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https://www.readbyqxmd.com/read/28644986/designing-novel-inhibitors-against-histone-acetyltransferase-hat-%C3%A2-gcn5-of-plasmodium-falciparum
#1
Amarjeet Kumar, Krishanu Bhowmick, Kunwar Somesh Vikramdeo, Neelima Mondal, Naidu Subbarao, Suman Kumar Dhar
During active proliferation phase of intra-erythrocytic cycle, the genome of P. falciparum is regulated epigenetically and evolutionary conserved parasite-specific histone proteins are extensively acetylated. The reversible process of lysine acetylation, causing transcriptional activation and its deacetylation, causing transcriptional repression is regulated by balanced activities of HATs and HDACs. They are also known to regulate antigenic variations and gametocytic conversion in P. falciparum. These histone modifying enzymes have been identified as potential targets for development of anitmalarials in literature...
June 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28644841/low-dimensional-spike-rate-models-derived-from-networks-of-adaptive-integrate-and-fire-neurons-comparison-and-implementation
#2
Moritz Augustin, Josef Ladenbauer, Fabian Baumann, Klaus Obermayer
The spiking activity of single neurons can be well described by a nonlinear integrate-and-fire model that includes somatic adaptation. When exposed to fluctuating inputs sparsely coupled populations of these model neurons exhibit stochastic collective dynamics that can be effectively characterized using the Fokker-Planck equation. This approach, however, leads to a model with an infinite-dimensional state space and non-standard boundary conditions. Here we derive from that description four simple models for the spike rate dynamics in terms of low-dimensional ordinary differential equations using two different reduction techniques: one uses the spectral decomposition of the Fokker-Planck operator, the other is based on a cascade of two linear filters and a nonlinearity, which are determined from the Fokker-Planck equation and semi-analytically approximated...
June 23, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28644799/hybrid-cs-dmri-periodic-time-variant-subsampling-and-omnidirectional-total-variation-based-reconstruction
#3
Yipeng Liu, Shan Wu, Xiaolin Huang, Bing Chen, Ce Zhu
Compressive sensing (CS) has been used to accelerate dynamic magnetic resonance imaging (DMRI). Currently, the online CS-DMRI is faster, whereas the offline CS-DMRI provides higher accuracy for image reconstruction. To achieve good image reconstruction performance in terms of both speed and accuracy, we propose a hybrid CS-DMRI method using periodic timevariant subsampling for different frames. In each period, there is one reference frame that is sampled at a higher subsampling ratio. The two nearby reference frames with good reconstruction quality can be used to provide rough predictions of the other frames between them...
June 20, 2017: IEEE Transactions on Medical Imaging
https://www.readbyqxmd.com/read/28644704/numerical-analysis-of-time-dependent-inhibition-kinetics-comparison-between-rat-liver-microsomes-and-rat-hepatocyte-data-for-mechanistic-model-fitting
#4
Chuong Pham, Swati Nagar, Ken Korzekwa
Time dependent inhibition (TDI) may confound drug interaction predictions. Recently, models were generated for an array of TDI kinetic schemes using numerical analysis of microsomal assays. Additionally, a distinct terminal inactivation step was identified for certain mechanism based inhibitors (MBI) following reversible metabolite intermediate complex (MIC) formation. Longer hepatocyte incubations potentially allow analysis of slow TDI and terminal inactivation. In the experiments presented here, we compared the quality of TDI parameterization by numerical analysis between hepatocyte and microsomal data...
June 23, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28644688/intraosseous-administration-of-antidotes-a-systematic-review
#5
Audrée Elliott, Pierre-André Dubé, Amélie Cossette-Côté, Laura Patakfalvi, Eric Villeneuve, Martin Morris, Sophie Gosselin
CONTEXT: Intraosseous (IO) access is an established route of administration in resuscitation situations. Patients with serious poisoning presenting to the emergency department may require urgent antidote therapy. However, intravenous (IV) access is not always readily available. OBJECTIVE: This study reviews the current evidence for IO administration of antidotes that could be used in poisoning. The primary outcome was mortality as a surrogate of efficacy. Secondary outcomes included hemodynamic variables, electrocardiographic variables, neurological status, pharmacokinetics outcomes, and adverse effects as defined by each article...
