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The Role of Fibroblasts in Atherosclerosis Progression
By Tadeja Kuret and Snežna Sodin-Šemrl
Submitted: January 28th 2021Reviewed: May 24th 2021Published: September 3rd 2021
Home > Books > Fibroblasts - Advances in Inflammation, Autoimmunity and Cancer
The following chapter addresses vascular fibroblasts in a healthy, quiescent state, as well during vascular inflammation, focusing on atherosclerosis. The development of atherosclerosis, an inflammatory disease of medium- and large-sized arteries, has traditionally been viewed as an "inside-out" mechanism, with prominent roles of the innermost layer of the artery, consisting of endothelial cells. However, emerging evidence suggests a new paradigm of "outside-in" mechanism, including an earlier role for fibroblasts, constituents of the outermost adventitial layer of the artery. Phenotypic and functional changes of fibroblasts in adventitia may even occur prior to, or alongside endothelial activation. Activated adventitial fibroblasts, implicated in atherosclerosis progression, begin to transform into myofibroblasts, upregulate production of different proinflammatory cytokines, chemokines, growth factors, proteolytic enzymes, extracellular matrix proteins and reactive oxygen species, leading to extensive matrix remodeling, chemotaxis and recruitment of immune cells. Due to their suitable location for drug delivery systems, preventing fibroblast activation, modulating their activity or inducing myofibroblast dedifferentiation could represent a promising therapeutic approach for atherosclerosis regression.
Tadeja Kuret
Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Slovenia
FAMNIT, University of Primorska, Slovenia
Snežna Sodin-Šemrl*
Department of Rheumatology, University Medical Centre Ljubljana, Slovenia
*Address all correspondence to: ssodin1@yahoo.com
FibroblastsAdvances in Inflammation, Autoimmunity and CancerEdited by Mojca Frank Bertoncelj
Fibroblasts - Advances in Inflammation, Autoimmunity and Cancer
Edited by Mojca Frank Bertoncelj and Katja Lakota
Fibroblasts are mesenchymal cells that are morphologically characterized as adherent, flat, elongated (spindle-shaped) cells with leveled, oval nuclei. One of their major roles is to produce and integrate structural proteins, such as collagen, elastin, and proteoglycans into the extracellular matrix (ECM) of most mesenchymal tissues and thus maintain their structural integrity [1].
In healthy arteries, fibroblasts can be found in the adventitia, the outermost layer of the vessel wall. Adventitial fibroblasts display numerous subtypes, even in a quiescent state, however, very little is known about their exact involvement in atherosclerosis development and progression [2]. Most of the attributed functions of adventitial fibroblasts have been largely extrapolated from findings describing fibroblasts in different tissues and organs, such as the skin. However, fibroblasts from different anatomic sites and tissues are functionally and phenotypically distinct. For example, cultured fetal and adult human skin fibroblasts derived from different anatomical sites expressed distinct transcriptional patterns of genes involved in extracellular matrix synthesis, lipid metabolism, and cell signaling pathways regulating proliferation, cell migration and fate determination [3]. The discovered topographic differences of fibroblasts might be connected to the positional memory since adult fibroblast maintain key features of the HOX gene pattern expression, established during embryogenesis. Indeed, many HOX genes that encode a family of evolutionarily conserved transcription factors, are differentially expressed in fibroblasts derived from different anatomical sites, indicating that fibroblasts from each topographic site express a unique HOX gene expression pattern [3, 4].
Fibroblasts are metabolically active cells that play a central role in, not only matrix maintenance and remodeling and regulating ECM, but also in managing interstitial fluid volume and pressure, new tissue formation and wound healing. They have been found to be associated with many connective tissue pathologies, either due to their direct implication in the disease mechanism or due to the resulting fibrosis associated with damage in other cell types [5]. Recently, novel mechanisms proposed a prominent role of fibroblasts also in the development and progression of atherosclerosis. Atherosclerosis is a chronic, fibro-proliferative disease of the arterial vessel walls that underlies the development of many cardiovascular diseases (CVDs) and affects the structure and function of the involved arteries [6].
Vascular inflammation, leading to atherosclerosis, has been traditionally viewed as an "inside-out" response, beginning with the activation of endothelium and an inflammatory response that spreads outwards, from the intima towards media and adventitia, ultimately forming fibrous plaque and damaging all three vessel wall layers [7, 8]. The classical mechanism of atherogenesis has been challenged recently with emerging evidence supporting a new hypothesis of an "outside-in" mechanism, in which vascular inflammation actually begins in the adventitia and progresses inward towards the media and intima [8, 9], suggesting a more prominent role of fibroblasts than previously thought.
So, in order to pinpoint, the potential role of fibroblasts during atherosclerosis progression, we need to first look at the arterial wall composition and function.
2. Vessel wall structure and fibroblasts
2.1 Arterial vessel wall structure
Characterization of the resident, stromal cell populations and subpopulations in a blood vessel is an important step in understanding cellular contribution to vascular development and disease. Since atherosclerosis is prevalently a disease of large- and medium-sized arteries [10], we will focus here on the description of the structure of these vessels and corresponding vascular stromal cell populations.
The walls of large- and medium-sized arteries are a heterogeneous three-layered structure consisting of the tunica intima, media and adventitia. Each layer is unique in its histologic, biochemical and functional properties and is differentially involved in maintaining vascular homeostasis and regulating the vascular response to stress or injury [8]. The tunica intima or innermost layer represents a monolayer of endothelial cells, which are in direct contact with the blood flow. The intima is separated from the tunica media by a basement membrane and an internal elastic lamina. The tunica media consists of multiple layers of vascular smooth muscle cells (VSMC). The tunica adventitia or the outermost layer is separated from the media by an external elastic lamina and represents the most complex layer of the blood vessel [11]. The adventitia is composed primarily of fibroblasts in a loose connective tissue matrix, and it also contains resident immune cells (e.g. dendritic cells, macrophages, mast cells), pericytes, small blood vessels with endothelial cells (vasa vasorum), several progenitor cells and adrenergic nerve cells (Figure 1) [13].
Heterogeneous cellular composition of the vascular adventitia. Compared to arterial intima and media, which are composed of endothelial and smooth muscle cells, respectively, the arterial adventitia is composed of a variety of heterogeneous cell populations, including fibroblasts, immunomodulatory cells (e.g. dendritic cells, macrophages), vasa vasorum, pericytes and adrenergic nerves. The figure was adapted from [12] and created using Biorender.
For many years, adventitial cells were thought to have a limited physiological "static" function serving as structural support to the blood vessel, supplying oxygen and nutrients to the media of large vessels, and sustaining sympathetic innervation of the vessel wall [14]. However, latest in vivoand in vitrostudies have shown that the adventitia represents a dynamic microenvironment that regulates both structural and functional properties of all three arterial layers [15]. The adventitia is an important source of cells that migrate towards the intima and media. For example, stem and progenitor cells that function and reside in the adventitia can transform into medial and intimal cells, such as VSMCs, and endothelial cells [16, 17, 18]. The adventitia of coronary arteries also contains cholinergic nerve terminals that release acetylcholine, diffusing to the intima layer of endothelium, where it induces the release of nitric oxide, causing VSMC relaxation and vasodilatation [19]. After stimulation with angiotensin II, adventitial fibroblasts can synthesize and release endothelin-1 (ET-1) that is important in mediating VSMC contraction [20]. The important role of adventitia is further supported by the role of vasa vasorumnetwork, serving as a pipeline for inflammatory cell infiltration during vascular inflammation. In atherosclerosis, inflammation contributes to increased neovascularization and enhanced permeability of the adventitial vasa vasorum, allowing more inflammatory cells to enter the atherosclerotic plaque. Indeed, by suppressing the neovascularization of vasa vasorum, Moulton et al. [21] observed reduction in numbers of macrophages in atherosclerotic plaques and inhibition of atherosclerosis progression in experimental mice models [21]. Additionally, adventitial resident cells participate in initiation and regulation of vascular development, response to injury and tissue repair and thus, importantly contribute to disease development, especially intimal hyperplasia. This is mediated by their ability of responding to external physiological stress with intensive tissue repair or arterial remodeling [9, 16, 22]. Importantly, resident adventitial cells (e.g. fibroblasts) are often the first cells in the vascular wall to become activated in response to hormonal and inflammatory stimuli, as well as environmental stress, such as hypoxia/ischemia and hypertension [8, 15].
2.2 Fibroblasts in healthy arterial vessel walls
Understanding the role of fibroblasts in normal and pathologic conditions is often obstructed by the lack of reliable and specific markers. The fibroblast is therefore still one of the most difficult cell types to define in vivo, likely due to their heterogeneity (multiple subtypes) and plasticity [23].
In a healthy artery, adventitial fibroblasts are found in a non-active, quiescent state, and are usually defined by their location in the vessel wall since they can be separated from the more generally recognized smooth muscle cell layer by an external elastic lamina [24, 25]. All currently used markers to identify fibroblasts, including vimentin, platelet derived growth factor receptor α (PDGFRα), fibroblast specific protein 1 (FSP1), discoidin-domain receptor, and prolyl-4-hydroxylase, are potentially problematic, as they are also expressed in other cell types and are not present in all fibroblasts [3, 26, 27]. Therefore, to identify fibroblasts, investigators have to rely on the lack of markers for other cell lineages (e.g. non-lymphoid, non-endothelium, and non-epithelium), along with morphologic, functional, and biochemical characteristics [3].
Adventitial fibroblasts show differences in morphology, size, function and activity in the healthy, as well as stressed conditions or disease states [15]. For example, An et al. [28] found two major fibroblast subpopulations in the adventitia of rat thoracic aorta. The two populations were described as epithelioid-like cells and spindle-like cells, however only epithelioid-like fibroblasts were sensitive to stimulation with angiotensin II, a hormone involved in the development of hypertension and atherosclerosis [28]. Studying fibroblasts from the adventitia of bovine pulmonary artery, Das et al. [29] concluded that numerous phenotypically and biochemically distinct fibroblast subpopulations can be found and only a selective increase in the number of resident fibroblast subpopulations with enhanced growth capability was observed under hypoxic conditions [29].
