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https://www.readbyqxmd.com/read/29127314/modulation-of-transcriptional-mineralocorticoid-receptor-activity-by-casein-kinase-2
#1
Stefanie Ruhs, Nicole Strätz, Katja Quarch, Antonia Masch, Mike Schutkowski, Michael Gekle, Claudia Grossmann
The pathogenesis of cardiovascular diseases is a multifunctional process in which the mineralocorticoid receptor (MR), a ligand-dependent transcription factor, is involved as proven by numerous clinical studies. The development of pathophysiological MR actions depends on the existence of additional factors e.g. inflammatory cytokines and seems to involve posttranslational MR modifications e.g. phosphorylation. Casein kinase 2 (CK2) is a ubiquitously expressed multifunctional serine/threonine kinase that can be activated under inflammatory conditions as the MR...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29111329/exosomes-derived-from-pancreatic-cancer-cells-induce-activation-and-profibrogenic-activities-in-pancreatic-stellate-cells
#2
Atsushi Masamune, Naoki Yoshida, Shin Hamada, Tetsuya Takikawa, Tatsuhide Nabeshima, Tooru Shimosegawa
Pancreatic cancer cells (PCCs) interact with pancreatic stellate cells (PSCs), which play a pivotal role in pancreatic fibrogenesis, to develop the cancer-conditioned tumor microenvironment. Exosomes are membrane-enclosed nanovesicles, and have been increasingly recognized as important mediators of cell-to-cell communications. The aim of this study was to clarify the effects of PCC-derived exosomes on cell functions in PSCs. Exosomes were isolated from the conditioned medium of Panc-1 and SUIT-2 PCCs. Human primary PSCs were treated with PCC-derived exosomes...
October 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29109176/candidalysin-drives-epithelial-signaling-neutrophil-recruitment-and-immunopathology-at-the-vaginal-mucosa
#3
Jonathan P Richardson, Hubertine M E Willems, David L Moyes, Saeed Shoaie, Katherine S Barker, Shir Lynn Tan, Glen E Palmer, Bernhard Hube, Julian R Naglik, Brian M Peters
Unlike other forms of candidiasis, vulvovaginal candidiasis, caused primarily by the fungal pathogen Candida albicans, is a disease of immunocompetent and otherwise healthy women. Despite its prevalence, the fungal factors responsible for initiating symptomatic infection remain poorly understood. One of the hallmarks of vaginal candidiasis is the robust recruitment of neutrophils to the site of infection, which seemingly do not clear the fungus, but rather exacerbate disease symptomatology. Candidalysin, a newly discovered peptide toxin secreted by C...
November 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29109025/fish-oil-feeding-attenuates-neuroinflammatory-gene-expression-without-concomitant-changes-in-brain-eicosanoids-and-docosanoids-in-a-mouse-model-of-alzheimer-s-disease
#4
Kathryn E Hopperton, Marc-Olivier Trépanier, Nicholas C E James, Raphaël Chouinard-Watkins, Richard P Bazinet
BACKGROUND: Neuroinflammation is a recognized hallmark of Alzheimer's disease, along with accumulation of amyloid-β plaques, neurofibrillary tangles and synaptic loss. n-3 polyunsaturated fatty acids (PUFA) and molecules derived from them, including eicosapentaenoic acid-derived eicosanoids and docosahexaenoic acid-derived docosanoids, are known to have both anti-inflammatory and pro-resolving properties, while human observational data links consumption of these fatty acids to a decreased risk of Alzheimer's disease...
November 3, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29102104/identification-of-two-conserved-b-cell-epitopes-in-the-gp90-of-reticuloendothelial-virus-using-peptide-microarray
#5
Wiaam O A Khairy, Kun Qian, Hongxia Shao, Jianqiang Ye, Aijian Qin
Since the gp90 protein of Reticuloendotheliosis virus (REV) plays vital roles in virus neutralization, so detailed analysis of REV-gp90 epitopes is important for the development of epitope based marker vaccines and diagnostic tools for REV infections. In this study, two monoclonal antibodies (mAbs) namely 6C12 and 09980 were used to map the epitopes in REVgp90 using peptide microarray and ELISA. Peptide microarray revealed that mAbs 6C12 and 09980 recognized (216)YHPLA(220) and (230)DPQTSDILEA(239) motifs, respectively...
