Acute knockdown of Kv4.1 regulates repetitive firing rates and clock gene expression in the suprachiasmatic nucleus and daily rhythms in locomotor behavior

AbstractRapidly activating and inactivating A-type K+currents (IA) encoded by Kv4.2 and Kv4.3 pore-forming (α) subunits of the Kv4 subfamily are key regulators of neuronal excitability. Previous studies have suggested a role for Kv4.1 α-subunits in regulating the firing properties of mouse suprachiasmatic nucleus (SCN) neurons. To test this, we utilized an RNA-interference strategy to knockdown Kv4.1, acutely and selectively, in the SCN. Current-clamp recordings revealed that thein vivoknockdown of Kv4.1 significantly (p&lt; 0.0001) increased mean ± SEM repetitive firing rates in SCN neurons during the day (6.4 ± 0.5 Hz) and at night (4.3 ± 0.6 Hz), compared with nontargeted shRNA-expressing SCN neurons (day: 3.1 ± 0.5 Hz; night: 1.6 ± 0.3 Hz). IAwas also significantly (p&lt; 0.05) reduced in Kv4.1-targeted shRNA-expressing SCN neurons (day: 80.3 ± 11.8 pA/pF; night: 55.3 ± 7.7 pA/pF), compared with nontargeted shRNA-expressing (day: 121.7 ± 10.2 pA/pF; night: 120.6 ± 16.5 pA/pF) SCN neurons. The magnitude of the effect of Kv4.1-targeted shRNA expression on firing rates and IAwas larger at night. In addition, Kv4.1-targeted shRNA expression significantly (p&lt; 0.001) increased mean ± SEM nighttime input resistance (Rin; 2256 ± 166 MΩ), compared to nontargeted shRNA-expressing SCN neurons (1143 ± 93 MΩ). Additional experiments revealed that acute knockdown of Kv4.1 significantly (p&lt; 0.01) shortened, by ∼0.5 h, the circadian period of spontaneous electrical activity, clock gene expression and locomotor activity demonstrating a physiological role for Kv4.1-encoded IAchannels in regulating circadian rhythms in neuronal excitability and behavior.</jats:p

Tropospheric Ozone Assessment Report: present-day distribution and trends of tropospheric ozone relevant to climate and global atmospheric chemistry model evaluation

The Tropospheric Ozone Assessment Report (TOAR) is an activity of the International Global Atmospheric Chemistry Project. This paper is a component of the report, focusing on the present-day distribution and trends of tropospheric ozone relevant to climate and global atmospheric chemistry model evaluation. Utilizing the TOAR surface ozone database, several figures present the global distribution and trends of daytime average ozone at 2702 non-urban monitoring sites, highlighting the regions and seasons of the world with the greatest ozone levels. Similarly, ozonesonde and commercial aircraft observations reveal ozone’s distribution throughout the depth of the free troposphere. Long-term surface observations are limited in their global spatial coverage, but data from remote locations indicate that ozone in the 21st century is greater than during the 1970s and 1980s. While some remote sites and many sites in the heavily polluted regions of East Asia show ozone increases since 2000, many others show decreases and there is no clear global pattern for surface ozone changes since 2000. Two new satellite products provide detailed views of ozone in the lower troposphere across East Asia and Europe, revealing the full spatial extent of the spring and summer ozone enhancements across eastern China that cannot be assessed from limited surface observations. Sufficient data are now available (ozonesondes, satellite, aircraft) across the tropics from South America eastwards to the western Pacific Ocean, to indicate a likely tropospheric column ozone increase since the 1990s. The 2014–2016 mean tropospheric ozone burden (TOB) between 60°N–60°S from five satellite products is 300 Tg ± 4%. While this agreement is excellent, the products differ in their quantification of TOB trends and further work is required to reconcile the differences. Satellites can now estimate ozone’s global long-wave radiative effect, but evaluation is difficult due to limited in situ observations where the radiative effect is greatest.Peer ReviewedPostprint (published version

Commissioning of the electron injector for the AWAKE experiment

The advanced wakefield experiment (AWAKE) at CERN is the first proton beam-driven plasma wakefield acceleration experiment. The main goal of AWAKE RUN 1 was to demonstrate seeded self-modulation (SSM) of the proton beam and electron witness beam acceleration in the plasma wakefield. For the AWAKE experiment, a 10-meter-long Rubidium-vapor cell together with a high-power laser for ionization was used to generate the plasma. The plasma wakefield is driven by a 400 GeV/c proton beam extracted from the super proton synchrotron (SPS), which undergoes a seeded self-modulation process in the plasma. The electron witness beam used to probe the wakefields is generated from an S-band RF photo-cathode gun and then accelerated by a booster structure up to energies between 16 and 20 MeV. The first run of the AWAKE experiment revealed that the maximum energy gain after the plasma cell is 2 GeV, and the SSM mechanism of the proton beam was verified. In this paper, we will present the details of the AWAKE electron injector. A comparison of the measured electron beam parameters, such as beam size, energy, and normalized emittance, with the simulation results was performed

