Auswahl der wissenschaftlichen Literatur zum Thema „Lineage-aracing modèle de souris“

Des études épidémiologiques et expérimentales suggèrent que la progression de la maladie rénale chronique (MRC) après une lésion initiale est génétiquement déterminée, mais les réseaux génétiques qui contribuent à cette prédisposition restent inconnus. Parmi les voies moléculaires potentielles impliquées dans la MRC, cette étude s'est concentrée sur la voie Hippo, une cascade de signalisation conservée au cours de l'évolution et cruciale pour la régulation de la taille des organes et de la prolifération cellulaire. Les protéines paralogues YAP et TAZ, deux coactivateurs transcriptionnels de la voie Hippo, ont récemment été identifiées comme étant également des mécanosenseurs, capables de détecter un large éventail de signaux mécaniques et de les traduire en programmes transcriptionnels spécifiques aux cellules. L'activation de YAP et TAZ a été impliquée dans la progression de plusieurs maladies rénales et dans la transition de la lésion rénale aiguë (LRA) à la MRC . Cependant, les mécanismes sous-jacents restent obscurs et leur rôle dans des conditions physiologiques n'est pas encore bien compris. L'objectif de ce projet est d'élucider le rôle de YAP et TAZ dans les tubules rénaux. Tout d'abord, en utilisant la combinaison de modèles de souris transgéniques et de néphrectomie comme modèle de MRC, nous avons étudié l'effet de l'inactivation sélective du gène Yap ou Taz dans les cellules tubulaires rénales dans ce contexte de maladie. Nos résultats ont révélé une redondance potentielle entre ces deux protéines dans les cellules épithéliales tubulaires. Il est intéressant de noter que nos souris déficientes à la fois en YAP et en TAZ ont développé spontanément un phénotype rénal sévère avec des lésions tubulaires, de la fibrose et de l'inflammation, qui a été décrit en détail dans ce travail. Grâce à l'analyse transcriptomique, nous avons identifié une nouvelle signature moléculaire qui pourrait permettre de mieux comprendre les mécanismes régulés par YAP et TAZ dans les cellules tubulaires. Paradoxalement, dans notre modèle de double knock-out, nous avons observé une aggravation de l'expression et de l'activation de YAP et TAZ, parallèlement à la progression des lésions. Ceci semble être le résultat d'une expansion des cellules « non recombinées », montrant les rôles complexes de YAP et TAZ dans la communication avec les cellules voisines. Ces données démontrent le rôle essentiel de YAP et TAZ dans le maintien de l'homéostasie tubulaire et l'équilibre complexe nécessaire à leur régulation. Cette complexité peut avoir des implications pour les stratégies thérapeutiques ciblant l'inhibition de YAP et TAZ dans les maladies rénales, surtout si l'on considère les effets secondaires potentiels qui pourraient rendre ces approches plus difficiles
Epidemiological and experimental studies suggest that the progression of Chronic Kidney Disease (CKD) after an initial injury is genetically determined, but the genetic networks that contribute to this predisposition remain unknown. Among the potential molecular pathways involved in CKD, this study focused on the Hippo pathway, an evolutionarily conserved signaling cascade crucial for regulating organ size and cell proliferation. The paralogs proteins YAP and TAZ, two transcriptional coactivators of the Hippo pathway, have recently been identified also as mechanosensors, capable of detecting a wide range of mechanical cues and translating them into cell-specific transcriptional programs. Activation of YAP and TAZ has been implicated to the progression of several kidney diseases and in the transition from acute kidney injury (AKI) to CKD. However, the underlying mechanisms remain unclear and their role under physiological conditions is still not well understood. The aim of this project is to elucidate the role of YAP and TAZ in the renal tubules. First, using the combination of inducing transgenic mouse models and nephrectomy as a model of CKD, we investigated the effect of the selective inactivation of Yap or Taz gene in renal tubular cells in this disease context. Our findings revealed a potential redundancy between these two proteins in tubular epithelial cells. Interestingly, our mice deficient in both YAP and TAZ developed a spontaneous severe renal phenotype with tubular injury, fibrosis and inflammation, which was described in detail in this work. Through transcriptomic analysis, we identified a new novel molecular signature that may provide further insight into the mechanisms regulated by YAP and TAZ in tubular cells. Paradoxically, in our double knock-out model, we observed a worsening of YAP and TAZ expression and activation, in parallel with the lesion progression. This appeared to be the result of an expansion of the "non-recombined" cells, showing the complex roles of YAP and TAZ in the cross-talk with the neighbouring cells. These data demonstrated the essential role of YAP and TAZ in maintaining tubular homeostasis and the intricate balance required for their regulation. This complexity may have implications for therapeutic strategies targeting the inhibition of YAP and TAZ in kidney disease, especially considering the potential side effects that could make such approaches more challenging

