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Ages of life, aesthetics, and art The paper aims to clarify the two notions whose relationship is thematized in the expression “ Art and ages of life”. First, it introduces to the various age-systems developed along the history of Europe and compares them with two other classifications of life courses : “ age group” and “ biological cycle”. The second part of the paper highlights the distinction between art and aesthetics, before exploring how the question of the ages of life can further our understanding of artistic creation and aesthetic reception., L’article se propose de clarifier les deux notions mises en relation dans l’expression «Les arts et les âges de la vie » . Il expose d’abord les différents systèmes des âges développés au fil de l’histoire européenne et les compare à deux autres classifications des parcours de vie : les classes d’âge et le cycle biologique. La seconde partie insiste sur la distinction entre art et esthétique avant d’explorer différentes manières selon lesquelles la question des âges de la vie peut nous aider à mieux comprendre la création artistique et la réception esthétique., Las edades de la vida, la estética y las artes El artículo pretende aclarar las dos nociones conjugadas en la expresión “ Las artes y las edades de la vida”. En la primera parte se exponen los distintos sistemas de las edades desarrollados a lo largo de la historia europea y se comparan con otras clasificaciones que atañen el curso de la vida : las clases de edad y el ciclo biológico. La segunda parte hace hincapié en la distinción entre el arte y la estética para luego explorar las distintas maneras en que la cuestión de las edades de la vida nos puede ayudar a comprender mejor la creación artística y la recepción estética., Schaeffer Jean-Marie. Âges de la vie, esthétique et arts. In: Communications, 109, 2021. Les arts et les âges de la vie. pp. 11-34.

Polycomb (Pc) group proteins are transcriptional regulators with key roles in development, cell identity and differentiation. Pc-bound chromatin regions form repressive domains that interact in 3D to assemble repressive nuclear compartments. Here, we used multiplexed chromatin imaging to investigate whether Pc compartments involve the clustering of multiple Pc domains during Drosophila development. Notably, 3D proximity between Pc targets is rare and involves predominantly pairwise interactions. These 3D proximities are particularly enhanced in segments where Pc genes are co-repressed. In addition, segment-specific expression of Hox Pc targets leads to their spatial segregation from Pc repressed genes. Finally, non-Hox Pc targets are proximal in regions where they are co-expressed. These results indicate that long-range Pc interactions are temporally and spatially regulated during differentiation and development but do not involve clustering of multiple distant Pc genes.

Inflammation driven by intracellular activation of the NLRP3 inflammasome is involved in the pathogenesis of a variety of diseases including vascular pathologies. Inflammasome specks are released into the extracellular compartment from disrupting pyroptotic cells. The potential uptake and function of extracellular NLRP3 inflammasomes in human coronary artery smooth muscle cells (HCASMC) are unknown. Fluorescently labeled NLRP3 inflammasome particles were isolated from a mutant NLRP3-YFP cell line and used to treat primary HCASMC for 4 and 24 h. Fluorescent and expressional analyses showed that extracellular NLRP3-YFP particles are internalized into HCASMC, where they remain active and stimulate intracellular caspase-1 (1.9-fold) and IL-1β (1.5-fold) activation without inducing pyroptotic cell death. Transcriptomic analysis revealed increased expression level of pro-inflammatory adhesion molecules (ICAM1, CADM1), NLRP3 and genes involved in cytoskleleton organization. The NLRP3-YFP particle-induced gene expression was not dependent on NLRP3 and caspase-1 activation. Instead, the effects were partly abrogated by blocking NFκB activation. Genes, upregulated by extracellular NLRP3 were validated in human carotid artery atheromatous plaques. Extracellular NLRP3-YFP inflammasome particles promoted the secretion of pro-atherogenic and inflammatory cytokines such as CCL2/MCP1, CXCL1 and IL-17E, and increased HCASMC migration (1.8-fold) and extracellular matrix production, such as fibronectin (5.8-fold) which was dependent on NFκB and NLRP3 activation. Extracellular NLRP3 inflammasome particles are internalized into human coronary artery smooth muscle cells where they induce pro-inflammatory and pro-atherogenic effects representing a novel mechanism of cell-cell communication and perpetuation of inflammation in atherosclerosis. Therefore, extracellular NLRP3 inflammasomes may be useful to improve the diagnosis of inflammatory diseases and the development of novel anti-inflammatory therapeutic strategies.

