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https://www.readbyqxmd.com/read/28933784/inhibition-of-the-deubiquitinase-usp5-leads-to-c-maf-protein-degradation-and-myeloma-cell-apoptosis
#1
Siyu Wang, Jiaxiang Juan, Zubin Zhang, Yanyun Du, Yujia Xu, Jiefei Tong, Biyin Cao, Michael F Moran, Yuanying Zeng, Xinliang Mao
The deubiquitinase USP5 stabilizes c-Maf, a key transcription factor in multiple myeloma (MM), but the mechanisms and significance are unclear. In the present study, USP5 was found to interact with c-Maf and prevented it from degradation by decreasing its polyubiquitination level. Specifically, the 308th and 347th lysine residues in c-Maf were critical for USP5-mediated deubiquitination and stability. There are five key domains in the USP5 protein and subsequent studies revealed that the cryptic ZnF domain and the C-box domain interacted with c-Maf but the UBA1/UBA2 domain partly increased its stability...
September 21, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28931032/a-microtubule-based-minimal-model-for-spontaneous-and-persistent-spherical-cell-polarity
#2
Panayiotis Foteinopoulos, Bela M Mulder
We propose a minimal model for the spontaneous and persistent generation of polarity in a spherical cell based on dynamic microtubules and a single mobile molecular component. This component, dubbed the polarity factor, binds to microtubules nucleated from a centrosome located in the center of the cell, is subsequently delivered to the cell membrane, where it diffuses until it unbinds. The only feedback mechanism we impose is that the residence time of the microtubules at the membrane increases with the local density of the polarity factor...
2017: PloS One
https://www.readbyqxmd.com/read/28930603/centchroman-a-safe-reversible-postcoital-contraceptive-with-curative-and-prophylactic-activity-in-many-disorders
#3
Ved P Kamboj, Suprabhat Ray, Nitya Anand
Centchroman (INN: Ormeloxifene), a reversible post-coital/weekly oral contraceptive (half-life of about 168 hours), designed and developed at CDRI, Lucknow is the only non-steroidal oral contraceptive in clinical use in the world today. Synthesized in 1967 and completing pre-clinical and clinical studies in 1989, this drug was approved for marketing in 1991, social marketing in 1995 and NFPW in April 2016. It acts by preventing implantation of blastocyst in endometrium. It is the only contraceptive which neither suppresses ovulation nor interferes with the hypothalamic-pituitary-ovarian axis...
January 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/28928405/nanopore-extended-field-effect-transistor-for-selective-single-molecule-biosensing
#4
Ren Ren, Yanjun Zhang, Binoy Paulose Nadappuram, Bernice Akpinar, David Klenerman, Aleksandar P Ivanov, Joshua B Edel, Yuri Korchev
There has been a significant drive to deliver nanotechnological solutions to biosensing, yet there remains an unmet need in the development of biosensors that are affordable, integrated, fast, capable of multiplexed detection, and offer high selectivity for trace analyte detection in biological fluids. Herein, some of these challenges are addressed by designing a new class of nanoscale sensors dubbed nanopore extended field-effect transistor (nexFET) that combine the advantages of nanopore single-molecule sensing, field-effect transistors, and recognition chemistry...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28923280/the-roles-of-ubiquitin-modifying-enzymes-in-neoplastic-disease
#5
REVIEW
Nishi Kumari, Patrick William Jaynes, Azad Saei, Prasanna Vasudevan Iyengar, John Lalith Charles Richard, Pieter Johan Adam Eichhorn
The initial experiments performed by Rose, Hershko, and Ciechanover describing the identification of a specific degradation signal in short-lived proteins paved the way to the discovery of the ubiquitin mediated regulation of numerous physiological functions required for cellular homeostasis. Since their discovery of ubiquitin and ubiquitin function over 30years ago it has become wholly apparent that ubiquitin and their respective ubiquitin modifying enzymes are key players in tumorigenesis. The human genome encodes approximately 600 putative E3 ligases and 80 deubiquitinating enzymes and in the majority of cases these enzymes exhibit specificity in sustaining either pro-tumorigenic or tumour repressive responses...
