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https://www.readbyqxmd.com/read/28637004/autophagy-is-required-for-crizotinib-induced-apoptosis-in-met-amplified-gastric-cancer-cells
#1
Rebecca D Schroeder, Woonyoung Choi, David S Hong, David J McConkey
MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood. Using whole-genome mRNA expression profiling, we identified autophagy as a top molecular pathway that was activated by the MET inhibitor crizotinib in drug-sensitive human gastric cancer cells, and functional studies confirmed that crizotinib increased autophagy levels in the drug-sensitive cells in a concentration-dependent manner...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636973/amide-to-triazole-switch-vs-in-vivo-nep-inhibition-approaches-to-promote-radiopeptide-targeting-of-grpr-positive-tumors
#2
Theodosia Maina, Aikaterini Kaloudi, Ibai E Valverde, Thomas L Mindt, Berthold A Nock
INTRODUCTION: Radiolabeled bombesin (BBN)-analogs have been proposed for diagnosis and therapy of gastrin-releasing peptide receptor (GRPR)-expressing tumors, such as prostate, breast and lung cancer. Metabolic stability represents a crucial factor for the success of this approach by ensuring sufficient delivery of circulating radioligand to tumor sites. The amide-to-triazole switch on the backbone of DOTA-PEG4-[Nle(14)]BBN(7-14) (1) was reported to improve the in vitro stability of resulting (177)Lu-radioligands...
June 10, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28636939/the-super-enhancer-derived-alncrna-ec7-bloodlinc-potentiates-red-blood-cell-development-in%C3%A2-trans
#3
Juan R Alvarez-Dominguez, Marko Knoll, Austin A Gromatzky, Harvey F Lodish
Enhancer-derived RNAs are thought to act locally by contributing to their parent enhancer function. Whether large domains of clustered enhancers (super-enhancers) also produce cis-acting RNAs, however, remains unclear. Unlike typical enhancers, super-enhancers form large spans of robustly transcribed chromatin, amassing capped and polyadenylated RNAs that are sufficiently abundant to sustain trans functions. Here, we show that one such RNA, alncRNA-EC7/Bloodlinc, is transcribed from a super-enhancer of the erythroid membrane transporter SLC4A1/BAND3 but diffuses beyond this site...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636347/the-structure-and-dynamics-of-alginate-gels-crosslinked-by-polyvalent-ions-probed-via-solid-state-nmr-spectroscopy
#4
Jiří Brus, Martina Urbanová, Jiri Czernek, Miroslava Pavelkova, Katerina Kubova, Jakub Vyslouzil, Sabina Abbrent, Rafal Konefal, Jiri Horsky, David Vetchy, Jan Vysloužil, Pavel Kulich
Alginate gels are an outstanding biomaterial widely applicable in tissue engineering, medicine, and pharmacy for cell transplantation, wound healing and efficient bioactive agent delivery, respectively. This contribution provides new and comprehensive insight into the atomic-resolution structure and dynamics of polyvalent ion-crosslinked alginate gels in microbead formulations. By applying various advanced solid-state NMR (ssNMR) spectroscopy techniques, we verified the homogenous distribution of the crosslinking ions in the alginate gels and the high degree of ion exchange...
June 21, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28636143/tetratricopeptide-repeat-protein-pyg7-is-essential-for-photosystem-i-assembly-by-interacting-with-psac-in-arabidopsis
#5
Huixia Yang, Pin Li, Aihong Zhang, Xiaogang Wen, Lixin Zhang, Congming Lu
Although progress has been made in determining the structure and understanding the function of photosystem I (PSI), the PSI assembly process remains poorly understood. PsaC is an essential subunit of PSI and participates in the transfer of electrons to ferredoxin. However, how PsaC is assembled during accumulation of the PSI complex is unknown. In the present study, we showed that Pyg7 localized to the stromal thylakoid and associated with the PSI complex. We also showed that Pyg7 interacted with PsaC. Furthermore, we found that the PSI assembly process was blocked following formation of the PsaAB heterodimer in the pyg7 mutant...
