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https://www.readbyqxmd.com/read/27933736/structural-insight-into-the-anti-prion-compound-inhibition-mechanism-of-native-prion-folding-over-misfolding
#1
Jiwon Choi, Rajiv Gandhi Govindaraj, Jae Wook Hyeon, Kyungro Lee, SongLing Ma, Su Yeon Kim, Jeongmin Lee, Kyoung Tai No
Transition of a physiological folded prion (PrP(C) ) into a pathogenic misfolded prion (PrP(S)(c) ) causes lethal neurodegenerative disorders and prion diseases. Anti-prion compounds have been developed to prevent this conversion; however, their mechanism of action remains unclear. Recently, we reported two anti-prion compounds, BMD29 and 35, identified by in silico and in vitro screening. In this study, we used extensive explicit-solvent molecular dynamics simulations to investigate ligand binding inhibition by anti-prion compounds in prion folding over misfolding behavior at acidic pH...
December 9, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27933726/inheritance-of-evolved-clethodim-resistance-in-lolium-rigidum-populations-from-australia
#2
Rupinder Kaur Saini, Jenna Malone, Gurjeet Gill, Christopher Preston
BACKGROUND: In Australia, the extensive use of clethodim for the control of Lolium rigidum has resulted in the evolution of many clethodim-resistant L.rigidum populations. Five clethodim-resistant populations of L. rigidum were analysed for the inheritance of clethodim resistance. RESULTS: Reciprocal crosses were made between resistant (R) and susceptible (S) populations. Within crosses, dose responses of reciprocal F1 families of all populations, except A61 were similar each other, indicating clethodim resistance in these populations is encoded on the nuclear genome...
December 8, 2016: Pest Management Science
https://www.readbyqxmd.com/read/27933717/mass-cytometry-analytical-approaches-reveal-cytokine-induced-changes-in-natural-killer-cells
#3
Elena Vendrame, Julia Fukuyama, Dara M Strauss-Albee, Susan Holmes, Catherine A Blish
BACKGROUND: Natural killer (NK) cells have antiviral and antitumor activity that could be harnessed for the treatment of infections and malignancies. To maintain cell viability and enhance antiviral and antitumor effects, NK cells are frequently treated with cytokines. Here we performed an extensive assessment of the effects of cytokines on the phenotype and function of human NK cells. METHODS: We used cytometry by time-of-flight (CyTOF) to evaluate NK cell repertoire changes after stimulation with interleukin (IL)-2, IL-15 or a combination of IL- 12/IL-15/IL-18...
December 9, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27933697/total-magnetic-resonance-imaging-burden-of-cerebral-small-vessel-disease-is-associated-with-post-stroke-depression-in-patients-with-acute-lacunar-stroke
#4
X Zhang, Y Tang, Y Xie, C Ding, J Xiao, X Jiang, H Shan, Y Lin, C Li, D Hu, T Li, L Sheng
BACKGROUND AND PURPOSE: Despite extensive studies on post-stroke depression (PSD), the role of the total burden of cerebral small-vessel disease (cSVD) in its pathogenesis remains unclear. METHODS: We conducted a magnetic resonance imaging (MRI)-based cohort study to investigate the relationship between total MRI burden of cSVD and PSD among patients with first-ever lacunar stroke. From June 2013 to January 2016, 374 patients were consecutively recruited. PSD was identified using the Chinese version of the Structured Clinical Interview for DSM-IV...
December 9, 2016: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/27933682/high-efficient-intramolecular-electrochemiluminescence-energy-transfer-for-ultrasensitive-bioanalysis-of-aflatoxin-m1
#5
Jiali Liu, Min Zhao, Ying Zhuo, Yaqin Chai, Ruo Yuan
The intermolecular electrochemiluminescence resonance energy transfer (ECL-RET) between luminol and Ru(bpy)32+ was studied extensively to achieve the sensitive bio-analysis owing to the perfect spectral overlap of the donor and acceptor, but it still suffers from the challenging issue of low energy transfer efficiency. Here, the intramolecular ECL-RET towards the novel ECL compound containing the donor of luminol and the acceptor of Ru(bpy)2(mcbpy)2+ was designed and investigated for the first time (The compound was abbreviated as Lum-Ru)...
