Mechanism of Future Spring Drying in the Southwest U.S. in CMIP5 Models

The net surface water budget, precipitation minus evaporation (P-E), shows a clear seasonal cycle in the American Southwest with net gain of surface water (positive P-E) in the cold half of the year (October to March) and net loss of water (negative P-E) in the warm half (April – September), with June and July being the driest months of the year. There is a significant shift of the summer drying toward earlier in the year under a CO2 warming scenario, resulting in substantial spring drying (MAM) of the American Southwest, from the near-term future to the end of the current Century with gradually increasing magnitude. While the spring drying has been identified in previous studies, its mechanism has not been fully addressed. Using moisture budget analysis, we found that the drying is mainly due to decreased mean moisture convergence, partially compensated by the increase in transient eddy moisture flux convergence. The decreased mean moisture convergence is further separated into components due to changes in circulation (dynamic changes) and changes in atmospheric moisture content (thermodynamic changes). The drying is found to be dominated by the thermodynamic driven changes in column averaged moisture convergence, due mainly to increased dry zonal advection caused by the climatological land-ocean thermal contrast, rather than by the well-known “dry get drier” mechanism. Furthermore, the enhanced dry advection in the warming climate is dominated by the robust zonal mean atmospheric warming, leading to equally robust spring drying in Southwest US

Molecular Basis of DNA Repair Defects in FUS-Associated ALS: Implications of a New Paradigm and Its Potential as Therapeutic Target

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disorder, characterized by a diverse etiopathology. While ALS is predominantly sporadic, mutations in one or more of a dozen risk factors have been linked to approximately 10% of familial ALS patients. The multifunctional RNA/DNA-binding protein fused in sarcoma (FUS) is one such protein whose autosomal dominant missense mutations were identified in a subset of familial and sporadic ALS patients. Initial studies linked FUS with both RNA-related and genome maintenance functions, yet the mechanisms and potential implications to neurodegeneration were not completely understood. We recently identified a novel function of FUS in repairing single-strand break (SSB) in the genome. FUS directly interacts and recruits XRCC1/DNA Ligase IIIα (LigIII) to DNA oxidative damage sites in a PARP1 activity-dependent manner, which facilitates optimal oxidative genome damage repair. Besides, FUS regulates DNA strand break sealing by enhancing ligation activity of LigIII. The mutation of FUS induces accumulation of oxidative DNA damage as well as DNA repair deficiency in ALS patients. The novel findings provide insights into a previously undescribed mechanism of DNA repair defect in FUS-associated neurodegeneration, and raise the pentientials of developing neuroprotective therapies by targeting DNA break ligating defects

Tobacco Smoke Exposure and Altered Nasal Responses to Live Attenuated Influenza Virus

BackgroundEpidemiologic evidence links tobacco smoke and increased risk for influenza in humans, but the specific host defense pathways involved are unclear.ObjectiveWe developed a model to examine influenza-induced innate immune responses in humans and test the hypothesis that exposure to cigarette smoke alters nasal inflammatory and antiviral responses to live attenuated influenza virus (LAIV).MethodsThis was an observational cohort study comparing nasal mucosal responses to LAIV among young adult active smokers (n = 17), nonsmokers exposed to secondhand smoke (SHS; n = 20), and unexposed controls (n = 23). Virus RNA and inflammatory factors were measured in nasal lavage fluids (NLF) serially after LAIV inoculation. For key end points, peak and total (area under curve) responses were compared among groups.ResultsCompared with controls, NLF interleukin-6 (IL-6) responses to LAIV (peak and total) were suppressed in smokers. Virus RNA in NLF cells was significantly increased in smokers, as were interferon-inducible protein 10:virus ratios. Responses in SHS-exposed subjects were generally intermediate between controls and smokers. We observed significant associations between urine cotinine and NLF IL-6 responses (negative correlation) or virus RNA in NLF cells (positive correlation) for all subjects combined.ConclusionsNasal inoculation with LAIV results in measurable inflammatory and antiviral responses in human volunteers, thus providing a model for investigating environmental effects on influenza infections in humans. Exposure to cigarette smoke was associated with suppression of specific nasal inflammatory and antiviral responses, as well as increased virus quantity, after nasal inoculation with LAIV. These data suggest mechanisms for increased susceptibility to influenza infection among persons exposed to tobacco smoke

Myosin II has distinct functions in PNS and CNS myelin sheath formation

The myelin sheath forms by the spiral wrapping of a glial membrane around the axon. The mechanisms responsible for this process are unknown but are likely to involve coordinated changes in the glial cell cytoskeleton. We have found that inhibition of myosin II, a key regulator of actin cytoskeleton dynamics, has remarkably opposite effects on myelin formation by Schwann cells (SC) and oligodendrocytes (OL). Myosin II is necessary for initial interactions between SC and axons, and its inhibition or down-regulation impairs their ability to segregate axons and elongate along them, preventing the formation of a 1:1 relationship, which is critical for peripheral nervous system myelination. In contrast, OL branching, differentiation, and myelin formation are potentiated by inhibition of myosin II. Thus, by controlling the spatial and localized activation of actin polymerization, myosin II regulates SC polarization and OL branching, and by extension their ability to form myelin. Our data indicate that the mechanisms regulating myelination in the peripheral and central nervous systems are distinct

