Viper toxins affect membrane characteristics of human erythrocytes

Elucidating electrokinetic stability by which surface charges regulate toxins interaction with erythrocytes is crucial for understanding the cell functionality. Electrokinetic properties of human erythrocytes upon treatment of Vipoxin, phospholipase A2 (PLA2) and Vipoxin acidic component (VAC), isolated from Vipera ammodytes meridionalis venom were studied using particle microelectrophoresis. PLA2 and Vipoxin treatments alter the osmotic fragility of erythrocyte membranes. The increased stability of cells upon viper toxins is presented by the increased zeta potential of erythrocytes before sedimentation of cells during electric field applied preventing the aggregation of cells. Lipid peroxidation of low dose toxin-treated erythrocytes shows reduced LP products compared to untreated cells. The apparent proton efflux and conductivity assays are performed and the effectiveness PLA2 > Vipoxin>VAC is discussed. The reported results open perspectives to a further investigation of the electrokinetic properties of the membrane after viper toxins treatment to shed light on the molecular mechanisms driving the mechanisms of inflammation and neurodegenerative diseases

Simple Applications of q-Bosons

A deformation of the harmonic oscillator algebra associated with the Morse potential and the SU(2) algebra is derived using the quantum analogue of the anharmonic oscillator. We use the quantum oscillator algebra or $q$-boson algebra which is a generalisation of the Heisenberg-Weyl algebra obtained by introducing a deformation parameter $q$. Further, we present a new algebraic realization of the $q$-bosons, for the case of $q$ being a root of unity, which corresponds to a periodic structure described by a finite-dimensional representation. We show that this structure represents the symmetry of a linear lattice with periodic boundary conditions.Comment: LATEX2e, 10 pages, v2: few misprints corrected, added Journal-re

Monomeric Alpha-Synuclein Exerts a Physiological Role on Brain ATP Synthase

Misfolded α-synuclein is a key factor in the pathogenesis of Parkinson's disease (PD). However, knowledge about a physiological role for the native, unfolded α-synuclein is limited. Using brains of mice lacking α-, β-, and γ-synuclein, we report that extracellular monomeric α-synuclein enters neurons and localizes to mitochondria, interacts with ATP synthase subunit α, and modulates ATP synthase function. Using a combination of biochemical, live-cell imaging and mitochondrial respiration analysis, we found that brain mitochondria of α-, β-, and γ-synuclein knock-out mice are uncoupled, as characterized by increased mitochondrial respiration and reduced mitochondrial membrane potential. Furthermore, synuclein deficiency results in reduced ATP synthase efficiency and lower ATP levels. Exogenous application of low unfolded α-synuclein concentrations is able to increase the ATP synthase activity that rescues the mitochondrial phenotypes observed in synuclein deficiency. Overall, the data suggest that α-synuclein is a previously unrecognized physiological regulator of mitochondrial bioenergetics through its ability to interact with ATP synthase and increase its efficiency. This may be of particular importance in times of stress or PD mutations leading to energy depletion and neuronal cell toxicity. SIGNIFICANCE STATEMENT: Misfolded α-synuclein aggregations in the form of Lewy bodies have been shown to be a pathological hallmark in histological staining of Parkinson's disease (PD) patient brains. It is known that misfolded α-synuclein is a key driver in PD pathogenesis, but the physiological role of unfolded monomeric α-synuclein remains unclear. Using neuronal cocultures and isolated brain mitochondria of α-, β-, and γ-synuclein knock-out mice and monomeric α-synuclein, this current study shows that α-synuclein in its unfolded monomeric form improves ATP synthase efficiency and mitochondrial function. The ability of monomeric α-synuclein to enhance ATP synthase efficiency under physiological conditions may be of importance when α-synuclein undergoes the misfolding and aggregation reported in PD

Optically targeted search for gravitational waves emitted by core-collapse supernovae during the first and second observing runs of advanced LIGO and advanced Virgo