December 8, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27933604/chemoresistant-lung-cancer-stem-cells-display-high-dna-repair-capability-to-remove-cisplatin-dna-damage
#6
Wai-Kin Yu, Zhigang Wang, Chi-Chun Fong, Dandan Liu, Tak-Chun Yip, Siu-Kie Au, Guangyu Zhu, Mengsu Yang
BACKGROUND AND PURPOSE: The persistence of lung cancer stem cells (LCSCs) has been proposed to be the main factor of lung cancer recurrence due to their high resistance to conventional chemotherapy. The underlying mechanisms, however, have not been fully addressed. EXPERIMENTAL APPROACH: In this study, we examined the cellular response of a human lung cancer stem cell line upon treatment with cisplatin, a DNA-damaging anticancer drug that is extensively applied in clinics...
December 9, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27933538/systems-genetics-of-liver-fibrosis
#7
Rabea A Hall, Frank Lammert
This systems genetics analysis comprises quantitative measurements of hepatic fibrogenesis in mouse models and mapping of quantitative traits in mouse genetic reference populations. It is part of a large mapping project of fibrogenic genes including the analyses of experimental crosses from different inbred mouse strains. Extensive quantitative trait loci (QTL) mapping of fibrosis phenotypes and liver expression profiling in combination with in silico mapping facilitated the identification of QTL regions and underlying candidate genes that confer fibrosis susceptibility also in humans...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933525/expression-qtls-mapping-and-analysis-a-bayesian-perspective
#8
Martha Imprialou, Enrico Petretto, Leonardo Bottolo
The aim of expression Quantitative Trait Locus (eQTL) mapping is the identification of DNA sequence variants that explain variation in gene expression. Given the recent yield of trait-associated genetic variants identified by large-scale genome-wide association analyses (GWAS), eQTL mapping has become a useful tool to understand the functional context where these variants operate and eventually narrow down functional gene targets for disease. Despite its extensive application to complex (polygenic) traits and disease, the majority of eQTL studies still rely on univariate data modeling strategies, i...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933521/genenetwork-a-toolbox-for-systems-genetics
#9
Megan K Mulligan, Khyobeni Mozhui, Pjotr Prins, Robert W Williams
The goal of systems genetics is to understand the impact of genetic variation across all levels of biological organization, from mRNAs, proteins, and metabolites, to higher-order physiological and behavioral traits. This approach requires the accumulation and integration of many types of data, and also requires the use of many types of statistical tools to extract relevant patterns of covariation and causal relations as a function of genetics, environment, stage, and treatment. In this protocol we explain how to use the GeneNetwork web service, a powerful and free online resource for systems genetics...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933484/dna-as-a-target-for-anticancer-phen-imidazole-pd-ii-complexes
#10
Maryam Heydari, Mahboube Eslami Moghadam, AliAkbar Tarlani, Hossein Farhangian
Imidazole ring is a known structure in many natural or synthetic drug molecules and its metal complexes can interact with DNA and do the cleavage. Hence, to study the influence of the structure and size of the ligand on biological behavior of metal complexes, two water-soluble Pd(II) complexes of phen and FIP ligands (where phen is 1,10-phenanthroline and FIP is 2-(Furan-2-yl)-1H-Imidazo[4,5-f][1, 10]phenanthroline) with the formula of [Pd(phen)(FIP)](NO3)2 and [Pd(FIP)2]Cl2, that were activated against chronic myelogenous leukemia cell line, K562, were selected...