With the development and increasing popularity of single cell RNA sequencing technology, it might now be possible to find markers, specific to adventitial fibroblasts, as well as to characterize in depth, their subpopulations in normal and diseased states [30]. Kalluri et al. [31] explored the cellular atlas of healthy mice aortas using single cell RNA sequencing. They showed that fibroblasts represent approximately 33% of all aortic cells and were defined by higher expression of PDGFRα and collagens/collagen-binding proteins (e.g. Col1a1, Col1a2, Dcn, Lum) whereas the expression of VSMC-associated contractile proteins (e.g. Myh11, Cnn1) was reduced. These fibroblasts clustered into two subpopulations and are probably derived from the adventitia, however their exact location needs to be confirmed by immunohistochemistry or in-situ hybridization [31]. Another study using the high resolution single cell analysis approach, was performed by Gu et al. [32] in aortic adventitial cells from wild type and apolipoprotein E-deficient (ApoE−/−)mice. They determined four heterogeneous mesenchymal populations with differential gene expression suggesting potential functions in ECM organization, immune regulation and bone formation. Furthermore, interaction of resident, mesenchymal cells with immune cells was enhanced in the adventitia of ApoE−/− mice. These data revealed a heterogeneous cellular landscape of the adventitia and confirmed fibroblast variability present already in the healthy, quiescent state [32].
3. Adventitial fibroblasts in vascular pathology
3.1 Contribution of adventitial fibroblasts to vascular pathology
In response to injury or environmental stress, adventitial fibroblasts can become activated, displaying altered phenotypic and functional properties. Activated fibroblasts intensely proliferate and increase production and deposition of ECM proteins, as well as proinflammatory cytokines, chemokines, adhesion molecules, matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), and growth factors, such as vascular endothelial growth factor (VEGF) [12, 33]. These molecules directly affect the phenotype of other resident cells in the vessel wall, such as VSMC and endothelial cells, promote neointima formation, regulate vasa vasorumexpansion and affect the recruitment of infiltrating immune cells [8, 24]. Despite an excessive proliferation of activated fibroblasts, no hyperplasia of adventitia is usually observed in vascular pathologies. It is likely that many different mediators can also activate replication repressor signals in fibroblasts to limit or control replication. For instance, protein tyrosine phosphatases that regulate growth factor signaling in vascular remodeling, are upregulated in adventitial fibroblasts in response to vascular injury presumably to mitigate proliferative responses [34]. It was also demonstrated that adventitial fibroblasts under hypoxic conditions activate protein kinase C-zeta and MAPK phosphatase-1 that repress proliferative signals and limit the proliferation of fibroblasts [35, 36].
Vascular fibroblasts may also produce large amounts of reactive oxygen species (ROS) that seem to regulate their proliferation and ECM deposition [37, 38]. Activated fibroblasts increasingly interact with other cell types in the arterial wall, such as endothelial cells and VSMC and regulate their functions, as well as recruit immune cells into the vessel wall [39]. After their activation, some fibroblasts differentiate into myofibroblasts that contain bundles of stress fibers and can be identified by expression of contractile proteins, such as α-smooth muscle actin (αSMA). Multiple stimuli in the microenvironment, such as mechanical stress, growth factors (e.g. TGF-β), proinflammatory cytokines (e,g, IL-1β, IL-6, TNF-α), adhesion molecules, and ECM molecules can cause differentiation of a fibroblast towards the myofibroblast phenotype. Myofibroblasts contribute to extensive remodeling, intimal hyperplasia, and luminal stenosis due to their invasion and migration into the intima and increased production and secretion of ECM proteins [40, 41, 42, 43].
The recognition that fibroblasts are not only able to generate, but also to sustain inflammatory responses, provides insight into why vascular inflammatory responses, in certain situations, fail to resolve. It is suggested that chronic inflammation occurs due to dysregulated fibroblast activity in which they fail to switch off their inflammatory programme, leading to the inappropriate survival and retention of leukocytes within inflamed tissue [44]. It is also clear that the activated adventitial fibroblasts play an important role in regulating vasa vasorumgrowth, which can contribute to ongoing vascular remodeling by acting as a conduit for delivery of inflammatory and progenitor cells [45].
Recent studies shed light on the implication of adventitial fibroblasts in different vascular pathologies, characterized by arterial remodeling and neointimal formation [43]. One of the most persistent findings in experimental in vitroand in vivomodels is intensive adventitial remodeling, found very early in response to vascular injury or stress [46, 47, 48]. Adventitial remodeling in the vasculature has been characterized by increased proliferation of fibroblasts, which appear to be the first cells in the vessel wall that respond to different stimuli by their activation [49]. Direct evidence of fibroblast migration into the intima was provided in a study, performed by Li et al. [50], in which primary syngeneic adventitial fibroblasts were transduced with β-galactosidase (LacZ) and introduced into the adventitia of rat carotid arteries immediately after baloon injury. MRNA expression of LacZand in situ enzymatic activity of β-galactosidase were detected in the media and the neointima, 7 days after injury. On the contrary, in the arteries that were not injured, the expression of LacZand enzymatic activity of β-galactosidase were restricted to the adventitia [50]. Similar findings were later reported by Han et al. [51] showing that adventitial fibroblasts migrated to the media and intima on seventh day after balloon injury in the rat carotid artery. The results were obtained by direct labeling of adventitial fibroblasts using in vivogene transfer technique, as well as transmission electron microscopy [51]. Furthermore, Dutzmann et al. [52] discovered that early activation of adventitial fibroblasts after wire-induced injury in C57BL/6 mice stimulated their proliferation and release of proinflammatory cytokines and growth factors, and the subsequent proliferation of VSMC, resulting in neointima formation [52].
Pulmonary artery hypertension (PAH) is one of the vascular pathologies, characterized by extensive arterial remodeling and neointima formation, in which fibroblasts were shown to play an important role [53]. For example, in the neonatal bovine hypoxic PAH model, adventitial fibroblasts were found to undergo the earliest and most significant increases in proliferation, among all the vascular wall cell types [54]. Fibroblasts derived from experimental hypoxia-induced PAH and patients with PAH, display a hyperproliferative, apoptosis-resistant, and proinflammatory phenotype, defined by increased production of IL-6, IL-1β, CCL2/MCP1, CCL12/SDF1, VCAM1 and osteopontin [12, 55]. Moreover, when naïve bone marrow derived macrophages were exposed in vitroto conditioned medium generated by adventitial fibroblasts from human PAH patients and hypoxia induced PAH animals, they increased the transcription of several markers of activation (e.g. Cd163, Cd206, Il4ra and Socs3) [56]. These findings suggest that activated adventitial fibroblasts in PAH secrete various soluble factors required for macrophage activation and polarization leading to the propagation of inflammation from adventitia towards media and intima, supporting the "outside-in" hypothesis [53].
3.2 The role of fibroblasts in atherosclerosis and potential fibroblast-targeted therapy
Several findings suggest a role of fibroblasts in all stages of atherosclerosis, from initial phase to fibrous cap and plaque formation. It is becoming evident that adventitial cells, including adventitial fibroblasts are one of the first cells to respond to injury and become activated in the initial stage of atherosclerosis, even before the formation of atherosclerotic lesions, supporting the new "outside-in" hypothesis [46, 48].
Studies have shown that in various presentations of CVDs, the adventitia becomes heavily populated with multiple immune cell types, including monocytes, macrophages and T-cells, while adventitial fibroblasts proliferate increasingly and differentiate into myofibroblasts [33, 57, 58, 59]. Furthermore, several studies reported on increased vasa vasorumneovascularization in early atherosclerosis prior to the development of endothelial dysfunction [60, 61]. Neovascularization may act as a pipeline, allowing the entry of immune cells into the site of injury, as the density of vasa vasorumis highly correlated with the extent of inflammatory infiltrates in ApoE−/−mice [21]. These studies indicate that increased neovascularization of vasa vasorumin adventitia, that promotes inflammatory response and plaque angiogenesis, can occur before the endothelial activation and dysfunction in the intima [8]. Adventitial fibroblasts can regulate the growth and neovascularization of vasa vasorumthrough the release of soluble angiogenic growth factors, such as VEGF, TGF-β and platelet-derived growth factor (PDGF). Furthermore, with the release of chemokines, such as monocyte chemoattractant protein (MCP1), fibroblasts facilitate infiltration of circulating leukocytes, further increasing the growth of the vasa vasorumand perpetuating the inflammatory response [37].
Xu et al. [62] investigated the role of adventitial fibroblasts in atherosclerotic lesion formation by comparing the characteristics of adventitial fibroblasts from ApoE−/−and wild type mice. They found αSMA expressing adventitial fibroblast in ApoE−/−mice, but not in wild type mice. The gene expression of collagen I and collagen III was upregulated in adventitial fibroblasts from ApoE−/−mice, compared to the wild type mice. Furthermore, adventitial fibroblasts from ApoE−/−mice synthesized more TGF-β, MCP1, and PDGFβ and exhibited proliferatory and migratory properties [62]. MCP1 is important in regulation of migration and infiltration of monocytes into the vessel wall, which differentiate into macrophages, form foam cells and importantly contribute to fatty streak formation [63]. The effects of adventitial fibroblasts are also ascribed to ROS produced by adventitial fibroblast NADPH oxidases that play important roles in neointimal formation and growth in vascular pathologies, including atherosclerosis [37]. Xu et al. [64] studied ROS production and expression of NADPH oxidase subunit p47phox in the hyperlipid diet-induced atherosclerosis in the ApoE−/−mouse model. The activated fibroblasts from aortas of ApoE−/−mice displayed upregulated NADPH oxidase activity, augmented ROS production, and increased p47phox levels, compared with wild-type mice. ROS production was also associated with the increased proliferation and migration of adventitial fibroblasts. In addition, silencing of p47phox decreased the proliferation and migration of fibroblasts from ApoE−/−mice [64]. Fibroblasts, in response to ROS proliferate and release a number of growth factors and other mediators that influence vascular function, including ET1, PDGF, endothelial growth factor (EGF), fibroblast growth factor2 (FGF2), prostaglandin H2 (PGH2), and cyclophilins [65, 66]. In addition, ROS can also stimulate phenotypic switch of VSMC from the contractile to the proliferative and migratory one, suggesting that fibroblasts can indirectly influence other cell types inside the vessel wall [38].
