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https://www.readbyqxmd.com/read/28092737/complex-molecular-changes-induced-by-chronic-progestogens-exposure-in-roach-rutilus-rutilus
#1
Gabor Maasz, Zita Zrinyi, Peter Takacs, Sandor Lovas, Istvan Fodor, Tibor Kiss, Zsolt Pirger
In our previous study, we measured 0.23-13.67ng/L progestogens (progesterone, drospirenone, levonorgestrel) in natural waters in the catchment area of the largest shallow lake of Central Europe, Lake Balaton. Progestogen contaminations act as potent steroids with mixed progestagenic, androgenic and mild estrogenic effects that is why our aim was to investigate the morphological and molecular effects of mixture of progesterone, drospirenone, and levonorgestrel in environmentally relevant (10ng/L) and higher (50 and 500ng/L) exposure concentrations in common roach, Rutilus rutilus...
January 13, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28092693/pathogenic-streptococcus-strains-employ-novel-escape-strategy-to-inhibit-bacteriostatic-effect-mediated-by-mammalian-peptidoglycan-recognition-protein
#2
Jing Wang, Youjun Feng, Changjun Wang, Swaminath Srinivas, Chen Chen, Hui Liao, Elaine He, Shibo Jiang, Jiaqi Tang
Pathogenic streptococcal species are responsible for some of the most lethal and prevalent animal and human infections. Previous reports have identified a candidate pathogenicity island (PAI) in two highly virulent clinical isolates of Streptococcus suis type 2 (SS2), a causative agent of high-mortality streptococcal toxic shock syndrome (STSS). This PAI contains a Type-IVC secretion system C subgroup (Type-IVC secretion system) that is involved in the secretion of unknown pathogenic effectors that are responsible for STSS caused by highly virulent strains of SS2...
January 16, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28092690/post-translational-selective-intracellular-silencing-of-acetylated-proteins-with-de-novo-selected-intrabodies
#3
Michele Chirichella, Simonetta Lisi, Marco Fantini, Martina Goracci, Mariantonietta Calvello, Rossella Brandi, Ivan Arisi, Mara D'Onofrio, Cristina Di Primio, Antonino Cattaneo
The ability to selectively interfere with post-translationally modified proteins would have many biological and therapeutic applications. However, post-translational modifications cannot be selectively targeted by nucleic-acid-based interference approaches. Here we describe post-translational intracellular silencing antibody technology (PISA), a method for selecting intrabodies against post-translationally modified proteins. We demonstrate our method by generating intrabodies against native acetylated proteins and showing functional interference in living cells...
January 16, 2017: Nature Methods
https://www.readbyqxmd.com/read/28092679/genome-wide-analysis-of-p53-regulated-transcription-in-myc-driven-lymphomas
#4
C Tonelli, M J Morelli, A Sabò, A Verrecchia, L Rotta, T Capra, S Bianchi, S Campaner, B Amati
The tumour suppressor p53 is a transcription factor that controls cellular stress responses. Here, we dissected the transcriptional programmes triggered upon restoration of p53 in Myc-driven lymphomas, based on the integrated analysis of p53 genomic occupancy and gene regulation. p53 binding sites were identified at promoters and enhancers, both characterized by the pre-existence of active chromatin marks. Only a small fraction of these sites showed the 20 base-pair p53 consensus motif, suggesting that p53 recruitment to genomic DNA was primarily mediated through protein-protein interactions in a chromatin context...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092676/intracellular-il-37b-interacts-with-smad3-to-suppress-multiple-signaling-pathways-and-the-metastatic-phenotype-of-tumor-cells
#5
C Luo, Y Shu, J Luo, D Liu, D-S Huang, Y Han, C Chen, Y-C Li, J-M Zou, J Qin, Y Wang, D Li, S-S Wang, G-M Zhang, J Chen, Z-H Feng
Multiple signaling pathways that promote tumor cell metastasis are differentially activated in low/non-metastatic and metastatic tumor cells, resulting in the differential expression of metastasis-related genes. The underlying mechanism may involve the alterations of the intrinsic negative regulation in tumor cells. Here we report that the differential expression of interleukin-37b (IL-37b) in tumor cells alters the intrinsic negative regulation of signaling pathways, resulting in the difference of metastatic capacity...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092671/pde4d-promotes-fak-mediated-cell-invasion-in-braf-mutated-melanoma
