used. The experiments showed that hierarchically structured surfaces with macro, meso and micro pores can be prepared with multi-step phase separation processes. Changes in polystyrene surface topography were characterized by atomic force microscopy, scanning electron microscopy and contact profilometry. The cell proliferation and changes in cell morphology were tested on the prepared structured surfaces. Four types of cell lines were used for the determination of impact of the 3D architecture on the cell behavior, namely the mouse embryonic fibroblast, human lung carcinoma, primary human keratinocyte and mouse embryonic stem cells. The increase of proliferation of embryonic stem cells and mouse fibroblasts was the most remarkable. Moreover, the embryonic stem cells express different morphology when cultured on the structured surface. The acquired findings expand the current state of knowledge in the field of cell behavior on structured surfaces and bring new technological procedures leading to their preparation without the use of problematic temporary templates or additives.