In the initial phase of fibrosis, injured arteries start with tissue remodeling, and the formation of initial fibrous plaque actually represents a protective process; however, as in all chronic inflammatory conditions, fibrotic components in the plaque produce surplus levels of cytokines and proteolytic enzymes, causing excessive remodeling and tissue damage [59]. In advanced stages of atherosclerosis, fibrosis plays a central role and fibroblasts are the major cell population involved in remodeling of ECM in the fibrous plaque [59]. The most important functions of fibroblasts in progressed atherosclerosis include regulation of the inflammatory response, ECM protein production, and maintenance of the structural integrity of the plaque as well as regulated balance of MMP production, to enable beneficial tissue remodeling, alongside preventing plaque rupture, for instance [59, 67]. The potential role of fibroblasts in the development of atherosclerosis is shown in Figure 2.
The potential role of fibroblasts during atherosclerosis progression. Emerging evidence suggests that adventitial fibroblasts are activated in the initial stage of atherosclerosis, supporting the new "outside-in" hypothesis, which proposes that vascular inflammation begins in the adventitia and progresses inward towards the media and intima. In contrast, the original "inside-out" hypothesis of atherosclerosis proposes that the inflammatory response spreads from the intima outward towards adventitia with a more prominent role of endothelial and smooth muscle cells. The figure was adapted from [68,69,70] and created using Biorender. Legend: ECM, extracellular matrix; LDL, low density lipoprotein; ROS, reactive oxygen species; VSMC, vascular smooth muscle cells.
Regulation of fibroblasts activities might be beneficial in controlling or reversing the progression of atherosclerosis, hence, the adventitial fibroblast may be an attractive target for therapeutic intervention. Furthermore, the location of the adventitia as the outermost arterial layer makes it suitable for drug delivery and gene therapy [24]. It has already been shown that local adventitial drug delivery into coronary arteries results in better efficiency compared to luminal or intimal delivery methods [71]. Low efficiency of gene transfer to cells in adventitia by intraluminal administration has been reported and efficient transfection of these cells is achieved only when endothelium is denuded or damaged. In atherosclerotic arteries, intimal hyperplasia might present an additional barrier for intraluminal delivery. To overcome these problems, delivery from the adventitial side might be considered. On the other hand, numerous attempts to transfect or deliver the therapeutic agents to the media from the adventitial side of large blood vessels have failed because of the impenetrable nature of the external elastic lamina, separating adventitia from the media layer. This barrier hence allows for selective adventitial delivery and specific targeting of cells residing in adventitia [72].
Perivascular delivery of an adenoviral vector expressing a NADPH oxidase inhibitor in the rat carotid artery adventitia significantly reduced neointimal formation after balloon angioplasty. This specific vector targeted adventitial fibroblasts, and it did not affect VSMC in the media [73]. Targeting proteins, expressed by activated fibroblasts could attenuate vascular inflammatory responses and ameliorate vascular disease, including atherosclerosis. Recently, it was discovered that inhibition of expression or activity of fibroblast activation protein (FAP), that is expressed in activated but not in quiescent fibroblasts and was found to be associated with atherosclerotic plaques, can attenuate progression of atherosclerosis by increasing plaque stability in experimental mice models of atherosclerosis [74]. Reports on animal models of cardiomyopathy have indicated that reversibility of fibrosis was possible, with losartan (a selective angiotensin II type 1 receptor antagonist), which suppressed TGF-β expression [75, 76]. However, angiotensin II type 1 receptor is expressed also on VSMC and TGF-β can be produced by multiple cell types, in addition to fibroblasts.
A substantial number of adventitial fibroblasts can differentiate into myofibroblasts during initial stages of atherosclerosis, upon the influence of proinflammatory cytokines, chemokines adhesion molecules, growth factors and ECM proteins [33, 77]. For example, TGF-β induces the transition of a fibroblast into the myofibroblast by stimulating αSMA expression and collagen production [41, 42]. These highly proliferative αSMA-positive cells were found to be widely distributed in atherosclerotic plaques [24]. However, myofibroblasts in the atherosclerotic plaques can derive from multiple other sources, including VSMC [39], the endothelial to mesenchymal transition [78], as well as resident macrophages [79] (Figure 3). Myofibroblasts can contribute to changes in the function and structure of the vessel wall that occur during atherosclerosis (i.e arterial remodeling) due to their contractile properties and enhanced ECM protein production [80]. Myofibroblasts migrate from the adventitia to the media and intima and contribute to intimal hyperplasia [81, 82].
Various cells from the arterial wall can differentiate into myofibroblasts in atherosclerosis. Macrophages, resident fibroblasts, smooth muscle cells and endothelial cells can differentiate into myofibroblasts, depending on tissue microenvironment and inflammatory mediators. Myofibroblasts are characterized by increased expression of α-smooth muscle actin and synthesize and release large amounts of ECM proteins, growth factors, proinflammatory cytokines, proteolytic enzymes and their inhibitors, as well as reactive oxygen species. They are responsible for extensive ECM remodeling, increased chemotaxis and recruitment of immune cells and provide signals for further myofibroblast differentiation. The figure was adapted from [41] and created using Biorender. Legend: αSMA: α-smooth muscle actin; ECM: extracellular matrix; EMT, endothelial mesenchymal transition FGF: fibroblast growth factor; IL: interleukin; NOS: nitric oxide synthase; MMPs: matrix metalloproteases; ROS: reactive oxygen species; TGF-β: transforming growth factor-β; TIMPs: tissue inhibitors of MMPs; VEGF: vascular endothelial growth factor.
Although myofibroblasts were previously considered to be terminally differentiated cells, their capacity for dedifferentiation, defined as the loss of αSMA, is now well recognized and necessary to resolve idiopathic pulmonary fibrosis [83]. Several factors, such as prostaglandin E2 (PGE2), nuclear factor erythroid 2-related factor2 (Nrf2) and FGFs have shown the ability to dedifferentiate established lung and corneal myofibroblasts and might be promising therapeutic targets also for adventitial myofibroblasts in atherosclerosis [84]. For example, treatment with PGE2 was shown to inhibit proliferation and collagen I expression in fibroblasts extracted from histologically normal lung tissue [85]. In TGF-β or ET-1-activated lung myofibroblasts, treatment with PGE2 induced a dose-dependent decrease in αSMA and collagen I expression that was associated with inhibition of focal adhesion kinase signaling [86]. Sulforaphane, a Nrf2 activator, induced myofibroblast dedifferentiation in cultured lung fibroblasts from patients with idiopathic pulmonary fibrosis, as well as inhibited TGF-β-mediated profibrotic effects [87]. Corneal myofibroblasts that were grown in the presence of FGF1 or FGF2 and heparin reduced expression of αSMA, TGF-β receptors, and cadherins, thus promoting the quiescent fibroblast phenotype [88]. FGF21 has been shown to induce angiotensin-converting enzyme 2 (ACE2), and thus inhibit vascular remodeling, hypertension and fibrosis, and when stimulating with adiponectin, FGF21 may inhibit aortic inflammation in atherosclerosis, as well as decrease cardiac dysfunction in myocardial infarction, attenuate smooth muscle cell proliferation and migration and lower macrophage oxidizes low-density lipoprotein uptake [89]. In addition, Fgf21 knock-out mice have been reported to show impaired lipid metabolism [90]. So, FGF21 has shown promise, as a potential therapeutic for atherosclerosis, but would need further investigation in regard to its effects on leukocytes and activities of its receptors.
3.3 The origin of fibroblasts in atherosclerosis
Fibroblast heterogeneity in quiescent and diseased state might be a result of their various origins, as well as plasticity, since they can transform into different cell types, subsequently to their adaptation to stress or injury. Evidence suggests that fibroblasts involved in atherosclerosis may originate from different adventitial mesenchymal stem/progenitor cells, however, recent studies revealed they can also originate from VSMC or endothelial cells [30].
Several distinct progenitor/stem cell populations with the capacity to differentiate into endothelial cells, VSMC, fibroblasts, and macrophages reside in a specialized niche in the adventitia at the media-adventitia border [91]. A population of vascular progenitor cells in the aortic adventitia of ApoE−/−mice expressing the stem cell markers Sca1 and CD34 was described that might differentiate to vascular fibroblasts [92]. However, the exact identity of adventitial progenitor/stem cells is still controversial, since fibroblast also have the ability to acquire stem cell properties by upregulating Sca1 [93, 94, 95]. Moreover, mesenchymal stem cells and fibroblasts are similar in terms of morphology and share the expression of a number of surface markers, such as CD90, CD73, CD105, vimentin and FSP1. Some researchers therefore suggest that these adventitial stem cells positive for Sca1 are actually fibroblasts [30, 93]. For example, Tang et al. [96] showed that 40% of Sca1-positive adventitial stem cells also express PDGFRα, found to be expressed on the surface of fibroblasts [96]. Using single cell RNA sequencing, Gu et al. [32] identified four mesenchymal clusters in the aortas of ApoE−/−,as well as wild type mice, but did not annotate them as stem or progenitor cells. However, one of the clusters displayed high expression of Sca1 indicating stem cell properties [32]. The separation between adventitial fibroblasts and progenitor/stem cells seem to be much smaller than previously thought and cell transition of stem cells into fibroblasts or vice versa appears to be common in atherosclerosis [30]. It would be interesting to further investigate how this transdifferentiation would affect the pathological process of atherosclerosis and whether it could be targeted to reverse atherosclerosis progression.
