Trapped lipopolysaccharide and LptD intermediates reveal lipopolysaccharide translocation steps across the Escherichia coli outer membrane

Lipopolysaccharide (LPS) is a main component of the outer membrane of Gram-negative bacteria, which is essential for the vitality of most Gram-negative bacteria and plays a critical role for drug resistance. LptD/E complex forms a N-terminal LPS transport slide, a hydrophobic intramembrane hole and the hydrophilic channel of the barrel, for LPS transport, lipid A insertion and core oligosaccharide and O-antigen polysaccharide translocation, respectively. However, there is no direct evidence to confirm that LptD/E transports LPS from the periplasm to the external leaflet of the outer membrane. By replacing LptD residues with an unnatural amino acid p-benzoyl-L-phenyalanine (pBPA) and UV-photo-cross-linking in E.coli, the translocon and LPS intermediates were obtained at the N-terminal domain, the intramembrane hole, the lumenal gate, the lumen of LptD channel, and the extracellular loop 1 and 4, providing the first direct evidence and “snapshots” to reveal LPS translocation steps across the outer membrane

A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries

Neural stem cells are activated within neurogenic niches in response to brain injuries. This results in the production of neuroblasts, which unsuccessfully attempt to migrate toward the damaged tissue. Injuries constitute a gliogenic/non-neurogenic niche generated by the presence of anti-neurogenic signals, which impair neuronal differentiation and migration. Kinases of the protein kinase C (PKC) family mediate the release of growth factors that participate in different steps of the neurogenic process, particularly, novel PKC isozymes facilitate the release of the neurogenic growth factor neuregulin. We have demonstrated herein that a plant derived diterpene, (EOF2; CAS number 2230806-06-9), with the capacity to activate PKC facilitates the release of neuregulin 1, and promotes neuroblasts differentiation and survival in cultures of subventricular zone (SVZ) isolated cells in a novel PKC dependent manner. Local infusion of this compound in mechanical cortical injuries induces neuroblast enrichment within the perilesional area, and noninvasive intranasal administration of EOF2 promotes migration of neuroblasts from the SVZ towards the injury, allowing their survival and differentiation into mature neurons, being some of them cholinergic and GABAergic. Our results elucidate the mechanism of EOF2 promoting neurogenesis in injuries and highlight the role of novel PKC isozymes as targets in brain injury regeneration

Enzymatic hydrophobic modification of jute fibers via grafting to reinforce composites

Horseradish peroxidase (HRP)/H2O2 system catalyzes the free-radical polymerization of aromatic compounds such as lignins and gallate esters. In this work, dodecyl gallate (DG) was grafted onto the surfaces of lignin-rich jute fabrics by HRP-mediated oxidative polymerization with an aim to enhance the hydrophobicity of the fibers. The DG-grafted jute fibers and reaction products of their model compounds were characterized by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The results clearly indicated the grafting of DG to the jute fiber by HRP. Furthermore, the hydrophobicity of jute fabrics was determined by measuring the wetting time and static contact angle. Compared to the control sample, the wetting time and static contact angle of the grated fabrics changed from ~1 s to 1 h and from ~0° to 123.68°, respectively. This clearly proved that the hydrophobicity of jute fabrics improved considerably. Conditions of the HRP-catalyzed DG-grafting reactions were optimized in terms of the DG content of modified jute fabrics. Moreover, the results of breaking strength and elongation of DG-grafted jute/ polypropylene (PP) composites demonstrated improved reinforcement of the composite due to enzymatic hydrophobic modification of jute fibers.This work was financially supported by the National Natural Science Foundation of China (51173071), the Program for New Century Excellent Talents in University (NCET-12-0883), Program for Changjiang Scholars and Innovative Research Team in University (No. IRT_15R26) the Fundamental Research Funds for the Central Universities (JUSRP51312B, JUSRP51505), and the Graduate Student Innovation Plan of Jiangsu Province of China (SJLX_0527)

The Role of miR-30d-5p in Neutrophil-Derived Exosomes in Promoting Systemic Lupus Erythematosus