We present the results from a search for gravitational-wave transients associated with core-collapse supernovae observed within a source distance of approximately 20 Mpc during the first and second observing runs of Advanced LIGO and Advanced Virgo. No significant gravitational-wave candidate was detected. We report the detection efficiencies as a function of the distance for waveforms derived from multidimensional numerical simulations and phenomenological extreme emission models. The sources with neutrino-driven explosions are detectable at the distances approaching 5 kpc, and for magnetorotationally driven explosions the distances are up to 54 kpc. However, waveforms for extreme emission models are detectable up to 28 Mpc. For the first time, the gravitational-wave data enabled us to exclude part of the parameter spaces of two extreme emission models with confidence up to 83%, limited by coincident data coverage. Besides, using ad hoc harmonic signals windowed with Gaussian envelopes, we constrained the gravitational-wave energy emitted during core collapse at the levels of 4.27×10-4 M·c2 and 1.28×10-1 M·c2 for emissions at 235 and 1304 Hz, respectively. These constraints are 2 orders of magnitude more stringent than previously derived in the corresponding analysis using initial LIGO, initial Virgo, and GEO 600 data

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO’s second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h95%0=3.47×10−25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering

Monomeric alpha-synuclein exerts a physiological role in brain ATP synthase

Misfolded α-synuclein is a key factor in the pathogenesis of Parkinson's disease (PD). However, knowledge about a physiological role for the native, unfolded α-synuclein is limited. Using brains of mice lacking α-, β-, and γ-synuclein, we report that extracellular monomeric α-synuclein enters neurons and localizes to mitochondria, interacts with ATP synthase subunit α, and modulates ATP synthase function. Using a combination of biochemical, live-cell imaging and mitochondrial respiration analysis, we found that brain mitochondria of α-, β-, and γ-synuclein knock-out mice are uncoupled, as characterized by increased mitochondrial respiration and reduced mitochondrial membrane potential. Furthermore, synuclein deficiency results in reduced ATP synthase efficiency and lower ATP levels. Exogenous application of low unfolded α-synuclein concentrations is able to increase the ATP synthase activity that rescues the mitochondrial phenotypes observed in synuclein deficiency. Overall, the data suggest that α-synuclein is a previously unrecognized physiological regulator of mitochondrial bioenergetics through its ability to interact with ATP synthase and increase its efficiency. This may be of particular importance in times of stress or PD mutations leading to energy depletion and neuronal cell toxicity

Gravitational-wave constraints on the equatorial ellipticity of millisecond pulsars

We present a search for continuous gravitational waves from five radio pulsars, comprising three recycled pulsars (PSR J0437−4715, PSR J0711−6830, and PSR J0737−3039A) and two young pulsars: the Crab pulsar (J0534+2200) and the Vela pulsar (J0835−4510). We use data from the third observing run of Advanced LIGO and Virgo combined with data from their first and second observing runs. For the first time, we are able to match (for PSR J0437−4715) or surpass (for PSR J0711−6830) the indirect limits on gravitational-wave emission from recycled pulsars inferred from their observed spin-downs, and constrain their equatorial ellipticities to be less than 10−8. For each of the five pulsars, we perform targeted searches that assume a tight coupling between the gravitational-wave and electromagnetic signal phase evolution. We also present constraints on PSR J0711−6830, the Crab pulsar, and the Vela pulsar from a search that relaxes this assumption, allowing the gravitational-wave signal to vary from the electromagnetic expectation within a narrow band of frequencies and frequency derivatives

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

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

Binary black hole population properties inferred from the first and second observing runs of advanced LIGO and advanced Virgo

We present results on the mass, spin, and redshift distributions with phenomenological population models using the 10 binary black hole (BBH) mergers detected in the first and second observing runs completed by Advanced LIGO and Advanced Virgo. We constrain properties of the BBH mass spectrum using models with a range of parameterizations of the BBH mass and spin distributions. We find that the mass distribution of the more massive BH in such binaries is well approximated by models with no more than 1% of BHs more massive than 45 M and a power-law index of (90% credibility). We also show that BBHs are unlikely to be composed of BHs with large spins aligned to the orbital angular momentum. Modeling the evolution of the BBH merger rate with redshift, we show that it is flat or increasing with redshift with 93% probability. Marginalizing over uncertainties in the BBH population, we find robust estimates of the BBH merger rate density of R= (90% credibility). As the BBH catalog grows in future observing runs, we expect that uncertainties in the population model parameters will shrink, potentially providing insights into the formation of BHs via supernovae, binary interactions of massive stars, stellar cluster dynamics, and the formation history of BHs across cosmic time