The evidence that fibroblasts might originate from VSMC came from Wirka et al. in 2019 [97]. They reported that VSMC can transform into fibroblast-like cells (termed "fibromyocytes"), found in the arteries of ApoE−/−mice, as well as atherosclerotic human coronary arteries. Fibromyocytes expressed lower levels of VSMC differentiation markers and increased expression of genes, associated with fibroblast cluster, such as lumican, decorin and biglycan. However, fibromyocytes were transcriptionally different from the fibroblasts indicating that either they will further dedifferentiate into fibroblasts or they might represent another distinct population of fibroblasts [97]. Furthermore, it is currently still unclear, whether fibroblasts might also transform into VSMC.
Endothelial cells can serve as a possible source of atherosclerotic fibroblasts since they can undergo endothelial-mesenchymal transition, promoting atherosclerosis progression [98]. This was elegantly shown in 2016 by Evrard et al. [78] using a tamoxifen-inducible endothelial lineage tracking system in ApoE−/−mice. After 8 weeks of high fat diet, the mouse atherosclerotic plaques consisted of one third endothelial-derived cells positive for FAP and a range of other fibroblast markers. These cells further expanded in number in advanced atherosclerotic plaques. In vitromodeling confirmed that endothelial-mesenchymal transition is driven by TGF-β signaling, oxidative stress and hypoxia that are all characteristic for atherosclerosis. Furthermore, the extent of this transition correlated with an unstable plaque phenotype in humans, driven by altered collagen and MMP production that might be associated with clinical events [78].
Whether functional differences between fibroblasts, originating from different sources exist and what is their exact contribution to development and/or progression of atherosclerosis, still remain two important and open questions.
Recently, the well-established "inside-out" hypothesis of atherosclerotic development and progression has been revitalized to involve an "outside-in" component, including an earlier role for fibroblasts in the tunica adventitia layer. It is now thought that early "outside-in" events, with more prominent roles of fibroblasts in adventitia may even occur prior to, or alongside endothelial activation. Adventitial fibroblasts involved in atherosclerosis comprise a very heterogeneous population, due to their differential origins (mesenchymal stem/progenitor cells, smooth muscle cells, endothelial cells, macrophages) and an extensive repertoire of possible cell transitions into αSMA+ myofibroblasts, or even back to stem cells. It is thought that when resident fibroblasts begin to transform into αSMA+ myofibroblasts, this allows for intense release of VEGF, TGF-β, collagens, IL-1, IL-6, MMPs, ROS and angiotensin II, among other factors, that could lead to perpetual autocrine differentiation and inflammatory, proliferative states, responsible for ECM remodeling, chemotaxis and recruitment of immune cells. Their heterogeneity and consequently, a general lack of specific markers, both contribute to difficulties in studying their exact phenotypes and functions in atherosclerosis. The recent development and accessibility of single cell RNA sequencing technology provides new opportunities to find answers to the remaining questions in an unbiased manner. Furthermore, modulating fibroblast activity, preventing their activation or inducing myofibroblast dedifferentiation in atherosclerotic arteries could represent a promising therapeutic approach for atherosclerosis regression. The plasticity of the atherosclerotic plaque may reform and dynamically remodel many times, before either rupturing or, on the other hand, stabilizing with a plaque cap or even regressing, depending on, among many factors, also molecules in the microenvironment (micro-exoproteome) and presence of certain cellular profiles that may help lean the process either way.
2.Vessel wall structure and fibroblasts
3.Adventitial fibroblasts in vascular pathology
Tadeja Kuret and Snežna Sodin-Šemrl (September 3rd 2021). The Role of Fibroblasts in Atherosclerosis Progression, Fibroblasts - Advances in Inflammation, Autoimmunity and Cancer, Mojca Frank Bertoncelj and Katja Lakota, IntechOpen, DOI: 10.5772/intechopen.98546. Available from:
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Imagine a school in a castle filled with moving staircases, a sport played on flying broomsticks, an evil wizard intent on domination, an ordinary boy who's the hero of a whole world he doesn't know. This is the story that comes to life in the marvelous Harry Potter series by J. K. Rowling.
The Dark Lord, Voldemort, tried to murder Harry when he was just a baby—but he failed, killing Harry's parents but leaving him with a lightning-bolt scar. After Voldemort's disappearance, Harry is sent to live with his nasty aunt and uncle, far away from any hint of magic. But at the age of eleven, he is invited to attend Hogwarts School of Witchcraft and Wizardry, and a magical world opens before him.
Each of the seven books in the series chronicles one year in Harry's adventures at Hogwarts and his battle against Lord Voldemort. Harry makes two marvelous best friends named Ron Weasley and Hermione Granger. He studies topics like Transfiguration and Potions under wise headmaster Albus Dumbledore and the malevolent Severus Snape. He becomes expert at a game called Quidditch; encounters incredible creatures like phoenixes and dragons; and discovers an entire Wizarding universe hidden just out of sight, as prone to the darker aspects of human experience as our own, but brightened by a quirky original magic.
And slowly, Harry unravels the mysteries of his original confrontation with Voldemort: why the Dark Lord tried to kill him, how he lived… and what he must do to survive another encounter.
Trailer: https://www.youtube.com/watch?v=PbdM1db3JbY
The unforgettable, heartbreaking story of the unlikely friendship between a wealthy boy and the son of his father's servant, The Kite Runner is a beautifully crafted novel set in a country that is in the process of being destroyed. It is about the power of reading, the price of betrayal, and the possibility of redemption; and an exploration of the power of fathers over sons—their love, their sacrifices, their lies.
Trailer: http://www.youtube.com/watch?v=muW9Ob7V7ME
Nitta Sayuri tells the story of her life as a geisha. It begins in a poor fishing village in 1929, when, as a nine-year-old girl with unusual blue-gray eyes, she is taken from her home and sold into slavery to a renowned geisha house. We witness her transformation as she learns the rigorous arts of the geisha: dance and music; wearing kimono, elaborate makeup, and hair; pouring sake to reveal just a touch of inner wrist; competing with a jealous rival for men's solicitude and the money that goes with it. In Memoirs of a Geisha, we enter a world where appearances are paramount; where a girl's virginity is auctioned to the highest bidder; where women are trained to beguile the most powerful men.
Trailer: http://www.youtube.com/watch?v=i_TXEEgNiWE
Jemima Jones is overweight. About one hundred pounds overweight. Treated like a maid by her thin and social-climbing roommates, and lorded over by the beautiful Geraldine (less talented but better paid) at the Kilburn Herald, Jemima finds that her only consolation is food. Add to this her passion for her charming, sexy, and unobtainable colleague Ben, and Jemima knows her life is in need of a serious change. When she meets Brad, an eligible California hunk, over the Internet, she has the perfect opportunity to reinvent herself — as JJ, the slim, beautiful, gym-obsessed glamour girl. But when her long-distance Romeo demands that they meet, she must conquer her food addiction to become the bone-thin model of her e-mails — no small feat.
* All of the Jane Green Books are amazing!
Sparks fly when spirited Elizabeth Bennet meets single, rich, and proud Mr. Darcy. But Mr. Darcy reluctantly finds himself falling in love with a woman beneath his class. Can each overcome their own pride and prejudice?
Trailer: http://www.youtube.com/watch?v=7Afx8MGg00g
Set at the turn of the century, November of the Heart tells of Lorna Barnett, a young woman from a wealthy Saint Paul family, and Jens Harken, the ambitious dreamer who works in the kitchen of her family's summer estate. Lorna's father, Gideon, an avid sailor, is determined to claim victory for his own White Bear Yacht Club in the next summer regatta. Having recently suffered defeat at the hands of the rival club, Gideon is willing to do almost anything to win back the prize he sees as his.
Jens, pressed into service as a waiter as an elegant family dinner party, overhears Gideon's lament, and is sure his boatbuilding skills can be put to use on behalf of his employer. Brazenly crossing the boundary between servant and master by offering to design and build a boat that is sure to win the race. Jens incites Gideon's ire but piques his interest too. With Lorna's help, he convinces Gideon to finance the project.
COULD YOU SURVIVE ON YOUR OWN, IN THE WILD, WITH EVERYONE FIGHTING AGAINST YOU?
Twenty-four are forced to enter. Only the winner survives.
In the ruins of a place once known as North America lies the nation of Panem, a shining Capitol surrounded by twelve outlying districts. Each year, the districts are forced by the Capitol to send one boy and one girl between the ages of twelve and eighteen to participate in the Hunger Games, a brutal and terrifying fight to the death – televised for all of Panem to see.
Survival is second nature for sixteen-year-old Katniss Everdeen, who struggles to feed her mother and younger sister by secretly hunting and gathering beyond the fences of District 12. When Katniss steps in to take the place of her sister in the Hunger Games, she knows it may be her death sentence. If she is to survive, she must weigh survival against humanity and life against love.
Trailer: http://www.youtube.com/watch?v=SMGRhAEn6K0
In To Kill a Mockingbird, author Harper Lee uses memorable characters to explore civil rights and racism in the segregated Southern United States of the 1930s. Told through the eyes of Scout Finch, you learn about her father Atticus Finch, an attorney who hopelessly strives to prove the innocence of a black man unjustly accused of rape; and about Boo Radley, a mysterious neighbor who saves Scout and her brother Jem from being killed.
Trailer: https://www.youtube.com/watch?v=_bLKmGsdM9s
An aspiring author during the civil rights movement of the 1960s decides to write a book detailing the African-American maids' point of view on the white families for which they work, and the hardships they go through on a daily basis.
Trailer: http://www.youtube.com/watch?v=1GYmhc8Xk8g
In the Salinas Valley, in and around World War I, Cal Trask feels he must compete against overwhelming odds with his brother Aron for the love of their father Adam. Cal is frustrated at every turn, from his reaction to the war, to how to get ahead in business and in life, to how to relate to estranged mother.
In this tale of passion and obsession, Diana Bishop, a young scholar and the descendant of witches, discovers a long-lost and enchanted alchemical manuscript deep in Oxford's Bodleian Library. Its reappearance summons a fantastical underworld, which she navigates with her leading man, vampire geneticist Matthew Clairmont.
