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https://www.readbyqxmd.com/read/28434044/faulty-rna-splicing-consequences-and-therapeutic-opportunities-in-brain-and-muscle-disorders
#1
REVIEW
Vittoria Pagliarini, Piergiorgio La Rosa, Claudio Sette
Alternative splicing is a powerful mechanism that largely expands the coding potential of eukaryotic genomes. Indeed, its complex and flexible regulation is exploited by cells to adapt to various environmental conditions, through production of protein variants displaying different functions. Such flexibility, however, is accompanied by high risk of errors, and dysregulation of splicing is now recognized as an important factor in human diseases. Notably, the RNA-based nature of splicing, which involves high specificity through base pair recognition, offers a remarkable therapeutic opportunity by allowing design of tools with elevated target selectivity...
April 22, 2017: Human Genetics
https://www.readbyqxmd.com/read/28434030/spatial-and-temporal-distributions-of-air-pollutants-and-size-distribution-of-aerosols-over-central-and-eastern-china
#2
Honglei Wang, Lijuan Shen, Bin Zhu, Hanqing Kang, Xuewei Hou, Qing Miao, Yang Yang, Shuangshuang Shi
The origins and spatial and temporal distributions of air pollutants (PM2.5, PM10, CO, SO2, NO2 and O3) during May to June of 2015 were investigated using data from 1490 monitoring sites in China. Aerosol number concentrations and meteorological data from Shijiazhuang, Nanjing, and Suzhou were combined with the MIX Asian emission data and the HYSPLIT model. Furthermore, the diurnal variation, size distribution, and main sources of air pollutants and aerosols were selectively characterized in the North China Plain (NCP) and the Yangtze River Delta (YRD)...
April 22, 2017: Archives of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/28433941/self-assembled-dual-responsive-micelles-stabilized-with-protein-for-co-delivery-of-drug-and-sirna-in-cancer-therapy
#3
M R Aji Alex, Chetan Nehate, Srivani Veeranarayanan, D Sakthi Kumar, Ritu Kulshreshtha, Veena Koul
Design of safe and efficient vehicles for the combinatorial delivery of drugs and genetic agents is an emerging requisite for achieving enhanced therapeutic effect in cancer. Even though several nanoplatforms have been explored for the co-delivery of drugs and genetic materials the translation of these systems to clinical phase is still a challenge, mainly due to tedious synthesis procedures, lack of serum stability, inefficient scalability etc. Here in, we report development of reduction and pH sensitive polymeric graft of low molecular weight poly (styrene -alt -maleic anhydride) and evaluation of its efficacy in co-delivering drug and siRNA...
April 17, 2017: Biomaterials
https://www.readbyqxmd.com/read/28433778/novel-lipid-mimetic-prodrugs-delivering-active-compounds-to-adipose-tissue
#4
Andrea Mattarei, Andrea Rossa, Veronica Bombardelli, Michele Azzolini, Martina La Spina, Cristina Paradisi, Mario Zoratti, Lucia Biasutto
Obesity and associated pathologies are a dramatically growing problem. New therapies to prevent and/or cure them are strongly needed. Adipose tissue is a logical target for pharmacological intervention, since it is now recognized to exert an important endocrine function, secreting a variety of adipokines affecting, for example, adiposity and insulin resistance. This proof of principle work focuses on the development of novel lipid-mimetic prodrugs reaching fat deposits by the same lymphatic absorption route followed by dietary triglycerides...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28433681/n-aryl-n-ethyleneaminothioureas-effectively-inhibit-acetylcholinesterase-1-from-disease-transmitting-mosquitoes
#5
Sofie Knutsson, Tomas Kindahl, Cecilia Engdahl, Dariush Nikjoo, Nina Forsgren, Stanley Kitur, Fredrik Ekström, Luna Kamau, Anna Linusson
Vector control of disease-transmitting mosquitoes by insecticides has a central role in reducing the number of parasitic- and viral infection cases. The currently used insecticides are efficient, but safety concerns and the development of insecticide-resistant mosquito strains warrant the search for alternative compound classes for vector control. Here, we have designed and synthesized thiourea-based compounds as non-covalent inhibitors of acetylcholinesterase 1 (AChE1) from the mosquitoes Anopheles gambiae (An...