June 23, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28644663/origin-of-structural-modulations-in-ultrathin-fe-films-on-cu-001
#6
Xie Zhang, Tilmann Hickel, Jutta Rogal, Jörg Neugebauer
Employing ab initio calculations we demonstrate that the complex structural modulations experimentally observed in ultrathin Fe films on Cu(001) originate from Fe bulk phases that arise under extreme deformations. Specifically, we show that the structural modulations correspond to the motifs observed when transforming fcc Fe to bcc Fe in the Pitsch orientation relationship [(001)_{fcc}||(11[over ¯]0)_{bcc}]. The observed structural equivalence between surface and unstable bulk structures naturally explains the experimentally reported magnetic and structural transitions when going from low (two to four MLs) to intermediate (four to ten MLs) film coverages...
June 9, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28644395/optical-tracking-and-digital-quantification-of-beating-behavior-in-bioengineered-human-cardiac-organoids
#7
Mahesh Devarasetty, Steven Forsythe, Thomas D Shupe, Shay Soker, Colin E Bishop, Anthony Atala, Aleksander Skardal
Organoid and organ-on-a-chip technologies are rapidly advancing towards deployment for drug and toxicology screening applications. Liver and cardiac toxicities account for the majority of drug candidate failures in human trials. Liver toxicity generally produces liver cell death, while cardiac toxicity causes adverse changes in heart beat kinetics. In traditional 2D cultures, beating kinetics can be measured by electrode arrays, but in some 3D constructs, quantifying beating kinetics can be more challenging...
June 23, 2017: Biosensors
https://www.readbyqxmd.com/read/28644390/the-electrosome-a-surface-displayed-enzymatic-cascade-in-a-biofuel-cell-s-anode-and-a-high-density-surface-displayed-biocathodic-enzyme
#8
Alon Szczupak, Dror Aizik, Sarah Moraïs, Yael Vazana, Yoav Barak, Edward A Bayer, Lital Alfonta
The limitation of surface-display systems in biofuel cells to a single redox enzyme is a major drawback of hybrid biofuel cells, resulting in a low copy-number of enzymes per yeast cell and a limitation in displaying enzymatic cascades. Here we present the electrosome, a novel surface-display system based on the specific interaction between the cellulosomal scaffoldin protein and a cascade of redox enzymes that allows multiple electron-release by fuel oxidation. The electrosome is composed of two compartments: (i) a hybrid anode, which consists of dockerin-containing enzymes attached specifically to cohesin sites in the scaffoldin to assemble an ethanol oxidation cascade, and (ii) a hybrid cathode, which consists of a dockerin-containing oxygen-reducing enzyme attached in multiple copies to the cohesin-bearing scaffoldin...
June 23, 2017: Nanomaterials
https://www.readbyqxmd.com/read/28644348/biomarkers-of-environmental-enteric-dysfunction-among-children-in-rural-bangladesh
#9
Rebecca K Campbell, Kerry J Schulze, Saijuddin Shaikh, Sucheta Mehra, Hasmot Ali, Lee Wu, Rubhana Raqib, Sarah Baker, Alain Labrique, Keith P West, Parul Christian
OBJECTIVES: Environmental enteric dysfunction (EED) may inhibit growth and development in low- and middle-income countries, but available assessment methodologies limit its study. In rural Bangladesh, we measured EED using the widely used lactulose mannitol ratio (L:M) test and a panel of intestinal and systemic health biomarkers to evaluate convergence among biomarkers and describe risk factors for EED. METHODS: In 539 18-month-old children finishing participation in a randomized food supplementation trial, serum, stool, and urine collected after lactulose and mannitol dosing were analyzed for biomarkers of intestinal absorption, inflammation, permeability and repair, and systemic inflammation...
July 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28644031/tris-cyclopentadienyl-lanthanide-complexes-as-catalysts-for-hydroboration-reaction-toward-aldehydes-and-ketones
#10
Sufang Chen, Dandan Yan, Mingqiang Xue, Yubiao Hong, Yingming Yao, Qi Shen
It was found that homoleptic cyclopentadienyl lanthanide complexes Cp3Ln (Ln = Y (1), Yb (2), Sm (3), Nd (4), La (5), Cp = cyclopentadienyl) can be employed as excellent catalysts for the hydroboration of various aldehydes and ketones toward pinacolborane. These robust lanthanide catalysts exhibited high reactivity with low catalyst loadings (0.01-1 mol %) under mild conditions and good functional group tolerability. These complexes also demonstrated uniquely carbonyl-selective hydroboration in the presence of alkenes and alkynes...
