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Biological models

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https://www.readbyqxmd.com/read/29054054/conformational-analysis-of-the-human-chemokine-receptor-cxcr3
#1
Raffaele Raucci, Andrea Polo, Alfredo Budillon, Giovanni Colonna, Susan Costantini
In the last years, some studies showed the patho-genetic role of CXCR3 bound to its ligands in many human inflammatory diseases and cancers. Thus, the blockage of the CXCR3 interaction site to its ligands is seen as a possible therapeutic target for the treatment of cancer. The presence of flexible regions in the chemokine receptors determines their capability to develop specific mechanisms of action. We have recently focused on the features of the N-terminal region of human CXCR3 free in solution, where we demonstrate the presence of numerous conformational ensembles, dynamically stabilized by H-bonds...
October 17, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29053961/maturation-of-xenopus-laevis-oocytes-under-cadmium-and-lead-exposures-cell-biology-investigations
#2
Sylvain Slaby, Julie Hanotel, Guillaume Marchand, Arlette Lescuyer, Jean-François Bodart, Alain Leprêtre, Sébastien Lemière, Matthieu Marin
Since amphibians are recognised as good models to assess the quality of environments, only few studies have dealt with the impacts of chemical contaminants on their gametes, while toxic effects at this stage will alter all the next steps of their life cycle. Therefore, we propose to investigate the oocyte maturation of Xenopus laevis in cadmium- and lead-contaminated conditions. The impacts of cadmium and lead ions were explored on events involved in the hormone-dependent process of maturation. In time-course experiments, cadmium, at the highest concentration, delayed and prevented the germinal vesicle breakdown...
October 16, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29053948/nanoscale-imaging-reveals-big-role-for-iron-in-alzheimer-s-disease
#3
Scott Ayton, Simon A James, Ashley I Bush
In this issue of Cell Chemical Biology, Telling et al. (2017) apply advanced X-ray microscopy techniques to reveal magnetite iron species in plaques from a mouse model of Alzheimer's disease. The characterization of abnormal iron chemistry in the disease model highlights the potential for iron to combine with the β-amyloid peptide and accelerate the disease process.
October 19, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29053920/turn-on-fluorene-push-pull-probes-with-high-brightness-and-photostability-for-visualizing-lipid-order-in-biomembranes
#4
Janah Shaya, Mayeul Collot, Frédéric Benailly, Najiba Mahmoud, Yves Mély, Benoît Y Michel, Andrey S Klymchenko, Alain Burger
The rational design of environment-sensitive dyes with superior properties is critical for elucidating the fundamental biological processes and understanding the biophysical behavior of cell membranes. In this study, a novel group of fluorene-based push-pull probes was developed for imaging membrane lipids. The design of these fluorogenic conjugates is based on a propioloyl linker to preserve the required spectroscopic features of the core dye. This versatile linker allowed the introduction of a polar deoxyribosyl head, a lipophilic chain, and an amphiphilic/anchoring group to tune the cell membrane binding and internalization...
October 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29053810/associations-between-cellular-aging-markers-and-metabolic-syndrome-findings-from-the-cardia-study
#5
Dóra Révész, Josine E Verhoeven, Martin Picard, Jue Lin, Stephen Sidney, Elissa S Epel, Brenda W J H Penninx, Eli Puterman
Background: Metabolic syndrome (MetS) is thought to promote biological aging, which might lead to cardiovascular and aging-related complications. This large-scale study investigated longitudinal relationships between MetS, its components, and cellular aging markers: leukocyte mitochondrial DNA copy number (mtDNAcn) and telomere length (TL). Methods: We included 989 participants from the Coronary Artery Risk Development in Young Adults Study. MtDNAcn (CARDIA Years 15, 25) and TL (Y15, Y20, Y25) were measured using quantitative PCR...
October 18, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29053679/measuring-the-effect-of-chemicals-on-the-growth-and-reproduction-of-caenorhabditis-elegans
#6
So Young Lee, Kyungsu Kang
Toxicological evaluation is crucial for understanding the effects of chemicals on living organisms in basic and applied biological science fields. A non-mammalian soil round worm, Caenorhabditis elegans, is a valuable model organism for toxicology studies due to its convenience and lack of animal ethics issues compared with mammalian animal systems. In this protocol, a detailed procedure of toxicological evaluation of chemicals in C. elegans is described. A clinical anticancer drug, etoposide, which targets human topoisomerase II and inhibits DNA replication of human cancer cells, was selected as a model testing chemical...
October 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053676/laminotomy-for-lumbar-dorsal-root-ganglion-access-and-injection-in-swine
#7
Mark D Unger, Timothy P Maus, Ross C Puffer, Laura K Newman, Bradford L Currier, Andreas S Beutler
Dorsal root ganglia (DRG) are anatomically well defined structures that contain all primary sensory neurons below the head. This fact makes DRG attractive targets for injection of novel therapeutics aimed at treating chronic pain. In small animal models, laminectomy has been used to facilitate DRG injection because it involves surgical removal of the vertebral bone surrounding each DRG. We demonstrate a technique for intraganglionic injection of lumbar DRG in a large animal species, namely, swine. Laminotomy is performed to allow direct access to DRG using standard neurosurgical techniques, instruments, and materials...
