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Published: 10 December 2022
Last updated: 28 January 2023

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1

Yeom, Jinki, Yi Shao, and Eduardo A. Groisman. "Small proteins regulateSalmonellasurvival inside macrophages by controlling degradation of a magnesium transporter." Proceedings of the National Academy of Sciences 117, no. 33 (August 4, 2020): 20235–43. http://dx.doi.org/10.1073/pnas.2006116117.

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All cells require Mg2+to replicate and proliferate. The macrophage protein Slc11a1 is proposed to protect mice from invading microbes by causing Mg2+starvation in host tissues. However, the Mg2+transporter MgtB enables the facultative intracellular pathogenSalmonella entericaserovar Typhimurium to cause disease in mice harboring a functional Slc11a1 protein. Here, we report that, unexpectedly, theSalmonellasmall protein MgtR promotes MgtB degradation by the protease FtsH, which raises the question: How doesSalmonellapreserve MgtB to promote survival inside macrophages? We establish that theSalmonellasmall protein MgtU prevents MgtB proteolysis, even when MgtR is absent. Like MgtB, MgtU is necessary for survival inSlc11a1+/+macrophages, resistance to oxidative stress, and growth under Mg2+limitation conditions. TheSalmonellaMg2+transporter MgtA is not protected by MgtU despite sharing 50% amino acid identity with MgtB and being degraded in an MgtR- and FtsH-dependent manner. Surprisingly, themgtB,mgtR, andmgtUgenes are part of the same transcript, providing a singular example of transcript-specifying proteins that promote and hinder degradation of the same target. Our findings demonstrate that small proteins can confer pathogen survival inside macrophages by altering the abundance of related transporters, thereby furthering homeostasis.
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2

Moncrief, Mary Beth C., and Michael E. Maguire. "Magnesium and the Role of mgtC in Growth of Salmonella typhimurium." Infection and Immunity 66, no. 8 (August 1, 1998): 3802–9. http://dx.doi.org/10.1128/iai.66.8.3802-3809.1998.

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ABSTRACT Salmonella typhimurium has three distinct transport systems for Mg2+: CorA, MgtA, and MgtB. ThemgtCB operon encodes two proteins, MgtC, a hydrophobic protein with a predicted molecular mass of 22.5 kDa, and MgtB, a 102-kDa P-type ATPase Mg2+ transport protein. ThemgtCB locus has been identified as part of a newSalmonella pathogenicity island, SPI-3. Transcription ofmgtCB is regulated by extracellular Mg2+ via the two-component PhoPQ regulatory system important for virulence. To elucidate MgtC’s role in a low-Mg2+ environment, we looked at growth and transport in strains lacking the CorA and MgtA Mg2+ transporters but expressing MgtB, MgtC, or both.mgtC mgtB+ and mgtC+mgtB+ strains exhibited growth in N minimal medium without added Mg2+ with a 1- to 2-h lag phase. AnmgtC+ mgtB strain was also able to grow in N minimal medium without added Mg2+ but only after a 24-h lag phase. In N minimal medium containing 10 mM Mg2+, all strains grew after a short lag phase; the mgtC+mgtB strain grew to a higher optical density at 600 nm than anmgtC+ mgtB+ strain and was comparable to wild type. The lengthy lag phase before growth in anmgtC+ mgtB strain was not due to lack of expression of MgtC. Western blot analysis indicated that substantial MgtC protein is present by 2 h after suspension in N minimal medium. Surprisingly, in an mgtC+mgtB+ strain, MgtC was undetectable during Mg2+ starvation, although large amounts of MgtB were observed. The lack of expression of MgtC is not dependent on functional MgtB, since a strain carrying a nonfunctional MgtB with a mutation (D379A) also did not make MgtC. Since, during invasion of eukaryotic cells, S. typhimurium appears to be exposed to a low-pH as well as a low-Mg2+ environment, the growth of anmgtC+ mgtB strain was tested at low pH with and without added Mg2+. While significant quantities of MgtC could be detected after suspension at pH 5.2, themgtC+ mgtB strain was unable to grow at pH 5.2 whether or not Mg2+ was present. Finally, using63Ni2+ and 57Co2+ as alternative substrates for the unavailable28Mg2+, cation uptake could not be detected in an mgtC+ mgtB strain after Mg2+starvation. We conclude that MgtC is not a Mg2+ transporter and that it does not have a primary role in the survival of S. typhimurium at low pH.
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3

Fishler, Kristen P., Erin H. Breese, Lauren Walters-Sen, and Michelle L. McGowan. "Experiences of a Multidisciplinary Genomic Tumor Board Interpreting Risk for Underlying Germline Variants in Tumor-Only Sequencing Results." JCO Precision Oncology, no. 3 (December 2019): 1–8. http://dx.doi.org/10.1200/po.18.00216.

