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https://www.readbyqxmd.com/read/28344173/exploring-the-structure-permeation-relationship-of-topical-tricyclic-antidepressants-used-for-skin-analgesia
#1
Kuo-Sheng Liu, Tse-Hung Huang, Ibrahim A Aljuffali, En-Li Chen, Jhi-Joung Wang, Jia-You Fang
The purpose of this study was to evaluate the skin permeation of tricyclic antidepressants (TCAs) with propamine moiety to select candidates for the development of topical analgesics to treat cutaneous pain. We sought to establish the structure-permeation relationship (SPR) of topical TCAs. The lipophilicity, melting point, and aqueous solubility were determined to develop the physicochemical characterization. The TCA permeation into pig and nude mouse skins was estimated using Franz diffusion cell. TCAs and lidocaine were comparatively examined for cutaneous analgesia by pinprick assay...
March 23, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28344088/development-of-a-robust-and-validated-2d-qspr-model-for-sweetness-potency-of-diverse-functional-organic-molecules
#2
Probir Kumar Ojha, Kunal Roy
In the present report, we have developed a predictive QSPR model using only easily computable two-dimensional (2D) descriptors from diverse classes of sweetening agents to find out the key structural properties which regulate their sweet potency. The available data set was curated to remove salts, mixtures and compounds without having a definite structure. A k-fold double cross validation technique was employed for variable selection prior to development of the final model. The final model was developed using partial least squares (PLS) regression analysis and selected based on a mean absolute error (MAE) based criteria for the validation sets...
March 24, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28342664/a-novel-live-attenuated-anthrax-spore-vaccine-based-on-an-acapsular-bacillus-anthracis-sterne-strain-with-mutations-in-the-htra-lef-and-cya-genes
#3
Theodor Chitlaru, Ma'ayan Israeli, Shahar Rotem, Uri Elia, Erez Bar-Haim, Sharon Ehrlich, Ofer Cohen, Avigdor Shafferman
We recently reported the development of a novel, next-generation, live attenuated anthrax spore vaccine based on disruption of the htrA (High Temperature Requirement A) gene in the Bacillus anthracis Sterne veterinary vaccine strain. This vaccine exhibited a highly significant decrease in virulence in murine, guinea pig and rabbit animal models yet preserved the protective value of the parental Sterne strain. Here, we report the evaluation of additional mutations in the lef and cya genes, encoding for the toxin components lethal factor (LF) and edema factor (EF), to further attenuate the SterneΔhtrA strain and improve its compatibility for human use...
March 22, 2017: Vaccine
https://www.readbyqxmd.com/read/28341535/as-a-nucleus-enters-a-small-pore-chromatin-stretches-and-maintains-integrity-even-with-dna-breaks
#4
Jerome Irianto, Yuntao Xia, Charlotte R Pfeifer, Roger A Greenberg, Dennis E Discher
As a cell pushes or pulls its nucleus through a small constriction, the chromatin must distort and somehow maintain genomic stability despite ever-present double-strand breaks in the DNA. Here we visualize within a living cell the pore-size dependent deformation of a specific locus engineered into chromosome-1 and cleaved. An mCherry-tagged nuclease targets the submicron locus, causing DNA cleavage and recruiting repair factors such as GFP-53BP1 to a large region around the locus. Aspiration of a cell and its nucleus into a micropipette shows that chromatin aligns and stretches parallel to the pore...
February 7, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28340507/understanding-the-contribution-of-disulphide-bridges-to-the-folding-and-misfolding-of-an-anti-a%C3%AE-scfv
#5
Laia Montoliu-Gaya, Jose C Martínez, Sandra Villegas
ScFv-h3D6 is a single chain variable fragment that precludes Aβ peptide-induced cytotoxicity by withdrawing Aβ oligomers from the amyloid pathway to the worm-like pathway. Production of scFv molecules is not a straightforward procedure because of the occurrence of disulphide scrambled conformations generated in the refolding process. Here, we separately removed the disulphide bond of each domain and solved the scrambling problem; and then, we intended to compensate the loss of thermodynamic stability by adding three C-terminal elongation mutations previously described to stabilize the native fold of scFv-h3D6...