Desarrollo y validación de una versión preliminar de la escala de competencia emocional en el deporte (ECE_D)

El importante papel que juegan las emociones en los contextos deportivos ha sido ampliamente defendido en la literatura sobre psicología del deporte. El objetivo de este estudio es desarrollar y validar un instrumento para evaluar la competencia emocional de los deportistas. La muestra la componen 367 deportistas de ambos géneros pertenecientes a diferentes disciplinas deportivas. Se analizaron los antecedentes y las características psicométricas de la Escala de Desarrollo Emocional (Schutte, Malouff, Hall, Haggerty, Cooper, Golden y Dornhein, 1998). Los resultados obtenidos confirmaron en términos generales el modelo de cuatro factores propuesto por los autores originales y además, plantea la posibilidad de incluir mejoras sustanciales del cuestionario para futuras versiones relacionadas con su aplicabilidad.The relevant role of emotions in competitive contexts has been widely supported in the sport psychology literature. The aim of this study was to create a valid measure of emotional development in sports. The sample is composed by 367 sportsmen/women belonging to different sporting disciplines. Analyses were performed about the antecedents and the psychometric properties of the Emotional Development Scale (Schutte, Malouff, Hall, Haggerty, Cooper, Golden & Dornhein, 1998). Results showed that, in general terms, the initially proposed four factor model was supported. Implications for considering the improvement of the applicability questionnaire are advance

High-order harmonic generation in Xe, Kr, and Ar driven by a 2.1-\mu m source: high-order harmonic spectroscopy under macroscopic effects

We experimentally and numerically study the atomic response and pulse propagation effects of high-order harmonics generated in Xe, Kr, and Ar driven by a 2.1-\mu m infrared femtosecond light source. The light source is an optical parametric chirped-pulse amplifier, and a modified strong-field approximation and 3-dimensional pulse propagation code are used for the numerical simulations. The extended cutoff in the long-wavelength driven high-harmonic generation has revealed the spectral shaping of high-order harmonics due to the atomic structure (or photo-recombination cross-section) and the macroscopic effects, which are the main factors of determining the conversion efficiency besides the driving wavelength. Using precise numerical simulations to determine the macroscopic electron wavepacket, we are able to extract the photo-recombination cross-sections from experimental high-order harmonic spectra in the presence of macroscopic effects. We have experimentally observed that the macroscopic effects shift the observed Cooper minimum of Kr from 80 eV to 60-70 eV and wash out the Cooper minimum of Ar. Measured high-harmonic conversion efficiencies per harmonic near the cutoff are ~10^{-9} for all three gases.Comment: 19 pages, 8 figure

Kv12-encoded K+ channels drive the day-night switch in the repetitive firing rates of SCN neurons

Considerable evidence suggests that day-night rhythms in the functional expression of subthreshold potassium (K+) channels regulate daily oscillations in the spontaneous firing rates of neurons in the suprachiasmatic nucleus (SCN), the master circadian pacemaker in mammals. The K+ conductance(s) driving these daily rhythms in the repetitive firing rates of SCN neurons, however, have not been identified. To test the hypothesis that subthreshold Kv12.1/Kv12.2-encoded K+ channels play a role, we obtained current-clamp recordings from SCN neurons in slices prepared from adult mice harboring targeted disruptions in the Kcnh8 (Kv12.1-/-) or Kcnh3 (Kv12.2-/-) locus. We found that mean nighttime repetitive firing rates were higher in Kv12.1-/- and Kv12.2-/- than in wild type (WT), SCN neurons. In marked contrast, mean daytime repetitive firing rates were similar in Kv12.1-/-, Kv12.2-/-, and WT SCN neurons, and the day-night difference in mean repetitive firing rates, a hallmark feature of WT SCN neurons, was eliminated in Kv12.1-/- and Kv12.2-/- SCN neurons. Similar results were obtained with in vivo shRNA-mediated acute knockdown of Kv12.1 or Kv12.2 in adult SCN neurons. Voltage-clamp experiments revealed that Kv12-encoded current densities in WT SCN neurons are higher at night than during the day. In addition, the pharmacological block of Kv12-encoded currents increased the mean repetitive firing rate of nighttime, but not daytime, in WT SCN neurons. Dynamic clamp-mediated subtraction of modeled Kv12-encoded currents also selectively increased the mean repetitive firing rates of nighttime WT SCN neurons. Despite the elimination of the nighttime decrease in the mean repetitive firing rates of SCN neurons, however, locomotor (wheel-running) activity remained rhythmic in Kv12.1-/-, Kv12.2-/-, and Kv12.1-targeted shRNA-expressing, and Kv12.2-targeted shRNA-expressing animals

Joint Effect of MCP-1 Genotype GG and MMP-1 Genotype 2G/2G Increases the Likelihood of Developing Pulmonary Tuberculosis in BCG-Vaccinated Individuals

