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https://www.readbyqxmd.com/read/28912886/the-ph-triggered-triblock-nanocarrier-enabled-highly-efficient-sirna-delivery-for-cancer-therapy
#1
Lili Du, Junhui Zhou, Lingwei Meng, Xiaoxia Wang, Changrong Wang, Yuanyu Huang, Shuquan Zheng, Liandong Deng, Huiqing Cao, Zicai Liang, Anjie Dong, Qiang Cheng
Small interfering RNA (siRNA) therapies have been hampered by lack of delivery systems in the past decades. Nowadays, a few promising vehicles for siRNA delivery have been developed and it is gradually revealed that enhancing siRNA release from endosomes into cytosol is a very important factor for successful delivery. Here, we designed a novel pH-sensitive nanomicelle, PEG-PTTMA-P(GMA-S-DMA) (PTMS), for siRNA delivery. Owing to rapid hydrolysis in acidic environment, PTMS NPs underwent hydrophobic-to-hydrophilic transition in endosomes that enabled combination of proton sponge effect and raised osmotic pressure in endosomes, resulting in vigorous release of siRNAs from endosomes into cytosol...
2017: Theranostics
https://www.readbyqxmd.com/read/28910574/o-glcnacylation-of-boundary-element-associated-factor-beaf-32-in-drosophila-melanogaster-correlates-with-active-histone-marks-at-the-promoters-of-its-target-genes
#2
Debaditya De, Satish Kallappagoudar, Jae-Min Lim, Rashmi U Pathak, Rakesh K Mishra
Boundary Element-Associated Factor 32 (BEAF 32) is a sequence specific DNA binding protein involved in functioning of chromatin domain boundaries in Drosophila. Several studies also show it to be involved in transcriptional regulation of a large number of genes, many of which are annotated to have cell cycle, development and differentiation related function. Since post-translational modifications (PTMs) of proteins add to their functional capacity, we investigated the PTMs on BEAF 32. The protein is known to be phosphorylated and O-GlcNAcylated...
September 14, 2017: Nucleus
https://www.readbyqxmd.com/read/28904641/histone-code-and-long-non-coding-rnas-lncrnas-aberrations-in-lung-cancer-implications-in-the-therapy-response
#3
REVIEW
Abril Marcela Herrera-Solorio, Leonel Armas-López, Oscar Arrieta, Joaquín Zúñiga, Patricia Piña-Sánchez, Federico Ávila-Moreno
Respiratory diseases hold several genome, epigenome, and transcriptional aberrations as a cause of the accumulated damage promoted by, among others, environmental risk factors. Such aberrations can also come about as an adaptive response when faced with therapeutic oncological drugs. In epigenetic terms, aberrations in DNA methylation patterns, histone code marks balance, and/or chromatin-remodeling complexes recruitment, among Polycomb Repressive Complex-2 (PRC2) versus Trithorax (TRX) Activator Complex, have been proposed to be affected by several previously characterized functional long non-coding RNAs (lncRNAs)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28902398/using-proteomescout-a-resource-of-post-translational-modifications-their-experiments-and-the-proteins-that-they-annotate
#4
Arshag D Mooradian, Jason M Held, Kristen M Naegle
Post-translational modifications (PTMs) of protein amino acids are ubiquitous and important to protein function, localization, degradation, and more. In recent years, there has been an explosion in the discovery of PTMs as a result of improvements in PTM measurement techniques, including quantitative measurements of PTMs across multiple conditions. ProteomeScout is a repository for such discovery and quantitative experiments and provides tools for visualizing PTMs within proteins, including where they are relative to other PTMS, domains, mutations, and structure...
September 13, 2017: Current Protocols in Bioinformatics
https://www.readbyqxmd.com/read/28901832/chemical-biology-approaches-for-studying-posttranslational-modifications
#5
Aerin Yang, Kyukwang Cho, Hee-Sung Park
Posttranslational modification (PTM) is a key mechanism for regulating diverse protein functions, and thus critically affects many essential biological processes. Critical for systematic study of the effects of PTMs is the ability to obtain recombinant proteins with defined and homogenous modifications. To this end, various synthetic and chemical biology approaches, including genetic code expansion and protein chemical modification methods, have been developed. These methods have proven effective for generating site-specific authentic modifications or structural mimics, and have demonstrated their value for in vitro and in vivo functional studies of diverse PTMs...
