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Endothelial to mesenchymal transition in cardiovascular disease : JACC state-of-the-art review
(2019)
Endothelial to mesenchymal transition (EndMT) is a process whereby an endothelial cell undergoes a series of molecular events that lead to a change in phenotype toward a mesenchymal cell (e.g., myofibroblast, smooth muscle cell). EndMT plays a fundamental role during development, and mounting evidence indicates that EndMT is involved in adult cardiovascular diseases (CVDs), including atherosclerosis, pulmonary hypertension, valvular disease, and fibroelastosis. Therefore, the targeting of EndMT may hold therapeutic promise for treating CVD. However, the field faces a number of challenges, including the lack of a precise functional and molecular definition, a lack of understanding of the causative pathological role of EndMT in CVDs (versus being a “bystander-phenomenon”), and a lack of robust human data corroborating the extent and causality of EndMT in adult CVDs. Here, we review this emerging but exciting field, and propose a framework for its systematic advancement at the molecular and translational levels.
Substantia nigra dopamine (SN DA) neurons are progressively lost in Parkinson disease (PD). While the molecular and cellular mechanisms of their differential vulnerability and degeneration have been extensively studied, we still know very little about potential functional adaptations of those SN DA neurons that – at least for some time – manage to survive during earlier stages of PD. We utilized a partial lesion 6-OHDA mouse model to characterize initial electrophysiological impairments and chronic adaptations of surviving identified SN DA neurons, both in vivo and in vitro. Early after lesion (3 weeks), we detected a selective loss of in vivo burst firing in surviving SN DA neurons, which was accompanied by in vitro pacemaker instability. In contrast, late after lesion (>2 months), in vivo firing properties of surviving SN DA neurons had recovered in the presence of 2-fold accelerated pacemaking in vitro. Finally, we show that this chronic cell-autonomous adaptation in surviving SN DA neurons was mediated by Kv4.3 channel downregulation. Our study demonstrates substantial homeostatic plasticity of surviving SN DA neurons after a single-hit non-progressive lesion, which might contribute to the phenotype of initially surviving SN DA neurons in PD.
Osteosarcomas are aggressive bone tumours with a high degree of genetic heterogeneity, which has historically complicated driver gene discovery. Here we sequence exomes of 31 tumours and decipher their evolutionary landscape by inferring clonality of the individual mutation events. Exome findings are interpreted in the context of mutation and SNP array data from a replication set of 92 tumours. We identify 14 genes as the main drivers, of which some were formerly unknown in the context of osteosarcoma. None of the drivers is clearly responsible for the majority of tumours and even TP53 mutations are frequently mapped into subclones. However, >80% of osteosarcomas exhibit a specific combination of single-base substitutions, LOH, or large-scale genome instability signatures characteristic of BRCA1/2-deficient tumours. Our findings imply that multiple oncogenic pathways drive chromosomal instability during osteosarcoma evolution and result in the acquisition of BRCA-like traits, which could be therapeutically exploited.
Multiple exponence in morphology has recently attracted a good deal of attention (see, among others, Harris 2017; Caballero & Inkelas 2018). In this paper, I examine Modern Greek verbs which take an extra verbalizer (implicit multiple exponence). The simple base (bare form) and the base with the verbalizer co-exist in the lexicon without any semantic or aspectual opposition and can be used in the same syntactic context. Thus, they raise important questions for morphological theory. I argue that the explanation of this pleonastic addition may be hidden in the relation between inflection and derivation and the polyfunctional character of verbalizers in synthetic languages. Since the two forms co-exist and one member of each pair features an idiomatic association of meaning and complex form, morphological theory is challenged. I argue that these formations find a natural account within the framework of Construction Morphology (Booij 2010; Jackendoff & Audring 2019).
