Página 9 dos resultados de 20101 itens digitais encontrados em 0.007 segundos

‣ HIV-1 envelope accessible surface and polarity: clade, blood, and brain

Sowmya, Gopichandran; Shamini, Gunasagaran; Anita, Sathyanarayanan; Sakharkar, Meena; Mathura, Venkat; Rodriguez, Hector; Levine, Andrew J; Singer, Elyse; Commins, Deborah; Somboonwit, Charurut; Sinnott, John T; Sidhu, Harcharan S; Rajaseger, Ganapathy; P
Fonte: Biomedical Informatics Publicador: Biomedical Informatics
Tipo: Artigo de Revista Científica
Publicado em 22/03/2011 Português
Relevância na Pesquisa
26.179395%
The human immunodeficiency virus type-1 (HIV-1) gp160 (gp120-gp41 complex) trimer envelope (ENV) protein is a potential vaccine candidate for HIV/AIDS. HIV-1 vaccine development has been problematic and charge polarity as well as sequence variation across clades may relate to the difficulties. Further obstacles are caused by sequence variation between blood and brain-derived sequences, since the brain is a separate compartment for HIV-1 infection. We utilize a threedimensional residue measure of solvent exposure, accessible surface area (ASA), which shows that major segments of gp120 and gp41 known structures are solvent exposed across clades. We demonstrate a large percent sequence polarity for solvent exposed residues in gp120 and gp41. The range of sequence polarity varies across clades, blood, and brain from different geographical locations. Regression analysis shows that blood and brain gp120 and gp41 percent sequence polarity range correlate with mean Shannon entropy. These results point to the use of protein modifications to enhance HIV-1 ENV vaccines across multiple clades, blood, and brain. It should be noted that we do not address the issue of protein glycosylation here; however, this is an important issue for vaccine design and development.

‣ Web-Accessible Database of hsp65 Sequences from Mycobacterium Reference Strains▿†

Dai, Jianli; Chen, Yuansha; Lauzardo, Michael
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /06/2011 Português
Relevância na Pesquisa
26.179395%
Mycobacteria include a large number of pathogens. Identification to species level is important for diagnoses and treatments. Here, we report the development of a Web-accessible database of the hsp65 locus sequences (http://msis.mycobacteria.info) from 149 out of 150 Mycobacterium species/subspecies. This database can serve as a reference for identifying Mycobacterium species.

‣ Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin

Nikitas, Georgios; Deschamps, Chantal; Disson, Olivier; Niault, Théodora; Cossart, Pascale; Lecuit, Marc
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 24/10/2011 Português
Relevância na Pesquisa
26.179395%
Listeria monocytogenes targets accessible E-cadherin expressed on mucus-producing goblet cells to invade the intestinal tissue.

‣ Targeting Free Prostate-Specific Antigen for In Vivo Imaging of Prostate Cancer Using a Monoclonal Antibody Specific for Unique Epitopes Accessible on Free Prostate-Specific Antigen Alone

