Search results for "structural"

Precision and accuracy of single-molecule FRET measurements-a multi-laboratory benchmark study

2018

Single-molecule Forster resonance energy transfer (smFRET) is increasingly being used to determine distances, structures, and dynamics of biomolecules in vitro and in vivo. However, generalized protocols and FRET standards to ensure the reproducibility and accuracy of measurements of FRET efficiencies are currently lacking. Here we report the results of a comparative blind study in which 20 labs determined the FRET efficiencies (E) of several dye-labeled DNA duplexes. Using a unified, straightforward method, we obtained FRET efficiencies with s.d. between +/- 0.02 and +/- 0.05. We suggest experimental and computational procedures for converting FRET efficiencies into accurate distances, and…

Parvovirus B19V Nonstructural Protein NS1 Induces Double-Stranded Deoxyribonucleic Acid Autoantibodies and End-Organ Damage in Nonautoimmune Mice

2018

Abstract Background Viral infection is implicated in development of autoimmunity. Parvovirus B19 (B19V) nonstructural protein, NS1, a helicase, covalently modifies self double-stranded deoxyribonucleic acid (dsDNA) and induces apoptosis. This study tested whether resulting apoptotic bodies (ApoBods) containing virally modified dsDNA could induce autoimmunity in an animal model. Methods BALB/c mice were inoculated with (1) pristane-induced, (2) B19V NS1-induced, or (3) staurosporine-induced ApoBods. Serum was tested for dsDNA autoantibodies by Crithidia luciliae staining and enzyme-linked immunosorbent assay. Brain, heart, liver, and kidney pathology was examined. Deposition of self-antigens…

Ultrastructural findings from paraffin embedded tissue in intraoral lesions caused by Leishmania infantum

2017

2019

Background: Network science provides powerful access to essential organizational principles of the brain. The aim of this study was to investigate longitudinal evolution of gray matter networks in early relapsing–remitting MS (RRMS) compared with healthy controls (HCs) and contrast network dynamics with conventional atrophy measurements. Methods: For our longitudinal study, we investigated structural cortical networks over 1 year derived from 3T MRI in 203 individuals (92 early RRMS patients with mean disease duration of 12.1 ± 14.5 months and 101 HCs). Brain networks were computed based on cortical thickness inter-regional correlations and fed into graph theoretical analysis. Network conne…

Ultrafast structural changes within a photosynthetic reaction centre

2021

Nature <London> / Physical science 589, 310 - 314 (2021). doi:10.1038/s41586-020-3000-7

Evolutionary stability of topologically associating domains is associated with conserved gene regulation

2018

AbstractBackgroundThe human genome is highly organized in the three-dimensional nucleus. Chromosomes fold locally into topologically associating domains (TADs) defined by increased intra-domain chromatin contacts. TADs contribute to gene regulation by restricting chromatin interactions of regulatory sequences, such as enhancers, with their target genes. Disruption of TADs can result in altered gene expression and is associated to genetic diseases and cancers. However, it is not clear to which extent TAD regions are conserved in evolution and whether disruption of TADs by evolutionary rearrangements can alter gene expression.ResultsHere, we hypothesize that TADs represent essential functiona…

On the structural connectivity of large-scale models of brain networks at cellular level

2021

AbstractThe brain’s structural connectivity plays a fundamental role in determining how neuron networks generate, process, and transfer information within and between brain regions. The underlying mechanisms are extremely difficult to study experimentally and, in many cases, large-scale model networks are of great help. However, the implementation of these models relies on experimental findings that are often sparse and limited. Their predicting power ultimately depends on how closely a model’s connectivity represents the real system. Here we argue that the data-driven probabilistic rules, widely used to build neuronal network models, may not be appropriate to represent the dynamics of the …

Artefactual band patterns by SDS-PAGE of the Vip3Af protein in the presence of proteases mask the extremely high stability of this protein.

2018

Abstract Vip3 proteins are secretable proteins from Bacillus thuringiensis with important characteristics for the microbiological control of agricultural pests. The exact details of their mode of action are yet to be disclosed and the crystallographic structure is still unknown. Vip3 proteins are expressed as protoxins that have to be activated by the insect gut proteases. A previous study on the peptidase processing of Vip3Aa revealed that the protoxin produced artefactual band patterns by SDS-PAGE due to the differential stability of this protein and the peptidases to SDS and heating (Bel et al., 2017 Toxins 9:131). To determine whether this phenomenon also applies to other Vip3A proteins…

Permeating disciplines: Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport

2017

Ion translocation across biological barriers is a fundamental requirement for life. In many cases, controlling this process-for example with neuroactive drugs-demands an understanding of rapid and reversible structural changes in membrane-embedded proteins, including ion channels and transporters. Classical approaches to electrophysiology and structural biology have provided valuable insights into several such proteins over macroscopic, often discontinuous scales of space and time. Integrating these observations into meaningful mechanistic models now relies increasingly on computational methods, particularly molecular dynamics simulations, while surfacing important challenges in data manage…

Automated selection of homologs to track the evolutionary history of proteins

2018

Background The selection of distant homologs of a query protein under study is a usual and useful application of protein sequence databases. Such sets of homologs are often applied to investigate the function of a protein and the degree to which experimental results can be transferred from one organism to another. In particular, a variety of databases facilitates static browsing for orthologs. However, these resources have a limited power when identifying orthologs between taxonomically distant species. In addition, in some situations, for a given query protein, it is advantageous to compare the sets of orthologs from different specific organisms: this recursive step-wise search might give …