June 21, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28635081/understanding-and-improving-photo-control-of-ion-channels-in-nociceptors-with-azobenzene-photoswitches
#6
Alexandre Mourot, Christian Herold, Michael A Kienzler, Richard H Kramer
BACKGROUND AND PURPOSE: We previously developed a photoisomerizable local anaesthetic, named QAQ, to gain rapid, optical control over pain signaling without involving genetic modification. In darkness or in green light, trans-QAQ blocks voltage-gated K(+) and Na(+) channels and silences action potentials in pain-sensing neurons. Upon photoisomerization to cis with near UV light, QAQ blockade is rapidly relieved and neuronal activity is restored. However, the molecular mechanism of cis and trans QAQ blockade is not known...
June 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28634320/comparison-of-2-analgesia-modalities-in-total-knee-replacement-surgery-is-there-an-effect-on-knee-function-rehabilitation
#7
Janis Zinkus, Lina Mockutė, Arūnas Gelmanas, Ramūnas Tamošiūnas, Arūnas Vertelis, Andrius Macas
BACKGROUND We compared the effects of continuous femoral nerve block (CFNB) and continuous intraarticular block (CIAB) on pain, functional recovery and adverse effects after total knee arthroplasty (TKA). MATERIAL AND METHODS We prospectively randomized 54 patients undergoing TKA into 2 groups: CFNB (Group F) and CIAB (Group I). Surgery was performed under spinal anesthesia. All patients received patient-controlled analgesia (PCA) with morphine, diclofenac, and acetaminophen for the first 72 h postoperatively...
June 20, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28634261/autophagy-gene-fip200-in-neural-progenitors-non-cell-autonomously-controls-differentiation-by-regulating-microglia
#8
Chenran Wang, Syn Yeo, Michael A Haas, Jun-Lin Guan
Recent studies have shown important roles for autophagy genes in the regulation of different tissue stem cells, including neural stem/progenitor cells (NSCs). However, little is known about whether autophagy can regulate NSCs through cell-extrinsic mechanisms. Here, we show that deletion of an essential autophagy gene, FIP200, in NSCs increased expression of Ccl5 and Cxcl10 in a p53-independent manner, mediating increased infiltration of microglia into the subventricular zone of both FIP200hGFAP conditional knockout (cKO) and FIP200;p53hGFAP 2cKO mice...
June 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28633655/inhibition-of-mmp-2-and-mmp-9-decreases-cellular-migration-and-angiogenesis-in-in-vitro-models-of-retinoblastoma
#9
Anderson H Webb, Bradley T Gao, Zachary K Goldsmith, Andrew S Irvine, Nabil Saleh, Ryan P Lee, Justin B Lendermon, Rajini Bheemreddy, Qiuhua Zhang, Rachel C Brennan, Dianna Johnson, Jena J Steinle, Matthew W Wilson, Vanessa M Morales-Tirado
BACKGROUND: Retinoblastoma (Rb) is the most common primary intraocular tumor in children. Local treatment of the intraocular disease is usually effective if diagnosed early; however advanced Rb can metastasize through routes that involve invasion of the choroid, sclera and optic nerve or more broadly via the ocular vasculature. Metastatic Rb patients have very high mortality rates. While current therapy for Rb is directed toward blocking tumor cell division and tumor growth, there are no specific treatments targeted to block Rb metastasis...
June 20, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28631539/regional-nerve-blocks-for-equine-dentistry
#10
Molly K Rice
Regional nerve blocks are necessary to facilitate equine oral surgery in the standing sedated patient. Step-by-step instruction on how to perform common regional nerve blocks are discussed, including infraorbital, maxillary, middle mental, and inferior alveolar nerve blocks. Regional nerve blocks are critical when performing dental procedures in the standing horse.(1) The infraorbital and maxillary nerve blocks provide anesthesia of the infraorbital nerve, which is a branch of the maxillary nerve. Both nerve blocks provide adequate anesthesia for all maxillary dental procedures...
