439 research outputs found
Screening, identification, and antibiotic activity of secondary metabolites of Penicillium sp. LPB2019K3-2 isolated from endemic amphipods of Lake Baikal
This study aimed to assess the influence of nutrient media content on the production of antibiotics and the ability of water fungi isolated from lake Baikal to synthesize novel natural products. Interest in this topic stems from the high demand for new drugs, and studies are carried out via the screening of new natural products with biological activity produced by unstudied or extremophilic microorganisms. For this study, a strain of Penicillium sp. was isolated from endemic Baikal phytophagous amphipod species. Here, we identified natural products using the following classical assays: biotechnological cultivation, MALDI identification of the strain, natural product extraction, antimicrobial activity determination, and modern methods such as HPLC-MS for the dereplication and description of natural products. It was found that many detected metabolites were not included in the most extensive database. Most of the identified metabolites were characterized by their biological activity and demonstrated antibiotic activity against model Gram-positive and Gram-negative bacteria. The isolated strain of water fungus produced penicolinate B, meleagrin A, austinoneol A, andrastin A, and other natural products. Additionally, we show that the synthesis of low-molecular-weight natural products depends on the composition of the microbiological nutrient media used for cultivation. Thus, although the golden age of antibiotics ended many years ago and microscopic fungi are well studied producers of known antibiotics, the water fungi of the Lake Baikal ecosystem possess great potential in the search for new natural products for the development of new drugs. These natural products can become new pharmaceuticals and can be used in therapy to treat new diseases such as SARS, MERS, H5N1, etc
FIRST REPORT ON TRUFFLE-INHABITING FUNGI AND METAGENOMIC COMMUNITIES OF TUBER AESTIVUM COLLECTED IN RUSSIA
Truffles are one of the least studied groups of fungi in terms of their biological and biotechnological aspects. This study aimed to isolate truffle-inhabiting fungi and assess the metagenomic communities of the most common Russian summer truffle, Tuber aestivum. This study is the first to characterize the biodiversity of prokaryotic and eukaryotic organisms living in the truffle T. aestivum using molecular analysis and sequencing. Plant pathogens involved in a symbiotic relationship with truffles were identified by sequencing the hypervariable fragments of the 16S rRNA and 18S rRNA genes. In addition, some strains of fungal symbionts and likely pathogens were isolated and recognized for the first time from the truffles. This study also compared and characterized the general diversity and distribution of microbial taxa of T. aestivum collected in Russia and Europe. The results revealed that the Russian and European truffle study materials demonstrated high similarity. In addition to the truffles, representatives of bacteria, fungi, and protists were found in the fruiting bodies. Many of these prokaryotic and eukaryotic species inhabiting truffles might influence them, help them form mycorrhizae with trees, and regulate biological processes. Thus, truffles are interesting and promising sources for modern biotechnological and agricultural studies
Bose-Einstein correlations of same-sign charged pions in the forward region in pp collisions at βs=7 TeV
Bose-Einstein correlations of same-sign charged pions, produced in protonproton collisions at a 7 TeV centre-of-mass energy, are studied using a data sample collected
by the LHCb experiment. The signature for Bose-Einstein correlations is observed in the
form of an enhancement of pairs of like-sign charged pions with small four-momentum
difference squared. The charged-particle multiplicity dependence of the Bose-Einstein correlation parameters describing the correlation strength and the size of the emitting source
is investigated, determining both the correlation radius and the chaoticity parameter. The
measured correlation radius is found to increase as a function of increasing charged-particle
multiplicity, while the chaoticity parameter is seen to decreas
Study of J /Ο production in Jets
The production of J/Ο mesons in jets is studied in the forward region of proton-proton collisions using data collected with the LHCb detector at a center-of-mass energy of 13 TeV. The fraction of the jet transverse momentum carried by the J/Ο meson, z(J/Ο)β‘pT(J/Ο)/pT(jet), is measured using jets with pT(jet)>20 GeV in the pseudorapidity range 2.5<Ξ·(jet)<4.0. The observed z(J/Ο)distribution for J/Ο mesons produced in b-hadron decays is consistent with expectations. However, the results for prompt J/Ο production do not agree with predictions based on fixed-order nonrelativistic QCD. This is the first measurement of the pT fraction carried by prompt J/Ο mesons in jets at any experiment
