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https://www.readbyqxmd.com/read/27911495/synthesis-and-evaluation-of-caged-sirna-with-terminal-single-vitamin-e-modification
#1
Jiali Yang, Lijia Yu, Liangliang Zhang, Xingsu Long, Yuzhuo Ji, Xinjing Tang
RNA-induced gene silencing has been widely applied as a powerful research tool in drug development due to its sequence-specific degradation of target mRNA. Conditional regulation of gene functions with small interfering RNAs (siRNAs) is highly useful, especially when specific gene expression regulation with spatiotemporal resolution and amplitude is desired. Here, the synthesis of a series of new caged siRNAs with vitamin E (vitE) modification and/or a single photolabile linker at the 5' terminal is described...
December 1, 2016: Current Protocols in Nucleic Acid Chemistry
https://www.readbyqxmd.com/read/27911404/using-capillary-electrophoresis-to-quantify-organic-acids-from-plant-tissue-a-test-case-examining-coffea-arabica-seeds
#2
Michael Joe Vaughan, Ann Chanon, Joshua J Blakeslee
Carboxylic acids are organic acids containing one or more terminal carboxyl (COOH) functional groups. Short chain carboxylic acids (SCCAs; carboxylic acids containing three to six carbons), such as malate and citrate, are critical to the proper functioning of many biological systems, where they function in cellular respiration and can serve as indicators of cell health. In foods, organic acid content can have significant impact on taste, with increased SCCA levels resulting in a sour or "acid" taste. Because of this, methods for the rapid analysis of organic acid levels are of particular interest to the food and beverage industries...
November 12, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911380/method-for-identifying-small-molecule-inhibitors-of-the-protein-protein-interaction-between-hcn1-and-trip8b
#3
Ye Han, Kyle A Lyman, Matt Clutter, Gary E Schiltz, Quratul-Ain Ismail, Xiangying Cheng, Chi-Hao Luan, Dane M Chetkovich
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed ubiquitously throughout the brain, where they function to regulate the excitability of neurons. The subcellular distribution of these channels in pyramidal neurons of hippocampal area CA1 is regulated by tetratricopeptide repeat-containing Rab8b interacting protein (TRIP8b), an auxiliary subunit. Genetic knockout of HCN pore forming subunits or TRIP8b, both lead to an increase in antidepressant-like behavior, suggesting that limiting the function of HCN channels may be useful as a treatment for Major Depressive Disorder (MDD)...
November 11, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911318/the-correlation-between-inflammatory-biomarkers-and-polygenic-risk-score-in%C3%A2-alzheimer-s-disease
#4
Angharad R Morgan, Samuel Touchard, Caroline O'Hagan, Rebecca Sims, Elisa Majounie, Valentina Escott-Price, Lesley Jones, Julie Williams, B Paul Morgan
Plasma biomarkers to aid the early diagnosis of Alzheimer's disease (AD) or to monitor disease progression have long been sought and continue to be widely studied. Biomarkers that correlate with AD polygenic risk score, a measure of the polygenic architecture of the disease and highly predictive of AD status, would be excellent candidates. Therefore, we undertook a preliminary study to assess the association of plasma inflammatory biomarkers with an overall AD polygenic risk score as well as with an inflammation-specific AD polygenic risk score in a sample set of 93 AD cases...
November 26, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911261/targeted-deletion-of-akap7-in-dentate-granule-cells-impairs-spatial-discrimination
#5
Brian W Jones, Jennifer Deem, Thomas J Younts, Michael Weisenhaus, Christina A Sanford, Margaret C Slack, Jenesa Chin, Daniela Nachmanson, Alex McKennon, Pablo E Castillo, G Stanley McKnight
Protein Kinase A (PKA) mediates synaptic plasticity and is widely implicated in learning and memory. The hippocampal dentate gyrus (DG) is thought to be responsible for processing and encoding distinct contextual associations in response to highly similar inputs. The mossy fiber (MF) axons of the dentate granule cells convey strong excitatory drive to CA3 pyramidal neurons and express presynaptic, PKA-dependent forms of plasticity. Here, we demonstrate an essential role for the PKA anchoring protein, AKAP7, in mouse MF axons and terminals...
