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https://www.readbyqxmd.com/read/28088129/in-vitro-eye-irritation-testing-using-the-open-source-reconstructed-hemicornea-a-ring-trial
#1
Karsten R Mewes, Maria Engelke, Michaela Zorn-Kruppa, Melinda Bartok, Rashmi Tandon, Johanna M Brandner, Dirk Petersohn
Aim of the present ring trial was to prove whether two new methodological approaches for the in vitro classification of eye irritating chemicals can be reliably transferred from the developers' laboratories to other sites.Both test methods are based on the well-established open source reconstructed 3D hemicornea models. In the first approach, the initial depth of injury in the hemicornea model after chemical treatment is derived from the quantitative analysis of histological sections. In the second approach tissue viability, as a measure for corneal damage after chemical treatment, is analyzed separately for epithelium and stroma of the hemicornea model...
January 14, 2017: ALTEX
https://www.readbyqxmd.com/read/28087976/the-role-of-diode-array-ultraviolet-detection-for-the-identification-of-synthetic-cathinones
#2
Walter F Rowe, Ioan Marginean, Stephanie Carnes, Ira S Lurie
The utility of diode array UV detection for aiding in the identification of synthetic cathinones, including different sub classes and positional isomers is presented. For 35 synthetic cathinones' unique UV spectra are obtained for seven sub classes including mostly beta ketones, where position and type of substitution on benzene rings give rise to differences in UV maxima and relative intensity of the spectral bands. This aspect is key to distinguishing positional isomers which contain differences in R substitution (mono and di) around the benzene ring, which provides complementary information to electron ionization mass spectrometry, where the latter technique cannot distinguish between these types of positional isomers...
January 14, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28087886/d-chiro-inositol-ameliorates-endothelial-dysfunction-via-inhibition-of-oxidative-stress-and-mitochondrial-fission
#3
Bobo Zhang, Xudan Guo, Yunlong Li, Qiang Peng, Jinfeng Gao, Baolin Liu, Min Wang
SCOPE: D-chiro inositol (DCI), an isomer of inositol, possesses anti-oxidative and endothelial protective properties. The mechanism by which DCI prevents endothelial dysfunction was investigated, with emphasis on oxidative stress. METHODS AND RESULTS: DCI was found to inhibit NOX4 induction and enhance Nrf2 activity in palmitate (PA)-stimulated cells, showing that DCI prevents oxidative stress. DCI suppressed Ser616 phosphorylation and increased Ser637 phosphorylation of Drp1 and inhibited PA-induced mitochondrial fission...
January 14, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28087809/trim13-potentiates-tlr2-mediated-nf-%C3%AE%C2%BAb-activation-via-k29-linked-polyubiquitination-of-traf6
#4
Bin Huang, Suk-Hwan Baek
Ubiquitination is a versatile post-translational modification involved in NF-κB activation of TLR signaling. Here, we demonstrated that Trim13, an E3 ubiquitin ligase, is up-regulated in macrophages upon stimulation with TLR2 ligand. Knock-down of Trim13 attenuated TLR2-mediated production of cytokines/chemokines and formation of foam cells, as well as activation of NF-κB. Trim13 interacts with TRAF6 and potentiates NF-κB activity via ubiquitination of TRAF6. Overexpression of inactive mutant (C10/13A) or RING deletion mutant of Trim13 did not potentiate ubiquitination of TRAF6 or activation of NF-κB...
January 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28087785/thermolytic-degradation-of-synthetic-cannabinoids-chemical-exposures-and-pharmacological-consequences
#5
Brian F Thomas, Timothy W Lefever, Ricardo A Cortes, Alexander L Kovach, Anderson O Cox, Purvi R Patel, Gerald T Pollard, Julie A Marusich, Richard A Kevin, Thomas F Gamage, Jenny L Wiley
Synthetic cannabinoids are manufactured clandestinely with little quality control and are distributed as herbal "Spice" for smoking or as bulk compound for mixing with a solvent and inhalation via electronic vaporizers. Intoxication with synthetic cannabinoids has been associated with seizure, excited delirium, coma, kidney damage, and other disorders. The chemical alterations produced by heating these structurally novel compounds for consumption are largely unknown. Here we show that heating synthetic cannabinoids containing tetramethylcyclopropyl-ring substituents produced thermal degradants with pharmacological activity that varied considerably from their parent compounds...