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PURPOSE Although analyzing germline and tumor samples concurrently provides the best opportunity for differentiating between germline and somatic mutations, tumor-only sequencing is becoming increasingly common in clinical care. The purpose of this study is to assess how a multidisciplinary genomic tumor board (MGTB) evaluated patients’ tumor-only sequencing results and made genetics referrals. With limited professional society guidance on how to manage pathogenic mutations identified via tumor-only sequencing, this study contemplates the professional knowledge and skills necessary to have represented on an MGTB to interpret these results in context of potential germline findings. METHODS Qualitative interviews with MGTB members and an ethnographic case study of a breast cancer MGTB at a National Cancer Institute cancer center were examined. RESULTS This MGTB discussed 34 cases of women with advanced-stage breast cancer over 13 months. Interviews and observations of MGTB meetings indicated that members of the MGTB contemplated whether variants were germline or somatic and potential for identification of germline cancer predisposition. On the basis of existing professional society guidelines, 18 patients would be eligible for germline testing. However, the MGTB only referred 11 patients (61%) for additional germline testing, and the remaining seven patients (39%) were not referred, raising questions about the kind of genomic expertise needed on an MGTB to optimize results interpretation and referrals. CONCLUSION To ensure adequate interpretation, recommendation, and communication of tumor sequencing results, an MGTB should include professionals with knowledge and experience in clinical translation of tumor sequencing, testing methodology, molecular pathology, cancer biology, genomic pathways, germline variant interpretation, evaluation of family history, and application of professional recommendations for germline testing after tumor-only sequencing. These skills may not be held by a single professional on an MGTB.
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4

Ford, Donna C., George W. P. Joshua, Brendan W. Wren, and Petra C. F. Oyston. "The importance of the magnesium transporter MgtB for virulence of Yersinia pseudotuberculosis and Yersinia pestis." Microbiology 160, no. 12 (December 1, 2014): 2710–17. http://dx.doi.org/10.1099/mic.0.080556-0.

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Mg2+ has been shown to be an important signal controlling gene regulation via the PhoPQ two-component regulatory system for a range of Gram-negative bacteria, including Yersinia pestis and Yersinia pseudotuberculosis. The magnesium ion transporter MgtB is part of the complex PhoPQ regulon, being upregulated in response to low Mg2+. Despite the presence of other Mg2+ transport systems in Yersinia, inactivation of mgtB had a significant effect on the ability of the bacteria to scavenge this crucial ion. Whereas inactivation of PhoPQ is reported to adversely affect intracellular survival, we show that Y. pestis and Y. pseudotuberculosis ΔmgtB mutants survived equally as well as the respective parent strain within macrophages, although they were more sensitive to killing in the Galleria model of infection. Surprisingly, despite MgtB being only one member of the Mg2+ stimulon and PhoPQ controlling the expression levels of a range of genes including mgtB, the Yersinia ΔmgtB mutants were more highly attenuated than the equivalent Yersinia ΔphoP mutants in mouse models of infection. MgtB may be a suitable target for development of novel antimicrobials, and investigation of its role may help elucidate the contribution of this component of the PhoPQ regulon to pathogenesis.
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5

Rabausch, U., J. Juergensen, N. Ilmberger, S. Böhnke, S. Fischer, B. Schubach, M. Schulte, and W. R. Streit. "Functional Screening of Metagenome and Genome Libraries for Detection of Novel Flavonoid-Modifying Enzymes." Applied and Environmental Microbiology 79, no. 15 (May 17, 2013): 4551–63. http://dx.doi.org/10.1128/aem.01077-13.

