Gating the electron transfer at a monocopper centre through the supramolecular coordination of water molecules within a protein chamber mimic.

Functionality of enzymes is strongly related to water dynamic processes. The control of the redox potential for metallo-enzymes is intimately linked to the mediation of water molecules in the first and second coordination spheres. Here, we report a unique example of supramolecular control of the redox properties of a biomimetic monocopper complex by water molecules.

Functions of the LIMP-2 and CD36 homologues in bacteria uptake, phagolysosome biogenesis and host cell defence.

Phagocytic cells take up, kill and digest microbes by a process called phagocytosis. To this end, these cells bind the particle, rearrange their actin cytoskeleton, and orchestrate transport of digestive factors to the particle-containing phagosome. The mammalian lysosomal membrane protein LIMP-2 (also known as SCARB2) and CD36, members of the class B of scavenger receptors, play a crucial role in lysosomal enzyme trafficking and uptake of mycobacteria, respectively, and generally in host cell defences against intracellular pathogens.

Metal-Organic Frameworks as Efficient Oral Detoxifying Agents.

Poisoning and accidental oral intoxication are major health problems worldwide. Considering the insufficient efficacy of the currently available detoxification treatments, a pioneering oral detoxifying adsorbent agent based on a single biocompatible metal-organic framework (MOF) is here proposed for the efficient decontamination of drugs commonly implicated in accidental or voluntary poisoning. Furthermore, the in vivo toxicity and biodistribution of a MOF via oral administration have been investigated for the first time.

Analysis of Minerals Produced by hFOB 1.19 and Saos-2 Cells Using Transmission Electron Microscopy with Energy Dispersive X-ray Microanalysis.

This video presents the use of transmission electron microscopy with energy dispersive X-ray microanalysis (TEM-EDX) to compare the state of minerals in vesicles released by two human bone cell lines: hFOB 1.19 and Saos-2. These cell lines, after treatment with ascorbic acid (AA) and β-glycerophosphate (β-GP), undergo complete osteogenic transdifferentiation from proliferation to mineralization and produce matrix vesicles (MVs) that trigger apatite nucleation in the extracellular matrix (ECM).

Coupled catabolism and anabolism in autocatalytic RNA sets.

The ability to process molecules available in the environment into useable building blocks characterizes catabolism in contemporary cells and was probably critical for the initiation of life. Here we show that a catabolic process in collectively autocatalytic sets of RNAs allows diversified substrates to be assimilated. We modify fragments of the Azoarcus group I intron and find that the system is able to restore the original native fragments by a multi-step reaction pathway.

Ependymal cilia beating induces an actin network to protect centrioles against shear stress.

Multiciliated ependymal cells line all brain cavities. The beating of their motile cilia contributes to the flow of cerebrospinal fluid, which is required for brain homoeostasis and functions. Motile cilia, nucleated from centrioles, persist once formed and withstand the forces produced by the external fluid flow and by their own cilia beating.

MyPMFs: a simple tool for creating statistical potentials to assess protein structural models.

Evaluating the model quality of protein structures that evolve in environments with particular physicochemical properties requires scoring functions that are adapted to their specific residue compositions and/or structural characteristics. Thus, computational methods developed for structures from the cytosol cannot work properly on membrane or secreted proteins. Here, we present MyPMFs, an easy-to-use tool that allows users to train statistical potentials of mean force (PMFs) on the protein structures of their choice, with all parameters being adjustable.

Persistent plasticizers and bisphenol in the cheese of Tunisian markets induced biochemical and histopathological alterations in male BALB/c mice.

Clinical evidences, experimental models, and epidemiology of many studies suggest that phthalate-based plasticizers, aliphatic ester, and bisphenol A (BPA) have major risks for humans by targeting different organs and body systems. The current study has been designed firstly to analyze three categories of cheese with and without their exposure to the sun and packed in packages with an inner surface plastic-covered film in order to identify the dibutyl phthalate (DBP); benzyl butyl phthalate (BBP); bis(2-ethylhexyl) phthalate (DEHP); diisodecyl phthalate (DiDP); diisononyl phthalate (DiNP); and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) by GC-MS/MS, except for the bisphenol A, which is by UPLC-MS/MS, and secondly to assess the toxicity of the identified chemical molecules and cheese samples on the liver and kidney of mice. Our results showed that the cheese contains high quantities of DBP and DEHP with the concentrations up to 0.