A modelling evaluation of electromagnetic fields emitted by buried subsea power cables and encountered by marine animals : considerations for marine renewable energy development

Part of this work was supported by the Bureau of Ocean Energy Management (contract number M14PC00009).The expanding marine renewable energy industry will increase the prevalence of electromagnetic fields (EMFs) from power cables in coastal waters. Assessments of environmental impacts are required within licensing/permitting processes and increased prevalence of cables will increase questions concerning EMF emissions and potential cumulative impacts. It is presumed that protecting a cable by burial, may also mitigate EMF emissions and potential impacts on species. Focussing on a bundled high voltage direct current (HVDC) transmission cable, we use computational and interpretive models to explore the influence of cable properties and burial depth on the DC magnetic field (DC-MF) potentially encountered by receptive species. Greater cable pair separation increased the deviations from the geomagnetic field and while deeper burial reduced the deviations, the DC-MF was present at intensities perceivable by receptive species. An animal moving along a cable route may be exposed to variable EMFs due to varied burial depth and that combined with an animal’s position in the water column determines the distance from source and EMF exposure. Modelling contextually realistic scenarios would improve assessments of potential effects. We suggest developers and cable industries make cable properties and energy transmission data available, enabling realistic modelling and environmental assessment supporting future developments.PostprintPeer reviewe

Reading In-Between the Lines: An Analysis of Dissenter

Efforts by content creators and social networks to enforce legal and policy-based norms, e.g. blocking hate speech and users, has driven the rise of unrestricted communication platforms. One such recent effort is Dissenter, a browser and web application that provides a conversational overlay for any web page. These conversations hide in plain sight - users of Dissenter can see and participate in this conversation, whereas visitors using other browsers are oblivious to their existence. Further, the website and content owners have no power over the conversation as it resides in an overlay outside their control. In this work, we obtain a history of Dissenter comments, users, and the websites being discussed, from the initial release of Dissenter in Feb. 2019 through Apr. 2020 (14 months). Our corpus consists of approximately 1.68M comments made by 101k users commenting on 588k distinct URLs. We first analyze macro characteristics of the network, including the user-base, comment distribution, and growth. We then use toxicity dictionaries, Perspective API, and a Natural Language Processing model to understand the nature of the comments and measure the propensity of particular websites and content to elicit hateful and offensive Dissenter comments. Using curated rankings of media bias, we examine the conditional probability of hateful comments given left and right-leaning content. Finally, we study Dissenter as a social network, and identify a core group of users with high comment toxicity.Comment: Accepted at IMC 202

Temporal structure/function variation in cultured differentiated human nasal epithelium associated with acute single exposure to tobacco smoke or E-cigarette vapor

Mucociliary clearance sustains a baseline functionality and an “on demand” capability to upregulate clearance upon irritant exposure involving mucus hypersecretion and accelerated ciliary beat frequency (CBF) modulated by nitric oxide (NO). This study characterized these elements as well as cellular and exogenous NO concentrations subsequent to a single exposure to tobacco smoke (TS) or e-cigarette vapor (EV) on cultured human airway epithelium

Alteration of the nasal responses to influenza virus by tobacco smoke

The purpose of this review is to highlight recent data regarding the impact of exposure to tobacco smoke on influenza virus infection. This is timely because of the continuing pattern for influenza to cause epidemics and pandemics

Synthesis and Interactions of 7-Deoxy-, 10-Deacetoxy, and 10-Deacetoxy-7-Deoxypaclitaxel with NCI/ADR-RES Cancer Cells and Bovine Brain Microvessel Endothelial Cells

Please note that this is an author-produced PDF of an article accepted for publication following peer review. The publisher version is available on its site.7-Deoxypaclitaxel, 10-deacetoxypaclitaxel and 10-deacetoxy-7-deoxypaclitaxel were prepared and evaluated for their ability to promote assembly of tubulin into microtubules, their cytotoxicity against NCI/ADR-RES cells and for their interactions with Pglycoprotein in bovine brain microvessel endothelial cells. The three compounds were essentially equivalent to paclitaxel in cytotoxicity against NCI/ADR-RES cells. They also appeared to interact with P-glycoprotein in the endothelial cells with the two 10-deacetoxy compounds having less interaction than paclitaxel and 7-deoxypaclitaxel. ©2000 Elsevier Science Ltd. All rights reserved