December 2, 2016: ELife
https://www.readbyqxmd.com/read/27911230/bromodomain-inhibitors-and-cancer-therapy-from-structures-to-applications
#6
Montserrat Pérez-Salvia, Manel Esteller
Aberrations in the epigenetic landscape are a hallmark of cancer. Alterations in enzymes that are "writers", "erasers", or "readers" of histone modification marks are common. Bromodomains are "readers" that bind acetylated lysines in histone tails. Their most important function is the regulation of gene transcription by the recruitment of different molecular partners. Moreover, proteins containing bromodomains are also epigenetic regulators, although little is known about the specific function of these domains...
December 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27910974/fine-tuning-terminal-solvent-ligands-to-rationally-enhance-the-energy-barrier-in-dinuclear-dysprosium-single-molecule-magnets
#7
Kun Zhang, Chen Yuan, Fu-Sheng Guo, Yi-Quan Zhang, Yao-Yu Wang
In search of simple approaches to rationally enhance the energy barriers in polynuclear dysprosium single-molecule magnets, a new system containing two structurally closely related dinuclear dysprosium complexes, namely [Dy2(L)2(DBM)2(DMF)2] (1) and [Dy2(L)2(DBM)2(DMA)2]·2DMA (2) (HDBM = dibenzoylmethane, H2L = 2-hydroxy-N'-(2-hydroxy-3-methoxybenzylidene)benzohydrazide), is introduced and the structure-dependent magnetic properties are investigated. The two complexes display only slight variations in the coordination geometries of the Dy(iii) ion but display remarkably different magnetic behaviors...
December 2, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/27910965/notable-deals-in-the-pharmaceutical-industry-in-the-third-quarter-of-2016
#8
E Cruces
During the third quarter of 2016, Cortellis Competitive Intelligence had 865 new deals added as part of its ongoing coverage of pharmaceutical licensing activity. This figure shows similar deal activity compared with the same quarter of 2015 (934), and 21% less than the previous quarter, although they had similar disclosed financial sizes in comparison with the first half of 2016. This article will focus on a number of the most valuable and notable deals forged during the quarter, as well as a selection of deals from some of the most prolific deal makers...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27910960/unc-5-homolog-b-unc5b-is-one-of-the-key-downstream-targets-of-n-%C3%AE-acetyltransferase-10-naa10
#9
Huiyu Xu, Yong Han, Bing Liu, Rong Li
N-α-acetyltransferase 10 (Naa10) displays alpha (N-terminal) acetyltransferase activity. It functions as a major modulator of cell growth and differentiation. Until now, a few downstream targets were found, but no studies have concerned about which gene is the early event of Naa10 downstream target. As we know, the earlier events may play more significant role in Naa10 pathway. Through construction of Naa10 stably knocked down H1299 cell line, we discovered cell morphological changes induced by Naa10. Moreover, potential function of Naa10 in cell morphogenesis was also indicated using cDNA microarray analysis of the Naa10 stably knock-down cell line...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910782/chemoprevention-of-colon-cancer-through-inhibition-of-angiogenesis-and-induction-of-apoptosis-by-nonsteroidal-anti-inflammatory-drugs
#10
Preety Ghanghas, Shelly Jain, Chandan Rana, Sankar Nath Sanyal
Cancer cells require nourishment for the growth of the primary tumor mass and spread of the metastatic colony. These needs are fulfilled by tumor-associated neovasculature known as angiogenesis, which also favors the transition from hyperplasia to neoplasia, that is, from a state of cellular multiplication to uncontrolled proliferation. Therefore, targeting angiogenesis is profitable as a mechanism to inhibit tumor growth. Furthermore, it is important to understand the cross-communication between vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in the neoplastic and proinflammatory milieu...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27910389/overview-of-diagnostic-performance-and-results-for-the-first-operation-phase-in-wendelstein-7-x-invited
#11