October 10, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053672/sample-extraction-and-simultaneous-chromatographic-quantitation-of-doxorubicin-and-mitomycin-c-following-drug-combination-delivery-in-nanoparticles-to-tumor-bearing-mice
#8
Rui Xue Zhang, Tian Zhang, King Chen, Ji Cheng, Paris Lai, Andrew M Rauth, K Sandy Pang, Xiao Yu Wu
Combination chemotherapy is frequently used in the clinic for cancer treatment; however, associated adverse effects to normal tissue may limit its therapeutic benefit. Nanoparticle-based drug combination has been shown to mitigate the problems encountered by free drug combination therapy. Our previous studies have shown that the combination of two anticancer drugs, doxorubicin (DOX) and mitomycin C (MMC), produced a synergistic effect against both murine and human breast cancer cells in vitro. DOX and MMC co-loaded polymer-lipid hybrid nanoparticles (DMPLN) bypassed various efflux transporter pumps that confer multidrug resistance and demonstrated enhanced efficacy in breast tumor models...
October 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053434/alpha-gal-inactivated-heart-valve-bioprostheses-exhibit-an-anti-calcification-propensity-similar-to-knockout-tissues
#9
Filippo Naso, Ugo Stefanelli, Edward Buratto, Giovanna Lazzari, Andrea Perota, Cesare Galli, Alessandro Gandaglia
BACKGROUND: Glutaraldehyde (GLA) has been used to crosslink bioprosthetic heart valve (BHVs) tissues to enhance their stability, besides ensuring a satisfactory degree of immunological tolerance. Unfortunately, GLA fixation does not guarantee a complete tissue biocompatibility of BHVs in currently used devices. The interaction between preformed human anti-alpha-Gal antibody and alpha-Gal antigens promotes the calcification of GLA-treated alpha-Gal-positive tissue. Recently, an alarming correlation between the presence of the alpha-Gal epitope and a premature BHVs degeneracy was reported...
October 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29053271/discovery-of-7-18-f-fluorotryptophan-as-a-novel-pet-probe-for-the-visualization-of-tryptophan-metabolism-in-vivo
#10
Boris D Zlatopolskiy, Johannes Zischler, Dominique Schäfer, Elizaveta A Urusova, Mehrab Guliyev, Olesia Bannykh, Heike Endepols, Bernd Neumaier
Tryptophan and its metabolites are involved in different physiological and pathophysiological processes. Consequently, PET tracers addressing tryptophan metabolic pathways should allow the detection of different pathologies like neurological disorders and cancer. Herein we report an efficient method for the preparation of fluorotryptophans labeled in different positions with (18)F and their biological evaluation. 4-7-[(18)F]Fluorotryptophans ([(18)F]FTrps) were prepared according to a modified protocol of alcohol-enhanced Cu-mediated radiofluorination in 30-53% radiochemical yields...
October 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29053260/qm-mm-study-of-the-nitrogenase-mofe-protein-resting-state-broken-symmetry-states-protonation-states-and-qm-region-convergence-in-the-femoco-active-site
#11
Bardi Benediktsson, Ragnar Bjornsson
Nitrogenase is one of the most fascinating enzymes in nature, being responsible for all biological nitrogen reduction. Despite decades of research, it is among the enzymes in bioinorganic chemistry whose mechanism is the most poorly understood. The MoFe protein of nitrogenase contains an iron-molybdenum-sulfur cluster, FeMoco, where N2 reduction takes place. The resting state of FeMoco has been characterized by crystallography, multiple spectroscopic techniques, and theory (broken-symmetry density functional theory), and all heavy atoms are now characterized...
October 20, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/29053164/narrmda-negative-aware-and-rating-based-recommendation-algorithm-for-mirna-disease-association-prediction
#12
Lihong Peng, Yeqing Chen, Ning Ma, Xing Chen
An increasing amount of evidence indicates that microRNAs (miRNAs) are closely related to many important biological processes and play a significant role in various human diseases. More and more researchers have begun to seek effective methods to predict potential miRNA-disease associations. However, reliable computational methods to predict potential disease-related miRNAs are lacking. In this study, we developed a new miRNA-disease association prediction model called Negative-Aware and rating-based Recommendation algorithm for miRNA-Disease Association prediction (NARRMDA) based on the known miRNA-disease associations in the HMDD database, miRNA functional similarity, disease semantic similarity and Gaussian interaction profile kernel similarity...
October 20, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/29053105/biological-and-dosimetric-characterisation-of-spatially-fractionated-proton-minibeams
#13
Juergen Meyer, Robert D Stewart, Daniel Smith, James Eagle, Eunsin Lee, Ning Cao, Eric Ford, Reza Hashemian, Jan Schuemann, Jatinder Saini, Steven Marsh, Robert Emery, Eric Dorman, Jeffrey L Schwartz, George A Sandison
The biological effectiveness of proton beams varies with depth, spot size and lateral distance from the beam central axis. The aim of this work is to incorporate proton relative biological effectiveness (RBE) and equivalent uniform dose (EUD) considerations into comparisons of broad beam and highly modulated proton minibeams. A Monte Carlo model of a small animal proton beamline is presented. Dose and variable RBE is calculated on a per-voxel basis for a range of energies (30-109 MeV). For an open beam, the RBE values at the beam entrance ranged from 1...
