Inhibition of HERG1 K+ channel protein expression decreases cell proliferation of human small cell lung cancer cells

HERG (human ether-à-go-go-related gene) K+ currents fulfill important ionic functions in cardiac and other excitable cells. In addition, HERG channels influence cell growth and migration in various types of tumor cells. The mechanisms underlying these functions are still not resolved. Here, we investigated the role of HERG channels for cell growth in a cell line (SW2) derived from small cell lung cancer (SCLC), a malignant variant of lung cancer. The two HERG1 isoforms (HERG1a, HERG1b) as well as HERG2 and HERG3 are expressed in SW2 cells. Inhibition of HERG currents by acute or sustained application of E-4031, a specific ERG channel blocker, depolarized SW2 cells by 10–15 mV. This result indicated that HERG K+ conductance contributes considerably to the maintenance of the resting potential of about −45 mV. Blockage of HERG channels by E-4031 for up to 72 h did not affect cell proliferation. In contrast, siRNA-induced inhibition of HERG1 protein expression decreased cell proliferation by about 50%. Reduction of HERG1 protein expression was confirmed by Western blots. HERG current was almost absent in SW2 cells transfected with siRNA against HERG1. Qualitatively similar results were obtained in three other SCLC cell lines (OH1, OH3, H82), suggesting that the HERG1 channel protein is involved in SCLC cell growth, whereas the ion-conducting function of HERG1 seems not to be important for cell growth

DISC1 genetics, biology and psychiatric illness

Psychiatric disorders are highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points towards DISC1 being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain

First Search for Unstable Sterile Neutrinos with the IceCube Neutrino Observatory

We present a search for an unstable sterile neutrino by looking for a matter-induced signal in eight years of atmospheric $\nu_\mu$ data collected from 2011 to 2019 at the IceCube Neutrino Observatory. Both the (stable) three-neutrino and the 3+1 sterile neutrino models are disfavored relative to the unstable sterile neutrino model, though with $p$-values of 2.5\% and 0.81\%, respectively, we do not observe evidence for 3+1 neutrinos with neutrino decay. The best-fit parameters for the sterile neutrino with decay model from this study are $\Delta m_{41}^2=6.7^{+3.9}_{-2.5}\,\rm{eV}^2$, $\sin^2 2\theta_{24}=0.33^{+0.20}_{-0.17}$, and $g^2=2.5\pi\pm1.5\pi$, where $g$ is the decay-mediating coupling. The preferred regions from short-baseline oscillation searches are excluded at 90\% C.L

Observation of high-energy neutrinos from the Galactic plane

The origin of high-energy cosmic rays, atomic nuclei that continuously impact Earth's atmosphere, has been a mystery for over a century. Due to deflection in interstellar magnetic fields, cosmic rays from the Milky Way arrive at Earth from random directions. However, near their sources and during propagation, cosmic rays interact with matter and produce high-energy neutrinos. We search for neutrino emission using machine learning techniques applied to ten years of data from the IceCube Neutrino Observatory. We identify neutrino emission from the Galactic plane at the 4.5$\sigma$ level of significance, by comparing diffuse emission models to a background-only hypothesis. The signal is consistent with modeled diffuse emission from the Galactic plane, but could also arise from a population of unresolved point sources.Comment: Submitted on May 12th, 2022; Accepted on May 4th, 202

A Combined Fit of the Diffuse Neutrino Spectrum using IceCube Muon Tracks and Cascades

The IceCube Neutrino Observatory first observed a diffuse flux of high energy astrophysical neutrinos in 2013. Since then, this observation has been confirmed in multiple detection channels such as high energy starting events, cascades, and through-going muon tracks. Combining these event selections into a high statistics global fit of 10 years of IceCube’s neutrino data could strongly improve the understanding of the diffuse astrophysical neutrino flux: challenging or confirming the simple unbroken power-law flux model as well as the astrophysical neutrino flux composition. One key component of such a combined analysis is the consistent modelling of systematic uncertainties of different event selections. This can be achieved using the novel SnowStorm Monte Carlo method which allows constraints to be placed on multiple systematic parameters from a single simulation set. We will report on the status of a new combined analysis of through-going muon tracks and cascades. It is based on a consistent all flavor neutrino signal and background simulation using, for the first time, the SnowStorm method to analyze IceCube’s high-energy neutrino data. Estimated sensitivities for the energy spectrum of the diffuse astrophysical neutrino flux will be shown

