Astrocytic Vesicle Mobility in Health and Disease

Astrocytes are no longer considered subservient to neurons, and are, instead, now understood to play an active role in brain signaling. The intercellular communication of astrocytes with neurons and other non-neuronal cells involves the exchange of molecules by exocytotic and endocytotic processes through the trafficking of intracellular vesicles. Recent studies of single vesicle mobility in astrocytes have prompted new views of how astrocytes contribute to information processing in nervous tissue. Here, we review the trafficking of several types of membrane-bound vesicles that are specifically involved in the processes of (i) intercellular communication by gliotransmitters (glutamate, adenosine 5′-triphosphate, atrial natriuretic peptide), (ii) plasma membrane exchange of transporters and receptors (EAAT2, MHC-II), and (iii) the involvement of vesicle mobility carrying aquaporins (AQP4) in water homeostasis. The properties of vesicle traffic in astrocytes are discussed in respect to networking with neighboring cells in physiologic and pathologic conditions, such as amyotrophic lateral sclerosis, multiple sclerosis, and states in which astrocytes contribute to neuroinflammatory conditions.     

Binding of mercury in soils and attic dust in the Idrija mercury mine area (Slovenia)

Total Hg concentrations and Hg speciation were determined in soils and attic dust in a 160 km2 area around Idrija mercury mine. Attic dust as well as a sample of soil was collected at 100 locations. Mercury phases were separated into cinnabar and non-cinnabar compounds via a thermo-desorption technique. The amount of the non-cinnabar fraction is important since it is potentially bioavailable and results are needed for further risk assessment studies. The concentrations of Hg in attic dust are many times higher than in surrounding soils and the attic dust/soil ratio changes with distance. The highest concentration ratios were identified at the greatest distance from the source of pollution and the lowest close to the source of pollution. This confirms the impact of air emissions on the wider area around Idrija. Furthermore the spatial mercury distribution in the attic dust shows that the influence of atmospheric emissions caused by the Idrija smelter resulted in impacts on the environment on a regional scale. The portions of non-cinnabar compounds increase with distance from the mercury source in both sampling media. Non-cinnabar fractions were found to be enriched in distant areas where fine grained material was deposited. There were two different transport mechanisms of dust particles and gaseous Hg(0) during the mercury production period. Obviously coarse grained particles, with mostly cinnabar-bound Hg settled in the immediate vicinity of the smokestack of the smelter, whereas the fine grained fraction could be dispersed further ahead. This is represented by the percentage of cinnabar-bound Hg in attic dust and soil decreasing with distance from the smelter. Gaseous Hg(0) is probably bound to fine and ultrafine aerosols with longer residence time against deposition. The consequence is that fine grained material with Hg2+ and Hg0 prevails in remote localities and is bound in soils and dust with matrix and organic matter as non-cinnabar mercury compounds. The distributions of mercury species in attic dust and soils along the Idrijca River show that in the region from Idrija to Spodnja Idrija the portions of cinnabar and non-cinnabar are about equal, while in the upper and in the lower Idrijca valley non-cinnabar bound mercury prevails. The applicability of attic dust for tracing the mercury halo in the Idrija area was successfully shown.     

Fuzzy control for the illumination and temperature comfort in a test chamber

The paper deals with the controlled dynamic thermal and illumination response of human-built environment in real-time conditions. The aim is to harmonize the thermal and optical behavior of a building with regulated energy flows through the envelope. A control system with fuzzy elements for changeable transparent elements of the building envelope was developed. For this purpose a test chamber with an opening on the south aside was built. Energy flows through the envelope are controlled with changeable geometry of the window, realized with the external roller blind, which is automatically positioned. The fuzzy controller for the corresponding positioning of the roller blind in a given combination of outside conditions as external disturbances is the subject of this paper.     

Do the Effects of Secondary Prevention of Cardiovascular Events in PAD Patients Differ from Other Atherosclerotic Disease?

Atherosclerosis is considered a generalized disease. Similar or identical etiopathogenetic mechanisms and risk factors are involved in various atherosclerotic diseases, and the positive effects of preventive measures on atherogenesis in different parts of the arterial system were shown. However, until know, great emphasis has been placed on the aggressive pharmacological management of coronary artery disease (CHD), while less attention has been devoted to the management of peripheral arterial disease (PAD), despite its significant morbidity and mortality. Data on the efficacy of preventive measures in PAD patients have mostly been gained from subgroup analyses from studies devoted primarily to the management of coronary patients. These data have shown that treatment of risk factors for atherosclerosis with drugs can reduce cardiovascular events also in patients with PAD. The effects of some preventive procedures in PAD patients differ from coronary patients. Aspirin as a basic antiplatelet drug has been shown to be less effective in PAD patients than in coronary patients. The latest Antithrombotic Trialists’ Collaboration (ATC) meta-analysis demonstrates no benefit of aspirin in reducing cardiovascular events in PAD. Statins reduce cardiovascular events in all three of the most frequently presented cardiovascular diseases, including PAD to a comparable extent. Recent studies indicate that in PAD patients, in addition to a reduction in cardiovascular events, statins may have some hemodynamic effects. They prolong walking distance and improve quality of life. Similarly, angiotensin enzyme inhibitors are also effective in the prevention of cardiovascular events in coronary, cerebrovascular, as well as PAD patients and show positive effects on the walking capacity of patients with intermittent claudication. In PAD patients, the treatment of hypertension and diabetes also effectively prevents cardiovascular morbidity and mortality. As PAD patients are at a highest risk of cardiovascular complications, the risk factors of atherosclerosis should be treated intensively in this group of patients. Most of the preventive measures, including the drugs used for prevention of CHD, are also effective in PAD patients.     

