Lung cancer is the leading cause of cancer related deaths and its incidence is highly correlated with cigarette smoking. Nicotine, the addictive component of tobacco smoke, cannot initiate tumors, ...but can promote proliferation, migration, and invasion of cells in vitro and promote tumor growth and metastasis in vivo. This nicotine-mediated tumor promotion is facilitated through the activation of nicotinic acetylcholine receptors (nAChRs), specifically the α7 subunit. More recently, nicotine has been implicated in promoting self-renewal of stem-like side-population cells from lung cancers. This subpopulation of cancer stem-like cells has been implicated in tumor initiation, generation of the heterogeneous tumor population, metastasis, dormancy, and drug resistance. Here we describe the molecular events driving nicotine and e-cigarette extract mediated stimulation of self-renewal of stem-like cells from non-small cell lung cancer.
Experiments were conducted using A549 and H1650 non-small cell lung cancer cell lines and human mesenchymal stem cells according to protocols described in this paper. 2 μM nicotine or e-cigarette extracts was used in all relevant experiments. Biochemical analysis using western blotting, transient transfections, RT-PCR and cell biological analysis using double immunofluorescence and confocal microscopy, as well as proximity ligation assays were conducted.
Here we demonstrate that nicotine can induce the expression of embryonic stem cell factor Sox2, which is indispensable for self-renewal and maintenance of stem cell properties in non-small cell lung adenocarcinoma (NSCLC) cells. We further demonstrate that this occurs through a nAChR-Yap1-E2F1 signaling axis downstream of Src and Yes kinases. Our data suggests Oct4 may also play a role in this process. Over the past few years, electronic cigarettes (e-cigarettes) have been promoted as healthier alternatives to traditional cigarette smoking as they do not contain tobacco; however, they do still contain nicotine. Hence we have investigated whether e-cigarette extracts can enhance tumor promoting properties similar to nicotine; we find that they can induce expression of Sox2 as well as mesenchymal markers and enhance migration and stemness of NSCLC cells.
Our findings shed light on novel molecular mechanisms underlying the pathophysiology of smoking-related lung cancer in the context of cancer stem cell populations, and reveal new pathways involved that could potentially be exploited therapeutically.
Terrestrial gamma‐ray flashes (TGFs) are bright, sub‐millisecond bursts of gamma‐rays, originating within the Earth's atmosphere. Most TGFs have been detected by spacecraft in low‐Earth orbit. Only ...two TGFs have previously been observed from within our atmosphere: one at ground level and one from an aircraft at 14.1 km. We report on a new TGF‐like gamma‐ray flash observed at ground level, detected by the 19‐station Thunderstorm Energetic Radiation Array (TERA) at the University of Florida/Florida Tech International Center for Lightning Research and Testing (ICLRT). The gamma‐ray flash, which had a duration of 52.7 μs, occurred on June 30, 2009 during a natural negative cloud‐to‐ground lightning return stroke, 191 μs after the start of the stroke. This event is the first definitive association of a gamma‐ray flash with natural CG lightning and is among the most direct links to a specific lightning process so far. For this event, 19 gamma‐rays were recorded, with the highest energy exceeding 20 MeV. The high‐energy radiation exhibited very different behavior from the typical x‐ray emission from lightning. Specifically, the gamma‐ray flash had a much harder energy spectrum, consistent with relativistic runaway electron avalanche (RREA) multiplication; it did not arrive in sub‐microsecond bursts, typical of leader emission from lightning, and it occurred well after the start of the return stroke, which has not been previously observed for the x‐ray emission from lightning. Nevertheless, we present evidence that the source region for the gamma ray flash was the same as that for the preceding leader x‐ray bursts.
Key Points
New observation of a ground level TGF
Third such event ever seen from within our atmosphere
First seen during a natural lightning return stroke
Abstract
Monolayer transition metal dichalcogenides (TMD) have numerous potential applications in ultrathin electronics and photonics. The exposure of TMD-based devices to light generates ...photo-carriers resulting in an enhanced conductivity, which can be effectively used, e.g., in photodetectors. If the photo-enhanced conductivity persists after removal of the irradiation, the effect is known as persistent photoconductivity (PPC). Here we show that ultraviolet light (λ = 365 nm) exposure induces an extremely long-living giant PPC (GPPC) in monolayer MoS
2
(ML-MoS
2
) field-effect transistors (FET) with a time constant of ~30 days. Furthermore, this effect leads to a large enhancement of the conductivity up to a factor of 10
7
. In contrast to previous studies in which the origin of the PPC was attributed to extrinsic reasons such as trapped charges in the substrate or adsorbates, we show that the GPPC arises mainly from the intrinsic properties of ML-MoS
2
such as lattice defects that induce a large number of localized states in the forbidden gap. This finding is supported by a detailed experimental and theoretical study of the electric transport in TMD based FETs as well as by characterization of ML-MoS
2
with scanning tunneling spectroscopy, high-resolution transmission electron microscopy, and photoluminescence measurements. The obtained results provide a basis for the defect-based engineering of the electronic and optical properties of TMDs for device applications.