March 24, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28340044/oral-ghrelin-receptor-agonist-mk-0677-increases-serum-insulin-like-growth-factor-1-in-hemodialysis-patients-a-randomized-blinded-study
#6
Garland A Campbell, James T Patrie, Bruce D Gaylinn, Michael O Thorner, Warren K Bolton
Background: . Protein-energy wasting (PEW) in end-stage renal disease (ESRD) patients is associated with increased morbidity and mortality, but options for treatment are limited. Growth hormone (GH) increases insulin-like growth factor 1 (IGF-1), with improved nutritional parameters, but must be given subcutaneously and does not provide normal GH secretion patterns. MK-0677, an oral ghrelin receptor agonist (GRA), maintains normal GH secretion and increases lean body mass in normal subjects; it has not been studied in dialysis patients, an essential step in assessing efficacy and safety prior to clinical trials...
March 3, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339208/doubly-resonant-photonic-antenna-for-single-infrared-quantum-dot-imaging-at-telecommunication-wavelengths
#7
Zhihua Xie, Yannick Lefier, Miguel Angel Suarez, Mathieu Mivelle, Roland Salut, Jean-Marc Merolla, Thierry Grosjean
Colloidal quantum dots (CQDs) have drawn strong interest in the past for their high prospects in scientific, medical, and industrial applications. However, the full characterization of these quantum emitters is currently restricted to the visible wavelengths, and it remains a key challenge to optically probe single CQDs operating in the infrared spectral domain, which is targeted by a growing number of applications. Here, we report the first experimental detection and imaging at room temperature of single infrared CQDs operating at telecommunication wavelengths...
March 24, 2017: Nano Letters
https://www.readbyqxmd.com/read/28338595/3-0-nacl-adenosine-lidocaine-mg-2-alm-bolus-and-4-hours-drip-infusion-reduces-non-compressible-hemorrhage-by-60-in-a-rat-model
#8
Hayley L Letson, Geoffrey P Dobson
BACKGROUND: Noncompressible torso hemorrhage is the leading cause of potentially survivable trauma in far-forward combat environments. Our aim was to examine the effect of small-volume 3% NaCl adenosine, lidocaine and Mg (ALM) bolus and 0.9% NaCl/ALM 'drip' on survivability and cardiac/gut/kidney function in a rat model of hepatic hemorrhage and shock. METHODS: Male Sprague-Dawley rats (428±4 g) were anesthetized and randomly assigned to one of five groups (n=16): 1) Sham, 2) No Treatment, 3) Saline controls, 4) ALM therapy and 5) Hextend®...
March 23, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28336611/self-assembly-of-genetically-encoded-dna-protein-hybrid-nanoscale-shapes
#9
Florian Praetorius, Hendrik Dietz
We describe an approach to bottom-up fabrication that allows integration of the functional diversity of proteins into designed three-dimensional structural frameworks. A set of custom staple proteins based on transcription activator-like effector proteins folds a double-stranded DNA template into a user-defined shape. Each staple protein is designed to recognize and closely link two distinct double-helical DNA sequences at separate positions on the template. We present design rules for constructing megadalton-scale DNA-protein hybrid shapes; introduce various structural motifs, such as custom curvature, corners, and vertices; and describe principles for creating multilayer DNA-protein objects with enhanced rigidity...
March 24, 2017: Science
https://www.readbyqxmd.com/read/28335582/nonradiative-relaxation-mechanisms-of-uv-excited-phenylalanine-residues-a-comparative-computational-study
#10
Momir Mališ, Nađa Došlić
The present work is directed toward understanding the mechanisms of excited state deactivation in three neutral model peptides containing the phenylalanine residue. The excited state dynamics of theγL(g+)folded form of N-acetylphenylalaninylamide (NAPA B) and its amide-N-methylated derivative (NAPMA B) is reviewed and compared to the dynamics of the monohydrated structure of NAPA (NAPAH). The goal is to unravel how the environment, and in particular solvation, impacts the photodynamics of peptides. The systems are investigated using reaction path calculations and surface hopping nonadiabatic dynamics based on the coupled cluster doubles (CC2) method and time-dependent density functional theory...
