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https://www.readbyqxmd.com/read/29671263/high-throughput-screening-method-to-identify-alternative-splicing-regulators
#1
Cheryl Stork, Sika Zheng
Misregulation of alternative pre-mRNA splicing contributes to various diseases. Understanding how alternative splicing is regulated paves the way to modulating or correcting molecular pathogenesis of the diseases. Alternative splicing is typically regulated by trans RNA binding proteins and their upstream modulators. Identification of these splicing regulators has been difficult and traditionally done piecemeal. High-throughput screening strategies to find multiple regulators of exon splicing have great potential to accelerate the discovery process, but typically confront low sensitivity and specificity of splicing assays...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29671087/severe-adverse-reactions-following-ketoconazole-fluconazole-and-environmental-exposures-a-case-report
#2
Allan Lieberman, Luke Curtis
In this case report, we describe a 66-year-old man who developed multiple adverse reactions beginning at age 56 after exposure to several azole antifungal drugs including ketoconazole and fluconazole. He also had a history of more than 40 years exposure to chemicals including pesticides, wood preservatives, fertilizers, and welding chemicals. His reactions involved dehydration (requiring several liters of intravenous fluids in less than an hour to alleviate this condition), angioedema, nausea, tinnitus, hypotension, and difficulty breathing...
April 18, 2018: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/29669112/a-critical-appraisal-of-the-sensitivity-of-in-vivo-genotoxicity-assays-in-detecting-human-carcinogens
#3
Andreas Zeller, Stefan Pfuhler, Silvio Albertini, Frank Bringezu, Andreas Czich, Yasmin Dietz, Rolf Fautz, Nicola J Hewitt, Annette Kirst, Peter Kasper
Genotoxicity testing is an important part of standard safety testing strategies. Animal studies have always been a key component, either as a mandatory part of the regulatory test battery, or to follow-up questionable in vitro findings. The strengths and weaknesses of in vivo assays is a continuous matter of debate, including their capacity to predict (human) carcinogenicity. We have therefore analysed the sensitivity of five routinely used in vivo tests to determine, in addition to other aspects, which tests or combination of tests best identify 73 chemicals classified as IARC Group 1 and 2A carcinogens...
April 13, 2018: Mutagenesis
https://www.readbyqxmd.com/read/29665293/multi-responsive-supramolecular-gels-based-on-charge-transfer-interactions
#4
Chen Li, Chengshuo Shen, Jiucheng Nie, Huibin Qiu
We report the co-assembly of aromatic donor (D) and acceptor (A) molecules into purple sponge-like supramolecular gels through susceptible charge transfer interactions with the aid of solvophobic interactions. The gel retained intact with the addition of up to 23% (v/v) of nonpolar good solvents, such as toluene and xylene, but dissociated in the presence of < 2% (v/v) of polar solvents, such as tetrahydrofuran, ethyl acetate, and alcohols, with highly distinguishable changes of color. Notably, the gel disappeared in 1 min and the solution turned blue when 0...
April 17, 2018: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/29662955/multiple-heteroatom-substitution-to-graphene-nanoribbon
#5
Shigeki Kawai, Soichiro Nakatsuka, Takuji Hatakeyama, Rémy Pawlak, Tobias Meier, John Tracey, Ernst Meyer, Adam S Foster
Substituting heteroatoms into nanostructured graphene elements, such as graphene nanoribbons, offers the possibility for atomic engineering of electronic properties. To characterize these substitutions, functionalized atomic force microscopy (AFM)-a tool to directly resolve chemical structures-is one of the most promising tools, yet the chemical analysis of heteroatoms has been rarely performed. We synthesized multiple heteroatom-substituted graphene nanoribbons and showed that AFM can directly resolve elemental differences and can be correlated to the van der Waals radii, as well as the modulated local electron density caused by the substitution...