Known by many names, the Chinese banyan (Ficus microcarpa L.) is a monoecious plant species originating from south-eastern Asia which has been introduced as an ornamental in numerous areas outside its native range, including the Mediterranean. Like every species of Ficus, it is associated with a series of chalcid wasp species, known as fig wasps. These species are distributed in the families Agaonidae, Epichrysomallidae, Eurytomidae, Ormyridae and Pteromalidae. In this publication, we describe a new species of Ormyrus Westwood, 1832 (Hymenoptera, Chalcidoidea, Ormyridae), O. microcarpae Askew & Koutsoukos sp. nov., reared from figs of F. microcarpa collected from Greece and Cyprus. The new species is compared with O. lini and O. watshami. This species is likely to be a parasitoid of Meselatus bicolor Chen, 1999 (Hymenoptera, Epichrysomallidae). In addition, the previously unknown female of O. lini is also described and illustrated. This publication constitutes the first report of species of Ormyrus associated with figs in Europe.
To unravel the short-term climate variability during Marine Isotope Stage (MIS) 11, which represents a close analogue to the Holocene with regard to orbital boundary conditions, we performed microfacies and time series analyses on a ~3200-yr-long record of annually laminated Holsteinian lake sediments from Dethlingen, northern Germany. These biogenic varves comprise two sub-layers: A light layer, which is controlled by spring/summer diatom blooms, and a dark layer consisting mainly of amorphous organic matter and fragmented diatom frustules deposited during autumn/winter. Time series analyses were performed on the thickness of the light and dark layers. Signals exceeding the 95 % and 99 % confidence levels occur at periods that are near-identical to those known from modern instrumental data and Holocene palaeoclimatic records. Spectral peaks at periods of 90, 25, and 10.5 yr are likely associated with the 88-, 22- and 11-yr solar cycles, respectively. This variability is mainly expressed in the light layer spectra, suggesting solar influence on the palaeoproductivity of the lake. Significant signals at periods between 3 and 5 yr and at ~6 yr are strongest expressed in the dark layer spectra and may reflect an influence of the El Niño-Southern Oscillation (ENSO) and the North Atlantic Oscillation (NAO) during autumn/winter. Our results suggest that solar forcing and ENSO/NAO-like variability influenced central European climate during MIS 11 similar to the present interglacial, thus demonstrating the comparability of the two interglacial periods at sub-decadal to decadal timescales.
To unravel the short-term climate variability during Marine Isotope Stage (MIS) 11, which represents a close analogue to the Holocene with regard to orbital boundary conditions, we performed microfacies and time series analyses on a ~3200-yr-long record of annually laminated Holsteinian lake sediments from Dethlingen, northern Germany. These biogenic varves comprise two sub-layers: a light sub-layer, which is controlled by spring/summer diatom blooms, and a dark sub-layer consisting mainly of amorphous organic matter and fragmented diatom frustules deposited during autumn/winter. Time series analyses were performed on the thickness of the light and dark sub-layers. Signals exceeding the 95% and 99% confidence levels occur at periods that are near-identical to those known from modern instrumental data and Holocene palaeoclimatic records. Spectral peaks at periods of 90, 25, and 10.5 yr are likely associated with the 88-, 22- and 11-yr solar cycles, respectively. This variability is mainly expressed in the light sub-layer spectra, suggesting solar influence on the palaeoproductivity of the lake. Significant signals at periods between 3 and 5 yr and at ∼6 yr are strongest expressed in the dark sub-layer spectra and may reflect an influence of the El Niño-Southern Oscillation (ENSO) and the North Atlantic Oscillation (NAO) during autumn/winter. Our results suggest that solar forcing and ENSO/NAO-like variability influenced central European climate during MIS 11 similarly to the present interglacial, thus demonstrating the comparability of the two interglacial periods at sub-decadal to decadal timescales.
