298 research outputs found

    Multidrug resistance phenotypes and MRS2 mitochondrial magnesium channel: two players from one stemness?

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    Commentary to:Human mitochondrial Mrs2 protein promotes multidrug resistance in gastric cancer cells by regulating p27, cyclin D1 expression and cytochrome C releaseYu Chen, Xufeng Wei, Pengfei Yan, Ying Han , Kai-Chun Wu, Shiren Sun, Daiming Fa

    Age-dependent modifications of expression level of VEGF and its receptors in the inner ear

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    The mechanisms responsible for age-associated hearing loss are still incompletely characterized. In this study, we used a murine model of age-dependent hearing loss and evaluated whether this condition is associated with vascular modifications of the structures of the inner ear. We used old C57BL/6J mice that are affected by rapid and severe age-related hearing loss, and analyzed the expression pattern of vascular endothelial growth factor (VEGF), a prototypical angiogenic cytokine, and its receptors Flt-1 and Flk-1 in the inner ear. We report for the first time morphological and quantitative data about the expression of these crucial angiogenic molecules in the murine cochlea. We also show that in this animal model, cochlear VEGF expression is significantly reduced as a function of age. Our findings provide new evidence of possible interdependent relationships between aging, VEGF, and presbycusis, suggesting that vascular abnormalities might play a role in aging-associated hearing loss, with potentially important fundamental and clinical implications. (C) 2004 Elsevier Inc. All rights reserved

    Deep Drilling in the Time Domain with DECam: Survey Characterization

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    This paper presents a new optical imaging survey of four deep drilling fields (DDFs), two Galactic and two extragalactic, with the Dark Energy Camera (DECam) on the 4 meter Blanco telescope at the Cerro Tololo Inter-American Observatory (CTIO). During the first year of observations in 2021, >>4000 images covering 21 square degrees (7 DECam pointings), with ∌\sim40 epochs (nights) per field and 5 to 6 images per night per filter in gg, rr, ii, and/or zz, have become publicly available (the proprietary period for this program is waived). We describe the real-time difference-image pipeline and how alerts are distributed to brokers via the same distribution system as the Zwicky Transient Facility (ZTF). In this paper, we focus on the two extragalactic deep fields (COSMOS and ELAIS-S1), characterizing the detected sources and demonstrating that the survey design is effective for probing the discovery space of faint and fast variable and transient sources. We describe and make publicly available 4413 calibrated light curves based on difference-image detection photometry of transients and variables in the extragalactic fields. We also present preliminary scientific analysis regarding Solar System small bodies, stellar flares and variables, Galactic anomaly detection, fast-rising transients and variables, supernovae, and active galactic nuclei.Comment: 22 pages, 17 figures, 2 tables. Accepted to MNRA

    Molecular evolution of a gene cluster of serine proteases expressed in the Anopheles gambiae female reproductive tract

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    <p>Abstract</p> <p>Background</p> <p>Genes involved in post-mating processes of multiple mating organisms are known to evolve rapidly due to coevolution driven by sexual conflict among male-female interacting proteins. In the malaria mosquito <it>Anopheles gambiae </it>- a monandrous species in which sexual conflict is expected to be absent or minimal - recent data strongly suggest that proteolytic enzymes specifically expressed in the female lower reproductive tissues are involved in the processing of male products transferred to females during mating. In order to better understand the role of selective forces underlying the evolution of proteins involved in post-mating responses, we analysed a cluster of genes encoding for three serine proteases that are down-regulated after mating, two of which specifically expressed in the atrium and one in the spermatheca of <it>A. gambiae </it>females.</p> <p>Results</p> <p>The analysis of polymorphisms and divergence of these female-expressed proteases in closely related species of the <it>A. gambiae </it>complex revealed a high level of replacement polymorphisms consistent with relaxed evolutionary constraints of duplicated genes, allowing to rapidly fix novel replacements to perform new or more specific functions. Adaptive evolution was detected in several codons of the 3 genes and hints of episodic selection were also found. In addition, the structural modelling of these proteases highlighted some important differences in their substrate specificity, and provided evidence that a number of sites evolving under selective pressures lie relatively close to the catalytic triad and/or on the edge of the specificity pocket, known to be involved in substrate recognition or binding. The observed patterns suggest that these proteases may interact with factors transferred by males during mating (e.g. substrates, inhibitors or pathogens) and that they may have differently evolved in independent <it>A. gambiae </it>lineages.</p> <p>Conclusions</p> <p>Our results - also examined in light of constraints in the application of selection-inference methods to the closely related species of the <it>A. gambiae </it>complex - reveal an unexpectedly intricate evolutionary scenario. Further experimental analyses are needed to investigate the biological functions of these genes in order to better interpret their molecular evolution and to assess whether they represent possible targets for limiting the fertility of <it>Anopheles </it>mosquitoes in malaria vector control strategies.</p