September 13, 2017: RNA Biology
https://www.readbyqxmd.com/read/28895719/radical-sam-enzymes-involved-in-ripp-biosynthesis
#6
Nilkamal Mahanta, Graham A Hudson, Douglas A Mitchell
Ribosomally synthesized and post-translationally modified peptides (RiPPs) display a diverse range of structures and continue to expand as a natural product class. Accordingly, RiPPs exhibit a wide array of bioactivities, such as broad and narrow spectrum growth suppressors, antidiabetics, as well as antinociception and anticancer agents. Owing to these properties, and the complex repertoire of post-translational modifications (PTMs) that give rise to these molecules, RiPP biosynthesis has been intensely studied...
September 12, 2017: Biochemistry
https://www.readbyqxmd.com/read/28894508/protein-posttranslational-modifications-roles-in-aging-and-age-related-disease
#7
REVIEW
Ana L Santos, Ariel B Lindner
Aging is characterized by the progressive decline of biochemical and physiological function in an individual. Consequently, aging is a major risk factor for diseases like cancer, obesity, and type 2 diabetes. The cellular and molecular mechanisms of aging are not well understood, nor is the relationship between aging and the onset of diseases. One of the hallmarks of aging is a decrease in cellular proteome homeostasis, allowing abnormal proteins to accumulate. This phenomenon is observed in both eukaryotes and prokaryotes, suggesting that the underlying molecular processes are evolutionarily conserved...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28894190/novel-detection-of-post-translational-modifications-in-human-monocyte-derived-dendritic-cells-after-chronic-alcohol-exposure-role-of-inflammation-regulator-h4k12ac
#8
Tiyash Parira, Gloria Figueroa, Alejandra Laverde, Gianna Casteleiro, Mario E Gomez Hernandez, Francisco Fernandez-Lima, Marisela Agudelo
Previous reports on epigenetic mechanisms involved in alcohol abuse have focus on hepatic and neuronal regions, leaving the immune system and specifically monocyte-derived dendritic cells (MDDCs) understudied. Our lab has previously shown histone deacetylases are modulated in cells derived from alcohol users and after in vitro acute alcohol treatment of human MDDCs. In the current study, we developed a novel screening tool using matrix assisted laser desorption ionization-fourier transform-ion cyclotron resonance mass spectrometry (MALDI-FT-ICR MS) and single cell imaging flow cytometry to detect post-translational modifications (PTMs) in human MDDCs due to chronic alcohol exposure...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28887379/a-comprehensive-open-source-platform-for-mass-spectrometry-based-glycoproteomics-data-analysis
#9
Gang Liu, Kai Cheng, Chi Y Lo, Jun Li, Jun Qu, Sriram Neelamegham
Glycosylation is among the most abundant and diverse protein post-translational modifications (PTMs) identified to date. The structural analysis of this PTM is challenging due to the diverse monosaccharides which are not conserved among organisms, the branched nature of glycans, their isomeric structures, and heterogeneity in the glycan distribution at a given site. Glycoproteomics experiments have adopted the traditional high-throughput LC-MS(n) proteomics workflow to analyze site-specific glycosylation. However, comprehensive computational platforms for data analyses are scarce...
September 8, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28877993/stabilization-of-dynamic-microtubules-by-mdia1-drives-tau-dependent-a%C3%AE-1-42-synaptotoxicity
#10
Xiaoyi Qu, Feng Ning Yuan, Carlo Corona, Silvia Pasini, Maria Elena Pero, Gregg G Gundersen, Michael L Shelanski, Francesca Bartolini
Oligomeric Amyloid β1-42 (Aβ) plays a crucial synaptotoxic role in Alzheimer's disease, and hyperphosphorylated tau facilitates Aβ toxicity. The link between Aβ and tau, however, remains controversial. In this study, we find that in hippocampal neurons, Aβ acutely induces tubulin posttranslational modifications (PTMs) and stabilizes dynamic microtubules (MTs) by reducing their catastrophe frequency. Silencing or acute inhibition of the formin mDia1 suppresses these activities and corrects the synaptotoxicity and deficits of axonal transport induced by Aβ...
