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https://www.readbyqxmd.com/read/29139623/extracellular-proteinases-of-candida-species-pathogenic-yeasts
#1
Maria Rapala-Kozik, Oliwia Bochenska, Dorota Zajac, Justyna Karkowska-Kuleta, Mariusz Gogol, Marcin Zawrotniak, Andrzej Kozik
The increased incidence of severe disseminated infections caused by opportunistic yeast-like fungi Candida spp. highlights the urgent need for research into the major virulence factors of these pathogens - extracellular aspartic proteinases of the candidapepsin and yapsin families. Classically, these enzymes were considered to be generally destructive factors that damage host tissues and provide nutrients for pathogen propagation. However, in recent decades, novel and more specific functions have been suggested for extracellular candidal proteinases...
November 15, 2017: Molecular Oral Microbiology
https://www.readbyqxmd.com/read/29137634/profiling-of-saccharomyces-cerevisiae-transcription-factors-for-engineering-the-resistance-of-yeast-to-lignocellulose-derived-inhibitors-in-biomass-conversion
#2
Guochao Wu, Zixiang Xu, Leif J Jönsson
BACKGROUND: Yeast transcription factors (TFs) involved in the regulation of multidrug resistance (MDR) were investigated in experiments with deletion mutants, transformants overexpressing synthetic genes encoding TFs, and toxic concentrations of lignocellulose-derived substances added to cultures as complex mixtures or as specific compounds, viz. coniferyl aldehyde, 5-hydroxymethylfurfural, and furfural. RESULTS: In the presence of complex mixtures of toxic substances from spruce wood, transformants overexpressing YAP1 and STB5, TFs involved in oxidative stress response, exhibited enhanced relative growth rates amounting to 4...
November 14, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/29128668/inhibition-of-the-complement-system-by-saliva-of-anopheles-nyssorhynchus-aquasalis
#3
Antonio Ferreira Mendes-Sousa, Vladimir Fazito Vale, Daniel Costa Queiroz, Adalberto Alves Pereira-Filho, Naylene Carvalho Sales da Silva, Leonardo Barbosa Koerich, Luciano Andrade Moreira, Marcos Horácio Pereira, Maurício Roberto Sant'Anna, Ricardo Nascimento Araújo, John Andersen, Jesus Gilberto Valenzuela, Nelder Figueiredo Gontijo
Anopheline mosquitoes are vectors of malaria parasites. Their saliva contains anti-hemostatic and immune-modulator molecules that favor blood feeding and parasite transmission. In this study, we describe the inhibition of the alternative pathway of the complement system (AP) by Anopheles aquasalis salivary gland extracts (SGE). According to our results, the inhibitor present in SGE acts on the initial step of the AP blocking deposition of C3b on the activation surfaces. Properdin, which is a positive regulatory molecule of the AP, binds to SGE...
November 8, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29119993/a-study-of-the-reactivity-of-s-vi-f-containing-warheads-with-nucleophilic-amino-acid-side-chains-under-physiological-conditions
#4
H Mukherjee, J Debreczeni, J Breed, S Tentarelli, B Aquila, J E Dowling, A Whitty, N P Grimster
Sulfonyl fluorides (SFs) have recently emerged as a promising warhead for the targeted covalent modification of proteins. Despite numerous examples of the successful deployment of SFs as covalent probe compounds, a detailed exploration of the factors influencing the stability and reactivity of SFs has not yet appeared. In this work we present an extensive study on the influence of steric and electronic factors on the reactivity and stability of the SF and related S(VI)-F groups. While SFs react rapidly with N-acetylcysteine, the resulting adducts were found to be unstable, rendering SFs inappropriate for the durable covalent inhibition of cysteine residues...
November 9, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29113783/multiple-legumain-isoenzymes-in-ticks
#5
David Hartmann, Radek Šíma, Jitka Konvičková, Jan Perner, Petr Kopáček, Daniel Sojka
By searching nucleotide databases for the North American Lyme disease vector, Ixodes scapularis, we have complemented the previously characterized European Ixodes ricinus legumain IrAE1 with a full set of nine analogous genes (isae1-9). Six of these were PCR confirmed as genes present in all tick genomes tested. The absolute mRNA copy number examined by quantitative (q)PCR enabled expression profiling and an absolute comparison of mRNA levels for individual I. scapularis (Is)AEs in tick tissues. Four IsAEs (1, 2, 4, 9) were expressed solely in the gut and thus are proposed to be involved in host blood digestion...