#6
J Delyon, A Servy, F Laugier, J André, N Ortonne, M Battistella, S Mourah, A Bensussan, C Lebbé, N Dumaz
The cyclic AMP (cAMP) signaling pathway is critical in melanocyte biology for regulating differentiation. It is downregulated by phosphodiesterase (PDE) enzymes, which degrade cAMP itself. In melanoma evidence suggests that inhibition of the cAMP pathway by PDE type 4 (PDE4) favors tumor progression. For example, in melanomas harboring RAS mutations, the overexpression of PDE4 is crucial for MAPK pathway activation and proliferation induced by oncogenic RAS. Here we showed that PDE4D is overexpressed in BRAF-mutated melanoma cell lines, constitutively disrupting the cAMP pathway activation...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092667/oncogenic-braf-fusions-in-mucosal-melanomas-activate-the-mapk-pathway-and-are-sensitive-to-mek-pi3k-inhibition-or-mek-cdk4-6-inhibition
#7
H S Kim, M Jung, H N Kang, H Kim, C-W Park, S-M Kim, S J Shin, S H Kim, S G Kim, E K Kim, M R Yun, Z Zheng, K Y Chung, J Greenbowe, S M Ali, T-M Kim, B C Cho
Despite remarkable progress in cutaneous melanoma genomic profiling, the mutational landscape of primary mucosal melanomas (PMM) remains unclear. Forty-six PMMs underwent targeted exome sequencing of 111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted on eight genes, including TP53 (13%), NRAS (13%), SNX31 (9%), NF1 (9%), KIT (7%) and APC (7%). Mitogen-activated protein kinase (MAPK; 37%), cell cycle (20%) and phosphatidylinositol 3-kinase (PI3K)-mTOR (15%) pathways were frequently mutated...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092665/antibody-10-1074-suppresses-viremia-in-hiv-1-infected-individuals
#8
Marina Caskey, Till Schoofs, Henning Gruell, Allison Settler, Theodora Karagounis, Edward F Kreider, Ben Murrell, Nico Pfeifer, Lilian Nogueira, Thiago Y Oliveira, Gerald H Learn, Yehuda Z Cohen, Clara Lehmann, Daniel Gillor, Irina Shimeliovich, Cecilia Unson-O'Brien, Daniela Weiland, Alexander Robles, Tim Kümmerle, Christoph Wyen, Rebeka Levin, Maggi Witmer-Pack, Kemal Eren, Caroline Ignacio, Szilard Kiss, Anthony P West, Hugo Mouquet, Barry S Zingman, Roy M Gulick, Tibor Keler, Pamela J Bjorkman, Michael S Seaman, Beatrice H Hahn, Gerd Fätkenheuer, Sarah J Schlesinger, Michel C Nussenzweig, Florian Klein
Monoclonal antibody 10-1074 targets the V3 glycan supersite on the HIV-1 envelope (Env) protein. It is among the most potent anti-HIV-1 neutralizing antibodies isolated so far. Here we report on its safety and activity in 33 individuals who received a single intravenous infusion of the antibody. 10-1074 was well tolerated and had a half-life of 24.0 d in participants without HIV-1 infection and 12.8 d in individuals with HIV-1 infection. Thirteen individuals with viremia received the highest dose of 30 mg/kg 10-1074...
January 16, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28092616/generation-and-characterization-of-a-monoclonal-antibody-against-duck-tembusu-virus-envelope-protein
#9
K Han, D Zhao, Y Liu, Q Liu, X Huang, J Yang, K Bi, T Xu, Y Li
Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has caused massive economic losses to the duck industry in China. Envelope (E) protein of DTMUV is an important structural protein, which is able to induce protective immune response in target animals and can be used as specific serological diagnosis tool. In this study, a novel monoclonal antibody, designated mAb 3E9, was generated against DTMUV E protein. It is positive in indirect ELISA against both His-E protein and the purified whole viral antigen...
December 1, 2016: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/28092463/ccaat-enhancer-binding-protein-%C3%AE-mediates-the-killing-of-toxoplasma-gondii-by-inducing-autophagy-in-nonhematopoietic-cells
#10
Yanhui Yu, Na Zhao, Jiaqi An, Xichen Zhang
Autophagy is a main defense strategy by which infected host cells can virtually induce the killing of parasite, including Toxoplasma gondii. However, the regulatory mechanisms of autophagy in T. gondii-infected nonhematopoietic cells are still unknown. Emerging evidence indicates that CCAAT/enhancer-binding protein β (C/EBP β) is associated with the regulation of autophagy. Herein, we hypothesized that C/EBP β plays roles in inducing autophagy in nonhematopoietic cells. Expression of C/EBP β was aberrantly regulated in endothelial cells and retinal pigment epithelial cells challenged by T...
