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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/28549975/knockdown-of-epigenetic-transcriptional-co-regulator-brd2a-disrupts-apoptosis-and-proper-formation-of-hindbrain-and-midbrain-hindbrain-boundary-mhb-region-in-zebrafish
#1
Tami Murphy, Heather Melville, Eliza Fradkin, Giana Bistany, Gregory Branigan, Kelly Olsen, Catharine R Comstock, Hayley Hanby, Ellie Garbade, Angela J DiBenedetto
Brd2 is a member of the bromodomain-extraterminal domain (BET) family of proteins and functions as an acetyl-histone-directed transcriptional co-regulator and recruitment scaffold in chromatin modification complexes affecting signal-dependent transcription. While Brd2 acts as a protooncogene in mammalian blood, developmental studies link it to regulation of neuronal apoptosis and epilepsy, and complete knockout of the gene is invariably embryonic lethal. In Drosophila, the Brd2 homolog acts as a maternal effect factor necessary for segment formation and identity and proper expression of homeotic loci, including Ultrabithorax and engrailed...
May 23, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28549385/identification-and-imaging-of-leukemia-cells-using-dual-aptamer-functionalized-graphene-oxide-complex
#2
Amirhossein Bahreyni, Rezvan Yazdian-Robati, Mohammad Ramezani, Mehdi Rasouli, Morteza Alinezhad Nameghi, Mona Alibolandi, Khalil Abnous, Seyed Mohammad Taghdisi
Acute lymphoblastic leukemia is the most common malignancy in children. Patient improvement completely depends on the diagnosis of acute lymphoblastic leukemia. So there is a great demand for diagnosis of acute lymphoblastic leukemia. In this study, a novel assay based on dual-aptamer (Sgc8c and ATP aptamers)-functionalized graphene oxide (DAFGO) complex was designed for the identification of Molt-4 cells (human acute lymphoblastic leukemia T-cell). This assay relies on the internalization of DAFGO complex into Molt-4 cells, but not into U266 cells, using Sgc8c aptamer as molecular recognition probe, and release of FAM-labeled ATP aptamer from the complex in the presence of high amounts of ATP in lysosome, leading to a strong fluorescence emission...
January 1, 2017: Journal of Biomaterials Applications
https://www.readbyqxmd.com/read/28549218/exosite-2-directed-ligands-attenuate-protein-c-activation-by-the-thrombin-thrombomodulin-complex
#3
Kai Chen, Alan R Stafford, Chengliang Wu, Calvin Yeh, Paul Y Kim, James C Fredenburgh, Jeffrey I Weitz
Thrombin activity, inhibition, and localization are regulated by two exosites that flank the active site. Substrates, cofactors and inhibitors bind to exosite 1 to promote active site access, whereas exosite 2 interactions retain thrombin on cells, platelets, and proteins. The exosites also serve allosteric roles, whereby ligand binding alters thrombin activity. Previously, we showed that ligands that bind exosite 2 attenuate the exosite 1-mediated interaction of thrombin with fibrin, demonstrating allosteric connection between the exosites...
May 26, 2017: Biochemistry
https://www.readbyqxmd.com/read/28549181/g-quadruplex-structure-of-an-anti-proliferative-dna-sequence
#4
Ngoc Quang Do, Wan Jun Chung, Thi Hong Anh Truong, Brahim Heddi, Anh Tuân Phan
AGRO100 (also known as AS1411) is a G-rich oligonucleotide that has long been established as a potent anti-cancer aptamer. However, the structure of AGRO100 remained unresolved, due to the co-existence of multiple different G-quadruplex conformations. We identified a DNA sequence named AT11, derived from AGRO100, which formed a single major G-quadruplex conformation and exhibited a similar anti-proliferative activity as AGRO100. The solution structure of AT11 revealed a four-layer G-quadruplex comprising of two propeller-type parallel-stranded subunits connected through a central linker...
May 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28549157/exposure-to-acute-psychosocial-stress-disrupts-the-luteinizing-hormone-surge-independent-of-estrous-cycle-alterations-in-female-mice
#5
Elizabeth R Wagenmaker, Suzanne M Moenter
The disruptive effects of severe stress on reproductive function are well documented, but surprisingly few studies exist that demonstrate milder psychosocial stressors interfere with the ovarian cycle in females. We hypothesized repeated application of psychosocial stress would disrupt estrous cycles in mice. Mice were transferred to a new cage, transported to a new room and restrained (2h) for 21 consecutive days. Contrary to our hypothesis, this paradigm did not affect estrous cycles. We next tested the hypothesis that a single exposure to mild stress disrupts a specific aspect of the cycle: the proestrous luteinizing hormone (LH) surge...