We previously reported that the – 2518 MCP-1 genotype GG increases the likelihood of developing tuberculosis (TB) in non-BCG-vaccinated Mexicans and Koreans. Here, we tested the hypothesis that this genotype, alone or together with the – 1607 MMP-1 functional polymorphism, increases the likelihood of developing TB in BCG-vaccinated individuals. We conducted population-based case-control studies of BCG-vaccinated individuals in Mexico and Peru that included 193 TB cases and 243 healthy tuberculin-positive controls from Mexico and 701 TB cases and 796 controls from Peru. We also performed immunohistochemistry (IHC) analysis of lymph nodes from carriers of relevant two-locus genotypes and in vitro studies to determine how these variants may operate to increase the risk of developing active disease. We report that a joint effect between the – 2518 MCP-1 genotype GG and the – 1607 MMP-1 genotype 2G/2G consistently increases the odds of developing TB 3.59-fold in Mexicans and 3.9-fold in Peruvians. IHC analysis of lymph nodes indicated that carriers of the two-locus genotype MCP-1 GG MMP-1 2G/2G express the highest levels of both MCP-1 and MMP-1. Carriers of these susceptibility genotypes might be at increased risk of developing TB because they produce high levels of MCP-1, which enhances the induction of MMP-1 production by M. tuberculosis-sonicate antigens to higher levels than in carriers of the other two-locus MCP-1 MMP-1 genotypes studied. This notion was supported by in vitro experiments and luciferase based promoter activity assay. MMP-1 may destabilize granuloma formation and promote tissue damage and disease progression early in the infection. Our findings may foster the development of new and personalized therapeutic approaches targeting MCP-1 and/or MMP-1

How Not to Be Seen -- Inpainting Dynamic Objects in Crowded Scenes

Removing dynamic objects from videos is an extremely challenging problem that even visual effects professionals often solve with time-consuming manual frame-by-frame editing. We propose a new approach to video completion that can deal with complex scenes containing dynamic background and non-periodical moving objects. We build upon the idea that the spatio-temporal hole left by a removed object can be filled with data available on other regions of the video where the occluded objects were visible. Video completion is performed by solving a large combinatorial problem that searches for an optimal pattern of pixel offsets from occluded to unoccluded regions. Our contribution includes an energy functional that generalizes well over different scenes with stable parameters, and that has the desirable convergence properties for a graph-cut-based optimization. We provide an interface to guide the completion process that both reduces computation time and allows for efficient correction of small errors in the result. We demonstrate that our approach can effectively complete complex, high-resolution occlusions that are greater in difficulty than what existing methods have shown

Early in-flight detection of SO₂ via Differential Optical Absorption Spectroscopy: a feasible aviation safety measure to prevent potential encounters with volcanic plumes

Volcanic ash constitutes a risk to aviation, mainly due to its ability to cause jet engines to fail. Other risks include the possibility of abrasion of windshields and potentially serious damage to avionic systems. These hazards have been widely recognized since the early 1980s, when volcanic ash provoked several incidents of engine failure in commercial aircraft. In addition to volcanic ash, volcanic gases also pose a threat. Prolonged and/or cumulative exposure to sulphur dioxide (SO₂) or sulphuric acid (H₂SO₄) aerosols potentially affects e.g. windows, air frame and may cause permanent damage to engines. SO₂ receives most attention among the gas species commonly found in volcanic plumes because its presence above the lower troposphere is a clear proxy for a volcanic cloud and indicates that fine ash could also be present. <br><br> Up to now, remote sensing of SO₂ via Differential Optical Absorption Spectroscopy (DOAS) in the ultraviolet spectral region has been used to measure volcanic clouds from ground based, airborne and satellite platforms. Attention has been given to volcanic emission strength, chemistry inside volcanic clouds and measurement procedures were adapted accordingly. Here we present a set of experimental and model results, highlighting the feasibility of DOAS to be used as an airborne early detection system of SO₂ in two spatial dimensions. In order to prove our new concept, simultaneous airborne and ground-based measurements of the plume of Popocatépetl volcano, Mexico, were conducted in April 2010. The plume extended at an altitude around 5250 m above sea level and was approached and traversed at the same altitude with several forward looking DOAS systems aboard an airplane. These DOAS systems measured SO₂ in the flight direction and at &pm;40 mrad (2.3&deg;) angles relative to it in both, horizontal and vertical directions. The approaches started at up to 25 km distance to the plume and SO₂ was measured at all times well above the detection limit. In combination with radiative transfer studies, this study indicates that an extended volcanic cloud with a concentration of 10¹² molecules cm^&minus;3 at typical flight levels of 10 km can be detected unambiguously at distances of up to 80 km away. This range provides enough time (approx. 5 min) for pilots to take action to avoid entering a volcanic cloud in the flight path, suggesting that this technique can be used as an effective aid to prevent dangerous aircraft encounters with potentially ash rich volcanic clouds