April 2018: Science Advances
https://www.readbyqxmd.com/read/29660612/perfluoroalkyl-substances-and-glycemic-status-in-pregnant-danish-women-the-odense-child-cohort
#6
Richard Christian Jensen, Dorte Glintborg, Clara Amalie Gade Timmermann, Flemming Nielsen, Henriette Boye Kyhl, Helle Raun Andersen, Philippe Grandjean, Tina Kold Jensen, Marianne Andersen
BACKGROUND: Perfluoroalkyl substances (PFASs) are persistent chemicals with suspected endocrine disrupting abilities applied in consumer products. PFASs have potentially modulating effects on glucose homeostasis. Insulin resistance prevails during third trimester of pregnancy, and this challenge of glucose homeostasis may reveal putative effects of PFAS concentrations on glycemic status. OBJECTIVE: To investigate associations between five serum PFASs and glucose-related outcomes in pregnant Danish women based on their risk of gestational diabetes mellitus (GDM)...
April 13, 2018: Environment International
https://www.readbyqxmd.com/read/29658714/activation-of-trpv3-by-wood-smoke-particles-and-roles-in-pneumotoxicity
#7
Cassandra Deering-Rice, Nam Nguyen, Zhenyu Lu, James Cox, Darien Shapiro, Erin G Romero, Virginia K Mitchell, Katherine L Burrell, John M Veranth, Christopher A Reilly
Wood/biomass smoke particulate materials (WBSPM) are pneumotoxic, but mechanisms by which these materials affect lung cells are not fully understood. We previously identified transient receptor potential (TRP) ankyrin-1 as a sensor for electrophiles in WBSPM and hypothesized that other TRP channels expressed by lung cells might also be activated by WBSPM, contributing to pneumotoxicity. Screening TRP channel activation by WBSPM using calcium flux assays revealed TRPV3 activation by materials obtained from burning multiple types of wood under fixed conditions...
April 16, 2018: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29658277/cavitation-enhancement-increases-the-efficiency-and-consistency-of-chromatin-fragmentation-from-fixed-cells-for-downstream-quantitative-applications
#8
Anna M Chiarella, Austin L Quimby, Marjan Mehrab-Mohseni, Brian Velasco, Sandeep K Kasoji, Ian Davis, Paul A Dayton, Nathaniel A Hathaway, Samantha Pattenden
One of the most sensitive, time consuming, and variable steps of chromatin immunoprecipitation (ChIP) is chromatin sonication. Traditionally, this process can take hours to properly sonicate enough chromatin for multiple ChIP assays. Further, the length of sheared DNA is often inconsistent. In order to faithfully measure chemical and structural changes at the chromatin level, sonication needs to be reliable. Thus, chromatin fragmentation by sonication represents a significant bottleneck to downstream quantitative analysis...
April 16, 2018: Biochemistry
https://www.readbyqxmd.com/read/29650538/kir-channel-blockages-by-proflavine-derivatives-via-multiple-modes-of-interaction
#9
Atsushi Inanobe, Hideaki Itamochi, Yoshihisa Kurachi
Many compounds inhibit tetrameric and pseudo-tetrameric cation channels by associating with the central cavity located in the middle of the membrane plane. They traverse the ion conduction pathway from intracellular side and access to the cavity. Previously we reported that the bacteriostatic agent, proflavine, preferentially blocked a subset of Kir channels. However, the development of the inhibition of Kir1.1 by the compound was obviously different from that operating in Kir3.2 as a pore blocker. To gain mechanistic insights into the compound-channel interaction, we analyzed its chemical specificity, subunit selectivity, and voltage dependency using 13 different combinations of Kir-channel family members and 11 proflavine derivatives...
April 12, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29621164/source-apportionment-and-influencing-factor-analysis-of-residential-indoor-pm-2-5-in-beijing
#10
Yibing Yang, Liu Liu, Chunyu Xu, Na Li, Zhe Liu, Qin Wang, Dongqun Xu
In order to identify the sources of indoor PM2.5 and to check which factors influence the concentration of indoor PM2.5 and chemical elements, indoor concentrations of PM2.5 and its related elements in residential houses in Beijing were explored. Indoor and outdoor PM2.5 samples that were monitored continuously for one week were collected. Indoor and outdoor concentrations of PM2.5 and 15 elements (Al, As, Ca, Cd, Cu, Fe, K, Mg, Mn, Na, Pb, Se, Tl, V, Zn) were calculated and compared. The median indoor concentration of PM2...
