During physiological activity neurons may experience localised energy demands which require intracellular signals for stimulation of mitochondrial NADH generation and subsequent delivery of ATP. To ...elucidate these mechanisms, we applied microfluorimetric monitoring of cytoplasmic (Fluo-3) and mitochondrial (Rhod-2) calcium concentration (Ca
2+
c, Ca
2+
m), as well as of mitochondrial oxidative metabolism (NAD(P)H), whilst simultaneously measuring changes in extracellular potassium concentration (K
+
o), as an indicator of neuronal activity in hippocampal slice cultures. Changes in neuronal activity were induced by repetitive stimulation at different frequencies (5, 20, 100 Hz) and intensities. Stimulation parameters were chosen to elicit rises in K
+
o of less than 3 mM which is comparable to physiologically occurring rises in K
+
o.
The mitochondrial uncoupler carbonyl cyanide
m-chlorophenyl hydrazone (CCCP) reduced stimulus-induced changes in Rhod-2 fluorescence by 79%, indicating that Rhod-2 signals were primarily of mitochondrial origin. Repetitive stimulation at 20 Hz applied to areas CA1 or CA3 resulted in moderate rises in K
+
o which were associated with stimulus-dependent elevations in Ca
2+
c and Ca
2+
m of up to 15%. The same stimuli also elicited biphasic changes in NAD(P)H fluorescence characterised by an initial decline and a subsequent prolonged elevation of up to 10%. Variation of stimulus parameters revealed close correlations between rises in K
+
o, in Ca
2+
m and changes in NAD(P)H fluorescence. To elucidate the role of intracellular Ca
2+ accumulation in induction of NAD(P)H fluorescence signals, the effect of application of Ca
2+-free solution on these signals evoked by repetitive antidromic stimulation of the alveus during recordings in area CA1 was studied. Lowering extracellular Ca
2+ led to complete blockade of postsynaptic field potential components as well as of rises in Ca
2+
c and Ca
2+
m. Amplitudes of NAD(P)H signals were reduced by 59%, though rises in K
+
o were comparable in presence and absence of extracellular Ca
2+.
The results suggest i) that mitochondrial oxidative metabolism is fine-tuned to graded physiological activity in neurons and ii) that rapid mitochondrial Ca
2+ signalling represents one of the main determinants for stimulation of oxidative metabolism under physiological conditions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A search for heavy neutral lepton (N) production in K+→e+N decays using the data sample collected by the NA62 experiment at CERN in 2017–2018 is reported. Upper limits of the extended neutrino mixing ...matrix element |Ue4|2 are established at the level of 10−9 over most of the accessible heavy neutral lepton mass range 144–462 MeV/c2, with the assumption that the lifetime exceeds 50 ns. These limits improve significantly upon those of previous production and decay searches. The |Ue4|2 range favoured by Big Bang Nucleosynthesis is excluded up to a mass of about 340 MeV/c2.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The NA62 experiment at CERN reports searches for K+→μ+N and K+→μ+νX decays, where N and X are massive invisible particles, using the 2016–2018 data set. The N particle is assumed to be a heavy ...neutral lepton, and the results are expressed as upper limits of O(10−8) of the neutrino mixing parameter |Uμ4|2 for N masses in the range 200–384 MeV/c2 and lifetime exceeding 50 ns. The X particle is considered a scalar or vector hidden sector mediator decaying to an invisible final state, and upper limits of the decay branching fraction for X masses in the range 10–370 MeV/c2 are reported for the first time, ranging from O(10−5) to O(10−7). An improved upper limit of 1.0×10−6 is established at 90% CL on the K+→μ+ννν¯ branching fraction.