The mammalian heart is derived from multiple cell lineages; however, our understanding of when and how the diverse cardiac cell types arise is limited. We mapped the origin of the embryonic mouse ...heart at single-cell resolution using a combination of transcriptomic, imaging, and genetic lineage labeling approaches. This mapping provided a transcriptional and anatomic definition of cardiac progenitor types. Furthermore, it revealed a cardiac progenitor pool that is anatomically and transcriptionally distinct from currently known cardiac progenitors. Besides contributing to cardiomyocytes, these cells also represent the earliest progenitor of the epicardium, a source of trophic factors and cells during cardiac development and injury. This study provides detailed insights into the formation of early cardiac cell types, with particular relevance to the development of cell-based cardiac regenerative therapies.
Arsenic-(As) pollution is an increasing threat across the globe and it is reaching harmful values in several areas of the world. In this perspective, we assayed bio-phyto-remediation technology using ...Arundo donax L., assisted by Plant Growth Promoting Bacteria (PGPB) consortium (BC) constituted of two strains of Stenotrophomonas maltophilia sp. and one of Agrobacterium sp.; furthermore, we assayed the epigenetic response to As pollution. The three bacterial strains initially evaluated for their As tolerance, revealed different resistance to both forms of AsAs(III) and As(V) however at concentration greater than those foreseen in the phytoremediation experiment (2.0, 10.0, 20.0 mgL−1 of NaAsO2). At the end of the trial plant biomass and As concentration were measured. Plants did not show any visible signs of toxicity, rather the leaf and stem biomass slightly increased in the presence of As and/or PGPBs; moreover, although the Bioaccumulation Factor was double in the presence of BC, the absolute values of As accumulation in the Arundo plants were very low, both in the presence or absence of BC and only detectable in the presence of the highest As dose (20 mgL−1 As). In this case, regardless the presence of PGPB, ≈25% of As remained in the sand and ≈0.15% was accumulated in the plant, whilst the remaining 75% was volatilized by transpiration. Finally, the methylation sensitive amplified polymorphisms (MSAP) of leaves were analyzed in order to investigate their epigenetic response to As and/or BC. Our results suggest that epigenetic modifications are involved in stress response and As detoxification.
•The PGBPs used in this study are differentially tolerant to As(V) and As(III).•The two S. maltophilia are resistant up to 165.00 mg L−1 of As(III), while the Agrobacterium up to 80.00 mg L−1 of As(III).•Arundo donax takes up and volatilizes As(III).•The percentage of As removal efficiency in Arundo plants was higher than 50%.•DNA methylation mechanism is involved in As stress response of Arundo.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cardiovascular disease is the leading cause of death globally. An advanced understanding of cardiovascular disease mechanisms is required to improve therapeutic strategies and patient risk ...stratification. State-of-the-art, large-scale, single-cell and single-nucleus transcriptomics facilitate the exploration of the cardiac cellular landscape at an unprecedented level, beyond its descriptive features, and can further our understanding of the mechanisms of disease and guide functional studies. In this Review, we provide an overview of the technical challenges in the experimental design of single-cell and single-nucleus transcriptomics studies, as well as a discussion of the type of inferences that can be made from the data derived from these studies. Furthermore, we describe novel findings derived from transcriptomics studies for each major cardiac cell type in both health and disease, and from development to adulthood. This Review also provides a guide to interpreting the exhaustive list of newly identified cardiac cell types and states, and highlights the consensus and discordances in annotation, indicating an urgent need for standardization. We describe advanced applications such as integration of single-cell data with spatial transcriptomics to map genes and cells on tissue and define cellular microenvironments that regulate homeostasis and disease progression. Finally, we discuss current and future translational and clinical implications of novel transcriptomics approaches, and provide an outlook of how these technologies will change the way we diagnose and treat heart disease.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
History can represent an effective marketing resource because it can establish an emotional relationship with consumers. This article examines trademark applications in order to show how Spanish ...companies used the past in their branding strategy during the twentieth century. The article analyses which historical themes were used the most, over which periods, for what types of products and services and according to which Spanish regions. The study indicates that this commercial use of the past was closely linked to the spread of Spanish nationalism. Brands try to connect emotionally with consumers by evoking historical national myths and, therefore, their use increased during the periods of intensive nationalist expression.