On a warm summer morning in North Carthage, Missouri, it is Nick and Amy Dunne's fifth wedding anniversary. Presents are being wrapped and reservations are being made when Nick's clever and beautiful wife disappears from their rented McMansion on the Mississippi River. Husband-of-the-Year Nick isn't doing himself any favors with cringe-worthy daydreams about the slope and shape of his wife's head, but passages from Amy's diary reveal the alpha-girl perfectionist could have put anyone dangerously on edge. Under mounting pressure from the police and the media—as well as Amy's fiercely doting parents—the town golden boy parades an endless series of lies, deceits, and inappropriate behavior. Nick is oddly evasive, and he's definitely bitter—but is he really a killer?
As the cops close in, every couple in town is soon wondering how well they know the one that they love. With his twin sister, Margo, at his side, Nick stands by his innocence. Trouble is, if Nick didn't do it, where is that beautiful wife? And what was in that silvery gift box hidden in the back of her bedroom closet?
Trailer: https://www.youtube.com/watch?v=esGn-xKFZdU
Set in South Carolina in 1964, The Secret Life of Bees tells the story of Lily Owens, whose life has been shaped around the blurred memory of the afternoon her mother was killed.
When Lily's fierce-hearted black "stand-in mother," Rosaleen, insults three of the town's most vicious racists, Lily decides they should both escape to Tiburon, South Carolina—a town that holds the secret to her mother's past. There they are taken in by an eccentric trio of black beekeeping sisters who introduce Lily to a mesmerizing world of bees, honey, and the Black Madonna who presides over their household. This is a remarkable story about divine female power and the transforming power of love—a story that women will share and pass on to their daughters for years to come.
Trailer: http://www.youtube.com/watch?v=pVCil2oSNYY
A poor boy of unknown origins is rescued from poverty and taken in by the Earnshaw family where he develops an intense relationship with his young foster sister, Cathy. Based on the classic novel by Emily Bronte.
Trailer: http://www.youtube.com/watch?v=HaIqzmRqSpQ
As our story opens, a horrific family tragedy sets sixteen-year-old Jacob journeying to a remote island off the coast of Wales, where he discovers the crumbling ruins of Miss Peregrine's Home for Peculiar Children. As Jacob explores its abandoned bedrooms and hallways, it becomes clear that the children were more than just peculiar. They may have been dangerous. They may have been quarantined on a deserted island for good reason. And somehow—impossible though it seems—they may still be alive.
Trailer: https://www.youtube.com/watch?v=XWrNyVhSJUU
Thirty-five-year-old American social media master Vanessa Roberts lives her thoroughly modern life with aplomb. So when her elderly Jane Austen–centric aunt needs her to take on the public relations for Julian Chancellor, a very private man from England who's written a book called My Year as Mr. Darcy, Vanessa agrees. But she's not "excessively diverted," as Jane Austen would say.
It is the story of three young, gifted anthropologists in 1933 caught in a passionate love triangle that threatens their bonds, their careers, and ultimately their lives. English Anthropologist Andrew Bankson has been alone in the field for several years, studying a tribe on the Sepik River in the Territory of New Guinea with little success. Increasingly frustrated and isolated by his research, Bankson is on the verge of suicide when he encounters the famous and controversial Nell Stone and her wry, mercurial husband Fen. Bankson is enthralled by the magnetic couple whose eager attentions pull him back from the brink of despair. Set between World War I and II and inspired by events in the life of revolutionary anthropologist Margaret Mead, Euphoria is an enthralling story of passion, possession, exploration and sacrifice from award-winning novelist Lily King.
Trailer: https://www.youtube.com/watch?t=101&v=ypXqg_fIuNk

redpajama_set_name: RedPajamaCommonCrawl


GopherCentral Library: History Video - Why Do We Vote on Tuesdays?
History Video - Why Do We Vote on Tuesdays?
As we gear up for Election Day have you ever wondered, "Why Do We Vote on Tuesdays?"
Today, you'll learn why Tuesday is the day, for the last 170 plus years, to cast your vote.
It's one of America's favorite holidays, but what's the real story behind the tricks and treats of Halloween?


It is winter, and the winter wind is strong and cold. I feel like a little boy who is trying to fly a kite. The ghost of my father is beside me. I am alone. I do my best to embrace the freedom of myself.
So, I am that little boy trying to fly his kite on a very windy day. As I become more centered, I am creative. And I become the painter who is falling into the rainbow of pigments on his canvas. I leave my body. I forget that it is cold. I am a soul. I am energy. I am the wind. I am the snow blowing in the wind. There is an invisible energy that flows in the current of my soul. I am the snowflake that melts on my face. I am transforming. I am completely alive in the moment.
I am the kite that is blowing. But the wind is so strong. The kite speeds up, spins around and around. The wind is wild and out of control. The kite nose-dives to the ground. My palette blows 20 feet across the field. My canvas blows away too – throws itself. It does not break. My bones are stronger. I am Rocky. I do not accept failure. I embrace the pleasure and the pain equally. It is intensely cold outside and my fingers are screaming. Blue blood. Red blood. I am that kite. I retrieve my palette and brushes. I have to smile. I smile and embrace the crazy beautiful moment. I am not complaining. I love the intensity of everything.
So I continue to be that boy learning to fly his kite. It is a dream, a crazy dream. The wind gets wilder. I am doing my best to satisfy my soul. The painting blows around and will not stay still. I feel like I am play fighting with a lover. I pin her down in the bed of my mind. Try to kiss her. She is resisting; she is trying to tickle me, but I want to make tender passionate love. My soul is open and my senses are alive. I am naked. I am completely vulnerable. I am distilled, cocooned, nested in this perfect intimate moment. I am a baker making bread. A carpenter building furniture. I am a make-up artist putting mascara on lashes. I am a gardener taking time to remove weeds.
I am a fragile egg that is falling. I keep falling and hold nothing back. I give and I give. I touch the canvas with great tenderness and abundant generosity. All the crocuses, tulips, daffodil bulbs bloom inside and break through my skin like Spring. I get goose bumps, or perhaps frostbite. I feel everything. I cut myself open. The zipper of Soul is open, and my skin is on the ground. I keep bleeding and I keep believing. I empty over 50 large tubes of paint in under 2 hours. It is a massive party, and I have all the voices singing inside my head. There are no rules, just pure freedom.
This moment continues… and I hold this bliss. Then suddenly the kite is free. The egg hits the ground. And everything inside of me has become the canvas.


text:
Hugo Wolf Quartett
Subgenre:
©H Hugo Wolf Quartett
Lineup/Description of Style
Discography, Performances, Projects
Field of Activity of (Person)
Performing Organisation of (Person)
Commissioning Organisation of (Person)
Performing Band/Ensemble of (Composition)
Commissioning Organisation of (Composition)
Dedicatee of (Composition)
"Grand personalities interact unsentimentally, considerately and with heart all at once, creating an emotional eddy that is difficult to explain."
The above qualities, together with a passionate will for expression and an unceasing artistic curiosity, are the trademarks of this quartet. For 20 years already, the Hugo Wolf Quartet has been a fixture on the international chamber music scene and has fascinated audiences around the globe.
Through training with the Alban Berg, Smetana, Amadeus and LaSalle Quartets, and also with Ferenc Rados, the ensemble laid the cornerstone for a highly successful career together. Founded in Vienna in 1993, the Hugo Wolf Quartet soon won such coveted awards as the Special Prize of the Vienna Philharmonic Orchestra and the European Chamber Music Prize, followed by the International String Quartet Competition in Cremona in 1995 - the same year that the ensemble made its debut in the Wiener Konzerthaus. In 1998, Vienna's Musikverein and Konzerthaus elected the four as Rising Stars. Since then, the quartet has regularly performed in Amsterdam's Concertgebouw, London's Wigmore Hall, New York's Lincoln Center and Carnegie Hall, and Berlin's Philharmonie, as well as at the Lockenhaus Chamber Music Festival, the Colmar Festival, La folle journée de Nantes and the Schubertiade Schwarzenberg.
In terms of program selection, the quartet equally emphasizes the classical/romantic and contemporary literature. Choosing Hugo Wolf as the namesake is telling in this regard, for Wolf was a composer on the cusp between romanticism and modernism, with an inquisitive artistic mindset that remained open to the past and future alike.
Numerous compositions have been written for, and premiered by, the Hugo Wolf Quartet – like Friedrich Cerha's String Quartet No. 4, Johannes Maria Staud's "Dichotomie" and "K'in", string quartets by Erich Urbanner, Dirk D'Ase and Otto M. Zykan, and a quartet and octet by jazz guitarist Wolfgang Muthspiel.
The recordings of Beethoven's String Quartet Op. 18/4 and Op. 132 (Gramola, 2001) and Franz Schubert's String Quartet D887 and D87 (VMS, 2009) both won Austrian radio station Ö1's Pasticcio Prize, and the quartet's close collaboration with legendary jazz trumpeter Kenny Wheeler and pianist John Taylor is documented on the recording Other People (CamJazz, 2006). Also available from the Hugo Wolf Quartet on the VMS label: a live performance from the Lockenhaus Chamber Music Festival (Haydn), the complete works for string quartet by Hugo Wolf, a live recording of the Schubert Octet D803 and the CD "Tristans langer Schatten" based on a 2013 concert-program.
Since 2011, the quartet has performed its own concert series in Vienna. Held in the renowned Wiener Konzerthaus, and generously supported by the Alban Berg Foundation, the ensemble enjoys this opportunity to present audiences with concerts and programs that feature a very personalized touch.
