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https://www.readbyqxmd.com/read/29778016/multiscale-reconstruction-of-a-synthetic-biomimetic-micro-niche-for-enhancing-and-monitoring-the-differentiation-of-stem-cells
#1
Rui Li, Jinming Li, Jianbin Xu, Dexter Siu Hong Wong, Xiaoyu Chen, Weihao Yuan, Liming Bian
Stem cells reside in a three-dimensional (3D) niche microenvironment, which provides specific cues, including cell-matrix interactions and soluble factors, that are essential to the differentiation of stem cells in vivo. Herein we demonstrate a general approach to the synthetic reconstruction of 3D biomimetic niche environment of stem cells by the multiscale combination of macroscopic porous hydrogels and a nanoscale upconversion nanoparticles (UCNP)-based nanocomplex. The porous biopolymeric hydrogels emulate the spongy bone microstructure and provide 3D environment conducive to the differentiation of seeded stem cells...
May 4, 2018: Biomaterials
https://www.readbyqxmd.com/read/29777795/sirna-in-ovarian-cancer-delivery-strategies-and-targets-for-therapy
#2
REVIEW
Dirk van den Brand, Vicky Mertens, Leon F A G Massuger, Roland Brock
Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, and the sixth leading cause of cancer related death in women overall. Despite improved surgical techniques and advances in chemotherapy, mortality hardly decreased over the last twenty years. The major problem is that (micro)metastases persevere in the abdominal cavity, causing incurable tumor recurrence. Therefore, there is an imminent need for new therapeutic strategies. Oligonucleotide (ON) based therapies such as RNA interference (RNAi) provide the possibility to specifically address disease-related pathways...
May 16, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29777615/tools-for-work-up-and-pre-purification-of-tritium-labelled-small-molecules
#3
Dieter Muri, Martin R Edelmann
This practitioner protocol describes the use and application of different types of solid phase extractions and metal scavengers for small scale reactions, particularly in the context of purifying tritiated molecules from heavily contaminated reaction mixtures. Polymer-bound strong cation exchangers are especially suitable for separating basic compounds from neutral or acidic molecules and have been widely applied in the work-up of Iridium-based hydrogen isotope exchange reactions. Polymer-bound strong anion exchangers can help to separate acidic compounds from their neutral or basic counterparts or to easily convert a TFA or formate salt to its free base after HPLC purification...
May 19, 2018: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29777374/the-tenascin-c-derived-peptide-vswrapta-promotes-neuronal-branching-via-transcellular-activation-of-the-focal-adhesion-kinase-fak-and-the-erk1-2-signaling-pathway-in-vitro
#4
Marvin Jarocki, Omar Sallouh, Ralf Weberskirch, Andreas Faissner
The central nervous system (CNS) of mammals has a limited regeneration capacity after traumatic events, which causes chronic functional disability. The development of biomaterials aims at providing support for the regeneration process. One strategy integrates peptides that mimic functional domains of extracellular matrix (ECM) or cell adhesion molecules with synthetic polymers designed to present growth-supporting cues to the neuronal microenvironment. Thus, small peptide sequences originating from molecules of the ECM may serve as promising bio-additives, acting as artificial matricryptins to gear cellular processes...
May 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29777301/role-of-the-nrp-1-mediated-vegfr2-independent-pathway-on-radiation-sensitivity-of-non-small-cell-lung-cancer-cells
#5
Chenxi Hu, Panrong Zhu, Youyou Xia, Kaiyuan Hui, Mei Wang, Xiaodong Jiang
PURPOSE: To determine if inhibiting neuropilin-1 (NRP-1) affects the radiosensitivity of NSCLC cells through a vascular endothelial growth factor receptor 2 (VEGFR2)-independent pathway, and to assess the underlying mechanisms. METHODS: The expression of VEGFR2, NRP-1, related signaling molecules, abelson murine leukemia viral oncogene homolog 1 (ABL-1), and RAD51 were determined by RT-PCR and Western blotting, respectively. Radiosensitivity was assessed using the colony-forming assay, and the cell apoptosis were analyzed by flow cytometry...
