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  • The American Society for Microbiology (ASM)  (117)
  • The American Society for Biochemistry and Molecular Biology (ASBMB)  (84)
  • American Association for the Advancement of Science (AAAS)  (35)
  • The Federation of American Societies for Experimental Biology (FASEB)  (23)
  • 1
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    A long noncoding RNA, lincRNA-Tnfaip3, acts as a coregulator of NF-{kappa}B to modulate inflammatory gene transcription in mouse macrophages [Research] (2017)
    The Federation of American Societies for Experimental Biology (FASEB)
    Details
    Publication Date: 2017-03-01
    Description: Long intergenic noncoding RNAs (lincRNAs) are long noncoding transcripts (〉200 nt) from the intergenic regions of annotated protein-coding genes. We report here that the lincRNA gene lincRNA-Tnfaip3 , located at mouse chromosome 10 proximal to the tumor necrosis factor α-induced protein 3 ( Tnfaip3 ) gene, is an early-primary response gene controlled by nuclear factor-B (NF-B) signaling in murine macrophages. Functionally, lincRNA- Tnfaip3 appears to mediate both the activation and repression of distinct classes of inflammatory genes in macrophages. Specifically, induction of lincRNA-Tnfaip3 is required for the transactivation of NF-B-regulated inflammatory genes in response to bacterial LPSs stimulation. LincRNA-Tnfaip3 physically interacts with the high-mobility group box 1 (Hmgb1), assembling a NF-B/Hmgb1/lincRNA-Tnfaip3 complex in macrophages after LPS stimulation. This resultant NF-B/Hmgb1/lincRNA-Tnfaip3 complex can modulate Hmgb1-associated histone modifications and, ultimately, transactivation of inflammatory genes in mouse macrophages in response to microbial challenge. Therefore, our data indicate a new regulatory role of NF-B-induced lincRNA-Tnfaip3 to act as a coactivator of NF-B for the transcription of inflammatory genes in innate immune cells through modulation of epigenetic chromatin remodeling.—Ma, S., Ming, Z., Gong, A.-Y., Wang, Y., Chen, X., Hu, G., Zhou, R., Shibata, A., Swanson, P. C., Chen, X.-M. A long noncoding RNA, LincRNA-Tnfaip3, acts as a coregulator of NF-B to modulate inflammatory gene transcription in mouse macrophages.
    Print ISSN: 0892-6638
    Electronic ISSN: 1530-6860
    Topics: Biology
    Published by The Federation of American Societies for Experimental Biology (FASEB)
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  • 2
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    A single transcription factor promotes both yield and immunity in rice (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-09-07
    Description: Plant immunity often penalizes growth and yield. The transcription factor Ideal Plant Architecture 1 (IPA1) reduces unproductive tillers and increases grains per panicle, which results in improved rice yield. Here we report that higher IPA1 levels enhance immunity. Mechanistically, phosphorylation of IPA1 at amino acid Ser 163 within its DNA binding domain occurs in response to infection by the fungus Magnaporthe oryzae and alters the DNA binding specificity of IPA1. Phosphorylated IPA1 binds to the promoter of the pathogen defense gene WRKY45 and activates its expression, leading to enhanced disease resistance. IPA1 returns to a nonphosphorylated state within 48 hours after infection, resuming support of the growth needed for high yield. Thus, IPA1 promotes both yield and disease resistance by sustaining a balance between growth and immunity.
