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https://www.readbyqxmd.com/read/29332387/proteome-wide-characterization-of-phosphorylation-induced-conformational-changes-in-breast-cancer
#1
He Meng, Michael C Fitzgerald
Because of the close link between protein function and protein folding stability, knowledge about phosphorylation-induced protein folding stability changes can lead to a better understanding of the functional effects of protein phosphorylation. Here, the Stability of Proteins from Rates of OXidation (SPROX) and Limited Proteolysis (LiP) techniques are used to compare the conformational properties of proteins in two MCF-7 cell lysates, including one that was and one that was not dephosphorylated with alkaline phosphatase...
January 15, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29330894/structure-function-and-evolution-of-the-hemerythrin-like-domain-superfamily
#2
Claudia Alvarez-Carreño, Vikram Alva, Arturo Becerra, Antonio Lazcano
Hemerythrin-like proteins have generally been studied for their ability to reversibly bind oxygen through their binuclear non-heme iron centers. However, in recent years, it has become increasingly evident that some members of the hemerythrin-like superfamily also participate in many other biological processes. For instance, the binuclear non-heme iron site of YtfE, a hemerythrin-like protein involved in the repair of iron centers in Escherichia coli, catalyzes the reduction of nitric oxide to nitrous oxide, and the human F-box/LRR-repeat protein 5, which contains a hemerythrin-like domain, is involved in intracellular iron homeostasis...
January 13, 2018: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29330303/mammalian-amyloidogenic-proteins-promote-prion-nucleation-in-yeast
#3
Pavithra Chandramowlishwaran, Meng Sun, Kristin L Casey, Andrey V Romanyuk, Anastasiya V Grizel, Julia V Sopova, Aleksandr A Rubel, Carmen Nussbaum-Krammer, Ina M Vorberg, Yury O Chernoff
Fibrous cross-β aggregates (amyloids) and their transmissible forms (prions) cause diseases in mammals (including humans) and control heritable traits in yeast. Initial nucleation of a yeast prion by transiently overproduced prion-forming protein or its (typically, QN-rich) prion domain is efficient only in the presence of another aggregated (in most cases, QN-rich) protein. Here, we demonstrate that a fusion of the prion domain of yeast protein Sup35 to some non-QN-rich mammalian proteins, associated with amyloid diseases, promotes nucleation of Sup35 prions in the absence of preexisting aggregates...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29330215/mir-195-regulates-metabolism-in-failing-myocardium-via-alterations-in-sirt3-expression-and-mitochondrial-protein-acetylation
#4
Xiaokan Zhang, Ruiping Ji, Xianghai Liao, Estibaliz Castillero, Peter J Kennel, Danielle L Brunjes, Marcus Franz, Sven Möbius-Winkler, Konstantinos Drosatos, Isaac George, Emily I Chen, Paolo C Colombo, P Christian Schulze
Background -Heart failure (HF) leads to mitochondrial dysfunction and metabolic abnormalities of the failing myocardium coupled with an energy-depleted state and cardiac remodeling. The mitochondrial deacetylase sirtuin 3 (SIRT3) plays a pivotal role in the maintenance of mitochondrial function through regulating the mitochondrial acetylome. Interestingly, unique cardiac and systemic miRNAs have been shown to play an important role in cardiac remodeling by modulating key signaling elements in the myocardium...
January 12, 2018: Circulation
https://www.readbyqxmd.com/read/29329550/systematic-quantitative-analysis-of-h2a-and-h2b-variants-by-targeted-proteomics
#5
Sara El Kennani, Annie Adrait, Olga Permiakova, Anne-Marie Hesse, Côme Ialy-Radio, Myriam Ferro, Virginie Brun, Julie Cocquet, Jérôme Govin, Delphine Pflieger
BACKGROUND: Histones organize DNA into chromatin through a variety of processes. Among them, a vast diversity of histone variants can be incorporated into chromatin and finely modulate its organization and functionality. Classically, the study of histone variants has largely relied on antibody-based assays. However, antibodies have a limited efficiency to discriminate between highly similar histone variants. RESULTS: In this study, we established a mass spectrometry-based analysis to address this challenge...