Este texto pone en diálogo la hermenéutica de Hans-Georg Gadamer, filósofo alemán, con la historiografía de François Hartog, historiador francés, a partir de sus libros más recientes: Croire en l’histoire y La Chambre de veille. Partiendo de una reflexión sobre la historicidad, se analiza el lugar que Hartog le otorga a la historia, en relación con la categoría de "regímenes de historicidad", así como respecto a una triple visión sobre el concepto historia: como creencia en la Historia, como pasado de la humanidad y como disciplina. Finalmente, se aborda la escritura de la historia en su relación con la novela, apuntando, así, a la discusión sobre la verdad y el tiempo en la historia, un problema tanto filosófico como histórico.

During pregnancy, maternal metabolic diseases and hormonal imbalance may alter fetal beta cell development and/or proliferation, thus leading to an increased risk for developing type 2 diabetes in adulthood. Although thyroid hormones play an important role in fetal endocrine pancreas development, the impact of maternal hypothyroidism on glucose homeostasis in adult offsprings remains poorly understood. Here, we show that when fed normal chow, adult mice born to hypothyroid mothers were more glucose-tolerant due to beta cell hyperproliferation and increased insulin sensitivity. However, following high fat feeding, these offsprings became profoundly hyperinsulinemic, insulin-resistant and glucose-intolerant compared to controls from euthyroid mothers. Suggesting presence of epigenetic changes, altered glucose metabolism was maintained in a second generation of animals. As such, gestational hypothyroidism induces long-term and persistent alterations in endocrine pancreas function, which may have important implications for type 2 diabetes prevention in affected individuals.SIGNIFICANCEDiabetes and hypothyroidism are two major public health issues, affecting ∼ 9 and 2 % of the population worldwide, respectively. As master metabolic gatekeepers, the thyroid hormones play an essential role in metabolism and fetal development. However, gestation increases demand on the thyroid axis in the mother, leading to hypothyroidism in 0.5 % of pregnancies. Maternal hypothyroidism is associated with deficits in fetal growth that may lead to long-term alterations in metabolism in the offspring. We therefore sought to investigate the effects of gestational hypothyroidism on glucose metabolism in adult offspring and their descendants, and how this may predispose to diabetes development.

Goats and sheep are valuable as they are a source of meat, milk, fleece, and other products. These livestock are also important both for agriculture and biomedical research. However, the efficient, sustainable, and profitable production of these small ruminants faces major obstacles. Hence, this review analyzes these major challenges specifically, their negative impacts on the industry, and suggests some science-based solutions to overcome them. Those challenged areas are education and training, research, translational research/biotechnology, goat and sheep health, and maintenance of an economically sustainable agribusiness. The suggested solutions include the effective teaching of goat and sheep science to the next generation and public empowerment, support for innovative and translational research, disease prevention and treatment, support for technology transfer, and development of sound agribusiness practices. This review is helpful particularly for scientists, students, and the goat and sheep producers. In general, these information on the current state of goat and sheep agriculture will also help the public to better understand and appreciate the challenges met and opportunities provided in small ruminant production enterprises.

Network coding simplifies routing decisions, improves throughput, and increases tolerance against packet loss. A fundamental limitation, however, is delay: decoding requires as many independent linear combinations as data blocks. Prioritized network coding reduces this delay problem by introducing a hierarchy of prioritization layers. What remains is the problem of choosing a layer to approach two often-contradicting goals: reduce delay until prioritized layers can be decoded and keep the total number of transmissions low. In this paper, we propose an algorithm for this problem that – based on limited feedback – primarily minimizes per-layer delay but identifies opportunities to reduce the required transmissions when per-layer delay is unaffected. Our evaluation shows that our algorithm improves per-layer delay compared to hierarchical network coding and is close to the theoretical optimum number of total transmissions. Moreover, we demonstrate how the proposed algorithm can benefit smart-factory applications that operationalize delay-sensitive information from the production process.