Test development for second-generation ColdFire microprocessors

This case study shows how test designers met fundamental microprocessor testing goals while adapting existing methodologies to a new architecture     

A conceptual model of security context

Ubiquitous environments which embrace the trends of enterprise mobility and the consumerization of IT have an increasing social importance. In these environments, the same device and applications are simultaneously used for both personal and professional purposes. Such usage blurs the boundaries between personal and professional domains and presents many challenges for information security. Context-aware security has been proposed as a solution for many of them. We argue that the existing approaches are limited and mainly deal with targeted use cases. They do not provide a clear and complete understanding of the context relevant for security, and use contextual information with an arbitrary level of abstraction. In order to address these issues, we propose a conceptual model of security context. The model identifies important concepts of security context and takes related social aspects into account. It represents the security context through a set of concepts at the appropriate level of abstraction. We show that our model is suitable to analyze various situations from the perspective of security and compare them with the existing approaches. The model promises to facilitate the specification and management of security policies containing contextual information as well.     

Intracellular delivery of cysteine protease inhibitor cystatin by polymeric nanoparticles

Two polymers chitosan and poly(lactide-co-glycolide) copolymer (PLGA) were investigated to develop nanoparticles (NPs) for delivery of protein drug substance into tumour cells. Cystatin was selected as a model protein drug due to its high potential to inhibit cysteine proteases, known to trigger the invasive process. Ionotropic gelation of chitosan with tripolyposphate and precipitation of PLGA polymer from a double emulsion system by a solvent diffusion process were used to produce 250-300 nm in diameter NPs. The cellular uptake of NPs was tested on a transformed human breast epithelial cell line, MCF-10A neoT, characterized by an increased expression of cysteine proteases and highly invasive cell phenotype. The influence of NPs on cell viability was evaluated by MTT test showing IC50 400 microg/ml for PLGA and 5 mg/ml for chitosan NPs. As determined by fluorescence microscopy chitosan NPs did not enter the cells during 1-hour incubation whereas the same amount of PLGA NPs were in the cells already after 5 min of incubation. Cystatin delivered into MCF-10A neoT cells by PLGA NPs effectively inhibited intracellular proteolytic activity of cathepsin B, as detected by specific fluorogenic substrate Z-Arg2 cresyl violet. On the contrary, free cystatin in solution did not internalise into the cells and inhibit cathepsin B. To conclude, PLGA NPs with cystatin but not chitosan NPs were targeted through endocytosis to the lysosomal compartments that are rich of proteases enzymes. Our results suggest new strategy to inactivate intracellular tumour-associated proteases, and consequently the invasion behaviour of tumour cells, which could contribute to cancer therapy.     

Killing Two Birds with One Stone: Potential Therapies Targeting Psoriasis and Atherosclerosis at the Same Time

Psoriasis is a chronic systemic inflammatory disease. Due to systemic inflammation, it is associated with many comorbidities. Among them, cardiovascular diseases represent the most common causes of morbidity and mortality in this population. Therefore, physicians treating patients with psoriasis should keep in mind that, as important as the treatment of psoriasis, awareness of cardiovascular risk deserves additional attention. Thus, in parallel with psoriasis treatment, a cardiovascular risk assessment must also be performed and addressed accordingly. In addition to encouraging non-pharmacologic strategies for a healthy lifestyle, physicians should be familiar with different pharmacologic options that can target psoriasis and reduce cardiovascular risk. In the present article, we present the pathophysiological mechanisms of the psoriasis and cardiometabolic interplay, our view on the interaction of psoriasis and cardiovascular disease, review the atherosclerotic effect of therapeutic options used in psoriasis, and vice versa, i.e., what the effect of medications used in the prevention of atherosclerosis could be on psoriasis.     

Development and Characterization of a Novel Soil Amendment Based on Biomass Fly Ash Encapsulated in Calcium Alginate Microspheres

Biomass fly ash (BFA) from a biomass cogeneration plant was encapsulated into calcium alginate microspheres (ALG/Ca) and characterized. An FTIR analysis indicated that BFA loading weakened molecular interactions between ALG/Ca constituents (mainly hydrogen bonding and electrostatic interactions), thus changing the crosslinking density. SEM and AFM analyses revealed a wrinkled and rough surface with elongated and distorted granules. The in vitro release of BFA’s main components (K, Ca, and Mg) was controlled by diffusion through the gel-like matrix, but the kinetics and released amounts differed significantly. The smaller released amounts and slower release rates of Ca and Mg compared to K resulted from the differences in the solubility of their minerals as well as from the interactions of divalent cations with alginate chains. The physicochemical properties of the novel microsphere formulation reveal significant potential for the prolonged delivery of nutrients to crops in a safe manner.