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Buki Kwon, Palinda Ruvan Munashingha, Yong-Keol Shin, Chul-Hwan Lee, Bing Li, Yeon-Soo Seo
Highly conserved eukaryotic histones are polybasic proteins that package DNA into nucleosomes, a building block of chromatin, allowing extremely long DNA molecules to form compact and discrete chromosomes. The histone N-terminal tails that extend from the nucleosome core act as docking sites for many proteins through diverse posttranslational modifications, regulating various DNA transactions. In this report, we present evidence that the nucleosomes can positively regulate the enzymatic activity of Rad27 (yeast Fen1), a major processing enzyme important for Okazaki fragment in eukaryotes...
October 19, 2016: FEBS Journal
Ivan Kozyryev, Louis Baum, Kyle Matsuda, John M Doyle
An experimentally feasible strategy for direct laser cooling of polyatomic molecules with six or more atoms is presented. Our approach relies on the attachment of a metal atom to a complex molecule, where it acts as an active photon cycling site. We describe a laser cooling scheme for alkaline earth monoalkoxide free radicals taking advantageof the phase space compression of a cryogenic buffer-gas beam. Possible applications are presented including laser cooling of chiral molecules and slowing of molecular beams using coherent photon processes...
October 19, 2016: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
Raquel Tonello, Camilla Fusi, Serena Materazzi, Ilaria M Marone, Francesco De Logu, Silvia Benemei, Muryel C Gonçalves, Elisabetta Coppi, Celio J Castro-Junior, Marcus Vinicius Gomez, Pierangelo Geppetti, Juliano Ferreira, Romina Nassini
BACKGROUND AND PURPOSE: Peptides from venomous animals have long been important tools for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide purified from the armed spider Phoneutria nigriventer venom, produces analgesia by blocking the transient receptor potential ankyrin 1 (TRPA1) channel. EXPERIMENTAL APPROACH: Cultured rat dorsal root ganglion (DRG) neurons, human IMR90 fibroblasts or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), TRPV1 (hTRPV1-HEK293) or TRPV4 (hTRPV4-HEK293), were used for calcium imaging and electrophysiology...
October 19, 2016: British Journal of Pharmacology
Ping Wei, Jia-Wei Yang, Hai-Wen Lu, Bei Mao, Wen-Lan Yang, Jin-Fu Xu
BACKGROUND AND OBJECTIVE: There is presently no clear evidence on the effect of combined treatment for non-cystic fibrosis (non-CF) bronchiectasis with inhaled corticosteroid (ICS) and long-acting β2-adrenergic agonist (LABA). The objective of this study is to assess the efficacy and safety of salmeterol-fluticasone combined inhaled therapy for non-CF bronchiectasis with airflow limitation. METHODS: An observational study was performed in 120 non-CF bronchiectasis patients diagnosed by high-resolution computed tomography (HRCT) scanning of the chest...
October 2016: Medicine (Baltimore)
Andrew Scrima, Meghan G Lubner, Scott King, Gregory Kennedy, Perry J Pickhardt
OBJECTIVE: To compare performance of junior (JR)/senior (SR) abdominal radiologists using multidetector computed tomography (MDCT) to predict surgical intervention, bowel resection, and presence of bowel ischemia in patients with suspected small-bowel obstruction (SBO). METHODS: Retrospective, institutional review board-approved, Health Insurance Portability and Accountability Act-compliant, blinded, independent review of MDCT studies for suspected SBO in 179 adults (mean age, 55...
October 18, 2016: Journal of Computer Assisted Tomography
Raffaella Sordella, Nitin H Shirole, Debjani Pal, Edward R Kastenhuber, Serif Senturk, Joseph Boroda, Paola Pisterzi, Madison Miller, Gustavo Munoz, Marko Anderluh, Marc Ladanyi, Scott W Lowe
TP53 truncating mutations are common in human tumors and are thought to give rise to p53-null alleles. Here, we show that TP53 exon-6 truncating mutations occur at higher than expected frequencies and produce proteins that lack canonical p53 tumor suppressor activities but promote cancer cell proliferation, survival, and metastasis. Functionally and molecularly, these p53 mutants resemble the naturally occurring alternative p53 splice variant, p53-psi. Accordingly, these mutants can localize to mitochondria where they promote tumor phenotypes by binding and activating the mitochondria inner pore permeability regulator, Cyclophilin D (CypD)...
October 19, 2016: ELife
Richard A I Bethlehem, Carrie Allison, Emma M van Andel, Alexander I Coles, Kym Neil, Simon Baron-Cohen
Why do people act altruistically? One theory is that empathy is a driver of morality. Experimental studies of this are often confined to laboratory settings, which often lack ecological validity. In the present study we investigated whether empathy traits predict if people will act altruistically in a real-world setting, 'in the wild'. We staged a situation in public that was designed to elicit helping, and subsequently measured empathic traits in those who either stopped to help or walked past and did not help...