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Several lines of evidence indicate that augmented neuronal activity is associated with increased mitochondrial function, however, the mechanisms of coupling are still unclear. In this study we used a ...low extracellular Mg2+ concentration and short stimulus trains to evoke neuronal hyperactivity in the form of seizure‐like events (SLE) in hippocampal slice cultures. Simultaneous microfluorimetric and electrophysiological techniques were applied to gain insight into changes of Ca2+ concentration in different compartments and into mitochondrial function. SLEs were associated with a large decrease of the extracellular Ca2+ concentration (Ca2+e), a spiking increase of the cytoplasmic and a smoothed elevation of the mitochondrial Ca2+ concentration (cytoplasmic concentration Ca2+i; intramitrochondrial concentration Ca2+m). Following an initial apparent decline in the mitochondrial membrane potential (ΔΨ) and NAD(P)H autofluorescence, mitochondria depolarized and NADH production was augmented. Furthermore, SLEs were associated with increased oxidation of dihydroethidine (HEt). Our data suggest that intramitochondrial Ca2+ accumulation stimulates NADH production and production of radical oxygen species (ROS). Interestingly, mitochondrial depolarization followed Ca2+i and Ca2+m changes with a delay implying that electrogenic extrusion of Ca2+ from the mitochondrial matrix might be responsible for the depolarization of the mitochondrial membrane.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
At sufficiently high temperature and energy density, nuclear matter undergoes a transition to a phase in which quarks and gluons are not confined: the quark-gluon plasma (QGP). Such an exotic state ...of strongly interacting quantum chromodynamics matter is produced in the laboratory in heavy nuclei high-energy collisions, where an enhanced production of strange hadrons is observed. Strangeness enhancement, originally proposed as a signature of QGP formation in nuclear collisions, is more pronounced for multi-strange baryons. Several effects typical of heavy-ion phenomenology have been observed in high-multiplicity proton-proton (pp) collisions, but the enhanced production of multi-strange particles has not been reported so far. Here we present the first observation of strangeness enhancement in high-multiplicity proton-proton collisions. We find that the integrated yields of strange and multi-strange particles, relative to pions, increases significantly with the event charged-particle multiplicity. The measurements are in remarkable agreement with the p-Pb collision results, indicating that the phenomenon is related to the final system created in the collision. In high-multiplicity events strangeness production reaches values similar to those observed in Pb-Pb collisions, where a QGP is formed.
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IJS, NUK, SBMB, UL, UM, UPUK
The NA62 experiment at CERN reports a search for the lepton number violating decays K+→π−e+e+ and K+→π−μ+μ+ using a data sample collected in 2017. No signals are observed, and upper limits on the ...branching fractions of these decays of 2.2×10−10 and 4.2×10−11 are obtained, respectively, at 90% confidence level. These upper limits improve on previously reported measurements by factors of 3 and 2, respectively.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In the present-day atmosphere, sulfuric acid is the most
important vapour for aerosol particle formation and initial growth. However,
the growth rates of nanoparticles (<10 nm) from sulfuric acid
...remain poorly measured. Therefore, the effect of stabilizing bases, the
contribution of ions and the impact of attractive forces on molecular
collisions are under debate. Here, we present precise growth rate
measurements of uncharged sulfuric acid particles from 1.8 to 10 nm, performed
under atmospheric conditions in the CERN (European
Organization for Nuclear Research) CLOUD chamber. Our results show
that the evaporation of sulfuric acid particles above 2 nm is negligible,
and growth proceeds kinetically even at low ammonia concentrations. The
experimental growth rates exceed the hard-sphere kinetic limit for the
condensation of sulfuric acid. We demonstrate that this results from
van der Waals forces between the vapour molecules and particles and
disentangle it from charge–dipole interactions. The magnitude of the
enhancement depends on the assumed particle hydration and collision
kinetics but is increasingly important at smaller sizes, resulting in a
steep rise in the observed growth rates with decreasing size. Including the
experimental results in a global model, we find that the enhanced growth rate of
sulfuric acid particles increases the predicted particle number concentrations
in the upper free troposphere by more than 50 %.