September 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28919787/computational-tool-for-optimizing-the-essential-oils-utilization-in-inhibiting-the-bacterial-growth
#6
Noha E El-Attar, Wael A Awad
Day after day, the importance of relying on nature in many fields such as food, medical, pharmaceutical industries, and others is increasing. Essential oils (EOs) are considered as one of the most significant natural products for use as antimicrobials, antioxidants, antitumorals, and anti-inflammatories. Optimizing the usage of EOs is a big challenge faced by the scientific researchers because of the complexity of chemical composition of every EO, in addition to the difficulties to determine the best in inhibiting the bacterial activity...
2017: Advances and Applications in Bioinformatics and Chemistry: AABC
https://www.readbyqxmd.com/read/28919039/a-linear-diubiquitin-based-probe-for-efficient-and-selective-detection-of-the-deubiquitinating-enzyme-otulin
#7
Aurelia Weber, Paul R Elliott, Adan Pinto-Fernandez, Sarah Bonham, Benedikt M Kessler, David Komander, Farid El Oualid, Daniel Krappmann
The methionine 1 (M1)-specific deubiquitinase (DUB) OTULIN acts as a negative regulator of nuclear factor κB signaling and immune homeostasis. By replacing Gly76 in distal ubiquitin (Ub) by dehydroalanine we designed the diubiquitin (diUb) activity-based probe UbG76Dha-Ub (OTULIN activity-based probe [ABP]) that couples to the catalytic site of OTULIN and thereby captures OTULIN in its active conformation. The OTULIN ABP displays high selectivity for OTULIN and does not label other M1-cleaving DUBs, including CYLD...
August 28, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28918526/coupling-population-dynamics-with-earth-system-models-the-popem-model
#8
Andrés Navarro, Raúl Moreno, Alfonso Jiménez-Alcázar, Francisco J Tapiador
Precise modeling of CO2 emissions is important for environmental research. This paper presents a new model of human population dynamics that can be embedded into ESMs (Earth System Models) to improve climate modeling. Through a system dynamics approach, we develop a cohort-component model that successfully simulates historical population dynamics with fine spatial resolution (about 1°×1°). The population projections are used to improve the estimates of CO2 emissions, thus transcending the bulk approach of existing models and allowing more realistic non-linear effects to feature in the simulations...
September 16, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28900014/regulation-of-the-cell-cycle-and-centrosome-biology-by-deubiquitylases
#9
REVIEW
Sarah Darling, Andrew B Fielding, Dorota Sabat-Pośpiech, Ian A Prior, Judy M Coulson
Post-translational modification of proteins by ubiquitylation is increasingly recognised as a highly complex code that contributes to the regulation of diverse cellular processes. In humans, a family of almost 100 deubiquitylase enzymes (DUBs) are assigned to six subfamilies and many of these DUBs can remove ubiquitin from proteins to reverse signals. Roles for individual DUBs have been delineated within specific cellular processes, including many that are dysregulated in diseases, particularly cancer. As potentially druggable enzymes, disease-associated DUBs are of increasing interest as pharmaceutical targets...
September 12, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28891575/sheared-edible-oils-studied-using-dissipative-particle-dynamics-and-ultra-small-angle-x-ray-scattering-tagwood-orientation-aggregation-and-disaggregation
#10
D A Pink, B Townsend, F Peyronel, E D Co, A G Marangoni
Previous work on the computer simulation of edible fats and oils showed that triglyceride crystalline nanoplatelets (CNPs) aggregated into cylindrical structures dubbed "TAGwoods". This was experimentally verified using Ultra Small Angle X-ray Scattering experiments. In this paper, the aggregation of these TAGwoods was studied using the fluid simulation technique, Dissipative Particle Dynamics. The intent was to predict the TAGwood aggregation structures which arise via the application of a series of shear rates, [small gamma, Greek, dot above]...