Owing to long-term similarities with regard to orbital climate forcing (i.e., low eccentricity and a dampened influence of precession), Marine Isotope Stage (MIS) 11 represents one of the closest astronomical analogues for present and future climate. Hence, insights into the climate variability of MIS 11 can contribute to a better understanding of the climatic evolution of the present (Holocene) interglacial as it would occur without human interference. In order to elucidate the natural climate variability during MIS 11, this study examines predominantly annually laminated lake sediments of Holsteinian age from Dethlingen, northern Germany. The Holsteinian interglacial is widely accepted to be the terrestrial equivalent of MIS 11c in central Europe and can be biostratigraphically correlated with the Hoxnian, Mazovian and Praclaux interglacials on the British Isles, in Poland and in France, respectively. These correlations yield the potential to cross-check the results from individual sites on a regional scale. This study is based on a multi-proxy approach including palynological, micropaleontological, sedimentological, geochemical and time series analyses within a wellconstrained chronological framework that has been established through varve counting and regional bio-stratigraphic correlations with other annually laminated archives of Holsteinian age. In particular, the here-presented study aims at (i) fingerprinting the long-term (centennial- to millennial-scale) and short-term (sub-decadal- to decadal-scale) climate variability during the Holsteinian interglacial, (ii) deciphering the nature, tempo and trigger mechanisms of abrupt climate change under interglacial boundary conditions, and (iii) assessing its impact on terrestrial ecosystems. With regard to long-term climate variability, the vegetation succession at Dethlingen as inferred from pollen data provides insights into the mesocratic to telocratic forest phases of a glacial-interglacial cycle spanning ~11500 (± 1000) years of the 15-16-ka-long Holsteinian interglacial. The development of temperate mixed forests suggests a general prevalence of mild climatic conditions during the Holsteinian. The older parts of the interglacial are characterised by the strong presence of boreal tree taxa (e.g., Picea), whereas the younger parts of the interglacial are marked by the expansion of sub-Atlantic to Atlantic forest elements (e.g., Abies, Buxus, Ilex, Quercus) and the decline of boreal tree taxa. This vegetation succession suggests a general warming trend and decreasing seasonality over the course of the Holsteinian interglacial. Based on the maximum pollen abundances of indicator tree taxa (e.g., Buxus and Quercus), peak warmth was reached during the later stages of the interglacial; it was accompanied by high humidity. The forest succession of the Holsteinian interglacial was punctuated by abrupt and gradual changes in the abundances of temperate plant taxa. These vegetation changes indicate considerable intra-interglacial climate variability. In particular, two marked declines of temperate taxa leading to the transient development of boreal and sub-boreal forests were triggered by centennial-scale climate oscillations, here termed Older and Younger Holsteinian Oscillations (OHO and YHO). These oscillations occurred ~6000 and ~9000 years after the onset of the interglacial pioneer forestation in central Europe, respectively. To assess the impact of abrupt climate change on terrestrial ecosystems during the Holsteinian and to investigate the underlying driving mechanisms, the intervals spanning the OHO and the YHO at Dethlingen were subjected to decadal-scale palynological and sedimentological analyses. Based on these data, the OHO comprises a 90-year-long decline of temperate taxa associated with expansion of Pinus and non-arboreal pollen, and a subsequent 130-year-long recovery of temperate taxa marked by the pioneer expansion of Betula and Alnus. Owing to its highly characteristic imprint on vegetation dynamics, the OHO can be identified in pollen records from the central European lowlands north of 50º latitude, from the British Isles to Poland. A close inspection of individual pollen records from that region reveals the prevalence of colder winters during the OHO, with a gradient of decreasing temperature and moisture availability, and increased continentality towards eastern Europe. This climate pattern points to a weakened influence of the westerlies and/or stronger influence of the Siberian High connected to the OHO. The vegetation dynamics during the YHO are characterised by a decline of temperate taxa (particularly of Carpinus) and the expansion of pioneer trees (mainly Betula). In contrast to the OHO, frost-sensitive taxa (e.g., Ilex, Buxus and Hedera) continued to thrive. This suggests that mean winter temperatures remained relatively high (>0 ºC) during the YHO pointing to a decrease of summer warmth related to the climatic deterioration. The YHO, which has a duration on the order of 300 years, is centered within a long-term (~1500-year) decline and