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https://www.readbyqxmd.com/read/28329689/the-human-cchc-type-zinc-finger-nucleic-acid-binding-protein-binds-g-rich-elements-in-target-mrna-coding-sequences-and-promotes-translation
#1
Daniel Benhalevy, Sanjay K Gupta, Charles H Danan, Suman Ghosal, Hong-Wei Sun, Hinke G Kazemier, Katrin Paeschke, Markus Hafner, Stefan A Juranek
The CCHC-type zinc finger nucleic acid-binding protein (CNBP/ZNF9) is conserved in eukaryotes and is essential for embryonic development in mammals. It has been implicated in transcriptional, as well as post-transcriptional, gene regulation; however, its nucleic acid ligands and molecular function remain elusive. Here, we use multiple systems-wide approaches to identify CNBP targets and function. We used photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) to identify 8,420 CNBP binding sites on 4,178 mRNAs...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28328998/combinatorial-selection-for-replicable-rna-by-q%C3%AE-replicase-while-maintaining-encoded-gene-function
#2
Mio Yumura, Natsuko Yamamoto, Katsushi Yokoyama, Hirotada Mori, Tetsuya Yomo, Norikazu Ichihashi
Construction of a complex artificial self-replication system is challenging in the field of in vitro synthetic biology. Recently, we developed a translation-coupled RNA replication system, wherein an artificial genomic RNA replicates with the Qβ RNA replicase gene encoded on itself. The challenge is to introduce additional genes into the RNA to develop a complex system that mimics natural living systems. However, most RNA sequence encoding genes are not replicable by the Qβ replicase owing to its requirement for strong secondary structures throughout the RNA sequence that are absent in most genes...
2017: PloS One
https://www.readbyqxmd.com/read/28328321/ultrafast-and-predictive-mass-spectrometry-based-autotaxin-assays-for-label-free-potency-screening
#3
Tom Bretschneider, Andreas Harald Luippold, Helmut Romig, Daniel Bischoff, Klaus Klinder, Paul Nicklin, Wolfgang Rist
Autotaxin (ATX) is a promising drug target for the treatment of several diseases, such as cancer and fibrosis. ATX hydrolyzes lysophosphatidyl choline (LPC) into bioactive lysophosphatidic acid (LPA). The potency of ATX inhibitors can be readily determined by using fluorescence-based LPC derivatives. While such assays are ultra-high throughput, they are prone to false positives compared to assays based on natural LPC. Here we report the development of ultrafast mass spectrometry-based ATX assays enabling the measurement of data points within 13 s, which is 10 times faster than classic liquid chromatography-mass spectrometry...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28327707/direct-visualization-of-carbon-nanotube-degradation-in-primary-cells-by-photothermal-imaging
#4
Julie Russier, Laura Oudjedi, Martin Piponnier, Cyrill Bussy, Maurizio Prato, Kostas Kostarelos, Brahim Lounis, Alberto Bianco, Laurent Cognet
Assessment of biodegradability of carbon nanotubes (CNTs) is a critically important aspect that needs to be solved before their translation into new biomedical tools. CNT biodegradation has been shown both in vitro and in vivo, but we are limited by the number of analytical techniques that can be used to follow the entire process. Photothermal imaging (PhI) is an innovative technique that enables the quantitative detection of nanometer-sized absorptive objects. In this study, we demonstrate that PhI allows the observation of the degradation process of functionalized multi-walled carbon nanotubes (MWCNTs) following their internalization by primary glial cells...
March 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28326353/in-vitro-osteogenic-capacity-of-bone-marrow-mscs-from-postmenopausal-women-reflect-the-osseointegration-of-their-cementless-hip-stems
#5
Jessica J Alm, Niko Moritz, Hannu T Aro
Age-related dysfunction of mesenchymal stromal cells (MSCs) is suggested as a main cause of altered bone repair with aging. We recently showed that in postmenopausal women undergoing cementless total hip arthroplasty (THA) aging, low bone mineral density (BMD) and age-related geometric changes of the proximal femur are risk factors for increased early migration and delayed osseointegration of the femoral stems. Extending these analyses, we have here explored how the in vitro osteogenic capacity of bone marrow MSCs from these patients reflects implant osseointegration, representing the patient's in vivo bone healing capacity...
