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https://www.readbyqxmd.com/read/28109880/dynamics-of-the-eag1-k-channel-selectivity-filter-assessed-by-molecular-dynamics-simulations
#1
Harald Bernsteiner, Michael Bründl, Anna Stary-Weinzinger
EAG1 channels belong to the KCNH family of voltage gated potassium channels. They are expressed in several brain regions and increased expression is linked to certain cancer types. Recent cryo-EM structure determination finally revealed the structure of these channels in atomic detail, allowing computational investigations. In this study, we performed molecular dynamics simulations to investigate the ion binding sites and the dynamical behavior of the selectivity filter. Our simulations suggest that sites S2 and S4 form stable ion binding sites, while ions placed at sites S1 and S3 rapidly switched to sites S2 and S4...
January 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28109158/using-the-volta-phase-plate-with-defocus-for-cryo-em-single-particle-analysis
#2
Radostin Danev, Dimitry Tegunov, Wolfgang Baumeister
Previously, we reported an in-focus data acquisition method for cryo-EM single particle analysis with the Volta phase plate (VPP) (Danev and Baumeister, 2016). Here, we extend the technique to include a small amount of defocus which enables contrast transfer function measurement and correction. This hybrid approach simplifies the experiment and increases the data acquisition speed. It also removes the resolution limit inherent to the in-focus method thus allowing 3D reconstructions with resolutions better than 3 Å...
January 21, 2017: ELife
https://www.readbyqxmd.com/read/28109132/echocardiographic-assessment-of-left-ventricular-function-in-healthy-horses-and-in-horses-with-heart-disease-using-pulsed-wave-tissue-doppler-imaging
#3
T R Koenig, K J Mitchell, C C Schwarzwald
BACKGROUND: Assessment of left ventricular (LV) function by tissue Doppler imaging (TDI) is not well established in horses with heart disease. OBJECTIVES: To describe the use of pulsed-wave (PW) TDI for the assessment of LV function, establish reference intervals, investigate effects of mitral regurgitation (MR), aortic regurgitation (AR), and primary myocardial disease (MD), and provide proof of concept for the use of PW TDI in Warmblood horses with heart disease...
January 21, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28109089/betulinic-acid-inhibits-cell-proliferation-in-human-oral-squamous-cell-carcinoma-via-modulating-ros-regulated-p53-signaling
#4
Huan Shen, Li Liu, Yongjin Yang, Wenxing Xun, Kewen Wei, Guang Zeng
Oral squamous cell carcinoma (OSCC) is a common cancer of the head and neck. Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid. The present study was designed to explore the effects of BA on OSCC KB cell proliferation <em>in vitro</em> and implanted tumor growth <em>in vivo</em> and to examine the possible molecular mechanisms. The results showed that BA dose-dependently inhibited KB cell proliferation and decreased implanted tumor volume. In addition, BA significantly promoted mitochondrial apoptosis, as reflected by increase of TUNEL-positive cells and activities of caspase 3 and 9, increase of Bax expression and decrease of Bcl-2 expression and mitochondrial oxygen consumption rate...
January 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28109085/silencing-of-interferon-induced-transmembrane-protein-1-ifitm1-inhibits-proliferation-migration-and-invasion-in-lung-cancer-cells
#5
Bing Jin, Hua Jin, Jing Wang
Interferon-induced transmembrane protein 1 (IFITM1), a 17-kDa membrane protein, is largely known as a player in many cellular functions. Recently, there have been studies showing overexpression of IFITM1 in cancers and a positive correlation of IFITM1 overexpression with tumor progression. However, it is poorly understood what role IFITM1 plays in lung cancer. In this study, we presented evidence that IFITM1 was highly expressed in lung cancer tissues and cell lines. IFITM1 silencing inhibited lung cancer cell proliferation, migration and invasion <em>in vitro</em>...
