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https://www.readbyqxmd.com/read/28916626/contextual-fear-conditioning-in-zebrafish
#1
Justin W Kenney, Ian C Scott, Sheena A Josselyn, Paul W Frankland
Zebrafish are a genetically tractable vertebrate that hold considerable promise for elucidating the molecular basis of behavior. Although numerous recent advances have been made in the ability to precisely manipulate the zebrafish genome, much less is known about many aspects of learning and memory in adult fish. Here, we describe the development of a contextual fear conditioning paradigm using an electric shock as the aversive stimulus. We find that contextual fear conditioning is modulated by shock intensity, prevented by an established amnestic agent (MK-801), lasts at least 14 d, and exhibits extinction...
October 2017: Learning & Memory
https://www.readbyqxmd.com/read/28916270/understanding-taurine-cns-activity-using-alternative-zebrafish-models
#2
REVIEW
Nathana J Mezzomo, Barbara D Fontana, Allan V Kalueff, Leonardo J G Barcellos, Denis B Rosemberg
Taurine is a highly abundant "amino acid" in the brain. Despite the potential neuroactive role of taurine in vertebrates has long been recognized, the underlying molecular mechanisms related to its pleiotropic effects in the brain remain poorly understood. Due to the genetic tractability, rich behavioral repertoire, neurochemical conservation, and small size, the zebrafish (Danio rerio) has emerged as a powerful candidate for neuropsychopharmacology investigation and in vivo drug screening. Here, we summarize the main physiological roles of taurine in mammals, including neuromodulation, osmoregulation, membrane stabilization, and antioxidant action...
September 12, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28915438/cell-wall-biomechanics-a-tractable-challenge-in-manipulating-plant-cell-walls-fit-for-purpose
#3
REVIEW
Kim L Johnson, Michael J Gidley, Antony Bacic, Monika S Doblin
The complexity and recalcitrance of plant cell walls has contributed to the success of plants colonising land. Conversely, these attributes have also impeded progress in understanding the roles of walls in controlling and directing developmental processes during plant growth and also in unlocking their potential for biotechnological innovation. Recent technological advances have enabled the probing of how primary wall structures and molecular interactions of polysaccharides define their biomechanical (and hence functional) properties...
September 12, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28910526/genetic-rodent-models-of-brain-disorders-perspectives-on-experimental-approaches-and-therapeutic-strategies
#4
Christopher M McGraw, Christopher S Ward, Rodney C Samaco
Neurobehavioral disorders comprised of neurodegenerative, neurodevelopmental, and psychiatric disorders together represent leading causes of morbidity and mortality. Despite significant academic research and industry efforts to elucidate the disease mechanisms operative in these disorders and to develop mechanism-based therapies, our understanding remains incomplete and our access to tractable therapeutic interventions severely limited. The magnitude of these short-comings can be measured by the growing list of disappointing clinical trials based on initially promising compounds identified in genetic animal models...
September 2017: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/28910389/cross-species-conservation-of-episome-maintenance-provides-a-basis-for-in-vivo-investigation-of-kaposi-s-sarcoma-herpesvirus-lana
#5
Aline C Habison, Marta Pires de Miranda, Chantal Beauchemin, Min Tan, Sofia A Cerqueira, Bruno Correia, Rajesh Ponnusamy, Edward J Usherwood, Colin E McVey, J Pedro Simas, Kenneth M Kaye
Many pathogens, including Kaposi's sarcoma herpesvirus (KSHV), lack tractable small animal models. KSHV persists as a multi-copy, nuclear episome in latently infected cells. KSHV latency-associated nuclear antigen (kLANA) binds viral terminal repeat (kTR) DNA to mediate episome persistence. Model pathogen murine gammaherpesvirus 68 (MHV68) mLANA acts analogously on mTR DNA. kLANA and mLANA differ substantially in size and kTR and mTR show little sequence conservation. Here, we find kLANA and mLANA act reciprocally to mediate episome persistence of TR DNA...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28902204/rational-design-and-structure-activity-relationship-studies-of-quercetin-amino-acid-hybrids-targeting-the-anti-apoptotic-protein-bcl-xl
#6
Tahsin F Kellici, Maria V Chatziathanasiadou, Min-Sung Lee, Nisar Sayyad, Elena G Geromichalou, Eirinaios I Vrettos, Antonis D Tsiailanis, Seung-Wook Chi, George D Geromichalos, Thomas Mavromoustakos, Andreas G Tzakos
Anti-apoptotic proteins, like the Bcl-2 family proteins, present an important therapeutic cancer drug target. Their activity is orchestrated through neutralization upon interaction of pro-apoptotic protein counterparts that leads to immortality of cancer cells. Therefore, generating compounds targeting these proteins is of immense therapeutic importance. Herein, Induced Fit Docking (IFD) and Molecular Dynamics (MD) simulations were performed to rationally design quercetin analogues that bind in the BH3 site of the Bcl-xL protein...