June 2017: Journal of Veterinary Dentistry
https://www.readbyqxmd.com/read/28630680/purely-entropic-self-assembly-of-the-bicontinuous-ia3d-gyroid-phase-in-equilibrium-hard-pear-systems
#11
Philipp W A Schönhöfer, Laurence J Ellison, Matthieu Marechal, Douglas J Cleaver, Gerd E Schröder-Turk
We investigate a model of hard pear-shaped particles which forms the bicontinuous Ia[Formula: see text]d structure by entropic self-assembly, extending the previous observations of Barmes et al. (2003 Phys. Rev. E68, 021708. (doi:10.1103/PhysRevE.68.021708)) and Ellison et al. (2006 Phys. Rev. Lett.97, 237801. (doi:10.1103/PhysRevLett.97.237801)). We specifically provide the complete phase diagram of this system, with global density and particle shape as the two variable parameters, incorporating the gyroid phase as well as disordered isotropic, smectic and nematic phases...
August 6, 2017: Interface Focus
https://www.readbyqxmd.com/read/28630262/dipeptidyl-peptidase-4-inhibitor-anagliptin-prevents-intracranial-aneurysm-growth-by-suppressing-macrophage-infiltration-and-activation
#12
Taichi Ikedo, Manabu Minami, Hiroharu Kataoka, Kosuke Hayashi, Manabu Nagata, Risako Fujikawa, Sei Higuchi, Mika Yasui, Tomohiro Aoki, Miyuki Fukuda, Masayuki Yokode, Susumu Miyamoto
BACKGROUND: Chronic inflammation plays a key role in the pathogenesis of intracranial aneurysms (IAs). DPP-4 (dipeptidyl peptidase-4) inhibitors have anti-inflammatory effects, including suppressing macrophage infiltration, in various inflammatory models. We examined whether a DPP-4 inhibitor, anagliptin, could suppress the growth of IAs in a rodent aneurysm model. METHODS AND RESULTS: IAs were surgically induced in 7-week-old male Sprague Dawley rats, followed by oral administration of 300 mg/kg anagliptin...
June 19, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28630138/targeting-the-ras-palmitoylation-depalmitoylation-cycle-in-cancer
#13
REVIEW
David Tse Shen Lin, Nicholas G Davis, Elizabeth Conibear
The Ras proteins are well-known drivers of many cancers and thus represent attractive targets for the development of anticancer therapeutics. Inhibitors that disrupt the association of the Ras proteins with membranes by blocking the addition of the farnesyl lipid moiety to the Ras C-terminus failed in clinical trials. Here, we explore the possibility of targeting a second lipid modification, S-acylation, commonly referred to as palmitoylation, as a strategy to disrupt the membrane interaction of specific Ras isoforms...
June 19, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28630100/nlrp2-and-faf1-deficiency-blocks-early-embryogenesis-in-the-mouse
#14
Hui Peng, Hai-Jun Liu, Fang Liu, Yuyun Gao, Jing Chen, Jianchao Huo, Jinglin Han, Tianfang Xiao, Wenchang Zhang
Nlrp2 is a maternal effect gene specifically expressed by mouse ovaries; deletion of this gene from zygotes is known to result in early embryonic arrest. In the present study, we identified FAF1 protein as a specific binding partner of the NLRP2 protein in both mouse oocytes and preimplantation embryos. In addition to early embryos, both Faf1 mRNA and protein were detected in multiple tissues. NLRP2 and FAF1 proteins were co-localized to both the cytoplasm and nucleus during the development of oocytes and preimplantation embryos...
June 19, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28629165/a-cost-effective-vehicle-localization-solution-using-an-interacting-multiple-model-unscented-kalman-filters-imm-ukf-algorithm-and-grey-neural-network
#15
Qimin Xu, Xu Li, Ching-Yao Chan
In this paper, we propose a cost-effective localization solution for land vehicles, which can simultaneously adapt to the uncertain noise of inertial sensors and bridge Global Positioning System (GPS) outages. First, three Unscented Kalman filters (UKFs) with different noise covariances are introduced into the framework of Interacting Multiple Model (IMM) algorithm to form the proposed IMM-based UKF, termed as IMM-UKF. The IMM algorithm can provide a soft switching among the three UKFs and therefore adapt to different noise characteristics...
