Structural Characterization of Encapsulin in Complex with Dye-Decolorizing Peroxide.

(Mtb) is the causative agent of tuberculosis, the world's deadliest infectious disease. Mtb uses a variety of mechanisms to evade the human host's defenses and survive intracellularly. Mtb's oxidative stress response enables Mtb to survive within activated macrophages, an environment with reactive oxygen species and low pH.

Proof-of-concept study of anti-Fel d 1 IgY antibodies in cat food using the MASK-air app.

Background: An innovation to better manage cat-allergic patients utilises anti-Fel d 1 IgY antibodies to neutralise Fel d 1 after its production by the cat. However, there is no published study showing its clinical efficacy in humans in a home setting. A longitudinal, open-label, proof-of-concept study was carried out to approach clinical efficacy of the cat food in cat-allergic patients.

Valitrack study: Objective evaluation of medical compression wearing time and patient activity with the Accutrack by Sigvaris Group sensor.

Introduction: Objective measurement of compliance is mandatory to evaluate therapeutic effects and clinical benefits of medical compression stockings. This Valitrack study evaluates the Accutrack sensor equipped with an accelerometer. The evaluation is done under controlled and free conditions and during washing.

From Transient to Stationary Transport in Porous Networks under Various Adsorption Conditions and Kinetics.

We investigate the interplay between adsorption and transport in a two-dimensional porous medium by means of an extended Lattice Boltzmann technique within the Two-Relaxation-Time framework. We focus on two canonical adsorption thermodynamics and kinetics formalisms: (1) the Henry model in which the adsorbed amount scales linearly with the free adsorbate concentration and (2) the Langmuir model that accounts for surface saturation upon adsorption. We simulate transport of adsorbing and nonadsorbing particles to investigate the effect of the adsorption/desorption ratio , initial free adsorbate concentration , surface saturation Γ, and Peclet numbers Pe on their dispersion behavior.

A Model for Epilepsy of Infectious Etiology using Theiler's Murine Encephalomyelitis Virus.

One of the main causes of epilepsy is an infection of the central nervous system (CNS); approximately 8% of patients who survive such an infection develop epilepsy as a consequence, with rates being significantly higher in less economically developed countries. This work provides an overview of modeling epilepsy of infectious etiology and using it as a platform for novel antiseizure compound testing. A protocol of epilepsy induction by non-stereotactic intracerebral injection of Theiler's murine encephalomyelitis virus (TMEV) in C57BL/6 mice is presented, which replicates many of the early and chronic clinical symptoms of viral encephalitis and subsequent epilepsy in human patients.

Lattice Boltzmann method for adsorption under stationary and transient conditions: Interplay between transport and adsorption kinetics in porous media.

A numerical method based on the Lattice Boltzmann formalism is presented to capture the effect of adsorption kinetics on transport in porous media. Through the use of a general adsorption operator, canonical models such as Henry and Langmuir adsorption as well as more complex adsorption mechanisms involving collective behavior with lateral interactions and surface aggregation can be investigated using this versatile model. By extending the description of adsorption phenomena to kinetic regimes with any underlying adsorption model, this effective technique allows assessing the coupled dynamics resulting from advection, diffusion, and adsorption in pores not only in stationary conditions but also under transient conditions (i.

Cooperative Effects Dominating the Thermodynamics and Kinetics of Surfactant Adsorption in Porous Media: From Lateral Interactions to Surface Aggregation.

Surfactant adsorption in porous media remains poorly understood, as the microscopic collective behavior of these amphiphilic molecules leads to nonconventional phenomena with complex underlying kinetics/structural organization. Here, we develop a simple thermodynamic model, which captures this rich behavior by including cooperative effects to account for lateral interactions between adsorbed molecules and the formation of ordered or disordered self-assemblies. In more detail, this model relies on a kinetic approach, involving adsorption/desorption rates that depend on the surfactant surface concentration to account for facilitated or hindered adsorption at different adsorption stages.

Coarse-Grained Models of Aqueous Solutions of Polyelectrolytes: Significance of Explicit Charges.

The structure of polyelectrolytes is highly sensitive to small changes in interactions between their monomers. In particular, interactions mediated by counterions play a significant role and are affected by both specific molecular effects and generic concentration effects. The ability of coarse-grained models to reproduce the structural properties of an atomic model is thus a challenging task.

Selective Kinase Inhibition Shows That Bur1 (Cdk9) Phosphorylates the Rpb1 Linker .

Cyclin-dependent kinases play multiple roles in RNA polymerase II transcription. Cdk7/Kin28, Cdk9/Bur1, and Cdk12/Ctk1 phosphorylate the polymerase and other factors to drive the dynamic exchange of initiation and elongation complex components over the transcription cycle. We engineered strains of the yeast for rapid, specific inactivation of individual kinases by addition of a covalent inhibitor.

The CDI toxin of Yersinia kristensenii is a novel bacterial member of the RNase A superfamily.

Contact-dependent growth inhibition (CDI) is an important mechanism of inter-bacterial competition found in many Gram-negative pathogens. CDI+ cells express cell-surface CdiA proteins that bind neighboring bacteria and deliver C-terminal toxin domains (CdiA-CT) to inhibit target-cell growth. CDI+ bacteria also produce CdiI immunity proteins, which specifically neutralize cognate CdiA-CT toxins to prevent self-inhibition.