International audience; Pancreatic β-cells modulate insulin secretion through rapid sensing of blood glucose and integration of gut-derived signals. Increased insulin demand during pregnancy and obesity alters islet function and mass and leads to gestational diabetes mellitus and type 2 diabetes in predisposed individuals. However, it is unclear how blood-borne factors dynamically access the islets of Langerhans. Thus, understanding the changes in circulating molecule distribution that accompany compensatory β-cell expansion may be key to developing novel antidiabetic therapies. Here, using two-photon microscopy in vivo in mice, we demonstrate that islets are almost instantly exposed to peaks of circulating molecules, which rapidly pervade the tissue before clearance. In addition, both gestation and short-term high-fat-diet feeding decrease molecule extravasation and uptake rates in vivo in islets, independently of β-cell expansion or islet blood flow velocity. Together, these data support a role for islet vascular permeability in shaping β-cell adaptive responses to metabolic demand by modulating the access and sensing of circulating molecules.

Endocrine organs secrete a variety of hormones involved in the regulation of a multitude of body functions. Although pancreatic islets were discovered at the turn of the 19th century, other endocrine glands remained commonly described as diffuse endocrine systems. Over the last two decades, development of new imaging techniques and genetically-modified animals with cell-specific fluorescent tags or specific hormone deficiencies have enabled in vivo imaging of endocrine organs and revealed intricate endocrine cell network structures and plasticity. Overall, these new tools have revolutionized our understanding of endocrine function. The overarching aim of this Review is to describe the current mechanistic understanding that has emerged from imaging studies of endocrine cell network structure/function relationships in animal models, with a particular emphasis on the pituitary gland and the endocrine pancreas.

La question de la relation entre vérité et littérature se pose autrement selon qu’on aborde la littérature comme une forme d’art ou comme une forme de discours. Il faut aussi distinguer plusieurs régimes de vérité/fausseté, voire plusieurs types de réussite et d’échec littéraires qui ne peuvent peut-être pas tous être analysés en termes de vérité/non-vérité. À partir de là on peut envisager la relation entre valeur de vérité et fonction cognitive., Answers to the problem of the relation of literature and truth differ according to whether one takes literature as a form of art or as a form of discourse. One must also distinguish various regimes of truth and falsity and various kinds of literary success or failures which cannot all be analysed in terms of truth and falsity. Once these points are examined on can deal with the relation between truth value and cognitive function.

Both endocrine and non-endocrine cells of the pituitary gland are organized into structural and functional networks which are formed during embryonic development but which may be modified throughout life. Structural mapping of the various endocrine cell types has highlighted the existence of distinct network motifs and relationships with the vasculature which may relate to temporal differences in their output. Functional characterization of the network activity of growth hormone and prolactin cells has revealed a role for cell organization in gene regulation, the plasticity of pituitary hormone output and remarkably the ability to memorize altered demand. As such, the description of these endocrine cell networks alters the concept of the pituitary from a gland which simply responds to external regulation to that of an oscillator which may memorize information and constantly adapt its coordinated networks’ responses to the flow of hypothalamic inputs.

The secretion of endocrine hormones from pituitary cells finely regulates a multitude of homeostatic processes. To dynamically adapt to changing physiological status and environmental stimuli, the pituitary gland must undergo marked structural and functional plasticity. Endocrine cell plasticity is thought to primarily rely on variations in cell proliferation and size. However, cell motility, a process commonly observed in a variety of tissues during development, may represent an additional mechanism to promote plasticity within the adult pituitary gland. To investigate this, we used multiphoton time-lapse imaging methods, GH-enhanced green fluorescent protein transgenic mice and sexual dimorphism of the GH axis as a model of divergent tissue demand. Using these methods to acutely (12 h) track cell dynamics, we report that ovariectomy induces a dramatic and dynamic increase in cell motility, which is associated with gross GH-cell network remodeling. These changes can be prevented by estradiol supplementation and are associated with enhanced network connectivity as evidenced by increased coordinated GH-cell activity during multicellular calcium recordings. Furthermore, cell motility appears to be sex-specific, because reciprocal alterations are not detected in males after castration. Therefore, GH-cell motility appears to play an important role in the structural and functional pituitary plasticity, which is evoked in response to changing estradiol concentrations in the female.

