PubMed Central (PMC3 - NLM DTD)
(2,081,148 recursos)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).
Mostrando recursos 21 - 40 de 184,040
21.
Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress - Kim, Raymond H.; Smith, Patrice D.; Aleyasin, Hossein; Hayley, Shawn; Mount, Matthew P.; Pownall, Scott; Wakeham, Andrew; You-Ten, Annick J.; Kalia, Suneil K.; Horne, Patrick; Westaway, David; Lozano, Andres M.; Anisman, Hymie; Park, David S.; Mak, Tak W.
Mutations of the DJ-1 (PARK7) gene are linked to familial Parkinson's disease. We used gene targeting to generate DJ-1-deficient mice that were viable, fertile, and showed no gross anatomical or neuronal abnormalities. Dopaminergic neuron numbers in the substantia nigra and fiber densities and dopamine levels in the striatum were normal. However, DJ-1/ mice showed hypolocomotion when subjected to amphetamine challenge and increased striatal denervation and dopaminergic neuron loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine. DJ-1/embryonic cortical neurons showed increased sensitivity to oxidative, but not nonoxidative, insults. Restoration of DJ-1 expression to DJ-1/ mice or cells via adenoviral vector delivery mitigated all phenotypes. WT...
22.
Kinetics and molecular properties of pheromone binding and release - Leal, Walter S.; Chen, Angela M.; Ishida, Yuko; Chiang, Vicky P.; Erickson, Melissa L.; Morgan, Tania I.; Tsuruda, Jennifer M.
Transient kinetic studies have shown that the uptake of the pheromone (bombykol) of the silkworm moth (Bombyx mori), by its pheromone-binding protein (PBP) BmorPBP, proceeds with an on rate of 0.068 ± 0.01 ?M1·s1. With the high concentration of PBP in the sensillar lymph (10 mM), the half-life for the uptake of pheromone in vivo is ?1 ms. A pH-dependent conformational change (BmorPBPB ? BmorPBPA), associated with the release of pheromone, is a first-order reaction (k = 74.1 ± 0.32 s1; t1/2, 9.3 ms). Under physiological conditions, both reactions proceed with half-life times on the order of milliseconds, as is...
23.
High-dose radiation with bone marrow transfer prevents neurodegeneration in an inherited glaucoma - Anderson, Michael G.; Libby, Richard T.; Gould, Douglas B.; Smith, Richard S.; John, Simon W. M.
Here, we show that high-dose ?-irradiation accompanied with syngeneic bone marrow transfer can confer complete protection against glaucoma in a mouse model. Because bone marrow genotype was unaltered by this procedure, it was not the causative agent. The neuroprotection is robust and highly reproducible. Glaucoma-prone DBA/2J mice received a single treatment at 58 weeks of age and were protected from glaucomatous retinal ganglion cell degeneration out to 14 months of age (oldest assessed). By 1214 months, retinal ganglion cell degeneration is usually very severe and essentially complete in the majority of untreated DBA/2J mice. To assess reproducibility, three groups of...
24.
A long-range attraction between aggregating 3T3 cells mediated by near-infrared light scattering - Albrecht-Buehler, Guenter
At what range can a mammalian cell sense the presence of another cell and through what medium? To approach these questions, the formation of aggregates of a 3T3 cell variant (3T3x cells) grown on solid substrates was studied. Each of the aggregates consisted of cells that, at the time of their seeding, were single and located randomly. Yet somehow they seemed to detect each other within a certain range (Ra) and move together to form aggregates. The article describes a simple assay to measure the value of Ra. When applied to 3T3x cells with altered intensities of near-infrared light scattering...
25.
Foxp3 interacts with nuclear factor of activated T cells and NF-?B to repress cytokine gene expression and effector functions of T helper cells - Bettelli, Estelle; Dastrange, Maryam; Oukka, Mohamed
Scurfy mice, which are deficient in a functional Foxp3, exhibit a severe lymphoproliferative disorder and display generalized over-production of cytokines. Here, we show that, among the Foxp transcriptional factor family, which includes Foxp1, Foxp2, and Foxp3, only Foxp3 has the ability to inhibit IL-2, IL-4, and IFN-? production by primary T helper cells. We found that Foxp3 physically associates with the Rel family transcription factors, nuclear factor of activated T cells (NFAT) and NF-?B, and blocks their ability to induce the endogenous expression of their target genes, including key cytokine genes. More importantly, T cells derived from scurfy mice have...