    Keywords: Botany
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Anderson localization of electrons in single crystals: LixFe7Se8 (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-02-21
    Description: Anderson (disorder-induced) localization, proposed more than half a century ago, has inspired numerous efforts to explore the absence of wave diffusions in disordered media. However, the proposed disorder-induced metal-insulator transition (MIT), associated with the nonpropagative electron waves, has hardly been observed in three-dimensional (3D) crystalline materials, let alone single crystals. We report the observation of an MIT in centimeter-size single crystals of Li x Fe 7 Se 8 induced by lattice disorder. Both specific heat and infrared reflectance measurements reveal the presence of considerable electronic states in the vicinity of the Fermi level when the MIT occurs, suggesting that the transition is not due to Coulomb repulsion mechanism. The 3D variable range hopping regime evidenced by electrical transport measurements at low temperatures indicates the localized nature of the electronic states on the Fermi level. Quantitative analyses of carrier concentration, carrier mobility, and simulated density of states (DOS) fully support that Li x Fe 7 Se 8 is an Anderson insulator. On the basis of these results, we provide a unified DOS picture to explain all the experimental results, and a schematic diagram for finding other potential Anderson insulators. This material will thus serve as a rich playground for both theoretical and experimental investigations on MITs and disorder-induced phenomena.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Microscopy with a single-molecule scanning electrometer (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018-06-30
    Description: The vibrational spectrum of a single carbon monoxide molecule, adsorbed on the tip apex of a scanning tunneling microscope, is used to image electrostatic fields with submolecular spatial resolution. The method takes advantage of the vibrational Stark effect to image local electrostatic fields and the single-molecule sensitivity of tip-enhanced Raman scattering (TERS) to optically relay the signal. We apply the method to single metalloporphyrins adsorbed on Au(111) to image molecular charges, intramolecular polarization, local photoconductivity, atomically resolved hydrogen bonds, and surface electron density waves.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    Monoubiquitination of Cancer Stem Cell Marker CD133 at Lysine 848 Regulates Its Secretion and Promotes Cell Migration [Research Article] (2018)
    The American Society for Microbiology (ASM)
    Details
    Publication Date: 2018-07-17
    Description: CD133, a widely known marker of cancer stem cells, was recently found in extracellular vesicles. However, the mechanisms underlying CD133 translocation to the extracellular space remain largely unknown. Here we report that CD133 is monoubiquitinated. Ubiquitination occurs primarily on complex glycosylated CD133. The lysine 848 residue at the intracellular carboxyl terminus is one of the sites for CD133 ubiquitination. The K848R mutation does not affect CD133 degradation by the lysosomal pathway but significantly reduces CD133 secretion by inhibiting the interaction between CD133 and tumor susceptibility gene 101 (Tsg101). Furthermore, knockdown of the E3 ubiquitin protein ligase Nedd4 largely impairs CD133 ubiquitination and vesicle secretion. Importantly, CD133-containing vesicles are taken up by recipient cells, consequently promoting cell migration. The K848R mutation reduces cell migration induced by CD133. Taken together, our findings show that monoubiquitination contributes to CD133 vesicle secretion and promotes recipient cell migration. These findings provide a clue to the mechanisms of CD133 secretion and cancer stem cell microenvironment interactional effects.
    Print ISSN: 0270-7306
    Electronic ISSN: 1098-5549
    Topics: Biology , Medicine
    Published by The American Society for Microbiology (ASM)
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  • 6
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    VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-07-20
    Description: Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bind VHL when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with VHL loss-of-function mutations usually had increased abundance and nuclear localization of ZHX2. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated chromatin immunoprecipitation sequencing and microarray analysis showed that ZHX2 promoted nuclear factor B activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC.
    Keywords: Cell Biology, Medicine, Diseases
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
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    Comparison of Immunogenicity and Protection of Two Pneumococcal Protein Vaccines Based on PsaA and PspA [Microbial Immunity and Vaccines] (2018)
    The American Society for Microbiology (ASM)
    Details
    Publication Date: 2018-05-23
    Description: Streptococcus pneumoniae is a major cause of invasive pneumococcal disease, septicemia, and meningitis that can result in high morbidity rates in children under 5 years old. The current polysaccharide-based vaccines can provide type-specific immunity, but a broad-spectrum vaccine would provide greater coverage. Therefore, developing pneumococcal-protein-based vaccines that can extend to more serum types is highly important. In this study, we vaccinated mice via the subcutaneous (s.c.) route with a systemic vaccine that is a mixture of fusion protein PsaA-PspA23 and a single protein, PspA4, with aluminum hydroxide as an adjuvant. As a comparison, mice were immunized intranasally with a mucosal vaccine that is a mixture of PspA2-PA-BLP (where PA is protein anchor and BLP is bacterium-like particle) and PspA4-PA-BLP, via the intranasal (i.n.) route. The two immunization processes were followed by challenge with Streptococcus pneumoniae bacteria from two different PspA families. Specific IgG titers in the serum and specific IgA titers in the mucosa were determined following immunizations. Bacterial loads and survival rates after challenge were compared. Both the systemic vaccine and the mucosal vaccine induced a significant increase of IgG against PspAs. Only the mucosal vaccine also induced specific IgA in the mucosa. The two vaccines provided protection, but each vaccine showed an advantage. The systemic vaccine induced higher levels of serum antibodies, whereas the mucosal vaccine limited the bacterial load in the lung and blood. Therefore, coimmunizations with the two types of vaccines may be implemented in the future.
