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https://www.readbyqxmd.com/read/29346775/brd4-promotes-dna-repair-and-mediates-the-formation-of-tmprss2-erg-gene-rearrangements-in-prostate-cancer
#1
Xiangyi Li, GuemHee Baek, Susmita G Ramanand, Adam Sharp, Yunpeng Gao, Wei Yuan, Jon Welti, Daniel N Rodrigues, David Dolling, Ines Figueiredo, Semini Sumanasuriya, Mateus Crespo, Adam Aslam, Rui Li, Yi Yin, Bipasha Mukherjee, Mohammed Kanchwala, Ashley M Hughes, Wendy S Halsey, Cheng-Ming Chiang, Chao Xing, Ganesh V Raj, Sandeep Burma, Johann de Bono, Ram S Mani
BRD4 belongs to the bromodomain and extraterminal (BET) family of chromatin reader proteins that bind acetylated histones and regulate gene expression. Pharmacological inhibition of BRD4 by BET inhibitors (BETi) has indicated antitumor activity against multiple cancer types. We show that BRD4 is essential for the repair of DNA double-strand breaks (DSBs) and mediates the formation of oncogenic gene rearrangements by engaging the non-homologous end joining (NHEJ) pathway. Mechanistically, genome-wide DNA breaks are associated with enhanced acetylation of histone H4, leading to BRD4 recruitment, and stable establishment of the DNA repair complex...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346720/nanoscale-control-of-molecular-self-assembly-induced-by-plasmonic-hot-electron-dynamics
#2
Sabrina Simoncelli, Yi Li, Emiliano Cortes, Stefan A Maier
Self-assembly processes allow designing and creating complex nanostructures using molecules as building blocks and surfaces as scaffolds. This autonomous driven construction is possible due to a complex thermodynamic balance of molecule-surface interactions. As such, nanoscale guidance and control over this process is hard to achieve. Here we use the highly localized light-to-chemical-energy conversion of plasmonic materials to spatially cleave Au-S bonds on pre-determined locations within a single nanoparticle, enabling a high degree of control over this archetypal system for molecular self-assembly...
January 18, 2018: ACS Nano
https://www.readbyqxmd.com/read/29346668/rad51-and-rtel1-compensate-telomere-loss-in-the-absence-of-telomerase
#3
Margaux Olivier, Cyril Charbonnel, Simon Amiard, Charles I White, Maria E Gallego
Replicative erosion of telomeres is naturally compensated by telomerase and studies in yeast and vertebrates show that homologous recombination can compensate for the absence of telomerase. We show that RAD51 protein, which catalyzes the key strand-invasion step of homologous recombination, is localized at Arabidopsis telomeres in absence of telomerase. Blocking the strand-transfer activity of the RAD51 in telomerase mutant plants results in a strikingly earlier onset of developmental defects, accompanied by increased numbers of end-to-end chromosome fusions...
January 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29346560/aggregation-and-travelling-wave-dynamics-in-a-two-population-model-of-cancer-cell-growth-and-invasion
#4
Vasiliki Bitsouni, Dumitru Trucu, Mark A J Chaplain, Raluca Eftimie
Cells adhere to each other and to the extracellular matrix (ECM) through protein molecules on the surface of the cells. The breaking and forming of adhesive bonds, a process critical in cancer invasion and metastasis, can be influenced by the mutation of cancer cells. In this paper, we develop a nonlocal mathematical model describing cancer cell invasion and movement as a result of integrin-controlled cell-cell adhesion and cell-matrix adhesion, for two cancer cell populations with different levels of mutation...
January 15, 2018: Mathematical Medicine and Biology: a Journal of the IMA
https://www.readbyqxmd.com/read/29346534/microbial-community-structure-of-sea-spray-aerosols-at-three-california-beaches
#5
Katherine Graham, Linsey C Marr, Lauren M Sassoubre, Alexandria B Boehm
We characterized the microbial communities in SSA, water, and sand of three beaches in central California (Cowell Beach, Baker Beach, and Lovers Point) by sequencing the V4 region of the 16S rRNA gene. Average concentrations of 16S rRNA genes in SSA ranged from 2.4 × 104 to 1.4 × 105 gene copies per m3 of air. A total of 9,781 distinct OTUs were identified in SSA and of these, 1,042 OTUs were found in SSA of all beaches. SSA microbial communities included marine taxa, as well as some associated with the terrestrial environment...