May 17, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29777057/glycogen-synthase-kinase-3-gsk-3-activity-regulates-mrna-methylation-in-mouse-embryonic-stem-cells
#6
Kelsie J Faulds, Jennifer N Egelston, Laura J Sedivy, Matthew K Mitchell, Sanjana Garimella, Hanna Kozlowski, Angelo D'Alessandro, Kirk C Hansen, Jeremy L Balsbaugh, Christopher J Phiel
Glycogen synthase kinase-3 (Gsk-3) activity regulates multiple signal transduction pathways, and is also a key component of the network responsible for maintaining stem cell pluripotency. Genetic deletion of Gsk-3α and Gsk-3β or inhibition of Gsk-3 activity via small molecules promotes stem cell pluripotency, yet the mechanism underlying the role for Gsk-3 in this process remains ambiguous. Another cellular process that has been shown to affect stem cell pluripotency is mRNA methylation (m6 A). Here, we describe an intersection between these components - the regulation of m6 A by Gsk-3...
May 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29776956/integrin-%C3%AE-3-inhibition-enhances-the-antitumor-activity-of-alk-inhibitor-in-alk-rearranged-nsclc
#7
Ka-Won Noh, Insuk Sohn, Ji-Young Song, Hyun-Tae Shin, Yu Jin Kim, Kyungsoo Jung, Minjung Sung, Mingi Kim, Sungbin An, Joungho Han, Se-Hoon Lee, Mi-Sook Lee, Yoon-La Choi
BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive cancers are sensitive to small molecule ALK kinase inhibitors, but most cases experience failure following treatment. Hence, additional drug targets and combination therapeutic treatments are needed. We investigated gene expression that is regulated by the expression of ALK and explored its roles in cancer progression and therapeutic implication. PATIENTS AND METHODS: We screened ALK-rearranged non-small cell lung cancer (NSCLC) cases using immunohistochemistry and fluorescence in situ hybridization, and then conducted multiplex gene expression analysis...
May 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29776438/uninterrupted-monitoring-of-drug-effects-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-with-bioluminescence-ca-2-microscopy
#8
Kazushi Suzuki, Takahito Onishi, Chieko Nakada, Shunsuke Takei, Matthew J Daniels, Masahiro Nakano, Tomoki Matsuda, Takeharu Nagai
OBJECTIVE: Cardiomyocytes derived from human-induced pluripotent stem cells are a powerful platform for high-throughput drug screening in vitro. However, current modalities for drug testing, such as electrophysiology and fluorescence imaging have inherent drawbacks. To circumvent these problems, we report the development of a bioluminescent Ca2+ indicator GmNL(Ca2+ ), and its application in a customized microscope for high-throughput drug screening. RESULTS: GmNL(Ca2+ ) gives a 140% signal change with Ca2+ , and can image drug-induced changes of Ca2+ dynamics in cultured cells...
May 18, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29776125/post-transcriptional-bursting-in-genes-regulated-by-small-rna-molecules
#9
Guillermo Rodrigo
Gene expression programs in living cells are highly dynamic due to spatiotemporal molecular signaling and inherent biochemical stochasticity. Here we study a mechanism based on molecule-to-molecule variability at the RNA level for the generation of bursts of protein production, which can lead to heterogeneity in a cell population. We develop a mathematical framework to show numerically and analytically that genes regulated post transcriptionally by small RNA molecules can exhibit such bursts due to different states of translation activity (on or off), mostly revealed in a regime of few molecules...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29775968/in-silico-structure-prediction-and-inhibition-mechanism-studies-of-athda14-as-revealed-by-homology-modeling-docking-molecular-dynamics-simulation
#10
Ming-Lang Zhao, Wang Wang, Hu Nie, Sha-Sha Cao, Lin-Fang Du
Histone deacetylases (HDACs) play a significant role in the epigenetic mechanism by catalyzing deacetylation of lysine on histone in both animals and plants. HDACs involved in growth, development and response to stresses in plants. Arabidopsis thaliana histone deacetylase 14 (AtHDA14) is found to localize in the mitochondria and chloroplasts, and it involved in photosynthesis and melatonin biosynthesis. However, its mechanism of action was still unknowns so far. Therefore, in this study, we constructed AtHDA14 protein model using homology modeling method, validated using PROCHECK and presented using Ramachandran plots...