October 19, 2016: Social Neuroscience
Scott J Hughes, Leanne Barnard, Katayoun Mottaghi, Wolfram Tempel, Tetyana Antoshchenko, Bum Soo Hong, Abdellah Allali-Hassani, David Smil, Masoud Vedadi, Erick Strauss, Hee-Won Park
The potent antistaphylococcal activity of N-substituted pantothenamides (PanAms) has been shown to at least partially be due to the inhibition of Staphylococcus aureus's atypical type II pantothenate kinase (SaPanKII), the first enzyme of coenzyme A biosynthesis. This mechanism of action follows from SaPanKII having a binding mode for PanAms that is distinct from those of other PanKs. To dissect the molecular interactions responsible for PanAm inhibitory activity, we conducted a mini SAR study in tandem with the cocrystallization of SaPanKII with two classic PanAms (N5-Pan and N7-Pan), culminating in the synthesis and characterization of two new PanAms, N-Pip-PanAm and MeO-N5-PanAm...
September 9, 2016: ACS Infectious Diseases
Chongjun Zhao, Xiaoxiao Shao, Yuxiao Zhang, Xiuzhen Qian
A Fe2O3/RGO/Fe3O4 nanocomposite in-situ grown on Fe foil was synthesized via a simple one-step hydrothermal growth process, where the iron foil served as support, reductant of GO, Fe source of Fe3O4 and also the current collector of electrode. When it was directly acted as the electrode of a supercapacitor, as-synthesized Fe2O3/RGO/Fe3O4@Fe exhibited excellent electrochemical performance with high capability of 337.5 mF/cm2 at 20 mA/cm2 and superior cyclability with 2.3 % of capacity loss from 600th cycle to 2000th cycle...
October 19, 2016: ACS Applied Materials & Interfaces
Bruno Henrique Fumes, Mariane Aissa Andrade, Maraíssa Silva Franco, Fernando Mauro Lanças
The determination of residues and contaminants in complex matrices such as in the case of food, environmental and biological samples requires a combination of several steps to succeed in the aimed goal. At least three independent steps are integrated to provide the best available situation to deal with such matrices: (1) a sample preparation technique is employed to isolate the target compounds from the rest of the matrix; (2) a chromatographic (second) step further "purifies" the isolated compounds from the co-extracted matrix interferences; (3) a spectroscopy-based device acts as chromatographic detector (ideally containing a tandem high-resolution mass analyzer) for the qualitative and quantitative analysis...
October 19, 2016: Journal of Separation Science
Sher Ali, Tao Xu, Xiaolan Xu
Ca(2+) release-activated Ca(2+) (CRAC) channels play an essential role in the immune system. The pore-forming subunit, Orai1, is an important pharmacological target. Here, we summarize the recent discoveries on the structure-function relationship of Orai1, as well as its interaction with the native channel opener STIM1 and chemical modulator 2-aminoethoxydiphenyl borate (2-APB). We first introduce the critical structural elements of Orai1, which include a Ca(2+) accumulating region (CAR), ion selectivity filter, hydrophobic centre, basic region, extended transmembrane orai1 N-terminal (ETON), transmembrane (TM) regions 2 and 3, P245 bend, (263) SHK(265) hinge linker and L273-L276 hydrophobic patch...
October 18, 2016: Journal of Physiology
Simon A Moss, Melanie Irons, Martin Boland
BACKGROUND AND AIMS: Lecturers often present entertaining videos, or organize a variety of amusing demonstrations, to foster student engagement or to encourage critical analysis. Magic tricks, in particular, have been shown to activate neural circuits that underpin motivation or problem-solving and, therefore, could be beneficial during lectures. Nevertheless, we hypothesize that, unless the method that underpins these tricks is revealed, students may ruminate over possible explanations, distracting attention from the lecture material...
October 18, 2016: British Journal of Educational Psychology
Anna Yu Alekseeva, Larisa V Kameneva, Svetlana V Kostyuk, Natalia N Veiko
Oxidized cell-free DNA acts as a stress signal molecule and triggers an adaptive response in human cells. Various membrane DNA recognizing receptors are known as potential sensors for such DNA fragments. In order to clarify which of these sensors are able to interact with cfDNA fragments, circulating in human blood flow in heath and disease, we studied the influence of various cfDNA types on endothelial cells. We incubated these fragments at a physiologically optimal concentration with HUVEC cells for 3-24 h and detected the expression of either TLR9 or AIM2, RIG1 and STING receptors at mRNA and protein levels...