26.
Immunological role of neuronal receptor vanilloid receptor 1 expressed on dendritic cells - Basu, Sreyashi; Srivastava, Pramod
Capsaicin (CP), the pungent component of chili pepper, acts on sensory neurons to convey the sensation of pain. The CP receptor, vanilloid receptor 1 (VR1), has been shown to be highly expressed by nociceptive neurons in dorsal root and trigeminal ganglia. We demonstrate here that the dendritic cell (DC), a key cell type of the vertebrate immune system, expresses VR1. Engagement of VR1 on immature DCs such as by treatment with CP leads to maturation of DCs as measured by up-regulation of antigen-presenting and costimulatory molecules. This effect is present in DCs of VR1+/+ but not VR1/ mice. In VR1+/+...
27.
LPS induces the interaction of a transcription factor, LPS-induced TNF-? factor, and STAT6(B) with effects on multiple cytokines - Tang, Xiaoren; Marciano, Deborah Levy; Leeman, Susan E.; Amar, Salomon
TNF-? is a pivotal cytokine whose overproduction can be lethal. Previously, we identified a transcription factor, LPS-induced TNF-? factor (LITAF), that regulates TNF-? transcription. We now report the discovery and characterization of a regulatory cofactor that we call signal transducer and activator of transcription (STAT) 6(B) because of its considerable homology to STAT6 [here referred to as STAT6(A)]. The STAT6(B) gene expression was found to be activated by LPS. Furthermore, we show that cotransfection of STAT6(B) and LITAF induces an interaction between the two proteins, consequently forming a complex that subsequently translocates into the nucleus and up-regulates the transcription of...
28.
A protein folding pathway with multiple folding intermediates at atomic resolution - Feng, Hanqiao; Zhou, Zheng; Bai, Yawen
Using native-state hydrogen-exchange-directed protein engineering and multidimensional NMR, we determined the high-resolution structure (rms deviation, 1.1 Å) for an intermediate of the four-helix bundle protein: Rd-apocytochrome b562. The intermediate has the N-terminal helix and a part of the C-terminal helix unfolded. In earlier studies, we also solved the structures of two other folding intermediates for the same protein: one with the N-terminal helix alone unfolded and the other with a reorganized hydrophobic core. Together, these structures provide a description of a protein folding pathway with multiple intermediates at atomic resolution. The two general features for the intermediates are (i) native-like...
29.
Phosphatidylinositol phosphate kinase type I? regulates dynamics of large dense-core vesicle fusion - Gong, Liang-Wei; Di Paolo, Gilbert; Diaz, Ester; Cestra, Gianluca; Diaz, Maria-Elena; Lindau, Manfred; De Camilli, Pietro; Toomre, Derek
Phosphatidylinositol-4,5-bisphosphate was proposed to be an important regulator of large dense-core vesicle exocytosis from neuroendocrine tissues. Here, we have examined the kinetics of secretion in chromaffin cells from mice lacking phosphatidylinositol phosphate kinase type I?, the major neuronal phosphatidylinositol-4-phosphate 5-kinase. Absence of this enzyme caused a reduction of the readily releasable vesicle pool and its refilling rate, with a small increase in morphologically docked vesicles, indicating a defect in vesicle priming. Furthermore, amperometry revealed a delay in fusion pore expansion. These results provide direct genetic evidence for a key role of phosphatidylinositol-4,5-bisphosphate synthesis in the regulation of large dense-core vesicle...
30.
Varicelloviruses avoid T cell recognition by UL49.5-mediated inactivation of the transporter associated with antigen processing - Koppers-Lalic, Danijela; Reits, Eric A. J.; Ressing, Maaike E.; Lipinska, Andrea D.; Abele, Rupert; Koch, Joachim; Rezende, Marisa Marcondes; Admiraal, Pieter; van Leeuwen, Daphne; Bienkowska-Szewczyk, Krystyna; Mettenleiter, Thomas C.; Rijsewijk, Frans A. M.; Tampé, Robert; Neefjes, Jacques; Wiertz, Emmanuel J. H. J.