September 13, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28901607/bias-variance-tradeoff-in-anticorrelated-noise-reduction-for-spectral-ct
#7
Mats Persson, Fredrik Grönberg
PURPOSE: In spectral CT, basis material decomposition is commonly used to generate a set of basis images showing the material composition at each point in the field of view. The noise in these images typically contains anticorrelations between the different basis images, which leads to increased noise in each basis image. These anticorrelations can be removed by changing the basis functions used in the material decomposition, but the resulting basis images can then no longer be used for quantitative measurements...
September 2017: Medical Physics
https://www.readbyqxmd.com/read/28900693/complete-genome-sequence-of-geobacillus-thermodenitrificans-t12-a-potential-host-for-biotechnological-applications
#8
Martinus J A Daas, Bastienne Vriesendorp, Antonius H P van de Weijer, John van der Oost, Richard van Kranenburg
In attempt to obtain a thermophilic host for the conversion of lignocellulose derived substrates into lactic acid, Geobacillus thermodenitrificans T12 was isolated from a compost heap. It was selected from over 500 isolates as a genetically tractable hemicellulolytic lactic acid producer, requiring little nutrients. The strain is able to ferment glucose and xylose simultaneously and can produce lactic acid from xylan, making it a potential host for biotechnological applications. The genome of strain T12 consists of a 3...
September 12, 2017: Current Microbiology
https://www.readbyqxmd.com/read/28891297/validating-missing-proteins-in-human-sperm-cells-by-targeted-mass-spectrometry-and-antibody-based-methods
#9
Christine Carapito, Paula Duek, Charlotte Macron, Marine Seffals, Karine Rondel, Francois Delalande, Cecilia Lindskog, Thomas Freour, Yves Vandenbrouck, Lydie Lane, Charles Pineau
The present study is a contribution to the "neXt50 challenge", a coordinated effort across C-HPP teams to identify the 50 most tractable missing proteins (MPs) on each chromosome. We report the targeted search of 38 theoretically detectable MPs from chromosomes 2 and 14 in Triton X-100 soluble and insoluble sperm fractions from a total of 15 healthy donors. A targeted mass spectrometry-based strategy consisting in the development of LC-PRM assays (with heavy labeled synthetic peptides) targeting 92 proteotypic peptides of the 38 selected MPs was used...
September 11, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28889378/defining-the-pathways-of-urogenital-schistosomiasis-associated-urothelial-carcinogenesis-through-transgenic-and-bladder-wall-egg-injection-models
#10
Evaristus C Mbanefo, Michael H Hsieh
Urogenital schistosomiasis (infection with Schistosoma haematobium) is a major cause of bladder carcinogenesis. However, the exact mechanisms of the sequelae leading up to the development of bladder cancer are poorly understood, mainly because of a dearth of tractable mouse models. We developed a mouse model of urogenital schistosomiasis through intramural injection of parasite eggs into the bladder wall to mimic the trapping of parasite eggs in the bladder. This approach recapitulates many of the sequelae observed in infected humans...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28889306/probing-protein-protein-interactions-with-genetically-encoded-photoactivatable-cross-linkers
#11
Richard B Cooley, Holger Sondermann
Fundamental to all living organisms is the ability of proteins to interact with other biological molecules at the right time and location, with the proper affinity, and to do so reversibly. One well-established technique to study protein interactions is chemical cross-linking, a process in which proteins in close spatial proximity are covalently tethered together. An emerging technology that overcomes many limitations of traditional cross-linking methods is one in which photoactivatable cross-linking noncanonical amino acids are genetically encoded into a protein of interest using the cell's native translational machinery...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28882206/mechanism-based-strategies-for-structural-characterization-of-radical-sam-reaction-intermediates
#12
Katherine M Davis, Amie K Boal
X-ray crystallographic characterization of enzymes at different stages in their reaction cycles can provide unique insight into the reaction pathway, the number and type of intermediates formed, and their structural context. The known mechanistic diversity in the radical S-adenosylmethionine (SAM) superfamily of enzymes makes it an appealing target for such studies as more than 100,000 sequences have been identified to date with wide-ranging reactivities that share a pattern of complex radical-mediated chemistry...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28881997/predicting-phenotypes-from-microarrays-using-amplified-initially-marginal-eigenvector-regression
#13
Lei Ding, Daniel J McDonald
Motivation: The discovery of relationships between gene expression measurements and phenotypic responses is hampered by both computational and statistical impediments. Conventional statistical methods are less than ideal because they either fail to select relevant genes, predict poorly, ignore the unknown interaction structure between genes, or are computationally intractable. Thus, the creation of new methods which can handle many expression measurements on relatively small numbers of patients while also uncovering gene-gene relationships and predicting well is desirable...