March 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28433580/description-of-a-novel-multiplex-avidity-assay-for-evaluating-hpv-antibodies
#6
Allison M Brady, Elizabeth R Unger, Gitika Panicker
Limited data exists regarding antibody avidity for human papillomavirus (HPV). We describe development of a multiplex electrochemiluminescent avidity ELISA for four HPV types (HPV 6, 11, 16, 18) by adding a dissociating step to our established multiplex HPV VLP ELISA. Initial experiments exploring ammonium thiocyanate, sodium thiocyanate and guanidine hydrochloride (GuHCl) as dissociating agents identified GuHCl as most promising. Dissociation conditions with GuHCl were varied (concentration, incubation time, temperature) to select conditions with minimal impact on VLP integrity as measured with monoclonal antibodies to conformational epitopes...
April 19, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28433433/design-selection-and-development-of-cyclic-peptide-ligands-for-human-erythropoietin
#7
William S Kish, Hiroyuki Sachi, Amith D Naik, Matthew K Roach, Benjamin G Bobay, Robert K Blackburn, Stefano Menegatti, Ruben G Carbonell
This work presents the selection and characterization of erythropoietin (EPO)-binding cyclic peptide ligands. The sequences were selected by screening a focused library of cyclic depsipeptides cyclo[(Nα-Ac)Dap(A)-X1-X6-AE], whose structure and amino acid compositions were tailored to mimic the EPO receptor. The sequences identified through library screening were synthesized on chromatographic resin and characterized via binding-and-elution studies against EPO to select a pool of candidate ligands. Sequences with higher hydrophobicity consistently showed stronger binding to EPO, with the exception of FSLLSH, which was noted for its lower hydrophobicity and high EPO binding...
April 12, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28433243/cocr-f75-scaffolds-produced-by-additive-manufacturing-influence-of-chemical-etching-on-powder-removal-and-mechanical-performance
#8
Brecht Van Hooreweder, Karel Lietaert, Bram Neirinck, Nicholas Lippiatt, Martine Wevers
Additive manufacturing techniques such as Selective Laser Melting (SLM) allow carefully controlled production of complex porous structures such as scaffolds. These advanced structures can offer many interesting advantages over conventionally produced products in terms of biological response and patient specific design. The surface finish of AM parts is often poor because of the layer wise nature of the process and adhering particles. Loosening of these particles after implantation should be avoided, as this could put the patient's health at risk...
June 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28433057/low-cost-humic-acid-bonded-silica-as-an-effective-solid-phase-extraction-sorbent-for-convenient-determination-of-aflatoxins-in-edible-oils
#9
Neng-Zhi Zhou, Ping Liu, Xiao-Chuan Su, Yan-Hua Liao, Ning-Sheng Lei, Yong-Hong Liang, Shao-Huan Zhou, Wen-Si Lin, Jie Chen, Yu-Qi Feng, Yang Tang
Aflatoxins (AFs) are highly toxic, mutagenic, carcinogenic, and teratogenic secondary metabolites produced by the toxigenic fungi Aspergillus flavus and Aspergillus parasiticus. AFs tend to contaminate a wide range of foods which is a serious and recurring food safety problem worldwide. Currently, immunoaffinity chromatography (IAC) has become the most conventional sample clean-up method for determining AFs in foodstuffs. However, IAC method is limited in the large-scale food analysis because it requires the use of expensive disposable cartridges and the IA procedure is time-consuming...
June 1, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28433027/potential-of-mean-force-for-insertion-of-antimicrobial-peptide-melittin-into-a-pore-in-mixed-dopc-dopg-lipid-bilayer-by-molecular-dynamics-simulation
#10
Yuan Lyu, Ning Xiang, Xiao Zhu, Ganesan Narsimhan
Antimicrobial peptides (AMPs) inactivate microorganisms by forming transmembrane pores in a cell membrane through adsorption and aggregation. Energetics of addition of an AMP to a transmembrane pore is important for evaluation of its formation and growth. Such information is essential for the characterization of pore forming ability of peptides in cell membranes. This study quantifies the potential of mean force through molecular dynamics (MD) simulation for the addition of melittin, a naturally occurring AMP, into a DOPC/DOPG mixed bilayer, a mimic of bacterial membrane, for different extents of insertion into either a bilayer or a pore consisting of three to six transmembrane peptides...