June 18, 2017: Sensors
https://www.readbyqxmd.com/read/28628783/automatic-retrieval-of-shoeprint-images-using-blocked-sparse-representation
#16
Sayyad Alizadeh, Cemal Kose
Shoe marks are regarded as remarkable clues which can be usually detected in crime scenes where forensic experts use them for investigating crimes and identifying the criminals. Hence, developing a robust method for matching shoeprints with one another is of critical significance which can be used for recognizing criminals. In this paper, a promising method is proposed for retrieving shoe marks by means of developing blocking sparse representation technique. In the proposed method, the queried image was divided into two blocks...
June 8, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28627626/hmgb1-regulates-p-glycoprotein-expression-in-status-epilepticus-rat-brains-via-the-rage-nf-%C3%AE%C2%BAb-signaling-pathway
#17
Yuan Xie, Nian Yu, Yan Chen, Kang Zhang, Hai-Yan Ma, Qing Di
Overexpression of P-glycoprotein (P-gp) in the brain is an important mechanism involved in drug‑resistant epilepsy (DRE). High-mobility group box 1 (HMGB1), an inflammatory cytokine, significantly increases following seizures and may be involved in upregulation of P‑gp. However, the underlying mechanisms remain elusive. The aim of the present study was to evaluate the role of HMGB1 and its downstream signaling components, receptor for advanced glycation end‑product (RAGE) and nuclear factor‑κB (NF‑κB), on P‑gp expression in rat brains during status epilepticus (SE)...
June 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627613/translocation-of-enterohemorrhagic-escherichia%C3%A2-coli-effector-tir-to-the-plasma-membrane-via-host-golgi-apparatus
#18
Chan Mao, Jiang Gu, Hai-Guang Wang, Yao Fang, Ping Yang, Bin Tang, Na Li, Ting-Ting Wang, Quan-Ming Zou, Qian Li
The translocated intimin receptor (Tir) is a canonical type III secretion system effector, secreted by the enterohemorrhagic Escherichia coli (E. coli). This receptor alters the regular cellular processing of host cells, to promote intracellular bacterial replication and evasion of the host immune system. Tir is translocated and integrated into the host cell plasma membrane, a process required for its pathogenic activity in these cells, however, the underlying mechanisms of how this occurs remain to be elucidated...
June 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627290/continuous-adductor-canal-block-added-to-local-infiltration-analgesia-lia-after-total-knee-arthroplasty-has-no-additional-benefits-on-pain-and-ambulation-on-postoperative-day-1-and-2-compared-with-lia-alone
#19
Svava Gudmundsdottir, Jonas L Franklin
Background and purpose - The additional effects of a continuous adductor canal block (ACB) compared with a single-dose local infiltration anesthesia (LIA) after total knee arthroplasty (TKA) has not been widely researched. Both methods have good effect individually. We hypothesized that a continuous ACB added to a single-dose LIA would lower pain scores while ambulating on postoperative day 1 (POD1) and postoperative day 2 (POD2). Patients and methods - 69 participants were included in this prospective, randomized, double-blind, placebo-controlled trial...
June 19, 2017: Acta Orthopaedica
https://www.readbyqxmd.com/read/28627137/effect-of-sympathetic-nerve-blockade-on-low-frequency-oscillations-of-forearm-and-leg-skin-blood-flow-in-healthy-humans
#20
Gary J Hodges, Matthew M Mallette, Zachary T Martin, Andrew T Del Pozzi
Examine the effect of inhibiting sympathetic function on cutaneous vasomotion in the forearm and leg METHODS: Intradermal microdialysis fibres were placed in the forearm and leg, one as an untreated control (lactated Ringer's) the other perfused with bretylium tosylate to block sympathetic nerves. Skin blood flow was monitored using laser-Doppler flowmetry. Baseline was collected for 10 min before local skin temperature was increased to 42°C. Spectral analysis was performed using a Morlet wavelet RESULTS: Bretylium tosylate increased skin blood flow during baseline in the forearm (d=1...
June 19, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
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