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https://www.readbyqxmd.com/read/27911380/method-for-identifying-small-molecule-inhibitors-of-the-protein-protein-interaction-between-hcn1-and-trip8b
#1
Ye Han, Kyle A Lyman, Matt Clutter, Gary E Schiltz, Quratul-Ain Ismail, Xiangying Cheng, Chi-Hao Luan, Dane M Chetkovich
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed ubiquitously throughout the brain, where they function to regulate the excitability of neurons. The subcellular distribution of these channels in pyramidal neurons of hippocampal area CA1 is regulated by tetratricopeptide repeat-containing Rab8b interacting protein (TRIP8b), an auxiliary subunit. Genetic knockout of HCN pore forming subunits or TRIP8b, both lead to an increase in antidepressant-like behavior, suggesting that limiting the function of HCN channels may be useful as a treatment for Major Depressive Disorder (MDD)...
November 11, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911363/generation-of-induced-pluripotent-stem-cells-from-human-melanoma-tumor-infiltrating-lymphocytes
#2
Hidehito Saito, Kumiko Iwabuchi, Noemi Fusaki, Fumito Ito
Adoptive transfer of ex vivo expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate durable and complete responses in significant subsets of patients with metastatic melanoma. Major obstacles of this approach are the reduced viability of transferred T cells, caused by telomere shortening, and the limited number of TILs obtained from patients. Less-differentiated T cells with long telomeres would be an ideal T cell subset for adoptive T cell therapy;however, generating large numbers of these less-differentiated T cells is problematic...
November 11, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911328/the-clinical-use-of-cerebrospinal-fluid-biomarkers-for-alzheimer-s-disease-diagnosis-the-italian-selfie
#3
Giulia M Sancesario, Sofia Toniolo, Davide Chiasserini, Simona G Di Santo, Josh Zegeer, Gaetano Bernardi, Massimo Musicco, Carlo Caltagirone, Lucilla Parnetti, Sergio Bernardini
Although the use of cerebrospinal fluid (CSF) amyloid β1-42 (Aβ42), tau (T-tau), and phosphorylated tau (p-tau181) gives added diagnostic and prognostic values, the diffusion is still limited in clinical practice and only a restricted number of patients receive an integrated clinico-biological diagnosis. By a survey, we aimed to do a "selfie" of the use and diffusion of CSF biomarkers of dementia in Italy, the standardization of pre-analytical procedures, the harmonization of ranges, and the participation to Quality Control programs...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911276/the-mtor-inhibitor-everolimus-in-combination-with-azacitidine-in-patients-with-relapsed-refractory-acute-myeloid-leukemia-a-phase-ib-ii-study
#4
Peter Tan, Ing Soo Tiong, Shaun Fleming, Giovanna Pomilio, Nik Cummings, Mark Droogleever, Julie McManus, Anthony Schwarer, John Catalano, Sushrut Patil, Sharon Avery, Andrew Spencer, Andrew Wei
Therapeutic options are limited in relapsed/refractory acute myeloid leukemia (AML). We evaluated the maximum tolerated dose (MTD) and preliminary efficacy of mammalian target of rapamycin (mTOR) inhibitor, everolimus (days 5-21) in combination with azacitidine 75 mg/m2 subcutaneously (days 1-5 and 8-9 every 28 days) in 40 patients with relapsed (n = 27), primary refractory (n = 11) or elderly patients unfit for intensive chemotherapy (n = 2). MTD was not reached following everolimus dose escalation (2.5, 5 or 10 mg; n = 19) to the 10 mg dose level which was expanded (n = 21)...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911086/affective-and-autonomic-responses-to-erotic-images-evidence-of-disgust-based-mechanisms-in-female-sexual-interest-arousal-disorder
#5
Natasha S DePesa, Jeffrey E Cassisi
Disgust has recently been implicated in the development and maintenance of female sexual dysfunction, yet most empirical studies have been conducted with a sexually healthy sample. The current study contributes to the literature by expanding the application of a disgust model of sexual functioning to a clinically relevant sample of women with low sexual desire/arousal and accompanying sexual distress. Young women (mean age = 19.12 years) with psychometrically defined sexual dysfunction (i.e., female sexual interest/arousal disorder [FSIAD] group) and a healthy control group were compared in their affective (i...
December 2, 2016: Journal of Sex Research
https://www.readbyqxmd.com/read/27911025/effect-of-balloon-expandable-transcatheter-aortic-valve-replacement-positioning-a-patient-specific-numerical-model
#6
Matteo Bianchi, Gil Marom, Ram P Ghosh, Harold A Fernandez, James R Taylor, Marvin J Slepian, Danny Bluestein
Transcatheter aortic valve replacement (TAVR) has emerged as a life-saving and effective alternative to surgical valve replacement in high-risk, elderly patients with severe calcific aortic stenosis. Despite its early promise, certain limitations and adverse events, such as suboptimal placement and valve migration, have been reported. In the present study, it was aimed to evaluate the effect of various TAVR deployment locations on the procedural outcome by assessing the risk for valve migration. The deployment of a balloon-expandable Edwards SAPIEN valve was simulated via finite element analysis in a patient-specific calcified aortic root, which was reconstructed from CT scans of a retrospective case of valve migration...