Hormones are dynamically collected by fenestrated capillaries to generate pulses, which are then decoded by target tissues to mount a biological response. To generate hormone pulses, endocrine systems have evolved mechanisms to tightly regulate blood perfusion and oxygenation, coordinate endocrine cell responses to secretory stimuli, and regulate hormone uptake from the perivascular space into the bloodstream. Based on recent findings, we review here the mechanisms that exist in endocrine systems to regulate blood flow, and facilitate coordinated cell activity and output under both normal physiological and pathological conditions in the pituitary gland and pancreas.

The pulsatile release of hormone is obligatory for the control of a range of important body homeostatic functions. To generate these pulses, endocrine organs have developed finely regulated mechanisms to modulate blood flow both to meet the metabolic demand associated with intense endocrine cell activity and to ensure the temporally precise uptake of secreted hormone into the bloodstream. With a particular focus on the pituitary gland as a model system, we review here the importance of the interplay between blood flow regulation and oxygen tensions in the functioning of endocrine systems, and the known regulatory signals involved in the modification of flow patterns under both normal physiological and pathological conditions.

There are well-recognized sex differences in many pituitary endocrine axes, usually thought to be generated by gonadal steroid imprinting of the neuroendocrine hypothalamus. However, the recognition that growth hormone (GH) cells are arranged in functionally organized networks raises the possibility that the responses of the network are different in males and females. We studied this by directly monitoring the calcium responses to an identical GH-releasing hormone (GHRH) stimulus in populations of individual GH cells in slices taken from male and female murine GH-eGFP pituitary glands. We found that the GH cell network responses are sexually dimorphic, with a higher proportion of responding cells in males than in females, correlated with greater GH release from male slices. Repetitive waves of calcium spiking activity were triggered by GHRH in some males, but were never observed in females. This was not due to a permanent difference in the network architecture between male and female mice; rather, the sex difference in the proportions of GH cells responding to GHRH were switched by postpubertal gonadectomy and reversed with hormone replacements, suggesting that the network responses are dynamically regulated in adulthood by gonadal steroids. Thus, the pituitary gland contributes to the sexually dimorphic patterns of GH secretion that play an important role in differences in growth and metabolism between the sexes.

SummaryMemory T cells circulate through lymph nodes where they are poised to respond rapidly upon re-exposure to a pathogen; however, the dynamics of memory T cell, antigen-presenting cell, and pathogen interactions during recall responses are largely unknown. We used a mouse model of infection with the intracellular protozoan parasite, Toxoplasma gondii, in conjunction with two-photon microscopy, to address this question. After challenge, memory T cells migrated more rapidly than naive T cells, relocalized toward the subcapsular sinus (SCS) near invaded macrophages, and engaged in prolonged interactions with infected cells. Parasite invasion of T cells occurred by direct transfer of the parasite from the target cell into the T cell and corresponded to an antigen-specific increase in the rate of T cell invasion. Our results provide insight into cellular interactions during recall responses and suggest a mechanism of pathogen subversion of the immune response.

The intracellular parasite Toxoplasma gondii can establish persistent infection in the brain of a mammalian host, a standoff that involves the active participation of host CD8 T cells to control infection. CD8 T cells generally protect against intracellular pathogens by local delivery of effector molecules upon recognition of specific pathogen Ags on invaded host cells. However, the interactions between CD8 T cells, T. gondii, and APCs in the brain have not yet been examined. In this study we have used a mouse infection model in conjunction with two-photon microscopy of living brain tissue and confocal microscopy of fixed brain sections to examine the interactions between CD8 T cells, parasites, and APCs from chronically infected mice. We found that Ag-specific CD8 T cells were recruited to the brains of infected mice and persisted there in the presence of ongoing Ag recognition. Cerebral CD8 T cells made transient contacts with granuloma-like structures containing parasites and with individual CD11b+ APCs, including some that did not contain parasites. In contrast, T cells ignored intact Ag-bearing cysts and did not contact astrocytes or neurons, including neurons containing parasites or cysts. Our data represent the first direct observation of the dynamics of T cell-parasite interactions within living tissue and provide a new perspective for understanding immune responses to persistent pathogens in the brain.