May 25, 2017: Endocrinology
https://www.readbyqxmd.com/read/28548675/inducible-bcl-2-gene-rna-interference-mediated-by-aptamer-integrated-hdv-ribozyme-switch
#6
Yuanyuan Zhang, Jine Wang, Hui Cheng, Na Sun, Min Liu, Zhengyan Wu, Renjun Pei
The regulation of RNA interference (RNAi) could be a powerful method for the study of temporal and dose dependent effects of gene expression. In this study, we designed the hepatitis delta virus (HDV) ribozyme with an embedded theophylline aptamer as the sensor domain and the pri-miRNA of endogenous gene Bcl-2 as the effector domain to engineer an RNAi-regulatory device in MCF-7 cells. The system allowed us to control gene expression by adding theophylline into the culture media in a dose dependent fashion...
May 26, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28548671/controllable-n-fe2o3-graphene-nanomaterials-by-ald-applied-in-an-aptasensor-with-enhanced-electrochemical-performance-for-thrombin-detection
#7
Hongfen Zhang, Baiyan Zhang, Anjia Chen, Yong Qin
An elegant atomic layer deposition (ALD) method has been employed for the controllable preparation of a uniform Fe2O3-coated graphene nanostructure (Fe2O3@graphene). The Fe2O3 coating thickness of the Fe2O3@graphene nanostructure can be tuned by varying the cycle number of Fe2O3 ALD. The produced Fe2O3@graphene composites are characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy and cyclic voltammetry (CV). It is revealed that Fe2O3 is effectively deposited on the surface of graphene...
May 26, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28548488/a-fluorescent-split-aptamer-for-visualizing-rna-rna-assembly-in-vivo
#8
Khalid K Alam, Kwaku D Tawiah, Matthew F Lichte, David Porciani, Donald H Burke
RNA-RNA assembly governs key biological processes and is a powerful tool for engineering synthetic genetic circuits. Characterizing RNA assembly in living cells often involves monitoring fluorescent reporter proteins, which are at best indirect measures of underlying RNA-RNA hybridization events and are subject to additional temporal and load constraints associated with translation and activation of reporter proteins. In contrast, RNA aptamers that sequester small molecule dyes and activate their fluorescence are increasingly utilized in genetically encoded strategies to report on RNA-level events...
May 26, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28548167/light-induced-antibiotic-release-from-a-coumarin-caged-compound-on-the-ultrafast-timescale
#9
L-M Herzig, I Elamri, H Schwalbe, J Wachtveitl
A synthesis route for puromycin caged with the photo-responsive 7-diethylaminocoumarinyl protecting group carbamate was developed. The inactivation and recovery of the cytotoxic effect of puromycin was tested with a XTT cell viability assay. The uncaging mechanism was studied by ultrafast transient absorption spectroscopy and by time-correlated single photon counting. The combination of these results with quantum-chemical calculations provided detailed insights in dynamics upon excitation. Interestingly, a change of the dipole moment due to structural rearrangements of the amino moiety led to an intermolecular charge transfer on the picosecond time-scale...
May 26, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28547816/three-component-aminoalkylations-yielding-dihydronaphthoxazine-based-sirtuin-inhibitors-scaffold-modification-and-exploration-of-space-for-polar-side-chains
#10
Steffen Vojacek, Katja Beese, Zayan Alhalabi, Sören Swyter, Anja Bodtke, Carola Schulzke, Manfred Jung, Wolfgang Sippl, Andreas Link
Nonpolar derivatives of heterocyclic aromatic screening hits like the non-selective sirtuin inhibitor splitomicin tend to be poorly soluble in biological fluids. Unlike sp(3) -rich natural products, flat aromatic compounds are prone to stacking and often difficult to optimize into leads with activity in cellular systems. The aim of this work was to identify anchor points for the introduction of sp(3) -rich fragments with polar functional groups into the newly discovered active (IC50  = 5 μM) but nonpolar scaffold 1,2-dihydro-3H-naphth[1,2-e][1,3]oxazine-3-thione by a molecular modeling approach...