Evans-Axelsson, Susan; Ulmert, David; Örbom, Anders; Peterson, Pernilla; Nilsson, Olle; Wennerberg, Johan; Strand, Joanna; Wingårdh, Karin; Olsson, Tomas; Hagman, Zandra; Tolmachev, Vladimir; Bjartell, Anders; Lilja, Hans; Strand, Sven-Erik
Fonte: Mary Ann Liebert, Inc. Publicador: Mary Ann Liebert, Inc.
Tipo: Artigo de Revista Científica
Publicado em /05/2012 Português
Relevância na Pesquisa
26.179395%
This study investigated the feasibility of targeting the free, unbound forms of prostate-specific antigen (fPSA) for in vivo imaging of prostate adenocarcinomas (PCa), as PSA is produced and secreted at abundance during every clinical stage and grade of PCa, including castration-resistant disease. We injected 125I-labeled monoclonal antibody PSA30 (specific for an epitope uniquely accessible on fPSA alone) intravenously in male nude mice carrying subcutaneous xenografts of LNCaP tumors (n=36). Mice were sacrificed over a time course from 4 hours to 13 days after injecting 125I-labeled PSA30. Tissue uptake of 125I-PSA30 at 48 and 168 hours after intravenous injection was compared with two clinically used positron emission tomography radiopharmaceuticals, 18F-fluoro-deoxy-glucose (18F-FDG) or 18F-choline, in cryosections using Digital AutoRadiography (DAR) and also compared with immunohistochemical staining of PSA and histopathology. On DAR, the areas with high 125I-PSA30 uptake corresponded mainly to morphologically intact and PSA-producing LNCaP cells, but did not associate with the areas of high uptake of either 18F-FDG or 18F-choline. Biodistribution of 125I-PSA30 measured in dissected organs ex vivo during 4 to 312 hours after intravenous injection demonstrated maximum selective tumor uptake 24–48 hours after antibody injection. Our data showed selective uptake in vivo of a monoclonal antibody highly specific for fPSA in LNCaP cells. Hence...

‣ Designed, Synthetically Accessible Bryostatin Analogues Potently Induce Activation of Latent HIV Reservoirs in vitro

DeChristopher, Brian A.; Loy, Brian A.; Marsden, Matthew D.; Schrier, Adam J.; Zack, Jerome A.; Wender, Paul A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.179395%
Bryostatin is a unique lead in the development of potentially transformative therapies for cancer, Alzheimer’s disease, and the eradication of HIV/AIDS. However, the clinical use of bryostatin has been hampered by its limited supply, difficulties in accessing clinically-relevant derivatives, and side effects. Herein, we address these problems through the step-economical syntheses of seven members of a new family of designed bryostatin analogues utilizing a highly convergent Prins-macrocyclization strategy. We also demonstrate for the first time that such analogues effectively induce latent HIV activation in vitro with potencies similar to or better than bryostatin. Significantly, these analogues are up to 1000-fold more potent in inducing latent HIV expression than prostratin, the current clinical candidate for latent virus induction. This study provides the first demonstration that designed, synthetically-accessible bryostatin analogues could serve as superior candidates for the eradication of HIV/AIDS through induction of latent viral reservoirs in conjunction with current antiretroviral therapy.

‣ Transcriptome Tomography for Brain Analysis in the Web-Accessible Anatomical Space

Okamura-Oho, Yuko; Shimokawa, Kazuro; Takemoto, Satoko; Hirakiyama, Asami; Nakamura, Sakiko; Tsujimura, Yuki; Nishimura, Masaomi; Kasukawa, Takeya; Masumoto, Koh-hei; Nikaido, Itoshi; Shigeyoshi, Yasufumi; Ueda, Hiroki R.; Song, Gang; Gee, James; Himeno,
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 19/09/2012 Português
Relevância na Pesquisa
26.179395%
Increased information on the encoded mammalian genome is expected to facilitate an integrated understanding of complex anatomical structure and function based on the knowledge of gene products. Determination of gene expression-anatomy associations is crucial for this understanding. To elicit the association in the three-dimensional (3D) space, we introduce a novel technique for comprehensive mapping of endogenous gene expression into a web-accessible standard space: Transcriptome Tomography. The technique is based on conjugation of sequential tissue-block sectioning, all fractions of which are used for molecular measurements of gene expression densities, and the block- face imaging, which are used for 3D reconstruction of the fractions. To generate a 3D map, tissues are serially sectioned in each of three orthogonal planes and the expression density data are mapped using a tomographic technique. This rapid and unbiased mapping technique using a relatively small number of original data points allows researchers to create their own expression maps in the broad anatomical context of the space. In the first instance we generated a dataset of 36,000 maps, reconstructed from data of 61 fractions measured with microarray, covering the whole mouse brain (ViBrism: http://vibrism.riken.jp/3dviewer/ex/index.html) in one month. After computational estimation of the mapping accuracy we validated the dataset against existing data with respect to the expression location and density. To demonstrate the relevance of the framework...