Peptide binding to a bacterial signal peptidase visualized by peptide tethering and carrier-driven crystallization.

Bacterial type I signal peptidases (SPases) are membrane-anchored serine proteases that process the signal peptides of proteins exported via the Sec and Tat secretion systems. Despite their crucial importance for bacterial virulence and their attractiveness as drug targets, only one such enzyme, LepB from Escherichia coli, has been structurally characterized, and the transient nature of peptide binding has stymied attempts to directly visualize SPase-substrate complexes. Here, the crystal structure of SpsB, the type I signal peptidase from the Gram-positive pathogen Staphylococcus aureus, is reported, and a peptide-tethering strategy that exploits the use of carrier-driven crystallization is described.

The Structure and Interactions of Periplasmic Domains of Crucial MmpL Membrane Proteins from Mycobacterium tuberculosis.

Mycobacterium tuberculosis mycobacterial membrane protein large (MmpL) proteins are important in substrate transport across the inner membrane. Here, we show that MmpL proteins are classified into two phylogenetic clusters, where MmpL cluster II contains three soluble domains (D1, D2, and D3) and has two full-length members, MmpL3 and MmpL11. Significantly, MmpL3 is currently the most druggable M.

Expression, purification and crystallization of a membrane-associated, catalytically active type I signal peptidase from Staphylococcus aureus.

Staphylococcus aureus infections are becoming increasingly difficult to treat as they rapidly develop resistance to existing antibiotics. Bacterial type I signal peptidases are membrane-associated, cell-surface serine proteases with a unique catalytic mechanism that differs from that of eukaryotic endoplasmic reticulum signal peptidases. They are thus potential antimicrobial targets.

Structures of a human blood group glycosyltransferase in complex with a photo-activatable UDP-Gal derivative reveal two different binding conformations.

Glycosyltransferases (GTs) catalyse the sequential addition of monosaccharides to specific acceptor molecules and play major roles in key biological processes. GTs are classified into two main families depending on the inverted or retained stereochemistry of the glycosidic bond formed during the reaction. While the mechanism of inverting enzymes is well characterized, the precise nature of retaining GTs is still a matter of much debate.

Dynamics of solutes with hydrodynamic interactions: comparison between Brownian dynamics and stochastic rotation dynamics simulations.

The dynamics of particles in solution or suspension is influenced by thermal fluctuations and hydrodynamic interactions. Several mesoscale methods exist to account for these solvent-induced effects such as Brownian dynamics with hydrodynamic interactions and hybrid molecular dynamics-stochastic rotation dynamics methods. Here we compare two ways of coupling solutes to the solvent with stochastic rotation dynamics (SRD) to Brownian dynamics with and without explicit hydrodynamic interactions.

Alteration of fluorescent protein spectroscopic properties upon cryoprotection.

Cryoprotection of a protein crystal by addition of small-molecule compounds may sometimes affect the structure of its active site. The spectroscopic and structural effects of the two cryoprotectants glycerol and ethylene glycol on the cyan fluorescent protein Cerulean were investigated. While glycerol had almost no noticeable effect, ethylene glycol was shown to induce a systematic red shift of the UV-vis absorption and fluorescence emission spectra.

Crystal structures of Burkholderia cenocepacia dihydropteroate synthase in the apo-form and complexed with the product 7,8-dihydropteroate.

Background: The enzyme dihydropteroate synthase (DHPS) participates in the de novo synthesis of folate cofactors by catalyzing the formation of 7,8-dihydropteroate from condensation of p-aminobenzoic acid with 6-hydroxymethyl-7,8-dihydropteroate pyrophosphate. DHPS is absent from humans, who acquire folates from diet, and has been validated as an antimicrobial therapeutic target by chemical and genetic means. The bacterium Burkholderia cenocepacia is an opportunistic pathogen and an infective agent of cystic fibrosis patients.

Biochemical and immunochemical properties of B lymphocyte cytochrome b558.

Like neutrophils, Epstein-Barr virus (EBV)-immortalized B lymphocytes express all constituents of the NADPH oxidase complex necessary to generate superoxide anion O2-. The NADPH oxidase activity in EBV-B lymphocytes is only 5% of that measured in neutrophils upon PMA stimulation. Cytochrome b558 is the sole redox membrane component of NADPH oxidase; it is the protein core around which cytosolic factors assemble in order to mediate oxidase activity.

Characterization of neutrophil NADPH oxidase activity reconstituted in a cell-free assay using specific monoclonal antibodies raised against cytochrome b558.

The immunochemical characterization of NADPH oxidase activity of cytochrome b558 purified from human neutrophils was determined after reconstitution in a cell-free assay using the native hemoprotein and recombinant purified cytosolic activating factors. The oxidase activity showed a strict dependence on the heme content at each step of the hemoprotein purification process. The immunochemical properties of the reconstituted oxidase made use of monoclonal antibodies raised against membrane-bound and octyl-glucoside-extracted cytochrome b.