June 23, 2017: Organic Letters
https://www.readbyqxmd.com/read/28644017/spectrally-undiscerned-isomers-might-lead-to-erroneous-determination-of-water-exchange-rates-of-paracest-eu-iii-agents
#11
Nevenka Cakić, Ben Tickner, Moritz Zaiss, David Esteban-Gómez, Carlos Platas-Iglesias, Goran Angelovski
We report a detailed study of the solution structure and water exchange rate of a Eu(III) complex with the cyclen-based ligand L(1), containing (S)-2-(2-acetamido)-3-(4-(trifluoromethyl)phenyl)propanoate pendant arms at positions 1 and 7 of the cyclen ring and acetylglycinate pendants at positions 4 and 10. The EuL(1) complex was characterized by a combination of NMR and luminescence spectroscopy and density functional theory (DFT) calculations. The chemical exchange saturation transfer (CEST) spectra obtained at different temperatures and saturation powers present a CEST signal attributed to the coordinated water molecule...
June 23, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28643795/the-genomic-landscape-of-tuberous-sclerosis-complex
#12
Katie R Martin, Wanding Zhou, Megan J Bowman, Juliann Shih, Kit Sing Au, Kristin E Dittenhafer-Reed, Kellie A Sisson, Julie Koeman, Daniel J Weisenberger, Sandra L Cottingham, Steven T DeRoos, Orrin Devinsky, Mary E Winn, Andrew D Cherniack, Hui Shen, Hope Northrup, Darcy A Krueger, Jeffrey P MacKeigan
Tuberous sclerosis complex (TSC) is a rare genetic disease causing multisystem growth of benign tumours and other hamartomatous lesions, which leads to diverse and debilitating clinical symptoms. Patients are born with TSC1 or TSC2 mutations, and somatic inactivation of wild-type alleles drives MTOR activation; however, second hits to TSC1/TSC2 are not always observed. Here, we present the genomic landscape of TSC hamartomas. We determine that TSC lesions contain a low somatic mutational burden relative to carcinomas, a subset feature large-scale chromosomal aberrations, and highly conserved molecular signatures for each type exist...
June 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28643794/enrichment-of-low-frequency-functional-variants-revealed-by-whole-genome-sequencing-of-multiple-isolated-european-populations
#13
Yali Xue, Massimo Mezzavilla, Marc Haber, Shane McCarthy, Yuan Chen, Vagheesh Narasimhan, Arthur Gilly, Qasim Ayub, Vincenza Colonna, Lorraine Southam, Christopher Finan, Andrea Massaia, Himanshu Chheda, Priit Palta, Graham Ritchie, Jennifer Asimit, George Dedoussis, Paolo Gasparini, Aarno Palotie, Samuli Ripatti, Nicole Soranzo, Daniela Toniolo, James F Wilson, Richard Durbin, Chris Tyler-Smith, Eleftheria Zeggini
The genetic features of isolated populations can boost power in complex-trait association studies, and an in-depth understanding of how their genetic variation has been shaped by their demographic history can help leverage these advantageous characteristics. Here, we perform a comprehensive investigation using 3,059 newly generated low-depth whole-genome sequences from eight European isolates and two matched general populations, together with published data from the 1000 Genomes Project and UK10K. Sequencing data give deeper and richer insights into population demography and genetic characteristics than genotype-chip data, distinguishing related populations more effectively and allowing their functional variants to be studied more fully...
June 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28643793/genomic-rearrangements-in-sporadic-lymphangioleiomyomatosis-an-evolving-genetic-story
#14
Stephen J Murphy, Simone B Terra, Faye R Harris, Aqsa Nasir, Jesse S Voss, James B Smadbeck, Sarah H Johnson, Vishnu Serla, Jay H Ryu, Eunhee S Yi, Benjamin R Kipp, George Vasmatzis, Eva M Carmona
Sporadic lymphangioleiomyomatosis is a progressive pulmonary cystic disease resulting from the infiltration of smooth muscle-like lymphangioleiomyomatosis cells into the lung. The migratory/metastasizing properties of the lymphangioleiomyomatosis cell together with the presence of somatic mutations, primarily in the tuberous sclerosis complex gene (TSC2), lead many to consider this a low-grade malignancy. As malignant tumors characteristically accumulate somatic structural variations, which have not been well studied in sporadic lymphangioleiomyomatosis, we utilized mate pair sequencing to define structural variations within laser capture microdissected enriched lymphangioleiomyomatosis cell populations from five sporadic lymphangioleiomyomatosis patients...