January 16, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28092380/chromatin-immunoprecipitation-in-microfluidic-droplets-towards-fast-and-cheap-analyses
#11
Bruno Teste, Jerome Champ, Arturo Londono-Vallejo, Stéphanie Descroix, Laurent Malaquin, Jean-Louis Viovy, Irena Draskovic, Guillaume Mottet
Genetic organization is governed by the interaction of DNA with histone proteins, and differential modifications of these proteins is a fundamental mechanism of gene regulation. Histone modifications are primarily studied through chromatin immunoprecipitation (ChIP) assays, however conventional ChIP procedures are time consuming, laborious and require a large number of cells. Here we report for the first time the development of ChIP in droplets based on a microfluidic platform combining nanoliter droplets, magnetic beads (MB) and magnetic tweezers (MT)...
January 16, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28092369/context-dependent-role-for-chromatin-remodeling-component-pbrm1-baf180-in-clear-cell-renal-cell-carcinoma
#12
A Murakami, L Wang, S Kalhorn, P Schraml, W K Rathmell, A C Tan, R Nemenoff, K Stenmark, B-H Jiang, M E Reyland, L Heasley, C-J Hu
A subset of clear cell renal cell carcinoma (ccRCC) tumors exhibit a HIF1A gene mutation, yielding two ccRCC tumor types, H1H2 type expressing both HIF1α and HIF2α, and H2 type expressing HIF2α, but not functional HIF1α protein. However, it is unclear how the H1H2 type ccRCC tumors escape HIF1's tumor-suppressive activity. The polybromo-1 (PBRM1) gene coding for the BAF180 protein, a component of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, is inactivated in 40% ccRCCs, the function and mechanism of BAF180 mutation is unknown...
January 16, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28092365/cancer-cell-chemokines-direct-chemotaxis-of-activated-stellate-cells-in-pancreatic-ductal-adenocarcinoma
#13
Ishan Roy, Kathleen A Boyle, Emily P Vonderhaar, Noah P Zimmerman, Egal Gorse, A Craig Mackinnon, Rosa F Hwang, Janusz Franco-Barraza, Edna Cukierman, Susan Tsai, Douglas B Evans, Michael B Dwinell
The mechanisms by which the extreme desmoplasia observed in pancreatic tumors develops remain unknown and its role in pancreatic cancer progression is unsettled. Chemokines have a key role in the recruitment of a wide variety of cell types in health and disease. Transcript and protein profile analyses of human and murine cell lines and human tissue specimens revealed a consistent elevation in the receptors CCR10 and CXCR6, as well as their respective ligands CCL28 and CXCL16. Elevated ligand expression was restricted to tumor cells, whereas receptors were in both epithelial and stromal cells...
January 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28092364/proof-of-the-quantitative-potential-of-immunofluorescence-by-mass-spectrometry
#14
Maria I Toki, Fabiola Cecchi, Todd Hembrough, Konstantinos N Syrigos, David L Rimm
Protein expression in formalin-fixed, paraffin-embedded patient tissue is routinely measured by Immunohistochemistry (IHC). However, IHC has been shown to be subject to variability in sensitivity, specificity and reproducibility, and is generally, at best, considered semi-quantitative. Mass spectrometry (MS) is considered by many to be the criterion standard for protein measurement, offering high sensitivity, specificity, and objective molecular quantification. Here, we seek to show that quantitative immunofluorescence (QIF) with standardization can achieve quantitative results comparable to MS...
January 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28092269/analysis-of-microtubule-growth-dynamics-arising-from-altered-actin-network-structure-and-contractility-in-breast-tumor-cells
#15
Eleanor Ory, Lekhana Bhandary, Amanda Boggs, Kristi Chakrabarti, Joshua Parker, Wolfgang Losert, Stuart S Martin
The periphery of epithelial cells is shaped by opposing cytoskeletal physical forces generated predominately by two dynamic force generating systems - growing microtubule ends push against the boundary from the cell center, and the actin cortex contracts the attached plasma membrane. Here we investigate how changes to the structure and dynamics of the actin cortex alter the dynamics of microtubules. Current drugs target actin polymerization and contraction to reduce cell division and invasiveness; however, the impacts on microtubule dynamics remain incompletely understood...