January 13, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28087759/separation-of-vitamin-e-on-a-100-%C3%A3-phenogel-column
#6
Salisa Chumsantea, Kornkanok Aryusuk, Supathra Lilitchan, Narumon Jeyashoke, Kanit Krisnangkura
The effect of π-electrons and hydroxyl group on the separations of vitamin E on a swelling-controlled polystyrene-divinylbenzene (Phenogel) column using toluene/isooctane as the mobile phase was investigated. The effect of the π-electrons was demonstrated in the baseline separation of α-tocopherol and α-tocotrienol on a 100-Å Phenogel column. In addition, baseline separation of α-, (β- + γ-)- and δ-tocopherol could be achieved on this column. The separation mechanism of these isomers are due to the difference in the interactions between the hydroxyl group on the chromanol ring of each tocopherol and the gel matrix caused by the steric hindrance of methyl group(s)...
February 2017: Journal of Chromatographic Science
https://www.readbyqxmd.com/read/28087699/activation-of-c-abl-kinase-potentiates-the-anti-myeloma-drug-lenalidomide-by-promoting-dda1-recruitment-to-the-crl4-ubiquitin-ligase
#7
Shaobing Gao, Chenlu Geng, Tianyu Song, Xuanru Lin, Jiye Liu, Zhen Cai, Yong Cang
Cullin Ring Ligase 4 (CRL4), a complex of Cul4 and DDB1, regulates cell cycle, DNA damage repair, and chromatin replication by targeting a variety of substrates for ubiquitination. CRL4 is also hijacked by viral proteins or thalidomide-derived compounds to degrade host restriction factors. Here we report that the c-Abl non-receptor kinase phosphorylates DDB1 at residue Y316 to recruit a small regulatory protein DDA1, leading to increased substrate ubiquitination. Pharmacological inhibition or genetic ablation of the Abl-DDB1-DDA1 axis decreases the ubiquitination of CRL4 substrates, including IKZF1 and IKZF3 in lenalidomide-treated multiple myeloma cells...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28087440/an-overlooked-horticultural-crop-smyrnium-olusatrum-as-a-potential-source-of-compounds-effective-against-african-trypanosomiasis
#8
Riccardo Petrelli, Farahnaz Ranjbarian, Stefano Dall'Acqua, Fabrizio Papa, Romilde Iannarelli, Stephane L Ngahang Kamte, Sauro Vittori, Giovanni Benelli, Filippo Maggi, Anders Hofer, Loredana Cappellacci
Among natural products, sesquiterpenes have showed promising inhibitory effects against bloodstream forms of Trypanosoma brucei, the protozoan parasite causing the human African trypanosomiasis (HAT). Smyrnium olusatrum (Apiaceae), also known as Alexanders or wild celery, is a neglected horticultural crop characterized by oxygenated sesquiterpenes containing a furan ring. In the present work we explored the potential of its essential oils obtained from different organs and the main oxygenated sesquiterpenes, namely isofuranodiene, germacrone and β-acetoxyfuranoeudesm-4(15)-ene, as inhibitors of Trypanosoma brucei...
January 10, 2017: Parasitology International
https://www.readbyqxmd.com/read/28087416/the-path-of-a-click-stimulus-from-ear-canal-to-umbo
#9
Mario Milazzo, Elika Fallah, Michael Carapezza, Nina S Kumar, Jason H Lei, Elizabeth S Olson
The tympanic membrane (TM) has a key role in transmitting sounds to the inner ear, but a concise description of how the TM performs this function remains elusive. This paper probes TM operation by applying a free field click stimulus to the gerbil ear and exploring the consequent motions of the TM and umbo. Motions of the TM were measured both on radial tracks starting close to the umbo and on a grid distal and adjacent to the umbo. The experimental results confirmed the high fidelity of sound transmission from the ear canal to the umbo...
January 10, 2017: Hearing Research
https://www.readbyqxmd.com/read/28087322/cutaneous-exposure-to-vesicant-phosgene-oxime-acute-effects-on-the-skin-and-systemic-toxicity
#10
Neera Tewari-Singh, Dinesh G Goswami, Rama Kant, Claire R Croutch, Robert P Casillas, David J Orlicky, Rajesh Agarwal
Phosgene Oxime (CX), an urticant or nettle agent categorized as a vesicant, is a potential chemical warfare and terrorist weapon. Its exposure can result in widespread and devastating effects including high mortality due to its fast penetration and ability to cause immediate severe cutaneous injury. It is one of the least studied chemical warfare agents with no effective therapy available. Thus, our goal was to examine the acute effects of CX following its cutaneous exposure in SKH-1 hairless mice to help establish a relevant injury model...