January 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28109080/microrna-21-inhibits-the-apoptosis-of-osteosarcoma-cell-line-saos-2-via-targeting-caspase-8
#6
Bin Xu, Hehuan Xia, Junming Cao, Zhihong Wang, Yipeng Yang, Yongsheng Lin
Currently, multiple microRNAs (miRNAs) have been found play vital roles in the pathogenesis of osteosarcoma. This studywas aimed to investigate the role of miR-21 in osteosarcoma. The level of miR-21 in 20 pairs of osteosarcoma and correspondingly adjacent tissues were monitored by qPCR. Human osteosarcoma cells line SAOS-2 was transfected with either miR-21 mimic or miR-21 inhibitor, and then cell viability, survival and apoptosis were respectively measured by MTT, colony formation assay, and flow cytometry...
January 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28109079/silencing-of-ribosomal-protein-l34-rpl34-inhibits-the-proliferation-and-invasion-of-esophageal-cancer-cells
#7
Huijie Fan, Jing Li, Yongxu Jia, Jingjing Wu, Long Yuan, Mingjun Li, Jiangqi Wei, Benling Xu
Ribosomal protein L34 (RPL34) belongs to the L34E family of ribosomal proteins and contains a zinc finger motif. Aberrant expression of RPL34 has been reported in several human malignancies. However, the precise role and potential underlying mechanisms of RPL34 in human esophageal cancer remain largely unknown. Thus, the objective of this study was to investigate the role of RPL34 in esophageal cancer progression. Our results showed that the expression of RPL34 at both mRNA and protein levels was frequently up-regulated in esophageal cancer cell lines...
January 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28109077/simultaneous-but-not-consecutive-combination-with-folinate-salts-potentiates-5-fluorouracil-antitumor-activity-in-vitro-and-in-vivo
#8
Antonello Di, Paola Orlandi, Teresa Di, Romano Danesi, Guido Bocci
The combination of folinate salts to 5-fluoruracil (5-FU)-based schedules is an established clinical routine in the landscape of the colorectal cancer treatment. The aim of this study was to investigate the pharmacological differences between the sequential administration of folinate salts (1 h before, as in clinical routine) followed by 5-FU and the simultaneous administration of both drugs. Proliferation and apoptotic assays were performed on human colon cancer cells exposed to 5-FU, calcium (CaLV) or disodium (NaLV) levofolinate or their simultaneous and sequential combination for 24 and 72h...
January 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28109075/knockdown-of-tacc3-inhibits-the-proliferation-and-invasion-of-human-renal-cell-carcinoma-cells
#9
Feng Guo, Yaquan Liu
Transforming acidic coiled-coil protein 3 (TACC3) is a member of the TACC family and plays an important role in regulating cell mitosis, transcription and tumorigenesis. However, the expression pattern and roles of TACC3 in renal cell carcinoma (RCC) remain unclear. The aim of this study was to investigate the role of TACC3 in RCC. We demonstrated overexpression of TACC3 in human RCC cell lines at both RNA and protein levels. Moreover, knockdown of TACC3 repressed RCC cell proliferation, migration and invasion <em>in vitro</em>...
January 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28106843/underwater-electromagnetic-sensor-networks-part-i-link-characterization
#10
Gara Quintana-Díaz, Pablo Mena-Rodríguez, Iván Pérez-Álvarez, Eugenio Jiménez, Blas-Pablo Dorta-Naranjo, Santiago Zazo, Marina Pérez, Eduardo Quevedo, Laura Cardona, J Joaquín Hernández
Underwater Wireless Sensor Networks (UWSNs) using electromagnetic (EM) technology in marine shallow waters are examined, not just for environmental monitoring but for further interesting applications. Particularly, the use of EM waves is reconsidered in shallow waters due to the benefits offered in this context, where acoustic and optical technologies have serious disadvantages. Sea water scenario is a harsh environment for radiocommunications, and there is no standard model for the underwater EM channel. The high conductivity of sea water, the effect of seabed and the surface make the behaviour of the channel hard to predict...
