3,318 research outputs found

    About the isocurvature tension between axion and high scale inflationary models

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    The present work suggests that the isocurvature tension between axion and high energy inflationary scenarios may be avoided by considering a double field inflationary model involving the hidden Peccei-Quinn Higgs and the Standard Model one. Some terms in the lagrangian we propose explicitly violate the Peccei-Quinn symmetry but, at the present era, their effect is completely negligible. The resulting mechanism allows a large value for the axion constant, of the order faMpf_a\sim M_p, thus the axion isocurvature fluctuations are suppressed even when the scale of inflation HinfH_{inf} is very high, of the order of HinfMgutH_{inf}\sim M_{gut}. This numerical value is typical in Higgs inflationary models. An analysis about topological defect formation in this scenario is also performed, and it is suggested that, under certain assumptions, their effect is not catastrophic from the cosmological point of view

    The Glutaredoxin GLRX-21 Functions to Prevent Selenium-Induced Oxidative Stress in Caenorhabditis elegans

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    Selenium is an essential micronutrient that functions as an antioxidant. Yet, at higher concentrations, selenium is pro-oxidant and toxic. In extreme cases, exposures to excess selenium can lead to death or selenosis, a syndrome characterized by teeth, hair and nail loss, and nervous system alterations. Recent interest in selenium as an anti- tumorigenic agent has reemphasized the need to understand the mechanisms underlying the cellular consequences of increased selenium exposure. We show here, that in the nematode, Caenorhabditis elegans, selenium has a concentration range in which it functions as an antioxidant, but beyond this range it exhibits a dose- and time-dependent lethality. Oxidation-induced fluorescence emitted by the dye, carboxy-H2DCFDA, indicative of reactive oxygen species formation was significantly higher in animals after a brief exposure to 5mM sodium selenite. Longer-term exposures lead to a progressive selenium-induced motility impairment that could be partially prevented by coincident exposure to the cellular antioxidant–reduced glutathione. The C elegans glrx-21 gene belongs to the family of glutaredoxins (glutathione-dependent oxidoreductases) and the glrx-21(tm2921) allele is a null mutation that renders animals hypersensitive for the selenium-induced motility impairment, but not lethality. In addition, the lethality of animals with the tm2921 mutation exposed to selenium was unaffected by the addition of reduced glutathione, suggesting that GLRX-21 is required for glutathione to moderate this selenium-induced lethality. Our findings provide the first description of selenium-induced toxicity in C elegans and support its use as a model for elucidating the mechanisms of selenium toxicity

    Piezo1 regulates calcium oscillations and cytokine release from astrocytes

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    Astrocytes are important for information processing in the brain and they achieve this by fine‐tuning neuronal communication via continuous uptake and release of biochemical modulators of neurotransmission and synaptic plasticity. Often overlooked are their important functions in mechanosensation. Indeed, astrocytes can detect pathophysiological changes in the mechanical properties of injured, ageing, or degenerating brain tissue. We have recently shown that astrocytes surrounding mechanically‐stiff amyloid plaques upregulate the mechanosensitive ion channel, Piezo1. Moreover, ageing transgenic Alzheimer's rats harboring a chronic peripheral bacterial infection displayed enhanced Piezo1 expression in amyloid plaque‐reactive astrocytes of the hippocampus and cerebral cortex. Here, we have shown that the bacterial endotoxin, lipopolysaccharide (LPS), also upregulates Piezo1 in primary mouse cortical astrocyte cultures in vitro. Activation of Piezo1, via the small molecule agonist Yoda1, enhanced Ca2+ influx in both control and LPS‐stimulated astrocytes. Moreover, Yoda1 augmented intracellular Ca2+ oscillations but decreased subsequent Ca2+ influx in response to adenosine triphosphate (ATP) stimulation. Neither blocking nor activating Piezo1 affected cell viability. However, LPS‐stimulated astrocyte cultures exposed to the Piezo1 activator, Yoda1, migrated significantly slower than reactive astrocytes treated with the mechanosensitive channel‐blocking peptide, GsMTx4. Furthermore, our data show that activating Piezo1 channels inhibits the release of cytokines and chemokines, such as IL‐1β, TNFα, and fractalkine (CX3CL1), from LPS‐stimulated astrocyte cultures. Taken together, our results suggest that astrocytic Piezo1 upregulation may act to dampen neuroinflammation and could be a useful drug target for neuroinflammatory disorders of the brain

    Shapes of the 192,190^{192,190}Pb ground states from beta decay studies using the total absorption technique

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    The beta decay of 192,190^{192,190}Pb has been studied using the total absorption technique at the ISOLDE(CERN) facility. The beta-decay strength deduced from the measurements, combined with QRPA theoretical calculations, allow us to infer that the ground states of the 192,190^{192,190}Pb isotopes are spherical. These results represent the first application of the shape determination method using the total absorption technique for heavy nuclei and in a region where there is considerable interest in nuclear shapes and shape effects

    Highly Chemoselective NH- and O-Transfer to Thiols Using Hypervalent Iodine Reagents: Synthesis of Sulfonimidates and Sulfonamides

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    Aryl thiols can be selectively converted to sulfonimidates or sulfonamides with three new S-X connections being made selectively in one pot. Using hypervalent iodine reagents in the presence of ammonium carbamate, NH- and O-groups are transferred under mild and practical conditions. Reducing the loading of ammonium carbamate changed the product distribution, converting the sulfonimidate to the sulfonamide. Studies into the possible intermediate species are presented, suggesting that multiple pathways may be possible via sulfinate esters, or related intermediates, with each species forming the same products

