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.     

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.     

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.     

Reward–Penalty Assignments and Genetic Algorithms for Ordinal Interval Number Group Decision Making

Ordinal interval number group decision making (GDM) is implemented using the closed interval preferences provided by the decision makers (DMs) for the potential courses of action. Two reward–penalty assignments (RPAs) are introduced, which express the compatibility between the ordinal intervals provided by the DMs in a purely binary and a fully graded manner, respectively. Genetic algorithms are employed for establishing a collectively preferred ranking, with chromosome‐validity‐enforcing crossover and gene‐swapping mutation being appropriately combined for efficient convergence. The effect that the consensus function, as derived from two RPAs, has on the fitness landscape and, consequently, on the preferred course(s) of action is illustrated in a number of GDM problems derived from the relevant literature covering (a) complete and incomplete problems, (b) perturbations of the relative importance values assigned to the DMs, (c) full and partial preferences, and (d) increasing numbers of DMs and/or available courses of action (scaling potential).     

Large-scale in vivo synthesis of the carbohydrate moieties of gangliosides GM1 and GM2 by metabolically engineered Escherichia coli

Two metabolically engineered Escherichia coli strains have been constructed to produce the carbohydrate moieties of gangliosides GM2 (GalNAcbeta-4(NeuAcalpha-3)Galbeta-4Glc; Gal = galactose, Glc = glucose, Ac = acetyl) and GM1 (Galbeta-3GalNAcbeta-4(NeuAcalpha-3)Galbeta-4Glc. The GM2 oligosaccharide-producing strain TA02 was devoid of both beta-galactosidase and sialic acid aldolase activities and overexpressed the genes for CMP-NeuAc synthase (CMP = cytidine monophosphate), alpha-2,3-sialyltransferase, UDP-GlcNAc (UDP = uridine diphosphate) C4 epimerase, and beta-1,4-GalNAc transferase. When this strain was cultivated on glycerol, exogenously added lactose and sialic acid were shown to be actively internalized into the cytoplasm and converted into GM2 oligosaccharide. The in vivo synthesis of GM1 oligosaccharide was achieved by taking a similar approach but using strain TA05, which additionally overexpressed the gene for beta-1,3-galactosyltransferase. In high-cell-density cultures, the production yields for the GM2 and GM1 oligosaccharides were 1.25 g L(-1) and 0.89 g L(-1), respectively.     

Nutrient balance of shifting cultivation by burning or mulching in the Eastern Amazon – evidence for subsoil nutrient accumulation

For over a hundred years shifting cultivation with slash-and-burn land preparation has been the predominant type of land use by smallholders in the Bragantina region of the Brazilian Eastern Amazon. This study contrasts the nutrient balance of slash-and-burn agriculture with a fire-free cultivation. Therefore, one half of a 3.5-year-old (28.7 t DM ha^–1) and a 7-year-old woody fallow vegetation (46.5 t DM ha^–1) was burnt and the other half mulched, leaving the biomass as a surface residue. Subsequently, a sequence of maize, beans and cassava was cropped for 1.5 year. Burning the 3.5- and 7-year-old fallow removed 97 and 94% of the C, 98 and 96% of the N, 90 and 63% of the P-stocks, and between 45 and 70% of the cations K, Mg and Ca of the aboveground biomass by volatilization or ash-particle transfer. These losses were avoided with the slash-and-mulch land preparation. Mulching did not increase the losses of nutrients by leaching, despite the high amount of rapidly decomposing surface mulch. Also the length of preceding fallow had no significant influence on leaching losses. At a depth of 3 m, leached nutrients were quantitatively negligible in both treatments. Comparing the nutrient fluxes at soil depths of 0.9 m, 1.8 m and 3 m, the amounts of all mobile nutrients, and also of chloride and sodium were markedly reduced during percolation and must have been retained. It is likely that nutrient retention in the subsoil layer is only temporary, emphasizing the need for a rapid re-establishment of the naturally deep-rooting secondary vegetation after abandonment of sites to enable uptake of these nutrients. The overall nutrient balance was highly negative for slash-and-burn. 291 and 403 kg N ha^–1, 21 and 18 kg P ha^–1, and 70 and 132 kg K ha^–1 were removed from the burnt plots with a preceding fallow of 3.5 and 7 years, respectively. A reduced fallow period (3.5 years), which is a common trend in the region, resulted in a higher mean annual rate of nutrient loss averaged over the duration of the cycle than a fallow period of 7 years. Eliminating the burning losses by mulching brought the agricultural system back to an equilibrated or even slightly positive nutrient balance, even after a reduced fallow period. Thus, slash-and-mulch is a viable alternative to maintain agricultural productivity and ecosystem functioning.