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(LIGHT AND CAGED) OR (aptamer) OR (UNNATURAL AMINO ACID) OR (OPTOGENETIC) OR (DNA DECOY) OR (MORPHOLINO) •

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https://www.readbyqxmd.com/read/29334187/surveying-the-landscape-of-optogenetic-methods-for-detection-of-protein-protein-interactions
#1
REVIEW
Matthew D Wiens, Robert E Campbell
Mapping the protein-protein interaction (PPi) landscape is of critical importance to furthering our understanding how cells and organisms function. Optogenetic methods, that is, approaches that utilize genetically encoded fluorophores or fluorogenic enzyme reactions, uniquely enable the visualization of biochemical phenomena in live cells with high spatial and temporal accuracy. Applying optogenetic methods to the detection of PPis requires the engineering of protein-based systems in which an optical signal undergoes a substantial change when the two proteins of interest interact...
January 15, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/29334115/label-free-multidimensional-information-acquisition-from-optogenetically-engineered-cells-using-a-graphene-transistor
#2
Gongxin Li, Jia Yang, Wenguang Yang, Feifei Wang, Yuechao Wang, Wenxue Wang, Lianqing Liu
The optogenetic technique, which allows the manipulation of cellular activity patterns in space and time by light, has transformed the field of neuroscience. However, acquiring multidimensional optogenetic information remains challenging despite the fact that several cellular information detection methods have been proposed. Herein, we present a new method to acquire label-free multidimensional information from optogenetically engineered cells using a graphene transistor. Using a graphene film to form a strong densely packed layer with cells, the cellular action potentials were characterized as light-activated transistor conductance signals, which quantified the multidimensional optogenetic information...
January 15, 2018: Nanoscale
https://www.readbyqxmd.com/read/29332836/fluorescent-and-colorimetric-dual-mode-aptasensor-for-thrombin-detection-based-on-target-induced-conjunction-of-split-aptamer-fragments
#3
Wenna Duan, Xiuzhong Wang, Haixia Wang, Feng Li
Since the lack of detection diversity of the single-signal readout strategy, it is urgent to develop fast and multisignal assay strategies. A highly selective and sensitive assay method with colorimetric and fluorometric dual signals readouts is presented in this paper. It is based on the principle that the target induced conjunction of split aptamer fragments assembled on the surface of Au nanoparticles (AuNPs). In the presence of targets, the color of solution changed from wine red to blue and can be measured both visual inspection and spectrophotometry because of the aggregation of AuNPs...
April 1, 2018: Talanta
https://www.readbyqxmd.com/read/29331900/a-catalytic-and-dual-recycling-amplification-atp-sensor-based-on-target-driven-allosteric-structure-switching-of-aptamer-beacons
#4
Ying Peng, Daxiu Li, Ruo Yuan, Yun Xiang
Abnormal concentrations of ATP are associated with many diseases and cancers, and quantitative detection of ATP is thus of great importance for disease diagnosis and prognosis. In the present work, we report a new dual recycling amplification sensor integrated with catalytic hairpin assembly (CHA) to achieve high sensitivity for fluorescent detection of ATP. The association of the target ATP with the aptamer beacons causes the allosteric structure switching of the aptamer beacons to expose the toehold regions, which hybridize with and unfold the fluorescently quenched hairpin signal probes (HP1) to recycle the target ATP and to trigger CHA between HP1 and the secondary hairpin probes (HP2) to form HP1/HP2 duplexes...
January 9, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29331378/loss-of-zebrafish-smyd1a-interferes-with-myofibrillar-integrity-without-triggering-the-misfolded-myosin-response
#5
Christoph Paone, Steven Rudeck, Christelle Etard, Uwe Strähle, Wolfgang Rottbauer, Steffen Just
Sarcomeric protein turnover needs to be tightly balanced to assure proper assembly and renewal of sarcomeric units within muscle tissues. The mechanisms regulating these fundamental processes are only poorly understood, but of great clinical importance since many cardiac and skeletal muscle diseases are associated with defective sarcomeric organization. The SET- and MYND domain containing protein 1b (Smyd1b) is known to play a crucial role in myofibrillogenesis by functionally interacting with the myosin chaperones Unc45b and Hsp90α1...