December 8, 2016: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/27933468/conditional-screening-for-ultra-high-dimensional-covariates-with-survival-outcomes
#11
Hyokyoung G Hong, Jian Kang, Yi Li
Identifying important biomarkers that are predictive for cancer patients' prognosis is key in gaining better insights into the biological influences on the disease and has become a critical component of precision medicine. The emergence of large-scale biomedical survival studies, which typically involve excessive number of biomarkers, has brought high demand in designing efficient screening tools for selecting predictive biomarkers. The vast amount of biomarkers defies any existing variable selection methods via regularization...
December 8, 2016: Lifetime Data Analysis
https://www.readbyqxmd.com/read/27933416/positron-emission-tomography-in-amyotrophic-lateral-sclerosis-towards-targeting-of-molecular-pathological-hallmarks
#12
Stefanie M A Willekens, Donatienne Van Weehaeghe, Philip Van Damme, Koen Van Laere
During the past decades, extensive efforts have been made to expand the knowledge of amyotrophic lateral sclerosis (ALS). However, clinical translation of this research, in terms of earlier diagnosis and improved therapy, remains challenging. Since more than 30% of motor neurons are lost when symptoms become clinically apparent, techniques allowing non-invasive, in vivo detection of motor neuron degeneration are needed in the early, pre-symptomatic disease stage. Furthermore, it has become apparent that non-motor signs play an important role in the disease and there is an overlap with cognitive disorders, such as frontotemporal dementia (FTD)...
December 8, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27933391/-tapering-and-termination-of-immunosuppressive-treatment-in-spondyloarthritides-including-psoriatic-arthritis
#13
REVIEW
G Scholz, B Möller
BACKGROUND: Immunomodulatory long-term treatment has also become the standard treatment for spondyloarthritides (SpA), including psoriatic arthritis (PsA); however, uncertainty exists about dose reduction or termination of treatment after remission or low disease activity. OBJECTIVE: When is it possible to reduce medication or terminate treatment for SpA? MATERIAL AND METHODS: An extensive non-systematic literature search was performed focusing on practice guidelines, systematic meta-analyses and clinical trials on medicinal long-term treatment and voluntary medication reduction in axial and peripheral SpA, including PsA...
December 8, 2016: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/27933361/biotransformation-and-detectability-of-the-new-psychoactive-substances-n-n-diallyltryptamine-dalt-derivatives-5-fluoro-dalt-7-methyl-dalt-and-5-6-methylenedioxy-dalt-in-urine-using-gc-ms-lc-ms-n-and-lc-hr-ms-ms
#14
Julian A Michely, Simon D Brandt, Markus R Meyer, Hans H Maurer
Derivatives of N,N-diallyltryptamine (DALT) can be classified as new psychoactive substances. Biotransformation and detectability of 5-fluoro-DALT (5-F-DALT), 7-methyl-DALT (7-Me-DALT), and 5,6-methylenedioxy-DALT (5,6-MD-DALT) are described here. Their metabolites detected in rat urine and pooled human liver microsomes were identified by liquid chromatography (LC)-high resolution (HR)-tandem mass spectrometry (MS/MS). In addition, the human cytochrome-P450 (CYP) isoenzymes involved in the main metabolic steps were identified and detectability tested in urine by the authors' urine screening approaches using GC-MS, LC-MS(n), or LC-HR-MS/MS...
December 8, 2016: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/27933350/endoscopic-ear-surgery%C3%A2-a%C3%A2-complement-to-microscopic-ear-surgery
#15
S Preyer
Wullstein, the founder of modern microscopic ear surgery, already used an oto-endoscope intraoperatively. However, it is only after the recent development of modern video-endoscopy with high-definition, 4K, and 3‑dimensional imaging that endoscopically guided surgery of the middle ear is gaining some importance. Key ventilation routes like the isthmus tympani and the epitympanic diaphragm can be visualized far better using an endoscope than with a microscope. Going through the external meatus, surgery of middle ear pathologies is possible without external incision...