Source: Biography of the quartet (September 2017)
Band/Ensemble Member
Gürtler Sebastian
Bringolf Regis
Berner Florian
further members:
Subin Lee - viola (since 2016)
Weinmeister Gertrud - viola (until 2016)
2016: Imagined Memories (musica omnia)
2016: Vartabed Komitas (Megadic Classics)
2016: Philippe Hersant Fantaisies (Megadic Classics)
2014: Tristans langer Schatten - Wagner, Webern, Berg (VMS)
2013: Schubert - Oktett F-Dur (VMS / Zappel Music)
2013: Hugo Wolf: Sämtliche Werke für Streichquartett (VMS)
2012: Ludwig van Beethoven - Streichquartett in c-moll Op. 18/4, Streichquartett in a-moll Op. 132 (Gramola)
2010: Josef Haydn Streichquartette op.20/3 & 4, op. 33/5 Live aus Lockenhaus (VMS)
2009: Franz Schubert Streichquartett D 87 in Es-Dur Streichquartett D 887 in G-Dur (VMS)
2008: Franz Mittler - Streichquartett No.1 in F-Dur, Streichquartett No.3 in d-moll (CPO/ORF)
2008: Kenny Wheeler - Other People (CamJazz)
1999: Joseph Haydn - Streichquartett in B-Dur (Extraplatte)
Urbanner Erich
4th String Quartet
Capriccio (III) giocoso, crudele e un poco amabile
Dichotomie - for string-quartet
K'in - for bassoon and string quartet
Streichquartettsatz
String Quartet No.5
Viertes Streichquartett
Website: Homepage Hugo Wolf Quartett
mica-Archive: Hugo Wolf Quartett


text:
J Hus is ready for you
© Crowns & Owls
Jacket: Bianca Saunders
Top: Vintage Moschino c/o 194 Local
Words by: Kieran Yates
J Hus is rubbing his temples as he recalls one of the most seismic music moments of the year. "That moment… was the moment I've been waiting for. Everyday I'd been saying to myself, 'I can't wait to be home,' and then I'm home and I get to shake the world like that."
He has a wide grin and he's back there, earlier this April when Drake, as part of his show at London's O2 Arena, invited J Hus onstage for his first public appearance since he'd been released from prison. He found out about it before his release. "I just kept it to myself," he says. "I prepared myself mentally. Before I went onstage, my manager was like, 'That stage is… kinda big.' I was nervous, but as soon as I went on, I was like, 'Yes, this stage is for me.'"
Full Look: Pronounce
Hus is sprawled out in a studio chair, shaking his head. "The reaction was crazy. People crying, the 'Welcome Home' sign! [the message was lit up onstage] I didn't know I was this supported. I didn't know people loved me like that."
People do love him like that, and it's with excitement (and relief) that today, Hus is in a recording studio, situated at the end of a meandering, single-lane countryside road by the River Medway in Kent. It's respite, miles away from the small, two-bedroom house on a Stratford estate in east London where he grew up with his mum, younger brother and sister. Growing up Muslim meant that Hus didn't have the usual musical education of church like many of his rap peers. Instead, the second generation British Gambian says his distinct ear was honed through his mum and stepdad playing African music, Whitney Houston and Beenie Man in the house.
The result is a playful and intoxicating mix of UK rap. In recent years he's been championed for bringing sounds of the diaspora together through Afrobeat and bashment-inspired hybrids. So much influence has he had that he's almost single-handedly spawned the (slightly hackneyed) genre classification 'Afro Swing'.
"People don't know how powerful they are, especially black men"
Hat: The Real McCoy's
Top: Visvim
Jacket: CP Company
Trousers: Monad
The last time I met Hus – real name Mamodou Jallow – was in 2017, around the release of Common Sense. He was stuffing socks into smoke alarms so that he could smoke weed in the backstage green room of a show. His underground ratings were bubbling on low heat for longer before that though, with his 2014 SoundCloud upload, Vacation, and freestyles that featured on the now-defunct Newham YouTube channel FLI5STAR. The hype led to 2015's anthemic Dem Boy Paigon, a record deal with Black Butter, and the genre-defying Brit, Mercury and MOBO-nominated Common Sense. His debut album, it cemented the universal party appeal of tracks like Friendly and the contagion of his 'hustler baby, hustler baby' adlibs, and clocked up more than 10 million streams and counting.
Then, last year, time stopped for a brief moment. Hus was caught in Stratford Westfield shopping centre carrying a knife and sentenced to eight months (serving four) in Pentonville prison. Today, a Wednesday afternoon, he's comfortable in an all-black Adidas tracksuit and white socks and sliders, shuffling around the place he's made his makeshift home for the last seven weeks. "Studio is home for me now," he grins. He's visibly different: contemplative, deeper voiced, and physically bulked up. He is, of course, as likeable as always, bragging about his maddeningly simple (but effective) skincare regime: "it's just olive oil, seriously!"
As moisture collects on the leaves outside of the tall windows, I ask whether London feels like a place to escape from now, all things considered. "You know what it is? Here's just quiet, peaceful. I don't have a phone. Right now, I'm low-key, not trying to be seen. Well, until the album comes out and then I'm—" he claps his hands enthusiastically, as if he just did a magic trick.
I ask what else is new and he cracks a wide smile. "I'm a vegan now!" he declares, describing his recipe sourcing. "I go on YouTube and I just type in 'vegan food' and follow directions from some next people… but I'm still a West African boy. The last thing I made was dumplings, okra chips, plantain, wild rice and Portobello mushrooms, but I made it into nuggets," he says proudly.
The cooking is, partly, a welcome dietary shift from prison food which he describes as "not good", but also a nod to being in what he calls a "good place". He is definitely focused on music as therapy. If last time he was incarcerated (in Feltham in 2015 for a litany of convictions, including knife possession) he recalls listening to Gangnam Style on TV, this time, it was strictly work, listening to instrumentals sourced from shared CDs and writing to them.
He namechecks Shakespeare poems, fashion magazines and books on "atoms and science and that" as part of his Pentonville reading list. Also a part of his lust for information gathering was finding the thrill in details of rumoured cannibalistic dictators. One of the first lyrics he wrote after his release was a verse on What Do You Mean, from Skepta's recently-released album Ignorance Is Bliss, that references tyrannical Ugandan despot Idi Amin and North Korean leader Kim Jong Un. "I've known about [Idi Amin] since I was young," he explains. "I heard rumours he used to eat people!"
"My plan wasn't 'I'm going to do this rap ting, and I'm going to be a role model'. But now I understand that, being in this position, it comes with it"
The psychological impact of being confined for four months then re-entering the music world in front of 20,000 people was, as Hus acknowledges, more than a homecoming. It was a slightly nerve-wracking coming-of-age. Part of that was getting right back to work. He welcomes me from the front door over plush rugs and settles down to play new music. He's smiling, between shyness and pride, but the songs aren't finished yet due to a brief Ramadan enforced break. "I didn't want to be recording while I was fasting, you get me?" Not that taking a breath has diminished his fan base. The night before we meet, J Hus is trending on Twitter after the tracklist for Ed Sheeran's new album shows him on a track with Young Thug. The tweets are jubilant – people love to love Hus, and the tweets implore him to make more music so that their summer can officially start.
He presses play, and the studio is filled with a charismatic jolt that reminds you of his fun spirit and sheer electricity. Some of these songs he's been sitting on since Common Sense, others are brand new. One is a pulsing, body-swaying blend of upbeat R&B which shouts out the aunties. Another is a gluttonous, icier foray into bashment, which namechecks fortune telling and er, Arnold Schwarzenegger. On one joyfully catchy Afrobeat track the hook is just an instrumental. "I'm saving that for someone like Wizkid or Burna Boy, not sure yet," he says nonchalantly.
It sounds like the music to come will also be massive, and between excitement, I tell him about how conflicting it feels to challenge an artist you're such a fan of. On the one hand, at 24, Hus is a young man who has undergone trauma from historical violence (in 2015 he was stabbed five times), suffered the loss of his father early last year, and found protection from his own fear the only way he knew how, caught in a moment. On the other, he is a global superstar, a role model who, some may say, has made the debate around knife crime and UK rap harder to defend.
He gets it. "You see, Common Sense times, all them times, I realised – being in jail – that I didn't appreciate, or understand what I had," he says. "The come-up was so fast, and I was so young… People are watching me grow from a boy into a man."
The hindrance to being such a celebrated artist with a rapid ascension is that news of your misdemeanours becomes part of your story whether you like it or not. For Hus, an eight-month prison term in the middle of his story brought into focus what he didn't see before.
"My plan wasn't 'I'm going to do this rap ting, and I'm going to be a role model, and all the kids are going to look up to me'. But now I understand that, being in this position, it comes with it."
Top: John Lawrence Sullivan
Vest & Trousers: ABAGA VELLI
Shoes: Asics x Kiko Kostadinov
"When I was in jail, people would look at me like I'm crazy, asking 'How have you had this opportunity and ended up in here?'" He pauses to think. "Being humble is good, yeah, but I feel like I didn't know how big I was."
"That's what I've learned. People don't know how powerful they are, especially black men. We always degrade ourselves. We don't know ourselves. If you look at rap culture, it promotes boy-ism, it doesn't promote men. So a lot of us, we're 30, 40, and we're still boys. Can I ask you a question? How many black men that are 30-plus, do you think other black men want to be like?"
The question is rhetorical, and isn't really for me to answer. I'm just a sounding board for him to consider his learnings in real time. As he reflects on his journey into manhood, he mentions the recent loss of his father. "I wish I could speak to him because there's certain things that I used to hate about him that I see in myself. He was closed off. He was strict. He was stiff. He should have been in the army, would have been perfect in the military, still."
It must be strange to draw comparisons between his dad being "closed off" and his own inability to process his fear. How much does he think PTSD brought on from his earlier stabbing played a part in his decision to take a knife to Westfield? He sighs and leans back in his black leather studio chair. "I was a zombie," he says. "You know what it is, all this knife crime stuff – I feel like people undermine it, they don't understand the effects of it. You know like soldiers that go to war have PTSD, there was a point in my life, even to this day, if I walk in the street I have to look at every car that's driving past…" he trails off.
Jacket: Pronounce
"See, the life I lived before this music thing, it was hard innit," he says quietly. "A lot of us youths, we take the wrong path, we make decisions when we're young that we don't know is gonna affect us later."
I ask him how it feels to be so visible compared to his previous life of concealing his body and cautiously looking around corners. He takes a long, 30-second pause and we sit in silence for a moment, the question hanging in the air as he contemplates the differences between us before gently answering.