A-Qiong Chen, A-Xiao Pan, Juan Liu, Dan-Qiong Zhang, Jia-Yuan Chen, Jin Zhang Department of Rheumatology and Clinical Immunology, Ningbo Medical Center Lihuili Hospital, The Affiliated Li Huili Hospital, Ningbo University, Ningbo, People’s Republic of ChinaCorrespondence: Jin Zhang, Email [email protected]: In this study, we investigated the role of neutrophil-derived exosomal miR-30d-5p in systemic lupus erythematosus (SLE).Methods: We extracted exosomes from the neutrophils collected from SLE patients and healthy donors and analyzed the relative level of miR-30d-5p. The exosomes were characterized by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). We mimicked SLE using MRL/lpr mice and treated the mice with exosomes and miR-30d-5p inhibitors. The RNA level of miR-30d-5p in serum of mice was analyzed by qPCR. The images of spleen were captured to evaluate splenomegaly. The serum levels of anti-nuclear antibodies (ANAs), total IgG, total IgM, and anti-dsDNA IgG were measured by ELISA. The kidney injury was analyzed by albumin level, haematoxylin and eosin (HE) staining, active index, and chronic index. The T cell differentiation and B cell activation were detected by flow cytometry. For T follicular helper (TfH) cell analysis, cells were stained with anti-CXCR5 and anti-PD-1 antibodies. Levels of inflammatory cytokines in serum were measured by ELISA.Results: The exosomes from SLE patients showed significant higher level of miR-30d-5p. Treatment with neutrophil-exosomes enhanced the degree of splenomegaly in MRL/lpr mice and production of anti-nuclear antibodies (ANAs), total IgG, total IgM, and anti-dsDNA IgG, which was repressed by miR-30d-5p inhibitor. Compared with MRL/lpr mice, mice treated with neutrophil-derive exosomes exhibited a notable increase of proteinuria and infiltration of lymphocytes in kidney, whereas inhibition of miR-30d-5p reduced this elevation. Exosome treatment elevated the number of IL17+ Th17 cells, CXCR5+PD-1+ TfH cells, reduced the portion of Foxp3+ Treg cells, and elevated B cells, and inhibition of miR-30d-5p reversed these effects.Conclusion: The neutrophils from SLE exhibited higher level of miR-30d-5p, and inhibition of miR-30d-5p could suppress the T cell and B cell activation, reduce inflammatory cytokine and antibodies production, and alleviate the lupus nephritis during SLE.Keywords: systemic lupus erythematosus, neutrophil, exosomes, miR-30d-5p, T cell, B cel

The origin of animals: can molecular clocks and the fossil record be reconciled?

The evolutionary emergence of animals is one of the most significant episodes in the history of life, but its timing remains poorly constrained. Molecular clocks estimate that animals originated and began diversifying over 100 million years before the first definitive metazoan fossil evidence in the Cambrian. However, closer inspection reveals that clock estimates and the fossil record are less divergent than is often claimed. Modern clock analyses do not predict the presence of the crown-representatives of most animal phyla in the Neoproterozoic. Furthermore, despite challenges provided by incomplete preservation, a paucity of phylogenetically informative characters, and uncertain expectations of the anatomy of early animals, a number of Neoproterozoic fossils can reasonably be interpreted as metazoans. A considerable discrepancy remains, but much of this can be explained by the limited preservation potential of early metazoans and the difficulties associated with their identification in the fossil record. Critical assessment of both records may permit better resolution of the tempo and mode of early animal evolution.JAC and AGL acknowledge support from Natural Environment Research Council (NERC) Fellowships [grant numbers NE/J018325/1 and NE/L011409/1]. SB and JAC acknowledge funding from the Danish National Research Foundation [DNRF53] and the Swedish Research Council [2013-4290]. PCJD was supported by a Royal Society Wolfson Merit Award, a Leverhulme Trust Research Fellowship and a NERC standard grant [NE/F00348X/1]

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing

Study of hadronic event-shape variables in multijet final states in pp collisions at √s=7 TeV

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QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Оценка качества образования на основе компетентностного подхода

В работе представлен практический опыт оценки качества образования в новом формате компетентностного подход

Constraints on parton distribution functions and extraction of the strong coupling constant from the inclusive jet cross section in pp collisions at √s=7 TeV

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