July 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28881357/a-novel-inhibitory-anti-invasive-mab-isolated-using-phenotypic-screening-highlights-anxa6-as-a-functionally-relevant-target-protein-in-pancreatic-cancer
#14
Dermot O'Sullivan, Paul Dowling, Helena Joyce, Edel McAuley, Andrew McCann, Michael Henry, Brianan McGovern, Paul Barham, Fergal C Kelleher, Jean Murphy, Susan Kennedy, Niall Swan, Michael Moriarty, Martin Clynes, Annemarie Larkin
BACKGROUND: Discovery and validation of new antibody tractable targets is critical for the development of new antibody therapeutics to address unmet needs in oncology. METHODS: A highly invasive clonal variant of the MDA-MB-435S cell line was used to generate monoclonal antibodies (MAbs), which were screened for anti-invasive activity against aggressive cancer cells in vitro. The molecular target of selected inhibitory MAb 9E1 was identified using immunoprecipitation/liquid chromatography-tandem mass spectrometry...
September 7, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28880159/bilinear-factor-matrix-norm-minimization-for-robust-pca-algorithms-and-applications
#15
Fanhua Shang, James Cheng, Yuanyuan Liu, Zhi-Quan Luo, Zhouchen Lin
The heavy-tailed distributions of corrupted outliers and singular values of all channels in low-level vision have proven effective priors for many applications such as background modeling, photometric stereo and image alignment. And they can be well modeled by a hyper-Laplacian. However, the use of such distributions generally leads to challenging non-convex, non-smooth and non-Lipschitz problems, and makes existing algorithms very slow for large-scale applications. Together with the analytic solutions to Lp-norm minimization with two specific values of p, i...
September 4, 2017: IEEE Transactions on Pattern Analysis and Machine Intelligence
https://www.readbyqxmd.com/read/28877482/high-yield-methods-for-accurate-two-alternative-visual-psychophysics-in-head-fixed-mice
#16
Christopher P Burgess, Armin Lak, Nicholas A Steinmetz, Peter Zatka-Haas, Charu Bai Reddy, Elina A K Jacobs, Jennifer F Linden, Joseph J Paton, Adam Ranson, Sylvia Schröder, Sofia Soares, Miles J Wells, Lauren E Wool, Kenneth D Harris, Matteo Carandini
Research in neuroscience increasingly relies on the mouse, a mammalian species that affords unparalleled genetic tractability and brain atlases. Here, we introduce high-yield methods for probing mouse visual decisions. Mice are head-fixed, facilitating repeatable visual stimulation, eye tracking, and brain access. They turn a steering wheel to make two alternative choices, forced or unforced. Learning is rapid thanks to intuitive coupling of stimuli to wheel position. The mouse decisions deliver high-quality psychometric curves for detection and discrimination and conform to the predictions of a simple probabilistic observer model...
September 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28874474/pyruvate-accumulation-is-the-first-line-of-cell-defense-against-heat-stress-in-a-fungus
#17
Xing Zhang, Raymond J St Leger, Weiguo Fang
Heat tolerance is well known to be key to fungal survival in many habitats, but our mechanistic understanding of how organisms adapt to heat stress is still incomplete. Using Metarhizium robertsii, an emerging model organism for assessing evolutionary processes, we report that pyruvate is in the vanguard of molecules that scavenge heat-induced reactive oxygen species (ROS). We show that, as well as inducing a rapid burst of ROS production, heat stress also downregulates genes for pyruvate consumption. The accumulating pyruvate is the fastest acting of several M...
September 5, 2017: MBio
https://www.readbyqxmd.com/read/28874467/an-evolutionarily-conserved-pathway-essential-for-orsay-virus-infection-of-caenorhabditis-elegans
#18
Hongbing Jiang, Kevin Chen, Luis E Sandoval, Christian Leung, David Wang
Many fundamental biological discoveries have been made in Caenorhabditis elegans The discovery of Orsay virus has enabled studies of host-virus interactions in this model organism. To identify host factors critical for Orsay virus infection, we designed a forward genetic screen that utilizes a virally induced green fluorescent protein (GFP) reporter. Following chemical mutagenesis, two Viro (virus induced reporter off) mutants that failed to express GFP were mapped to sid-3, a nonreceptor tyrosine kinase, and B0280...
September 5, 2017: MBio
https://www.readbyqxmd.com/read/28873409/fine-scale-mapping-of-genomic-introgressions-within-the-drosophila-yakuba-clade
#19
David A Turissini, Daniel R Matute
The process of speciation involves populations diverging over time until they are genetically and reproductively isolated. Hybridization between nascent species was long thought to directly oppose speciation. However, the amount of interspecific genetic exchange (introgression) mediated by hybridization remains largely unknown, although recent progress in genome sequencing has made measuring introgression more tractable. A natural place to look for individuals with admixed ancestry (indicative of introgression) is in regions where species co-occur...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28873088/identifying-genetic-variants-that-affect-viability-in-large-cohorts
#20
Hakhamanesh Mostafavi, Tomaz Berisa, Felix R Day, John R B Perry, Molly Przeworski, Joseph K Pickrell
A number of open questions in human evolutionary genetics would become tractable if we were able to directly measure evolutionary fitness. As a step towards this goal, we developed a method to examine whether individual genetic variants, or sets of genetic variants, currently influence viability. The approach consists in testing whether the frequency of an allele varies across ages, accounting for variation in ancestry. We applied it to the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort and to the parents of participants in the UK Biobank...
September 2017: PLoS Biology
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