November 4, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/29111970/complementation-of-a-metk-deficient-e-coli-strain-with-heterologous-adomet-synthetase-genes
#6
Gwenn G Parungao, Mojun Zhao, Qinzhe Wang, Stephen P Zano, Ronald E Viola, Robert M Blumenthal
S-adenosyl-l-methionine (AdoMet) is an essential metabolite, playing a wide variety of metabolic roles. The enzyme that produces AdoMet from l-methionine and ATP (methionine adenosyltransferase, MAT) is thus an attractive target for anti-cancer and antimicrobial agents. It would be very useful to have a system that allows rapid identification of species-specific inhibitors of this essential enzyme. A previously generated E. coli strain, lacking MAT (∆metK) but containing a heterologous AdoMet transporter, was successfully complemented with heterologous metK genes from several bacterial pathogens, as well as with MAT genes from a fungal pathogen and Homo sapiens...
November 7, 2017: Microbiology
https://www.readbyqxmd.com/read/29110694/effects-of-freezer-storage-time-on-levels-of-complement-biomarkers
#7
Angharad R Morgan, Caroline O'Hagan, Samuel Touchard, Simon Lovestone, B Paul Morgan
BACKGROUND: There is uncertainty regarding how stable complement analytes are during long-term storage at - 80 °C. As part of our work program we have measured 17 complement biomarkers (C1q, C1 inhibitor, C3, C3a, iC3b, C4, C5, C9, FB, FD, FH, FI, TCC, Bb, sCR1, sCR2, Clusterin) and the benchmark inflammatory marker C-reactive protein (CRP) in a large set of plasma samples (n = 720) that had been collected, processed and subsequently stored at - 80 °C over a period of 6.6-10.6 years, prior to laboratory analysis...
November 6, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29107952/hereditary-angioedema-assessing-the-hypothesis-for-underlying-autonomic-dysfunction
#8
Maddalena A Wu, Francesco Casella, Francesca Perego, Chiara Suffritti, Nada Afifi Afifi, Eleonora Tobaldini, Andrea Zanichelli, Chiara Cogliati, Nicola Montano, Marco Cicardi
BACKGROUND: Attacks of Hereditary Angioedema due to C1-inhibitor deficiency (C1-INH-HAE)are often triggered by stressful events/hormonal changes. OBJECTIVE: Our study evaluates the relationship between autonomic nervous system (ANS) and contact/complement system activation. METHODS: Twenty-three HAE patients (6 males, mean age 47.5±11.4 years) during remission and 24 healthy controls (8 males, mean age 45.3±10.6 years) were studied. ECG, beat-by-beat blood pressure, respiratory activity were continuously recorded during rest (10') and 75-degrees-head-up tilt (10')...
2017: PloS One
https://www.readbyqxmd.com/read/29107384/binding-of-human-complement-c1-sterase-inhibitor-to-leptospira-spp
#9
Leandro Carvalho Dantas Breda, Silvio Arruda Vasconcellos, Dewton de Moraes Vasconcelos, Lourdes Isaac
Leptospirosis is an important zoonosis of global importance caused by bacteria Leptospira spp. Pathogenic Leptospira is resistant to Complement System killing while non-pathogenic Leptospira is rapidly killed by exposure to normal human serum (NHS). Pathogenic Leptospira interact with Complement Regulators such as Factor H, C4b binding protein and Vitronectin avoiding Complement activation and killing by Alternative and Classical Pathways. One important regulator is C1-inhibitor (C1INH) that interacts with C1s or MASPs controlling the cleavage of C4 and C2 molecules, thereby inhibiting the activation of the Classical and Lectin Pathways...
October 13, 2017: Immunobiology
https://www.readbyqxmd.com/read/29101826/ligand-based-computational-modelling-of-platelet-derived-growth-factor-beta-receptor-leading-to-new-angiogenesis-inhibitory-leads
#10
Rua'a A Al-Aqtash, Malek A Zihlif, Hana Hammad, Zeyad D Nassar, Jehad Al Meliti, Mutasem O Taha
Platelet derived growth factor beta receptor (PDGFR- β) plays an important role in angiogenesis. PDGFR-β expression is correlated with increased vascularity and maturation of blood vessels in cancer. Pharmacophore modeling and quantitative structure-activity relationship (QSAR) analysis were combined to explore the structural requirements for ligand-PDGFR-β recognition using 107 known PDGFR-β inhibitors. Genetic function algorithm (GFA) coupled to k nearest neighbor (kNN) and multiple linear regression (MLR) analysis were employed to generate predictive QSAR models based on optimal combinations of pharmacophores and physicochemical descriptors...