April 5, 2018: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29619469/electrically-controlled-mass-transport-into-microfluidic-droplets-from-nanodroplet-carriers-with-application-in-controlled-nanoparticle-flow-synthesis
#11
Tonghan Gu, Cao Zheng, Fan He, Yunfei Zhang, Saif A Khan, T Alan Hatton
Microfluidic droplets have been applied extensively as reaction vessels in a wide variety of chemical and biological applications. Typically, once the droplets are formed in a flow channel, it is a challenge to add new chemicals to the droplets for subsequent reactions in applications involving multiple processing steps. Here, we present a novel and versatile method that employs a high strength alternating electrical field to tunably transfer chemicals into microfluidic droplets using nanodroplets as chemical carriers...
April 5, 2018: Lab on a Chip
https://www.readbyqxmd.com/read/29614085/interactions-between-seed-traits-and-digestive-processes-determine-the-germinability-of-bird-dispersed-seeds
#12
Erik Kleyheeg, Mascha Claessens, Merel B Soons
Waterbirds disperse a wide range of plant seeds via their guts, promoting biotic connectivity between isolated habitat patches. However, the intensity of digestive forces encountered by seeds, and therefore their potential to survive digestive tract passage, varies within and between waterbird species. Here, we investigate under controlled conditions how the interaction between seed traits and digestive strategies affect the germinability of seeds following waterbird-mediated dispersal. We exposed seeds of 30 wetland plant species to the main digestive processes in the dabbling duck digestive system: mechanical, chemical and intestinal digestion...
2018: PloS One
https://www.readbyqxmd.com/read/29600450/quantum-cascade-lasers-based-detection-of-nitric-oxide
#13
Gracia Montilla-Bascón, Julien Mandon, Frans J M Harren, Luis A J Mur, Simona M Cristescu, Elena Prats
Despite the established importance of nitric oxide (NO) in many physiological and molecular processes in plants, most methods for quantifying NO are open to criticism This reflects the differing methods either lacking specificity or sensitivity, or even from an undue dependence of results on experimental conditions (i.e., chemical concentrations, pH, etc.). In this chapter we describe a protocol to measure gaseous NO produced by a biological sample using quantum cascade laser (QCL)-based spectroscopy. This technique is based on absorption of the laser light by the NO molecules which have been passed from a biological sample into an optical s cell that is equipped with two mirrors placed at both ends...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29595890/risk-factors-associated-with-mortality-of-age-0-smallmouth-bass-in-the-susquehanna-river-basin-pennsylvania
#14
Heather L Walsh, Vicki S Blazer, Geoffrey D Smith, Michael Lookenbill, David A Alvarez, Kelly L Smalling
Evidence of disease and mortalities of young of the year (age-0) Smallmouth Bass Micropterus dolomieu has occurred during the late spring and summer in many parts of the Susquehanna River watershed since 2005. To better understand contributing factors, fish collected from multiple areas throughout the watershed as well as out-of-basin reference populations (Allegheny and Delaware River basins; experimental ponds, Kearneysville, West Virginia) were examined grossly and histologically for abnormalities. Tissue contaminant concentrations were determined from whole-body homogenates, and water contaminant concentrations were estimated using time-integrated passive samplers at selected sites...
March 2018: Journal of Aquatic Animal Health
https://www.readbyqxmd.com/read/29593404/in-vitro-studies-on-oxidative-stress-independent-ag-nanoparticles-induced-cell-toxicity-of-candida-albicans-an-opportunistic-pathogen
#15
Venkatraman Srinivasan Radhakrishnan, Surya Prakash Dwivedi, Mohammed Haris Siddiqui, Tulika Prasad
Silver nanoparticles (AgNps) have attracted maximal attention among all metal nanoparticles, and the study of their biological properties has gained impetus for further medical adoption. This study evaluated the cellular and molecular mechanisms associated with the action of AgNps against an opportunistic pathogen, Candida albicans . Spherical, stable AgNp (average size 21.6 nm) prepared by a chemical reduction method showed minimum inhibitory concentration (required to inhibit the growth of 90% of organisms) at 40 μg/mL...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29590495/prediction-of-drug-induced-hepatotoxicity-using-long-term-stable-primary-hepatic-3d-spheroid-cultures-in-chemically-defined-conditions
#16
Sabine Vorrink, Yitian Zhou, Magnus Ingelman-Sundberg, Volker M Lauschke
High failure rates of drug candidates in the clinics, restricted-use warnings and as well as withdrawals of drugs in post-marketing stages are of substantial concern for the pharmaceutical industry and drug-induced liver injury (DILI) constitutes one of the most frequent reasons for such safety failures. Importantly, as DILI cannot be accurately predicted using animal models, animal safety tests are commonly complemented with assessments in human in vitro systems. 3D spheroid cultures of primary human hepatocytes (PHH) in chemically defined conditions, hereafter termed CD-spheroids, have recently emerged as a microphysiological model system in which hepatocytes retain their molecular phenotypes and hepatic functions for multiple weeks in culture...
