NMSC (non-melanoma skin cancer) is a common tumor in the Caucasian population, accounting for 90% of skin cancers. Among them, squamous cell carcinomas (SCCs) can metastasize and, due to its high ...incidence, constitute a severe health problem. It has been suggested that cutaneous SCCs with more risk to metastasize express high levels of nuclear IKKα. However, the molecular mechanisms that lead to this enhanced aggressiveness are largely unknown. To understand in depth the influence of nuclear IKKα in skin SCC progression, we have generated murine PDVC57 skin carcinoma cells expressing exogenous IKKα either in the nucleus or in the cytoplasm to further distinguish the tumor properties of IKKα in both localizations. Our results show that IKKα promotes changes in both subcellular compartments, resembling EMT (epithelial-mesenchymal transition), which are more pronounced when IKKα is in the nucleus of these tumor cells. These EMT-related changes include a shift toward a migratory phenotype and induction of the expression of proteins involved in cell matrix degradation, cell survival and resistance to apoptosis. Additionally, we have found that apigenin, a flavonoid with anti-cancer properties, inhibits the expression of IKKα and attenuates most of the pro-tumoral EMT changes induced by IKKα in mouse tumor keratinocytes. Nevertheless, we have found that apigenin only inhibits the expression of the IKKα protein when it is localized in the cytoplasm.
An increased risk of venous thromboembolism (VTE) in patients with COVID-19 pneumonia admitted to intensive care unit (ICU) has been reported. Whether COVID-19 increases the risk of VTE in non-ICU ...wards remains unknown. We aimed to evaluate the burden of asymptomatic deep vein thrombosis (DVT) in COVID-19 patients with elevated D-dimer levels.
In this prospective study consecutive patients hospitalized in non-intensive care units with diagnosis of COVID-19 pneumonia and D-dimer > 1000 ng/ml were screened for asymptomatic DVT with complete compression doppler ultrasound (CCUS). The study was approved by the Institutional Ethics Committee.
The study comprised 156 patients (65.4% male). All but three patients received standard doses of thromboprophylaxis. Median days of hospitalization until CCUS was 9 (IQR 5–17). CCUS was positive for DVT in 23 patients (14.7%), of whom only one was proximal DVT. Seven patients (4.5%) had bilateral distal DVT. Patients with DVT had higher median D-dimer levels: 4527 (IQR 1925-9144) ng/ml vs 2050 (IQR 1428-3235) ng/ml; p < 0.001. D-dimer levels > 1570 ng/ml were associated with asymptomatic DVT (OR 9.1; CI 95% 1.1–70.1). D-dimer showed an acceptable discriminative capacity (area under the ROC curve 0.72, 95% CI 0.61–0.84).
In patients admitted with COVID-19 pneumonia and elevated D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series. Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.
•An increased risk of VTE in patients with COVID-19 pneumonia admitted to intensive care unit has been reported.•The most consistent hemostatic abnormalities with COVID-19 include mild thrombocytopenia and increased D-dimer levels.•In COVID-19 patients with high D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.•Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.
This paper presents an overview of the parabolic-trough collectors that have been built and marketed during the past century, as well as the prototypes currently under development. It also presents a ...survey of systems which could incorporate this type of concentrating solar system to supply thermal energy up to 400°C, especially steam power cycles for electricity generation, including examples of each application.
Multi-epoch radial velocity measurements of stars can be used to identify stellar, substellar, and planetary-mass companions. Even a small number of observation epochs can be informative about ...companions, though there can be multiple qualitatively different orbital solutions that fit the data. We have custom-built a Monte Carlo sampler (The Joker) that delivers reliable (and often highly multimodal) posterior samplings for companion orbital parameters given sparse radial velocity data. Here we use The Joker to perform a search for companions to 96,231 red giant stars observed in the APOGEE survey (DR14) with ≥3 spectroscopic epochs. We select stars with probable companions by making a cut on our posterior belief about the amplitude of the variation in stellar radial velocity induced by the orbit. We provide (1) a catalog of 320 companions for which the stellar companion's properties can be confidently determined, (2) a catalog of 4898 stars that likely have companions, but would require more observations to uniquely determine the orbital properties, and (3) posterior samplings for the full orbital parameters for all stars in the parent sample. We show the characteristics of systems with confidently determined companion properties and highlight interesting systems with candidate compact object companions.