September 11, 2017: Food & Function
https://www.readbyqxmd.com/read/28887412/enzymatic-modules-of-the-saga-chromatin-modifying-complex-play-distinct-roles-in-drosophila-gene-expression-and-development
#11
Xuanying Li, Christopher W Seidel, Leanne T Szerszen, Jeffrey J Lange, Jerry L Workman, Susan M Abmayr
The Spt-Ada-Gcn5-acetyltransferase (SAGA) chromatin-modifying complex is a transcriptional coactivator that contains four different modules of subunits. The intact SAGA complex has been well characterized for its function in transcription regulation and development. However, little is known about the roles of individual modules within SAGA and whether they have any SAGA-independent functions. Here we demonstrate that the two enzymatic modules of Drosophila SAGA are differently required in oogenesis. Loss of the histone acetyltransferase (HAT) activity blocks oogenesis, while loss of the H2B deubiquitinase (DUB) activity does not...
September 8, 2017: Genes & Development
https://www.readbyqxmd.com/read/28887042/hinokitiol-copper-complex-inhibits-proteasomal-deubiquitination-and-induces-paraptosis-like-cell-death-in-human-cancer-cells
#12
Xin Chen, Xiaolan Zhang, Jinghong Chen, Qianqian Yang, Li Yang, Dacai Xu, Peiquan Zhang, Xuejun Wang, Jinbao Liu
The ubiquitin-proteasome system (UPS) plays a central role in the regulation of proteins that control cell growth and apoptosis and has therefore become an important target for anticancer therapy. Several constitutive subunits of the 19S proteasome display deubiquitinase (DUB) activity, suggesting that ubiquitin modification of proteins is dynamically regulated. Our study and others have shown that metal complexes, such as copper complexes, can induce cancer cell apoptosis through inhibiting 19S proteasome-associated DUBs and/or 20S proteasome activity...
September 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28885059/viral-deubiquitinases-role-in-evasion-of-anti-viral-innate-immunity
#13
Puja Kumari, Himanshu Kumar
Host anti-viral innate-immune signalling pathways are regulated by a variety of post-translation modifications including ubiquitination, which is critical to regulate various signalling pathways for synthesis of anti-viral molecules. A homeostasis of host immune responses, induced due to viral infection and further ubiquitination, is maintained by the action of deubiquitinases (DUB). Infecting viruses utilize the process of deubiquitination for tricking host immune system wherein viral DUBs compete with host DUBs for inhibition of innate-immune anti-viral signalling pathways, which instead of maintaining an immune homeostasis bring about virus-mediated pathogenesis...
September 8, 2017: Critical Reviews in Microbiology
https://www.readbyqxmd.com/read/28883492/on-the-role-of-initial-velocities-in-pair-dispersion-in-a-microfluidic-chaotic-flow
#14
Eldad Afik, Victor Steinberg
Chaotic flows drive mixing and efficient transport in fluids, as well as the associated beautiful complex patterns familiar to us from our every day life experience. Generating such flows at small scales where viscosity takes over is highly challenging from both the theoretical and engineering perspectives. This can be overcome by introducing a minuscule amount of long flexible polymers, resulting in a chaotic flow dubbed 'elastic turbulence'. At the basis of the theoretical frameworks for its study lie the assumptions of a spatially smooth and random-in-time velocity field...