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ABSTRACTThe functional detection of novel enzymes other than hydrolases from metagenomes is limited since only a very few reliable screening procedures are available that allow the rapid screening of large clone libraries. For the discovery of flavonoid-modifying enzymes in genome and metagenome clone libraries, we have developed a new screening system based on high-performance thin-layer chromatography (HPTLC). Thismetagenomeextractthin-layer chromatographyanalysis (META) allows the rapid detection of glycosyltransferase (GT) and also other flavonoid-modifying activities. The developed screening method is highly sensitive, and an amount of 4 ng of modified flavonoid molecules can be detected. This novel technology was validated against a control library of 1,920 fosmid clones generated from a singleBacillus cereusisolate and then used to analyze more than 38,000 clones derived from two different metagenomic preparations. Thereby we identified two novel UDP glycosyltransferase (UGT) genes. The metagenome-derivedgtfCgene encoded a 52-kDa protein, and the deduced amino acid sequence was weakly similar to sequences of putative UGTs fromFibrisomaandDyadobacter. GtfC mediated the transfer of different hexose moieties and exhibited high activities on flavones, flavonols, flavanones, and stilbenes and also accepted isoflavones and chalcones. From the control library we identified a novel macroside glycosyltransferase (MGT) with a calculated molecular mass of 46 kDa. The deduced amino acid sequence was highly similar to sequences of MGTs fromBacillus thuringiensis. Recombinant MgtB transferred the sugar residue from UDP-glucose effectively to flavones, flavonols, isoflavones, and flavanones. Moreover, MgtB exhibited high activity on larger flavonoid molecules such as tiliroside.
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6

Snavely, M. D., S. A. Gravina, T. T. Cheung, C. G. Miller, and M. E. Maguire. "Magnesium transport in Salmonella typhimurium. Regulation of mgtA and mgtB expression." Journal of Biological Chemistry 266, no. 2 (January 1991): 824–29. http://dx.doi.org/10.1016/s0021-9258(17)35247-x.

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7

Maguire, Michael E. "MgtA and MgtB: Prokaryotic P-type ATPases that mediate Mg2+ influx." Journal of Bioenergetics and Biomembranes 24, no. 3 (June 1992): 319–28. http://dx.doi.org/10.1007/bf00768852.

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8

Günzel, Dorothee, Lisa M. Kucharski, David G. Kehres, Michael F. Romero, and Michael E. Maguire. "The MgtC Virulence Factor of Salmonella enterica Serovar Typhimurium Activates Na+,K+-ATPase." Journal of Bacteriology 188, no. 15 (August 1, 2006): 5586–94. http://dx.doi.org/10.1128/jb.00296-06.

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ABSTRACT The mgtC gene of Salmonella enterica serovar Typhimurium encodes a membrane protein of unknown function that is important for full virulence in the mouse. Since mgtC is part of an operon with mgtB which encodes a Mg2+-transporting P-type ATPase, MgtC was hypothesized to function in ion transport, possibly in Mg2+ transport. Consequently, MgtC was expressed in Xenopus laevis oocytes, and its effect on ion transport was evaluated using ion selective electrodes. Oocytes expressing MgtC did not exhibit altered currents or membrane potentials in response to changes in extracellular H+, Mg2+, or Ca2+, thus ruling out a previously postulated function as a Mg2+/H+ antiporter. However, addition of extracellular K+ markedly hyperpolarized membrane potential instead of the expected depolarization. Addition of ouabain to block the oocyte Na+,K+-ATPase completely prevented hyperpolarization and restored the normal K+-induced depolarization response. These results suggested that the Na+,K+-ATPase was constitutively activated in the presence of MgtC resulting in a membrane potential largely dependent on Na+,K+-ATPase. Consistent with the involvement of Na+,K+-ATPase, oocytes expressing MgtC exhibited an increased rate of 86Rb+ uptake and had increased intracellular free [K+] and decreased free [Na+] and ATP. The free concentrations of Mg2+ and Ca2+ and cytosolic pH were unchanged, although the total intracellular Ca2+ content was slightly elevated. These results suggest that the serovar Typhimurium MgtC protein may be involved in regulating membrane potential but does not directly transport Mg2+ or another ion.
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9

Park, Myungseo, Daesil Nam, Dae-Hyuk Kweon, and Dongwoo Shin. "ATP reduction by MgtC and Mg2+homeostasis by MgtA and MgtB enablesSalmonellato accumulate RpoS upon low cytoplasmic Mg2+stress." Molecular Microbiology 110, no. 2 (October 2018): 283–95. http://dx.doi.org/10.1111/mmi.14105.