Detection and elimination of virus-infected cells by cytotoxic T lymphocytes depends on recognition of virus-derived peptides presented by MHC class I molecules. A critical step in this process is the translocation of peptides from the cytoplasm into the endoplasmic reticulum by the transporter associated with antigen processing (TAP). Here, we identified the bovine herpesvirus 1-encoded UL49.5 protein as a potent inhibitor of TAP. The expression of UL49.5 results in down-regulation of MHC class I molecules at the cell surface and inhibits detection and lysis of the cells by cytotoxic T lymphocytes. UL49.5 homologs encoded by two other varicelloviruses, pseudorabies-virus and...
31.
Intracellular Helicobacter pylori in gastric epithelial progenitors - Oh, Jung D.; Karam, Sherif M.; Gordon, Jeffrey I.
Helicobacter pylori is generally viewed as an extracellular pathogen. We have analyzed the tropism of H. pylori clinical isolates in a gnotobiotic transgenic mouse model of human chronic atrophic gastritis, a preneoplastic condition. These mice lack acid-producing parietal cells and have an amplified population of dividing gastric epithelial progenitors (GEPs) that express NeuAc?2,3Gal?1,4-glycans recognized by H. pylori adhesins. Scanning confocal and transmission electron microscopic studies of stomachs that had been colonized for 1 month or 1 year revealed intracellular bacterial collections (IBCs) in a small subset of multi- and oligopotential epithelial progenitors. Transmission electron microscopic and multilabel immunohistochemical analyses disclosed...
32.
Cytolysin-dependent evasion of lysosomal killing - Håkansson, Anders; Bentley, Colette Cywes; Shakhnovic, Elizabeth A.; Wessels, Michael R.
Local host defenses limit proliferation and systemic spread of pathogenic bacteria from sites of mucosal colonization. For pathogens such as streptococci that fail to grow intracellularly, internalization and killing by epithelial cells contribute to the control of bacterial growth and dissemination. Here, we show that group A Streptococcus (GAS), the agent of streptococcal sore throat and invasive soft tissue infections, evades internalization and intracellular killing by pharyngeal epithelial cells. Production of the cholesterol-binding cytotoxin streptolysin O (SLO) prevented internalization of GAS into lysosomes. In striking contrast, GAS rendered defective in production of SLO were internalized directly or rapidly transported into...
33.
Genomic characterization reveals a simple histone H4 acetylation code - Dion, Michael F.; Altschuler, Steven J.; Wu, Lani F.; Rando, Oliver J.
The histone code hypothesis holds that covalent posttranslational modifications of histone tails are interpreted by the cell to yield a rich combinatorial transcriptional output. This hypothesis has been the subject of active debate in the literature. Here, we investigated the combinatorial complexity of the acetylation code at the four lysine residues of the histone H4 tail in budding yeast. We constructed yeast strains carrying all 15 possible combinations of mutations among lysines 5, 8, 12, and 16 to arginine in the histone H4 tail, mimicking positively charged, unacetylated lysine states, and characterized the resulting genome-wide changes in gene expression by...
34.
Perceptual learning in clear displays optimizes perceptual expertise: Learning the limiting process - Dosher, Barbara Anne; Lu, Zhong-Lin
Human operators develop expertise in perceptual tasks by practice or perceptual learning. For noisy displays, practice improves performance by learned external-noise filtering. For clear displays, practice improves performance by improved amplification or enhancement of the stimulus. Can these two mechanisms of perceptual improvement be trained separately? In an orientation task, we found that training with clear displays generalized to performance in noisy displays, but we did not find the reverse to be true. In noisy displays, the noise in the stimulus limits performance. In clear displays, performance is limited by noisiness of internal representations and processes. Our results suggest that...
35.
Generalized BienenstockCooperMunro rule for spiking neurons that maximizes information transmission - Toyoizumi, Taro; Pfister, Jean-Pascal; Aihara, Kazuyuki; Gerstner, Wulfram
Maximization of information transmission by a spiking-neuron model predicts changes of synaptic connections that depend on timing of pre- and postsynaptic spikes and on the postsynaptic membrane potential. Under the assumption of Poisson firing statistics, the synaptic update rule exhibits all of the features of the BienenstockCooperMunro rule, in particular, regimes of synaptic potentiation and depression separated by a sliding threshold. Moreover, the learning rule is also applicable to the more realistic case of neuron models with refractoriness, and is sensitive to correlations between input spikes, even in the absence of presynaptic rate modulation. The learning rule is found by...