December 2016: Bone Reports
https://www.readbyqxmd.com/read/28324594/polymers-in-the-delivery-of-sirna-for-the-treatment-of-virus-infections
#6
REVIEW
Nicholas Reynolds, Megan Dearnley, Tracey M Hinton
Viral diseases remain a major cause of death worldwide. Despite advances in vaccine and antiviral drug technology, each year over three million people die from a range of viral infections. Predominant viruses include human immunodeficiency virus, hepatitis viruses, and gastrointestinal and respiratory viruses. Now more than ever, robust, easily mobilised and cost-effective antiviral strategies are needed to combat both known and emerging disease threats. RNA interference and small interfering (si)RNAs were initially hailed as a "magic bullet", due to their ability to inhibit the synthesis of any protein via the degradation of its complementary messenger RNA sequence...
April 2017: Topics in Current Chemistry (Journal)
https://www.readbyqxmd.com/read/28324015/paternally-inherited-dlk1-deletion-associated-with-familial-central-precocious-puberty
#7
Andrew Dauber, Marina Cunha-Silva, Delanie B Macedo, Vinicius N Brito, Ana Paula Abreu, Stephanie A Roberts, Luciana R Montenegro, Melissa Andrew, Andrew Kirby, Matthew T Weirauch, Guillaume Labilloy, Danielle S Bessa, Rona S Carroll, Dakota C Jacobs, Patrick E Chappell, Berenice B Mendonca, David Haig, Ursula B Kaiser, Ana Claudia Latronico
Context: Central precocious puberty (CPP) results from premature activation of the hypothalamic-pituitary-gonadal axis. Few genetic causes of CPP have been identified with the most common being mutations in the paternally expressed imprinted gene MKRN3. Objective: To identify the genetic etiology of CPP in a large multigenerational family. Design: Linkage analysis followed by whole genome sequencing was performed in a family with 5 female members with nonsyndromic CPP...
January 27, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323924/guanabenz-sensitizes-pancreatic-%C3%AE-cells-to-lipotoxic-endoplasmic-reticulum-stress-and-apoptosis
#8
Baroj Abdulkarim, Miriam Hernangomez, Mariana Igoillo Esteve, Daniel A Cunha, Lorella Marselli, Piero Marchetti, Laurence Ladriere, Miriam Cnop
Deficient as well as excessive/prolonged endoplasmic reticulum (ER) stress signaling can lead to pancreatic β cell failure and the development of diabetes. Saturated free fatty acids (FFAs) such as palmitate induce lipotoxic ER stress in pancreatic β cells. One of the main ER stress response pathways is under the control of the protein kinase R-like endoplasmic reticulum kinase (PERK), leading to phosphorylation of the eukaryotic translation initiation factor 2 (eIF2α). The antihypertensive drug guanabenz has been shown to inhibit eIF2α dephosphorylation and protect cells from ER stress...
March 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323411/engineering-an-injectable-muscle-specific-microenvironment-for-improved-cell-delivery-using-a-nanofibrous-extracellular-matrix-hydrogel
#9
Nikhil Rao, Gillie Agmon, Matthew T Tierney, Jessica L Ungerleider, Rebecca L Braden, Alessandra Sacco, Karen L Christman
Injection of skeletal muscle progenitors has the potential to be a minimally invasive treatment for a number of diseases that negatively affect vasculature and skeletal muscle, including peripheral artery disease (PAD). However, success with this approach has been limited because of poor transplant cell survival. This is primarily attributed to cell death due to extensional flow through the needle, the harsh ischemic environment of the host tissue, a deleterious immune cell response, and a lack of biophysical cues supporting exogenous cell viability...
March 21, 2017: ACS Nano
https://www.readbyqxmd.com/read/28323047/biochemical-and-chemical-characterization-of-cynara-cardunculus-l-extract-and-its-potential-use-as-co-adjuvant-therapy-of-chronic-myeloid-leukemia
#10
Antonio Russo, Mariarita Perri, Erika Cione, Maria Luisa Di Gioia, Monica Nardi, Maria Cristina Caroleo
ETHNOPHARMACOLOGICAL RELEVANCE: Ancient mediterranean diet was characterized by consuming the spontaneous forms of Cynara Cardunculus L. (CCL), commonly called artichoke. Cultivated and/or spontaneous forms of CC studies have demonstrated that methanol extract of CCL flower and/or cynaropicrin showed remarkable anti-proliferative activity in vitro models of leukocyte cancer cell. AIM OF THE STUDY: Chronic myeloid leukemia (CML) is associated with a reciprocal translocation of the long arms of chromosomes 9 and 22 generating the BCR/ABL fusion gene, translated in the p210(BCR/ABL) oncoprotein kinase...
