401 research outputs found

    Wyoming

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    In 2019, Wyoming ranked eighth nationally in both crude oil and natural gas production. Sales of crude oil production totaled 101.8 million barrels, up 16% from 2018, while natural gas production totaled 1.456 trillion cubic feet, which was down 8.52% from 2018.1 However, as of August 1, 2020, Wyoming had zero oil and natural rigs in operation for the first time since 1884

    Axonal stress kinase activation and tau misbehavior induced by kinesin-1 transport defects

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    Many neurodegenerative diseases exhibit axonal pathology, transport defects, and aberrant phosphorylation and aggregation of the microtubule binding protein tau. While mutant tau protein in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP17) causes aberrant microtubule binding and assembly of tau into filaments, the pathways leading to tau-mediated neurotoxicity in Alzheimer's disease and other neurodegenerative disorders in which tau protein is not genetically modified remain unknown. To test the hypothesis that axonal transport defects alone can cause pathological abnormalities in tau protein and neurodegeneration in the absence of mutant tau or amyloid β deposits, we induced transport defects by deletion of the kinesin light chain 1 (KLC1) subunit of the anterograde motor kinesin-1. We found that upon aging, early selective axonal transport defects in mice lacking the KLC1 protein (KLC1-/-) led to axonopathies with cytoskeletal disorganization and abnormal cargo accumulation. In addition, increased c-jun N-terminal stress kinase activation colocalized with aberrant tau in dystrophic axons. Surprisingly, swollen dystrophic axons exhibited abnormal tau hyperphosphorylation and accumulation. Thus, directly interfering with axonal transport is sufficient to activate stress kinase pathways initiating a biochemical cascade that drives normal tau protein into a pathological state found in a variety of neurodegenerative disorders including Alzheimer's disease.Fil: Falzone, Tomas Luis. Howard Hughes Medical Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Stokin, Gorazd B.. University Psychiatric Hospital; EsloveniaFil: Lillo, Concepción. University of California at San Diego; Estados UnidosFil: Rodrigues, Elizabeth M.. Howard Hughes Medical Institute; Estados UnidosFil: Westerman, Eileen L.. Howard Hughes Medical Institute; Estados UnidosFil: Williams, David S.. University of California at San Diego; Estados UnidosFil: Goldstein, Lawrence S. B.. Howard Hughes Medical Institute; Estados Unido

    High precision tilt observation at Mt. Etna Volcano, Italy

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    In 2007-2008, we installed on Mt. Etna two deep tilt stations using high resolution, self-leveling instruments. These installations are the result of accurate instrument tests, site selection, drilling and sensor positioning that has allowed detecting variations related to the principal diurnal and semidiurnal tides for first time on Mt. Etna using tilt data. We analyzed the tidal effects recorded on tilt signals and we removed tidal effects from signals, thereby allowing to detect changes of about 20 nanoradians with a considerable improvement respect to the previous installation. Tilt changes have accompanied the Mt. Etna main eruptive phases and are generally related to the rapid rise of magma and formation of dikes and eruptive fissures. However, tilt changes characterize lava fountains, earthquakes and inflation-deflation phases. The 2008-2009 eruption represents an example of the potential of these tiltmeters providing new perspectives for highly precise monitoring of ground deformation on volcanoes

    INSTALLAZIONE DI UN CLINOMETRO AD ALTA PRECISIONE IN AREA TETTONICA (SETTORE NORD-ORIENTALE DELL’ALTIPIANO IBLEO)

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    In questo rapporto sono riportati i dettagli dell’installazione di un clinometro profondo effettuata nel 2010 in prossimità di Pedagaggi (SR) nel settore nord-orientale dell’altipiano ibleo. L'installazione è stata possibile utilizzando uno strumento digitale autolivellante modello AGI (Applied Geomechanics Incorporated) Lily, con sensibilità pari a 0.005 microradianti. Sono illustrati i dettagli dell’installazione ed i primi dati che evidenziano la loro ottima qualità, la presenza delle componenti mareali e la minima variazione di inclinazione ottenibile ripulendo il segnale dalle stesse

    Cancer management during COVID-19 pandemic: is immune checkpoint inhibitors-based immunotherapy harmful or beneficial?