December 2016: Artificial Organs
https://www.readbyqxmd.com/read/27910910/genome-wide-characterisation-and-expression-profile-of-the-grapevine-atl-ubiquitin-ligase-family-reveal-biotic-and-abiotic-stress-responsive-and-development-related-members
#7
Pietro Ariani, Alice Regaiolo, Arianna Lovato, Alejandro Giorgetti, Andrea Porceddu, Salvatore Camiolo, Darren Wong, Simone Castellarin, Elodie Vandelle, Annalisa Polverari
The Arabidopsis Tóxicos en Levadura (ATL) protein family is a class of E3 ubiquitin ligases with a characteristic RING-H2 Zn-finger structure that mediates diverse physiological processes and stress responses in plants. We carried out a genome-wide survey of grapevine (Vitis vinifera L.) ATL genes and retrieved 96 sequences containing the canonical ATL RING-H2 domain. We analysed their genomic organisation, gene structure and evolution, protein domains and phylogenetic relationships. Clustering revealed several clades, as already reported in Arabidopsis thaliana and rice (Oryza sativa), with an expanded subgroup of grapevine-specific genes...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910894/calcium-ions-function-as-a-booster-of-chromosome-condensation
#8
Rinyaporn Phengchat, Hideaki Takata, Kenichi Morii, Noriko Inada, Hideji Murakoshi, Susumu Uchiyama, Kiichi Fukui
Chromosome condensation is essential for the faithful transmission of genetic information to daughter cells during cell division. The depletion of chromosome scaffold proteins does not prevent chromosome condensation despite structural defects. This suggests that other factors contribute to condensation. Here we investigated the contribution of divalent cations, particularly Ca(2+), to chromosome condensation in vitro and in vivo. Ca(2+) depletion caused defects in proper mitotic progression, particularly in chromosome condensation after the breakdown of the nuclear envelope...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#9
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27910807/magnesium-intake-and-depression-the-sun-cohort
#10
Miguel Ángel Martínez-González, Almudena Sánchez-Villegas
A higher magnesium intake may reduce the risk of depression. We analyzed this association in the SUN Mediterranean cohort with an expanded sample size (n = 15,836) and a long follow-up (median = 10.2 y). We followed 9,289 women (age = 34.8, SD = 10.4) and 6,547 men (age = 42.8, SD = 13.1) initially free of any history of depression for a new-onset of medically diagnosed depression (maximum follow-up = 15.9 y). All participants in this cohort were university educated. We systematically reviewed previous studies relating magnesium to depression...
March 1, 2016: Magnesium Research: Official Organ of the International Society for the Development of Research on Magnesium
https://www.readbyqxmd.com/read/27910632/recent-advances-and-results-from-the-solid-radiochemistry-nuclear-diagnostic-at-the-national-ignition-facility
#11
N Gharibyan, D A Shaughnessy, K J Moody, P M Grant, J D Despotopulos, S A Faye, D R Jedlovec, C B Yeamans
The solid debris collection capability at the National Ignition Facility has been expanded to include a third line-of-sight assembly. The solid radiochemistry nuclear diagnostic measurement of the ratio of gold isotopes is dependent on the efficient collection of neutron-activated hohlraum debris by passive metal disks. The collection of target debris at this new location is more reliable in comparison to the historic locations, and it appears to be independent of collector surface ablation.
November 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/27910418/observation-of-hohlraum-wall-motion-with-spectrally-selective-x-ray-imaging-at-the-national-ignition-facility
#12
N Izumi, N B Meezan, L Divol, G N Hall, M A Barrios, O Jones, O L Landen, J J Kroll, S A Vonhof, A Nikroo, J Jaquez, C G Bailey, C M Hardy, R B Ehrlich, R P J Town, D K Bradley, D E Hinkel, J D Moody
The high fuel capsule compression required for indirect drive inertial confinement fusion requires careful control of the X-ray drive symmetry throughout the laser pulse. When the outer cone beams strike the hohlraum wall, the plasma ablated off the hohlraum wall expands into the hohlraum and can alter both the outer and inner cone beam propagations and hence the X-ray drive symmetry especially at the final stage of the drive pulse. To quantitatively understand the wall motion, we developed a new experimental technique which visualizes the expansion and stagnation of the hohlraum wall plasma...
November 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/27910402/towards-10-mev-resolution-the-design-of-an-ultrahigh-resolution-soft-x-ray-rixs-spectrometer
#13
Joseph Dvorak, Ignace Jarrige, Valentina Bisogni, Scott Coburn, William Leonhardt
We present the optical design of the Centurion soft X-ray resonant inelastic X-ray scattering (RIXS) spectrometer to be located on the SIX beamline at NSLS-II. The spectrometer is designed to reach a resolving power of 100 000 at 1000 eV at its best resolution. It is also designed to have continuously variable 2θ motion over a range of 112° using a custom triple rotating flange. We have analyzed several possible spectrometer designs capable of reaching the target resolution. After careful analysis, we have adopted a Hettrick-Underwood spectrometer design, with an additional plane mirror to maintain a fixed direction for the outgoing beam...