Searching for eV-scale sterile neutrinos with eight years of atmospheric neutrinos at the IceCube Neutrino Telescope

We report in detail on searches for eV-scale sterile neutrinos, in the context of a 3+1 model, using eight years of data from the IceCube Neutrino Telescope. By analyzing the reconstructed energies and zenith angles of 305,735 atmospheric νμ and ¯νμ events we construct confidence intervals in two analysis spaces: sin2(2θ$_{24}$) vs Δm2¦41 under the conservative assumption θ$_{34}$=0; and sin$^{2}$ (2θ$_{24}$) vs sin$^{2}$ (2θ$_{34}$) given sufficiently large Δm2¦41 that fast oscillation features are unresolvable. Detailed discussions of the event selection, systematic uncertainties, and fitting procedures are presented. No strong evidence for sterile neutrinos is found, and the best-fit likelihood is consistent with the no sterile neutrino hypothesis with a p value of 8% in the first analysis space and 19% in the second

Searches for Neutrinos from Gamma-Ray Bursts Using the IceCube Neutrino Observatory

Gamma-ray bursts (GRBs) are considered as promising sources of ultra-high-energy cosmic rays (UHECRs) due to their large power output. Observing a neutrino flux from GRBs would offer evidence that GRBs are hadronic accelerators of UHECRs. Previous IceCube analyses, which primarily focused on neutrinos arriving in temporal coincidence with the prompt gamma-rays, found no significant neutrino excess. The four analyses presented in this paper extend the region of interest to 14 days before and after the prompt phase, including generic extended time windows and targeted precursor searches. GRBs were selected between 2011 May and 2018 October to align with the data set of candidate muon-neutrino events observed by IceCube. No evidence of correlation between neutrino events and GRBs was found in these analyses. Limits are set to constrain the contribution of the cosmic GRB population to the diffuse astrophysical neutrino flux observed by IceCube. Prompt neutrino emission from GRBs is limited to ≲1% of the observed diffuse neutrino flux, and emission on timescales up to 10$^{4}$ s is constrained to 24% of the total diffuse flux

Searching for High-energy Neutrino Emission from Galaxy Clusters with IceCube

Galaxy clusters have the potential to accelerate cosmic rays (CRs) to ultrahigh energies via accretion shocks or embedded CR acceleration sites. The CRs with energies below the Hillas condition will be confined within the cluster and eventually interact with the intracluster medium gas to produce secondary neutrinos and gamma rays. Using 9.5 yr of muon neutrino track events from the IceCube Neutrino Observatory, we report the results of a stacking analysis of 1094 galaxy clusters with masses ≳10$^{14}$ M⊙ and redshifts between 0.01 and ∼1 detected by the Planck mission via the Sunyaev–Zel’dovich effect. We find no evidence for significant neutrino emission and report upper limits on the cumulative unresolved neutrino flux from massive galaxy clusters after accounting for the completeness of the catalog up to a redshift of 2, assuming three different weighting scenarios for the stacking and three different power-law spectra. Weighting the sources according to mass and distance, we set upper limits at a 90% confidence level that constrain the flux of neutrinos from massive galaxy clusters (≳10$^{14}$ M⊙) to be no more than 4.6% of the diffuse IceCube observations at 100 TeV, assuming an unbroken E−$^{2.5}$ power-law spectrum

Searches for Neutrinos from Gamma-Ray Bursts using the IceCube Neutrino Observatory

Gamma-ray bursts (GRBs) are considered as promising sources of ultra-high-energy cosmic rays (UHECRs) due to their large power output. Observing a neutrino flux from GRBs would offer evidence that GRBs are hadronic accelerators of UHECRs. Previous IceCube analyses, which primarily focused on neutrinos arriving in temporal coincidence with the prompt gamma rays, found no significant neutrino excess. The four analyses presented in this paper extend the region of interest to 14 days before and after the prompt phase, including generic extended time windows and targeted precursor searches. GRBs were selected between May 2011 and October 2018 to align with the data set of candidate muon-neutrino events observed by IceCube. No evidence of correlation between neutrino events and GRBs was found in these analyses. Limits are set to constrain the contribution of the cosmic GRB population to the diffuse astrophysical neutrino flux observed by IceCube. Prompt neutrino emission from GRBs is limited to $\lesssim$1% of the observed diffuse neutrino flux, and emission on timescales up to $10^4$ s is constrained to 24% of the total diffuse flux