981 research outputs found
Assessment of ROS Production in the Mitochondria of Live Cells
Production of reactive oxygen species (ROS) in the mitochondria plays multiple roles in physiology, and excessive production of ROS leads to the development of various pathologies. ROS in the mitochondria are generated by various enzymes, mainly in the electron transporvt chain, and it is important to identify not only the trigger but also the source of free radical production. It is important to measure mitochondrial ROS in live, intact cells, because activation of ROS production could be initiated by changes in extramitochondrial processes which could be overseen when using isolated mitochondria. Here we describe the approaches, which allow to measure production of ROS in the matrix of mitochondria in live cells. We also demonstrate how to measure kinetic changes in lipid peroxidation in mitochondria of live cells. These methods could be used for understanding the mechanisms of pathology in a variety of disease models and also for testing neuro- or cardioprotective chemicals
Generalized Heisenberg Algebras and Fibonacci Series
We have constructed a Heisenberg-type algebra generated by the Hamiltonian,
the step operators and an auxiliar operator. This algebra describes quantum
systems having eigenvalues of the Hamiltonian depending on the eigenvalues of
the two previous levels. This happens, for example, for systems having the
energy spectrum given by Fibonacci sequence. Moreover, the algebraic structure
depends on two functions f(x) and g(x). When these two functions are linear we
classify, analysing the stability of the fixed points of the functions, the
possible representations for this algebra.Comment: 24 pages, 2 figures, subfigure.st
Functional Oxygen Sensitivity of Astrocytes
In terrestrial mammals, the oxygen storage capacity of the CNS is limited, and neuronal function is rapidly impaired if oxygen supply is interrupted even for a short period of time. However, oxygen tension monitored by the peripheral (arterial) chemoreceptors is not sensitive to regional CNS differences in partial pressure of oxygen (PO2 ) that reflect variable levels of neuronal activity or local tissue hypoxia, pointing to the necessity of a functional brain oxygen sensor. This experimental animal (rats and mice) study shows that astrocytes, the most numerous brain glial cells, are sensitive to physiological changes in PO2 . Astrocytes respond to decreases in PO2 a few millimeters of mercury below normal brain oxygenation with elevations in intracellular calcium ([Ca(2+)]i). The hypoxia sensor of astrocytes resides in the mitochondria in which oxygen is consumed. Physiological decrease in PO2 inhibits astroglial mitochondrial respiration, leading to mitochondrial depolarization, production of free radicals, lipid peroxidation, activation of phospholipase C, IP3 receptors, and release of Ca(2+) from the intracellular stores. Hypoxia-induced [Ca(2+)]i increases in astrocytes trigger fusion of vesicular compartments containing ATP. Blockade of astrocytic signaling by overexpression of ATP-degrading enzymes or targeted astrocyte-specific expression of tetanus toxin light chain (to interfere with vesicular release mechanisms) within the brainstem respiratory rhythm-generating circuits reveals the fundamental physiological role of astroglial oxygen sensitivity; in low-oxygen conditions (environmental hypoxia), this mechanism increases breathing activity even in the absence of peripheral chemoreceptor oxygen sensing. These results demonstrate that astrocytes are functionally specialized CNS oxygen sensors tuned for rapid detection of physiological changes in brain oxygenation. Significance statement: Most, if not all, animal cells possess mechanisms that allow them to detect decreases in oxygen availability leading to slow-timescale, adaptive changes in gene expression and cell physiology. To date, only two types of mammalian cells have been demonstrated to be specialized for rapid functional oxygen sensing: glomus cells of the carotid body (peripheral respiratory chemoreceptors) that stimulate breathing when oxygenation of the arterial blood decreases; and pulmonary arterial smooth muscle cells responsible for hypoxic pulmonary vasoconstriction to limit perfusion of poorly ventilated regions of the lungs. Results of the present study suggest that there is another specialized oxygen-sensitive cell type in the body, the astrocyte, that is tuned for rapid detection of physiological changes in brain oxygenation
Active Membrane Fluctuations Studied by Micropipet Aspiration
We present a detailed analysis of the micropipet experiments recently
reported in J-B. Manneville et al., Phys. Rev. Lett. 82, 4356--4359 (1999),
including a derivation of the expected behaviour of the membrane tension as a
function of the areal strain in the case of an active membrane, i.e.,
containing a nonequilibrium noise source. We give a general expression, which
takes into account the effect of active centers both directly on the membrane,
and on the embedding fluid dynamics, keeping track of the coupling between the
density of active centers and the membrane curvature. The data of the
micropipet experiments are well reproduced by the new expressions. In
particular, we show that a natural choice of the parameters quantifying the
strength of the active noise explains both the large amplitude of the observed
effects and its remarkable insensitivity to the active-center density in the
investigated range. [Submitted to Phys Rev E, 22 March 2001]Comment: 14 pages, 5 encapsulated Postscript figure
Extensions, expansions, Lie algebra cohomology and enlarged superspaces
After briefly reviewing the methods that allow us to derive consistently new
Lie (super)algebras from given ones, we consider enlarged superspaces and
superalgebras, their relevance and some possible applications.Comment: 9 pages. Invited talk delivered at the EU RTN Workshop, Copenhagen,
Sep. 15-19 and at the Argonne Workshop on Branes and Generalized Dynamics,
Oct. 20-24, 2003. Only change: wrong number of a reference correcte
The FEL SASE operation, bunch compression and the beam heater
We discuss the conditions required for an optimal SASE FEL operation when
bunch compression techniques are exploited to enhance the bunch peak current.