January 12, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29329547/microfluidic-co-culture-of-pancreatic-tumor-spheroids-with-stellate-cells-as-a-novel-3d-model-for-investigation-of%C3%A2-stroma-mediated-cell-motility-and-drug-resistance
#6
Ji-Hyun Lee, Seul-Ki Kim, Iftikhar Ali Khawar, Su-Yeong Jeong, Seok Chung, Hyo-Jeong Kuh
BACKGROUND: Pancreatic stellate cells (PSCs), a major component of the tumor microenvironment in pancreatic cancer, play roles in cancer progression as well as drug resistance. Culturing various cells in microfluidic (microchannel) devices has proven to be a useful in studying cellular interactions and drug sensitivity. Here we present a microchannel plate-based co-culture model that integrates tumor spheroids with PSCs in a three-dimensional (3D) collagen matrix to mimic the tumor microenvironment in vivo by recapitulating epithelial-mesenchymal transition and chemoresistance...
January 12, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29329425/comparison-of-hepatic-2d-sandwich-cultures-and-3d-spheroids-for-long-term-toxicity-applications-a-multi-center-study
#7
Catherine C Bell, Anita C A Dankers, Volker M Lauschke, Rowena Sison-Young, Roz Jenkins, Cliff Rowe, Chris Goldring, Kevin Park, Sophie Regan, Tracy Walker, Chris Schofield, Audrey Baze, Alison J Foster, Dominic Williams, Amy W M van de Ven, Frank Jacobs, Jos van Houdt, Tuula Lähteenmäki, Jan Snoeys, Satu Juhila, Lysiane Richert, Magnus Ingelman-Sundberg
Primary human hepatocytes (PHH) are commonly used for in vitro studies of drug-induced liver injury. However, when cultured as 2D monolayers, PHH lose crucial hepatic functions within hours. This dedifferentiation can be ameliorated when PHH are cultured in sandwich configuration (2Dsw), particularly when cultures are regularly re-overlaid with extracellular matrix, or as 3D spheroids. In this study, the six participating laboratories evaluated the robustness of these two model systems made from cryopreserved PHH from the same donors considering both inter-donor and inter-lab variability and compared their suitability for use in repeated-dose toxicity studies using 5 different hepatotoxins with different toxicity mechanisms...
January 10, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29329019/salidroside-influences-the-cellular-cross-talk-of-human-fetal-lung-diploid-fibroblasts-a-proteomic-approach
#8
Wenmin Xing, Wenyan Gao, Huili Su, Sanying Wang, Jing Zhang, Genxiang Mao, Jing Yan
Senescence is a complex multiple factor proces, which is still poorly understood. The purpose of this study was to find the proteome of cultured human fetal lung diploid fibroblasts (2BS) of different population doubling (PD), as well as the altered proteome induced by salidroside (SAL) in 2BS cells. Proteins were identified by two-dimensional electrophoresis (2-DE) combining matrix-assisted laser desorption/ionization-time and flight mass spectrometry (MAL DI-TOF/MS). As a result, we found 16 proteins with two-fold variations in senescent cells or after SAL treatment, some being reduced such as reticulocalbin-1, heat shock protein beta-6, elongation factor 1-delta, F-actin-capping protein subunit alpha-1, and chloride intracellular channel 1...
January 5, 2018: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29328367/tumorigenic-proteins-upregulated-in-the-mycn-amplified-imr-32-human-neuroblastoma-cells-promote-proliferation-and-migration
#9
Hayat Zaatiti, Jad Abdallah, Zeina Nasr, George Khazen, Anthony Sandler, Tamara J Abou-Antoun
Childhood neuroblastoma is one of the most common types of extra-cranial cancer affecting children with a clinical spectrum ranging from spontaneous regression to malignant and fatal progression. In order to improve the clinical outcomes of children with high-risk neuroblastoma, it is crucial to understand the tumorigenic mechanisms that govern its malignant behaviors. MYCN proto-oncogene, bHLH transcription factor (MYCN) amplification has been implicated in the malignant, treatment-evasive nature of aggressive, high-risk neuroblastoma...
January 4, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29327913/proteomic-analysis-of-the-downstream-signaling-network-of-parp1
#10
Yuanli Zhen, Yonghao Yu
Poly-ADP-ribosylation (PARylation) is a protein posttranslational modification (PTM) that is critically involved in many biological processes that are linked to cell stress responses. It is catalyzed by a class of enzymes known as poly-ADP-ribose polymerases (PARPs). In particular, PARP1 is a nuclear protein that is activated upon sensing nicked DNA. Once activated, PARP1 is responsible for the synthesis of a large number of PARylated proteins and initiation of the DNA damage response (DDR) mechanisms. This observation provided the rationale for developing PARP1 inhibitors for the treatment of human malignancies...