January 15, 2018: FEMS Microbiology Ecology
https://www.readbyqxmd.com/read/29346504/baum-improving-genome-assembly-by-adaptive-unique-mapping-and-local-overlap-layout-consensus-approach
#6
Anqi Wang, Zhanyu Wang, Zheng Li, Lei M Li
Motivation: It is highly desirable to assemble genomes of high continuity and consistency at low cost. The current bottleneck of draft genome continuity using the Second Generation Sequencing (SGS) reads is primarily caused by uncertainty among repetitive sequences. Even though the Single-Molecule Real-Time sequencing technology is very promising to overcome the uncertainty issue, its relatively high cost and error rate add burden on budget or computation. Many long-read assemblers take the overlap-layout-consensus (OLC) paradigm, which is less sensitive to sequencing errors, heterozygosity and variability of coverage...
January 15, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29346291/filaments-production-and-fused-deposition-modelling-of-abs-carbon-nanotubes-composites
#7
Sithiprumnea Dul, Luca Fambri, Alessandro Pegoretti
Composite acrylonitrile-butadiene-styrene (ABS)/carbon nanotubes (CNT) filaments at 1, 2, 4, 6 and 8 wt %, suitable for fused deposition modelling (FDM) were obtained by using a completely solvent-free process based on direct melt compounding and extrusion. The optimal CNT content in the filaments for FDM was found to be 6 wt %; for this composite, a detailed investigation of the thermal, mechanical and electrical properties was performed. Presence of CNT in ABS filaments and 3D-printed parts resulted in a significant enhancement of the tensile modulus and strength, accompanied by a reduction of the elongation at break...
January 18, 2018: Nanomaterials
https://www.readbyqxmd.com/read/29345925/catalytic-mechanism-of-the-ubiquitin-like-nedd8-transfer-in-ring-e3-e2-nedd8-target-complex-from-qm-mm-free-energy-simulations
#8
Yufei Yue, Yue Ma, Ping Qian, Hong Guo
Ubiquitin-like (UBL) protein modifications play a key role in regulating protein function. In contrast to the ubiquitin (UB) and small ubiquitin-like modifier (SUMO) which are ligated to a massive segment of proteome, the UBL NEDD8 is highly selective for modifying a lysine residue on closely related cullin proteins (CULs). In this study, the X-ray structure of a trapped E3-E2~NEDD8-target intermediate (RBX1-UBC1~NEDD8-CUL1-DCN1) is used to build computer models, and combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) and free energy (potential of mean force) simulations are performed to investigate the catalytic mechanism of the NEDD8 transfer from E2 to the lysine residue (K720) on the substrate in the complex...
January 18, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29345572/breaking-the-dna-damage-response-via-serine-threonine-kinase-inhibitors-to-improve-cancer-treatment
#9
Wioletta Rozpedek, Dariusz Pytel, Alicja Nowak-Zdunczyk, Dawid Lewko, Radoslaw Wojtczak, John Alan Diehl, Ireneusz Majsterek
Multiple, both endogenous and exogenous, sources may induce DNA damage and DNA replication stress. Cells have developed DNA damage response (DDR) signaling pathways to maintain genomic stability and effectively detect and repair DNA lesions. Serine/threonine kinases such as Ataxia-telangiectasia mutated (ATM) and Ataxia-telangiectasia and Rad3-Related (ATR) are the major regulators of DDR, since after sensing stalled DNA replication forks, DNA double- or single-strand breaks, may directly phosphorylate and activate their downstream targets, that play a key role in DNA repair, cell cycle arrest and apoptotic cell death...
January 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29345420/integration-of-gas-enhanced-oil-recovery-in-multiphase-fermentations-for-the-microbial-production-of-fuels-and-chemicals
#10
Susana Pedraza-de la Cuesta, Lore Keijzers, Luuk A M van der Wielen, Maria C Cuellar
In multiphase fermentations where the product forms a second liquid phase or where solvents are added for product extraction, turbulent conditions disperse the oil phase as droplets. Surface-active components (SACs) present in the fermentation broth can stabilize the product droplets thus forming an emulsion. Breaking this emulsion increases process complexity and consequently the production cost. In previous works, it has been proposed to promote demulsification of oil/supernatant emulsions in an off-line batch bubble column operating at low gas flow rate...