May 6, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29775731/targeted-and-controlled-drug-delivery-by-multifunctional-mesoporous-silica-nanoparticles-with-internal-fluorescent-conjugates-and-external-polydopamine-and-graphene-oxide-layers
#11
Anh-Vy Tran, KyuHwan Shim, Thu-Thao Vo Thi, Jeong-Keun Kook, Seong Soo A An, Sang-Wha Lee
This study demonstrated the targeted delivery and controlled release of cisplatin drug molecules from doubly decorated mesoporous silica nanoparticles (MSNs), which were internally grafted with fluorescent conjugates and externally coated with polydopamine (PDA) and graphene oxide (GO) layers. The brush-like internal conjugates conferred fluorescent functionality and high capacity of cisplatin loading into MSNs, as well as contributing to a sustained release of the cisplatin through a porous channel with the assistance of external PDA layer...
May 15, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29775632/controlled-delivery-of-a-focal-adhesion-kinase-inhibitor-results-in-accelerated-wound-closure-with-decreased-scar-formation
#12
Kun Ma, Sun Hyung Kwon, Jagannath Padmanabhan, Dominik Duscher, Artem A Trotsyuk, Yixiao Dong, Mohammed Inayathullah, Jayakumar Rajadas, Geoffrey C Gurtner
Formation of scars following wounding or trauma represents a significant healthcare burden costing the economy billions of dollars every year. Activation of focal adhesion kinase (FAK) has been shown to play a pivotal role in transducing mechanical signals to elicit fibrotic responses and scar formation during wound repair. We have previously shown that inhibition of FAK using local injections of a small molecule FAK inhibitor (FAKI) can attenuate scar development in a hypertrophic scar model. Clinical translation of FAKI therapy has been challenging, however, due to the lack of an effective drug delivery system for extensive burn injuries, blast injuries, and large excisional injuries...
May 15, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29775584/conformational-activation-of-argonaute-by-distinct-yet-coordinated-actions-of-the-hsp70-and-hsp90-chaperone-systems
#13
Kotaro Tsuboyama, Hisashi Tadakuma, Yukihide Tomari
Loading of small RNAs into Argonaute, the core protein in RNA silencing, requires the Hsp70/Hsp90 chaperone machinery. This machinery also activates many other clients, including steroid hormone receptors and kinases, but how their structures change during chaperone-dependent activation remains unclear. Here, we utilized single-molecule Förster resonance energy transfer (smFRET) to probe the conformational changes of Drosophila Ago2 mediated by the chaperone machinery. We found that empty Ago2 exists in various closed conformations...
May 17, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29775438/breakdown-of-water-super-permeation-in-electrically-insulating-graphene-oxide-films-role-of-dual-interlayer-spacing
#14
M K Kavitha, Tushar Sakorikar, Pramitha V, Manu Jaiswal
Conventional graphene oxide is characterized by low sp<sup>2</sup> content in a sp<sup>3</sup> rich matrix, which is responsible both for electrical insulation and water super-permeation. Upon reduction, electrical conduction is achieved at the expense of water permeation ability. Here, we demonstrate that charge conduction and water permeation can be simultaneously restricted in a functionalized form of graphene oxide. Gravimetric studies reveal that diffusion of water vapour through glassy polymer membranes is arrested by loading hydrophobic form of GO in the polymer matrix, even as such water inhibition cannot be realized by substantially increasing the thickness of the bare polymer...
May 18, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29775409/transactivation-domain-of-p53-regulates-dna-repair-and-integrity-in-human-ips-cells
#15
Ramaswamy Kannappan, Saidulu Mattapally, Pooja A Wagle, Jianyi Zhang
The role of p53 transactivation domain (p53-TAD), a multifunctional and dynamic domain, on DNA repair and retaining DNA integrity in human iPS cells has never been studied. p53-TAD was knocked out in iPS cells using CRISPR/Cas9 and was confirmed by DNA sequencing. p53-TAD KO cells were characterized by: accelerated proliferation, decreased population doubling time, and unaltered Bcl2, BBC3, IGF1R, Bax and altered Mdm2, p21, and PIDD transcripts expression. In p53-TAD KO cells p53 regulated DNA repair proteins XPA, DNA polH and DDB2 expression were found to be reduced compared to p53-WT cells...