January 16, 2017: Physical Biology
https://www.readbyqxmd.com/read/28092110/simultaneous-detection-of-three-sex-steroid-hormone-classes-using-a-novel-yeast-based-biosensor
#16
Alexandre Chamas, Ha Thi Minh Pham, Martin Jähne, Karina Wettwer, Steffen Uhlig, Kirsten Simon, Almuth Einspanier, Kim Baronian, Gotthard Kunze
A biosensor detecting estrogens, progestogens and androgens in complex samples and in a single step is described. Three Arxula adeninivorans yeast strains were created, each strain producing a different recombinant human hormone receptor and a different fluorescent reporter protein. These strains were then mixed to create G1212/YRC102-hHR-fluo, the biological component of the biosensor. During incubation with G1212/YRC102-hHR-fluo, hormones present in a sample bind to their target receptor, which leads to the production of a specific fluorescent protein...
January 16, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28092085/evidence-that-nf-%C3%AE%C2%BAb-and-mapk-signaling-promotes-nlrp-inflammasome-activation-in-neurons-following-ischemic-stroke
#17
David Yang-Wei Fann, Yun-An Lim, Yi-Lin Cheng, Ker-Zhing Lok, Prasad Chunduri, Sang-Ha Baik, Grant R Drummond, S Thameem Dheen, Christopher G Sobey, Dong-Gyu Jo, Christopher Li-Hsian Chen, Thiruma V Arumugam
Multi-protein complexes, termed "inflammasomes," are known to contribute to neuronal cell death and brain injury following ischemic stroke. Ischemic stroke increases the expression and activation of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) Pyrin domain containing 1 and 3 (NLRP1 and NLRP3) inflammasome proteins and both interleukin (IL)-1β and IL-18 in neurons. In this study, we provide evidence that activation of either the NF-κB and MAPK signaling pathways was partly responsible for inducing the expression and activation of NLRP1 and NLRP3 inflammasome proteins and that these effects can be attenuated using pharmacological inhibitors of these two pathways in neurons and brain tissue under in vitro and in vivo ischemic conditions, respectively...
January 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28092041/in-solution-sh2-domain-binding-assay-based-on-proximity-ligation
#18
Kazuya Machida
Protein-protein interactions mediated by SH2 domains confer specificity in tyrosine kinase pathways. Traditional assays for assessing interactions between an SH2 domain and its interacting protein such as far-Western and pull-down are inherently low throughput. We developed SH2-PLA, an in-solution SH2 domain binding assay, that takes advantage of the speed and sensitivity of proximity ligation and real-time PCR. SH2-PLA allows for rapid assessment of SH2 domain binding to a target protein using only a few microliters of cell lysate, thereby making it an attractive new tool to study tyrosine kinase signaling...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28092033/purification-of-socs-suppressor-of-cytokine-signaling-sh2-domains-for-structural-and-functional-studies
#19
Nicholas P D Liau, Artem Laktyushin, Jeffrey J Babon
Src Homology 2 (SH2) domains are protein domains which have a high binding affinity for specific amino acid sequences containing a phosphorylated tyrosine residue. The Suppressors of Cytokine Signaling (SOCS) proteins use an SH2 domain to bind to components of certain cytokine signaling pathways to downregulate the signaling cascade. The recombinantly produced SH2 domains of various SOCS proteins have been used to undertake structural and functional studies elucidating the method of how such targeting occurs...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28092029/an-efficient-semi-supervised-learning-approach-to-predict-sh2-domain-mediated-interactions
#20
Kousik Kundu, Rolf Backofen
Src homology 2 (SH2) domain is an important subclass of modular protein domains that plays an indispensable role in several biological processes in eukaryotes. SH2 domains specifically bind to the phosphotyrosine residue of their binding peptides to facilitate various molecular functions. For determining the subtle binding specificities of SH2 domains, it is very important to understand the intriguing mechanisms by which these domains recognize their target peptides in a complex cellular environment. There are several attempts have been made to predict SH2-peptide interactions using high-throughput data...
2017: Methods in Molecular Biology
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