The Toxoplasma gondii peptides recognized by protective CD8+ T cells remain uncharacterized. Shastri and colleagues identify an immunodominant T. gondii peptide generated by a mechanism dependent on the endoplasmic reticulum aminopeptidase ERAAP. The parasite Toxoplasma gondii replicates in a specialized intracellular vacuole and causes disease in many species. Protection from toxoplasmosis is mediated by CD8+ T cells, but the T. gondii antigens and host genes required for eliciting protective immunity are poorly defined. Here we identified GRA6, a polymorphic protein secreted in the parasitophorous vacuole, as the source of the immunodominant and protective decapeptide HF10 presented by the H-2Ld major histocompatibility complex class I molecule. Presentation of the HF10–H-2Ld ligand required proteolysis by ERAAP, the endoplasmic reticulum aminopeptidase associated with antigen processing. Consequently, expansion of protective CD8+ T cell populations was impaired in T. gondii–infected ERAAP-deficient mice, which were more susceptible to toxoplasmosis. Thus, endoplasmic reticulum proteolysis is critical for eliciting protective immunity to a vacuolar parasite.

James Joyce and the common man. Joyce differs from most of the great modernist novelists in that he is convinced that history is not an essential dimension of humanity. Joyce's fictional worlds dissolve history into everyday time, the time of individuals' lived lives. Nor is he a standard-bearer for the literary absolute or of the artistic absolute in general : the youthful enthusiasm for the religion of art is no longer endorsed by the author of Ulysses. Rather, his indifference to grand History is based on the conviction that the only measure of time suited to human beings is the individual life of each of them. To open up to the beauty of things, one must accept the inevitably contingent and open nature of life. Finnegan's Wake represents the epitome of this radical equalization, reducing to equal perplexity the cultured or ignorant reader, and even the author himself, faced with the proliferation of a work adhering rigorously to contingency., Joyce se distingue de la plupart des autres grands romanciers modernistes parce qu'il est convaincu que l'histoire n'est pas une dimension essentielle de l'humanité. Les mondes fictionnels joyciens dissolvent l'histoire dans le temps de la quotidienneté, donc dans la temporalité de la vie vécue des individus. Il n'est pas davantage le porte-voix de la thèse de l'absolu littéraire et, plus généralement, de l'absolu artistique : l'enthousiasme juvénile pour la religion de l'art n'est plus endossé par l'auteur d'Ulysse. Plutôt, son indifférence à la grande Histoire est fondée sur la conviction que la seule unité de mesure temporelle qui convienne aux humains est celle de la vie individuelle de chacun d'entre eux. Pour s'ouvrir à la beauté des choses, il faut accepter le caractère inévitablement contingent et ouvert de la vie. Finnegans Wake représente l'apogée de cette égalisation radicale, réduisant à une même perplexité le lecteur cultivé ou ignorant, et l'auteur lui-même, face au foisonnement d'une œuvre au plus près de la contingence., James Joyce y el hombre común. Joyce se distingue de la mayoría de los otros escritores modernistas por estar convencido de que la historia no es una dimensión esencial de la humanidad. Los mundos ficcionales joyceistas disuelven la historia en el tiempo de la cotidianidad, en la temporalidad de la vida vivida por los individuos. No es el portavoz de la tesis del absoluto literario y más generalmente del absoluto artístico : el entusiasmo juvenil por la religión del arte no recibe la aprobación del autor de Ulises. Mejor dicho, la indiferencia a la gran Historia está fundada sobre la convicción de que la única unidad de medida temporal que conviene a los humanos es la vida individual de cada uno. Para abrirse a la belleza de las cosas es necesario aceptar el carácter inevitablemente contingente y abierto de la vida. Finnegans Wake representa el apogeo de esa igualación radical, reduciendo a una misma perplejidad al lector cultivado o ignorante y al propio autor, frente a la expansión de una obra más cercana a la contingencia., Schaeffer Jean-Marie. James Joyce et l'homme du commun. In: Communications, 99, 2016. Démocratie et littérature. Expériences quotidiennes, espaces publics, régimes politiques. pp. 95-107.