May 26, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28546340/the-golgi-matrix-protein-giantin-is-required-for-normal-cilia-function-in-zebrafish
#11
Dylan J M Bergen, Nicola L Stevenson, Roderick E H Skinner, David J Stephens, Christina L Hammond
The Golgi is essential for glycosylation of newly synthesised proteins including almost all cell-surface and extracellular matrix proteoglycans. Giantin, encoded by the golgb1 gene, is a member of the golgin family of proteins that reside within the Golgi stack but its function remains elusive. Loss-of-function of giantin in rats causes osteochondrodysplasia; knockout mice show milder defects, notably a cleft palate. In vitro, giantin has been implicated in Golgi organisation, biosynthetic trafficking, and ciliogenesis...
May 25, 2017: Biology Open
https://www.readbyqxmd.com/read/28546308/dentate-gyrus-contributes-to-retrieval-as-well-as-encoding-evidence-from-context-fear-conditioning-recall-and-extinction
#12
Brian E Bernier, Anthony F Lacagnina, Adam Ayoub, Francis Shue, Boris V Zemelman, Franklin B Krasne, Michael R Drew
Dentate gyrus (DG) is widely thought to provide a teaching signal that enables hippocampal encoding of memories, but its role during retrieval is poorly understood. Some data and models suggest that DG plays no role in retrieval; others encourage the opposite conclusion. To resolve this controversy, we evaluated the effects of optogenetic inhibition of dorsal DG during context fear conditioning, recall, generalization, and extinction in male mice. We found that (1) inhibition during training impaired context fear acquisition; (2) inhibition during recall did not impair fear expression in the training context, unless mice had to distinguish between similar feared and neutral contexts; (3) inhibition increased generalization of fear to an unfamiliar context that was similar to a feared one and impaired fear expression in the conditioned context when it was similar to a neutral one; (4) inhibition impaired fear extinction...
May 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28546212/rapid-binge-like-eating-and-body-weight-gain-driven-by-zona-incerta-gaba-neuron-activation
#13
Xiaobing Zhang, Anthony N van den Pol
The neuronal substrate for binge eating, which can at times lead to obesity, is not clear. We find that optogenetic stimulation of mouse zona incerta (ZI) γ-aminobutyric acid (GABA) neurons or their axonal projections to paraventricular thalamus (PVT) excitatory neurons immediately (in 2 to 3 seconds) evoked binge-like eating. Minimal intermittent stimulation led to body weight gain; ZI GABA neuron ablation reduced weight. ZI stimulation generated 35% of normal 24-hour food intake in just 10 minutes. The ZI cells were excited by food deprivation and the gut hunger signal ghrelin...
May 26, 2017: Science
https://www.readbyqxmd.com/read/28544929/rem-sleep-and-memory
#14
REVIEW
Richard Boyce, Sylvain Williams, Antoine Adamantidis
Memory consolidation, a process which stabilizes recently acquired information into long-term storage, is thought to be optimized during sleep. Although recent evidence indicates that non-rapid-eye movement sleep (NREMs) is directly involved in memory consolidation, the role of rapid-eye movement sleep (REMs) in this process has remained controversial due to the extreme difficulty in experimentally isolating neural activity during REMs. Using a combination of electrophysiological recording and optogenetic techniques, recent work demonstrated for the first time that neural activity occurring specifically during REMs is required for spatial and contextual memory consolidation...
May 22, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28544018/next-generation-nucleic-acid-aptamers-with-two-base-modified-nucleotides-improve-the-binding-affinity-and-potency
#15
Rakesh Naduvile Veedu, Hadi AlShamaileh
Aptamers are single-stranded oligonucleotides (RNA or DNA) that can bind to their targets with high affinities and specificities because of their ability to adopt three-dimensional shapes in solution. Traditionally, aptamers are developed by SELEX (Systematic Evolution of Ligands by Exponential enrichment), a reiterative process involving selection by target molecule incubation with an oligonucleotide library and enrichment of the selected oligonucleotides by amplification. One drawback of current aptamer selection approach is the lack of diversity in the nucleic acid library with only four nucleobases compositions...