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    The coronavirus disease 2019 (COVID-19) is currently representing a global health threat especially for fragile individuals, such as cancer patients. It was demonstrated that cancer patients have an increased risk of developing a worse symptomatology upon severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) infection, often leading to hospitalization and intensive care. The consequences of this pandemic for oncology are really heavy, as the entire healthcare system got reorganized. Both oncologists and cancer patients are experiencing rescheduling of treatments and disruptions of appointments with a concurrent surge of fear and stress. In this review all the up-to-date findings, concerning the association between COVID-19 and cancer, are reported. A remaining very debated question regards the use of an innovative class of anti-cancer molecules, the immune checkpoint inhibitors (ICIs), given their modulating effects on the immune system. For that reason, administration of ICIs to cancer patients represents a question mark during this pandemic, as its correlation with COVID-19-associated risks is still under investigation. Based on the mechanisms of action of ICIs and the current evidence, we suggest that ICIs not only can be safely administered to cancer patients, but they might even be beneficial in COVID-19-positive cancer patients, by exerting an immune-stimulating action

    Dopamine D 4 Receptor-Deficient Mice Display Cortical Hyperexcitability

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    The dopamine D(4) receptor (D(4)R) is predominantly expressed in the frontal cortex (FC), a brain region that receives dense input from midbrain dopamine (DA) neurons and is associated with cognitive and emotional processes. However, the physiological significance of this dopamine receptor subtype has been difficult to explore because of the slow development of D(4)R agonists and antagonists the selectivity and efficacy of which have been rigorously demonstrated in vivo. We have attempted to overcome this limitation by taking a multidimensional approach to the characterization of mice completely deficient in this receptor subtype. Electrophysiological current and voltage-clamp recordings were performed in cortical pyramidal neurons from wild-type and D(4)R-deficient mice. The frequency of spontaneous synaptic activity and the frequency and duration of paroxysmal discharges induced by epileptogenic agents were increased in mutant mice. Enhanced synaptic activity was also observed in brain slices of wild-type mice incubated in the presence of the selective D(4)R antagonist PNU-101387G. Consistent with greater electrophysiological activity, nerve terminal glutamate density associated with asymmetrical synaptic contacts within layer VI of the motor cortex was reduced in mutant neurons. Taken together, these results suggest that the D(4)R can function as an inhibitory modulator of glutamate activity in the FC.Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Cepeda, Carlos. University of California at Los Angeles; Estados UnidosFil: Hurst, Raymond S.. University of California at Los Angeles; Estados UnidosFil: Flores Hernandez, Jorge. University of California at Los Angeles; Estados UnidosFil: Ariano, Marjorie A.. The Chicago Medical School; Estados UnidosFil: Falzone, Tomas Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Kozell, Laura B.. Oregon Health Sciences University; Estados UnidosFil: Meshul, Charles K.. Oregon Health Sciences University; Estados UnidosFil: Bunzow, James R.. Oregon Health Sciences University; Estados UnidosFil: Low, Malcolm J.. Oregon Health Sciences University; Estados UnidosFil: Levine, Michael S.. University of California at Los Angeles; Estados UnidosFil: Grandy, David K.. Oregon Health Sciences University; Estados Unido

    The Role of Serotonin in Fear Learning and Memory: A Systematic Review of Human Studies

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    Fear is characterized by distinct behavioral and physiological responses that are essential for the survival of the human species. Fear conditioning (FC) serves as a valuable model for studying the acquisition, extinction, and expression of fear. The serotonin (5-hydroxytryptamine, 5-HT) system is known to play a significant role in emotional and motivational aspects of human behavior, including fear learning and expression. Accumulating evidence from both animal and human studies suggests that brain regions involved in FC, such as the amygdala, hippocampus, and prefrontal cortex, possess a high density of 5-HT receptors, implicating the crucial involvement of serotonin in aversive learning. Additionally, studies exploring serotonin gene polymorphisms have indicated their potential influence on FC. Therefore, the objective of this work was to review the existing evidence linking 5-HT with fear learning and memory in humans. Through a comprehensive screening of the PubMed and Web of Science databases, 29 relevant studies were included in the final review. These studies investigated the relationship between serotonin and fear learning using drug manipulations or by studying 5-HT-related gene polymorphisms. The results suggest that elevated levels of 5-HT enhance aversive learning, indicating that the modulation of serotonin 5-HT2A receptors regulates the expression of fear responses in humans. Understanding the role of this neurochemical messenger in associative aversive learning can provide insights into psychiatric disorders such as anxiety and post-traumatic stress disorder (PTSD), among others