‣ The use of a conventional tissue culture plate as an optically accessible perfusion chamber for in situ assays and for long-term cultivation of mammalian cells

Freyberg, M. A.; Friedl, P.
Fonte: Kluwer Academic Publishers Publicador: Kluwer Academic Publishers
Tipo: Artigo de Revista Científica
Publicado em /01/1998 Português
Relevância na Pesquisa
26.179395%
An alternative culture system has been developed based on a conventional tissue culture plate (3.5 cm diameter) which is changed into a closed perfusion chamber. The system can easily be scaled up from one to several chambers. The shape and the size of the area of cell growth may be designed to individual experimental demands. The whole culture chamber is optically accessible, so cell growth and morphology can be evaluated by light microscopy. Furthermore the cellular physiology can be characterised by any fluorimetric assay using a bottom type fluorescence reader. A peristaltic pump sustains a constant medium flow through the chamber thus creating true homeostasis. The use of HPLC-valves and connectors allows the switching between different media or assay solutions. Thus it is possible to perform in situ assays also measuring transient effects. A protocol for vitality tests using calcein-AM is worked out for an adherent cell line and for a suspension cell line. The lower detection limits are 7 × 102 cells cm-2 for the adherent cells and 5 × 104 cells mL-1 for the suspension cells. The upper limits are 1–2 × 105 cells cm-2 respectively 8 × 106 cells mL-1.

‣ GPU/CPU Algorithm for Generalized Born/Solvent-Accessible Surface Area Implicit Solvent Calculations

Tanner, David E.; Phillips, James C.; Schulten, Klaus
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.179395%
Molecular dynamics methodologies comprise a vital research tool for structural biology. Molecular dynamics has benefited from technological advances in computing, such as multi-core CPUs and graphics processing units (GPUs), but harnessing the full power of hybrid GPU/CPU computers remains difficult. The generalized Born/solvent-accessible surface area implicit solvent model (GB/SA) stands to benefit from hybrid GPU/CPU computers, employing the GPU for the GB calculation and the CPU for the SA calculation. Here, we explore the computational challenges facing GB/SA calculations on hybrid GPU/CPU computers and demonstrate how NAMD, a parallel molecular dynamics program, is able to efficiently utilize GPUs and CPUs simultaneously for fast GB/SA simulations. The hybrid computation principles demonstrated here are generally applicable to parallel applications employing hybrid GPU/CPU calculations.

‣ Electroretinograms in Drosophila: A Robust and Genetically Accessible Electrophysiological System for the Undergraduate Laboratory

Vilinsky, Ilya; Johnson, Karl G.
Fonte: Faculty for Undergraduate Neuroscience Publicador: Faculty for Undergraduate Neuroscience
Tipo: Artigo de Revista Científica
Publicado em 15/10/2012 Português
Relevância na Pesquisa
26.179395%
Laboratory courses in neurophysiology fulfill a critical need for inquiry-based training in undergraduate programs in neuroscience and biology. These courses typically use classical electrophysiological preparations to explore the basic features of neuronal function. However, current neuroscience research also focuses on elucidating the molecular and genetic mechanisms of neuronal function, using model systems that include mutant and transgenic animals. To bridge laboratory training in neurophysiology with modern molecular genetics, we describe a teaching model based on electroretinography of the fruit fly Drosophila melanogaster, a long-established model system for basic neuroscience research. Drosophila are easily maintained, economical, and have hundreds of neurophysiologically relevant mutant strains and genetic tools readily available. The Drosophila electroretinogram (ERG) is a simple and accessible extracellular recording of a neural signal in the fly eye in response to flashes of light. The signal is multifaceted and the response is sensitive to stimulation parameters such as intensity, duration and wavelength, thus forming a rich source of analysis for students. Most importantly, different mutations affecting key components of intracellular signaling...