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10

Snavely, M. D., J. B. Florer, C. G. Miller, and M. E. Maguire. "Magnesium transport in Salmonella typhimurium: 28Mg2+ transport by the CorA, MgtA, and MgtB systems." Journal of Bacteriology 171, no. 9 (1989): 4761–66. http://dx.doi.org/10.1128/jb.171.9.4761-4766.1989.

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11

Xie, Feiyan, Junhao Li, Zhiyue Dong, Dawei Wen, Jianxin Shi, Jing Yan, and Mingmei Wu. "Energy transfer and luminescent properties of Ca8MgLu(PO4)7:Tb3+/Eu3+ as a green-to-red color tunable phosphor under NUV excitation." RSC Advances 5, no. 74 (2015): 59830–36. http://dx.doi.org/10.1039/c5ra08680a.

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Ca8MgTb(PO4)7:Eu3+ phosphor, a potential candidate for application in NUV-based WLEDs, can show efficient energy transfer from Tb3+ to Eu3+, color-tunable emission from green to pure red and excellent thermal stability.
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12

Blanc-Potard, Anne-Béatrice, Felix Solomon, Jayson Kayser, and Eduardo A. Groisman. "The SPI-3 Pathogenicity Island ofSalmonella enterica." Journal of Bacteriology 181, no. 3 (February 1, 1999): 998–1004. http://dx.doi.org/10.1128/jb.181.3.998-1004.1999.

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ABSTRACT Pathogenicity islands are chromosomal clusters of pathogen-specific virulence genes often found at tRNA loci. We have determined the molecular genetic structure of SPI-3, a 17-kb pathogenicity island located at the selC tRNA locus of Salmonella enterica serovar Typhimurium. The G+C content of SPI-3 (47.5%) differs from that of the Salmonella genome (52%), consistent with the notion that these sequences have been horizontally acquired. SPI-3 harbors 10 open reading frames organized in six transcriptional units, which include the previously describedmgtCB operon encoding the macrophage survival protein MgtC and the Mg2+ transporter MgtB. Among the newly identified open reading frames, one exhibits sequence similarity to the ToxR regulatory protein of Vibrio cholerae and one is similar to the AIDA-I adhesin of enteropathogenic Escherichia coli. The distribution of SPI-3 sequences varies among the salmonellae: the right end of the island, which harbors the virulence genemgtC, is present in all eight subspecies ofSalmonella; however, a four-gene cluster at the center of SPI-3 is found in only some of the subspecies and is bracketed by remnants of insertion sequences, suggesting a multistep process in the evolution of SPI-3 sequences.
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13

Wang, Hanbo, Xuefeng Yin, Mona Wu Orr, Michael Dambach, Rebecca Curtis, and Gisela Storz. "Increasing intracellular magnesium levels with the 31-amino acid MgtS protein." Proceedings of the National Academy of Sciences 114, no. 22 (May 16, 2017): 5689–94. http://dx.doi.org/10.1073/pnas.1703415114.

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Synthesis of the 31-amino acid, inner membrane protein MgtS (formerly denoted YneM) is induced by very low Mg2+ in a PhoPQ-dependent manner in Escherichia coli. Here we report that MgtS acts to increase intracellular Mg2+ levels and maintain cell integrity upon Mg2+ depletion. Upon development of a functional tagged derivative of MgtS, we found that MgtS interacts with MgtA to increase the levels of this P-type ATPase Mg2+ transporter under Mg2+-limiting conditions. Correspondingly, the effects of MgtS upon Mg2+ limitation are lost in a ∆mgtA mutant, and MgtA overexpression can suppress the ∆mgtS phenotype. MgtS stabilization of MgtA provides an additional layer of regulation of this tightly controlled Mg2+ transporter and adds to the list of small proteins that regulate inner membrane transporters.
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14

Marshall, Bryan, Alain Stintzi, Christie Gilmour, Jean-Marie Meyer, and Keith Poole. "Citrate-mediated iron uptake in Pseudomonas aeruginosa: involvement of the citrate-inducible FecA receptor and the FeoB ferrous iron transporter." Microbiology 155, no. 1 (January 1, 2009): 305–15. http://dx.doi.org/10.1099/mic.0.023531-0.