October 10, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29098911/targeted-treatments-for-hidradenitis-suppurativa-a-review-of-the-current-literature-and-ongoing-clinical-trials
#11
Melody Maarouf, Ashley K Clark, Dylan E Lee, Vivian Y Shi
PURPOSE: Targeted, immune-modulating drugs are at the forefront of therapy for HS, and a comprehensive clinical trial registry is needed to facilitate data pooling and clinical efficacy comparison. MATERIALS AND METHODS: A systematic review of the ClinicalTrials.gov database was searched for planned, in-progress, completed, or terminated trials investigating the effect of targeted biologic therapies for hidradenitis suppurativa (HS). When results of RCTs were not available, case reports or series were included...
November 10, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29097196/recurrent-allograft-c3-glomerulonephritis-and-unsuccessful-eculizumab-treatment
#12
Kati Kaartinen, Leena Martola, Anne Räisänen-Sokolowski, Seppo Meri
There is a great lack of efficient treatments for membranoproliferative glomerulonephritis (MPGN) and recently emerged complement therapies have been proposed to be useful. We report a patient with a complement-mediated MPGN having recurrencies in kidney allografts and an unsuccessful treatment with complement inhibitor, eculizumab (anti-C5 monoclonal antibody). Nephritic factor (C3Nef), an autoantibody against C3bBb, in the patient serum activated C3 but not C5 showing that major damage was mediated by C3 activation with clearly less involvement of C5 explaining unresponsiveness to eculizumab...
October 31, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29095719/novel-and-preclinical-treatment-strategies-in-pneumococcal-meningitis
#13
Jan P Bewersdorf, Denis Grandgirard, Uwe Koedel, Stephen L Leib
PURPOSE OF REVIEW: Pneumococcal meningitis is the most frequent form of bacterial meningitis in Europe and the United States. Although early antimicrobial and adjuvant therapy with dexamethasone have helped to improve disease outcome in adults, mortality and morbidity rates remain unsatisfactorily high, emphasizing the need for additional treatment options. Promising targets for adjuvant therapy have been identified recently and will be the focus of this review. RECENT FINDINGS: Brain disease in pneumococcal meningitis is caused by direct bacterial toxicity and excessive meningeal inflammation...
November 1, 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/29093731/twin-sister-of-ft-tsf-interacts-with-fructokinase6-and-inhibits-its-kinase-activity-in-arabidopsis
#14
Suhyun Jin, Sun Young Kim, Ji Hoon Ahn
In flowering plants, the developmental switch to the reproductive phase is tightly regulated and involves the integration of internal and external signals. FLOWERING LOCUS T (FT) and TWIN SISTER OF FT (TSF) integrate signals from multiple pathways. FT and TSF function as florigenic substances, and share high sequence similarity with mammalian Raf kinase inhibitor protein (RKIP). Despite their strong similarity to RKIP, the kinase inhibitory activity of FT and TSF remains to be investigated. We performed a yeast two-hybrid screen and found that TSF interacted with FRUCTOKINASE6 (FRK6), which phosphorylates fructose for various metabolic pathways...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29093647/freeze-dried-plasma-proteins-are-stable-at-room-temperature-for-at-least-1-year
#15
Jaimie Dufresne, Trung Hoang, Juliet Ajambo, Angelique Florentinus-Mefailoski, Peter Bowden, John Marshall
Thirty human EDTA plasma samples from male and female subjects ranging in age from 24 to 74 years were collected on ice, processed ice cold and stored frozen at -80 °C, in liquid nitrogen (LN2), or freeze dried and stored at room temperature in a desiccator (FDRT) or freeze dried and stored at -20 °C for 1 year (FD-20). In a separate experiment, EDTA plasma samples were collected onto ice, processed ice cold and maintained on ice ± protease inhibitors versus incubated at room temperature for up to 96 h...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/29089933/curaxin-cbl0100-blocks-hiv-1-replication-and-reactivation-through-inhibition-of-viral-transcriptional-elongation
#16