Predicting the most appropriate wood biomass for selected industrial applications: comparison of wood, pulping, and enzymatic treatments using fluorescent-tagged carbohydrate-binding modules.

Background: Lignocellulosic biomass will progressively become the main source of carbon for a number of products as the Earth's oil reservoirs disappear. Technology for conversion of wood fiber into bioproducts (wood biorefining) continues to flourish, and access to reliable methods for monitoring modification of such fibers is becoming an important issue. Recently, we developed a simple, rapid approach for detecting four different types of polymer on the surface of wood fibers.

VLITL is a major cross-β-sheet signal for fibrinogen Aα-chain frameshift variants.

The first case of hereditary fibrinogen Aα-chain amyloidosis was recognized >20 years ago, but disease mechanisms still remain unknown. Here we report detailed clinical and proteomics studies of a French kindred with a novel amyloidogenic fibrinogen Aα-chain frameshift variant, Phe521Leufs, causing a severe familial form of renal amyloidosis. Next, we focused our investigations to elucidate the molecular basis that render this Aα-chain variant amyloidogenic.

Characterization of a Novel Alkalophilic Lipase From Aneurinibacillus thermoaerophilus: Lid Heterogeneity and Assignment to Family I.5.

Recent investigations of Aneurinibacillus thermoaerophilus strains have allowed identification of a unique solvent tolerant lipase, distinct from known lipases. This work reports the expression and purification of this lipase (LipAT) and the first characterization of its structure and temperature and pH-dependent behaviour. LipAT has a secondary structural content compatible with the canonical lipase α/β hydrolase fold, and is dimeric at neutral pH.

Potato spindle tuber viroid infection triggers degradation of chloride channel protein CLC-b-like and Ribosomal protein S3a-like mRNAs in tomato plants.

It is well established that viroid derived small RNA (vd-sRNA) induces RNA silencing of endogenous mRNA. However, it remains not clear how exactly viroid infections can lead to severe symptom induction given the fact that fewer vd-sRNAs binding the specific target mRNAs were recovered from the infected plants. To answer this question, the two least expressed (+) and (-) strand vd-sRNAs of potato spindle tuber viroid (PSTVd) binding to both the 3' UTR and the coding region of tomato mRNAs were analyzed by infecting tomato plants with two variants of PSTVd.

Plasticizers and bisphenol A, in packaged foods sold in the Tunisian markets: study of their acute in vivo toxicity and their environmental fate.

Today, processed and packaged foods are considered as among the major sources of human exposure to plasticizers and bisphenol which migrate from plastic packing. In the present study, a wide range of food products sold on the Tunisian market such as grain and grain products, milk and dairy products, fats and oil, drink, fish, and sweets have been analyzed firstly in order to identify the presence of phthalates and bisphenol. Then, the identified chemical molecules were studied for their environmental fate and tested in vivo for its toxicity in mice models.

Eco-evolutionary dynamics in a contemporary human population.

Recent studies of the joint dynamics of ecological and evolutionary processes show that changes in genotype or phenotype distributions can affect population, community and ecosystem processes. Such eco-evolutionary dynamics are likely to occur in modern humans and may influence population dynamics. Here, we study contributions to population growth from detailed genealogical records of a contemporary human population.

Effect of enzyme replacement therapy with alglucosidase alfa (Myozyme®) in 12 patients with advanced late-onset Pompe disease.

Background: The efficacy of enzyme replacement therapy (ERT) in patients at an advanced stage of Pompe disease has only been addressed in a few studies. Our objective was to assess the long term effects of ERT in a cohort of patients with severe Pompe disease.

Methods: We identified patients from the French Pompe Registry with severe respiratory failure and permanent wheelchair use (assisted walk for a few meters was allowed) when starting ERT.

A novel algorithm identifies stress-induced alterations in mitochondrial connectivity and inner membrane structure from confocal images.

Mitochondria exist as a highly interconnected network that is exquisitely sensitive to variations in nutrient availability, as well as a large array of cellular stresses. Changes in length and connectivity of this network, as well as alterations in the mitochondrial inner membrane (cristae), regulate cell fate by controlling metabolism, proliferation, differentiation, and cell death. Given the key roles of mitochondrial dynamics, the process by which mitochondria constantly fuse and fragment, the measure of mitochondrial length and connectivity provides crucial information on the health and activity of various cell populations.