Chapter 2 addresses the idea of male lineage as a stable, intergenerational source of authority for medieval men. Continuing the argument of the book as a whole, it argues that Chaucer seeks to shake men’s faith in such modes of earthly power, deploying the Wife of Bath to undermine the system of lineage itself. The Wife intrudes into typical models of male heredity, criticizes the linear male temporality upon which lineage depends, and has the hag of her Tale offer a speech against the very mechanisms of male descent and likeness. This chapter also contrasts the Wife of Bath’s Tale to the ballad, the Knight and the Shepherd’s Daughter, arguing that while the scene of rape in each is very similar, the Wife of Bath renders her narrative deliberately less procreative in its orientation. Finally, the chapter argues that Chaucer also has the Wife of Bath attack modes of poetic genealogy, alienating poets from their literary forebears.

This chapter examines how DNA can provide temporal information: the longer genomes evolve separately the more different they will be. For molecular dates, we should expect the confidence intervals to be quite wide, because there are so many things that can influence the number of substitutions that accumulate in a lineage over time. Given that we rarely know what the underlying rates are, our confidence limits must include our uncertainty in the patterns of rate evolution, as well as the possible effect on date estimates of the various assumptions inherent in our models. Sometimes our confidence intervals might be formally expressed as a distribution of values derived from statistical analysis, other times they may represent the upper and lower estimates obtained by varying the assumptions on which the date estimates are based. The fossil record remains the primary source of information on the evolutionary past.

Abstract The third chapter focuses on the formative ambient albums of Brian Eno and his collaborators: Eno’s Discreet Music and the albums of the Ambient series. It examines the genesis, sound, and reception of these albums, which set the stylistic and discursive terms by which ambient would attain distinction from other genres of atmospheric music, especially new age. It explores how Eno applied the lessons of his experimental art training to the recorded medium, and how he constructed an avant-garde lineage for his records through references to artists like Erik Satie. It also explores how he, with collaborators Harold Budd and Laraaji, exuded pop sensibilities through modal improvisations that displayed a distinctive affective bent toward the detached, dreamy, introspective, and ambivalent. These records’ sensuous sounds, alongside Eno’s erudite authentications, provided the expressive and conceptual latticework for future musicians, listeners, and critics to reconceive ambient audio as hip and highbrow art.

Abstract Knowledge of the early evolution of the Mollusca comes from three main areas: the anatomy and fine structure of living primitive molluscs (Salvini-Plawen, 1980, 1991; Haas, 1981; Wingstrand, 1985; Haszprunar, 1988, 1992; Scheltema, 1993); the comparison of rRNA sequences (Field, Olsen, Lane, Giovannoni, Ghiselin, Raff, Pace and Raff, 1988; Ghiselin, 1988; Patterson, 1989; Lake, 1990; Tillier, Masselot, Phillipe and Tillier, 1992; Winnepennickx, Backeljau, van de Peer and De Wachter, 1992); and the Cambrian fossil record (Yochelson, 1963, 1978; Runnegar and Pojeta, 1974, 1985; Morris, 1990; Peel, 1990a-b; Yu, 1990). In addition, the unexpected discovery of head and tail valves on articulated individuals of Halkieria evangelista from the Early Cambrian of Greenland (Conway Morris and Peel, 1990) has stimulated interest in the molluscan stem lineage and its extinct side branches (Bengtson, 1992). The challenge for the future is to meld these very different sources of information into a coherent model for the early history of the phylum and its place within the Metazoa. Here, I examine the strengths and weaknesses of existing models in an attempt to provide a framework for future research.