March 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28333648/mobile-stride-length-estimation-with-deep-convolutional-neural-networks
#11
Julius Hannink, Thomas Kautz, Cristian Pasluosta, Jens Barth, Samuel Schulein, Karl-Gunter Gassmann, Jochen Klucken, Bjoern Eskofier
OBJECTIVE: Accurate estimation of spatial gait characteristics is critical to assess motor impairments resulting from neurological or musculoskeletal disease. Currently, however, methodological constraints limit clinical applicability of state-ofthe- art double integration approaches to gait patterns with a clear zero-velocity phase. METHODS: We describe a novel approach to stride length estimation that uses deep convolutional neural networks to map stride-specific inertial sensor data to the resulting stride length...
March 9, 2017: IEEE Journal of Biomedical and Health Informatics
https://www.readbyqxmd.com/read/28333185/randomized-open-trial-comparing-a-modified-double-lumen-needle-follicular-flushing-system-with-a-single-lumen-aspiration-needle-in-ivf-patients-with-poor-ovarian-response
#12
Kyra von Horn, Marion Depenbusch, Askan Schultze-Mosgau, Georg Griesinger
STUDY QUESTION: Is a modified double-lumen aspiration needle system with follicular flushing able to increase the mean oocyte yield by at least one in poor response IVF patients as compared to single-lumen needle aspiration without flushing? SUMMARY ANSWER: Follicular flushing with the modified flushing system did not increase the number of oocytes, but increased the procedure duration. WHAT IS KNOWN ALREADY: Most studies on follicular flushing were performed with conventional double-lumen needles in patients who were normal responders...
February 9, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28330872/nadph-oxidase-1-supports-proliferation-of-colon-cancer-cells-by-modulating-reactive-oxygen-species-dependent-signal-transduction
#13
Agnes Juhasz, Susan Markel, Shikha Gaur, Han Liu, Jiamo Lu, Guojian Jiang, Xiwei Wu, Smitha Antony, Yongzhong Wu, Giovanni Melillo, Jennifer L Meitzler, Diana C Haines, Donna Butcher, Krishnendu Roy, James H Doroshow
Reactive oxygen species (ROS) play a critical role in cell signaling and proliferation. NADPH oxidase 1 (NOX1), a membrane-bound flavin dehydrogenase that generates superoxide, is highly expressed in colon cancer. To investigate the role that NOX1 plays in colon cancer growth, we used shRNA to decrease NOX1 expression stably in HT-29 human colon cancer cells. The 80-90% decrease in NOX1 expression achieved by RNAi produced a significant decline in ROS production and a G1/S block that translated into a 2-3-fold increase in tumor cell doubling time without increased apoptosis...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28330633/association-between-psychotropic-and-cardiovascular-iatrogenic-alerts-and-risk-of-hospitalizations-in-elderly-people-treated-for-dementia-a-self-controlled-case-series-study-based-on-the-matching-of-2-french-health-insurance-databases
#14
Lorene Zerah, Jacques Boddaert, Armelle Leperre-Desplanques, Dominique Bonnet-Zamponi, Marc Verny, Jean Deligne, Pierre-Yves Boelle
BACKGROUND: Elderly people are at risk of repeated hospitalizations, some of which may be drug related and preventable. In 2011, a group of French healthcare experts selected 5 iatrogenic alerts (IAs), based on criteria identified in a literature search and from their professional experience, to assess the appropriateness of medication in elderly patients. OBJECTIVES: Our objective was to examine the association between hospitalizations and IAs in elderly patients treated for Alzheimer disease who are particularly sensitive to adverse drug events...
March 18, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/28327504/theoretical-study-of-monolayer-and-double-layer-waveguide-love-wave-sensors-for-achieving-high-sensitivity
#15
Shuangming Li, Ying Wan, Chunhai Fan, Yan Su
Love wave sensors have been widely used for sensing applications. In this work, we introduce the theoretical analysis of the monolayer and double-layer waveguide Love wave sensors. The velocity, particle displacement and energy distribution of Love waves were analyzed. Using the variations of the energy repartition, the sensitivity coefficients of Love wave sensors were calculated. To achieve a higher sensitivity coefficient, a thin gold layer was added as the second waveguide on top of the silicon dioxide (SiO₂) waveguide-based, 36 degree-rotated, Y-cut, X-propagating lithium tantalate (36° YX LiTaO₃) Love wave sensor...