January 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28087298/the-utility-of-sex-hormone-binding-globulin-in-hypogonadism-and-infertile-males
#11
Joshua Ring, Charles Welliver, Mike Parenteau, Stephen Markwell, Robert E Brannigan, Tobias S Köhler
PURPOSE: We sought to determine what role SHBG played with male infertility patients. METHODS: Retrospective review of 168 males seen in a fertility clinic from 2012-2014, to investigate the accuracy of TT in the biochemical diagnosis of hypogonadism using cBT as the reference value. We used a multivariable analysis to assess SHBG as an independent predictor of infertility. RESULTS: Computations using cBT as a standard in the measurement of definitive biochemical hypogonadism (<156 ng/dL) revealed a sensitivity, specificity, PPV, and NPV respectively of 81%, 83%, 81%, and 82% in diagnosing hypogonadism with TT alone...
January 10, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28087168/synthesis-structure-activity-relationships-studies-of-benzoxazinone-derivatives-as-%C3%AE-chymotrypsin-inhibitors
#12
Bishnu P Marasini, Fazal Rahim, Shahnaz Perveen, Aneela Karim, Khalid Mohammed Khan, Atta-Ur-Rahman, M Iqbal Choudhary
A series of benzoxazinones 1-28 were synthesized via reaction of anthranilic acid with various substituted benzoyl chlorides in the presence of triethylamine in chloroform. Compounds 1-18 showed a good inhibition of α-chymotrypsin with IC50±SEM values between 6.5 and 341.1μM. Preliminary structure-activity relationships studies indicated that the presence of substituents on benzene ring reduces the inhibitory potential of benzoxazinone. Also the increased inhibitory potential due to fluoro group at phenyl substituent was observed followed by chloro and bromo substituents...
January 4, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28087052/contraceptive-practices-of-women-with-complex-congenital-heart-disease
#13
Pamela D Miner, Mary M Canobbio, Dorothy D Pearson, Mary Schlater, Yvonne Balon, Kathryn J Junge, Ami Bhatt, Deena Barber, Michelle J Nickolaus, Adrienne H Kovacs, Philip Moons, Kate Shaw, Susan M Fernandes
Understanding the contraceptive practices of women with complex congenital heart disease (CHD) and providing them individualized contraception counseling may prevent adverse events and unplanned high-risk pregnancies. Given this, we sought to examine the contraceptive practices in women with CHD, describe adverse events associated with contraceptive use, and describe the provision of contraception counseling. Women >18 years were recruited from 2011 to 2014 from 9 adult CHD (ACHD) centers throughout North America...
December 18, 2016: American Journal of Cardiology
https://www.readbyqxmd.com/read/28086263/observation-of-the-ring-puckering-vibrational-mode-in-thietane-cation
#14
Yu Ran Lee, Chung Bin Park, Jiye Hwang, Bongjune Sung, Hong Lae Kim, Chan Ho Kwon
We have measured the high-resolution vibrational spectra of a thietane (trimethylene sulfide) cation in the gas phase by employing the vacuum ultraviolet mass-analyzed threshold ionization (VUV-MATI) spectroscopic technique. Peaks in the low frequency region of the observed MATI spectrum of thietane originate from a progression of the ring puckering vibrational mode (typical in small heterocyclic molecules), which is successfully reproduced by quantum chemical calculations with one-dimensional (1D) symmetric double-well potentials along the ring puckering coordinates on both the S0 and D0 states, the ground electronic states of neutral and cation of thietane, respectively...
January 13, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/28081528/rapid-decrease-in-populations-of-wild-ring-tailed-lemurs-lemur-catta-in-madagascar
#15
Marni LaFleur, Tara A Clarke, Kim Reuter, Toby Schaeffer
Lemurs are the most threatened group of mammals on earth. Lemur catta (ring-tailed lemur) represents one of the most iconic lemur species and faces numerous anthropogenic threats in the wild. In this study, we present population estimates from 32 sites across the range of L. catta, collected from primary and secondary data sources, to assess the number of ring-tailed lemurs left in the wild. We estimate that there are approximately 2,220 individual L. catta remaining in the 32 sites considered. We note local extinctions of populations of L...