January 12, 2018: Biochemistry
https://www.readbyqxmd.com/read/29327467/erbb3-binding-protein-ebp1-is-a-novel-dppa4-cofactor-in-human-pluripotent-cells
#11
Priyanka Somanath, Kelly M Bush, Paul S Knoepfler
Developmental Pluripotency-Associated-4 (DPPA4) is one of the few core pluripotency genes lacking clearly defined molecular and cellular functions. Here we used a proteomics screening approach of human embryonic stem cell (hESC) nuclear extract to determine DPPA4 molecular functions through identification of novel cofactors. Unexpectedly, the signaling molecule ERBB3-binding protein 1 (EBP1) was the strongest candidate binding partner for DPPA4 in hESC. EBP1 is a growth factor signaling mediator present in two isoforms, p48 and p42...
January 12, 2018: Stem Cells
https://www.readbyqxmd.com/read/29327448/the-saliva-proteome-of-dogs-variations-within-and-between-breeds-and-between-species
#12
Sabah Pasha, Taichi Inui, Iain Chapple, Stephen Harris, Lucy Holcombe, Melissa M Grant
Saliva is a complex multifunctional fluid that bathes the oral cavity to assist in soft and hard tissue maintenance, lubrication, buffering, defence against microbes and initiating digestion of foods. It has been extensively characterised in humans but its protein composition in dogs remains poorly characterised, yet could explain (patho) physiological differences between individuals, breeds and with humans. This pilot discovery study aimed to characterise canine saliva from two breeds, Labrador retrievers and Beagles, and to compare this with human saliva using quantitative mass spectrometry...
January 12, 2018: Proteomics
https://www.readbyqxmd.com/read/29326975/identifying-the-substrate-proteins-of-u-box-e3s-e4b-and-chip-by-orthogonal-ubiquitin-transfer
#13
Karan Bhuripanyo, Yiyang Wang, Xianpeng Liu, Li Zhou, Ruochuan Liu, Duc Duong, Bo Zhao, Yingtao Bi, Han Zhou, Geng Chen, Nicholas T Seyfried, Walter J Chazin, Hiroaki Kiyokawa, Jun Yin
E3 ubiquitin (UB) ligases E4B and carboxyl terminus of Hsc70-interacting protein (CHIP) use a common U-box motif to transfer UB from E1 and E2 enzymes to their substrate proteins and regulate diverse cellular processes. To profile their ubiquitination targets in the cell, we used phage display to engineer E2-E4B and E2-CHIP pairs that were free of cross-reactivity with the native UB transfer cascades. We then used the engineered E2-E3 pairs to construct "orthogonal UB transfer (OUT)" cascades so that a mutant UB (xUB) could be exclusively used by the engineered E4B or CHIP to label their substrate proteins...
January 2018: Science Advances
https://www.readbyqxmd.com/read/29326176/combinatorial-omics-analysis-reveals-perturbed-lysosomal-homeostasis-in-collagen-vii-deficient-keratinocytes
#14
Kerstin Thriene, Björn Andreas Grüning, Olivier Bornert, Anika Erxleben, Juna Leppert, Ioannis Athanasiou, Ekkehard Weber, Dimitra Kiritsi, Alexander Nyström, Thomas Reinheckel, Rolf Backofen, Cristina Has, Leena Bruckner-Tuderman, Joern Dengjel
The extracellular matrix protein collagen VII is part of the microenvironment of stratified epithelia and critical in organismal homeostasis. Mutations in the encoding gene COL7A1 lead to the skin disorder dystrophic epidermolysis bullosa (DEB), are linked to skin fragility and progressive inflammation-driven fibrosis that facilitates aggressive skin cancer. So far, these changes have been linked to mesenchymal alterations, the epithelial consequences of collagen VII loss remaining under-addressed. As epithelial dysfunction is a principal initiator of fibrosis, we performed a comprehensive transcriptome and proteome profiling of primary human keratinocytes to generate global and detailed images of dysregulated epidermal molecular pathways linked to loss of collagen VII...
January 11, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29326001/coxsackievirus-and-type-1-diabetes-mellitus-the-wolf-s-footprints
#15
Decio L Eizirik, Anne Op de Beeck
Enteroviruses are important environmental contributors to islet inflammation (insulitis) in type 1 diabetes mellitus (T1DM). A recent study characterized the proteomic alterations induced by Coxsackievirus type B (CVB) infection of human islets. This provides relevant information to decipher the words of the virus-induced 'dialog' between β cells and the immune system that leads to autoimmunity.