"See… for you, you walk into a room and you ain't gotta worry about nothing, you're calm. But me, I'm worrying, it's a distraction, it's a weakness. It's weird when I say it, but it makes some of your senses more stronger than others. When you walk into a room you see certain things, but for me, my head is elsewhere. I'm thinking about other things like…"
"…This could be a dangerous situation?"
I tell him that 24 hours prior, drill rappers Skengdo and AM were in parliament with Diane Abbott discussing the censorship of drill music, the rap movement that is accused of contributing to the increasingly high numbers of knife murders in the UK. The result has been widespread censorship of the sound.
"If you feel like the things they're rapping about are so shocking, why do you just want to put them in a cage?" he questions. "Give them some mental help! I feel like a lot of black people are suffering from mental illness. The argument shouldn't be about drill, the argument should be about: what can we all do? Everyone's saying 'it's drill, it's the drill artists.' But the person that's saying that, what have they done for knife crime?"
Spending time with Hus, even in these reflective moments, is energising. He is wickedly funny, quietly confident and disarmingly sweet. His real story, away from the tabloid headlines, is one of artistic exceptionalism – someone who has shifted the musical landscape so much, that it's difficult to think what the current charts, festival line-ups or radio would sound like without him. Contemporaries like MoStack, Dave and Stormzy all consider him inspirations, and Jae 5, his producer who re-joins him for this album, is hot property thanks to the magic of Common Sense.
His future plans will see him breaking out of this moment of quiet again, and include a trip to the Gambia later in the year, as well as festival appearances and a new album. This time, he's drinking it all in. If he didn't before, it seems like he finally gets it. He is a big deal. People are rooting for him. Before I leave the studio, I give him a hug and mention that he must be excited to go home. He gives a mock puzzled look in response: "…I'm home!"
Photography: Crowns & Owls
Styling & Direction: Ade & Michelle
J Hus appears at Lovebox, Gunnersbury Park, London, 12 July


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There are currently no public changelogs for the Mariculture Mod.


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The first round-the-world tour: the expedition of Ferdinand Magellan and Juan Sebastián Elcano
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The expedition organized and led by the Portuguese navigator Ferdinand Magellan was the first circumnavigation of the World of history. But he could not complete it because he died in a confrontation with the natives in the Philippines Islands. Juan Sebastian Elcano, who captained the expedition from Tidore to Spain, and the 18 sailors who survived such an impressive feat, did. This trip was entirely financed by the Spanish crown. At that time the young Carlos I of Spain reigned and with it the old dream of Cristopher Columbus to reach the Indies always sailing westward was achieved. Although the South Sea had already been discovered by Vasco Núñez de Balboa in 1513 and it was known that crossing the Central American isthmus on foot and then embarking could make this trip, but the size of the South Sea was unknown and no one had appeared interested in venturing into something so risky.
Portrait of Ferdinand Magellan
The Capitulations of Valladolid in 1519
Magellan had sailed for a long time in the Indian Ocean so he knew well the Asian and African coasts, but not the American ones. The Portuguese sailor had the idea of taking up again the project of Christopher Columbus and reaching the islands of the Spice by sailing westwards and overcoming the already known American continent at its southern end and crossing the South Sea to reach its goal. This project was proposed to the king of Portugal Manuel I but he considered that with the route already known to the Portuguese bordering Africa to reach Asian products made it uninteresting, besides the problems that could arise from the Treaty of Tordesillas that granted control of the area to Castile. But Magellan did not surrender and after asking the King of Portugal for permission to offer his services in other places, which eliminates the possibility of treating him as a traitor, he traveled to Spain and proposed the same project to Burgos Bishop Juan Rodríguez de Fonseca, right hand of King Carlos I and head of everything related to the Indies and overseas expeditions. There was some interest this time. For his peace of mind, the navigator assured the king that the entire route would always fall in the Castilian area, thus avoiding unwanted conflicts with the Portuguese. The initial idea of the trip was to get to the Moluccas and then return by the same route, that is, to cross the Pacific Ocean again and then ascend the Atlantic to Spain.
Through the Capitulations of Valladolid on March 22th, 1518 the king granted Magellan financial and material support and the title of governor and adelantado of the lands he discovered:
"Because you, Ferdinand Magellan, a knight born in the Kingdom of Portugal, and the Ruy Faleiro baccalaureate, also born in the Kingdom of Portugal, wanting to make us do a marked service, you are obliged to discover in the terms that belong to us and are ours in the ocean sea, within the limits of our demarcation, islands and firm lands, rich spices and other things that we will be very useful…"
In them was reflected some of the rights and grants granted to the capitulants:
The fifth part of the rights and profits corresponding to King Carlos I.
The title of governors and forwarders of conquered and discovered lands, these titles being inheritable in perpetuity.
They are allowed to buy whatever they want in Asia and sell it in Castile just by paying the monarch one-fifth of the profits obtained.
Of every six islands they discovered they could choose two where they would not have to pay the fifth real.
Map of Jorge Reinel in 1519. One can observe what was known about the Brazilian coast and the alleged distance to the Moluccan islands. Retrieved from www.iaph.es
The expedition consisted of 5 naos, 239 men and provisions that had to allow sailing for two years. The captain ship was the Trinidad captained by Ferdinand Magellan and the rest of the ships were the San Antonio of Juan de Cartagena, the Concepción of Gaspar de Quesada, the Victoria of Luis de Mendoza and the Santiago of Juan Serrano. Among the crew members were Antonio Pigafetta, an Italian writer and diplomat who enlisted to be the official chronicler of the expedition and who would relate in his "Relation of the first voyage around the world" all the details of the trip. Although the task of doing so was not for a hobby of historical science and literature, but because the Spanish crown demanded to be informed of all the details of the expedition, also traveled in it accountants and royal officers who monitored and recorded all the economic facts of it. Nothing remained unrecorded. Astronomer Ruy Faleiro, the main organizer along with Magellan and who claimed that the South Sea was very small, was expelled from the expedition, it is said for health reasons, and the Spanish captain Juan de Cartagena was included instead.
Rout Map of the Expedition of Magellan and Juan Sebastián Elcano
Departure from Seville, 10th August 1519
They left Seville on 10th August 1519 sailing the Guadalquivir River towards its mouth. After a few days they arrived in Sanlúcar de Barrameda (Cádiz – Spain), already on the Atlantic coast, where new adjustments were made to the expedition and several unforeseen problems were resolved. From here they departed on September 20th towards the Canary Islands where a first stopover would be made in Tenerife to provide themselves with more water and firewood, and continued to the Cape Verde Islands where Magellan on October 3th gave the order to turn west and set sail towards the coast of Brazil.
They sailed for a little over a month crossing the Atlantic Ocean undergoing several quite dangerous storms and after spending a month in South America, they arrived on December 13th at the Bay of Guanabara (Rio de Janeiro) where they disembarked to stretch their legs and recharge water and firewood and products from the area. They continued their journey along the Juan Díaz de Solís in his expedition of 1515 that led them to get into the Río de la Plata, known at that time as Río de Solís, during several kilometers thinking that this was the southern cape that would allow them to surpass the American continent. Disappointed sailors veered east to resume the current Argentine coast.
The Port of San Julián
They explored each bay, always to the south, each inlet of the sea trying to find that passage to the other Ocean but there was no luck and the weather was becoming more severe and colder. This led Magellan to decide to stop for a while to let winter pass. On March 31st, 1520 they found a sheltered bay called Puerto de San Julián and set out to winter for 6 months until the temperatures rose again. But what suddenly rose was the temperature of the expeditionaries when there was a rebellion of the Spanish captains who demanded to vote the return to Spain. They thought it was madness and certain death. The only answer they got was a resounding refusal from Magellan. Serious riots broke out that were suffocated and the rebels were finally apprehended. Three of the four captains were executed, only Juan de Cartagena was saved, who was banished and abandoned in those inhospitable lands. Something similar to being executed but slower and more painful.
On August 24th, the four surviving ships departed from San Julián, the nao Santiago had been stranded by a storm and had to abandon it, and they set out south, arriving at the end of October in a large bay called Todos los Santos. From there, and to minimize risks, they sent two ships to explore it and see what was there. After 3 days they returned, confirming that it did look like the southern passage, because after that bay there was another one with salt water. But that moment of joy had its bitter side for Magellan. The San Antonio pilot, Esteban Gómez, seeing the success, asked to return to Spain, argued that with that discovery had already fulfilled the mission and that they should return to inform, reorganize a new expedition and return to the route already discovered. But this did not please the Portuguese who refused roundly. Even so, the Castilian captain did not give his arm to twist and, disregarding the orders, one of the following nights he left for San Antonio and disappeared on his way to Spain. Luck wanted these fugitives on their way back to discover the Falkland Islands.
Mapa del extrecho de Magellan. Extraído de www.iaph.es
In the Strait of All Saints or Strait of Magellan
They continued sailing along the strait they called Todos los Santos, as well as the bay where they entered, observing the local fauna and flavor, the bonfires of the natives at night and anything that might be useful. Until suddenly they found themselves in the open sea on 27th November, they had managed to reach the Pacific Ocean. Magellan mistakenly decided not to touch the Chilean coast, a territory that had not yet been conquered by the Spaniards, and to go deep into the ocean, which he thought was the Indian Ocean and which in a few weeks would reach the Moluccan islands. I had no idea he was getting into the world's largest mass of water. It would be three long months of sailing without finding a single island to obtain water and food. Hunger and scurvy scourged the sailors. Pigafetta narrates it very starkly in her Relationship of the journey:
"The sponge cake we were eating was no longer bread, but a powder mixed with worms that had devoured all its substance, and also had an unbearable stench because it was impregnated with rat urine. The water we were forced to drink was equally rotten and stinking. In order not to starve to death, we were still forced to eat pieces of cow leather lined with the big cock to prevent the wood from destroying the ropes. This leather, always exposed to the water, the sun and the winds, was so hard that it was necessary to immerse it for four or five days in the sea to soften it a little; to eat it we put it immediately on the embers. Often we were still reduced to feeding on sawdust, and even rats, so repellent to man, had become such a delicate food that half a ducat was paid for each…"
The Mariana Islands
After three hellish months surrounded by salt water and sunshine, starvation and disease in which more than 30 men died on March 6th,1521, they spotted a tropical island full of palm trees and vegetation. They were on the island of Guam, which they called Thieves' Island because of the indiscriminate assault of expeditionaries by the local natives on board the ships to rob them of everything they could. Once the thieves had been subjected and normality recovered, they loaded the ships with water, meat and fruit and set out to continue sailing in search of the islands of the Species.