Exposure to Bordetella pertussis adenylate cyclase toxin affects integrin-mediated adhesion and mechanics in alveolar epithelial cells.

Background Information: The adenylate cyclase (CyaA) toxin is a major virulent factor of Bordetella pertussis, the causative agent of whooping cough. CyaA toxin is able to invade eukaryotic cells where it produces high levels of cyclic adenosine monophosphate (cAMP) affecting cellular physiology. Whether CyaA toxin can modulate cell matrix adhesion and mechanics of infected cells remains largely unknown.

Topological and thermodynamic factors that influence the evolution of small networks of catalytic RNA species.

An RNA-directed recombination reaction can result in a network of interacting RNA species. It is now becoming increasingly apparent that such networks could have been an important feature of the RNA world during the nascent evolution of life on the Earth. However, the means by which such small RNA networks assimilate other available genotypes in the environment to grow and evolve into the more complex networks that are thought to have existed in the prebiotic milieu are not known.

Clinical Analysis of Algerian Patients with Pompe Disease.

Pompe's disease is a metabolic myopathy caused by a deficiency of acid alpha-glucosidase (GAA), also called acid maltase, an enzyme that degrades lysosomal glycogen. The clinical presentation of Pompe's disease is variable with respect to the age of onset and rate of disease progression. Patients with onset of symptoms in early infancy (infantile-onset Pompe disease (IOPD)) typically exhibit rapidly progressive hypertrophic cardiomyopathy and marked muscle weakness.

Impurity determination for hepcidin by liquid chromatography-high resolution and ion mobility mass spectrometry for the value assignment of candidate primary calibrators.

In metrology institutes, the state-of-the-art for purity analysis of peptides/proteins mainly addresses short and unfolded peptides. Important developments are anticipated for the characterization of nonlinear peptides or proteins. Hepcidin 1-25 is an interesting model system because this small protein contains four disulfide bridges with a particular connectivity that is difficult to reproduce and could induce a bias in quantification.

Mimicking the Regulation Step of Fe-Monooxygenases: Allosteric Modulation of Fe -Oxo Formation by Guest Binding in a Dinuclear Zn -Fe Calix[6]arene-Based Funnel Complex.

A heteroditopic ligand associated with a calix[6]arene scaffold bearing a tris(imidazole) coordinating site at its small rim and an amine/pyridine ligand at its large rim has been prepared, and its regioselective coordination to Zn at the small rim and Fe in the amine/pyridine ligand has been achieved. The heterodinuclear complex obtained displays an overall cone conformation capped by the tris(imidazole)Zn moiety and bears a non-heme Fe complex at its base. Each of the metal centers exhibits one labile position, allowing the coordination inside the cavity of a guest alkylamine at Zn and the generation of reaction intermediates (Fe (OOH) and Fe O) at the large rim.

Translational misreading, amino acid misincorporation and misinterpretations. The case of the flavocytochrome b H373Q variant.

Amino acid misincorporation during protein synthesis occurs naturally at a low level. Protein sequence errors, depending on the level and the nature of the misincorporation, can have various consequences. When site-directed mutagenesis is used as a tool for understanding the role of a side chain in enzyme catalysis, misincorporation in a variant with intrinsically low activity may lead to misinterpretations concerning the enzyme mechanism.

Non Random Distribution of DMD Deletion Breakpoints and Implication of Double Strand Breaks Repair and Replication Error Repair Mechanisms.

Background: Dystrophinopathies are mostly caused by copy number variations, especially deletions, in the dystrophin gene (DMD). Despite the large size of the gene, deletions do not occur randomly but mainly in two hot spots, the main one involving exons 45 to 55. The underlying mechanisms are complex and implicate two main mechanisms: Non-homologous end joining (NHEJ) and micro-homology mediated replication-dependent recombination (MMRDR).

Cryo-EM study of start codon selection during archaeal translation initiation.

Eukaryotic and archaeal translation initiation complexes have a common structural core comprising e/aIF1, e/aIF1A, the ternary complex (TC, e/aIF2-GTP-Met-tRNA) and mRNA bound to the small ribosomal subunit. e/aIF2 plays a crucial role in this process but how this factor controls start codon selection remains unclear. Here, we present cryo-EM structures of the full archaeal 30S initiation complex showing two conformational states of the TC.