M Krychowiak, A Adnan, A Alonso, T Andreeva, J Baldzuhn, T Barbui, M Beurskens, W Biel, C Biedermann, B D Blackwell, H S Bosch, S Bozhenkov, R Brakel, T Bräuer, B Brotas de Carvalho, R Burhenn, B Buttenschön, A Cappa, G Cseh, A Czarnecka, A Dinklage, P Drews, A Dzikowicka, F Effenberg, M Endler, V Erckmann, T Estrada, O Ford, T Fornal, H Frerichs, G Fuchert, J Geiger, O Grulke, J H Harris, H J Hartfuß, D Hartmann, D Hathiramani, M Hirsch, U Höfel, S Jabłoński, M W Jakubowski, J Kaczmarczyk, T Klinger, S Klose, J Knauer, G Kocsis, R König, P Kornejew, A Krämer-Flecken, N Krawczyk, T Kremeyer, I Książek, M Kubkowska, A Langenberg, H P Laqua, M Laux, S Lazerson, Y Liang, S C Liu, A Lorenz, A O Marchuk, S Marsen, V Moncada, D Naujoks, H Neilson, O Neubauer, U Neuner, H Niemann, J W Oosterbeek, M Otte, N Pablant, E Pasch, T Sunn Pedersen, F Pisano, K Rahbarnia, L Ryć, O Schmitz, S Schmuck, W Schneider, T Schröder, H Schuhmacher, B Schweer, B Standley, T Stange, L Stephey, J Svensson, T Szabolics, T Szepesi, H Thomsen, J-M Travere, H Trimino Mora, H Tsuchiya, G M Weir, U Wenzel, A Werner, B Wiegel, T Windisch, R Wolf, G A Wurden, D Zhang, A Zimbal, S Zoletnik
Wendelstein 7-X, a superconducting optimized stellarator built in Greifswald/Germany, started its first plasmas with the last closed flux surface (LCFS) defined by 5 uncooled graphite limiters in December 2015. At the end of the 10 weeks long experimental campaign (OP1.1) more than 20 independent diagnostic systems were in operation, allowing detailed studies of many interesting plasma phenomena. For example, fast neutral gas manometers supported by video cameras (including one fast-frame camera with frame rates of tens of kHz) as well as visible cameras with different interference filters, with field of views covering all ten half-modules of the stellarator, discovered a MARFE-like radiation zone on the inboard side of machine module 4...
November 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/27909989/orexin-and-central-modulation-of-cardiovascular-and-respiratory-function
#12
Pascal Carrive, Tomoyuki Kuwaki
Orexin makes an important contribution to the regulation of cardiorespiratory function. When injected centrally under anesthesia, orexin increases blood pressure, heart rate, sympathetic nerve activity, and the amplitude and frequency of respiration. This is consistent with the location of orexin neurons in the hypothalamus and the distribution of orexin terminals at all levels of the central autonomic and respiratory network. These cardiorespiratory responses are components of arousal and are necessary to allow the expression of motivated behaviors...
December 2, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27909983/4-4-%C3%A3-resolution-cryo-em-structure-of-human-mtor-complex-1
#13
Huirong Yang, Jia Wang, Mengjie Liu, Xizi Chen, Min Huang, Dan Tan, Meng-Qiu Dong, Catherine C L Wong, Jiawei Wang, Yanhui Xu, Hong-Wei Wang
Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates signals from growth factors, cellular energy levels, stress and amino acids to control cell growth and proliferation through regulating translation, autophagy and metabolism. Here we determined the cryo-electron microscopy structure of human mTORC1 at 4.4 Å resolution. The mTORC1 comprises a dimer of heterotrimer (mTOR-Raptor-mLST8) mediated by the mTOR protein. The complex adopts a hollow rhomboid shape with 2-fold symmetry. Notably, mTORC1 shows intrinsic conformational dynamics...
December 1, 2016: Protein & Cell
https://www.readbyqxmd.com/read/27909922/production-of-biologically-active-recombinant-goose-fsh-in-a-single-chain-form-with-a-ctp-linker-sequence
#14
Hui Li, Huanxi Zhu, Qinming Qin, Mingming Lei, Zhendan Shi
FSH is a glycoprotein hormone secreted by the pituitary gland that is essential for gonadal development and reproductive function. In avian reproduction study, especially in avian reproduction hormone study, it is hindered by the lack of biologically active FSH. In order to overcome this shortcoming, we prepared recombinant goose FSH as a single chain molecule and tested its biological activities in the present study. Coding sequences for mature peptides of goose FSH α and β subunits were amplified from goose pituitary cDNA...
December 1, 2016: Molecular Biology Reports
https://www.readbyqxmd.com/read/27909841/the-shaping-of-intrinsic-membrane-potential-oscillations-positive-negative-feedback-ionic-resonance-amplification-nonlinearities-and-time-scales
#15
Horacio G Rotstein
The generation of intrinsic subthreshold (membrane potential) oscillations (STOs) in neuronal models requires the interaction between two processes: a relatively fast positive feedback that favors changes in voltage and a slower negative feedback that opposes these changes. These are provided by the so-called resonant and amplifying gating variables associated to the participating ionic currents. We investigate both the biophysical and dynamic mechanisms of generation of STOs and how their attributes (frequency and amplitude) depend on the model parameters for biophysical (conductance-based) models having qualitatively different types of resonant currents (activating and inactivating) and an amplifying current...