January 13, 2017: Folia Primatologica; International Journal of Primatology
https://www.readbyqxmd.com/read/28081137/anillin-phosphorylation-controls-timely-membrane-association-and-successful-cytokinesis
#16
Hyunjung Kim, James M Johnson, Robert F Lera, Sarang Brahma, Mark E Burkard
During cytokinesis, a contractile ring generates the constricting force to divide a cell into two daughters. This ring is composed of filamentous actin and the motor protein myosin, along with additional structural and regulatory proteins, including anillin. Anillin is a required scaffold protein that links the actomyosin ring to membrane and its organizer, RhoA. However, the molecular basis for timely action of anillin at cytokinesis remains obscure. Here, we find that phosphorylation regulates efficient recruitment of human anillin to the equatorial membrane...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28081085/coherent-and-incoherent-seeding-of-dissipative-modulation-instability-in-a-nonlinear-fiber-ring-cavity
#17
A Bendahmane, J Fatome, C Finot, G Millot, B Kibler
We investigate the coherent or incoherent seeding of dissipative modulation instability (MI) in a nonlinear fiber ring cavity. By varying wavelength and degree of coherence of the seed signal across the MI gain band, we observe a strong sensitivity of the resulting MI sidebands in terms of bandwidth and amplification. Both spectral and temporal characterizations are performed to reveal intensity coherence properties (over a single round-trip) of the generated temporal patterns. Experimental observations are well confirmed by numerical simulations...
January 15, 2017: Optics Letters
https://www.readbyqxmd.com/read/28081067/guiding-terahertz-orbital-angular-momentum-beams-in-multimode-kagome-hollow-core-fibers
#18
Haisu Li, Guobin Ren, Bofeng Zhu, Yixiao Gao, Bin Yin, Jing Wang, Shuisheng Jian
We explore terahertz (THz) orbital angular momentum (OAM) modes supported in multimode Kagome hollow-core fibers. Numerical models are adopted to characterize the effective indices and confinement losses of vector modes over 0.2-0.9 THz, where two low-loss transmission windows are observed. Linearly combining the vector modes, THz OAM states can be generated. Covering a broad bandwidth of 0.25 THz, the purity values of OAM modes are beyond 0.9. Using numerical simulations, the hollow-core THz fibers with one and two rings of Kagome structures are also comparably investigated...
January 15, 2017: Optics Letters
https://www.readbyqxmd.com/read/28080972/towards-a-psychophysics-of-interoceptive-processes-the-measurement-of-heartbeat-detection
#19
REVIEW
Jasper Brener, Christopher Ring
It is difficult to collect objective evidence of interoception. Unlike exteroception, the effective stimuli for interoception are often unknown, and even when identifiable, they are difficult to control experimentally. Furthermore, direct stimulation of the interoceptors is seldom appropriate in human experimentation. Hence, non-invasive behavioural measures of accuracy in heartbeat detection have frequently been adopted to index interoceptive sensitivity. However, there has been little standardization and the two most popular methods for assessing heartbeat detection, heartbeat tracking and two alternative forced choice methods, appear to be biased and of questionable validity...
November 19, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28080063/optimization-of-2-anilino-4-amino-substituted-quinazolines-into-potent-antimalarial-agents-with-oral-in-vivo-activity
#20
Paul R Gilson, Cyrus Tan, Kate E Jarman, Kym N Lowes, Joan M Curtis, William Nguyen, Adrian E Di Rago, Hayley E Bullen, Boris Prinz, Sandra Duffy, Jonathan B Baell, Craig A Hutton, Helene Jousset Sabroux, Brendan S Crabb, Vicky M Avery, Alan F Cowman, Brad E Sleebs
Novel antimalarial therapeutics that target multiple stages of the parasites lifecycle are urgently required to tackle the emerging problem of resistance with current drugs. Here we describe the optimization of the 2-anilino quinazoline class as antimalarial agents. The class, identified from publicly available antimalarial screening data, was optimized to generate lead compounds that possess potent antimalarial activity against P. falciparum parasites equivalent to the known antimalarials, chloroquine and mefloquine...
January 12, 2017: Journal of Medicinal Chemistry
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