36.
High-resolution functional proteomics by active-site peptide profiling - Okerberg, Eric S.; Wu, Jiangyue; Zhang, Baohong; Samii, Babak; Blackford, Kelly; Winn, David T.; Shreder, Kevin R.; Burbaum, Jonathan J.; Patricelli, Matthew P.
Characterization and functional annotation of the large number of proteins predicted from genome sequencing projects poses a major scientific challenge. Whereas several proteomics techniques have been developed to quantify the abundance of proteins, these methods provide little information regarding protein function. Here, we present a gel-free platform that permits ultrasensitive, quantitative, and high-resolution analyses of protein activities in proteomes, including highly problematic samples such as undiluted plasma. We demonstrate the value of this platform for the discovery of both disease-related enzyme activities and specific inhibitors that target these proteins.
37.
Visual working memory in decision making by honey bees - Zhang, Shaowu; Bock, Fiola; Si, Aung; Tautz, Juergen; Srinivasan, Mandyam V.
The robustness and plasticity of working memory were investigated in honey bees by using a delayed matching-to-sample (DMTS) paradigm. The findings are summarized as follows: first, performance in the DMTS task decreases as the duration between the presentation of the sample stimulus and the presentation of the comparison stimuli is increased. This decrease is well approximated by an exponential decay function. Performance is significantly better than random-choice level even at delays as long as 5 sec and is reduced to random-choice levels at an average delay time of 8.68 ± 0.06 sec. Second, when the DMTS task involves two samples...
38.
23S rRNA base pair 20572611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A?G - Pfister, Peter; Corti, Natascia; Hobbie, Sven; Bruell, Christian; Zarivach, Raz; Yonath, Ada; Böttger, Erik C.
The 23S rRNA A2058G alteration mediates macrolide, lincosamide, and streptogramin B resistance in the bacterial domain and determines the selectivity of macrolide antibiotics for eubacterial ribosomes, as opposed to eukaryotic ribosomes. However, this mutation is associated with a disparate resistance phenotype: It confers high-level resistance to ketolides in mycobacteria but only marginally affects ketolide susceptibility in streptococci. We used site-directed mutagenesis of nucleotides within domain V of 23S rRNA to study the molecular basis for this disparity. We show that mutational alteration of the polymorphic 20572611 base pair from A-U to G-C in isogenic mutants of Mycobacterium smegmatis significantly affects...
39.
Transcriptome analysis of the aphid bacteriocyte, the symbiotic host cell that harbors an endocellular mutualistic bacterium, Buchnera - Nakabachi, Atsushi; Shigenobu, Shuji; Sakazume, Naoko; Shiraki, Toshiyuki; Hayashizaki, Yoshihide; Carninci, Piero; Ishikawa, Hajime; Kudo, Toshiaki; Fukatsu, Takema
Aphids possess bacteriocytes, cells specifically differentiated to harbor obligatory mutualistic bacteria of the genus Buchnera, which have lost many genes that are essential for common bacterial functions. To understand the host's role in maintaining the symbiotic relationship, bacteriocytes were isolated from the pea aphid, Acyrthosiphon pisum, and the host transcriptome was investigated by using EST analysis and real-time quantitative RT-PCR. A number of genes were highly expressed specifically in the bacteriocyte, including (i) genes for amino acid metabolism, including those for biosynthesis of amino acids that Buchnera cannot produce, and those for utilization of amino acids that Buchnera can synthesize;...
40.
Functional genomic analysis of the rates of protein evolution - Wall, Dennis P.; Hirsh, Aaron E.; Fraser, Hunter B.; Kumm, Jochen; Giaever, Guri; Eisen, Michael B.; Feldman, Marcus W.
The evolutionary rates of proteins vary over several orders of magnitude. Recent work suggests that analysis of large data sets of evolutionary rates in conjunction with the results from high-throughput functional genomic experiments can identify the factors that cause proteins to evolve at such dramatically different rates. To this end, we estimated the evolutionary rates of >3,000 proteins in four species of the yeast genus Saccharomyces and investigated their relationship with levels of expression and protein dispensability. Each protein's dispensability was estimated by the growth rate of mutants deficient for the protein. Our analyses of these improved evolutionary and functional...
21.
