Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of the organism’s nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress.     

Defining Dry Eye from a Clinical Perspective

Over the past decades, the number of patients with dry eye disease (DED) has increased dramatically. The incidence of DED is higher in Asia than in Europe and North America, suggesting the involvement of cultural or racial factors in DED etiology. Although many definitions of DED have been used, discrepancies exist between the various definitions of dry eye disease (DED) used across the globe. This article presents a clinical consensus on the definition of DED, as formulated in four meetings with global DED experts. The proposed new definition is as follows: “Dry eye is a multifactorial disease characterized by a persistently unstable and/or deficient tear film (TF) causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation and neurosensory abnormalities.” The key criteria for the diagnosis of DED are unstable TF, inflammation, ocular discomfort and visual impairment. This definition also recommends the assessment of ocular surface epitheliopathy and neurosensory abnormalities in each patient with suspected DED. It is easily applicable in clinical practice and should help practitioners diagnose DED consistently. This consensus definition of DED should also help to guide research and clinical trials that, to date, have been hampered by the lack of an established surrogate endpoint.     

Semirigid inclusions in elastic bodies: Mechanical interplay and optimal control

The paper concerns an analysis of an equilibrium problem for 2D elastic body with two semirigid inclusions. It is assumed that inclusions have a joint point, and we investigate a junction problem for these inclusions. The existence of solutions is proved, and different equivalent formulations of the problem are proposed. We investigate a convergence to infinity of a rigidity parameter of the semirigid inclusion. It is proved that in the limit, we obtain an equilibrium problem for the elastic body with a rigid inclusion and a semirigid one. A parameter identification problem is investigated. In particular, the existence of a solution to a suitable optimal control problem is proved.     

Al-Cu-Fe QUASICRYSTALLINE PHASE FORMATION BY MECHANICAL ALLOYING

Al-Cu-Fe alloys were prepared from elemental powders in a high-energy planetary ball mill. A sequence of solid state reactions resulting in quasicrystal (QC) phase formation takes place during heating of the as-milled powder. These reactions were studied by both differential scanning calorimetry and x-ray diffraction methods. Mechanically alloyed powders were consolidated by cold and hot pressing, as well as by explosive compaction. After annealing at sufficiently high temperatures, the consolidated samples are single-phase QC, except the ones consolidated by explosion. The high reactivity of the as-milled alloys causes the appearance of high porosity of the consolidated samples after the annealing.     

Artistic Surface Rendering Using Layout of Text

An artistic rendering method of free-form surfaces with the aid of half-toned text that is laid-out on the given surface is presented. The layout of the text is computed using symbolic composition of the free-form parametric surface  S(u, v)  with cubic or linear Bézier curve segments  C(t) = {c_u (t), c_v (t)}  , comprising the outline of the text symbols. Once the layout is constructed on the surface, a shading process is applied to the text, affecting the width of the symbols as well as their color, according to some shader function. The shader function depends on the surface orientation and the view direction as well as the color and the direction or position of the light source.     

Towards hybrid Triple Helix indicators: A study of university-related patents and a survey of academic inventors

This paper presents work directed at capturing the entrepreneurial and collaborative activity of university researchers. The Triple Helix points to the emergence of the entrepreneurial university as well as to an increasing overlay of activities in universities, industry and government. This study explores ways in which patent-based metrics could be utilized in a Triple Helix context, and how hybrid indicators could be developed by combining patent with survey data. More specifically, it aims to develop indicators that connect technological inventiveness of university researchers to both funding organizations and users, as well as to entrepreneurial activities by academics. The paper develops a simplified model of the innovation process to benchmark the relevance of the indicators to the Triple Helix. An analysis of Finnish academic patents illustrates that patent data can already provide useful indicators but, on its own, cannot provide information about how academic patents are interconnected with government or industry through funding or utilization links. An exclusive analysis of patents can point to patent concentrations on certain universities, to inventors and assignees, or to potential gaps in translating applied science into industrial technology. However, the patent data had to be combined with an inventor survey in order to relate academic patents more to their Triple Helix environment. The survey indicated that most patented academic inventions are connected to (often publicly funded) scientific research by the inventors and tend to be utilized in large firms rather than in start-up companies founded by academic entrepreneurs.     