Highly oxygenated organic molecules (HOMs) contribute
substantially to the formation and growth of atmospheric aerosol particles,
which affect air quality, human health and Earth's climate. HOMs are ...formed
by rapid, gas-phase autoxidation of volatile organic compounds (VOCs) such
as α-pinene, the most abundant monoterpene in the atmosphere. Due to
their abundance and low volatility, HOMs can play an important role in
new-particle formation (NPF) and the early growth of atmospheric aerosols,
even without any further assistance of other low-volatility compounds such
as sulfuric acid. Both the autoxidation reaction forming HOMs and their
NPF rates are expected to be strongly dependent on
temperature. However, experimental data on both effects are limited.
Dedicated experiments were performed at the CLOUD (Cosmics Leaving OUtdoor
Droplets) chamber at CERN to address this question. In this study, we show
that a decrease in temperature (from +25 to −50 ∘C) results in
a reduced HOM yield and reduced oxidation state of the products, whereas the
NPF rates (J1.7 nm) increase substantially.
Measurements with two different chemical ionization mass spectrometers
(using nitrate and protonated water as reagent ion, respectively) provide
the molecular composition of the gaseous oxidation products, and a
two-dimensional volatility basis set (2D VBS) model provides their volatility
distribution. The HOM yield decreases with temperature from 6.2 % at 25 ∘C to 0.7 % at −50 ∘C. However, there is a strong
reduction of the saturation vapor pressure of each oxidation state as the
temperature is reduced. Overall, the reduction in volatility with
temperature leads to an increase in the nucleation rates by up to 3
orders of magnitude at −50 ∘C compared with 25 ∘C. In
addition, the enhancement of the nucleation rates by ions decreases with
decreasing temperature, since the neutral molecular clusters have increased
stability against evaporation. The resulting data quantify how the interplay
between the temperature-dependent oxidation pathways and the associated
vapor pressures affect biogenic NPF at the molecular
level. Our measurements, therefore, improve our understanding of pure
biogenic NPF for a wide range of tropospheric
temperatures and precursor concentrations.
Mechanisms of seizure-induced cell death were studied in organotypic hippocampal slice cultures. These develop after withdrawal of magnesium recurrent seizure-like events (SLE), which lead to ...intracellular and intramitochondrial calcium accumulation. The intramitochondrial Ca accumulation seems to be involved in causing increased production of NADH, measured as NAD(P)H autofluorescence. During SLEs, depolarization of mitochondria and increased production of free radicals is indicated by fluorescence measurements with appropriate dyes. During recurrent seizures, an increased failure to produce NADH is noted while at the same time free radical production seems to increase. This increase and the decline in NADH production could be involved in transition to late recurrent discharges, a phase in which status epilepticus becomes pharmacoresistant. It also coincides with increased cell death as determined with propidium iodide fluorescence. Interestingly, some of these changes can be prevented by application of alpha-tocopherol, a free radical scavenger, which also has neuroprotective effects under our experimental conditions. The results suggest that free radical-induced mitochondrial impairment is involved in seizure-induced cell death.
Direct photon production at mid-rapidity in Pb–Pb collisions at sNN=2.76 TeV was studied in the transverse momentum range 0.9<pT<14 GeV/c. Photons were detected with the highly segmented ...electromagnetic calorimeter PHOS and via conversions in the ALICE detector material with the e+e− pair reconstructed in the central tracking system. The results of the two methods were combined and direct photon spectra were measured for the 0–20%, 20–40%, and 40–80% centrality classes. For all three classes, agreement was found with perturbative QCD calculations for pT≳5 GeV/c. Direct photon spectra down to pT≈1 GeV/c could be extracted for the 20–40% and 0–20% centrality classes. The significance of the direct photon signal for 0.9<pT<2.1 GeV/c is 2.6σ for the 0–20% class. The spectrum in this pT range and centrality class can be described by an exponential with an inverse slope parameter of (297±12stat±41syst) MeV. State-of-the-art models for photon production in heavy-ion collisions agree with the data within uncertainties.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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