Study of charmonium production in b -hadron decays and first evidence for the decay Bs0
Using decays to Ο-meson pairs, the inclusive production of charmonium states in b-hadron decays is studied with pp collision data corresponding to an integrated luminosity of 3.0 fbβ1, collected by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. Denoting byBC β‘ B(b β C X) Γ B(C β ΟΟ) the inclusive branching fraction of a b hadron to a charmonium state C that decays into a pair of Ο mesons, ratios RC1C2 β‘ BC1 /BC2 are determined as RΟc0Ξ·c(1S) = 0.147 Β± 0.023 Β± 0.011, RΟc1Ξ·c(1S) =0.073 Β± 0.016 Β± 0.006, RΟc2Ξ·c(1S) = 0.081 Β± 0.013 Β± 0.005,RΟc1 Οc0 = 0.50 Β± 0.11 Β± 0.01, RΟc2 Οc0 = 0.56 Β± 0.10 Β± 0.01and RΞ·c(2S)Ξ·c(1S) = 0.040 Β± 0.011 Β± 0.004. Here and below the first uncertainties are statistical and the second systematic.Upper limits at 90% confidence level for the inclusive production of X(3872), X(3915) and Οc2(2P) states are obtained as RX(3872)Οc1 < 0.34, RX(3915)Οc0 < 0.12 andRΟc2(2P)Οc2 < 0.16. Differential cross-sections as a function of transverse momentum are measured for the Ξ·c(1S) andΟc states. The branching fraction of the decay B0s β ΟΟΟ is measured for the first time, B(B0s β ΟΟΟ) = (2.15Β±0.54Β±0.28Β±0.21B)Γ10β6. Here the third uncertainty is due to the branching fraction of the decay B0s β ΟΟ, which is used for normalization. No evidence for intermediate resonances is seen. A preferentially transverse Ο polarization is observed.The measurements allow the determination of the ratio of the branching fractions for the Ξ·c(1S) decays to ΟΟ and p p asB(Ξ·c(1S)β ΟΟ)/B(Ξ·c(1S)β p p) = 1.79 Β± 0.14 Β± 0.32
Folding of Matrix Metalloproteinase-2 Prevents Endogenous Generation of MHC Class-I Restricted Epitope
BACKGROUND: We previously demonstrated that the matrix metalloproteinase-2 (MMP-2) contained an antigenic peptide recognized by a CD8 T cell clone in the HLA-A*0201 context. The presentation of this peptide on class I molecules by human melanoma cells required a cross-presentation mechanism. Surprisingly, the classical endogenous processing pathway did not process this MMP-2 epitope. METHODOLOGY/PRINCIPAL FINDINGS: By PCR directed mutagenesis we showed that disruption of a single disulfide bond induced MMP-2 epitope presentation. By Pulse-Chase experiment, we demonstrated that disulfide bonds stabilized MMP-2 and impeded its degradation. Finally, using drugs, we documented that mutated MMP-2 epitope presentation used the proteasome and retrotranslocation complex. CONCLUSIONS/SIGNIFICANCE: These data appear crucial to us since they established the existence of a new inhibitory mechanism for the generation of a T cell epitope. In spite of MMP-2 classified as a self-antigen, the fact that cross-presentation is the only way to present this MMP-2 epitope underlines the importance to target this type of antigen in immunotherapy protocols
Measurement of the inelastic pp cross-section at a centre-of-mass energy of 13TeV
The cross-section for inelastic proton-proton collisions at a centre-of-mass energy of 13TeV is measured with the LHCb detector. The fiducial cross-section for inelastic interactions producing at least one prompt long-lived charged particle with momentum p > 2 GeV/c in the pseudorapidity range 2 < Ξ· < 5 is determined to be Ο acc = 62:2 Β± 0:2 Β± 2:5mb. The first uncertainty is the intrinsic systematic uncertainty of the measurement, the second is due to the uncertainty on the integrated luminosity. The statistical uncertainty is negligible. Extrapolation to full phase space yields the total inelastic proton-proton cross-section Ο inel = 75:4 Β± 3:0 Β± 4:5mb, where the first uncertainty is experimental and the second due to the extrapolation. An updated value of the inelastic cross-section at a centre-of-mass energy of 7TeV is also reported
Diffusion of MMPs on the Surface of Collagen Fibrils: The Mobile Cell Surface β Collagen Substratum Interface