subsequent, millennial-scale recovery of temperate taxa. Because the impact of the OHO and the YHO on the vegetation at Dethlingen was markedly different, both short-term climate oscillations may have been caused by different trigger mechanisms. For the OHO, the inferred regional-scale winter cooling over central Europe lasting for several decades points to a decrease in ocean heat transport, most likely related to a transient slowdown in North Atlantic Deep Water formation. This view is supported by the strong resemblance of the OHO to the 8.2 ka event of the Holocene with regard to the duration, imprint on terrestrial ecosystems, spatial pattern of the climatic impact, timing within the respective interglacial, and prevailing interglacial boundary conditions. In contrast, the presence of frost-sensitive taxa during the YHO appears to exclude a reduction in oceanic heat transport as postulated for the OHO. Instead, the long-lasting, gradual changes in the abundances of temperate taxa suggest a connection to orbital forcing, with the triggering mechanism causing the centennial-scale vegetation setback itself remaining unclear. The characteristics of short-term climate variability were investigated based on microfacies and time series analyses of a ~3200-year-long, annually laminated window of the Dethlingen record. The annual laminations at Dethlingen comprise biogenic varves consisting of two discrete sub-layers. The light layers, which are controlled by the intensity of diatoms blooms during spring/summer, reflect changes in the productivity of the Dethlingen palaeolake. In contrast, the dark layers, which consist predominantly of amorphous organic matter and fragmented diatom frustules, represent sediment deposition during autumn/winter. Spectral analyses of the thicknesses of the light and dark layers have revealed several peaks exceeding the 95% and 99% confidence levels that are near-identical to those known from modern instrumental data and Holocene records. Decadal-scale signals at periods of 90, 25, and 10.5 years are likely associated with the 88-, 22- and 11-year solar cycles; hence, solar activity appears to have been a forcing agent in productivity changes of the Dethlingen palaeolake. Sub-decadal-scale signals at periods between 3 and 5 years and ~6 years may reflect an influence of the El Niño-Southern Oscillation (ENSO) and the North Atlantic Oscillation (NAO) on varve formation during winter.
The Mediterranean realm, comprising the Mediterranean and Macaronesian regions, has long been recognized as one of the world’s biodiversity hotspots, owing to its remarkable species richness and endemism. Several hypotheses on biotic and abiotic drivers of species diversification in the region have been often proposed but rarely tested in an explicit phylogenetic framework. Here, we investigate the impact of both species-intrinsic and -extrinsic factors on diversification in the species-rich, cosmopolitan Limonium, an angiosperm genus with center of diversity in the Mediterranean. First, we infer and time-calibrate the largest Limonium phylogeny to date. We then estimate ancestral ranges and diversification dynamics at both global and regional scales. At the global scale, we test whether the identified shifts in diversification rates are linked to specific geological and/or climatic events in the Mediterranean area and/or asexual reproduction (apomixis). Our results support a late Paleogene origin in the proto-Mediterranean area for Limonium, followed by extensive in situ diversification in the Mediterranean region during the late Miocene, Pliocene, and Pleistocene. We found significant increases of diversification rates in the “Mediterranean lineage” associated with the Messinian Salinity Crisis, onset of Mediterranean climate, Plio-Pleistocene sea-level fluctuations, and apomixis. Additionally, the Euro-Mediterranean area acted as the major source of species dispersals to the surrounding areas. At the regional scale, we infer the biogeographic origins of insular endemics in the oceanic archipelagos of Macaronesia, and test whether woodiness in the Canarian Nobiles clade is a derived trait linked to insular life and a biotic driver of diversification. We find that Limonium species diversity on the Canary Islands and Cape Verde archipelagos is the product of multiple colonization events followed by in situ diversification, and that woodiness of the Canarian endemics is indeed a derived trait but is not associated with a significant shift to higher diversification rates. Our study expands knowledge on how the interaction between abiotic and biotic drivers shape the uneven distribution of species diversity across taxonomic and geographical scales.
This is the tenth article in our series Trouble on the Far-Right.
How can a racist party that was getting less than 0.2% of the vote for years, enter parliament with 18 MPs? How can a party that promotes violence, hate, sexism and murders amplify its reach after each pogrom? How can Golden Dawn remain the third political power in Greece for four years? And what’s in the mind of a Golden Dawner?...