Energetic radiation is known to be produced by lightning. To investigate these emissions, ground‐based observations are being conducted at the International Center for Lightning Research and Testing ...(ICLRT) at Camp Blanding, FL where measurements of energetic radiation from both natural and rocket‐triggered lightning discharges are recorded. In the present study, data from two natural negative cloud‐to‐ground stepped leaders and one rocket‐triggered “chaotic” dart leader are analyzed in detail to investigate X‐ray energy spectra and spatial X‐ray distributions around the source. These measurements are compared with Monte Carlo simulations of runaway electron propagation with the goal of understanding the underlying mechanism of runaway electron production and their role in lightning initiation and propagation. We show that the energetic electrons that produce X‐rays exhibit a characteristic energy less than 3 MeV for two natural and one rocket‐triggered leaders investigated. In addition to studying these three leaders, energetic electron luminosity, total energy, and energetic electron per meter are compared to the following return stroke currents for 28 leaders from 12 different triggered flashes. Electron luminosity is found to increase exponentially with return stroke current up to about 10 kA and to be roughly constant for larger currents. The maximum electron luminosity, which is determined indirectly through X‐ray luminosities, is on the order of 1017 electrons/s, which is less than the value found from theoretical calculations.
Key Points
To present new X‐ray observations from natural and rocket‐triggered lightning
Electron luminosity was compared to the return stroke currents for 28 leaders
Energetic electrons exhibit a characteristic energy less than 3 MeV
Fish hatcheries are widely used to enhance fisheries and supplement declining wild populations. However, substantial evidence suggests that hatchery fish are subject to differential selection ...pressures compared to their wild counterparts. Domestication selection, or adaptation to the hatchery environment, poses a risk to wild populations if traits specific to success in the hatchery environment have a genetic component and there is subsequent introgression between hatchery and wild fish. Few studies have investigated domestication selection in hatcheries on a genomic level, and even fewer have done so in parallel across multiple hatchery–wild population pairs. In this study, we used low‐coverage whole‐genome sequencing to investigate signals of domestication selection in three separate hatchery populations of Chinook salmon, Oncorhynchus tshawytscha, after approximately seven generations of divergence from their corresponding wild progenitor populations. We sequenced 192 individuals from populations across Southeast Alaska and estimated genotype likelihoods at over six million loci. We discovered a total of 14 outlier peaks displaying high genetic differentiation (FST) between hatchery–wild pairs, although no peaks were shared across the three comparisons. Peaks were small (53 kb on average) and often displayed elevated absolute genetic divergence (Dxy) and linkage disequilibrium, suggesting some level of domestication selection has occurred. Our study provides evidence that domestication selection can lead to genetic differences between hatchery and wild populations in only a few generations. Additionally, our data suggest that population‐specific adaptation to hatchery environments likely occurs through different genetic pathways, even for populations with similar standing genetic variation. These results highlight the need to collect paired genotype–phenotype data to understand how domestication may be affecting fitness and to identify potential management practices that may mitigate genetic risks despite multiple pathways of domestication.
Abstract
Genomic methods are becoming increasingly valuable and established in ecological research, particularly in nonmodel species. Supporting their progress and adoption requires investment in ...resources that promote (i) reproducibility of genomic analyses, (ii) accessibility of learning tools and (iii) keeping pace with rapidly developing methods and principles.
We introduce marineomics.io, an open‐source, living document to disseminate tutorials, reproducibility tools and best principles for ecological genomic research in marine and nonmodel systems.
The website's existing content spans population and functional genomics, including current recommendations for whole‐genome sequencing, RAD‐seq, Pool‐seq and RNA‐seq. With the goal to facilitate the development of new, similar resources, we describe our process for aggregating and synthesizing methodological principles from the ecological genomics community to inform website content. We also detail steps for authorship and submission of new website content, as well as protocols for providing feedback and topic requests from the community.
