237 research outputs found

    Morphological evidence for geologically young thaw of ice on Mars: a review of recent studies using high-resolution imaging data

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    Liquid water is generally only meta-stable on Mars today; it quickly freezes, evaporates or boils in the cold, dry, thin atmosphere (surface pressure is about 200 times lower than on Earth). Nevertheless, there is morphological evidence that surface water was extensive in more ancient times, including the Noachian Epoch (~4.1 Ga to ~3.7 Ga bp), when large lakes existed and river-like channel networks were incised, and early in the Hesperian Epoch (~3.7 Ga to ~2.9 Ga bp), when megafloods carved enormous channels and smaller fluvial networks developed in association with crater-lakes. However, by the Amazonian Epoch (~3.0 Ga to present), most surface morphogenesis associated with liquid water had ceased, with long periods of water sequestration as ice in the near-surface and polar regions. However, inferences from observations using imaging data with sub-metre pixel sizes indicate that periglacial landscapes, involving morphogenesis associated with ground-ice and/or surface-ice thaw and liquid flows, has been active within the last few million years. In this paper, three such landform assemblages are described: a high-latitude assemblage comprising features interpreted to be sorted clastic stripes, circles and polygons, non-sorted polygonally patterned ground, fluvial gullies, and solifluction lobes; a mid-latitude assemblage comprising gullies, patterned ground, debris-covered glaciers and hillslope stripes; and an equatorial assemblage of linked basins, patterned ground, possible pingos, and channel-and-scarp features interpreted to be retrogressive thaw-slumps. Hypotheses to explain these observations are explored, including recent climate change, and hydrated minerals in the regolith ‘thawing’ to form liquid brines at very low temperatures. The use of terrestrial analogue field sites is also discussed

    VIRTUAL FARMER: CONTROLLING PHYTOCHROME SIGNALING IN PLANTS THROUGH CYBER-PHYSICAL SYSTEM

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    Under external environment stimuli seedlings undergo variation of morphology and alterations in its genetic sequences. Phytochrome signaling i.e., feedback reaction of plants to photons and other nutrient cycle plays a crucial role in its maturation. In this research work we create a cyber physical system to control such morphogenesis of plants through the help of artificial intelligence framework which identifies and control the crucial feedback between plant's genetic transcription with respect to the external stimuli such as nutrients, electricity, magnetism. This leads to autonomously grow a plant without its disadvantageous traits by destabilizing its negatively acting transcriptional regulators and enhance the plant's advantageous features by controlling its positively acting transcriptional regulators. This has leaded us to control the plant metabolism, plant growth without soil, manipulate the immunity of plant against disease, develop a plant metabolic profile and maximizes its yield deprived off from its seasonal attribute.Â

    The role of glial cells in a mouse model of inherited retinal dystrophies

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    PhD ThesisInherited retinal dystrophies are a heterogeneous group of degenerative disorders characterised by genetically induced photoreceptor loss, leading to vision loss. Despite their genetic and clinical complexity, most inherited retinal dystrophies follow a common pathological pathway characterised by photoreceptor death and glial activation. Although glial activation has been widely reported in retinal degenerative diseases, the underlying mechanisms involved in the neuron-glial interaction and the role of glial activation in the degenerative process remain unclear. In this thesis, investigation of the relationship between glial activation and photoreceptor loss was conducted using a mouse model of Leber congenital amaurosis, the cone-rod homeobox (Crx) knockout mouse. The first part of the study aimed to establish a framework of photoreceptor death and glial activity during the degeneration process. Thinning of the outer nuclear layer suggested that, in the Crx retina, photoreceptors do not die at a constant rate, but occurred mostly during two rapid degeneration periods. Analysis of the glial activities revealed that changes in both microglial activity and Müller activity are highly correlated with the two waves of photoreceptor death. The second part of the study investigated the role of microglial activation in the photoreceptor degeneration process using a microglial inhibitor, Neurostatin. The results suggest that microglial activation accelerates photoreceptor loss and that inhibiting microglial activity could slow the process down. These findings demonstrate a spatiotemporal relationship between microglial activity and photoreceptor degeneration, indicating a possible contribution of microglial cells towards photoreceptor loss. Taken together, these observations suggest that microglial inhibition is a promising strategy for visual restoration in retinal degeneration and provides important insights for future studies on microglial activation in retinal diseases

    Dietary Polyunsaturated Fatty Acids Regulate Mammary Tumor Growth and Metastasis by Modulating Tissue Microenvironments