January 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29331265/mechanisms-of-memory-disruption-in-depression
#6
REVIEW
Daniel G Dillon, Diego A Pizzagalli
Depressed individuals typically show poor memory for positive events, potentiated memory for negative events, and impaired recollection. These phenomena are clinically important but poorly understood. Compelling links between stress and depression suggest promising candidate mechanisms. Stress can suppress hippocampal neurogenesis, inhibit dopamine neurons, and sensitize the amygdala. We argue that these phenomena may impair pattern separation, disrupt the encoding of positive experiences, and bias retrieval toward negative events, respectively, thus recapitulating core aspects of memory disruption in depression...
January 10, 2018: Trends in Neurosciences
https://www.readbyqxmd.com/read/29330802/microinjection-of-antisense-morpholinos-crispr-cas9-rnp-and-rna-dna-into-zebrafish-embryos
#7
Yi Xin, Cunming Duan
In this chapter, we describe a stepwise protocol of microinjection. Using this method, antisense morpholinos, CRISPR-Cas9 ribonucleoprotein complexes, capped mRNA, and DNA can be delivered into fertilized zebrafish eggs to manipulate gene expression during development. This protocol can also be adapted for microinjection in other fish and amphibian species.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330504/unique-roles-of-%C3%AE-arrestin-in-gpcr-trafficking-revealed-by-photoinducible-dimerizers
#8
Osamu Takenouchi, Hideaki Yoshimura, Takeaki Ozawa
Intracellular trafficking of G protein-coupled receptors (GPCRs) controls their localization and degradation, which affects a cell's ability to adapt to extracellular stimuli. Although the perturbation of trafficking induces important diseases, these trafficking mechanisms are poorly understood. Herein, we demonstrate an optogenetic method using an optical dimerizer, cryptochrome (CRY) and its partner protein (CIB), to analyze the trafficking mechanisms of GPCRs and their regulatory proteins. Temporally controlling the interaction between β-arrestin and β2-adrenergic receptor (ADRB2) reveals that the duration of the β-arrestin-ADRB2 interaction determines the trafficking pathway of ADRB2...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329202/epcam-immunotherapy-versus-specific-targeted-delivery-of-drugs
#9
REVIEW
Joanna Macdonald, Justin Henri, Kislay Roy, Emma Hays, Michelle Bauer, Rakesh Naduvile Veedu, Normand Pouliot, Sarah Shigdar
The epithelial cell adhesion molecule (EpCAM), or CD326, was one of the first cancer associated biomarkers to be discovered. In the last forty years, this biomarker has been investigated for use in personalized cancer therapy, with the first monoclonal antibody, edrecolomab, being trialled in humans more than thirty years ago. Since then, several other monoclonal antibodies have been raised to EpCAM and tested in clinical trials. However, while monoclonal antibody therapy has been investigated against EpCAM for almost 40 years as primary or adjuvant therapy, it has not shown as much promise as initially heralded...
January 12, 2018: Cancers
https://www.readbyqxmd.com/read/29329072/development-of-potent-and-proteolytically-stable-human-neuromedin-u-receptor-agonists
#10
An De Prins, Charlotte Martin, Yannick Van Wanseele, Louise Julie Skov, Csaba Tömböly, Dirk Tourwé, Vicky Caveliers, Ann Van Eeckhaut, Birgitte Holst, Mette Marie Rosenkilde, Ilse Smolders, Steven Ballet
Neuromedin U (NMU) is a highly conserved endogenous peptide that is involved in a wide range of physiological processes such as regulation of feeding behavior, the stress response and nociception. The major limitation to use NMU as a therapeutic is its short half-life. Here, we describe the development of a set of novel NMU-analogs based on NMU-8, by introducing unnatural amino acids into the native sequence. This approach shows that it is possible to generate molecules with increased potency and improved plasma stability without major changes of the peptidic nature or the introduction of large conjugates...