September 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28867585/protein-phosphorylation-and-its-role-in-the-regulation-of-annexin-a2-function
#11
REVIEW
Ann Kari Grindheim, Jaakko Saraste, Anni Vedeler
BACKGROUND: Annexin A2 (AnxA2) is a multifunctional protein involved in endocytosis, exocytosis, membrane domain organisation, actin remodelling, signal transduction, protein assembly, transcription and mRNA transport, as well as DNA replication and repair. SCOPE OF REVIEW: The current knowledge of the role of phosphorylation in the functional regulation of AnxA2 is reviewed. To provide a more comprehensive treatment of this topic, we also address in depth the phosphorylation process in general and discuss its possible conformational effects...
September 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28867216/the-effect-of-phosphorylation-on-the-salt-tolerance-related-functions-of-the-soybean-protein-pm18-a-member-of-the-group-3-lea-protein-family
#12
Yun Liu, Meiyan Yang, Hua Cheng, Nan Sun, Simu Liu, Shuiming Li, Yong Wang, Yizhi Zheng, Vladimir N Uversky
Enzymatically driven post-translated modifications (PTMs) usually happen within the intrinsically disordered regions of a target protein and can modulate variety of protein functions. Late embryogenesis abundant (LEA) proteins are a family of the plant intrinsically disordered proteins (IDPs). Despite their important roles in plant stress response, there is currently limited knowledge on the presence and functional and structural effects of phosphorylation on LEA proteins. In this study, we identified three phosphorylation sites (Ser(90), Tyr(136), and Thr(266)) in the soybean PM18 protein that belongs to the group-3 LEA proteins...
September 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28857561/identification-of-missing-proteins-in-the-phosphoproteome-of-kidney-cancer
#13
Xuehui Peng, Feng Xu, Shu Liu, Suzhen Li, Qingbo Huang, Lei Chang, Lei Wang, Xin Ma, Fuchu He, Ping Xu
Identifying missing proteins (MPs) has been one of the critical missions of the Chromosome-Centric Human Proteome Project (C-HPP). Since 2012, over 30 research teams from 17 countries have been trying to search adequate and accurate evidence of MPs through various biochemical strategies. MPs mainly fall into the following classes: (1) low-molecular-weight (LMW) proteins, (2) membrane proteins, (3) proteins that contained various post-translational modifications (PTMs), (4) nucleic acid-associated proteins, (5) low abundance, and (6) unexpressed genes...
September 12, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28856379/vertebrate-gaf-thpok-emerging-functions-in-chromatin-architecture-and-transcriptional-regulation
#14
REVIEW
Avinash Srivastava, Amitha Sampath Kumar, Rakesh K Mishra
GAGA factor of Drosophila melanogaster (DmGAF) is a multifaceted transcription factor with diverse roles in chromatin regulation. Recently, ThPOK/c-Krox was identified as its vertebrate homologue (vGAF), which has a basic domain structure similar to DmGAF and is decorated with a number of post-translationally modified residues. In vertebrate genomes, vGAF associates with purine-rich GAGA sequences and performs diverse chromatin-mediated functions, viz., gene activation, repression and enhancer blocking. Expansion of regulatory chromatin proteins with the acquisition of PTMs appears to be the general trend that facilitated the evolution of complexity in vertebrates...
August 30, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28855397/inflammatory-monocytes-expressing-tissue-factor-drive-siv-and-hiv-coagulopathy
#15
Melissa E Schechter, Bruno B Andrade, Tianyu He, George Haret Richter, Kevin W Tosh, Benjamin B Policicchio, Amrit Singh, Kevin D Raehtz, Virginia Sheikh, Dongying Ma, Egidio Brocca-Cofano, Cristian Apetrei, Russel Tracy, Ruy M Ribeiro, Alan Sher, Ivo M B Francischetti, Ivona Pandrea, Irini Sereti
In HIV infection, persistent inflammation despite effective antiretroviral therapy is linked to increased risk of noninfectious chronic complications such as cardiovascular and thromboembolic disease. A better understanding of inflammatory and coagulation pathways in HIV infection is needed to optimize clinical care. Markers of monocyte activation and coagulation independently predict morbidity and mortality associated with non-AIDS events. We identified a specific subset of monocytes that express tissue factor (TF), persist after virological suppression, and trigger the coagulation cascade by activating factor X...