November 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/29101228/mass-spectrometric-revival-of-an-l-rhamnose-and-d-galactose-specific-lectin-from-a-lost-strain-of-streptomyces
#6
Yoko Fujita-Yamaguchi, Karine Bagramyan, Yoshiki Yamaguchi, Akemi Ikeda, Naoshi Dohmae, Teresa B Hong, Markus Kalkum
Blood type B-specific Streptomyces S27S5 hemagglutinin (SHA) was discovered and characterized in the 1970s. Although strain 27S5 has been lost, the purified SHA protein survived intact under frozen conditions and retained its activity. Using modern techniques, here we further characterized SHA. Fourier-transform ion cyclotron resonance MS analysis determined SHA's average molecular mass as 13,314.67 Da. MS of digested SHA peptides, Streptomyces genomic database matching, and N-terminal sequencing solved the 131-residue amino acid sequence of SHA...
November 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29079036/apela-promotes-tumour-growth-and-cell-migration-in-ovarian-cancer-in-a-p53-dependent-manner
#7
Yuyin Yi, Shu-Huei Tsai, Jung-Chien Cheng, Evan Y Wang, Michael S Anglesio, Dawn R Cochrane, Megan Fuller, Ewan A Gibb, Wei Wei, David G Huntsman, Aly Karsan, Pamela A Hoodless
OBJECTIVE: APELA is a small, secreted peptide that can function as a ligand for the G-protein coupled receptor, Apelin Receptor (APLNR, APJ). APELA plays an essential role in endoderm differentiation and cardiac development during embryogenesis. We investigated whether APELA exerts any functions in cancer progression. METHODS: The Cancer Genome Atlas (TCGA) RNA sequencing datasets, microarray from an OCCC mouse model, and RNA isolated from fresh frozen and FFPE patient tissue were used to assess APELA expression...
October 24, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29045792/glycopeptides-as-targets-for-dendritic-cells-exploring-muc1-glycopeptides-binding-profile-toward-macrophage-galactose-type-lectin-mgl-orthologs
#8
Gerard Artigas, João T Monteiro, Hiroshi Hinou, Shin-Ichiro Nishimura, Bernd Lepenies, Fayna Garcia-Martin
The macrophage galactose-type lectin (MGL) recognizes glycan moieties exposed by pathogens and malignant cells. Particularly, mucin-1 (MUC1) glycoprotein presents an altered glycosylation in several cancers. To estimate the ability of distinct MGL orthologs to recognize aberrant glycan cores in mucins, we applied evanescent-field detection to a versatile MUC1-like glycopeptide microarray platform. Here, as binding was sequence-dependent, we demonstrated that not only sugars but also peptide region impact the recognition of murine MGL1 (mMGL1)...
November 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29030620/transcriptomic-profiles-of-clostridium-ljungdahlii-during-lithotrophic-growth-with-syngas-or-h2-and-co2-compared-to-organotrophic-growth-with-fructose
#9
Muktak Aklujkar, Ching Leang, Pravin M Shrestha, Minita Shrestha, Derek R Lovley
Clostridium ljungdahlii derives energy by lithotrophic and organotrophic acetogenesis. C. ljungdahlii was grown organotrophically with fructose and also lithotrophically, either with syngas - a gas mixture containing hydrogen (H2), carbon dioxide (CO2), and carbon monoxide (CO), or with H2 and CO2. Gene expression was compared quantitatively by microarrays using RNA extracted from all three conditions. Gene expression with fructose and with H2/CO2 was compared by RNA-Seq. Upregulated genes with both syngas and H2/CO2 (compared to fructose) point to the urea cycle, uptake and degradation of peptides and amino acids, response to sulfur starvation, potentially NADPH-producing pathways involving (S)-malate and ornithine, quorum sensing, sporulation, and cell wall remodeling, suggesting a global and multicellular response to lithotrophic conditions...
October 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29024724/paxgene-fixation-enables-comprehensive-metabolomic-and-proteomic-analyses-of-tissue-specimens-by-maldi-msi
#10
Christian Urban, Achim Buck, Jens T Siveke, Florian Lordick, Birgit Luber, Axel Walch, Michaela Aichler
An alcohol-based non-crosslinking tissue fixative, PAXgene Tissue System, has been proposed as alternative fixation method to formalin, providing superior and morphological preservation. To date, metabolites have not been assessed in PAXgene-fixed tissues. The study focuses on a comparison between PAXgene and standard formalin fixation for metabolomic analysis by MALDI mass spectrometry imaging. Therefore, fifty-six samples from seven mice organs were fixed with PAXgene (PFPE) or formalin (FFPE), embedded in paraffin, and processed to a tissue microarray...