Death of Ferdinand Magellan
Hundreds of islands opened before them. They called them Islas del Poniente, later known as Islas Filipinas in honor of the then Prince of Asturias Felipe, who in a few years would become King Felipe II. They made their first contact with the natives, specifically on the island of Mactan, in the village of Cebu, they reached an agreement with King Hamubon to help him in his war against the chieftain Silapulapu. On April 27th,1521 Magellan marched along with some of his men to the island of said cacique with the intention of taking it by force and thus fulfill their commitment, but the natives were waiting for them and fell into an ambush in which Magellan was mortally wounded by a poisoned arrow. His corpse remained there and could not be picked up by his men.
He was replaced at the head of the expedition by Captain Duarte Barbosa. But the misfortune of the expedition did not end here. King Hamubón suspected that the Spaniards could betray him and murdered 27 Spaniards deceived with a fictitious banquet, including Barbosa. The survivors fled from there before falling into the hands of the natives in two of the naos, the Trinity, commanded by Gomez Espinosa who was appointed as the new captain general of the expedition, and the Victoria, commanded by Juan Sebastian Elcano. Nao Concepcion had to be abandoned and burned on the island of Bohol to keep it from falling into enemy hands. The low number of survivors would not be able to rule 3 naos, there was no other remedy.
During the month of May and June they sailed between the islands of the Chinese Sea until they arrived in July on the island of Borneo. There, the rajá Siripada invited the foreigners to a banquet where they could observe that the Bornanos wrote and had refined and very advanced customs. But they saw nothing more commercially interesting and decided to continue in search of the Moluccan islands that were, after all, the goal of their journey and what would get them out of the filth and poverty in which they found themselves.
Arrival to Tidore Island
Finally, on November 8th,1521, they arrived at the island of Tidore, one of the Moluccan islands. These islands are a group of about thirty small islands of volcanic origin. The welcome was very pleasant and they began to negotiate with Sultan Almansur offering Castilian utensils in exchange for cloves and nutmeg. They had to act quickly because these islands were in the Portuguese zone, not as promised by the astronomer to King Charles. They loaded the two ships with Asian wealth and tried to leave but in the same port the Trinity began to make waters and had to stay to be repaired, this increased the risk of being intercepted by the Portuguese so the captains of the expedition decided that Victoria nao continued the trip to Spain to the west and not as was planned to return where they had come from. The reason for this decision is not exactly known, but in my opinion this made the journey more difficult because they would have to cross through the centre of the Indian Ocean, an unknown route because there were no known islands, although this reduced the possibility of falling into Portuguese hands. The Trinity nao, once repaired tried the tournaviaje as planned but the continuous storms returned it to the Moluccas islands and finally, as feared, was captured by the Portuguese. Of its 50 crew members, 30 died while trying the Pacific tour. Of the rest, only four managed to return to Europe.
Placa en Sanlúcar de Barrameda (Cádiz – España) con los nombres de los supervivientes de la nao Victoria
Return to Spain
They arrived in Timor where they stocked up to start the crossing of the Indian Ocean. From there they departed on 11th February 1522, rounded the Cape of Good Hope avoiding the African ports but at the height of the Cape Verdean islands they had neither water nor food and the nao presented several waterways of concern. They decided to dock on the island of Santiago and pretending to come from America on an expedition to ask for help from the Portuguese, who initially showed themselves collaborators but when they realized that this ship was coming from the Moluccan islands they stopped the fifteen Spanish sailors who had landed but not the rest who managed to flee to Spain.
Juan Sebastián Elcano arrived in Sanlúcar de Barrameda on 6 September and in the port of Seville on 8th September 1522. The first circumnavigation of history had been completed, which took them about 75,000 km and was the first definitive test of the Earth's sphericity, although this fact had long been known. The day after the arrival in Seville, the 18 survivors in shirts and barefoot with a candle in their hands made good on their promise to visit the churches of Nuestra Señora de la Victoria and Santa María de la Antigua.
Two hundred and thirty-nine men departed from Sanlúcar and only 18 returned to the command of Juan Sebastian Elcano and another four months after the Trinity nao. With the spices transported, the expedition made considerable profits.
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Etiquetas Discoverys Expeditions Navigations XVI century
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By moviehangover1989 February 1, 2018 February 1, 2018
Leave a Comment on Early Man
Starring (voices): Eddie Redmayne, Tom Hiddleston, Maisie Williams
Director: Nick Park
Running Time: 89 mins
Synopsis: The Stone Age is almost over with only a small band of eccentric cavemen left. Content in their small patch of land they face losing it all when the Bronze Age rudely arrives at their door led by Lord Nooth (Hiddleston). However caveman Dug (Redmayne) will not go down without a fight challenging Nooth and his men to a game of football in order to decide their freedom.
Aardman have always carried with them a certain expectation of just what you're going to get with each new release, and particularly ones directed by their leader Nick Park (who returns here with his first feature since the 2008 Wallace and Gromit special). Of course you can be prepared for those painstakingly detailed claymation visuals, a gentle lightheartedness wherein plot machinations are kept remarkably simple, warm characters with delicately designed personalities and that comedic wit driven home in ceaseless usually genius puns. Now Early Man has some of these aspects but suffers in the main from a simplistic (even for them) storyline populated by remarkably thin characters.
Set thousands of years ago, caveman and dinosaur live side by side before the arrival of that pesky asteroid strangely wipes just the dinos out leaving the cavemen to discover the game of football using the charred up remains of said comet (don't ask!) It is a lovingly witty opening, taking such a large and defining event but skewering it through that low-key none more British sense of humour. Alas through the years the love of sport has died off, as have the cavemen, leaving but a small patch of land wherein resides Dug and his eccentric family. A collection of oddballs, one has a girlfriend who just so happens to be an inanimate rock, whom spend their days hunting rabbits with barely a thought about the bigger world. Even Dug, our hero, dreams of nothing more than the chance to hunt something bigger. Aardman are usually the kings of constructing interesting off-kilter peripheral characters, good with a one liner or humorous personality trait. But this time they all feel just a little bit staid and broad. We have the stupid one (voiced by Johnny Vegas, who else), the clingy one, the brash one and of course the wise elder leader (adeptly voiced by Timothy Spall). You can't help but like them even whilst none particularly stick in the mind.
This is especially troubling when even the central hero, Dug, makes little impact. Despite energetic voice work from Eddie Redmayne, he is little more than the cliched brave underdog. Out of his depth but persistently determined. There is none of the shrewd characterisation that gave Wallace and Gromit its heft. Although their gift for cheeky anthropomorphised animals is present and correct. Some life is given in the introduction of Lord Nooth. A pompous poorly French accented Tom Hiddleston (in a good way) smashes into Dug's home in a quest for metal. You see Nooth represents the incoming Bronze Age, slowly conquering the world with their newfound breakthrough. Much could have been made about the rise of one culture in place of another, and Park has fun juxtaposing the rugged nature of Dug against this technological might, but it rarely catches fire. Dug visits the home of Lord Nooth in a desperate plea to save his people. It is in this setting where that terrific Aardman visual play is in full effect. The screen chock full of clever sight gags that demand repeated viewings (one personal fave is the skinned coat of an actual zebra used as a zebra crossing), and verbally the lines vibe with numerously devilish puns.
Soon Dug finds himself in the midst of the centrepiece of Bronze Age life, mass congregations at the local stadium to watch football. The stadium a dazzingly constructed piece of artistry, so good is Aardman's work that sometimes you forget that this is all handcrafted and painstakingly put together. Throughout that loving attention to detail keeps you involved when the story tries hard to push you away. Sculpted with such care, those token glimpses of thumb prints in the figures are present and correct. Stop-motion never failing to fascinate me no matter how many times I see it (remember it takes 1000s of man hours to construct just 2 seconds of footage). It certainly helps to mask the sheer familiarity of the plot. After challenging Nooth's highly skilled football champions to a match whereby they could win their land back or if they lose end up working in a mine for life, Dug's family must then train to become worthy opponents. In turn giving rise to that ole so cliched moment, the montage. Sporadically funny it may be, and I'm quite partial to a sports montage, sadly it all too often limps along with no sense of engrossing excitement. Struggling along with little in the way of surprises before the inevitable and painfully obvious conclusion. At a scant 89 mins there is a brevity here that works against it rather than for it. Ending so soon after it has started only adding to its forgettable nature.
Production wise nothing can be faulted. Early Man coated in that homegrown charm, and voice work is uniformly brilliant. A bevy of names from the likes of TV, film and theatre show up to breathe some sense of fun into the unsurprising script. Particular praise should go to Hiddleston and Maisie Williams, brazenly confident as a local girl with big dreams, only to be pushed down thanks to some loosely described sexism. Broadly speaking shes a girl, so can't play football, adept complexity is not on the cards here. It is also nice to see that no matter the loud histrionics and noisy chaos Aardman's animated competitors seek out, that they are not afraid to keep to those gentle warm-hearted values that so dominated their earlier successes. What Early Man does make evident though is that after all these years evolution is required, a maturity in its storytelling should be pursued. After all, all the loquacious eloquent puns in the world don't make a heap of difference when you lack investment in the central conceit or its inhabitants. Doing a bad film would not be so bad if it meant they were tackling something new, doing a bland one, however, is just undeserving of the manpower invested to create it.
Verdict: Early Man has all the handcrafted charm, gentle tones and visual playfulness we've come to expect from Aardman. Sadly a painfully slight story populated by forgettable characters leaves it feeling largely listless.
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