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    Omega (ω)-6 and ω-3 polyunsaturated fatty acids (PUFAs) are essential fatty acids (FAs) and the precursors of pro- and anti-inflammatory mediators respectively. Epidemiological studies have shown a lower incidence of breast cancer (BC) in the countries where long-chain (LC)-ω-3FAs consumption is higher; however, the role of ω-3FAs in BC growth and metastasis is poorly understood. We used isocaloric, isolipidic ω-6 and ω-3 (contains LC-ω-3FAs) diets and a pair-fed model to evaluate the effects of dietary PUFAs in mammary tumor metastasis. Our studies have resulted in several novel observations including that dietary LC-ω-3FAs modulate mammary gland (MG) microenvironments in non-tumor bearing (NTB) mice by lowering MG ductal density, epithelial cell proliferation, adipocyte hypertrophy and adipose tissue inflammation compared to the MGs in the ω-6 group. Similarly, we reported that dietary LC-ω-3FAs modulate the hepatic microenvironment (a common site of metastasis) by lowering hepatic steatosis, hepatocyte apoptosis, extramedullary myelopoiesis and NFκB expression relative to the respective observations in the ω-6 group. Finally, 4T1 mammary tumor studies in mice pre-exposed to these diets showed that, dietary LC-ω-3FAs delays mammary tumor induction and growth, and enhances survival of mice by lowering incidences/frequencies of spontaneous metastases to multiple organs including, lungs, liver, bone, heart, kidneys, ovaries and contralateral mammary glands compared to the respective analyses in the mice fed a ω-6 diet. In tumor microenvironments of mice fed a ω-3 diet, there were significantly lower numbers of proliferating tumor cells, neo-vascularization and a higher incidence of apoptotic tumor cells. Similarly, there was a significantly lower infiltration of myeloid cells including F-4/80+ macrophages and neutrophil elastase positive cell (granulocytes), and a higher infiltration of CD3+ T-Cells in tumors from mice fed an ω-3 diet relative to the ω-6 diet-fed group. There was a direct correlation between the neutrophil to T-cell ratio with tumor size and macrophage infiltration with neovascularization. There was also a direct correlation between T-cell infiltration and frequency of apoptotic tumor cells, indicating their roles in tumor growth. IL10 mRNA expression in tumors of mice fed an ω-3 diet was six fold higher, relative to the expression in the tumors from the ω-6 group, indicating a potential role of IL10 in the tumor growth suppression by dietary LC-ω-3FAs. In summary, our studies using isocaloric/isolipidic diets and a pair-fed model showed for the first time that dietary LC-ω-3FAs delay tumor growth and lower metastasis, and enhance survival by modulating the tissue microenvironments including MGs and liver

    Gardening Cyber-Physical Systems

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    cote interne IRCAM: Stepney12aNational audienceToday’s artefacts, from small devices to buildings and cities, are, or are becoming, cyber-physical socio-technical systems, with tightly interwoven material and computational parts. Currently, we have to la- boriously build such systems, component by component, and the results are often difficult to maintain, adapt, and reconfigure. Even “soft”ware is brittle and non-trivial to adapt and change. If we look to nature, how- ever, large complex organisms grow, adapt to their environment, and repair themselves when damaged. In this position paper, we present Gro-CyPhy, an unconventional computational framework for growing cyber-physical systems from com- putational seeds, and gardening the growing systems, in order to adapt them to specific needs. The Gro-CyPhy architecture comprises: a Seed Factory, a process for designing specific computational seeds to meet cyber-physical system requirements; a Growth Engine, providing the computational processes that grow seeds in simulation; and a Computational Garden, where mul- tiple seeds can be planted and grown in concert, and where a high-level gardener can shape them into complex cyber-physical systems. We outline how the Gro-CyPhy architecture might be applied to a significant exemplar application: a (simulated) skyscraper, comprising several mutually interdependent physical and virtual subsystems, such as the shell of exterior and interior walls, electrical power and data net- works, plumbing and rain-water harvesting, heating and air-conditioning systems, and building management control systems

    Modeling plant morphogenesis and growth

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    A Cdh3-β-catenin-laminin signaling axis in a subset of breast tumor leader cells control leader cell polarization and directional collective migration