September 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28881649/identification-of-deubiquitinase-targets-of-isothiocyanates-using-silac-assisted-quantitative-mass-spectrometry
#15
Ann P Lawson, Daniel W Bak, D Alexander Shannon, Marcus J C Long, Tushara Vijaykumar, Runhan Yu, Farid El Oualid, Eranthie Weerapana, Lizbeth Hedstrom
Cruciferous vegetables such as broccoli and kale have well documented chemopreventative and anticancer effects that are attributed to the presence of isothiocyanates (ITCs). ITCs modulate the levels of many oncogenic proteins, but the molecular mechanisms of ITC action are not understood. We previously reported that phenethyl isothiocyanate (PEITC) inhibits two deubiquitinases (DUBs), USP9x and UCH37. DUBs regulate many cellular processes and DUB dysregulation is linked to the pathogenesis of human diseases including cancer, neurodegeneration, and inflammation...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878255/adaptive-aggregation-by-spider-mites-under-predation-risk
#16
Lena Dittmann, Peter Schausberger
Grouping together is a commonly observed anti-predator strategy. Possible anti-predator benefits of aggregation include the encounter/avoidance effect for visually hunting predators and the dilution effect, together dubbed attack abatement. Possible costs opposing the dilution effect are easier detection of aggregated than scattered individuals. The benefits of attack abatement, and opposing costs after group detection, are poorly understood for chemosensory predator-prey interactions. We tackled this issue by assessing the aggregation behavior of spider mites Tetranychus urticae under predation risk emanating from predatory mites Phytoseiulus persimilis...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28874458/the-deubiquitinating-enzyme-usp48-stabilizes-traf2-and-reduces-e-cadherin-mediated-adherens-junctions
#17
Shuang Li, Dan Wang, Jing Zhao, Nathaniel M Weathington, Dong Shang, Yutong Zhao
The tumor necrosis factor receptor-associated factor 2 (TRAF2) is a second messenger adaptor protein that plays an essential role in propagating TNF-α-mediated signaling pathways. Modulation of TRAF2 activity by ubiquitination is well studied; however, the deubiquitinating enzyme (DUB), which regulates TRAF2 stability, has not been identified. Here we reveal USP48 as the first identified DUB to deubiquitinate and stabilize TRAF2 in epithelial cells. Down-regulation of USP48 increases K48-linked polyubiquitination of TRAF2 and reduces TRAF2 protein levels...
September 5, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28871056/position-paper-the-science-of-deep-specification
#18
Andrew W Appel, Lennart Beringer, Adam Chlipala, Benjamin C Pierce, Zhong Shao, Stephanie Weirich, Steve Zdancewic
We introduce our efforts within the project 'The science of deep specification' to work out the key formal underpinnings of industrial-scale formal specifications of software and hardware components, anticipating a world where large verified systems are routinely built out of smaller verified components that are also used by many other projects. We identify an important class of specification that has already been used in a few experiments that connect strong component-correctness theorems across the work of different teams...
October 13, 2017: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
https://www.readbyqxmd.com/read/28871052/program-synthesis-challenges-and-opportunities
#19
REVIEW
Cristina David, Daniel Kroening
Program synthesis is the mechanized construction of software, dubbed 'self-writing code'. Synthesis tools relieve the programmer from thinking about how the problem is to be solved; instead, the programmer only provides a description of what is to be achieved. Given a specification of what the program should do, the synthesizer generates an implementation that provably satisfies this specification. From a logical point of view, a program synthesizer is a solver for second-order existential logic. Owing to the expressiveness of second-order logic, program synthesis has an extremely broad range of applications...
October 13, 2017: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
https://www.readbyqxmd.com/read/28861086/immunobiography-and-the-heterogeneity-of-immune-responses-in-the-elderly-a-focus-on-inflammaging-and-trained-immunity
#20
REVIEW
Claudio Franceschi, Stefano Salvioli, Paolo Garagnani, Magda de Eguileor, Daniela Monti, Miriam Capri
Owing to its memory and plasticity, the immune system (IS) is capable of recording all the immunological experiences and stimuli it was exposed to. The combination of type, dose, intensity, and temporal sequence of antigenic stimuli that each individual is exposed to has been named "immunobiography." This immunological history induces a lifelong continuous adaptation of the IS, which is responsible for the capability to mount strong, weak or no response to specific antigens, thus determining the large heterogeneity of immunological responses...
2017: Frontiers in Immunology
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