    Search for massive resonances in dijet systems containing jets tagged as W or Z boson decays in pp collisions at √s=8 TeV

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    Peer reviewe

    Multimessenger Gamma-Ray and Neutrino Coincidence Alerts using HAWC and IceCube sub-threshold Data

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    The High Altitude Water Cherenkov (HAWC) and IceCube observatories, through the Astrophysical Multimessenger Observatory Network (AMON) framework, have developed a multimessenger joint search for extragalactic astrophysical sources. This analysis looks for sources that emit both cosmic neutrinos and gamma rays that are produced in photo-hadronic or hadronic interactions. The AMON system is running continuously, receiving sub-threshold data (i.e. data that is not suited on its own to do astrophysical searches) from HAWC and IceCube, and combining them in real-time. We present here the analysis algorithm, as well as results from archival data collected between June 2015 and August 2018, with a total live-time of 3.0 years. During this period we found two coincident events that have a false alarm rate (FAR) of <1<1 coincidence per year, consistent with the background expectations. The real-time implementation of the analysis in the AMON system began on November 20th, 2019, and issues alerts to the community through the Gamma-ray Coordinates Network with a FAR threshold of <4<4 coincidences per year.Comment: 14 pages, 5 figures, 3 table

    Search for Quantum Gravity Using Astrophysical Neutrino Flavour with IceCube

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    Along their long propagation from production to detection, neutrino states undergo quantum interference which converts their types, or flavours. High-energy astrophysical neutrinos, first observed by the IceCube Neutrino Observatory, are known to propagate unperturbed over a billion light years in vacuum. These neutrinos act as the largest quantum interferometer and are sensitive to the smallest effects in vacuum due to new physics. Quantum gravity (QG) aims to describe gravity in a quantum mechanical framework, unifying matter, forces and space-time. QG effects are expected to appear at the ultra-high-energy scale known as the Planck energy, EP≡1.22×1019E_{P}\equiv 1.22\times 10^{19}~giga-electronvolts (GeV). Such a high-energy universe would have existed only right after the Big Bang and it is inaccessible by human technologies. On the other hand, it is speculated that the effects of QG may exist in our low-energy vacuum, but are suppressed by the Planck energy as EP−1E_{P}^{-1} (∌10−19\sim 10^{-19}~GeV−1^{-1}), EP−2E_{P}^{-2} (∌10−38\sim 10^{-38}~GeV−2^{-2}), or its higher powers. The coupling of particles to these effects is too small to measure in kinematic observables, but the phase shift of neutrino waves could cause observable flavour conversions. Here, we report the first result of neutrino interferometry~\cite{Aartsen:2017ibm} using astrophysical neutrino flavours to search for new space-time structure. We did not find any evidence of anomalous flavour conversion in IceCube astrophysical neutrino flavour data. We place the most stringent limits of any known technologies, down to 10−4210^{-42}~GeV−2^{-2}, on the dimension-six operators that parameterize the space-time defects for preferred astrophysical production scenarios. For the first time, we unambiguously reach the signal region of quantum-gravity-motivated physics.Comment: The main text is 7 pages with 3 figures and 1 table. The Appendix includes 5 pages with 3 figure

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

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    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 ≳1014^{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 (≳1014^{14} M⊙) to be no more than 4.6% of the diffuse IceCube observations at 100 TeV, assuming an unbroken E−2.5^{2.5} power-law spectrum
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