Search results for "complex"

2020

Coxsackievirus B (CVB) enteroviruses are common pathogens that can cause acute and chronic myocarditis, dilated cardiomyopathy, aseptic meningitis, and they are hypothesized to be a causal factor in type 1 diabetes. The licensed enterovirus vaccines and those currently in clinical development are traditional inactivated or live attenuated vaccines. Even though these vaccines work well in the prevention of enterovirus diseases, new vaccine technologies, like virus-like particles (VLPs), can offer important advantages in the manufacturing and epitope engineering. We have previously produced VLPs for CVB3 and CVB1 in insect cells. Here, we describe the production of CVB3-VLPs with enhanced pro…

Whole Exome Sequencing Is the Preferred Strategy to Identify the Genetic Defect in Patients With a Probable or Possible Mitochondrial Cause

2018

Mitochondrial disorders, characterized by clinical symptoms and/or OXPHOS deficiencies, are caused by pathogenic variants in mitochondrial genes. However, pathogenic variants in some of these genes can lead to clinical manifestations which overlap with other neuromuscular diseases, which can be caused by pathogenic variants in non-mitochondrial genes as well. Mitochondrial pathogenic variants can be found in the mitochondrial DNA (mtDNA) or in any of the 1,500 nuclear genes with a mitochondrial function. We have performed a two-step next-generation sequencing approach in a cohort of 117 patients, mostly children, in whom a mitochondrial disease-cause could likely or possibly explain the phe…

Mitochondrial introgression suggests extensive ancestral hybridization events among Saccharomyces species.

2017

Horizontal gene transfer (HGT) in eukaryotic plastids and mitochondrial genomes is common, and plays an important role in organism evolution. In yeasts, recent mitochondrial HGT has been suggested between S. cerevisiae and S. paradoxus. However, few strains have been explored given the lack of accurate mitochondrial genome annotations. Mitochondrial genome sequences are important to understand how frequent these introgressions occur, and their role in cytonuclear incompatibilities and fitness. Indeed, most of the Bateson-Dobzhansky-Muller genetic incompatibilities described in yeasts are driven by cytonuclear incompatibilities. We herein explored the mitochondrial inheritance of several wor…

Revisiting the pH-gated conformational switch on the activities of HisKA-family histidine kinases

2020

13 páginas, 6 figuras, 3 tablas

Probing Differential Binding Mechanisms of Phenylalanine-Glycine-Rich Nucleoporins by Single-Molecule FRET

2018

Abstract Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex. They are highly dynamic under physiological conditions and studying their interaction with nuclear transport receptors (NTRs) is key to understanding the molecular mechanism of nucleocytoplasmic transport. Distinct conformational features of FG-Nups interacting with diverse NTRs can be detected by multiparameter single-molecule fluorescence energy transfer (smFRET), which is a powerful technique for studying the dynamics and interactions of biomolecules in solution. Here we provide a detailed protocol utilizing smFRET to reveal dif…

Two differential binding mechanisms of FG-nucleoporins and nuclear transport receptors

2018

Summary Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC). Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an “archetypal-fuzzy” complex through the rapid formation and breakage of interactions with many individual FG motifs. Here, we use single-molecule studies combined with atomistic simulations to show that, in sharp contrast, FG-Nup214 undergoes a coupled reconfiguration-binding mechanism when interacting with the export receptor CRM1. Association and dissociation rate constants are more than an order of magnitude lowe…

2016

AbstractThe different factors involved in the growth process of complex networks imprint valuable information in their observable topologies. How to exploit this information to accurately predict structural network changes is the subject of active research. A recent model of network growth sustains that the emergence of properties common to most complex systems is the result of certain trade-offs between node birth-time and similarity. This model has a geometric interpretation in hyperbolic space, where distances between nodes abstract this optimisation process. Current methods for network hyperbolic embedding search for node coordinates that maximise the likelihood that the network was pro…

Centrality in Complex Networks with Overlapping Community Structure

2019

AbstractIdentifying influential spreaders in networks is an essential issue in order to prevent epidemic spreading, or to accelerate information diffusion. Several centrality measures take advantage of various network topological properties to quantify the notion of influence. However, the vast majority of works ignore its community structure while it is one of the main features of many real-world networks. In a recent study, we show that the centrality of a node in a network with non-overlapping communities depends on two features: Its local influence on the nodes belonging to its community, and its global influence on the nodes belonging to the other communities. Using global and local co…

Toward a direct and scalable identification of reduced models for categorical processes.

2017

The applicability of many computational approaches is dwelling on the identification of reduced models defined on a small set of collective variables (colvars). A methodology for scalable probability-preserving identification of reduced models and colvars directly from the data is derived—not relying on the availability of the full relation matrices at any stage of the resulting algorithm, allowing for a robust quantification of reduced model uncertainty and allowing us to impose a priori available physical information. We show two applications of the methodology: (i) to obtain a reduced dynamical model for a polypeptide dynamics in water and (ii) to identify diagnostic rules from a standar…

Identification of Cysteine Ubiquitylation Sites on the Sec23A Protein of the COPII Complex Required for Vesicle Formation from the ER

2017

Background COPII is a multiprotein complex that surrounds carrier vesicles budding from the Endoplasmic Reticulum and allows the recruitment of secretory proteins. The Sec23a protein plays a crucial role in the regulation of the dynamics of COPII formation ensuring the proper function of the secretory pathway. Objective Since few evidences suggest that ubiquitylation could have a role in the COPII regulation, the present study was aimed to establish whether the Sec23a component of the vesicular envelope COPII could be ubiquitylated. Method Sec23a ubiquitylation was revealed by co-immunoprecipitation experiments. Recombinant Sec23a was gel-purified and analyzed by mass spectrometry subjected…