Cylindromatosis (CYLD) is a deubiquitinase (DUB) enzyme that was initially characterized as a tumor suppressor of adnexal skin tumors in patients with CYLD syndrome. Later, it was also shown that the ...expression of functionally inactive mutated forms of CYLD promoted tumor development and progression of non-melanoma skin cancer (NMSC). However, the ability of wild-type CYLD to inhibit skin tumorigenesis in vivo in immunocompetent mice has not been proved. Herein, we generated transgenic mice that express the wild type form of CYLD under the control of the keratin 5 (K5) promoter (K5-CYLDwt mice) and analyzed the skin properties of these transgenic mice by WB and immunohistochemistry, studied the survival and proliferating characteristics of primary keratinocytes, and performed chemical skin carcinogenesis experiments. As a result, we found a reduced activation of the nuclear factor kappa B (NF-κB) pathway in the skin of K5-CYLDwt mice in response to tumor necrosis factor-α (TNF-α); accordingly, when subjected to insults, K5-CYLDwt keratinocytes are prone to apoptosis and are protected from excessive hyperproliferation. Skin carcinogenesis assays showed inhibition of tumor development in K5-CYLDwt mice. As a mechanism of this tumor suppressor activity, we found that a moderate increase in CYLD expression levels reduced NF-κB activation, which favored the differentiation of tumor epidermal cells and inhibited its proliferation; moreover, it decreased tumor angiogenesis and inflammation. Altogether, our results suggest that increased levels of CYLD may be useful for anti-skin cancer therapy.
Mediterranean mountains are extraordinarily diverse and hold a high proportion of endemic plants, but they are particularly vulnerable to climate change, and most species distribution models project ...drastic changes in community composition. Retrospective studies and long‐term monitoring also highlight that Mediterranean high‐mountain plants are suffering severe range contractions. The aim of this work is to review the current knowledge of climate change impacts on the process of plant regeneration by seed in Mediterranean high‐mountain plants, by combining available information from observational and experimental studies. We also discuss some processes that may provide resilience against changing environmental conditions and suggest some research priorities for the future. With some exceptions, there is still little evidence of the direct effects of climate change on pollination and reproductive success of Mediterranean high‐mountain plants, and most works are observational and/or centred only in the post‐dispersal stages (germination and establishment). The great majority of studies agree that the characteristic summer drought and the extreme heatwaves, which are projected to be more intense in the future, are the most limiting factors for the regeneration process. However, there is an urgent need for studies combining elevational gradient approaches with experimental manipulations of temperature and drought to confirm the magnitude and variability of species′ responses. There is also limited knowledge about the ability of Mediterranean high‐mountain plants to cope with climate change through phenotypic plasticity and local adaptation processes. This could be achieved by performing common garden and reciprocal translocation experiments with species differing in life history traits.
Van der Waals Spin Valves Cardoso, C; Soriano, D; García-Martínez, N A ...
Physical review letters,
2018-Aug-10, Letnik:
121, Številka:
6
Journal Article
Recenzirano
Odprti dostop
We propose spin valves where a 2D nonmagnetic conductor is intercalated between two ferromagnetic insulating layers. In this setup, the relative orientation of the magnetizations of the insulating ...layers can have a strong impact on the in-plane conductivity of the 2D conductor. We first show this for a graphene bilayer, described with a tight-binding model, placed between two ferromagnetic insulators. In the antiparallel configuration, a band gap opens at the Dirac point, whereas in the parallel configuration, the graphene bilayer remains conducting. We then compute the electronic structure of graphene bilayer placed between two monolayers of the ferromagnetic insulator CrI_{3}, using density functional theory. Consistent with the model, we find that a gap opens at the Dirac point only in the antiparallel configuration.
We report chemical abundances obtained by Sloan Digital Sky Survey (SDSS)-III/Apache Point Observatory Galactic Evolution Experiment for giant stars in five globular clusters located within 2.2 kpc ...of the Galactic Centre. We detect the presence of multiple stellar populations in four of those clusters (NGC 6553, NGC 6528, Terzan 5 and Palomar 6) and find strong evidence for their presence in NGC 6522. All clusters with a large enough sample present a significant spread in the abundances of N, C, Na and Al, with the usual correlations and anticorrelations between various abundances seen in other globular clusters. Our results provide important quantitative constraints on theoretical models for self-enrichment of globular clusters, by testing their predictions for the dependence of yields of elements such as Na, N, C and Al on metallicity. They also confirm that, under the assumption that field N-rich stars originate from globular cluster destruction, they can be used as tracers of their parental systems in the high-metallicity regime.
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