January 19, 2017: Sensors
https://www.readbyqxmd.com/read/28106073/high-resolution-cryo-em-structure-of-the-proteasome-in-complex-with-adp-alfx
#11
Zhanyu Ding, Zhenglin Fu, Cong Xu, Yifan Wang, Yanxing Wang, Junrui Li, Liangliang Kong, Jinhuan Chen, Na Li, Rongguang Zhang, Yao Cong
The 26S proteasome is an ATP-dependent dynamic 2.5 MDa protease that regulates numerous essential cellular functions through degradation of ubiquitinated substrates. Here we present a near-atomic-resolution cryo-EM map of the S. cerevisiae 26S proteasome in complex with ADP-AlFx. Our biochemical and structural data reveal that the proteasome-ADP-AlFx is in an activated state, displaying a distinct conformational configuration especially in the AAA-ATPase motor region. Noteworthy, this map demonstrates an asymmetric nucleotide binding pattern with four consecutive AAA-ATPase subunits bound with nucleotide...
January 20, 2017: Cell Research
https://www.readbyqxmd.com/read/28105983/effect-of-bone-marrow-aspirate-concentrate-platelet-rich-plasma-on-tendon-derived-stem-cells-and-rotator-cuff-tendon-tear
#12
Sun Jeong, Da Hyun, Jong Wook, Silvia Park, Sang Jun
Bone marrow aspirate concentrates (BMACs) and platelet-rich plasma (PRP) are good sources to control the differentiation of tendon derived stem cells (TDSCs) but there has been no study about the effect of BMAC-PRP complex on TDSCs and tendinopathy. The aim of this study was to investigate the effect of BMAC-PRP on the TDSCs and to find the therapeutic effect of BMAC-PRP on the rotator cuff tendon tear. Chondrogenic and osteogenic potential of TDSCs decreased, but adipogenic potential of TDSCs revealed no significant difference when they were co-cultured with BMAC-PRP...
January 20, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28105982/human-umbilical-cord-mesenchymal-stem-cells-inhibit-t-follicular-helper-cell-expansion-through-the-activation-of-inos-in-lupus-prone-b6-mrl-faslpr-mice
#13
Zhuoya Zhang, Ruihai Feng, Lingying Niu, Saisai Huang, Wei Deng, Bingyu Shi, Genhong Yao, Weiwei Chen, Xiaojun Tang, Xiang Gao, Xuebing Feng, Lingyun Sun
The aberrant generation or activation of T follicular helper (Tfh) cells contributes to the pathogenesis of systemic lupus erythematosus (SLE), yet little is known about how these cells are regulated. In this study, we demonstrated that the frequency of Tfh cells was increased in lupus-prone B6.MRL-<em>Fas<sup>lpr</sup></em> (B6.<em>lpr</em>) mice and positively correlated to plasma cell proportions and serum total IgG as well as anti-dsDNA antibody levels. Transplantation of human umbilical cord mesenchymal stem cells (UC-MSCs) ameliorated lupus symptoms in B6...
January 20, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28105975/simultaneous-determination-of-first-line-4-fdc-antituberculosis-drugs-by-uhplc-uv-and-hplc-uv-a-comparative-study
#14
Pedro H C Franco, Paula R Chellini, Marcone A L Oliveira, Gerson A Pianetti
Tuberculosis is the second most deadly infectiousdisease, surpassed only by HIV/AIDS, and hasresulted in over 1 billion deaths in the last200 years. The World Health Organization estimatesthat in 2014, 9.6 million people were infected bythis disease and 1.5 million had died. First-choicetreatment consists of fixed-dose combinationtablets containing rifampicin, isoniazid,pyrazinamide, and ethambutol hydrochloride(4-FDC). There are pharmacopeial protocolsavailable to test 4-FDC, but they are prolonged,two-step methods...
January 19, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28105972/comparative-validation-of-the-determination-of-sofosbuvir-in-pharmaceuticals-by-several-inexpensive-ecofriendly-chromatographic-electrophoretic-and-spectrophotometric-methods
#15
Amira F El-Yazbi
Sofosbuvir (SOFO) was approved by the U.S. Food and Drug Administration in 2013 for the treatment of hepatitis C virusinfection with enhanced antiviral potency compared with earlier analogs. Notwithstanding, all current editions of the pharmacopeias still do not present any analytical methods for the quantification of SOFO. Thus, rapid, simple, and ecofriendly methods for the routine analysis of commercial formulations of SOFO are desirable. In this study, five accurate methods for the determination of SOFO in pharmaceutical tablets were developed and validated...