‣ SAHBNET, an Accessible Surface-Based Elastic Network: An Application to Membrane Protein

Dony, Nicolas; Crowet, Jean Marc; Joris, Bernard; Brasseur, Robert; Lins, Laurence
Fonte: Molecular Diversity Preservation International (MDPI) Publicador: Molecular Diversity Preservation International (MDPI)
Tipo: Artigo de Revista Científica
Publicado em 30/05/2013 Português
Relevância na Pesquisa
26.179395%
Molecular Dynamics is a method of choice for membrane simulations and the rising of coarse-grained forcefields has opened the way to longer simulations with reduced calculations times. Here, we present an elastic network, SAHBNET (Surface Accessibility Hydrogen-Bonds elastic NETwork), that will maintain the structure of soluble or membrane proteins based on the hydrogen bonds present in the atomistic structure and the proximity between buried residues. This network is applied on the coarse-grained beads defined by the MARTINI model, and was designed to be more physics-based than a simple elastic network. The SAHBNET model is evaluated against atomistic simulations, and compared with ELNEDYN models. The SAHBNET is then used to simulate two membrane proteins inserted in complex lipid bilayers. These bilayers are formed by self-assembly and the use of a modified version of the GROMACS tool genbox (which is accessible through the gcgs.gembloux.ulg.ac.be website). The results show that SAHBNET keeps the structure close to the atomistic one and is successfully used for the simulation of membrane proteins.

‣ A genome-wide RNAi screen reveals that mRNA decapping restricts bunyaviral replication by limiting the pools of Dcp2-accessible targets for cap-snatching

Hopkins, Kaycie C.; McLane, Laura M.; Maqbool, Tariq; Panda, Debasis; Gordesky-Gold, Beth; Cherry, Sara
Fonte: Cold Spring Harbor Laboratory Press Publicador: Cold Spring Harbor Laboratory Press
Tipo: Artigo de Revista Científica
Publicado em 01/07/2013 Português
Relevância na Pesquisa
26.179395%
Bunyaviruses are a group of medically important viruses, many of which are insect-borne. Using genome-wide screening in Drosophila with the bunyavirus Rift Valley fever virus (RVFV), Hopkins et al. now identify mRNA decapping as a control point for viral RNA transcription. Depletion of the mRNA decapping enzyme Dcp2 enhances viral transcription, whereas ectopic expression impedes it. This study suggests a model whereby RVFV competes for the Dcp2-accessible mRNA pool, which can present a bottleneck for viral replication.

‣ Highly potent, synthetically accessible prostratin analogs induce latent HIV expression in vitro and ex vivo

Beans, Elizabeth J.; Fournogerakis, Dennis; Gauntlett, Carolyn; Heumann, Lars V.; Kramer, Rainer; Marsden, Matthew D.; Murray, Danielle; Chun, Tae-Wook; Zack, Jerome A.; Wender, Paul A.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.179395%
Highly active antiretroviral therapy (HAART) decreases plasma viremia below the limits of detection in the majority of HIV-infected individuals, thus serving to slow disease progression. However, HAART targets only actively replicating virus and is unable to eliminate latently infected, resting CD4+ T cells. Such infected cells are potentially capable of reinitiating virus replication upon cessation of HAART, thus leading to viral rebound. Agents that would eliminate these reservoirs, when used in combination with HAART, could thus provide a strategy for the eradication of HIV. Prostratin is a preclinical candidate that induces HIV expression from latently infected CD4+ T cells, potentially leading to their elimination through a virus-induced cytopathic effect or host anti-HIV immunity. Here, we report the synthesis of a series of designed prostratin analogs and report in vitro and ex vivo studies of their activity relevant to induction of HIV expression. Members of this series are up to 100-fold more potent than the preclinical lead (prostratin) in binding to cell-free PKC, and in inducing HIV expression in a latently infected cell line and prostratin-like modulation of cell surface receptor expression in primary cells from HIV-negative donors. Significantly...