Remodeling of the extracellular matrix catalyzed by MMPs is central to morphogenetic phenomena during development and wound healing as well as in numerous pathologic conditions such as fibrosis and cancer. We have previously demonstrated that secreted MMP-2 is tethered to the cell surface and activated by MT1-MMP/TIMP-2-dependent mechanism. The resulting cell-surface collagenolytic complex (MT1-MMP)2/TIMP-2/MMP-2 can initiate (MT1-MMP) and complete (MMP-2) degradation of an underlying collagen fibril. The following question remained: What is the mechanism of substrate recognition involving the two structures of relatively restricted mobility, the cell surface enzymatic complex and a collagen fibril embedded in the ECM? Here we demonstrate that all the components of the complex are capable of processive movement on a surface of the collagen fibril. The mechanism of MT1-MMP movement is a biased diffusion with the bias component dependent on the proteolysis of its substrate, not adenosine triphosphate (ATP) hydrolysis. It is similar to that of the MMP-1 Brownian ratchet we described earlier. In addition, both MMP-2 and MMP-9 as well as their respective complexes with TIMP-1 and -2 are capable of Brownian diffusion on the surface of native collagen fibrils without noticeable dissociation while the dimerization of MMP-9 renders the enzyme immobile. Most instructive is the finding that the inactivation of the enzymatic activity of MT1-MMP has a detectable negative effect on the cell force developed in miniaturized 3D tissue constructs. We propose that the collagenolytic complex (MT1-MMP)2/TIMP-2/MMP-2 represents a Mobile Cell Surface β Collagen Substratum Interface. The biological implications of MT1-MMP acting as a molecular ratchet tethered to the cell surface in complex with MMP-2 suggest a new mechanism for the role of spatially regulated peri-cellular proteolysis in cell-matrix interactions
Occupancy maps of 208 chromatin-associated proteins in one human cell type
Transcription factors are DNA-binding proteins that have key roles in gene regulation. Genome-wide occupancy maps of transcriptional regulators are important for understanding gene regulation and its effects on diverse biological processes. However, only a minority of the more than 1,600 transcription factors encoded in the human genome has been assayed. Here we present, as part of the ENCODE (Encyclopedia of DNA Elements) project, data and analyses from chromatin immunoprecipitation followed by high-throughput sequencing (ChIPβseq) experiments using the human HepG2 cell line for 208 chromatin-associated proteins (CAPs). These comprise 171 transcription factors and 37 transcriptional cofactors and chromatin regulator proteins, and represent nearly one-quarter of CAPs expressed in HepG2 cells. The binding profiles of these CAPs form major groups associated predominantly with promoters or enhancers, or with both. We confirm and expand the current catalogue of DNA sequence motifs for transcription factors, and describe motifs that correspond to other transcription factors that are co-enriched with the primary ChIP target. For example, FOX family motifs are enriched in ChIPβseq peaks of 37 other CAPs. We show that motif content and occupancy patterns can distinguish between promoters and enhancers. This catalogue reveals high-occupancy target regions at which many CAPs associate, although each contains motifs for only a minority of the numerous associated transcription factors. These analyses provide a more complete overview of the gene regulatory networks that define this cell type, and demonstrate the usefulness of the large-scale production efforts of the ENCODE Consortium
Matrix Metalloproteinase-Induced Epithelial-Mesenchymal Transition in Breast Cancer
Matrix metalloproteinases (MMPs) degrade and modify the extracellular matrix (ECM) as well as cell-ECM and cell-cell contacts, facilitating detachment of epithelial cells from the surrounding tissue. MMPs play key functions in embryonic development and mammary gland branching morphogenesis, but they are also upregulated in breast cancer, where they stimulate tumorigenesis, cancer cell invasion and metastasis. MMPs have been investigated as potential targets for cancer therapy, but clinical trials using broad-spectrum MMP inhibitors yielded disappointing results, due in part to lack of specificity toward individual MMPs and specific stages of tumor development. Epithelial-mesenchymal transition (EMT) is a developmental process in which epithelial cells take on the characteristics of invasive mesenchymal cells, and activation of EMT has been implicated in tumor progression. Recent findings have implicated MMPs as promoters and mediators of developmental and pathogenic EMT processes in the breast. In this review, we will summarize recent studies showing how MMPs activate EMT in mammary gland development and in breast cancer, and how MMPs mediate breast cancer cell motility, invasion, and EMT-driven breast cancer progression. We also suggest approaches to inhibit these MMP-mediated malignant processes for therapeutic benefit
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