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Brain aminergic pathways are organized in parallel and interacting systems, which support a range of functions, from homoeostatic regulations to cognitive, and motivational processes. Despite overlapping functional influences, dopamine, serotonin, noradrenaline and histamine systems provide different contributions to these processes. The histaminergic system, long ignored as a major regulator of the sleep-wake cycle, has now been fully acknowledged also as a major coordinator of attention, learning and memory, decision making. Although histaminergic neurons project widely to the whole brain, they are functionally heterogeneous, a feature which may provide the substrate for differential regulation, in a region-specific manner, of other neurotransmitter systems. Neurochemical preclinical studies have clearly shown that histamine interacts and modulates the release of neurotransmitters that are recognized as major modulators of cognitive processing and motivated behaviours. As a consequence, the histamine system has been proposed as a therapeutic target to treat sleep-wake disorders and cognitive dysfunctions that accompany neurodegenerative and neuroinflammatory pathologies. Last decades have witnessed an unexpected explosion of interest in brain histamine system, as new receptors have been discovered and selective ligands synthesised. Nevertheless, the complete picture of the histamine systems fine-tuning and its orchestration with other pathways remains rather elusive. This Research Topic is intended to offer an inter-disciplinary forum that will improve our current understanding of the role of brain histamine and provide the fundamentals necessary to drive innovation in clinical practice and to improve the management and treatment of neurological disorders.
histamine receptors --- cognition --- wakefulness --- heterogeneity --- anxiety
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Psychologists studying cognitive processes and personality have increasingly benefited from the wealth of theory, methodology, and decision making paradigms used in economics and game theory. Similarly, for the economists, personality traits and basic cognitive processes offer a set of coherent explanatory constructs in economic behavior. Given the debate on preference invariance and behavioral consistency across contexts and domains, the papers in this topic shed light on the existence and effect of stable sets of idiosyncratic features on economic decision-making. While the effects of personality and cognition on economic decisions remain under-explored, the papers contributed in this topic offer more than a stimulus for further research. The general message could be that personality and cognitive processes offer the stable idiosyncratic ground on which individual decisions are made.
Personality --- Cognition --- Decision Making --- Experiments --- Behavioral Economics --- Heterogeneity --- Games
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Stochastic fluctuations are intrinsic to and unavoidable at every stage of neural dynamics. For example, ion channels undergo random conformational changes, neurotransmitter release at synapses is discrete and probabilistic, and neural networks are embedded in spontaneous background activity. The mathematical and computational tool sets contributing to our understanding of stochastic neural dynamics have expanded rapidly in recent years. New theories have emerged detailing the dynamics and computational power of the balanced state in recurrent networks. At the cellular level, novel stochastic extensions to the classical Hodgkin-Huxley model have enlarged our understanding of neuronal dynamics and action potential initiation. Analytical methods have been developed that allow for the calculation of the firing statistics of simplified phenomenological integrate-and-fire models, taking into account adaptation currents or temporal correlations of the noise. This Research Topic is focused on identified physiological/internal noise sources and mechanisms. By "internal", we mean variability that is generated by intrinsic biophysical processes. This includes noise at a range of scales, from ion channels to synapses to neurons to networks. The contributions in this Research Topic introduce innovative mathematical analysis and/or computational methods that relate to empirical measures of neural activity and illuminate the functional role of intrinsic noise in the brain.
Balanced network --- Channel noise --- heterogeneity --- Hodgkin-Huxley model --- neural networks --- neuronal variability --- stochastic dynamics
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This Research Topic covers the pathogenetic processes in Autism Spectrum Disorder (ASD) that underpin the translation of genetic vulnerability to clinically significant symptoms. Available research data in ASD suggests that it is a neural connectivity disorder and that the social communication and related neurobehavioural symptoms result from reduced synchronization between key _social brain_ regions. These interconnected neural systems can be understood through the relationship between functionally relevant anatomic areas and neurochemical pathways, the programming of which are genetically modulated during neurodevelopment and mediated through a range of epigenetic and environmental modulators. Elucidating the underlying molecular mechanisms can provide an invaluable window for understanding the neural wiring that regulates higher brain functions and consequent clinical phenotypes. In keeping with the multi modal and diverse origins of ASD, this Research Topic explores the genetic underpinnings and environmental modulation in the aetiology; neural substrates, biomarkers and endophenotypes that underlie clinical characteristics; as well as neurochemical pathways and pathophysiological mechanisms that pave the way for therapeutic interventions. Furthermore, since genetically mediated deficits and consequent functional impairments involve activity-dependent synapse development that depends on postnatal learning and experience, the trajectory towards the final clinical expression could be modulated by early interventions that exploit the neuronal maturation and brain plasticity. However, identifying these diverse pathogenetic processes and tailoring interventions would require subtyping ASD into homogeneous subgroups. In this regard, this topic covers the current state of evidence in the literature through topic reviews as well as ongoing original work that provides tangible hypotheses and directions for future research.