October 20, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/29053080/aerosolizing-lipid-dispersions-enables-antibiotic-transport-across-mimics-of-the-lung-airway-surface-even-in-the-presence-of-pre-existing-lipid-monolayers
#14
Steven V Iasella, Amy Z Stetten, Timothy E Corcoran, Stephen Garoff, Todd M Przybycien, Robert D Tilton
BACKGROUND: Secondary lung infections are the primary cause of morbidity associated with cystic fibrosis lung disease. Aerosolized antibiotic inhalation is potentially advantageous but has limited effectiveness due to altered airway aerodynamics and deposition patterns that limit drug access to infected regions. One potential strategy to better reach infected areas is to formulate aerosols with surfactants that induce surface tension gradients and drive postdeposition drug dispersal via Marangoni transport along the airway surface liquid (ASL)...
October 20, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/29052843/animal-models-in-translational-research-rosetta-stone-or-stumbling-block
#15
REVIEW
Jessica A Bolker
Leading animal models are powerful tools for translational research, but they also present obstacles. Poorly conducted preclinical research in animals is a common cause of translational failure, but even when such research is well-designed and carefully executed, challenges remain. In particular, dominant models may bias research directions, elide essential aspects of human disease, omit important context, or subtly shift research targets. Recognizing these stumbling blocks can help us find ways to avoid them: employing a wider range of models, incorporating more realistic environmental conditions, better aligning studies between animals and patients, and focusing on human biology and therapeutic goals...
October 20, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/29052800/dermatologist-and-patient-preferences-in-choosing-treatments-for-moderate-to-severe-psoriasis
#16
Matthew Alcusky, Seina Lee, Gordon Lau, Gretchen R Chiu, Nandini Hadker, Aparna Deshpande, Stephen Fleming, Nicola Vance, Steve Fakharzadeh
INTRODUCTION: The objective of the study was to determine the relative importance (RI) of treatment attributes psoriasis patients and physicians consider when choosing between biologic therapies based on psoriasis severity. METHODS: A discrete choice experiment (DCE) weighting preference for eight sets of hypothetical treatments for moderate or severe psoriasis was conducted. DCE hypothetical treatments were defined and varied on combinations of efficacy, safety, and dosing attributes [frequency/setting/route of administration (ROA)]...
October 20, 2017: Dermatology and Therapy
https://www.readbyqxmd.com/read/29052279/combining-protein-sequence-structure-and-dynamics-a-novel-approach-for-functional-evolution-analysis-of-pas-domain-superfamily
#17
Zheng Dong, Hongyu Zhou, Peng Tao
OBJECTIVES: PAS domains are widespread in archaea, bacteria and eukaryota, and play important roles in various functions. In this study, we aim to explore functional evolutionary relationship among proteins in the PAS domain superfamily in view of the sequence-structure-dynamics-function relationship. METHODS: We collected protein sequences and crystal structures data from RCSB Protein Data Bank of the PAS domain superfamily belonging to three biological functions (nucleotide binding, photoreceptor activity and transferase activity)...
October 20, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29052234/measuring-precision-in-bioassays-rethinking-assay-validation
#18
Michael P Fay, Michael C Sachs, Kazutoyo Miura
The m:n:θb procedure is often used for validating an assay for precision, where m levels of an analyte are measured with n replicates at each level, and if all m estimates of coefficient of variation (CV) are less than θb , then the assay is declared validated for precision. The statistical properties of the procedure are unknown so there is no clear statistical statement of precision upon passing. Further, it is unclear how to modify the procedure for relative potency assays in which the constant standard deviation (SD) model fits much better than the traditional constant CV model...
October 19, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/29052221/advance-in-physiologically-based-pharmacokinetic-modelling-from-the-organ-level-to-sub-organ-level-based-on-experimental-data
#19
Zhoumeng Lin
Understanding the pharmacokinetics and target organ dosimetry properties of small molecular drugs and large molecular biologics is essential in the design of proper therapeutic regimens for disease treatments. This article is protected by copyright. All rights reserved.
October 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29052210/a-method-for-testing-random-spatial-models-on-nuclear-object-distributions
#20
Javier Arpòn, Valérie Gaudin, Philippe Andrey
The cell nucleus is a structurally complex and dynamic organelle ensuring key biological functions. Complex relationships between nuclear structure and functions require a better understanding of the three-dimensional organization of the genome and of the subnuclear compartments. Quantitative image analysis coupled with spatial statistics and modeling is a relevant approach to address these questions. In this chapter, we describe a step-by-step procedure to process images and to test a spatial random model for the distribution of nuclear objects using chromocenters as an example...
2018: Methods in Molecular Biology
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