‣ Rotational Scanning Electron Micrographs (rSEM): A novel and accessible tool to visualize and communicate complex morphology

Cheung, David K-B; Brunke, Adam J.; Akkari, Nesrine; Souza, Carina Mara; Pape, Thomas
Fonte: Pensoft Publishers Publicador: Pensoft Publishers
Tipo: Artigo de Revista Científica
Publicado em 03/09/2013 Português
Relevância na Pesquisa
26.179395%
An accessible workflow is presented to create interactive, rotational scanning electron micrographs (rSEM). These information-rich animations facilitate the study and communication of complex morphological structures exemplified here by male arthropod genitalia. Methods are outlined for the publication of rSEMs on the web or in journal articles as SWF files. Image components of rSEMs were archived in MorphBank to ensure future data access. rSEM represents a promising new addition to the toolkit of a new generation of digital taxonomy.

‣ Disarming the Jasmonate-Dependent Plant Defense Makes Nonhost Arabidopsis Plants Accessible to the American Serpentine Leafminer1

Abe, Hiroshi; Tateishi, Ken; Seo, Shigemi; Kugimiya, Soichi; Hirai, Masami Yokota; Sawada, Yuji; Murata, Yoshiyuki; Yara, Kaori; Shimoda, Takeshi; Kobayashi, Masatomo
Fonte: American Society of Plant Biologists Publicador: American Society of Plant Biologists
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.179395%
Loss of jasmonate-dependent plant defense converts nonhost plants to host plants that are accessible to leafminers, and demonstrates a role for jasmonate in regulating host plant suitability of herbivores.

‣ Accessible online neuroplasticity-targeted training for children with ADHD

Mishra, Jyoti; Merzenich, Michael M; Sagar, Rajesh
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 14/11/2013 Português
Relevância na Pesquisa
26.179395%
Childhood Attention Deficit Hyperactivity Disorder (ADHD) is a growing mental health concern worldwide. Effective, accessible and low-cost therapeutics for the disorder are urgently needed. Here we introduce a novel internet-based cognitive training intervention: Online Neuroplasticity-based Training for the Remediation of ADHD in Children (ONTRAC). The intervention is deployed in the home setting; it is customized to the cognitive capacities of each child and progressively improves performance in the specific neuro-cognitive domains deficient in ADHD. A feasibility trial of ONTRAC is being conducted in a resource limited clinical setting in New Delhi, India and is an exemplar of hi-tech global psychiatry.

‣ On Flat Objects of Finitely Accessible Categories

Crivei, Septimiu
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Publicado em 28/10/2013 Português
Relevância na Pesquisa
26.179395%
Flat objects of a finitely accessible additive category

‣ Analysis of Brain Nuclei Accessible to Ghrelin Present in the Cerebrospinal Fluid

Cabral, Agustina; Fernandez, Gimena; Perello, Mario
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.179395%
Ghrelin is a stomach-derived peptide hormone that acts in the brain to regulate many important physiological functions. Ghrelin receptor, named the growth hormone secretagogue receptor (GHSR), is present in many brain areas with or without obvious direct access to ghrelin circulating in the bloodstream. Ghrelin is also present in the cerebrospinal fluid (CSF) but the brain targets of CSF ghrelin are unclear. Here, we studied which brain areas are accessible to ghrelin present in the CSF. For this purpose, we centrally injected mice with fluorescein-labeled ghrelin (F-ghrelin) peptide tracer and then systematically mapped the distribution of F-ghrelin signal trough the brain. Our results indicated that centrally injected F-ghrelin labels neurons in most of the brain areas where GHSR is present. Also, we detected F-ghrelin uptake in the ependymal cells of both wild type and GHSR-null mice. We conclude that CSF ghrelin is able to reach most of brain areas expressing GHSR. Also, we propose that the accessibility of CSF ghrelin to the brain parenchyma occurs through the ependymal cells in a GHSR-independent manner.