Bi Tirga
(2011)
Leonard Bi Tirga, son of a poor peasant, is a studious pupil. Due to shortage of finances, he has to leave school to make ends meet and pursue his studies. Leonard becomes a sweatshop labourer. As a young labourer, his life like that of his peers is hard. The pay rate is low and the work is hard. With his friends, they engage in trade union activism. A series of complicated and trying events reinforces their conviction to militate. Thus, Leonard and his friend Camille become Union leaders. Leonard's character trait and uprightness explains the book title, Bi Tirga. In the Moore language, this means a well educated, honest, hardworking, courageous and well-behaved youth.
DEDICACES GRATITUDES INTRODUCTION- - - -- - - - - - - - - - - - - - - - - - - -7 Formulation, délimitation et choix du sujet- - -- - - - - - - - - - - - - - - - - - - - - 9 Hypothèse de recherche- - - - - - -- - - - - - - - - - - - - - - - - - - - - -11 Cadre méthodologique- - - - - - -- - - - - - - - - - - - - - - - - - - - - - - - 13 PREMIERE PARTIE : INSCRIPTION DU DON DANS L’OEUVRE D’AMINATA SOW FALL CHAPITRE I : TYPOLOGIE DES DONS- - - - - - - - - - - - - - - - - - - - - - - 17 I.1.Le don des biens et services I.2.Le don de soi et de temps CHAPITRE II : ACTEURS DU DON- - - - - - - - - - - - - - - - - - - - - - - - - - - - 19 II.1.Le donateur II.2.Le donataire II.3.L’intermédiaire CHAPITRE III : AUTOUR DU DON- - - - - - - - - - - - - - - - - - - - - - - - - - - -21 III.1.Le don comme forme d’échange III.2.Le don comme facteur d’intérêt DEUXIEME PARTIE : DON ET SOCIETE CHAPITRE IV : MOTIVATIONS DU DON- - - - - - - - - - - - - - - - - - - - - - -25 IV.1.La religion et l’indigence IV.2.La culture africaine CHAPITRE V : AVANTAGES DU DON- - - - - - - - - - - - - - - - - - - - - - - - - 27 V.1.Le don comme acte humanitaire V.2.Le don comme vecteur du lien social CHAPITRE VI : DESAGREMENTS DU DON- - - - - - - - - - - - - - - - - - - - -29 VI.1.L’émergence des classes VI.2.La dette morale CONCLUSION- - - - - - - - - - - - - - - - - - - - - - - - - - - - - 31 BIBLIOGRAPHIE- - - - - - - - - - - - - - - - - - - - - - - - - - - - 32 -------------------------------------------------------------------------------------------------- CRELAF (Cercle de Reflexion des Etudiants en Littératures Africaines), Département de Littératures Africaines, Université Omar Bongo, Gabon
« Et si les crocodiles pleuraient pour de vrai… » est une nouvelle dans laquelle, semblet-il, l’écrivain et théoricien Ludovic Emane Obiang paraît asseoir une conception du monde et de la littérature basée sur une figure profonde de même qu’un phénomène essentiel que sont la figure du crocodile et le phénomène de la reconstruction. Sa nouvelle paraît nous plonger au coeur d’une question essentielle source de véritables angoisses. Les crocodiles pleurent-ils ? Et s’ils pleurent, pleurent-ils pour de vrai ? A quoi devons nous faire attention lorsqu’on nous invite à penser à partir de la figure du crocodile ? Ensuite, en quoi cette figue de crocodile a-t-elle rapport avec quelque chose de l’ordre de la reconstruction, car comme le souligne Ludovic Obiang, le maître mot de sa nouvelle est le phénomène de la reconstruction ? Qu’est-ce que la reconstruction ? A quoi renvoie la réalité du crocodile ?
