Search results for "dynamics."

MYC Induces a Hybrid Energetics Program Early in Cell Reprogramming

2018

Summary Cell reprogramming is thought to be associated with a full metabolic switch from an oxidative- to a glycolytic-based metabolism. However, neither the dynamics nor the factors controlling this metabolic switch are fully understood. By using cellular, biochemical, protein array, metabolomic, and respirometry analyses, we found that c-MYC establishes a robust bivalent energetics program early in cell reprogramming. Cells prone to undergo reprogramming exhibit high mitochondrial membrane potential and display a hybrid metabolism. We conclude that MYC proteins orchestrate a rewiring of somatic cell metabolism early in cell reprogramming, whereby somatic cells acquire the phenotypic plast…

The Importance of Cerebellar Connectivity on Simulated Brain Dynamics

2020

The brain shows a complex multiscale organization that prevents a direct understanding of how structure, function and dynamics are correlated. To date, advances in neural modeling offer a unique opportunity for simulating global brain dynamics by embedding empirical data on different scales in a mathematical framework. The Virtual Brain (TVB) is an advanced data-driven model allowing to simulate brain dynamics starting from individual subjects' structural and functional connectivity obtained, for example, from magnetic resonance imaging (MRI). The use of TVB has been limited so far to cerebral connectivity but here, for the first time, we have introduced cerebellar nodes and interconnecting…

2019

The DNA-binding of the natural benzophenanthridine alkaloid chelerythrine (CHE) has been assessed by combining molecular modeling and optical absorption spectroscopy. Specifically, both double-helical (B-DNA) and G-quadruplex sequences—representative of different topologies and possessing biological relevance, such as telomeric or regulatory sequences—have been considered. An original multiscale protocol, making use of molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations, allowed us to compare the theoretical and experimental circular dichroism spectra of the different DNA topologies, readily providing atomic-level details of the CHE–DNA binding…

Secondary structure and dynamics study of the intrinsically disordered silica-mineralizing peptide P5S3during silicic acid condensation and silica de…

2017

The silica forming repeat R5 of sil1 from Cylindrotheca fusiformis was the blueprint for the design of P5 S3 , a 50-residue peptide which can be produced in large amounts by recombinant bacterial expression. It contains 5 protein kinase A target sites and is highly cationic due to 10 lysine and 10 arginine residues. In the presence of supersaturated orthosilicic acid P5 S3 enhances silica-formation whereas it retards the dissolution of amorphous silica (SiO2 ) at globally undersaturated concentrations. The secondary structure of P5 S3 during these 2 processes was studied by circular dichroism (CD) spectroscopy, complemented by nuclear magnetic resonance (NMR) spectroscopy of the peptide in …

[Au(9-methylcaffein-8-ylidene) 2 ] + /DNA Tel23 System: Solution, Computational, and Biological Studies

2017

International audience; Physicochemical methods have been used to investigate interactions occurring in solution between the dicarbene gold(I) complex [Au(9‐methylcaffein‐8‐ylidene)2]BF4 (AuNHC) and a human telomeric DNA sequence, namely Tel23. Circular dichroism measurements allow identification of the conformational changes experienced by Tel23 upon interaction with AuNHC, and the respective binding stoichiometries and constants were determined. Computational studies provide a good link between previous crystallographic results of the same system and the present solution data, offering an exhaustive description of the inherent noncovalent metallodrug–DNA interactions. Remarkably, we found…

Structure and Stability of Hsp60 and Groel in Solution

2016

Molecular chaperones are a class of proteins able to prevent non-specific aggregation of mitochondrial proteins and to promote their proper folding. Among them, human Hsp60 is currently considered as a ubiquitous molecule with multiple roles both in maintaining health conditions and as a trigger of several diseases. Of particular interest is its role in neurodegenerative disorders since it is able to inhibit the formation of amyloid fibrils.Hsp60 structure was considered, until recent years, analogue to the one of its bacterial homolog GroEL, one of the most investigated chaperones, whose crystallographic structure is a homo-tetradecamer, made up of two seven member rings. On the contrary, …

Hydrodynamic IL10 Gene Transfer in Human Colon: Results from an "EX VIVO" Study with Potential Clinical Application in Crohn's Disease.

2017

Background: The aim of this work is to evaluate the efficacy of hydrodynamic venous IL10 gene delivery to "ex vivo" human colon segments and to determine its potential interest in Crohn's disease treatment. Methods: Twenty human colon segments were obtained from surgical resections. Hydrodynamic transfection through the main vein of the pedicle with 50 mL of hIL10 plasmid (20 mu g/mL) solution was performed on 13 of them. Tissue sections were cultured and DNA, RNA, and protein copies were determined after 1, 2, and 4 days. Data obtained were compared with 6 nontransfected specimens. Finally, 1 specimen was injected with gold nanoparticles, and their distribution was examined under electron …

Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer

2018

Solid malignancies have been speculated to depend on cancer stem cells (CSCs) for expansion and relapse after therapy. Here we report on quantitative analyses of lineage tracing data from primary colon cancer xenograft tissue to assess CSC functionality in a human solid malignancy. The temporally obtained clone size distribution data support a model in which stem cell function in established cancers is not intrinsically, but is entirely spatiotemporally orchestrated. Functional stem cells that drive tumour expansion predominantly reside at the tumour edge, close to cancer-associated fibroblasts. Hence, stem cell properties change in time depending on the cell location. Furthermore, although…

All-atom simulations to studying metallodrugs/target interactions.

2021

Abstract Metallodrugs are extensively used to treat and diagnose distinct disease types. The unique physical–chemical properties of metal ions offer tantalizing opportunities to tailor effective scaffolds for selectively targeting specific biomolecules. Modern experimental techniques have collected a large body of structural data concerning the interactions of metallodrugs with their biomolecular targets, although being unable to exhaustively assess the molecular basis of their mechanism of action. In this scenario, the complementary use of accurate computational methods allows uncovering the minutiae of metallodrugs/targets interactions and their underlying mechanism of action at an atomic…

2017

Functional near infrared spectroscopy (fNIRS) is a promising neuroimaging method for investigating networks of cortical regions over time. We propose a directed effective connectivity method (TPDC) allowing the capture of both time and frequency evolution of the brain’s networks using fNIRS data acquired from healthy subjects performing a continuous finger-tapping task. Using this method we show the directed connectivity patterns among cortical motor regions involved in the task and their significant variations in the strength of information flow exchanges. Intra and inter-hemispheric connections during the motor task with their temporal evolution are also provided. Characterisation of the …