January 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29018805/insight-into-the-selectivity-of-the-g7-18nate-inhibitor-peptide-for-the-grb7-sh2-domain-target
#11
Gabrielle M Watson, William A H Lucas, Menachem J Gunzburg, Jacqueline A Wilce
Growth factor receptor bound protein 7 (Grb7) is an adaptor protein with established roles in the progression of both breast and pancreatic cancers. Through its C-terminal SH2 domain, Grb7 binds to phosphorylated tyrosine kinases to promote proliferative and migratory signaling. Here, we investigated the molecular basis for the specificity of a Grb7 SH2-domain targeted peptide inhibitor. We identified that arginine 462 in the BC loop is unique to Grb7 compared to Grb2, another SH2 domain bearing protein that shares the same consensus binding motif as Grb7...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28978141/ex-vivo-multiplex-profiling-of-protein-tyrosine-kinase-activities-in-early-stages-of-human-lung-adenocarcinoma
#12
Stephan Arni, Thi Hong Nhung Le, Rik de Wijn, Refugio Garcia-Villegas, Martjin Dankers, Walter Weder, Sven Hillinger
Despite constant improvement in existing therapeutic efforts, the overall survival rate of lung cancer patients remains low. Enzyme activities may identify new therapeutically targetable biomarkers and overcome the marked lack of correlation between cellular abundance of translated proteins and corresponding mRNA expression levels. We analysed tyrosine kinase activities to classify lung adenocarcinoma (LuAdCa) resection specimens based on their underlying changes in cellular processes and pathways that are agents of or result from malignant transformation...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28978037/peptide-microarray-profiling-identifies-phospholipase-c-gamma-1-plc-%C3%AE-1-as-a-potential-target-for-t-8-21-aml
#13
Hasan Mahmud, Frank J G Scherpen, Tiny Meeuwsen de Boer, Harm-Jan Lourens, Caroline Schoenherr, Matthias Eder, Michaela Scherr, Victor Guryev, Eveline S De Bont
The t(8;21) (q22;q22) chromosomal translocation is one of the most frequent genetic alterations in acute myeloid leukemia (AML) which has a need for improved therapeutic strategies. We found PLC-γ1 as one of the highest phosphorylated peptides in t(8;21) AML samples compared to NBM or CN-AML in our previous peptide microarray. PLC-γ1 is known to play a role in cancer progression, however, the impact of PLC-γ1 in AML is currently unknown. Therefore, we aimed to study the functional role of PLC-γ1 by investigating the cellular growth, survival and its underlying mechanism in t(8;21) AML...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974743/targeting-the-alternative-sigma-factor-rpon-to-combat-virulence-in-pseudomonas-aeruginosa
#14
Megan G Lloyd, Benjamin R Lundgren, Clayton W Hall, Luke B-P Gagnon, Thien-Fah Mah, Jennifer F Moffat, Christopher T Nomura
Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that infects immunocompromised and cystic fibrosis patients. Treatment is difficult due to antibiotic resistance, and new antimicrobials are needed to treat infections. The alternative sigma factor 54 (σ(54), RpoN), regulates many virulence-associated genes. Thus, we evaluated inhibition of virulence in P. aeruginosa by a designed peptide (RpoN molecular roadblock, RpoN*) which binds specifically to RpoN consensus promoters. We expected that RpoN* binding to its consensus promoter sites would repress gene expression and thus virulence by blocking RpoN and/or other transcription factors...
October 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28970963/ultrasensitive-tumour-penetrating-nanosensors-of-protease-activity
#15
Ester J Kwon, Jaideep S Dudani, Sangeeta N Bhatia
The ability to identify cancer lesions with endogenous biomarkers is currently limited to tumours ~1 cm in diameter. We recently reported an exogenously administered tumour-penetrating nanosensor that sheds, in response to tumour-specific proteases, peptide fragments that can then be detected in the urine. Here, we report the optimization, informed by a pharmacokinetic mathematical model, of the surface presentation of the peptide substrates to both enhance on-target protease cleavage and minimize off-target cleavage, and of the functionalization of the nanosensors with tumour-penetrating ligands that engage active trafficking pathways to increase activation in the tumour microenvironment...