December 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29327939/blockade-of-the-complement-c5a-c5ar1-axis-impairs-lung-cancer-bone-metastasis-by-cxcl16-mediated-effects
#11
Daniel Ajona, Carolina Zandueta, Leticia Corrales, Haritz Moreno, María J Pajares, Sergio Ortiz-Espinosa, Elena Martínez-Terroba, Naiara Perurena, Fernando J de Miguel, Eloisa Jantus-Lewintre, Carlos Camps, Silvestre Vicent, Jackeline Agorreta, Luis M Montuenga, Ruben Pio, Fernando Lecanda
RATIONALE: C5aR1(CD88), a receptor for complement anaphylatoxin C5a, is a potent immune mediator. Its impact on malignant growth and dissemination of NSCLC cells is poorly understood. OBJECTIVES: To investigate the contribution of the C5a/C5aR1 axis to the malignant phenotype of NSCLC cells, particularly in skeletal colonization, a preferential lung metastasis site. METHODS: Association between C5aR1 expression and clinical outcome was assessed in silico and validated by immunohistochemistry...
January 12, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29327920/generation-of-optogenetically-modified-adenovirus-vector-for-spatiotemporally-controllable-gene-therapy
#12
Kazuo Takayama, Hiroyuki Mizuguchi
Gene therapy is expected to be utilized for the treatment of various diseases. However, the spatiotemporal resolution of current gene therapy technology is not high enough. In this study, we generated a new technology for spatiotemporally controllable gene therapy. We introduced optogenetic and CRISPR/Cas9 techniques into a recombinant adenovirus (Ad) vector, which is widely used in clinical trials and exhibits high gene transfer efficiency, to generate an illumination-dependent spatiotemporally controllable gene regulation system (designated the Opt/Cas-Ad system)...
January 12, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29327496/modulation-of-bace1-activity-by-chemically-modified-aptamers
#13
Cécile Gasse, Marwa Zaarour, Sam Noppen, Mikhail Abramov, Philippe Marlière, Sandra Liekens, Bart De Strooper, Piet Herdewijn
A modified DNA aptamer was developed that binds BACE1, a therapeutic target involved in Alzheimer's disease. This ssXNA not only tightly binds to BACE1 but also inhibits its protease activity in vitro in the same range as a previously described unmodified aptamer. We report the in vitro selection of functional oligonucleotides using two nucleobase modifications: 5-chlorouracil and 7-deazaadenine. The nucleoside analog 5-chloro-2'-deoxyuridine has already been explored to replace thymidine in a chemically modified genome of a bacterium...
January 11, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29327202/transient-disruption-of-adenosine-signaling-during-embryogenesis-triggers-a-pro-epileptic-phenotype-in-adult-zebrafish
#14
Fabiano Peres Menezes, Felipe Machado Torresini, Laura Roesler Nery, Rosane Souza da Silva
Adenosinergic signaling has important effects on brain function, anatomy, and physiology in both late and early stages of development. Exposure to caffeine, a non-specific blocker of adenosine receptor, has been indicated as a developmental risk factor. Disruption of adenosinergic signaling during early stages of development can change the normal neural network formation and possibly lead to an increase in susceptibility to seizures. In this work, morpholinos (MO) temporarily blocked the translation of adenosine receptor transcripts, adora1, adora2aa, and adora2ab, during the embryonic phase of zebrafish...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29325460/targeted-delivery-of-melittin-to-cancer-cells-by-as1411-anti-nucleolin-aptamer
#15
Seyed Hossein Rajabnejad, Ahad Mokhtarzadeh, Khalil Abnous, Seyed Mohammad Taghdisi, Mohammad Ramezani, Bibi Marjan Razavi
Melittin, a small water-soluble cationic amphipathic α-helical linear peptide, consisted of 26 amino acids, is the honeybee venom major constituent. Several reports have proved the lytic and apoptotic effects of melittin in several cancerous cell lines. In this study, we aimed to fabricate an AS1411 aptamer-melittin to specifically deliver melittin to nucleolin positive cells (A549). Melittin was covalently attached to antinucleolin aptamer (AS1411) and its toxicity in A549 (Nucleolin positive) and L929 (Nucleolin negative) was studied using MTT and Annexin V flow cytometry methods...