2016: Advances in Experimental Medicine and Biology
Anna V Savelyeva, Dmitriy N Baryakin, Elena D Chikova, Elena V Kuligina, Vladimir A Richter, Dmitriy V Semenov
Human blood contains a great variety of membrane-covered RNA carrying vesicles which are spherical or tubular particles enclosed by a phospholipid bilayer. Circulating vesicles are thought to mediate cell-to-cell communication and their RNA cargo can act as regulatory molecules. In this work, we separated blood plasma of healthy donors by centrifugation and determined that vesicles precipitated at 16,000 g were enriched with CD41a, marker of platelets. At 160,000 g, the pellets were enriched with CD3 marker of T cells...
2016: Advances in Experimental Medicine and Biology
Irina A Tikhonova, Martin W Hoyle, Tristan M Snowsill, Chris Cooper, Joanna L Varley-Campbell, Claudius E Rudin, Ruben E Mujica Mota
The National Institute for Health and Care Excellence (NICE) invited the manufacturer of azacitidine (Celgene) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of acute myeloid leukaemia with more than 30 % bone marrow blasts in adults who are not eligible for haematopoietic stem cell transplantation, as part of the NICE's Single Technology Appraisal process. The Peninsula Technology Assessment Group was commissioned to act as the Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE...
October 17, 2016: PharmacoEconomics
Asrul Akmal Shafie, Chin Hui Ng, Yui Ping Tan, Nathorn Chaiyakunapruk
BACKGROUND: Insulin analogues have a pharmacokinetic advantage over human insulin and are increasingly used to treat diabetes mellitus. A summary of their cost effectiveness versus other available treatments was required. OBJECTIVE: Our objective was to systematically review the published cost-effectiveness studies of insulin analogues for the treatment of patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). METHODS: We searched major databases and health technology assessment agency reports for economic evaluation studies published up until 30 September 2015...
October 17, 2016: PharmacoEconomics
Darrell G Kirch, Cori E Ast
The health care system of the United States has been in a period of dramatic transformation since the passage of the Affordable Care Act in 2010, and the rate of change is accelerating. Historically, health care delivery was focused on the efforts of independent individual providers related to single patients, but the future will require interprofessional teamwork to achieve successful transformation. Academic health centers must identify nimble leaders who can harness the expertise of every team member to succeed in yielding the triple aim-better care for individuals, better health for populations, and lower overall cost...
October 17, 2016: Journal of Clinical Psychology in Medical Settings
Valmiki B Koli, Sagar D Delekar, Shivaji H Pawar
In this study, nanocomposites of Fe-doped TiO2 with multi-walled carbon nanotubes (0.1- 0.5 wt. %) were prepared by using sol-gel method. The structural and morphological analysis were carried out with using X-ray diffraction pattern and transmission electron microscopy, which confirm the presence of pure anatase phase and particle sizes in the range 15-20 nm. X-ray photoelectron spectroscopy was used to determine the surface compositions of the nanocomposites. UV-vis diffuse reflectance spectra confirm redshift in the optical absorption edge of nanocomposites with increasing amount of multi-walled carbon nanotubes...
December 2016: Journal of Materials Science. Materials in Medicine
Zoraida Verde, Jose M Rodríguez González-Moro, Luis M Chicharro, Luis Reinoso-Barbero, Fernando Bandrés, Félix Gómez-Gallego, Catalina Santiago
Reports regarding smoking differences in α-klotho expression have provided conflicting results. In the current study we focused on the influence of smoking intensity to serum levels of the aging molecule α-klotho in healthy smokers. 40 middle aged healthy smokers without airway obstruction or restriction were selected for the analysis. Serum levels of soluble α-klotho were significantly higher in heavy smokers (P < 0.001). These results are in agreement with the possibility that α-klotho acts as anti-inflammatory molecule and strengthen the hypothesis that an increase of serum levels of α-klotho might be a compensatory response to smoking stress in healthy population...
October 17, 2016: Lung
Han Sol Kim, Ha Ra Cho, Myoung Jin Ho, Myung Joo Kang, Yong Seok Choi
Osteoarthritis (OA) is the most common type of arthritis. To manage OA, in general, oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) is used. Recently, the analgesic and anti-inflammatory efficacy of piroxicam (PX), a long-acting NSAID, by intra-articular (IA) administration in OA was reported, and the possibility that PX is distributed in articular tissues at a certain concentration was raised. Thus, herein, novel LC-MS/MS methods to detect PX in rat articular tissue and plasma are presented...
October 17, 2016: Archives of Pharmacal Research
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