scholarly journals High-order functional interactions in ageing explained via alterations in the connectome in a whole-brain model

2021 ◽  
Author(s):  
Marilyn Gatica ◽  
Fernando E. Rosas ◽  
Pedro A.M. Mediano ◽  
Ibai Diez ◽  
Stephan P. Swinnen ◽  
...  
Keyword(s):  
Structural Changes ◽  
Activity Patterns ◽  
High Order ◽  
Order Structure ◽  
Whole Brain ◽  
Functional Interactions ◽  
Age Variations ◽  
Starting Point ◽  
Spatio Temporal ◽  
Precise Relationship

The human brain generates a rich repertoire of spatio-temporal activity patterns, which support a wide variety of motor and cognitive functions. These patterns of activity change with age in a multi-factorial manner. One of these factors is the variations in the brain's connectomics that occurs along the lifespan. However, the precise relationship between high-order functional interactions and connnectomics, as well as their variations with age are largely unknown, in part due to the absence of mechanistic models that can efficiently map brain connnectomics to functional connectivity in aging. To investigate this issue, we have built a neurobiologically-realistic whole-brain computational model using both anatomical and functional MRI data from 161 participants ranging from 10 to 80 years old. We show that the age differences in high-order functional interactions can be largely explained by variations in the connectome. Based on this finding, we propose a simple neurodegeneration model that is representative of normal physiological aging. As such, when applied to connectomes of young participant it reproduces the age-variations that occur in the high-order structure of the functional data. Overall, these results begin to disentangle the mechanisms by which structural changes in the connectome lead to functional differences in the ageing brain. Our model can also serve as a starting point for modelling more complex forms of pathological ageing or cognitive deficits.

Folding-Controlled Assembly of Ortho-Phenylene-Based Macrocycles

2020 ◽  
Author(s):  
Viraj kirinda ◽  
Scott Hartley
Keyword(s):  
Self Assembly ◽  
Structural Control ◽  
Structural Changes ◽  
Condensation Product ◽  
Gel Permeation Chromatography ◽  
Emergent Behavior ◽  
Order Structure ◽  
High Level ◽  
Alkoxy Groups ◽  
Energy Surfaces

The self-assembly of foldamers into macrocycles is a simple approach to non-biological higher-order structure. Previous work on the co-assembly of ortho-phenylene foldamers with rod-shaped linkers has shown that folding and self-assembly affect each other; that is, the combination leads to new emergent behavior, such as access to otherwise unfavorable folding states. To this point this relationship has been passive. Here, we demonstrate control of self-assembly by manipulating the foldamers’ conformational energy surfaces. A series of o-phenylene decamers and octamers have been assembled into macrocycles using imine condensation. Product distributions were analyzed by gel-permeation chromatography and molecular geometries extracted from a combination of NMR spectroscopy and computational chemistry. The assembly of o-phenylene decamers functionalized with alkoxy groups or hydrogens gives both [2+2] and [3+3] macrocycles. The mixture results from a subtle balance of entropic and enthalpic effects in these systems: the smaller [2+2] macrocycles are entropically favored but require the oligomer to misfold, whereas a perfectly folded decamer fits well within the larger [3+3] macrocycle that is entropically disfavored. Changing the substituents to fluoro groups, however, shifts assembly quantitatively to the [3+3] macrocycle products, even though the structural changes are well-removed from the functional groups directly participating in bond formation. The electron-withdrawing groups favor folding in these systems by strengthening arene–arene stacking interactions, increasing the enthalpic penalty to misfolding. The architectural changes are substantial even though the chemical perturbation is small: analogous o-phenylene octamers do not fit within macrocycles when perfectly folded, and quantitatively misfold to give small macrocycles regardless of substitution. Taken together, these results represent both a high level of structural control in structurally complex foldamer systems and the demonstration of large-amplitude structural changes as a consequence of a small structural effects.

scholarly journals Multi-Targeting Bioactive Compounds Extracted from Essential Oils as Kinase Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2174 ◽  
Author(s):  
Annalisa Maruca ◽  
Delia Lanzillotta ◽  
Roberta Rocca ◽  
Antonio Lupia ◽  
Giosuè Costa ◽  
...  
Keyword(s):  
Essential Oils ◽  
Binding Affinity ◽  
Structural Changes ◽  
Kinase Inhibitors ◽  
Synergistic Effects ◽  
Data Bank ◽  
Binding Modes ◽  
Starting Point ◽  
Target Action ◽  
Potential Resource

Essential oils (EOs) are popular in aromatherapy, a branch of alternative medicine that claims their curative effects. Moreover, several studies reported EOs as potential anti-cancer agents by inducing apoptosis in different cancer cell models. In this study, we have considered EOs as a potential resource of new kinase inhibitors with a polypharmacological profile. On the other hand, computational methods offer the possibility to predict the theoretical activity profile of ligands, discovering dangerous off-targets and/or synergistic effects due to the potential multi-target action. With this aim, we performed a Structure-Based Virtual Screening (SBVS) against X-ray models of several protein kinases selected from the Protein Data Bank (PDB) by using a chemoinformatics database of EOs. By evaluating theoretical binding affinity, 13 molecules were detected among EOs as new potential kinase inhibitors with a multi-target profile. The two compounds with higher percentages in the EOs were studied more in depth by means Induced Fit Docking (IFD) protocol, in order to better predict their binding modes taking into account also structural changes in the receptor. Finally, given its good binding affinity towards five different kinases, cinnamyl cinnamate was biologically tested on different cell lines with the aim to verify the antiproliferative activity. Thus, this work represents a starting point for the optimization of the most promising EOs structure as kinase inhibitors with multi-target features.