August 30, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28854392/transport-of-pharmaceuticals-and-their-metabolites-between-water-and-sediments-as-a-further-potential-exposure-for-aquatic-organisms
#16
Olga Koba, Katerina Grabicova, Daniel Cerveny, Jan Turek, Jitka Kolarova, Tomas Randak, Vladimir Zlabek, Roman Grabic
Although pharmaceuticals are frequently studied contaminants, their fate in the environment is still not completely clear. During a one year study, a complex approach including water, sediment and fish sampling was used to describe the behaviour of pharmaceuticals and their metabolites (PTMs) in the environment. Eighteen pharmaceuticals and seven of their metabolites were determined in a pond used for the tertiary treatment of wastewater effluent. A liquid chromatography-tandem mass spectrometry method was applied to determine the PTMs concentrations in all matrices...
August 23, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28853897/progress-on-the-hupo-draft-human-proteome-2017-metrics-of-the-human-proteome-project
#17
Gilbert S Omenn, Lydie Lane, Emma K Lundberg, Christopher M Overall, Eric W Deutsch
The Human Proteome Organization (HUPO) Human Proteome Project (HPP) continues to make progress on its two overall goals: (1) completing the protein parts list, with an annual update of the HUPO draft human proteome, and (2) making proteomics an integrated complement to genomics and transcriptomics throughout biomedical and life sciences research. neXtProt version 2017-01-23 has 17,008 confident protein identifications (Protein Existence [PE] level 1) that are compliant with the HPP Guidelines v2.1 (https://hupo...
August 30, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28845672/proteome-wide-analysis-of-n-glycosylation-stoichiometry-using-swath-technology
#18
Xiangyun Yang, Wang Zhiyuan, Lin Guo, Zheng-Jiang Zhu, Yaoyang Zhang
N-glycosylation is a crucial post-translational modification (PTM) and plays essential roles in biological processes. Several methods have been developed for the relative quantification of N-glycosylation at the proteome scale. However, the proportion of N-glycosylated forms in a total protein population, or the "N-glycosylation stoichiometry," varies greatly among proteins or cellular states and is frequently missing due to the lack of robust technologies. In the present study, we developed a data-independent acquisition (DIA) based strategy that enabled the in-depth measurement of N-glycosylation stoichiometry...
August 28, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28840552/the-emerging-role-of-proteomics-in-precision-medicine-applications-in-neurodegenerative-diseases-and-neurotrauma
#19
Rana Alaaeddine, Mira Fayad, Eliana Nehme, Hisham F Bahmad, Firas Kobeissy
Inter-individual variability in response to pharmacotherapy has provoked a higher demand to personalize medical decisions. As the field of pharmacogenomics has served to translate personalized medicine from concept to practice, the contribution of the "omics" disciplines to the era of precision medicine seems to be vital in improving therapeutic outcomes. Although we have observed significant advances in the field of genomics towards personalized medicine , the field of proteomics-with all its capabilities- is still in its infancy towards the area of personalized precision medicine...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28832116/chemically-sumoylated-histone-h4-stimulates-intranucleosomal-demethylation-by-the-lsd1-corest-complex
#20
Abhinav Dhall, Caroline E Weller, Aurea Chu, Patrick M M Shelton, Champak Chatterjee
Lysine-specific demethylase 1 (LSD1) downregulates eukaryotic gene activity by demethylating mono- and dimethylated Lys4 in histone H3. Elucidating the biochemical crosstalk of LSD1 with histone post-translational modifications (PTMs) is essential for developing LSD1-targeted therapeutics in human cancers. We interrogated the small ubiquitin-like modifier (SUMO)-driven regulation of LSD1 activity with semisynthetic nucleosomes containing site-specifically methylated and sumoylated histones. We discovered that nucleosomes containing sumoylated histone H4 (suH4), a modification associated with gene repression, stimulate LSD1 activity by a mechanism dependent upon the SUMO-interaction motif in CoREST...
August 30, 2017: ACS Chemical Biology
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