December 1, 2016: Journal of Computational Neuroscience
https://www.readbyqxmd.com/read/27909815/homoeologous-recombination-in-the-presence-of-ph1-gene-in-wheat
#16
Dal-Hoe Koo, Wenxuan Liu, Bernd Friebe, Bikram S Gill
A crossover (CO) and its cytological signature, the chiasma, are major features of eukaryotic meiosis. The formation of at least one CO/chiasma between homologous chromosome pairs is essential for accurate chromosome segregation at the first meiotic division and genetic recombination. Polyploid organisms with multiple sets of homoeologous chromosomes have evolved additional mechanisms for the regulation of CO/chiasma. In hexaploid wheat (2n = 6× = 42), this is accomplished by pairing homoeologous (Ph) genes, with Ph1 having the strongest effect on suppressing homoeologous recombination and homoeologous COs...
December 1, 2016: Chromosoma
https://www.readbyqxmd.com/read/27909723/inhibition-of-jnk-suppresses-autophagy-and-attenuates-insulin-resistance-in-a-rat-model-of-nonalcoholic-fatty-liver-disease
#17
Hua Yan, Yanqiong Gao, Ying Zhang
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, the pathological process of which is complex. Activation of the c‑Jun N‑terminal kinase (JNK) signaling pathway is associated with the mechanism underlying obesity-induced insulin resistance. Furthermore, the JNK signaling pathway and dysfunctional autophagy serve important roles in hepatic lipid metabolism. However, the exact role of JNK in autophagy and obesity‑induced insulin resistance is not fully understood. Therefore, the present study aimed to investigate the underlying mechanisms by which the JNK signaling pathway regulates autophagy and insulin resistance in fatty liver...
November 24, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27909717/restorative-effects-of-hydroxysafflor-yellow%C3%A2-a-on-hepatic-function-in-an-experimental-regression-model-of-hepatic-fibrosis-induced-by-carbon-tetrachloride
#18
Yanuo Li, Yan Shi, Yan Sun, Luying Liu, Xianyong Bai, Dong Wang, Hongxing Li
Hepatic fibrosis is a reversible pathological process, in which fibrotic tissue is excessively deposited in the liver during the repair process that follows hepatic injury. Early prevention or treatment of hepatic fibrosis has great significance on the treatment of chronic hepatic diseases. Hydroxysafflor yellow A (HSYA) is a water-soluble monomer extracted from safflower, which serves numerous pharmacological roles. However, it remains to be elucidated how HSYA regulates hepatic fibrogenesis. The aim of the present study was to reveal the possible mechanisms underlying the effects of HSYA on the prevention and treatment of hepatic fibrosis...
November 24, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27909707/in-vitro-study-of-the-host-responses-to-model-biomaterials-via-a-fibroblast-macrophage-co-culture-system
#19
Guoying Zhou, Andrea Liedmann, Chandralekha Chatterjee, Thomas Groth
Surface properties are believed to play important roles in initial inflammatory and subsequent wound healing/fibrotic responses after implantation of biomaterials. To investigate the surface property effect in mediating these host responses, we used an in vitro fibroblast/macrophage co-culture model established with a cell migration chamber, and a series of self-assembling monolayers (SAMs) bearing different terminal groups as model surfaces to study the effect of surface properties on macrophage fusion, fibroblast attachment, spreading morphology, proliferation, outgrowth, as well as pro-(interleukin-6) and anti-(interleukin-10) inflammatory cytokine production, expression of ED-A fibronectin (FN) and alpha-smooth muscle actin (α-SMA)...
December 2, 2016: Biomaterials Science
https://www.readbyqxmd.com/read/27909619/the-role-of-ultra-mini-percutaneous-nephrolithotomy-in-the-treatment-of-kidney-stones
#20
Abdulkadir Tepeler, İsmail Başıbüyük, Muhammed Tosun, Abdullah Armağan
OBJECTIVE: In our study we aimed to evaluate outcomes of ultra-mini-percutaneous nephrolithotomy (UMP) performed for the treatment of kidney stones. MATERIAL AND METHODS: Between October 2014 and September 2015, a single surgeon performed UMP on a total of 49 consecutive patients with symptomatic kidney stones at our center. Pregnants, anticogulant users, patients with bleeding diathesis pyonephrosis, and partial/complete staghorn stones were excluded from the study...
December 2016: Turkish Journal of Urology
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