January 8, 2018: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29324989/synaptic-markers-of-cognitive-decline-in-neurodegenerative-diseases-a-proteomic-approach
#16
Erika Bereczki, Rui M Branca, Paul T Francis, Joana B Pereira, Jean-Ha Baek, Tibor Hortobágyi, Bengt Winblad, Clive Ballard, Janne Lehtiö, Dag Aarsland
Cognitive changes occurring throughout the pathogenesis of neurodegenerative diseases are directly linked to synaptic loss. We used in-depth proteomics to compare 32 post-mortem human brains in the prefrontal cortex of prospectively followed patients with Alzheimer's disease, Parkinson's disease with dementia, dementia with Lewy bodies and older adults without dementia. In total, we identified 10 325 proteins, 851 of which were synaptic proteins. Levels of 25 synaptic proteins were significantly altered in the various dementia groups...
January 9, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29323384/tracking-iron-associated-proteomes-in-pathogens-by-a-fluorescence-approach
#17
Nan Jiang, Tianfan Cheng, Minji Wang, Godfrey Chi-Fung Chan, Lijian Jin, Hongyan Li, Hongzhe Sun
Porphyromonas gingivalis is a key oral anaerobic bacterium involved in human periodontitis, which may affect up to 15% adults worldwide. Using the membrane permeable fluorescent probe Fe-TRACER, we identified 17 iron-associated proteins in Porphyromonas gingivalis. We demonstrated the specific binding of the probe towards iron-associated proteins using transferrin as an example and provided an X-ray structure of the fluorescent probe-bound transferrin. Our study provides a basis for the understanding of iron homeostasis in pathogens, and our approach based on the integration of fluorescence imaging with proteomics and bioinformatics can be readily extended to mine other metalloproteomes in microbials...
January 11, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29323160/glutathione-s-transferase-gst-of-american-cockroach-periplaneta-americana-classes-isoforms-and-allergenicity
#18
Nitat Sookrung, Onrapak Reamtong, Rojana Poolphol, Nitaya Indrawattana, Watee Seesuay, Nawannaporn Saelim, Pongsakorn Tantilipikorn, Chaweewan Bunnag, Wanpen Chaicumpa, Anchalee Tungtrongchitr
Insect glutathione S-transferases (GSTs) play important roles in insecticide/drug resistance and stress response. Medically, GSTs of house dust mites (Dermatophagoides pteronyssinus and Blomia tropicalis) and German cockroach (Blattella germanica) are human allergens. In this study, classes, isoforms and B-cell and allergenic epitopes of GST of American cockroach, Periplaneta americana, the predominant species in the tropics and subtropics were investigated for the first time. Enzymatically active native and recombinant P...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29323144/defining-tissue-proteomes-by-systematic-literature-review
#19
Sarah A Hibbert, Matiss Ozols, Christopher E M Griffiths, Rachel E B Watson, Mike Bell, Michael J Sherratt
Defining protein composition is a key step in understanding the function of both healthy and diseased biological systems. There is currently little consensus between existing published proteomes in tissues such as the aorta, cartilage and organs such as skin. Lack of agreement as to both the number and identity of proteins may be due to issues in protein extraction, sensitivity/specificity of detection and the use of disparate tissue/cell sources. Here, we developed a method combining bioinformatics and systematic review to screen >32M articles from the Web of Science for evidence of proteins in healthy human skin...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29322922/analysis-of-viral-diversity-for-vaccine-target-discovery
#20
Asif M Khan, Yongli Hu, Olivo Miotto, Natascha M Thevasagayam, Rashmi Sukumaran, Hadia Syahirah Abd Raman, Vladimir Brusic, Tin Wee Tan, J Thomas August
BACKGROUND: Viral vaccine target discovery requires understanding the diversity of both the virus and the human immune system. The readily available and rapidly growing pool of viral sequence data in the public domain enable the identification and characterization of immune targets relevant to adaptive immunity. A systematic bioinformatics approach is necessary to facilitate the analysis of such large datasets for selection of potential candidate vaccine targets. RESULTS: This work describes a computational methodology to achieve this analysis, with data of dengue, West Nile, hepatitis A, HIV-1, and influenza A viruses as examples...
December 21, 2017: BMC Medical Genomics
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