What is a stem cell? The term is a combination of ‘cell’ and ‘stem’. A cell is a major category of living thing, while a stem is a site of growth and support for something else. In science today, a stem cell is defined as a cell derived from a multicellular organism, which is able to both self-renew (produce more stem cells of the same kind) and differentiate (produce cells corresponding to later developmental stages of the source organism). So the concept of a stem cell is somewhat complex, bearing on questions of biological individuality, relations between cells and organisms, and our understanding of development. Stem cell phenomena range from everyday to extraordinary laboratory products. On the everyday side: hair, skin, and blood cells are shed and replaced by ongoing stem cell activities. Stem cells help maintain organs and tissues in mature multicellular organisms. Regeneration in wound-healing is also, often, stem-cell mediated. The hydra’s mythic regeneration potential is due to its plentiful stem cells; similarly for plants. Looking to earlier developmental stages, embryonic cells also exhibit stem cell capacities. If such cells are removed from an early embryo and grown in artificial cell culture, this produces an embryonic stem cell line – an indefinitely renewable source of cells that can, under appropriate conditions, develop to produce many (even all) cell types found in a mature organism. Other experimental products of stem cells include embryoid bodies, organoids, and embryo-like structures. Stem cells are thus found in living organisms (in vivo) and grown artificially (in vitro). Stem cells raise several important metaphysical questions for philosophers of biology. One concerns biological individuality. Multicellular organisms are paradigmatic biological individuals. There are strong reasons to think cells are individuals. Stem cells are cells that divide and develop into other kinds of cell, tissues, organs, and even analogues of whole organisms. Are stem cells individuals? One way to answer this question is in terms of cell lineages. Complicating matters, stem cells mediate between cell and organismal levels of biological organisation. This raises questions about individuality and development for organisms and constituent cell lineages. Metaphysical theories about the nature of stem cells – natural kinds, causal mechanisms, processes – are also unsettled, as is the science. Different metaphysical theories about the nature of stem cells present a problem of theory choice. Alternatives include: stem cells as entities, stemness as a state, disposition to develop, and cell-environment systems. Our knowledge about stem cells is incomplete, based on many different kinds of experiment. The main ways of identifying stem cells are to find, grow, or make them: cell-sorting, in vitro culture, and reprogramming, respectively. The basic design is to remove cells from an organismal source and place them in an environment where they can self-renew. After measuring cell traits in this environment, some cells are moved to a new environment to encourage differentiation. Cell traits in the new environment are then measured. The results correlate traits of an organismal source, candidate stem cells, and differentiated cells. Collectively, these experiments yield many different varieties of stem cell. Characterisation of these varieties is closely tied to technologies and experimental methods for culturing, visualising, and manipulating cells. Uncertainty is a constant, however. It’s impossible to experimentally show that a single cell is a stem cell; all methods of identifying stem cells require populations of homogeneous stem cells. But homogeneity for cells that by definition transform into other things is a fragile assumption. Consequently, stem cells are identified relative to particular experimental methods. Our knowledge of stem cells accumulates by multiplying experimental contexts and relating their outcomes to one another. In practice, knowledge about stem cells has the form of a proliferating network of models. In vitro stem cells are a prominent example: concrete approximations of early developmental stages of a multicellular organism of a particular species. Other important stem cell-based models are organoids and human-animal chimeras. Different stem cell models complement one another, highlighting different aspects of development. More generally, stem cell biology is replete with abstract and concrete models. Social organisation of experiments and resultant models is important for understanding the epistemology of stem cell research. Abstract models play a less prominent role in stem cell research, although lineage tree models are important representations of stem cells and their potential. Classifying stem cells is an unsettled and messy affair, with many different cross-cutting or overlapping distinctions used in practice. There are many varieties of stem cell, but no single agreed-upon system for classifying them. Lineage tree models offer one prospect for such a system. In popular culture, stem cells are associated with medical promise on the one hand, and embryo destruction on the other. Stem cells are tokens of medical promise and hope; the idea being to use their potential to cure a wide range of injuries and diseases. This promise motivates stem cell ‘clinics’ alongside scientific research. The former peddle cures for many ailments unencumbered by scientific evidence or regulatory approval. The latter challenged by ethical questions about human embryo research. Tension between medical hopes and objections to human embryo research has produced a large bioethics literature. Key ethical debates are about research using human embryos, creating human–animal chimeras, and how to balance hope and hype in regulating and funding stem cell research. Broad anti-science cultural movements encourage proliferation of stem cell ‘clinics’ that market alleged cures directly to consumers, bypassing scientific and medical standards.