Lithium is generally considered to be a simple metal, given its simple electronic structure with one valence electron. It is considered to follow a nearly free electron model and have a nearly spherical Fermi surface. However, away from ambient conditions, the behavior of lithium become much less simple. Under high pressures, lithium undergoes a series of symmetry-breaking phase transitions, even a metal to insulator transition; at low temperatures, lithium also undergoes a temperature-driven martensitic transformation. In this work, these deviations from simple models in lithium are investigated, both at ambient pressure and under high pressures, from the relative high temperature phenomenon of melting to low temperature measurements of superconductivity.

Dans Croire en l’histoire, il y a beaucoup de choses qui sont bonnes a penser, meme, ou peut-etre surtout, pour quelqu’un qui n’est pas historien, ce qui est evidemment mon cas. Mais je me limiterai a quelques questions abordees dans « Une inquietante etrangete » et par ricochet dans les belles pages du chapitre « Du cote des ecrivains : les temps du roman ». Les questions qui sont abordees dans « Une inquietante etrangete » sont multiples, puisqu’elles vont du linguistic turn au probleme de ...

International audience; Feeding behavior is exquisitely regulated by homeostatic and hedonic neural substrates that integrate energy demand as well as the reinforcing and rewarding aspects of food. Understanding the net contribution of homeostatic and reward-driven feeding has become critical because of the ubiquitous source of energy-dense foods and the consequent obesity epidemic. Hypothalamic agouti-related peptide-secreting neurons (AgRP neurons) provide the primary orexigenic drive of homeostatic feeding. Using models of neuronal inhibition or ablation, we demonstrate that the feeding response to a fast ghrelin or serotonin receptor agonist relies on AgRP neurons. However, when palatable food is provided, AgRP neurons are dispensable for an appropriate feeding response. In addition, AgRP-ablated mice present exacerbated stress-induced anorexia and palatable food intake--a hallmark of comfort feeding. These results suggest that, when AgRP neuron activity is impaired, neural circuits sensitive to emotion and stress are engaged and modulated by food palatability and dopamine signaling.

The age neutrality of the Social Communication Questionnaire (SCQ) was examined as a common screener for ASD. Mixed findings have been reported regarding the recommended cutoff score's ability to accurately classify an individual as at-risk for autism spectrum disorder (ASD) (sensitivity) versus accurately classifying an individual as not at-risk for ASD (specificity). With a sample from the National Database for Autism Research, this study examined the SCQ's sensitivity versus specificity. Analyses indicated that the actual sensitivity and specificity scores were lower than initially reported by the creators of the SCQ. Autism Res 2016, 9: 838-845. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Pyroglutamyl peptidases I (PPI) are cysteine peptidases of the clan CF, family C15, which hydrolyse N-terminal l -pyroglutamyl residues ( l -pGlu). The l -pGlu modification is a post-transcriptional modification that confers relative aminopeptidase resistance and, in some cases, is essential to the modified peptides’ biological activity. PPIs have been identified in a variety of organisms, although definitive biological functions have yet to be attributed to them. The L. major PPI was expressed in Escherichia coli as active recombinant enzyme, and shown to have biochemical properties more similar to mammalian than bacterial PPIs. The LmPPI active site catalytic triad of E101, C210, and H234 was confirmed by mutagenesis. PPI activity was detected in L. major promastigotes, and the enzyme localised to the parasite cytosol. No detectable phenotype could be observed for L . major PPI -deficient mutants, which retained infectivity to macrophages in vitro and mice. However, over-expression of the active PPI, but not inactive PPI C210A , in L . major impaired differentiation from the procyclic promastigote to the infective metacyclic promastigote. Susceptibility to a natural l -pGlu-modified antimicrobial peptide, gomesin, was tested using the different cell lines, which were all equally susceptible. Whilst PPI is widespread through the eukaryotic kingdom, this study now suggests that the enzyme is not essential for normal eukaryotic cell function. However, PPI could be involved in regulating the action of l -pGlu-modified peptides required for differentiation of L. major .