April 21, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28433025/a-combined-theoretical-and-experimental-study-of-phenol-acetylene-n-n-%C3%A2-7-clusters
#11
Gurmeet Singh, Apurba Nandi, Shridhar R Gadre, Takashi Chiba, Asuka Fujii
Structures and vibrational spectra of phenol-(acetylene)n (Ph(Ac)n) clusters are studied by a combination of theoretical calculations and infrared (IR) spectroscopy. The molecular electrostatic potential features are utilized for generating trial geometries of the medium-sized Ph(Ac)n (n = 1, 2, 4, 6, and 7) clusters. These initial geometries are subjected to geometry optimization within the second-order Møller-Plesset (MP2) theory, employing correlation consistent aug-cc-pVDZ (aVDZ) basis set. Minimal nature of the reported structures is confirmed by doing vibrational frequency run at MP2/aVDZ level of theory using full calculations for n = 1 and 2 and employing grafting based molecular tailoring approach for the n = 4, 6, and 7...
April 21, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28432957/nanoencapsulation-strategies-for-the-delivery-of-novel-bifunctional-antioxidant-%C3%AF-1-selective-ligands
#12
Claudia Carbone, Emanuela Arena, Veronica Pepe, Orazio Prezzavento, Ivana Cacciatore, Hasan Turkez, Agostino Marrazzo, Antonio Di Stefano, Giovanni Puglisi
Nowadays sigma-1 receptors are considered as new therapeutic objectives for central nervous system neurodegenerative diseases. Among different molecules, alpha lipoic acid has been identified as a natural potent antioxidant drug, whose therapeutic efficacy is limited by its many drawbacks, such as fast metabolism, poor bioavailability and high physico-chemical instability. Alfa-lipoic acid derivatives have been recently developed demonstrating their neuroprotective activity and effectiveness in different types of oxidative stress...
April 12, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28432793/single-and-dual-cyclodextrins-systems-for-the-enantiomeric-and-diastereoisomeric-separations-of-structurally-related-dihydropyridone-analogues
#13
Thibaut Delplanques, Rajaa Boulahjar, Julie Charton, Corentin Houze, Michaël Howsam, Anne-Catherine Servais, Marianne Fillet, Emmanuelle Lipka
Cyclodextrin capillary electrophoresis methods (CD-CZE) were developed for complete enantiomeric and diastereoisomeric separations of a series of ten dihydropyridone analogues, of which eight were neutral, one was anionic and one was cationic. Ten different systems comprising one or two cyclodextrins were found to successfully separate the isomers thanks to a screening approach. Among the tested cyclodextrins, HS-γ-CD, either in a single or in a dual system, in a phosphate buffer using capillaries dynamically coated with polyethylene oxide (PEO), and SBE-β-CD, either in a single or in a dual system, in a borate buffer using uncoated capillaries, were the most selective selectors...
April 22, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28432687/impact-of-caring-for-patients-with-severe-and-complex-disabilities-on-health-care-workers-quality-of-life-determinants-and-specificities
#14
Marie-Christine Rousseau, Karine Baumstarck, Tanguy Leroy, Cherazad Khaldi-Cherif, Catherine Brisse, Laurent Boyer, Noémie Resseguier, Claire Morando, Thierry Billette De Villemeur, Pascal Auquier
AIM: Individuals with severe and complex disabilities, defined by a combination of profound intellectual impairment and serious motor deficit resulting in extreme dependence, often remain in hospital or at residential facilities. The aim of this study was to identify the determinants of quality of life (QoL) of 238 health care workers (HCWs) caring for individuals with severe and complex disabilities. METHOD: We conducted a cross-sectional study. The recruitment of the HCWs was performed in five French centres specializing in patients with severe and complex disabilities...