    Print ISSN: 0019-9567
    Electronic ISSN: 1098-5522
    Topics: Medicine
    Published by The American Society for Microbiology (ASM)
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  • 8
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    Serine-Rich Repeat Adhesins Mediate Shear-Enhanced Streptococcal Binding to Platelets [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions] (2018)
    The American Society for Microbiology (ASM)
    Details
    Publication Date: 2018-05-23
    Description: The binding of bacteria to platelets is thought to be a central event in the pathogenesis of infective endocarditis. The serine-rich repeat (SRR) glycoproteins of viridans group streptococci have been shown to mediate platelet binding in vitro and to contribute to virulence in animal models. However, it is not known whether SRR adhesins can mediate streptococcal binding under the high fluidic shear stress conditions present on the endocardial surface. We found that three streptococcal SRR adhesins (GspB, Hsa, and SrpA) with differing structures and sialoglycan binding specificities nevertheless exhibited similar biomechanical properties. All three adhesins mediated shear-enhanced streptococcal binding to immobilized platelets through the platelet receptor GPIbα. Shear-enhanced adhesion was manifested in three ways. First, the number of circulating streptococci binding via SRR adhesins to immobilized platelet receptors peaked at 1 dyn/cm 2 . Second, bound streptococci switched from weak rolling to strong stationary adhesion as shear stress increased to 10 dyn/cm 2 . Third, while a few streptococci detached each time the flow was increased, the majority of streptococci bound to platelets remained firmly attached through 20 to 80 dyn/cm 2 (shear levels typical of arteries and the endocardium). Thus, all three adhesins mediated shear-enhanced streptococcal binding to platelets under the flow conditions found in heart valves. The ability of the SRR adhesins to mediate shear-enhanced binding strongly suggests that they form catch bonds that are activated by tensile force and provides a mechanism for the selective targeting of bacteria to platelet receptors immobilized on the endocardial surface.
    Print ISSN: 0019-9567
    Electronic ISSN: 1098-5522
    Topics: Medicine
    Published by The American Society for Microbiology (ASM)
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  • 9
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    Biosynthesis of Tropolones in Streptomyces spp.: Interweaving Biosynthesis and Degradation of Phenylacetic Acid and Hydroxylations on the Tropone Ring [Genetics and Molecular Biology] (2018)
    The American Society for Microbiology (ASM)
    Details
    Publication Date: 2018-06-01
    Description: Tropolonoids are important natural products that contain a unique seven-membered aromatic tropolone core and exhibit remarkable biological activities. 3,7-Dihydroxytropolone (DHT) isolated from Streptomyces species is a multiply hydroxylated tropolone exhibiting antimicrobial, anticancer, and antiviral activities. In this study, we determined the DHT biosynthetic pathway by heterologous expression, gene deletion, and biotransformation. Nine trl genes and some of the aerobic phenylacetic acid degradation pathway genes ( paa ) located outside the trl biosynthetic gene cluster are required for the heterologous production of DHT. The trlA gene encodes a single-domain protein homologous to the C-terminal enoyl coenzyme A (enoyl-CoA) hydratase domain of PaaZ. TrlA truncates the phenylacetic acid catabolic pathway and redirects it toward the formation of heptacyclic intermediates. TrlB is a 3-deoxy- d -arabino-heptulosonic acid-7-phosphate (DAHP) synthase homolog. TrlH is an unusual bifunctional protein bearing an N-terminal prephenate dehydratase domain and a C-terminal chorismate mutase domain. TrlB and TrlH enhanced de novo biosynthesis of phenylpyruvate, thereby providing abundant precursor for the prolific production of DHT in Streptomyces spp. Six seven-membered carbocyclic compounds were identified from the trlC , trlD , trlE , and trlF deletion mutants. Four of these chemicals, including 