Entertainment Education (EE) drama intentionally designs and executes a media message to fulfill entertainment and education purposes to increase audiences' knowledge and awareness about educational issues. It is a strategy for consciously crafting drama serials to increase audience knowledge about social issues, change their behavior, shift social norms, and create attitudes (Wang et al., 2020). EE dramas can help by providing a lens that not only involves women's specific gendered roles but broadcasts programs on male identity that address gender equality and express the relationship between men and women (Lapsansky & Chatterjee, 2013). With the help of storytelling techniques, EE drama spreads awareness about a social problem. Still, it is necessary to understand how EE dramas directly or indirectly support women's empowerment and social awareness and how they portray female characters in programs. There is a chance to improve women's status by appealing to audiences' behaviour and providing information about women's social status. The study aims to explore how EE dramas have put forth women's development and social awareness by involving both men and women through storytelling techniques. This study analyzes the content of three entertainment–education dramas Adhafull (Half Full) (2016), Navrangi Re! (Nine to a Shade) (2019), and Life Navrangi (2022). The study traces the lineage of the arguments to the Entertainment-education programs, EE program, women empowerment, the portrayal of female characters, social awareness, and gender equality. This study assesses the research findings in changing behaviour, and the results show that the portrayal of the female characters and direct information about the social issue (gender inequality, domestic violence, health, and hygiene) is essential to motivate women to fight their battles against invisibility by getting inspired by role models and social awareness programs. The outcome explains that EE programs portray women as career-oriented, strong, choosing different career paths, and aware of health and sanitation. This study will spread consciousness in society on recognizing EE programs as a source of social awareness and women's development. The government and NGOs will have a new approach to launching new schemes for social issues by learning about EE drama and the characters' role in persuading an individual behaviour.

A continuing goal in biomaterials research is to understand how cell adhesion to the surrounding materials and/or matrix regulates cell behavior in 3D. Advanced understanding of these processes may aid the development of synthetic biomaterials for tissue engineering applications, as well as to help understand basic cellular processes. The majority of past work, however, has focused on cell behavior atop 2D substrates that poorly recapitulate the 3D in vivo microenvironment [1]. Recent reports have suggested that within 3D hydrogels, encapsulated human mesenchymal stem cell (hMSC) fate is not determined by cell morphology or matrix mechanics alone [2], but by gel-structure dependent traction force generation [3]. As hMSCs represent a promising cell source for regenerative applications [4], it is critical to better develop our understanding of the link between cell fate and microenvironmental physical and biochemical cues in 3D, with a focus on the range of materials used in regenerative medicine. In the current work, hMSCs were encapsulated within degradable and non-degradable hyaluronic acid (HA) hydrogels of similar elastic moduli to assess the influence of hydrogel remodeling and cellular traction generation on differentiation lineage specification.