We discuss the case of velocity bunching and magnetic bunch compression. With
the reference to the latter technique we provide a quantitative estimate of the
amount of laser heater power necessary to suppress the micro-bunching
instability without creating any problem to the SASE dynamic
Natural chain-breaking antioxidants and their synthetic analogs as modulators of oxidative stress
Oxidative stress is associated with the increased production of reactive oxygen species or with a significant decrease in the effectiveness of antioxidant enzymes and nonenzymatic defense. The penetration of oxygen and free radicals in the hydrophobic interior of biological membranes initiates radical disintegration of the hydrocarbon “tails” of the lipids. This process is known as “lipid peroxidation”, and the accumulation of the oxidation products as peroxides and the alde-hydes and acids derived from them are often used as a measure of oxidative stress levels. In total, 40 phenolic antioxidants were selected for a comparative study and analysis of their chain-breaking antioxidant activity, and thus as modulators of oxidative stress. This included natural and natural-like ortho-methoxy and ortho-hydroxy phenols, nine of them newly synthesized. Applied experimental and theoretical methods (bulk lipid autoxidation, chemiluminescence, in silico methods such as density functional theory (DFT) and quantitative structure–activity relationship ((Q)SAR) modeling) were used to clarify their structure–activity relationship. Kinetics of non-inhibited and inhibited lipid oxidation in close connection with inhibitor transformation under oxidative stress is considered. Special attention has been paid to chemical reactions resulting in the initiation of free radicals, a key stage of oxidative stress. Effects of substituents in the side chains and in the phenolic ring of hydroxylated phenols and biphenols, and the concentration were discussed
Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry.
Mouse models are critical in pre-clinical studies of cancer therapy, allowing dissection of mechanisms through chemical and genetic manipulations that are not feasible in the clinical setting. In studies of the tumour microenvironment (TME), multiplexed imaging methods can provide a rich source of information. However, the application of such technologies in mouse tissues is still in its infancy. Here we present a workflow for studying the TME using imaging mass cytometry with a panel of 27 antibodies on frozen mouse tissues. We optimise and validate image segmentation strategies and automate the process in a Nextflow-based pipeline (imcyto) that is scalable and portable, allowing for parallelised segmentation of large multi-image datasets. With these methods we interrogate the remodelling of the TME induced by a KRAS G12C inhibitor in an immune competent mouse orthotopic lung cancer model, highlighting the infiltration and activation of antigen presenting cells and effector cells
Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry
Mouse models are critical in pre-clinical studies of cancer therapy, allowing dissection of mechanisms through chemical and genetic manipulations that are not feasible in the clinical setting. In studies of the tumour microenvironment (TME), multiplexed imaging methods can provide a rich source of information. However, the application of such technologies in mouse tissues is still in its infancy. Here we present a workflow for studying the TME using imaging mass cytometry with a panel of 27 antibodies on frozen mouse tissues. We optimise and validate image segmentation strategies and automate the process in a Nextflow-based pipeline (imcyto) that is scalable and portable, allowing for parallelised segmentation of large multi-image datasets. With these methods we interrogate the remodelling of the TME induced by a KRAS G12C inhibitor in an immune competent mouse orthotopic lung cancer model, highlighting the infiltration and activation of antigen presenting cells and effector cells
Current knowledge on biomarkers for contact sensitization and allergic contact dermatitis.
Contact sensitization is common and affects up to 20% of the general population. The clinical manifestation of contact sensitization is allergic contact dermatitis. This is a clinical expression that is sometimes difficult to distinguish from other types of dermatitis, for example irritant and atopic dermatitis. Several studies have examined the pathogenesis and severity of allergic contact dermatitis by measuring the absence or presence of various biomarkers. In this review, we provide a non-systematic overview of biomarkers that have been studied in allergic contact dermatitis. These include genetic variations and mutations, inflammatory mediators, alarmins, proteases, immunoproteomics, lipids, natural moisturizing factors, tight junctions, and antimicrobial peptides. We conclude that, despite the enormous amount of data, convincing specific biomarkers for allergic contact dermatitis are yet to be described
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