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BFBNIB, IZUM, KILJ, NUK, PILJ, SAZU, UL, UM, UPUK
The mammalian heartbeat is thought to begin just prior to the linear heart tube stage of development. How the initial contractions are established and the downstream consequences of the earliest ...contractile function on cardiac differentiation and morphogenesis have not been described. Using high-resolution live imaging of mouse embryos, we observed randomly distributed spontaneous asynchronous Ca
-oscillations (SACOs) in the forming cardiac crescent (stage E7.75) prior to overt beating. Nascent contraction initiated at around E8.0 and was associated with sarcomeric assembly and rapid Ca
transients, underpinned by sequential expression of the Na
-Ca
exchanger (NCX1) and L-type Ca
channel (LTCC). Pharmacological inhibition of NCX1 and LTCC revealed rapid development of Ca
handling in the early heart and an essential early role for NCX1 in establishing SACOs through to the initiation of beating. NCX1 blockade impacted on CaMKII signalling to down-regulate cardiac gene expression, leading to impaired differentiation and failed crescent maturation.
Ischemic heart disease remains the foremost cause of death globally, with survivors at risk for subsequent heart failure. Paradoxically, cell therapies to offset cardiomyocyte loss after ischemic ...injury improve long-term cardiac function despite a lack of durable engraftment. An evolving consensus, inferred preponderantly from non-human models, is that transplanted cells benefit the heart via early paracrine signals. Here, we tested the impact of paracrine signals on human cardiomyocytes, using human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) as the target of mouse and human cardiac mesenchymal stromal cells (cMSC) with progenitor-like features. In co-culture and conditioned medium studies, cMSCs markedly inhibited human cardiomyocyte death. Little or no protection was conferred by mouse tail tip or human skin fibroblasts. Consistent with the results of transcriptomic profiling, functional analyses showed that the cMSC secretome suppressed apoptosis and preserved cardiac mitochondrial transmembrane potential. Protection was independent of exosomes under the conditions tested. In mice, injecting cMSC-conditioned media into the infarct border zone reduced apoptotic cardiomyocytes > 70% locally. Thus, hPSC-CMs provide an auspicious, relevant human platform to investigate extracellular signals for cardiac muscle survival, substantiating human cardioprotection by cMSCs, and suggesting the cMSC secretome or its components as potential cell-free therapeutic products.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The function of a cell is defined by its intrinsic characteristics and its niche: the tissue microenvironment in which it dwells. Here we combine single-cell and spatial transcriptomics data to ...discover cellular niches within eight regions of the human heart. We map cells to microanatomical locations and integrate knowledge-based and unsupervised structural annotations. We also profile the cells of the human cardiac conduction system
. The results revealed their distinctive repertoire of ion channels, G-protein-coupled receptors (GPCRs) and regulatory networks, and implicated FOXP2 in the pacemaker phenotype. We show that the sinoatrial node is compartmentalized, with a core of pacemaker cells, fibroblasts and glial cells supporting glutamatergic signalling. Using a custom CellPhoneDB.org module, we identify trans-synaptic pacemaker cell interactions with glia. We introduce a druggable target prediction tool, drug2cell, which leverages single-cell profiles and drug-target interactions to provide mechanistic insights into the chronotropic effects of drugs, including GLP-1 analogues. In the epicardium, we show enrichment of both IgG
and IgA
plasma cells forming immune niches that may contribute to infection defence. Overall, we provide new clarity to cardiac electro-anatomy and immunology, and our suite of computational approaches can be applied to other tissues and organs.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
This article deals with the influence of the country brand in the fashion industries. It explains how some Spanish fashion companies have achieved a prominent position in the international market ...without the support of a positive 'country-of-origin effect' and why their success has not generated a reinforcement of the image of Spain in the fashion market. The paper examines the evolution of the image of Spain and the Spanish fashion abroad, and the internationalisation of the main Spanish fashion companies, highlighting the keys of the limited influence of the country brand in the success of these companies.
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BFBNIB, IZUM, KILJ, NUK, PILJ, SAZU, UL, UM, UPUK
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