April 22, 2017: Developmental Medicine and Child Neurology
https://www.readbyqxmd.com/read/28432357/in-silico-drug-discovery-approach-targeting-receptor-tyrosine-kinase-like-orphan-receptor-1-for-cancer-treatment
#15
Onkar Nath, Archana Singh, Indrakant K Singh
Receptor tyrosine kinases (RTK) are important cell signaling molecules that influence many cellular processes. Receptor tyrosine kinase such as orphan receptor 1 (Ror1), a surface antigen, is a member of the RTK family of Ror, which plays a crucial role in cancers that have high-grade histology. As Ror1 has been implicated to be a potential target for cancer therapy, we selected this protein for further investigation. The secondary and tertiary structure of this protein was determined, which revealed that this protein contained three β-sheets, seven α-helices, and coils...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432260/dual-histone-reader-zmynd8-inhibits-cancer-cell-invasion-by-positively-regulating-epithelial-genes
#16
Moitri Basu, Isha Sengupta, Wasim Khan, Dushyant Kumar Srivastava, Partha Chakrabarti, Siddhartha Roy, Chandrima Das
Enhanced migratory potential and invasiveness of cancer cells attribute crucially.in cancer progression. These phenotypes are achieved by precise alteration of invasion-associated genes through local epigenetic modifications which are recognized by a class of proteins termed as chromatin reader. ZMYND8 (zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8), a key component of transcription regulatory network, has been recently shown to be a novel reader of H3.1K36Me2/H4K16Ac marks. Through differential gene expression analysis upon silencing this chromatin reader, we identified a subset of genes involved in cell proliferation and invasion/migration regulated by ZMYND8...
April 21, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28432139/feature-selective-attention-adaptively-shifts-noise-correlations-in-primary-auditory-cortex
#17
Joshua Downer, Brittany Rapone, Jessica Verhein, Kevin N O'Connor, Mitchell L Sutter
Sensory environments often contain an overwhelming amount of information, with both relevant and irrelevant information competing for neural resources. Feature attention mediates this competition by selecting the sensory features needed to form a coherent percept. How attention affects the activity of populations of neurons to support this process is poorly understood because population coding is typically studied through simulations in which one sensory feature is encoded without competition. Therefore, to study the effects of feature attention on population-based neural coding, investigations must be extended to include stimuli with both relevant and irrelevant features...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28432052/genomic-instability-in-cancer-teetering-on-the-limit-of-tolerance
#18
REVIEW
Noemi Andor, Carlo C Maley, Hanlee P Ji
Cancer genomic instability contributes to the phenomenon of intratumoral genetic heterogeneity, provides the genetic diversity required for natural selection, and enables the extensive phenotypic diversity that is frequently observed among patients. Genomic instability has previously been associated with poor prognosis. However, we have evidence that for solid tumors of epithelial origin, extreme levels of genomic instability, where more than 75% of the genome is subject to somatic copy number alterations, are associated with a potentially better prognosis compared with intermediate levels under this threshold...
April 21, 2017: Cancer Research
https://www.readbyqxmd.com/read/28431929/effects-of-naturally-occurring-charged-mutations-on-the-structure-stability-and-binding-of-the-pin1-ww-domain
#19
Xiaoya Qiao, Ying Liu, Liting Luo, Lei Chen, Caixian Zhao, Xuanjun Ai
Pin1 is a peptidyl-prolyl cis-trans isomerase, whose WW domain specifically recognizes the pSer/Thr-Pro motif. Pin1 is involved in multiple phosphorylation events that regulate the activities of various substrates, and Pin1 deregulation has been reported in various diseases, including cancer and Alzheimer's disease. The WW domain of Pin1 has been used as a small model protein to investigate the folding mechanisms of the β-sheet structure by studying the effect of mutations or its naturally occurring variants...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28431748/a-benchtop-biorobotic-platform-for-in-vitro-observation-of-muscle-tendon-dynamics-with-parallel-mechanical-assistance-from-an-elastic-exoskeleton
#20
Benjamin D Robertson, Siddarth Vadakkeveedu, Gregory S Sawicki
We present a novel biorobotic framework comprised of a biological muscle-tendon unit (MTU) mechanically coupled to a feedback controlled robotic environment simulation that mimics in vivo inertial/gravitational loading and mechanical assistance from a parallel elastic exoskeleton. Using this system, we applied select combinations of biological muscle activation (modulated with rate-coded direct neural stimulation) and parallel elastic assistance (applied via closed-loop mechanical environment simulation) hypothesized to mimic human behavior based on previously published modeling studies...
March 21, 2017: Journal of Biomechanics
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