    Identification of candidate host serum and saliva biomarkers for a better diagnosis of active and latent tuberculosis infection

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    In our work, we aim to identify new candidate host biomarkers to discriminate between active TB patients (n = 28), latent infection (LTBI; n = 27) and uninfected (NoTBI; n = 42) individuals. For that, active TB patients and their contacts were recruited that donated serum and saliva samples. A multiplex assay was performed to study the concentration of different cytokines, chemokines and growth factors. Proteins with significant differences between groups were selected and logistic regression and the area under the ROC curve (AUC) was used to assess the diagnostic accuracy. The best marker combinations that discriminate active TB from NoTBI contacts were [IP-10 + IL-7] in serum and [Fractalkine + IP-10 + IL-1alpha + VEGF] in saliva. Best discrimination between active TB and LTBI was achieved using [IP-10 + BCA-1] in serum (AUC = 0.83) and IP-10 in saliva (p = 0.0007; AUC = 0.78). The levels of TNFalpha (p = 0.003; AUC = 0.73) in serum and the combination of [Fractalkine+IL-12p40] (AUC = 0.83) in saliva, were able to differentiate between NoTBI and LTBI contacts. In conclusion, different individual and combined protein markers could help to discriminate between active TB and both uninfected and latently-infected contacts. The most promising ones include [IP-10 + IL-7], [IP-10 + BCA-1] and TNFalpha in serum and [Fractalkine + IP-10 + IL-1alpha + VEGF], IP-10 and [Fractalkine+IL-12p40] in saliva

    South American Expert Roundtable : increasing adaptive governance capacity for coping with unintended side effects of digital transformation

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    This paper presents the main messages of a South American expert roundtable (ERT) on the unintended side effects (unseens) of digital transformation. The input of the ERT comprised 39 propositions from 20 experts representing 11 different perspectives. The two-day ERT discussed the main drivers and challenges as well as vulnerabilities or unseens and provided suggestions for: (i) the mechanisms underlying major unseens; (ii) understanding possible ways in which rebound effects of digital transformation may become the subject of overarching research in three main categories of impact: development factors, society, and individuals; and (iii) a set of potential action domains for transdisciplinary follow-up processes, including a case study in Brazil. A content analysis of the propositions and related mechanisms provided insights in the genesis of unseens by identifying 15 interrelated causal mechanisms related to critical issues/concerns. Additionally, a cluster analysis (CLA) was applied to structure the challenges and critical developments in South America. The discussion elaborated the genesis, dynamics, and impacts of (groups of) unseens such as the digital divide (that affects most countries that are not included in the development of digital business, management, production, etc. tools) or the challenge of restructuring small- and medium-sized enterprises (whose service is digitally substituted by digital devices). We identify specific issues and effects (for most South American countries) such as lack of governmental structure, challenging geographical structures (e.g., inclusion in high-performance transmission power), or the digital readiness of (wide parts) of society. One scientific contribution of the paper is related to the presented methodology that provides insights into the phenomena, the causal chains underlying “wanted/positive” and “unwanted/negative” effects, and the processes and mechanisms of societal changes caused by digitalization

    Linkage mapping, comparative genome analysis, and QTL detection for growth in a non-model teleost, the meagre Argyrosomus regius, using ddRAD sequencing

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    Meagre (Argyrosomus regius), is a benthopelagic species rapidly emerging in aquaculture, due to its low food to biomass conversion rate, good fillet yield and ease of production. Tracing a species genomic background along with describing the genetic basis of important traits can greatly influence both conservation strategies and production perspectives. In this study, we employed ddRAD sequencing of 266 fish from six F1 meagre families, to construct a high-density genetic map comprising 4529 polymorphic SNP markers. The QTL mapping analysis provided a genomic appreciation for the weight trait identifying a statistically significant QTL on linkage group 15 (LG15). The comparative genomics analysis with six teleost species revealed an evolutionarily conserved karyotype structure. The synteny observed, verified the already well-known fusion events of the three-spine stickleback genome, reinforced the evidence of reduced evolutionary distance of Sciaenids with the Sparidae family, reflected the evolutionary proximity with Dicentrarchus labrax, traced several putative chromosomal rearrangements and a prominent putative fusion event in meagre’s LG17. This study presents novel elements concerning the genome evolutionary history of a non-model teleost species recently adopted in aquaculture, starts to unravel the genetic basis of the species growth-related traits, and provides a high-density genetic map as a tool that can help to further establish meagre as a valuable resource for research and production.info:eu-repo/semantics/publishedVersio

    Catheter-based intervention for symptomatic patient with severe mitral regurgitation and very poor left ventricular systolic function - Safe but no room for complacency

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    Many patients with left ventricular systolic dysfunction have concomitant mitral regurgitation (MR). Their symptoms and prognosis worsen with increasing severity of MR. Percutaneous MitraClip((R)) can be used safely to reduce the severity of MR even in patients with advanced heart failure and is associated with improved symptoms, quality of life and exercise tolerance. However, a few patients with very poor left ventricular systolic function may experience significant haemodynamic disturbance in the peri-procedural period. We present three such patients, highlighting some of the potential problems encountered and discuss their possible pathophysiological mechanisms and safety measures.published_or_final_versio
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