A Preliminary Study of Abnormal Centrality of Cortical Regions and Subsystems in Whole Brain Functional Connectivity of Autism Spectrum Disorder Boys

2021 ◽  
pp. 155005942110262
Author(s):  
Bo Chen
Keyword(s):  
Autism Spectrum Disorder ◽  
Activity Patterns ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Eigenvector Centrality ◽  
Information Process ◽  
Whole Brain ◽  
Functional Connections ◽  
Cortical Regions ◽  
Prefrontal Lobe

The abnormal cortices of autism spectrum disorder (ASD) brains are uncertain. However, the pathological alterations of ASD brains are distributed throughout interconnected cortical systems. Functional connections (FCs) methodology identifies cooperation and separation characteristics of information process in macroscopic cortical activity patterns under the context of network neuroscience. Embracing the graph theory concepts, this paper introduces eigenvector centrality index (EC score) ground on the FCs, and further develops a new framework for researching the dysfunctional cortex of ASD in holism significance. The important process is to uncover noticeable regions and subsystems endowed with antagonistic stance in EC-scores of 26 ASD boys and 28 matched healthy controls (HCs). For whole brain regional EC scores of ASD boys, orbitofrontal superior medial cortex, insula R, posterior cingulate gyrus L, and cerebellum 9 L are endowed with different EC scores significantly. In the brain subsystems level, EC scores of DMN, prefrontal lobe, and cerebellum are aberrant in the ASD boys. Generally, the EC scores display widespread distribution of diseased regions in ASD brains. Meanwhile, the discovered regions and subsystems, such as MPFC, AMYG, INS, prefrontal lobe, and DMN, are engaged in social processing. Meanwhile, the CBCL externalizing problem scores are associated with EC scores.

P1-269: Application of Brain Atrophy Lesion Index (BALI) to Common Clinical MRI Sequences: Evaluation of Whole Brain Structural Changes in Aging and Dementia

2016 ◽  
Vol 12 ◽  
pp. P518-P518
Author(s):  
Xiaowei Song ◽  
Hui Guo ◽  
Ryan C.N. D'Arcy ◽  
William Siu ◽  
John Diggle ◽  
...  
Keyword(s):  
Brain Atrophy ◽  
Structural Changes ◽  
Whole Brain ◽  
Mri Sequences ◽  
Clinical Mri ◽  
Lesion Index

Wankelende wetenschap. De studie van de journalistiek & de revolutie in de media

2010 ◽  
Vol 38 (3) ◽  
Author(s):  
Frank van Vree
Keyword(s):  
Professional Practice ◽  
Structural Changes ◽  
Traditional Media ◽  
The Public ◽  
Journalism Studies ◽  
Starting Point ◽  
The Media ◽  
The Public Sphere ◽  
New Research ◽  
The Revolution

An Unstable Discipline. Journalism Studies & the Revolution in the Media An Unstable Discipline. Journalism Studies & the Revolution in the Media During the last decade media and journalism have got into turmoil; landslides have changed the traditional media landscape, overturning familiar marking points, institutions and patterns. To understand these radical changes journalism studies should not only develop a new research agenda, but also review its approach and perspective.This article looks back on recent development in the field and argues for a more cohesive perspective, taking journalism as a professional practice as its starting point. Furthermore a plea is made for a thorough research into the structural changes of the public sphere and the role and position of journalism.

scholarly journals Relative Earnings and Manpower Allocation in Developing Economies

1969 ◽  
Vol 9 (1) ◽  
pp. 14-34 ◽  
Author(s):  
Lloyd G. Reynolds
Keyword(s):  
Economic Growth ◽  
Subject Matter ◽  
Structural Changes ◽  
Developing Economies ◽  
Developed Countries ◽  
The Other ◽  
Labour Economics ◽  
Economic Behaviour ◽  
Agriculture Industry ◽  
Starting Point

The less developed countries (LDC) present two kinds of challenge to economists. First, they invite us to develop hypotheses about how economic growth begins and about structural changes during the early decades of growth. Second, they provide a fresh terrain on which specialists in particular subject-matter areas can test accepted notions about economic behaviour. For investigations in labour economics, the structure of earnings provides a convenient starting point. (It is best to say "earnings" rather than "wages" because most workers in the LDC's are self-emplqyed.) Analysis of earnings requires an examination of manpower supplies and requirements. This leads into the economics of agriculture, industry, government, and other labour demanding sectors on one side, and into a study of education and other skill-producing agencies, on the other. Thus by starting with the earnings structure, one is led rather directly into the heart of the economy.

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