November 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/27910344/icrf-wave-field-measurements-in-the-presence-of-scrape-off-layer-turbulence-on-the-asdex-upgrade-tokamak-invited
#14
R Ochoukov, V Bobkov, H Faugel, H Fünfgelder, J Jacquot, J-M Noterdaeme, G Suárez López
A new array of B-dot probes was installed on ASDEX Upgrade. The purpose of the new diagnostic is to study Ion Cyclotron Range-off Frequencies (ICRF) wave field distributions in the evanescent scrape-off layer (SOL) plasma region on the low field side of ASDEX Upgrade. The vacuum measurements (no gas, BT = 0 T) reveal ICRF wave field measurements consistent with the profiles expected from the newly installed 3-strap ICRF antennas outside the antenna box: the shape of the toroidal distribution of both the amplitude and the phase is the same for the case of only the central straps being active, as for the case of only the side straps being active...
November 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/27910326/thomson-scattering-at-general-fusion
#15
W C Young, D Parfeniuk
This paper provides an overview of the Thomson scattering diagnostic in use at General Fusion, including recent upgrades and upcoming plans. The plasma experiment under examination produces temperatures in the 50-500 eV range with density on the order of 10(20) m(-3). A four spatial point collection optics scheme has been implemented, with plans to expand to six spatial points. Recent changes to the optics of the laser beamline have reduced stray light. The system employs a frequency doubled Nd:YAG laser (532 nm), a grating spectrometer, and a photomultiplier array based detector...
November 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/27910107/gestating-times-women-s-accounts-of-the-temporalities-of-pregnancies-that-end-in-abortion-in-england
#16
Siân M Beynon-Jones
Tensions between the 'clock time' of medicine and the embodied times of its subjects are central to feminist writing concerning Western obstetric practice. In this article, I expand the focus of this literature by addressing the temporal dynamics of another site of reproductive healthcare: abortion provision. Echoing obstetric accounts of birth, time in legal, healthcare and social scientific discourse on abortion is routinely conceptualised as a finite resource contained within the pregnant/foetal body, which can be measured using clocks and calendars...
December 2, 2016: Sociology of Health & Illness
https://www.readbyqxmd.com/read/27910045/synthesis-of-modified-mrna-for-myocardial-delivery
#17
Jason Kondrat, Nishat Sultana, Lior Zangi
Cardiac gene therapy shows tremendous promise in combating the growing problem of heart disease. Modified mRNA (modRNA) is a novel gene delivery system used in vitro or in vivo to achieve transient expression of therapeutic proteins in a heterogeneous population of cells. Incorporation of specific modified nucleosides enables modRNA to be translated efficiently without triggering antiviral and innate immune responses. ModRNA has been shown to be effective at delivering short-term robust gene expression to the heart and its use in the field of cardiac gene therapy is expanding...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909991/the-role-of-orexins-hypocretins-in-alcohol-use-and-abuse
#18
Leigh C Walker, Andrew J Lawrence
Addiction is a chronic relapsing disorder characterized by compulsive drug seeking and drug taking despite negative consequences. Alcohol abuse and addiction have major social and economic consequences and cause significant morbidity and mortality worldwide. Currently available therapeutics are inadequate, outlining the need for alternative treatments. Detailed knowledge of the neurocircuitry and brain chemistry responsible for aberrant behavior patterns should enable the development of novel pharmacotherapies to treat addiction...
December 2, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27909920/beyond-ferryl-mediated-hydroxylation-40%C3%A2-years-of-the-rebound-mechanism-and-c-h-activation
#19
REVIEW
Xiongyi Huang, John T Groves
Since our initial report in 1976, the oxygen rebound mechanism has become the consensus mechanistic feature for an expanding variety of enzymatic C-H functionalization reactions and small molecule biomimetic catalysts. For both the biotransformations and models, an initial hydrogen atom abstraction from the substrate (R-H) by high-valent iron-oxo species (Fe(n)=O) generates a substrate radical and a reduced iron hydroxide, [Fe(n-1)-OH ·R]. This caged radical pair then evolves on a complicated energy landscape through a number of reaction pathways, such as oxygen rebound to form R-OH, rebound to a non-oxygen atom affording R-X, electron transfer of the incipient radical to yield a carbocation, R(+), desaturation to form olefins, and radical cage escape...
December 1, 2016: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/27909910/biological-mechanisms-for-the-effect-of-obesity-on-cancer-risk-experimental-evidence
#20
Mauricio Berriel Diaz, Stephan Herzig, Tobias Schafmeier
Multiple epidemiological studies demonstrated that overweight and obesity significantly increase the risk of several types of cancer. As the prevalence of obesity is dramatically rising, it is expected that it will represent one of the major lifestyle-associated risk factors for cancer development in the near future. Numerous recent studies expanded knowledge about key players and pathways, which are deregulated in the obese state and potentially promote cancer initiation, progression and aggressiveness via remote and local effects...
2016: Recent Results in Cancer Research
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