These web resources were constructed with guidance for doing rigorous, reproducible science. Collaboration and contributions to the website are encouraged from scientists of all skill sets and levels of expertise.
Across many species where inversions have been implicated in local adaptation, genomes often evolve to contain multiple, large inversions that arise early in divergence. Why this occurs has yet to be ...resolved. To address this gap, we built forward-time simulations in which inversions have flexible characteristics and can invade a metapopulation undergoing spatially divergent selection for a highly polygenic trait. In our simulations, inversions typically arose early in divergence, captured standing genetic variation upon mutation, and then accumulated many small-effect loci over time. Under special conditions, inversions could also arise late in adaptation and capture locally adapted alleles. Polygenic inversions behaved similarly to a single supergene of large effect and were detectable by genome scans. Our results show that characteristics of adaptive inversions found in empirical studies (e.g. multiple large, old inversions that are
outliers, sometimes overlapping with other inversions) are consistent with a highly polygenic architecture, and inversions do not need to contain any large-effect genes to play an important role in local adaptation. By combining a population and quantitative genetic framework, our results give a deeper understanding of the specific conditions needed for inversions to be involved in adaptation when the genetic architecture is polygenic. This article is part of the theme issue 'Genomic architecture of supergenes: causes and evolutionary consequences'.
Adaptation to environmental conditions, and the mechanisms underlying these adaptations, can vary greatly among species. This variation can be attributed to a variety of factors including the ...strength of evolutionary processes like selection, gene flow, time since divergence, and/or genetic drift, as well as the interactions between these processes. A number of simulation and theoretical studies have helped elucidate the role of these processes on the genomic basis of adaptation (Schaal et al., 2022; Yeaman et al., 2016). However, complementary empirical studies to test these theoretical expectations for within‐species adaptation have been limited due to the challenging nature of evaluating these processes in a comparative framework. To do this effectively, it is necessary to have systems where the range of environmental variation is similar between species, but where one or more of these evolutionary processes vary. In a From the Cover article in this issue of Molecular Ecology, Shi et al. (2022) provide an excellent example of a freshwater system where rates of gene flow differ between populations of six riverine species due to variation in spawning strategies (i.e., broadcast spawners = high gene flow, nest spawners = low gene flow), but all experience the same variation in environmental conditions across their distributions. The authors take a multivariate approach to evaluate the genomic basis of adaptation by using a combination of differentiation‐based and genotype‐environment association (GEA) methods. By comparing the amount of gene flow between species and the resulting genomic basis of local adaptation, they are able to infer how genomic architecture may be shaped by rates of gene flow. Their results identify a general pattern of increased genomic clustering in species with increasing levels of gene flow. However, two of six species did not follow this pattern, which could be due to additional factors not assessed. Additionally, they provide convincing evidence that the underlying evolutionary mechanisms that formed genomic clusters within each species vary. These deviations from a general pattern highlight how difficult evaluating these processes in natural populations are, particularly because species‐specific responses can vary dramatically. Taken together, their comparative framework for assessing the genomic architecture of adaptation is unique, sheds important light on how evolutionary processes can impact adaptation, and provides robust empirical support of foundational theoretical and simulation studies.
We report on the first search for Terrestrial Gamma‐ray Flashes (TGFs) from altitudes where they are thought to be produced. The Airborne Detector for Energetic Lightning Emissions (ADELE), an array ...of gamma‐ray detectors, was flown near the tops of Florida thunderstorms in August/September 2009. The plane passed within 10 km horizontal distance of 1213 lightning discharges and only once detected a TGF. If these discharges had produced TGFs of the same intensity as those seen from space, every one should have been seen by ADELE. Separate and significant nondetections are established for intracloud lightning, negative cloud‐to‐ground lightning, and narrow bipolar events. We conclude that TGFs are not a primary triggering mechanism for lightning. We estimate the TGF‐to‐flash ratio to be on the order of 10−2 to 10−3 and show that TGF intensities cannot follow the well‐known power‐law distribution seen in earthquakes and solar flares, due to our limits on the presence of faint events.
Key Points
TGFs are not associated with most lightning flashes
Therefore TGFs are not an important lightning trigger
There is no large population of “mini” TGFs
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