June 23, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28643629/faecal-immunochemical-tests-to-triage-patients-with-lower-abdominal-symptoms-for-suspected-colorectal-cancer-referrals-in-primary-care-a-systematic-review-and-cost-effectiveness-analysis
#15
Marie Westwood, Isaac Corro Ramos, Shona Lang, Marianne Luyendijk, Remziye Zaim, Lisa Stirk, Maiwenn Al, Nigel Armstrong, Jos Kleijnen
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in the UK. Presenting symptoms that can be associated with CRC usually have another explanation. Faecal immunochemical tests (FITs) detect blood that is not visible to the naked eye and may help to select patients who are likely to benefit from further investigation. OBJECTIVES: To assess the effectiveness of FITs [OC-Sensor (Eiken Chemical Co./MAST Diagnostics, Tokyo, Japan), HM-JACKarc (Kyowa Medex/Alpha Laboratories Ltd, Tokyo, Japan), FOB Gold (Sentinel/Sysmex, Sentinel Diagnostics, Milan, Italy), RIDASCREEN Hb or RIDASCREEN Hb/Hp complex (R-Biopharm, Darmstadt, Germany)] for primary care triage of people with low-risk symptoms...
May 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28643478/critical-role-of-tnf-inhibition-in-combination-therapy-for-elderly-mice-with-atherosclerosis
#16
Kyung-Yeon Park, Tae-Hwe Heo
We have previously shown that the combination of pravastatin and sarpogrelate is synergistically beneficial for atherosclerosis. In this study, we investigated whether the pravastatin-sarpogrelate combination was sufficient for treatment in an old mouse model of atherosclerosis or if additional intervention would be needed to address the newly included aging factor and its complex pathophysiological impact on the atherosclerogenic state. We added an anti-TNF biologic to the combination treatment cocktail because of the known pathologic roles of TNF in the aging process...
June 23, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28643250/genome-editing-in-mouse-zygotes-and-embryonic-stem-cells-by-introducing-sgrna-cas9-expressing-plasmids
#17
Taichi Noda, Asami Oji, Masahito Ikawa
In mammalian cells, genome editing with the single guide RNA (sgRNA)/Cas9 complex allows for high targeting efficiency within a relatively short time frame with the added benefits of being low cost and easy to design. sgRNA/Cas9-mediated editing in mouse zygotes has accelerated the analysis of gene functions and the generation of mouse models of human diseases. Despite the benefits, this method still suffers from several problems, such as mosaicism in the founder generation which complicates genotyping and phenotypical analyses, and the low efficiency of more complicated genome editing...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28643202/specific-igm-and-regulation-of-antibody-responses
#18
Anna Sörman, Birgitta Heyman
Specific IgM, administered together with the antigen it recognizes, enhances primary antibody responses, formation of germinal centers, and priming for secondary antibody responses. The response to all epitopes on the antigen to which IgM binds is usually enhanced. IgM preferentially enhances responses to large antigens such as erythrocytes, malaria parasites, and keyhole limpet hemocyanine. In order for an effect to be seen, antigens must be administered in suboptimal concentrations and in close temporal relationship to the IgM...
June 23, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28643084/influence-of-knockout-of-at4g20990-gene-encoding-%C3%AE-ca4-on-photosystem-ii-light-harvesting-antenna-in-plants-grown-under-different-light-intensities-and-day-lengths
#19
Natalia N Rudenko, Tatyana P Fedorchuk, Daria V Vetoshkina, Elena M Zhurikova, Lyudmila K Ignatova, Boris N Ivanov
Effect of knockout of the At4g20990 gene encoding α-carbonic anhydrase 4 (α-CA4) in Arabidopsis thaliana in plants grown in low light (LL, 80 μmol photons m(-2) s(-1)) or in high light (HL, 400 μmol photons m(-2) s(-1)) under long (LD, 16 h) or short (SD, 8 h) day length was studied. In α-CA4 knockout plants, under all studied conditions, the non-photochemical quenching was lower; the decrease was more pronounced under HL. This pointed to α-CA4 implication in the processes leading to energy dissipation in PSII antenna...
June 22, 2017: Protoplasma
https://www.readbyqxmd.com/read/28642774/increasing-provasculature-complexity-in-the-arabidopsis-embryo-may-increase-total-iron-content-in-seeds-a-hypothesis
#20
Hannetz Roschzttardtz, Sofía Bustos, Maria F Coronas, Miguel A Ibeas, Susana Grant-Grant, Joaquín Vargas-Pérez
Anemia due to iron deficiency is a worldwide issue, affecting mainly children and women. Seed iron is a major source of this micronutrient for feeding, however, in most crops these levels are too low to meet daily needs. Thus, increasing iron allocation and its storage in seeds can represent an important step to enhance iron provision for humans and animals. Our knowledge on seed iron homeostasis is mainly based on studies performed in the model plant Arabidopsis thaliana, where iron accumulates in endodermis cells surrounding the embryo provasculature...
2017: Frontiers in Plant Science
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