May 18, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29775325/absence-of-long-range-order-in-a-triangular-spin-system-with-dipolar-interactions
#16
Ahmet Keleş, Erhai Zhao
The antiferromagnetic Heisenberg model on the triangular lattice is perhaps the best known example of frustrated magnets, but it orders at low temperatures. Recent density matrix renormalization group (DMRG) calculations find that the next nearest neighbor interaction J_{2} enhances the frustration, and it leads to a spin liquid for J_{2}/J_{1}∈(0.08,0.15). In addition, a DMRG study of a dipolar Heisenberg model with longer range interactions gives evidence for a spin liquid at a small dipole tilting angle θ∈[0,10°)...
May 4, 2018: Physical Review Letters
https://www.readbyqxmd.com/read/29775306/mechanistic-study-on-water-splitting-reactions-by-small-silicon-clusters-si-3-x-x-si-be-mg-ca
#17
Tran Dieu Hang, Minh Tho Nguyen
(Abstract) Interaction, dissociation and dehydrogenation reactions of water monomer and dimer with pure and mixed tetrameric silicon clusters Si3X with X = Si, Be, Mg, Ca were investigated using high accuracy quantum chemical calculations. While geometries were optimized using the DFT/B3LYP functional with the aug-cc-pVTZ basis set, reaction energy profiles were constructed making use of the coupled-cluster theory with extrapolation to complete basis set, CCSD(T)/CBS. Cleavage of the O-H bond in water dimer is found to be more favored than that of water monomer in the reaction with Si4...
May 18, 2018: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/29775273/the-role-of-clpp-protease-in-bacterial-pathogenesis-and-human-diseases
#18
Vaibhav Bhandari, Keith S Wong, Jin Lin Zhou, Mark F Mabanglo, Robert A Batey, Walid A Houry
In prokaryotic cells and eukaryotic organelles, the ClpP protease plays an important role in proteostasis. The disruption of ClpP function has been shown to influence the infectivity and virulence of a number of bacterial pathogens. More recently, ClpP has been found to be involved in various forms of carcinomas and in Perrault syndrome, which is an inherited condition characterized by hearing loss in males and females and by ovarian abnormalities in females. Hence, targeting ClpP is a potentially viable, attractive option for the treatment of different ailments...
May 18, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29774984/comments-on-recent-reports-on-infrared-spectral-detection-of-disease-markers-in-blood-components
#19
Max Diem
The search for disease markers in whole blood, or easily accessible blood components by spectral methods is a highly important aspect in the field of biophotonic research for disease diagnostics and screening, since it promises a minimally invasive approach to assess an individual's state of health. Fourier transform infrared spectroscopy, in particular, promises to be a fast, inexpensive method to search for markers of disease, since it detects variation in the proteome, lipidome and metabolome of biofluids, or activation of immune cells...
May 18, 2018: Journal of Biophotonics
https://www.readbyqxmd.com/read/29774926/an-anionic-shell-shields-a-cationic-core-allowing-for-uptake-and-release-of-polyelectrolytes-within-core-shell-responsive-microgels
#20
Arjan P H Gelissen, Andrea Scotti, Sarah K Turnhoff, Corinna Janssen, Aurel Radulescu, Andrij Pich, Andrey A Rudov, Igor I Potemkin, Walter Richtering
To realize carriers for drug delivery, cationic containers are required for anionic guests. Nevertheless, the toxicity of cationic carriers limits their practical use. In this study, we investigate a model system of polyampholyte N-isopropylacrylamide (NIPAM)-based microgels with a cationic core and an anionic shell to study whether the presence of a negative shell allows the cationic core to be shielded while still enabling the uptake and release of the anionic guest polyelectrolytes. These microgels are loaded with polystyrene sulfonate of different molecular weights to investigate the influence of their chain length on the uptake and release process...
May 18, 2018: Soft Matter
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