2017: Nature biomedical engineering
https://www.readbyqxmd.com/read/28961244/high-resolution-profiling-of-linear-b-cell-epitopes-from-mucin-associated-surface-proteins-masps-of-trypanosoma-cruzi-during-human-infections
#16
Ignacio M Durante, Pablo E La Spina, Santiago J Carmona, Fernán Agüero, Carlos A Buscaglia
BACKGROUND: The Trypanosoma cruzi genome bears a huge family of genes and pseudogenes coding for Mucin-Associated Surface Proteins (MASPs). MASP molecules display a 'mosaic' structure, with highly conserved flanking regions and a strikingly variable central and mature domain made up of different combinations of a large repertoire of short sequence motifs. MASP molecules are highly expressed in mammal-dwelling stages of T. cruzi and may be involved in parasite-host interactions and/or in diverting the immune response...
September 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28957638/augmented-responses-to-ozone-in-obese-mice-require-il-17a-and-gastrin-releasing-peptide
#17
Joel A Mathews, Nandini Krishnamoorthy, David I Kasahara, John Hutchinson, Youngji Cho, Jeffrey D Brand, Alison S Williams, Allison P Wurmbrand, Luiza Ribeiro, Frank Cuttitta, Mary E Sunday, Bruce D Levy, Stephanie A Shore
Ozone and obesity both increase IL-17A in the lungs. In mice, obesity augments the airway hyperresponsiveness and neutrophil recruitment induced by acute ozone exposure. Therefore, we examined the role of IL-17A in obesity-related increases in the response to ozone observed in obese mice. Lean wildtype and obese db/db mice were pretreated with IL-17A blocking or isotype antibodies, exposed to air or ozone (2 ppm for 3 h), and evaluated 24 h later. Microarray analysis of lung tissue gene expression was used to examine the mechanistic basis for effects of anti-IL-17A...
September 28, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28952593/focused-screening-of-ecm-selective-adhesion-peptides-on-cellulose-bound-peptide-microarrays
#18
Kei Kanie, Yuto Kondo, Junki Owaki, Yurika Ikeda, Yuji Narita, Ryuji Kato, Hiroyuki Honda
The coating of surfaces with bio-functional proteins is a promising strategy for the creation of highly biocompatible medical implants. Bio-functional proteins from the extracellular matrix (ECM) provide effective surface functions for controlling cellular behavior. We have previously screened bio-functional tripeptides for feasibility of mass production with the aim of identifying those that are medically useful, such as cell-selective peptides. In this work, we focused on the screening of tripeptides that selectively accumulate collagen type IV (Col IV), an ECM protein that accelerates the re-endothelialization of medical implants...
November 19, 2016: Bioengineering
https://www.readbyqxmd.com/read/28951215/structure-insights-into-the-molecular-mechanism-of-the-interaction-between-uhrf2-and-pcna
#19
Wanbiao Chen, Minhao Wu, Tianrong Hang, Chengliang Wang, Xuan Zhang, Jianye Zang
UHRF2 (Ubiquitin-like with PHD and ring finger domains 2) is an E3 ubiquitin ligase that plays important roles in DNA methylation, histone modifications and cell cycle regulation by interacting with multiple epigenetic or cell-cycle related proteins. Previous studied have identified PCNA (Proliferating cell nuclear antigen) as an interacting partner of UHRF2 by using the antibody microarray. However, the molecular mechanism and the function of UHRF2-PCNA interaction remains unclear. Here, we report the complex structure of PCNA and the peptide ((784)NEILQTLLDLFFPGYSK(800)) derived from UHRF2 that contains a PIP box...
September 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28949514/identifying-dysregulated-epigenetic-enzyme-activity-in-castrate-resistant-prostate-cancer-development
#20
Jin-Hee Lee, Bing Yang, Anastasia J Lindahl, Nathan Damaschke, Melissa D Boersma, Wei Huang, Eva Corey, David F Jarrard, John M Denu
There is a tremendous need for novel strategies aimed at directly assessing activities of histone modifiers to probe epigenetic determinants associated with disease progression. Here, we developed a high-throughput peptide microarray assay to identify altered histone lysine (de)acetylation activity in prostate cancer (PCa). This microarray-based activity assay revealed up-regulated histone acetyltransferase (HAT) activity against specific histone H3 sites in a castrate-resistant (CR) PCa cell line compared to its hormone-sensitive (HS) isogenic counterpart...
October 11, 2017: ACS Chemical Biology
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