December 8, 2016: HNO
https://www.readbyqxmd.com/read/27933314/tunneling-nanotubes-an-alternate-route-for-propagation-of-the-bystander-effect-following-oncolytic-viral-infection
#16
Justin Ady, Venugopal Thayanithy, Kelly Mojica, Phillip Wong, Joshua Carson, Prassanna Rao, Yuman Fong, Emil Lou
Tunneling nanotubes (TNTs) are ultrafine, filamentous actin-based cytoplasmic extensions which form spontaneously to connect cells at short and long-range distances. We have previously described long-range intercellular communication via TNTs connecting mesothelioma cells in vitro and demonstrated TNTs in intact tumors from patients with mesothelioma. Here, we investigate the ability of TNTs to mediate a viral thymidine kinase based bystander effect after oncolytic viral infection and administration of the nucleoside analog ganciclovir...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27933310/dynamics-of-antigen-presentation-to-transgene-product-specific-cd4-t-cells-and-of-treg-induction-upon-hepatic-aav-gene-transfer
#17
George Q Perrin, Irene Zolotukhin, Alexandra Sherman, Moanaro Biswas, Ype P de Jong, Cox Terhorst, Andrew M Davidoff, Roland W Herzog
The tolerogenic hepatic microenvironment impedes clearance of viral infections but is an advantage in viral vector gene transfer, which often results in immune tolerance induction to transgene products. Although the underlying tolerance mechanism has been extensively studied, our understanding of antigen presentation to transgene product-specific CD4(+) T cells remains limited. To address this, we administered hepatotropic adeno-associated virus (AAV8) vector expressing cytoplasmic ovalbumin (OVA) into wt mice followed by adoptive transfer of transgenic OVA-specific T cells...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933204/risk-factors-for-developing-colorectal-cancer-in-japanese-patients-with-ulcerative-colitis-a-retrospective-observational-study-capital-cohort-and-practice-for-ibd-total-management-in-kyoto-shiga-links-study-i
#18
Takuya Yoshino, Hiroshi Nakase, Tomohisa Takagi, Shigeki Bamba, Yusuke Okuyama, Takuji Kawamura, Teruki Oki, Hirozumi Obata, Chiharu Kawanami, Shinji Katsushima, Toshihiro Kusaka, Tomoyuki Tsujikawa, Yuji Naito, Akira Andoh, Takafumi Kogawa
BACKGROUND AND AIMS: Patients with ulcerative colitis (UC) are at risk for developing colorectal cancer (CRC), despite the development of new therapeutic agents. Stratification of the individual UC-patient's risk would be helpful to validate the risk factors for CRC. The aim of this study was to evaluate the risk factors for the development of CRC in a large cohort of patients with UC. METHODS: Data were obtained from 12 hospitals in the Kyoto-Shiga region during 2003-2013...
2016: BMJ Open Gastroenterology
https://www.readbyqxmd.com/read/27933150/implementing-mobile-devices-to-reduce-non-rostered-workload-for-junior-doctors
#19
Allan Plant, Suzanne Round, Joe Bourne
There is a large body of evidence demonstrating the detrimental effect of long work hours on the performance, mood, and job satisfaction of junior doctors. By extension these effects carry over into the realm of patient safety, compromising the quality of care provision. House officers in the general surgery department of Tauranga Hospital, New Zealand are often required to arrive at work well before their rostered start time of 7.30am to hand write the results of clinical investigations on their patient lists...
2016: BMJ Quality Improvement Reports
https://www.readbyqxmd.com/read/27933085/plant-physiological-morphological-and-yield-related-responses-to-night-temperature-changes-across-different-species-and-plant-functional-types
#20
Panpan Jing, Dan Wang, Chunwu Zhu, Jiquan Chen
Land surface temperature over the past decades has shown a faster warming trend during the night than during the day. Extremely low night temperatures have occurred frequently due to the influence of land-sea thermal difference, topography and climate change. This asymmetric night temperature change is expected to affect plant ecophysiology and growth, as the plant carbon consumption processes could be affected more than the assimilation processes because photosynthesis in most plants occurs during the daytime whereas plant respiration occurs throughout the day...
2016: Frontiers in Plant Science
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