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Accurate molecular concentrations are essential for reliable analyses of biochemical networks and the creation of predictive models for molecular and systems biology, yet protein and metabolite concentrations used in such models are often poorly constrained or irreproducible. Challenges of using data from different sources include conflicts in nomenclature and units, as well as discrepancies in experimental procedures, data processing and implementation of the model. To obtain a consistent estimate of protein and metabolite levels, we integrated and normalized data from a large variety of sources to calculate Adjusted Molecular Concentrations. We found a high degree of reproducibility and consistency of many molecular species across brain regions and cell types, consistent with tight homeostatic regulation. We demonstrated the value of this normalization with differential protein expression analyses related to neurodegenerative diseases, brain regions and cell types. We also used the results in proof-of-concept simulations of brain energy metabolism. The standardized Brain Molecular Atlas overcomes the obstacles of missing or inconsistent data to support systems biology research and is provided as a resource for biomolecular modeling.

The neocortex is densely innervated by basal forebrain (BF) cholinergic neurons. Long-range axons of cholinergic neurons regulate higher-order cognitive function and dysfunction in the neocortex by releasing acetylcholine (ACh). ACh release dynamically reconfigures neocortical microcircuitry through differential spatiotemporal actions on cell-types and their synaptic connections. At the cellular level, ACh release controls neuronal excitability and firing rate, by hyperpolarizing or depolarizing target neurons. At the synaptic level, ACh impacts transmission dynamics not only by altering the presynaptic probability of release, but also the magnitude of the postsynaptic response. Despite the crucial role of ACh release in physiology and pathophysiology, a comprehensive understanding of the way it regulates the activity of diverse neocortical cell-types and synaptic connections has remained elusive. This review aims to summarize the state-of-the-art anatomical and physiological data to develop a functional map of the cellular, synaptic and microcircuit effects of ACh in the neocortex of rodents and non-human primates, and to serve as a quantitative reference for those intending to build data-driven computational models on the role of ACh in governing brain states.

This study examines the heterogeneity of the 'visiting friends and relatives' (VFR) travel market with respect to a large urban destination in Russia, including trip planning, travel concerns, on-site destination experience, and post-travel behavior variables. Specifically, the study investigates whether place of residence, accommodation type, and VFR type can serve as segmentation bases for the city's destination management organization. It was found that place of residence and accommodation type best discriminate among VFR tourists. Marketing implications for improving destination experience and communications with tourist segments are discussed. [ABSTRACT FROM AUTHOR]

Accurate molecular concentrations are essential for reliable analyses of biochemical networks and the creation of predictive models for molecular and systems biology, yet protein and metabolite concentrations used in such models are often poorly constrained or irreproducible. Challenges of using data from different sources include conflicts in nomenclature and units, as well as discrepancies in experimental procedures, data processing and implementation of the model. To obtain a consistent estimate of protein and metabolite levels, we integrated and normalized data from a large variety of sources to calculate Adjusted Molecular Concentrations. We found a high degree of reproducibility and consistency of many molecular species across brain regions and cell types, consistent with tight homeostatic regulation. We demonstrated the value of this normalization with differential protein expression analyses related to neurodegenerative diseases, brain regions and cell types. We also used the results in proof-of-concept simulations of brain energy metabolism. The standardized Brain Molecular Atlas overcomes the obstacles of missing or inconsistent data to support systems biology research and is provided as a resource for biomolecular modeling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shichkova, Coggan, Markram and Keller.)

The neocortex is densely innervated by basal forebrain (BF) cholinergic neurons. Long-range axons of cholinergic neurons regulate higher-order cognitive function and dysfunction in the neocortex by releasing acetylcholine (ACh). ACh release dynamically reconfigures neocortical microcircuitry through differential spatiotemporal actions on cell-types and their synaptic connections. At the cellular level, ACh release controls neuronal excitability and firing rate, by hyperpolarizing or depolarizing target neurons. At the synaptic level, ACh impacts transmission dynamics not only by altering the presynaptic probability of release, but also the magnitude of the postsynaptic response. Despite the crucial role of ACh release in physiology and pathophysiology, a comprehensive understanding of the way it regulates the activity of diverse neocortical cell-types and synaptic connections has remained elusive. This review aims to summarize the state-of-the-art anatomical and physiological data to develop a functional map of the cellular, synaptic and microcircuit effects of ACh in the neocortex of rodents and non-human primates, and to serve as a quantitative reference for those intending to build data-driven computational models on the role of ACh in governing brain states.