En 1999, un roman vient révolutionner la pratique littéraire au Gabon : Le jeune officier. OEuvre dédiée à Martin Heidegger, elle développe à sa manière les préoccupations du philosophe concernant l’être, l’oubli de l’être et le caractère aléthéique de la vérité. Les pages qui suivent sont consacrées à ce roman d’un style particulier qui insère le roman gabonais entre modernité et post-modernité. A travers un résumé, un commentaire du discours du jeune officier et la lecture du discours de soutenance de Brice levy Koumba1, nous tenterons de découvrir l’oeuvre. Le résumé est à la première personne, fait par le jeune officier lui-même. -------------------------------------------------------------------------------------------- CRELAF (Cercle de Reflexion des Etudiants en Littératures Africaines), Département de Littératures Africaines, Université Omar Bongo, Gabon
Un moment de ma vie
(2008)
Pour Eric Joël Békalé, la chasse illustre « le parcours de l’homme sur terre ». Ce parcours vise la réalisation de l’homme véritable. L’homme véritable, se conçoit comme « un être pas comme les autres1 ». A la base, il prend conscience que l’homme est un état qui se construit. Au final il n’a plus rien de commun car il devient « le début et la fin de toute chose». La chasse comme processus de réalisation de l’humain dans sa propriété, est aussi l’opération par laquelle l’homme quête son bonheur par le plaisir, le savoir et le pouvoir. Il doit pour se faire réduire la peur et trouver sa place. Car celui qui a peur n’est pas un homme et celui qui n’est pas un homme se prive l’accès au bonheur. « La chasse est une affaire d'homme. Que celui qui a peur de mourir mange les feuilles de manioc ».
L’analyse qui suit a pour objet la notion du double chez Alain Mabanckou. Cette notion est étudiée telle qu’elle se donne à lire dans Mémoire de porc-épic, roman paru en 2006 aux éditions du Seuil. Ce qui nous intéresse ici c’est le rapport possible existant entre double, parole et ponctuation. Présenté ainsi, nous cherchons à comprendre cette particularité du texte de Mabanckou qui est une longue phrase sans ponctuation, sinon n’étant ponctuée que par des virgules.
This paper proposes a new approach for modeling investor fear after rare disasters. The key element is to take into account that investors’ information about fundamentals driving rare downward jumps in the dividend process is not perfect. Bayesian learning implies that beliefs about the likelihood of rare disasters drop to a much more pessimistic level once a disaster has occurred. Such a shift in beliefs can trigger massive declines in price-dividend ratios. Pessimistic beliefs persist for some time. Thus, belief dynamics are a source of apparent excess volatility relative to a rational expectations benchmark. Due to the low frequency of disasters, even an infinitely-lived investor will remain uncertain about the exact probability. Our analysis is conducted in continuous time and offers closed-form solutions for asset prices. We distinguish between rational and adaptive Bayesian learning. Rational learners account for the possibility of future changes in beliefs in determining their demand for risky assets, while adaptive learners take beliefs as given. Thus, risky assets tend to be lower-valued and price-dividend ratios vary less under adaptive versus rational learning for identical priors. Keywords: beliefs, Bayesian learning, controlled diffusions and jump processes, learning about jumps, adaptive learning, rational learning. JEL classification: D83, G11, C11, D91, E21, D81, C61
Modern macroeconomics empirically addresses economy-wide incentives behind economic actions by using insights from the way a single representative household would behave. This analytical approach requires that incentives of the poor and the rich are strictly aligned. In empirical analysis a challenging complication is that consumer and income data are typically available at the household level, and individuals living in multimember households have the potential to share goods within the household. The analytical approach of modern macroeconomics would require that intra-household sharing is also strictly aligned across the rich and the poor. Here we have designed a survey method that allows the testing of this stringent property of intra-household sharing and find that it holds: once expenditures for basic needs are subtracted from disposable household income, household-size economies implied by the remainder household incomes are the same for the rich and the poor.
Most simulated micro-founded macro models use solely consumer-demand aggregates in order to estimate deep economy-wide preference parameters, which are useful for policy evaluation. The underlying demand-aggregation properties that this approach requires, should be easy to empirically disprove: since household-consumption choices differ for households with more members, aggregation can be rejected if appropriate data violate an affine equation regarding how much individuals benefit from within-household sharing of goods. We develop a survey method that tests the validity of this equation, without utility-estimation restrictions via models. Surprisingly, in six countries, this equation is not rejected, lending support to using consumer-demand aggregates.