    Tilt measurements at Vulcano Island

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    A network of tiltmeters has been operational on Vulcano Island for numerous years. At present, the network comprises five functioning borehole stations, four of which are installed at 8-10 m and allow recording very stable, high precision signals with very low noise. We report observations over the last 12 years that illustrate impulsive variations linked to seismicity and long-term (several years) trends in the signals. We suggest a relationship between tilt changes correlated to the strongest regional seismic events and site acceleration; long-term tilt variations analyzed in combination with other ground deformation data seem to represent the evidence of a contraction of the La Fossa cone. We also analyzed how the tilt device has the capability to detect possible magma migrations; we considered previous studies that have imaged spatially well-defined levels of magma accumulation beneath La Fossa, and Vulcanello; we concluded that the Vulcano tilt network should be capable of detecting the upward migration of small magma volumes. Finally, we show that no evidence of changes are visible on tilt signals during anomalous degassing episodes (linked to a building up input of magmatic fluids) at the La Fossa thereby evidencing that no magma migration occurred during such events

    Diagnostic and prognostic value of three micrornas in environmental asbestiform fibers-associated malignant mesothelioma

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    Fluoro-edenite (FE) is an asbestiform fiber identified in Biancavilla (Sicily, Italy). Environmental exposure to FE has been associated with a higher incidence of malignant mesothelioma (MM). The present study aimed to validate the predicted diagnostic significance of hsa-miR-323a-3p, hsa-miR-101-3p, and hsa-miR-20b-5p on a subset of MM patients exposed to FE and matched with healthy controls. For this purpose, MM tissues vs. nonmalignant pleura tissues were analyzed through droplet digital PCR (ddPCR) to evaluate differences in the expression levels of the selected miRNAs and their MM diagnostic potential. In addition, further computational analysis has been performed to establish the correlation of these miRNAs with the available online asbestos exposure data and clinic-pathological parameters to verify the potential role of these miRNAs as prognostic tools. ddPCR results showed that the three analyzed miRNAs were significantly down-regulated in MM cases vs. controls. Receiver operating characteristic (ROC) analysis revealed high specificity and sensitivity rates for both hsa-miR-323a-3p and hsa-miR-20b-5p, which thus acquire a diagnostic value for MM. In silico results showed a potential prognostic role of hsa-miR-101-3p due to a significant association of its higher expression and increased overall survival (OS) of MM patients

    Evidence of abnormal scalar timing property in alexithymia

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    : Evidence suggests that incidental modulation of affective states affects the ability to keep track of time. Alexithymia represents an ideal condition to further address the emotion-time processing link, as it refers to a trait characterized by a deficit of affective processing. 31 healthy participants completed an online version of the TAS-20 scale, which measures alexithymia, and a time reproduction task of visual stimuli related to positive (i.e., happiness) and negative (i.e., anger) facial expressions. Results documented a positive correlation between TAS-20 score and the variability in reproducing sub-second durations of the anger expression stimuli We also found an overestimation of sub-second durations of non-affective expressions in borderline/alexithymic participants. Finally, in line with the literature, we confirmed the overall tendency to overestimate the duration of anger expression stimuli. These findings, which can be interpreted in terms of abnormal scalar timing property in alexithymia, expand previous investigations linking this personality trait with abnormal processing of negative emotions. The evidence that alexithymia predicts the reproduction variability of sub-second durations of negative affective stimuli corroborates previous neuroimaging studies documenting cerebellar deficits in these individuals
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