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Achieving a just transition to a low carbon economy and society, in the wake of the COVID-19 pandemic, is arguably one of the greatest policy challenges facing governments. It is also of deep concern to businesses, employees and the organisations that represent them. Much of the focus, particularly at policy level, has been on the potential of this transition to create new jobs especially through the growth of renewable energy and clean technology. In this paper, we argue that this focus on 'green jobs', and in particular new green jobs, grossly underestimates the skills needs of a future workforce able to deliver a transition to a more sustainable low-carbon economy. The focus of this study is to gain an understanding of what skills are required to support the transition beyond these sectors. It critically reports on the results of a series of in-depth interviews with senior managers in key organisations within Cambridgeshire and Peterborough, UK. It sheds a light on the significant employment transitions taking place in organisations who are not specifically focused on delivering 'green' products or services. It finds widespread acknowledgement of the importance of a green recovery, albeit predicated by economic growth. The key skills needs reported, at all levels were likely to be 'soft' transferrable skills rather than 'hard' technical skills. COVID-19 was recognised as both a disrupter and as a catalyst for a green transition.
RESUMEN
Ankylosauria is a diverse clade of armoured dinosaurs whose members were important constituents of many Cretaceous faunas. Phylogenetic analyses imply that the clade diverged from its sister taxon, Stegosauria, during the late Early Jurassic, but the fossil records of both clades are sparse until the Late Jurassic (~150 million years ago). Moreover, Ankylosauria is almost entirely restricted to former Laurasian continents, with only a single valid Gondwanan taxon. Spicomellus afer gen. et sp. nov. appears to represent the earliest-known ankylosaur and the first to be named from Africa, from the Middle Jurassic (Bathonian-Callovian) of Morocco, filling an important gap in dinosaur evolution. The specimen consists of a rib with spiked dermal armour fused to its dorsal surface, an unprecedented morphology among extinct and extant vertebrates. The specimen reveals an unrealized morphological diversity of armoured dinosaurs during their early evolution, and implies the presence of an important but undiscovered Gondwanan fossil record.
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Dinosaurios , África , Animales , Dinosaurios/anatomía & histología , Fósiles , FilogeniaRESUMEN
Acute myeloid leukemia (AML) is a heterogeneous malignant disease characterized by a collection of genetic and epigenetic changes. As a consequence, AML can evolve towards more aggressive subtypes during treatment, which require additional therapies to prevent future relapse. As we have previously detected double-stranded DNA (dsDNA) in tumor-derived extracellular vesicles (EVs), in this current study we attempted to evaluate the potential diagnostic applications of AML EV-dsDNA derived from primary bone marrow and peripheral blood plasma samples. EVs from plasma of 29 pediatric AML patients (at initial diagnosis or during treatment) were isolated by ultracentrifugation, after which dsDNA was extracted from obtained EVs and analyzed for leukemia-specific mutations using next generation sequencing (NGS) and GeneScan-based fragment-length analysis. In 18 out of 20 patients, dsDNA harvested from EVs mirrored the (leukemia-specific) mutations found in the genomic DNA obtained from primary leukemia cells. In the nanoparticle tracking analysis (NTA), a decrease in EV numbers was observed in patients after treatment compared with initial diagnosis. Following treatment, in 75 samples out of the 79, these mutations were no longer detectable in EV-dsDNA. In light of our results, we propose the use of leukemia-derived EV-dsDNA as an additional measure for mutational status and, potentially, treatment response in pediatric AML.
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ADN de Neoplasias , Vesículas Extracelulares , Leucemia Mieloide Aguda , Mutación , Adolescente , Niño , Preescolar , ADN de Neoplasias/sangre , ADN de Neoplasias/genética , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Femenino , Humanos , Lactante , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , MasculinoRESUMEN
Despite high remission rates, almost 25% of patients with AML will suffer relapse 3-5 years after diagnosis. Therefore, in addition to existing diagnostic and MRD detection tools, there is still a need for the development of novel approaches that can provide information on the state of the disease. Extracellular vesicles (EVs), containing genetic material reflecting the status of the parental cell, have gained interest in recent years as potential diagnostic biomarkers in cancer. Therefore, isolation and characterization of blood and bone marrow plasma-derived EVs from pediatric AML patients could be an additional approach in AML diagnostics and disease monitoring. In this study, we attempt to establish a plasma EV-RNA-based method to detect leukemia-specific FLT3-ITD and NPM1 mutations using established leukemia cell lines and primary pediatric AML plasma samples. We were successfully able to detect FLT3-ITD and NPM1 mutations in the EV-RNA using GeneScan-based fragment-length analysis and real-time PCR assays, respectively, in samples before therapy. This was corresponding to the gDNA mutational analysis from leukemic blasts, and supports the potential of using EV-RNA as a diagnostic biomarker in pediatric AML.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Adulto , Animales , Antraciclinas/uso terapéutico , Cladribina/uso terapéutico , Citarabina/uso terapéutico , Supervivencia sin Enfermedad , Humanos , Leucemia Mieloide Aguda/mortalidad , Nucleofosmina , Inducción de Remisión , Tasa de SupervivenciaRESUMEN
Tumor-associated neutrophils (TANs) regulate many processes associated with tumor progression, and depending on the microenvironment, they can exhibit pro- or antitumor functions. However, the molecular mechanisms regulating their tumorigenicity are not clear. Using transplantable tumor models, we showed here that nicotinamide phosphoribosyltransferase (NAMPT), a molecule involved in CSF3R downstream signaling, is essential for tumorigenic conversion of TANs and their pro-angiogenic switch. As a result tumor vascularization and growth are strongly supported by these cells. Inhibition of NAMPT in TANs leads to their antitumor conversion. Adoptive transfer of such TANs into B16F10-tumor bearing mice attenuates tumor angiogenesis and growth. Of note, we observe that the regulation of NAMPT signaling in TANs, and its effect on the neutrophil tumorigenicity, are analogous in mice and human. NAMPT is up-regulated in TANs from melanoma and head-and-neck tumor patients, and its expression positively correlates with tumor stage. Mechanistically, we found that targeting of NAMPT suppresses neutrophil tumorigenicity by inhibiting SIRT1 signaling, thereby blocking transcription of pro-angiogenic genes. Based on these results, we propose that NAMPT regulatory axis is important for neutrophils to activate angiogenic switch during early stages of tumorigenesis. Thus, identification of NAMPT as the critical molecule priming protumor functions of neutrophils provides not only mechanistic insight into the regulation of neutrophil tumorigenicity, but also identifies a potential pathway that may be targeted therapeutically in neutrophils. This, in turn, may be utilized as a novel mode of cancer immunotherapy.