March 18, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28322844/a-harmine-derived-beta-carboline-displays-anti-cancer-effects-in-vitro-by-targeting-protein-synthesis
#11
Annelise Carvalho, Jennifer Chu, Céline Meinguet, Robert Kiss, Guy Vandenbussche, Bernard Masereel, Johan Wouters, Alexander Kornienko, Jerry Pelletier, Véronique Mathieu
Growing evidence indicates that protein synthesis is deregulated in cancer onset and progression and targeting this process might be a selective way to combat cancers. While harmine is known to inhibit DYRK1A and intercalate into the DNA, tri-substitution was shown previously to modify its activity profile in favor of protein synthesis inhibition. In this study, we thus evaluated the optimized derivative CM16 in vitro anti-cancer effects unfolding its protein synthesis inhibition activity. Indeed, the growth inhibitory profile of CM16 in the NCI 60-cancer-cell-line-panel correlated with those of other compounds described as protein synthesis inhibitors...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28322794/involvement-of-vimentin-in-neurite-outgrowth-damage-induced-by-fipronil-in-sh-sy5y-cells
#12
Theetat Ruangjaroon, Daranee Chokchaichamnankit, Chantragan Srisomsap, Jisnuson Svasti, N Monique Paricharttanakul
Fipronil, a phenylpyrazole insecticide, is more selective in its potency towards insects than humans and is thus commonly used. In this study, we demonstrated that exposure to fipronil may pose a human health risk. We observed in vitro the shortening of neurite outgrowths of SH-SY5Y neuroblastoma cells upon treatment with fipronil, even at a non-cytotoxic concentration. Fipronil induced apoptosis involving caspase-6, which is an apoptotic effector highly implicated in neurodegenerative diseases. Moreover, at a concentration that did not induce apoptosis, mitochondrial dysfunction and autophagic vacuole formation were detected...
March 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28322292/a-structure-and-chemical-genomics-based-approach-for-repositioning-of-drugs-against-vcp-p97-atpase
#13
Aldo Segura-Cabrera, Reshmi Tripathi, Xiaoyi Zhang, Lin Gui, Tsui-Fen Chou, Kakajan Komurov
Valosin-containing protein (VCP/p97) ATPase (a.k.a. Cdc48) is a key member of the ER-associated protein degradation (ERAD) pathway. ERAD and VCP/p97 have been implicated in a multitude of human diseases, such as neurodegenerative diseases and cancer. Inhibition of VCP/p97 induces proteotoxic ER stress and cell death in cancer cells, making it an attractive target for cancer treatment. However, no drugs exist against this protein in the market. Repositioning of drugs towards new indications is an attractive alternative to the de novo drug development due to the potential for significantly shorter time to clinical translation...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28321632/metastatic-melanoma-moves-on-translational-science-in-the-era-of-personalized-medicine
#14
Mitchell P Levesque, Phil F Cheng, Marieke I G Raaijmakers, Annalisa Saltari, Reinhard Dummer
Progress in understanding and treating metastatic melanoma is the result of decades of basic and translational research as well as the development of better in vitro tools for modeling the disease. Here, we review the latest therapeutic options for metastatic melanoma and the known genetic and non-genetic mechanisms of resistance to these therapies, as well as the in vitro toolbox that has provided the greatest insights into melanoma progression. These include next-generation sequencing technologies and more complex 2D and 3D cell culture models to functionally test the data generated by genomics approaches...
March 20, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28321424/cell-based-meniscus-repair-and-regeneration-at-the-brink-of-clinical-translation-a-systematic-review-of-preclinical-studies
#15
Jasmijn V Korpershoek, Tommy S de Windt, Michella H Hagmeijer, Lucienne A Vonk, Daniel B F Saris
BACKGROUND: Meniscus damage can be caused by trauma or degeneration and is therefore common among patients of all ages. Repair or regeneration of the menisci could be of great importance not only for pain relief or regaining function but also to prevent degenerative disease and osteoarthritis. Current treatment does not offer consistent long-term improvement. Although preclinical research focusing on augmentation of meniscal tear repair and regeneration after meniscectomy is encouraging, clinical translation remains difficult...