1,4,6-cycloheptatriene-1-carboxylic acid, tropone, tropolone, and 7-hydroxytropolone, were verified as key biosynthetic intermediates. TrlF is required for the conversion of 1,4,6-cycloheptatriene-1-carboxylic acid into tropone. The monooxygenases TrlE and TrlCD catalyze the regioselective hydroxylations of tropone to produce DHT. This study reveals a natural association of anabolism of chorismate and phenylpyruvate, catabolism of phenylacetic acid, and biosynthesis of tropolones in Streptomyces spp. IMPORTANCE Tropolonoids are promising drug lead compounds because of the versatile bioactivities attributed to their highly oxidized seven-membered aromatic ring scaffolds. Our present study provides clear insight into the biosynthesis of 3,7-dihydroxytropolone (DHT) through the identification of key genes responsible for the formation and modification of the seven-membered aromatic core. We also reveal the intrinsic mechanism of elevated production of DHT and related tropolonoids in Streptomyces spp. The study on DHT biosynthesis in Streptomyces exhibits a good example of antibiotic production in which both anabolic and catabolic pathways of primary metabolism are interwoven into the biosynthesis of secondary metabolites. Furthermore, our study sets the stage for metabolic engineering of the biosynthetic pathway for natural tropolonoid products and provides alternative synthetic biology tools for engineering novel tropolonoids.
    Print ISSN: 0099-2240
    Electronic ISSN: 1098-5336
    Topics: Biology
    Published by The American Society for Microbiology (ASM)
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  • 10
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    Candida glabrata Med3 Plays a Role in Altering Cell Size and Budding Index To Coordinate Cell Growth [Physiology] (2018)
    The American Society for Microbiology (ASM)
    Details
    Publication Date: 2018-07-18
    Description: Candida glabrata is a promising microorganism for the production of organic acids. Here, we report deletion and quantitative-expression approaches to elucidate the role of C. glabrata Med3AB ( Cg Med3AB), a subunit of the mediator transcriptional coactivator, in regulating cell growth. Deletion of Cg Med3AB caused an 8.6% decrease in final biomass based on growth curve plots and 10.5% lower cell viability. Based on transcriptomics data, the reason for this growth defect was attributable to changes in expression of genes involved in pyruvate and acetyl-coenzyme A (CoA)-related metabolism in a Cgmed3ab strain. Furthermore, the mRNA level of acetyl-CoA synthetase was downregulated after deleting Cgmed3ab , resulting in 22.8% and 21% lower activity of acetyl-CoA synthetase and cellular acetyl-CoA, respectively. Additionally, the mRNA level of Cg Cln3, whose expression depends on acetyl-CoA, was 34% lower in this strain. As a consequence, the cell size and budding index in the Cgmed3ab strain were both reduced. Conversely, overexpression of Cgmed3ab led to 16.8% more acetyl-CoA and 120% higher Cg Cln3 mRNA levels, as well as 19.1% larger cell size and a 13.3% higher budding index than in wild-type cells. Taken together, these results suggest that Cg Med3AB regulates cell growth in C. glabrata by coordinating homeostasis between cellular acetyl-CoA and Cg Cln3. IMPORTANCE This study demonstrates that Cg Med3AB can regulate cell growth in C. glabrata by coordinating the homeostasis of cellular acetyl-CoA metabolism and the cell cycle cyclin Cg Cln3. Specifically, we report that Cg Med3AB regulates the cellular acetyl-CoA level, which induces the transcription of Cgcln3 , finally resulting in alterations to the cell size and budding index. In conclusion, we report that Cg Med3AB functions as a wheel responsible for driving cellular acetyl-CoA metabolism, indirectly inducing the transcription of Cgcln3 and coordinating cell growth. We propose that Mediator subunits may represent a vital regulatory target modulating cell growth in C. glabrata .
    Print ISSN: 0099-2240
    Electronic ISSN: 1098-5336
    Topics: Biology
    Published by The American Society for Microbiology (ASM)
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