‣ YPED: A Web-Accessible Database System for Protein Expression Analysis

Shifman, Mark A.; Li, Yuli; Colangelo, Christopher M.; Stone, Kathryn L.; Wu, Terence L.; Cheung, Kei-Hoi; Miller, Perry L.; Williams, Kenneth R.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.179395%
We have developed an integrated web-accessible software system called the Yale Protein Expression Database (YPED) to address the need for storage, retrieval, and integrated analysis of large amounts of data from high throughput proteomic technologies. YPED is an open source system which integrates gel analysis results with protein identifications from DIGE experiments. The system associates the DIGE gel spots and image, analyzed with DeCyder, with mass spectrometric protein identifications from selected gel spots. Following in gel trypsin digestion, proteins in spots of interest are analyzed using MALDI-TOF/TOF on an AB 4700 or, more recently, on an AB 4800 with protein identifications performed by Mascot in conjunction with the AB GPS Explorer system. In addition to DIGE, YPED currently handles protein identifications from MudPIT, iTRAQ, and ICAT experiments. Sample descriptions are compatible with the evolving MIAPE standards. Tandem MS/MS results from MudPIT, and ICAT analyses are validated with the Trans-Proteomic Pipeline and then stored in the database for viewing and linking to the identified proteins. Researchers can view, subset, and download their data through a secure Web interface that includes a table containing proteins identified...

‣ How Modification of Accessible Lysines to Phenylalanine Modulates the Structural and Functional Properties of Horseradish Peroxidase: A Simulation Study

Navapour, Leila; Mogharrab, Navid; Amininasab, Mehriar
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 14/10/2014 Português
Relevância na Pesquisa
26.179395%
Horseradish Peroxidase (HRP) is one of the most studied peroxidases and a great number of chemical modifications and genetic manipulations have been carried out on its surface accessible residues to improve its stability and catalytic efficiency necessary for biotechnological applications. Most of the stabilized derivatives of HRP reported to date have involved chemical or genetic modifications of three surface-exposed lysines (K174, K232 and K241). In this computational study, we altered these lysines to phenylalanine residues to model those chemical modifications or genetic manipulations in which these positively charged lysines are converted to aromatic hydrophobic residues. Simulation results implied that upon these substitutions, the protein structure becomes less flexible. Stability gains are likely to be achieved due to the increased number of stable hydrogen bonds, improved heme-protein interactions and more integrated proximal Ca2+ binding pocket. We also found a new persistent hydrogen bond between the protein moiety (F174) and the heme prosthetic group as well as two stitching hydrogen bonds between the connecting loops GH and F′F″ in mutated HRP. However, detailed analysis of functionally related structural properties and dynamical features suggests reduced reactivity of the enzyme toward its substrates. Molecular dynamics simulations showed that substitutions narrow the bottle neck entry of peroxide substrate access channel and reduce the surface accessibility of the distal histidine (H42) and heme prosthetic group to the peroxide and aromatic substrates...

‣ Exploring the accessible conformations of N-terminal acetylated α-synuclein

Moriarty, Gina M.; Janowska, Maria K.; Kang, Lijuan; Baum, Jean
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.179395%
Alpha synuclein (αsyn) fibrils are found in the Lewy Bodies of patients with Parkinson’s disease (PD). The aggregation of the αsyn monomer to soluble oligomers and insoluble fibril aggregates is believed to be one of the causes of PD. Recently, the view of the native state of αsyn as a monomeric ensemble was challenged by a report suggesting that αsyn exists in its native state as a helical tetramer. This review reports on our current understanding of αsyn within the context of these recent developments and describes the work performed by a number of groups to address the monomer/tetramer debate. A number of in depth studies have subsequently shown that both non-acetylated and acetylated αsyn purified under mild conditions are primarily monomer. A description of the accessible states of acetylated αsyn monomer and the ability of αsyn to self-associate is explored.