January 18, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29345402/association-of-long-term-glycaemic-control-on-tear-break-up-times-and-dry-eye-symptoms-in-chinese-patients-with-type-2-diabetes
#11
Andre Ma, Martin Sy Mak, Kendrick Co Shih, Claudia Ky Tsui, Rachel Ky Cheung, Sherman Haynam Lee, Hubert Leung, Joyce Ns Leung, Jason Th Leung, Marco Zhenji Van-Boswell, Michael Tl Wong, Alex Lap-Ki Ng, Chi-Ho Lee, Vishal Jhanji, Louis Tong
Importance Diabetes mellitus is known to be associated with dry eye syndrome (DES), but the effects of long term glycaemic control on tear film metrics and dry eye symptoms are not known in the Chinese population. BACKGROUND: To evaluate tear film stability and dry eye symptoms and their associations with systemic risk factors in Chinese patients with type 2 diabetes (T2DM) Design Cross-sectional study set at the Lo Fong Siu Po Eye Centre (Grantham Hospital), Hong Kong.
January 18, 2018: Clinical & Experimental Ophthalmology
https://www.readbyqxmd.com/read/29345386/quinoline-flanked-diketopyrrolopyrrole-copolymers-breaking-through-electron-mobility-over-6-cm2-v-1-s-1-in-flexible-thin-film-devices
#12
Zhenjie Ni, Huanli Dong, Hanlin Wang, Shang Ding, Ye Zou, Qiang Zhao, Yonggang Zhen, Feng Liu, Lang Jiang, Wenping Hu
Herein, the design and synthesis of novel π-extended quinoline-flanked diketopyrrolopyrrole (DPP) [abbreviated as QDPP] motifs and corresponding copolymers named PQDPP-T and PQDPP-2FT for high performing n-type organic field-effect transistors (OFETs) in flexible organic thin film devices are reported. Serving as DPP-flankers in backbones, quinoline is found to effectively tune copolymer optoelectric properties. Compared with TDPP and pyridine-flanked DPP (PyDPP) analogs, widened bandgaps and strengthened electron deficiency are achieved...
January 18, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29344644/inactivation-of-dna-pk-by-knockdown-dna-pkcs-or-nu7441-impairs-non-homologous-end-joining-of-radiation-induced-double-strand-break-repair
#13
Jun Dong, Yufeng Ren, Tian Zhang, Zhenyu Wang, Clifton C Ling, Gloria C Li, Fuqiu He, Chengtao Wang, Bixiu Wen
The DNA-dependent protein kinase (DNA-PK) complex plays a pivotal role in non-homologous end-joining (NHEJ) repair. We investigated the mechanism of NU7441, a highly selective DNA-PK inhibitor, in NHEJ-competent mouse embryonic fibroblast (MEF) cells and NHEJ-deficient cells and explored the feasibility of its application in radiosensitizing nasopharyngeal carcinoma (NPC) cells. We generated wild-type and DNA-PKcs-/- MEF cells. Clonogenic survival assays, flow cytometry, and immunoblotting were performed to study the effect of NU7441 on survival, cell cycle, and DNA repair...
January 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29344636/analysis-of-the-prolonged-infusion-of-dfp-10917-a-deoxycytidine-analog-as-a-therapeutic-strategy-for-the-treatment-of-human-tumor-xenografts-in-vivo
#14
Kenzo Iizuka, Chun Zhang, Kokoro Eshima, Cheng Jin, Kiyoshi Eshima, Masakazu Fukushima
2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofranocyl-cytosine (DFP-10917, CNDAC) is a 2'-deoxycytidine analog with antitumor activity against various tumor cells. However, a clinically available therapeutic regimen for this compound needs to be established and its functional mechanisms in relation to the dosing schedule need to be clarified. In this study, we evaluated the antitumor activity and toxicity of DFP-10917 by varying the dose and administration schedule in human solid tumor and leukemia xenografts in vivo...
January 16, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29344589/magnetism-tuning-strategies-for-graphene-oxide-based-on-magnetic-oligoacene-oxide-patches-model
#15
Yanjie Wen, Chia-Liang Yen, Linyin Yan, Hirohiko Kono, Sheng-Hsien Lin, Yong-Chien Ling
Graphene oxide (GO) has wide application potential owing to its 2D structure and diverse modification sites for various targeted uses. The introduction of magnetism into GO structures has further advanced the controllability of the application of GO materials. Herein, the concept of modular design and modeling was applied to tune the magnetism of GO. To obtain desirable magnetic properties, diradical-structured GO patches were formed by the introduction of two functional groups to break the Kekule structure of the benzene ring...