Organization of cell junctions and cytoskeleton in the reticular lamina in normal and ototoxically damaged organ of Corti

The reticular lamina creates an ion barrier, withstands mechanical stress in the organ of Corti and is able to maintain its integrity during and after severe hair cell loss. Tight junctions maintain the ionic gradient whereas adherens junctions and the cytoskeleton are responsible for the integrity and mechanical resistance of tissues. In this study we used immunofluorescence and electron microscopy to examine the distribution of proteins of tight junctions (cingulin), adherens junctions (E-cadherin, alpha- and beta-catenin) and the cytoskeleton (actin, cytokeratin and tubulin) in whole-mounts of the normal and ototoxically damaged organ of Corti. In normal ears the proteins of adherens junctions were found in all cell types of the reticular lamina. We now demonstrate that all cells forming the reticular lamina partially overlap each other organizing extensive cell contacts with a complex three-dimensional shape. During scar formation, the tight junctions as well as adherens junctions between hair and supporting cells appeared in two distinct focal planes, which could help to preserve the ionic barrier and tissue integrity during hair cell degeneration. During scar formation all cytoskeletal structures in the reticular lamina were reorganized in a specific spatio-temporal pattern. We present a three-dimensional model of cell contact organization in the reticular lamina of normal ears and during scar formation.     

Therapeutic Effects of hiPSC-Derived Glial and Neuronal Progenitor Cells-Conditioned Medium in Experimental Ischemic Stroke in Rats

Transplantation of various types of stem cells as a possible therapy for stroke has been tested for years, and the results are promising. Recent investigations have shown that the administration of the conditioned media obtained after stem cell cultivation can also be effective in the therapy of the central nervous system pathology (hypothesis of their paracrine action). The aim of this study was to evaluate the therapeutic effects of the conditioned medium of hiPSC-derived glial and neuronal progenitor cells in the rat middle cerebral artery occlusion model of the ischemic stroke. Secretory activity of the cultured neuronal and glial progenitor cells was evaluated by proteomic and immunosorbent-based approaches. Therapeutic effects were assessed by overall survival, neurologic deficit and infarct volume dynamics, as well as by the end-point values of the apoptosis- and inflammation-related gene expression levels, the extent of microglia/macrophage infiltration and the numbers of formed blood vessels in the affected area of the brain. As a result, 31% of the protein species discovered in glial progenitor cells-conditioned medium and 45% in neuronal progenitor cells-conditioned medium were cell type specific. The glial progenitor cell-conditioned media showed a higher content of neurotrophins (BDNF, GDNF, CNTF and NGF). We showed that intra-arterial administration of glial progenitor cells-conditioned medium promoted a faster decrease in neurological deficit compared to the control group, reduced microglia/macrophage infiltration, reduced expression of pro-apoptotic gene Bax and pro-inflammatory cytokine gene Tnf, increased expression of anti-inflammatory cytokine genes (Il4, Il10, Il13) and promoted the formation of blood vessels within the damaged area. None of these effects were exerted by the neuronal progenitor cell-conditioned media. The results indicate pronounced cytoprotective, anti-inflammatory and angiogenic properties of soluble factors secreted by glial progenitor cells.     

Pre-Senescence Induction in Hepatoma Cells Favors Hepatitis C Virus Replication and Can Be Used in Exploring Antiviral Potential of Histone Deacetylase Inhibitors

Recent evidence suggests that fibrotic liver injury in patients with chronic hepatitis C correlates with cellular senescence in damaged liver tissue. However, it is still unclear how senescence can affect replication of the hepatitis C virus (HCV). In this work, we report that an inhibitor of cyclin-dependent kinases 4/6, palbociclib, not only induced in hepatoma cells a pre-senescent cellular phenotype, including G1 arrest in the cell cycle, but also accelerated viral replicon multiplication. Importantly, suppression of HCV replication by direct acting antivirals (DAAs) was barely affected by pre-senescence induction, and vice versa, the antiviral activities of host-targeting agents (HTAs), such as inhibitors of human histone deacetylases (HDACi), produced a wide range of reactions—from a dramatic reduction to a noticeable increase. It is very likely that under conditions of the G1 arrest in the cell cycle, HDACi exhibit their actual antiviral potency, since their inherent anticancer activity that complicates the interpretation of test results is minimized.