March 24, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29584430/bicyclic-helical-peptides-as-dual-inhibitors-selective-for-bcl2a1-and-mcl-1-proteins
#17
Aline D de Araujo, Junxian Lim, Kai-Chen Wu, Yibin Xiang, Andrew C Good, Renato Skerlj, David P Fairlie
A 26-residue peptide BimBH3 binds indiscriminately to multiple oncogenic Bcl2 proteins that regulate apoptosis of cancer cells. Specific inhibition of the BimBH3-Bcl2A1 protein-protein interaction was obtained in vitro and in cancer cells by shortening the peptide to 14 residues, inserting two cyclization constraints to stabilize a water-stable α-helix, and incorporating an N-terminal acrylamide electrophile for selective covalent bonding to Bcl2A1. Mass spectrometry of trypsin-digested bands on electrophoresis gels established covalent bonding of an electrophilic helix to just one of the three cysteines in Bcl2A1, the one (Cys55) at the BimBH3-Bcl2A1 protein-protein interaction interface...
March 27, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29575327/changes-in-the-proteome-of-the-problem-weed-blackgrass-correlating-with-multiple-herbicide-resistance
#18
Catherine Tétard-Jones, Federico Sabbadin, Stephen Moss, Richard Hull, Paul Neve, Robert Edwards
Herbicide resistance in grass weeds is now one of the greatest threats to sustainable cereal production in Northern Europe. Multiple herbicide resistance (MHR), a poorly understood multigenic and quantitative trait, is particularly problematic as it provides tolerance to most classes of chemistries currently used for post-emergence weed control. Using a combination of transcriptomics and proteomics, the evolution of MHR in populations of the weed blackgrass (Alopecurus myosuroides) has been investigated. While over 4500 genes showed perturbation in their expression in MHR vs...
March 25, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29572431/a-gain-of-function-mutation-in-the-%C3%AE-9-nicotinic-acetylcholine-receptor-alters-medial-olivocochlear-efferent-short-term-synaptic-plasticity
#19
Carolina Wedemeyer, Lucas G Vattino, Marcelo J Moglie, Jimena Ballestero, Stéphane F Maison, Mariano N Di Guilmi, Julian Taranda, M Charles Liberman, Paul A Fuchs, Eleonora Katz, Ana Belén Elgoyhen
Gain control of the auditory system operates at multiple levels. Cholinergic medial olivocochlear (MOC) fibers originate in the brainstem and make synaptic contacts at the base of the outer hair cells (OHCs), the final targets of several feedback loops from the periphery and higher processing centers. Efferent activation inhibits OHC active amplification within the mammalian cochlea, through the activation of a calcium permeable α9α10 ionotropic cholinergic nicotinic receptor (nAChR), functionally coupled to calcium activated SK2 potassium channels...
March 23, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29561583/multifunctional-fibers-as-tools-for-neuroscience-and-neuroengineering
#20
Andres Canales, Seongjun Park, Antje Kilias, Polina Anikeeva
Multifunctional devices for modulation and probing of neuronal activity during free behavior facilitate studies of functions and pathologies of the nervous system. Probes composed of stiff materials, such as metals and semiconductors, exhibit elastic and chemical mismatch with the neural tissue, which is hypothesized to contribute to sustained tissue damage and gliosis. Dense glial scars have been found to encapsulate implanted devices, corrode their surfaces, and often yield poor recording quality in long-term experiments...
March 21, 2018: Accounts of Chemical Research
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