January 18, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29344267/break-breast-cancer-addiction-by-crispr-cas9-genome-editing
#16
REVIEW
Haitao Yang, MariaLynn Jaeger, Averi Walker, Daniel Wei, Katie Leiker, Tao Weitao
Breast cancer is the leading diagnosed cancer for women globally. Evolution of breast cancer in tumorigenesis, metastasis and treatment resistance appears to be driven by the aberrant gene expression and protein degradation encoded by the cancer genomes. The uncontrolled cancer growth relies on these cellular events, thus constituting the cancerous programs and rendering the addiction towards them. These programs are likely the potential anticancer biomarkers for Personalized Medicine of breast cancer. This review intends to delineate the impact of the CRSPR/Cas-mediated genome editing in identification and validation of these anticancer biomarkers...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29343889/first-two-bilateral-hand-transplantations-in-india-part-1-from-vision-to-reality
#17
Subramania Iyer, Mohit Sharma, P Kishore, Jimmy Mathew, Sundeep Vijayaraghavan, Janarthanan Ramu, Abhijeet Wakure, Raghuveer Reddy, S M Mali Chetan, Visakh Varma, Ashish Chaudhari, Swapnil Dhake, Akshay Omkumar, V G Prasad
Introduction: Vascularized composite tissue allotransplantation is a relatively new concept, which was unavailable in the Indian subcontinent till a bilateral hand transplant was carried out successfully in January 2015. Materials and Methods: The setting up of the transplant programme involved obtaining legal clearances, creating public awareness, harnessing the institutional facilities, drawing up protocols, assembling the surgical team, managing immunological issues, rehabilitation and preparing the ancillary services...
May 2017: Indian Journal of Plastic Surgery: Official Publication of the Association of Plastic Surgeons of India
https://www.readbyqxmd.com/read/29343882/can-productivity-and-profitability-be-enhanced-in-intensively-managed-cereal-systems-while-reducing-the-environmental-footprint-of-production-assessing-sustainable-intensification-options-in-the-breadbasket-of-india
#18
Virender Kumar, Hanuman S Jat, Parbodh C Sharma, Balwinder-Singh, Mahesh K Gathala, Ram K Malik, Baldev R Kamboj, Arvind K Yadav, Jagdish K Ladha, Anitha Raman, D K Sharma, Andrew McDonald
In the most productive area of the Indo-Gangetic Plains in Northwest India where high yields of rice and wheat are commonplace, a medium-term cropping system trial was conducted in Haryana State. The goal of the study was to identify integrated management options for further improving productivity and profitability while rationalizing resource use and reducing environmental externalities (i.e., "sustainable intensification", SI) by drawing on the principles of diversification, precision management, and conservation agriculture...
January 15, 2018: Agriculture, Ecosystems & Environment
https://www.readbyqxmd.com/read/29343774/an-improved-method-of-crafting-a-multi-electrode-spiral-cuff-for-the-selective
#19
Janez Rozman, Polona Pečlin, Samo Ribarič, Matjaž Godec, Jaka Burja
This article reviews an improved methodology and technology for crafting a multi-electrode spiral cuff for the selective activation of nerve fibres in particular superficial regions of a peripheral nerve. The analysis, structural and mechanical properties of the spot welds used for the interconnections between the stimulating electrodes and stainless-steel lead wires are presented. The cuff consisted of 33 platinum electrodes embedded within a self-curling 17-mm-long silicone spiral sheet with a nominal internal diameter of 2...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343617/methods-to-determine-the-silicone-oil-layer-thickness-in-sprayed-on-siliconized-syringes
#20
Viviane Loosli, Oliver Germershaus, Henrik Steinberg, Sascha Dreher, Ulla Grauschopf, Stefanie Funke
The silicone lubricant layer in prefilled syringes (PFS) has been investigated with regards to siliconization process performance, PFS functionality and drug product attributes such as subvisible particle levels in several studies in the past. However, adequate methods to characterize the silicone oil layer thickness and -distribution are limited and systematic evaluation is missing. In this study, white light interferometry (WLI) was evaluated to close this gap in method understanding. WLI demonstrated a good accuracy of 93-99 % for MgF2 coated, curved standards covering a thickness range of 115-473 nm...
January 17, 2018: PDA Journal of Pharmaceutical Science and Technology
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