May 24, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28542563/evaluation-of-somatostatin-and-nucleolin-receptors-for-therapeutic-delivery-in-non-small-cell-lung-cancer-stem-cells-applying-the-somatostatin-analog-dotatate-and-the-nucleolin-targeting-aptamer-as1411
#16
Sif Holmboe, Pernille Lund Hansen, Helge Thisgaard, Ines Block, Carolin Müller, Niels Langkjær, Poul Flemming Høilund-Carlsen, Birgitte Brinkmann Olsen, Jan Mollenhauer
Cancer stem cells represent the putative tumor-driving subpopulation thought to account for drug resistance, relapse, and metastatic spread of epithelial and other cancer types. Accordingly, cell surface markers for therapeutic delivery to cancer stem cells are subject of intense research. Somatostatin receptor 2 and nucleolin are known to be overexpressed by various cancer types, which have elicited comprehensive efforts to explore their therapeutic utilization. Here, we evaluated somatostatin receptor 2 targeting and nucleolin targeting for therapeutic delivery to cancer stem cells from lung cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28542195/differential-excitatory-control-of-2-parallel-basket-cell-networks-in-amygdala-microcircuits
#17
Tibor Andrási, Judit M Veres, Laura Rovira-Esteban, Richárd Kozma, Attila Vikór, Erzsébet Gregori, Norbert Hájos
Information processing in neural networks depends on the connectivity among excitatory and inhibitory neurons. The presence of parallel, distinctly controlled local circuits within a cortical network may ensure an effective and dynamic regulation of microcircuit function. By applying a combination of optogenetics, electrophysiological recordings, and high resolution microscopic techniques, we uncovered the organizing principles of synaptic communication between principal neurons and basket cells in the basal nucleus of the amygdala...
May 2017: PLoS Biology
https://www.readbyqxmd.com/read/28541889/distinct-responses-of-purkinje-neurons-and-roles-of-simple-spikes-during-associative-motor-learning-in-larval-zebrafish
#18
Thomas C Harmon, Uri Magaram, David L McLean, Indira M Raman
To study cerebellar activity during learning, we made whole-cell recordings from larval zebrafish Purkinje cells while monitoring fictive swimming during associative conditioning. Fish learned to swim in response to visual stimulation preceding tactile stimulation of the tail. Learning was abolished by cerebellar ablation. All Purkinje cells showed task-related activity. Based on how many complex spikes emerged during learned swimming, they were classified as multiple, single, or zero complex spike (MCS, SCS, ZCS) cells...
May 25, 2017: ELife
https://www.readbyqxmd.com/read/28541659/multifunctional-screening-platform-for-the-highly-efficient-discovery-of-aptamers-with-high-affinity-and-specificity
#19
Shao-Li Hong, Ya-Tao Wan, Man Tang, Dai-Wen Pang, Zhi-Ling Zhang
Aptamers have attracted much attention as next generation of affinity reagents. Unfortunately, the selection efficiency remains a critical bottleneck for the widespread application of aptamers. Herein, to accelerate aptamers discovery, a multifunctional microfluidic selection platform was developed, on which the selection efficiency was greatly improved and high affinity and specificity aptamers were generated within two round selections. The multifunctional screening platform, precisely manipulating magnetic beads on micrometer scale, improved selection performance based on microfluidic continuous flow and enhanced the selection process control via in-situ monitoring and real-time evaluation...
May 25, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28541183/pausing-guides-rna-folding-to-populate-transiently-stable-rna-structures-for-riboswitch-based-transcription-regulation
#20
Hannah Steinert, Florian Sochor, Anna Wacker, Janina Buck, Christina Helmling, Fabian Hiller, Sara Keyhani, Jonas Noeske, Steffen Kaspar Grimm, Martin M Rudolph, Heiko Keller, Rachel Anne Mooney, Robert Landick, Beatrix Suess, Boris Fürtig, Jens Wöhnert, Harald Schwalbe
In bacteria, the regulation of gene expression by cis-acting transcriptional riboswitches located in the 5'-untranslated regions of messenger RNA requires the temporal synchronization of RNA synthesis and ligand binding-dependent conformational refolding. Ligand binding to the aptamer domain of the riboswitch induces premature termination of the mRNA synthesis of ligand-associated genes due to the coupled formation of 3'-structural elements acting as terminators. To date, there has been no high resolution structural description of the concerted process of synthesis and ligand-induced restructuring of the regulatory RNA element...
May 25, 2017: ELife
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