January 12, 2018: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29325019/deep-molecular-phenotypes-link-complex-disorders-and-physiological-insult-to-cpg-methylation
#16
Shaza B Zaghlool, Dennis O Mook-Kanamori, Sara Kader, Nisha Stephan, Anna Halama, Rudolf Engelke, Hina Sarwath, Eman K Al-Dous, Yasmin A Mohamoud, Werner Roemisch-Margl, Jerzy Adamski, Gabi Kastenmüller, Nele Friedrich, Alessia Visconti, Pei-Chien Tsai, Tim Spector, Jordana Bell, Mario Falchi, Annika Wahl, Melanie Waldenberger, Annette Peters, Christian Gieger, Maija Pezer, Gordan Lauc, Johannes Graumann, Joel A Malek, Karsten Suhre
Epigenetic regulation of cellular function provides a mechanism for rapid organismal adaptation to changes in health, lifestyle, and environment. Associations of cytosine-guanine di-nucleotide (CpG) methylation with clinical endpoints that overlap with metabolic phenotypes suggest a regulatory role for these CpG sites in the body's response to disease or environmental stress. We previously identified 20 CpG sites in an epigenome-wide association study (EWAS) with metabolomics that were also associated in recent EWASs with diabetes-, obesity-, and smoking-related endpoints...
January 8, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29323871/microfluidic-device-for-aptamer-based-cancer-cell-capture-and-genetic-mutation-detection
#17
Sarah Jessica Reinholt, Harold G Craighead
We present a microfluidic device for specifically capturing cancer cells and isolating their genomic DNA (gDNA) for specific amplification and sequence analysis. To capture cancer cells within the device, nucleic acid aptamers that specifically bind to cancer cells were immobilized within a channel containing micropillars designed to increase capture efficiency. The cap-tured cells were lysed in situ and their gDNA was isolated by physical entanglement within a second smaller-dimensioned micropillar array. This type of isolation allowed the gDNA to be retained and purified within the channel, and enables ampli-fication and analysis to be performed on the gDNA without the loss of the original template...
January 11, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29323683/ru-ii-polypyridyl-complexes-as-photocages-for-bioactive-compounds-containing-nitriles-and-aromatic-heterocycles
#18
Ao Li, Claudia Turro, Jeremy J Kodanko
Photocaging allows for precise spatiotemporal control over the release of biologically active compounds with light. Most photocaged molecules employ organic photolabile protecting groups; however, biologically active compounds often contain functionalities such as nitriles and aromatic heterocycles that cannot be caged with organic groups. Despite their prevalence, only a few studies have reported successful caging of nitriles and aromatic heterocycles. Recently, Ru(ii)-based photocaging has emerged as a powerful method for the release of bioactive molecules containing these functional groups, in many cases providing high levels of spatial and temporal control over biological activity...
January 11, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29323226/lateral-and-basal-amygdala-account-for-opposite-behavioral-responses-during-the-long-term-expression-of-fearful-memories
#19
Eugenio Manassero, Annamaria Renna, Luisella Milano, Benedetto Sacchetti
Memories of fearful events can be maintained throughout the lifetime of animals. Here we showed that lesions of the lateral nucleus (LA) performed shortly after training impaired the retention of long-term memories, assessed by the concomitant measurement of two dissociable defensive responses, freezing and avoidance in rats. Strikingly, when LA lesions were performed four weeks after training, rats did not show freezing to a learned threat stimulus, but they were able to direct their responses away from it...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29322773/sers-based-label-free-insulin-detection-at-physiological-concentrations-for-analysis-of-islet-performance
#20
Hyunjun Cho, Shailabh Kumar, Daejong Yang, Sagar R Vaidyanathan, Kelly Woo, Ian Garcia, Hao Jan Shue, Youngzoon Yoon, Kevin Ferreri, Hyuck Choo
Label-free optical detection of insulin would allow in vitro assessment of pancreatic cell functions in their natural state and expedite diabetes-related clinical research and treatment, however no existing method has met these criteria at physiological concentrations. Using spatially-uniform 3D gold-nanoparticle sensors, we have demonstrated surface-enhanced Raman sensing of insulin in the secretions from human pancreatic islets under low and high glucose environments without the use of labels such as antibodies or aptamers...
January 11, 2018: ACS Sensors
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