January 20, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28105971/determination-of-tryptamines-and-%C3%AE-carbolines-in-ayahuasca-beverage-consumed-during-brazilian-religious-ceremonies
#16
Mônica Cardoso Santos, Sandro Navickiene, Alain Gaujac
Ayahuasca is a potent hallucinogenicbeverage prepared from <em>Banisteriopsis caapi</em>in combination with other psychoactive plants.<em>N</em>,<em>N</em>-dimethyltryptamine, tryptamine, harmine,harmaline, harmalol, and tetrahydroharmine werequantified in ayahuasca samples using a simpleand low-cost method based on SPE and LC with UVdiode-array detection. The experimental variablesthat affect the SPE method, such as type of solidphase and nature of solvent, were optimized...
January 19, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28104363/insights-into-the-distinct-mechanisms-of-action-of-taxane-and-non-taxane-microtubule-stabilizers-from-cryo-em-structures
#17
Elizabeth H Kellogg, Nisreen M A Hejab, Stuart Howes, Peter Northcote, John H Miller, J Fernando Díaz, Kenneth H Downing, Eva Nogales
A number of microtubule-stabilizing agents have demonstrated or predicted potential as anticancer agents, but a detailed structural basis for their mechanism of action is still lacking. We have obtained high-resolution (3.9-4.2Å) cryo-EM reconstructions of microtubules stabilized by the taxane-site binders Taxol and zampanolide, and by peloruside, which targets a distinct, non-taxoid pocket on β-tubulin. We find that each molecule has unique distinct structural effects on the microtubule lattice structure...
January 16, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28103954/differential-correlation-for-sequencing-data
#18
Charlotte Siska, Katerina Kechris
BACKGROUND: Several methods have been developed to identify differential correlation (DC) between pairs of molecular features from -omics studies. Most DC methods have only been tested with microarrays and other platforms producing continuous and Gaussian-like data. Sequencing data is in the form of counts, often modeled with a negative binomial distribution making it difficult to apply standard correlation metrics. We have developed an R package for identifying DC called Discordant which uses mixture models for correlations between features and the Expectation Maximization (EM) algorithm for fitting parameters of the mixture model...
January 19, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28103803/variational-inference-for-rare-variant-detection-in-deep-heterogeneous-next-generation-sequencing-data
#19
Fan Zhang, Patrick Flaherty
BACKGROUND: The detection of rare single nucleotide variants (SNVs) is important for understanding genetic heterogeneity using next-generation sequencing (NGS) data. Various computational algorithms have been proposed to detect variants at the single nucleotide level in mixed samples. Yet, the noise inherent in the biological processes involved in NGS technology necessitates the development of statistically accurate methods to identify true rare variants. RESULTS: We propose a Bayesian statistical model and a variational expectation maximization (EM) algorithm to estimate non-reference allele frequency (NRAF) and identify SNVs in heterogeneous cell populations...
January 19, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28103632/global-health-and-emergency-care-defining-clinical-research-priorities
#20
Bhakti Hansoti, Adam R Aluisio, Meagan A Barry, Kevin Davey, Brian A Lentz, Payal Modi, Jennifer A Newberry, Melissa H Patel, Tricia A Smith, Alexandra M Vinograd, Adam C Levine
OBJECTIVES: Despite recent strides in the development of Global Emergency Medicine (EM), the field continues to lag in applying a scientific approach to identifying critical knowledge gaps and advancing evidence-based solutions to clinical and public health problems seen in emergency departments worldwide. Here, progress on the Global EM research agenda created at the 2013 Academic Emergency Medicine Global Health and Emergency Care Consensus Conference is evaluated and critical areas for future development in emergency care research internationally are identified...
January 19, 2017: Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine
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