March 22, 2017: Sensors
https://www.readbyqxmd.com/read/28325874/ion-and-inhibitor-binding-of-the-double-ring-ion-selectivity-filter-of-the-mitochondrial-calcium-uniporter
#16
Chan Cao, Shuqing Wang, Tanxing Cui, Xun-Cheng Su, James J Chou
The calcium (Ca(2+)) uniporter of mitochondria is a holocomplex consisting of the Ca(2+)-conducting channel, known as mitochondrial calcium uniporter (MCU), and several accessory and regulatory components. A previous electrophysiology study found that the uniporter has high Ca(2+) selectivity and conductance and this depends critically on the conserved amino acid sequence motif, DXXE (Asp-X-X-Glu) of MCU. A recent NMR structure of the MCU channel from Caenorhabditis elegans revealed that the DXXE forms two parallel carboxylate rings at the channel entrance that seem to serve as the ion selectivity filter, although direct ion interaction of this structural motif has not been addressed...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28325847/specialized-diacylglycerol-acyltransferase-contributes-to-extreme-fatty-acid-content-of-cuphea-seed-oil
#17
Umidjon Iskandarov, Jillian E Silva, Hae Jin Kim, Mariette Andersson, Rebecca E Cahoon, Keithanne Mockaitis, Edgar B Cahoon
Seed oils of many Cuphea sp. contain >90% of medium-chain fatty acids, such as decanoic acid (10:0). These seed oils, which are among the most compositionally variant in the plant kingdom, arise from specialized fatty acid biosynthetic enzymes and specialized acyltransferases. These include lysophosphatidic acid acyltransferases (LPAT) and diacylglycerol acyltransferases (DGAT) that are required for successive acylation of medium-chain fatty acids in the sn-2 and sn-3 positions of seed triacylglycerols (TAGs)...
March 21, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28322775/pregnancy-and-birth-outcomes-in-couples-with-infertility-with-and-without-assisted-reproductive-technology-with-an-emphasis-on-us-population-based-studies
#18
REVIEW
Barbara Luke
Infertility, defined as the inability to conceive within one year of unprotected intercourse, affects an estimated 80 million individuals worldwide, or 10-15 percent of couples of reproductive age. Assisted reproductive technology (ART) includes all infertility treatments to achieve conception; in vitro fertilization (IVF) is the process by which an oocyte is fertilized by semen outside the body; non-IVF ART treatments include ovulation induction, artificial insemination, and intrauterine insemination. Use of ART has risen steadily in the United States during the past two decades due to several reasons, including childbearing at older maternal ages and increasing insurance coverage...
March 18, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28320463/hyaluronan-coating-improves-liver-engraftment-of-transplanted-human-biliary-tree-stem-progenitor-cells
#19
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/28320116/in-vitro-non-viral-murine-pro-neurotrophin-3-gene-transfer-into-rat-bone-marrow-stromal-cells
#20
Shahram Darabi, Taki Tiraihi, AliReza Delshad, Majid Sadeghizadeh, Wisam Khalil, Taher Taheri
Neurotrophin 3 (NT-3) is an important factor for promoting prenatal neural development, as well as regeneration, axogenesis and plasticity in postnatal life. Therapy with NT-3 was reported to improve the condition of patients suffering from degenerative diseases and traumatic injuries, however, the disadvantage of NT-3 protein delivery is its short half-life, thus our alternative approach is the use of NT-3 gene therapy. In this study, the bone marrow stromal cells (BMSCs) were isolated from adult rats, cultured for 4 passages and transfected with either pEGFP-N1 or a constructed vector containing murine proNT-3 (pSecTag2/HygroB-murine proNT-3) using Lipofectamine 2000 followed by Hygromycin B (200mg/kg)...
April 15, 2017: Journal of the Neurological Sciences
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