Maxime J Jean, Tsuyoshi Hayashi, Huachao Huang, Justin Brennan, Sydney Simpson, Andrei Purmal, Katerina Gurova, Michael C Keefer, James J Kobie, Netty G Santoso, Jian Zhu
Despite combination antiretroviral therapy (cART), acquired immunodeficiency syndrome (AIDS), predominantly caused by the human immunodeficiency virus type 1 (HIV-1), remains incurable. The barrier to a cure lies in the virus' ability to establish a latent infection in HIV/AIDS patients. Unsurprisingly, efforts for a sterilizing cure have focused on the "shock and kill" strategy using latency-reversing agents (LRAs) to complement cART in order to eliminate these latent reservoirs. However, this method faces numerous challenges...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29081812/peptide-inhibitor-of-complement-c1-inhibits-the-peroxidase-activity-of-hemoglobin-and-myoglobin
#17
Pamela S Hair, Kenji M Cunnion, Neel K Krishna
Hemoglobin is the natural carrier of oxygen in red blood cells (RBCs). While intracellular hemoglobin provides life-sustaining oxygen transport, extracellular free hemoglobin displays toxicity due to inherent peroxidase activity generating reactive oxygen species that subsequently react with the hemoglobin molecule to produce toxic heme degradation products resulting in free radicals, oxidative stress damage, and lipid peroxidation. We have recently demonstrated that Peptide Inhibitor of Complement C1 (PIC1) inhibits peroxidase activity of the heme-based enzyme myeloperoxidase...
2017: International Journal of Peptides
https://www.readbyqxmd.com/read/29078333/rat-embryonic-stem-cells-produce-fertile-offspring-through-tetraploid-complementation
#18
Tian-Da Li, Gui-Hai Feng, Yu-Fei Li, Mei Wang, Jun-Jie Mao, Jia-Qiang Wang, Xin Li, Xue-Peng Wang, Bin Qu, Le-Yun Wang, Xin-Xin Zhang, Hai-Feng Wan, Tong-Tong Cui, Cong Wan, Lei Liu, Xiao-Yang Zhao, Bao-Yang Hu, Wei Li, Qi Zhou
Pluripotency of embryonic stem cells (ESCs) can be functionally assessed according to the developmental potency. Tetraploid complementation, through which an entire organism is produced from the pluripotent donor cells, is taken as the most stringent test for pluripotency. It remains unclear whether ESCs of other species besides mice can pass this test. Here we show that the rat ESCs derived under 2i (two small molecule inhibitors) conditions at very early passages are able to produce fertile offspring by tetraploid complementation...
October 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29078325/necroptosis-controls-net-generation-and-mediates-complement-activation-endothelial-damage-and-autoimmune-vasculitis
#19
Adrian Schreiber, Anthony Rousselle, Jan Ulrich Becker, Anne von Mässenhausen, Andreas Linkermann, Ralph Kettritz
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes life-threatening autoimmune diseases affecting every organ, including the kidneys, where they cause necrotizing crescentic glomerulonephritis. ANCA activates neutrophils and activated neutrophils damage the endothelium, leading to vascular inflammation and necrosis. Better understanding of neutrophil-mediated AAV disease mechanisms may reveal novel treatment strategies. Here we report that ANCA induces neutrophil extracellular traps (NETs) via receptor-interacting protein kinase (RIPK) 1/3- and mixed-lineage kinase domain-like (MLKL)-dependent necroptosis...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29073268/compartmented-neuronal-cultures-reveal-two-distinct-mechanisms-for-alpha-herpesvirus-escape-from-genome-silencing
#20
Orkide O Koyuncu, Margaret A MacGibeny, Ian B Hogue, Lynn W Enquist
Alpha herpesvirus genomes encode the capacity to establish quiescent infections (i.e. latency) in the peripheral nervous system for the life of their hosts. Multiple times during latency, viral genomes can reactivate to start a productive infection, enabling spread of progeny virions to other hosts. Replication of alpha herpesviruses is well studied in cultured cells and many aspects of productive replication have been identified. However, many questions remain concerning how a productive or a quiescent infection is established...
October 2017: PLoS Pathogens
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