February 2017: Orthopaedic Journal of Sports Medicine
https://www.readbyqxmd.com/read/28320882/contributions-of-the-n-terminal-and-c-terminal-domains-of-initiation-factor-3-towards-its-functions-in-the-fidelity-of-initiation-and-anti-association-of-the-ribosomal-subunits
#16
Shreya Ayyub, Divya Dobriyal, Umesh Varshney
Initiation factor 3 (IF3) is one of the three conserved prokaryotic translation initiation factors essential for protein synthesis and cellular survival. Bacterial IF3 is composed of a conserved architecture of N- and C- terminal globular domains (NTD and CTD) joined by a linker region. IF3 is a ribosome anti-association factor which also modulates selection of start codon and initiator tRNA. All the functions of IF3 have been attributed to its CTD by in vitro studies. However, in vivo relevance of these findings has not been investigated...
March 20, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28320463/hyaluronan-coating-improves-liver-engraftment-of-transplanted-human-biliary-tree-stem-progenitor-cells
#17
Lorenzo Nevi, Guido Carpino, Daniele Costantini, Vincenzo Cardinale, Olga Riccioni, Sabina Di Matteo, Fabio Melandro, Pasquale Bartolomeo Berloco, Lola Reid, Eugenio Gaudio, Domenico Alvaro
BACKGROUND: Cell therapy of liver diseases with human biliary tree stem cells (hBTSCs) is biased by low engraftment efficiency. Coating the hBTSCs with hyaluronans (HAs), the primary constituents of all stem cell niches, could facilitate cell survival, proliferation, and, specifically, liver engraftment given that HAs are cleared selectively by the liver. METHODS: We developed a fast and easy method to coat hBTSCs with HA and assessed the effects of HA-coating on cell properties in vitro and in vivo...
March 20, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28320070/dexpramipexole-improves-bioenergetics-and-outcome-in-experimental-stroke
#18
Mirko Muzzi, Elisabetta Gerace, Daniela Buonvicino, Elisabetta Coppi, Francesco Resta, Laura Formentini, Riccardo Zecchi, Laura Tigli, Daniele Guasti, Martina Ferri, Emidio Camaioni, Alessio Masi, Domenico E Pellegrini-Giampietro, Guido Mannaioni, Daniele Bani, Anna M Pugliese, Alberto Chiarugi
BACKGROUND AND PURPOSE: To investigate the effects of dexpramipexole, a drug recently tested in ALS patients able to bind F1Fo ATP synthase and increase mitochondrial ATP production, on experimental ischemic brain injury. EXPERIMENTAL APPROACH: The effects of dexpramipexole on bioenergetics, Ca(2+) fluxes, electrophysiological functions and death were evaluated in primary neural cultures and hippocampal slices exposed to oxygen-glucose deprivation (OGD). The drug's impact on infarct volumes and neurological functions was also evaluated in mice subjected to proximal or distal MCAo...
March 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28317976/albumin-based-nanoparticles-loaded-with-hydrophobic-gadolinium-chelates-as-t1-t2-dual-mode-contrast-agents-for-accurate-liver-tumor-imaging
#19
Lirong Wang, Hongyu Lin, Lingceng Ma, Jianbin Jin, Taipeng Shen, Ruixue Wei, Xiaomin Wang, Hua Ai, Zhong Chen, Jinhao Gao
Magnetic resonance contrast agents with T1-T2 dual mode contrast capability have attracted considerable interest because they offer complementary and synergistic diagnostic information, leading to high imaging sensitivity and accurate diagnosis. Here, we reported a facile strategy to construct albumin based nanoparticles loaded with hydrophobic gadolinium chelates by hydrophobic interaction for magnetic resonance imaging (MRI). We synthesized a glycyrrhetinic acid-containing Gd-DOTA derivative (GGD) and loaded GGD molecules into BSA nanoparticles to form GGD-BSA nanoparticles (GGD-BSA NPs)...
March 20, 2017: Nanoscale
https://www.readbyqxmd.com/read/28316123/the-msc-adhesion-cascade-insights-into-homing-and-transendothelial-migration
#20
Franziska Nitzsche, Claudia Müller, Barbara Lukomska, Jukka Jolkkonen, Alexander Deten, Johannes Boltze
Mesenchymal stem cells (MSC) are promising candidates for adult cell therapies in regenerative medicine. To fully exert their potential, efficient homing and migration towards lesion sites plays an important role. Local transplantation deposits MSC in spatial proximity to the lesion, but often requires invasive procedures. Systemic administration routes are favored, but require the targeted extravasation of the circulating MSC at the site of injury. Transplanted MSC can indeed leave the blood flow and transmigrate through the endothelial barrier, and reach the lesion site...
March 18, 2017: Stem Cells
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