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    Carcinoma dissemination can occur when heterogeneous tumor and tumor-stromal cell clusters migrate together via collective migration. Cells at the front lead and direct collective migration, yet how these leader cells form and direct migration are not fully appreciated. From live videos of primary mouse and human breast tumor organoids in a 3D microfluidic system mimicking native breast tumor microenvironment, we developed 3D computational models, which hypothesize that leader cells need to generate high protrusive forces and overcome extracellular matrix (ECM) resistance at the leading edge. From single-cell sequencing analyses, we find that leader cells are heterogeneous and identify and isolate a keratin 14- and cadherin-3-positive subpopulation sufficient to lead collective migration. Cdh3 controls leader cell protrusion dynamics through local production of laminin, which is required for integrin/focal adhesion function. Our findings highlight how a subset of leader cells interact with the microenvironment to direct collective migration

    The "Neuro-Glial-Vascular" Unit: The Role of Glia in Neurovascular Unit Formation and Dysfunction

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    The neurovascular unit (NVU) is a complex multi-cellular structure consisting of endothelial cells (ECs), neurons, glia, smooth muscle cells (SMCs), and pericytes. Each component is closely linked to each other, establishing a structural and functional unit, regulating central nervous system (CNS) blood flow and energy metabolism as well as forming the blood-brain barrier (BBB) and inner blood-retina barrier (BRB). As the name suggests, the "neuro" and "vascular" components of the NVU are well recognized and neurovascular coupling is the key function of the NVU. However, the NVU consists of multiple cell types and its functionality goes beyond the resulting neurovascular coupling, with cross-component links of signaling, metabolism, and homeostasis. Within the NVU, glia cells have gained increased attention and it is increasingly clear that they fulfill various multi-level functions in the NVU. Glial dysfunctions were shown to precede neuronal and vascular pathologies suggesting central roles for glia in NVU functionality and pathogenesis of disease. In this review, we take a "glio-centric" view on NVU development and function in the retina and brain, how these change in disease, and how advancing experimental techniques will help us address unanswered questions

    Chromatin and Epigenetics

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    Genomics has gathered broad public attention since Lamarck put forward his top-down hypothesis of 'motivated change' in 1809 in his famous book "Philosophie Zoologique" and even more so since Darwin published his famous bottom-up theory of natural selection in "The Origin of Species" in 1859. The public awareness culminated in the much anticipated race to decipher the sequence of the human genome in 2002. Over all those years, it has become apparent that genomic DNA is compacted into chromatin with a dedicated 3D higher-order organization and dynamics, and that on each structural level epigenetic modifications exist. The book "Chromatin and Epigenetics" addresses current issues in the fields of epigenetics and chromatin ranging from more theoretical overviews in the first four chapters to much more detailed methodologies and insights into diagnostics and treatments in the following chapters. The chapters illustrate in their depth and breadth that genetic information is stored on all structural and dynamical levels within the nucleus with corresponding modifications of functional relevance. Thus, only an integrative systems approach allows to understand, treat, and manipulate the holistic interplay of genotype and phenotype creating functional genomes. The book chapters therefore contribute to this general perspective, not only opening opportunities for a true universal view on genetic information but also being key for a general understanding of genomes, their function, as well as life and evolution in general

    Rule-based multi-level modeling of cell biological systems

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    <p>Abstract</p> <p>Background</p> <p>Proteins, individual cells, and cell populations denote different levels of an organizational hierarchy, each of which with its own dynamics. Multi-level modeling is concerned with describing a system at these different levels and relating their dynamics. Rule-based modeling has increasingly attracted attention due to enabling a concise and compact description of biochemical systems. In addition, it allows different methods for model analysis, since more than one semantics can be defined for the same syntax.</p> <p>Results</p> <p>Multi-level modeling implies the hierarchical nesting of model entities and explicit support for downward and upward causation between different levels. Concepts to support multi-level modeling in a rule-based language are identified. To those belong rule schemata, hierarchical nesting of species, assigning attributes and solutions to species at each level and preserving content of nested species while applying rules. Further necessities are the ability to apply rules and flexibly define reaction rate kinetics and constraints on nested species as well as species that are nested within others. An example model is presented that analyses the interplay of an intracellular control circuit with states at cell level, its relation to cell division, and connections to intercellular communication within a population of cells. The example is described in ML-Rules - a rule-based multi-level approach that has been realized within the plug-in-based modeling and simulation framework JAMES II.</p> <p>Conclusions</p> <p>Rule-based languages are a suitable starting point for developing a concise and compact language for multi-level modeling of cell biological systems. The combination of nesting species, assigning attributes, and constraining reactions according to these attributes is crucial in achieving the desired expressiveness. Rule schemata allow a concise and compact description of complex models. As a result, the presented approach facilitates developing and maintaining multi-level models that, for instance, interrelate intracellular and intercellular dynamics.</p
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