Autism Spectrum Disorder --- genotypes --- phenotypes --- neurodevelopment --- Early Intervention --- Neuroimaging --- Genetic Heterogeneity --- immune response --- subtypes --- brain plasticity
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The process of Epithelial-Mesenchymal-Transition (EMT) is known to result in a phenotype change in cells from a proliferative state to a more invasive state. EMT has been reported to drive the metastatic spread of various cancers and has also been associated with drug resistance to cytotoxics and targeted therapeutics. Recently phenotype switching akin to EMT has been reported in non-epithelial cancers such as metastatic melanoma. This process involves changes in EMT-Transcription Factors (EMT-TFs), suggesting that phenotype-switching may be common to several tumour types. It remains unclear as to whether the presence of both Epilthelial-like and Mesenchymal-like cells are a pre-requisite for phenotype switching within a tumour, how this heterogeneity is regulated, and if alteration of cell phenotype is sufficient to mediate migratory changes, or whether drivers of cell migration result in an associated phenotype switch in cancer cells. Similarly it has yet to be clarified if cells in an altered phenotype can be refractory to drug therapy or whether mediators of drug resistance induce a concurrent phenotypic change. Little is known today about the underlying genetic, epigenetic and transient changes that accompany this phenotypic switch and about the role for the tumor micro-environment in influencing it. Hence this is currently an area of speculation and keen interest in the Oncology field with wide-ranging translational implications. In this Frontiers Research Topic, we discuss our current understanding of these concepts in various cancer types including breast cancer, colorectal cancer and metastatic melanoma. This topic covers how these processes of cellular and phenotypic plasticity are regulated and how they relate to cancer initiation, progression, dormancy, metastases and response to cytotoxics or targeted therapies.
EMT --- Cancer --- signalling --- plasticity --- heterogeneity --- Therapy-resistance --- Phenotype-switching --- crosstalk --- Exosomes --- Immune System
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This book examines the measurement and econometric effects of ethnic diversity. This issue is of great relevance to research and policy and is currently being discussed a great deal in the literature. In particular, a sizable literature has suggested that ethnic diversity constitutes a significant barrier to economic development. The precise measurement and interpretation of these results are a matter of substantial controversy. In this book, the dynamics of ethnic diversity are being empirically analyzed for the first time. Furthermore, it develops and applies a new measure of ethnic diversity which takes the distance between groups into account, thus focusing on diversity rather than mere fragmentation. This book convincingly confronts theoretical considerations with (new) data and thereby provides a good mix of theory and empirics, making significant contributions to the current debates.
Approaches --- Cultural heterogeneity --- Diversity --- Dynamics --- Economic --- Ethnic --- Ethno-liguistic fractionalization (ELF) --- Implications --- Kolo --- Measurement --- minorities
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There are few more active frontiers in plant science than helping understand and predict the ecological consequences of on-going, global changes in climate, land use and cover, nutrient cycling, and acidity. This collection of research papers and reviews focuses on how these changes are likely to interact with two important factors, clonal growth in plants and the introduction of species into new regions by humans, to reshape the ecology of our world. Clonal growth is vegetative reproduction in which offspring remain attached to the parent at least until establishment. Clonal growth is associated with the invasiveness of introduced species, their tendency to spread after introduction and negatively affect other species. Will changes in climate, land cover, or nutrients further increase biological invasions by introduced, clonal plants? The articles in this book seek to address this question with new research and theory on clonal growth and its interactions with invasiveness and other components of global change.
Anthoxanthera philoxeroides --- clonal architecture and growth --- endophytic bacteria --- environmental heterogeneity --- epigenetics --- global change --- physiological integration --- phenotypic plasticity --- biological invasions --- Rapid evolution
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This book will cover topics related to the preparation and use of heterogeneous catalytic systems for the transformation of renewable sources, as well as of materials deriving from agro-industrial wastes and by-products. At the same time, the ever-increasing importance of bioproducts, due to the acceptance and request of consumers, makes the upgrade of biomass into chemicals and materials not only an environmental issue, but also an economical advantage.
selenium --- methylselenoesters --- entosis --- anticancer agent --- hypoxia --- tumor microenvironment --- tumor heterogeneity --- cancer --- cancer stem cells --- EMT --- cell plasticity --- DNA damage and repair --- immune evasion --- HIF --- selenium --- glutathione --- malignant --- viability --- DNA damage --- ER stress --- methylselenocysteine --- seleno-l-methionine --- clear-cell renal cell carcinoma microRNAs --- hypoxia-inducible factor --- antitumor activity --- selenium-binding protein 1 --- SBP1 --- SELENBP1 --- hSP56 --- cancer --- disease --- clear cell renal cell carcinoma --- hypoxia-inducible factors (HIFs) --- selenium --- PD-L1 --- miRNA --- VEGF --- mTOR inhibitors --- selenium species --- Se-containing nanoparticles --- anticancer --- chemotherapeutics --- epigenetics --- head and neck cancer --- selenium --- methylseleninic acid --- radiation --- lipid peroxidation --- glutathione --- tocopherol --- selenium --- isoselenourea --- melanoma --- STAT3 --- apoptosis
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