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In an attempt to identify components of a ferric citrate uptake system in Pseudomonas aeruginosa, a mutant library of a siderophore-deficient strain (IA614) was constructed and screened for defects in citrate-promoted growth in an Fe-restricted medium. A mutant disrupted in gene PA3901, encoding a homologue of the outer-membrane ferric citrate receptor, FecA, of Escherichia coli (FecAE.c.), was recovered and shown to be deficient in citrate-promoted growth and citrate-mediated Fe uptake. A mutant disrupted in gene PA4825, encoding a homologue of the MgtA/MgtB Mg2+ transporters in Salmonella enterica, was similarly deficient in citrate-promoted growth, though this was due to a citrate sensitivity of the mutant apparently resulting from citrate-promoted acquisition of Fe2+ and resultant oxidative stress. Consistent with citrate delivering Fe to cells as Fe2+, a P. aeruginosa mutant lacking the FeoB Fe2+ transporter homologue, PA4358, was compromised for citrate-promoted growth in Fe-restricted medium and showed markedly reduced citrate-mediated Fe uptake. Subsequent elimination of two Fe3+ transporter homologues, PA5216 and PA4687, in the feoB mutant failed to further compromise citrate-promoted growth or Fe uptake, though the additional loss of pcoA, encoding a periplasmic ferroxidase implicated in Fe2+ acquisition, completely abrogated citrate-mediated Fe uptake. Fe acquisition mediated by other siderophores (e.g. pyoverdine) was, however, unaffected in the quadruple knockout strain. These data indicate that Fe delivered to P. aeruginosa by citrate is released as Fe2+, probably in the periplasm, prior to its transport into cells via Fe transport components.
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15

Cunrath, Olivier, and Dirk Bumann. "Host resistance factor SLC11A1 restricts Salmonella growth through magnesium deprivation." Science 366, no. 6468 (November 21, 2019): 995–99. http://dx.doi.org/10.1126/science.aax7898.

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The pleiotropic host resistance factor SLC11A1 (NRAMP1) defends against diverse intracellular pathogens in mammals by yet-unknown mechanisms. We compared Salmonella infection of coisogenic mice with different SLC11A1 alleles. SLC11A1 reduced Salmonella replication and triggered up-regulation of uptake systems for divalent metal cations but no other stress responses. SLC11A1 modestly diminished iron availability and acutely restricted Salmonella access to magnesium. Growth of Salmonella cells in the presence of SLC11A1 was highly heterogeneous and inversely correlated with expression of the crucial magnesium transporter gene mgtB. We observed superimposable single-cell patterns in mice lacking SLC11A1 when we restricted Salmonella access to magnesium by impairing its uptake. Together, these findings identify deprivation of the main group metal magnesium as the main resistance mechanism of SLC11A1 against Salmonella.
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16

Snavely, M. D., C. G. Miller, and M. E. Maguire. "The mgtB Mg2+ transport locus of Salmonella typhimurium encodes a P-type ATPase." Journal of Biological Chemistry 266, no. 2 (January 1991): 815–23. http://dx.doi.org/10.1016/s0021-9258(17)35246-8.

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17

Smith, D. L., T. Tao, and M. E. Maguire. "Membrane topology of a P-type ATPase. The MgtB magnesium transport protein of Salmonella typhimurium." Journal of Biological Chemistry 268, no. 30 (October 1993): 22469–79. http://dx.doi.org/10.1016/s0021-9258(18)41553-0.

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18

Tao, T., M. D. Snavely, S. G. Farr, and M. E. Maguire. "Magnesium transport in Salmonella typhimurium: mgtA encodes a P-type ATPase and is regulated by Mg2+ in a manner similar to that of the mgtB P-type ATPase." Journal of bacteriology 177, no. 10 (1995): 2654–62. http://dx.doi.org/10.1128/jb.177.10.2654-2662.1995.

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19

Kato, Akinori, Hiroyuki Tanabe, and Ryutaro Utsumi. "Molecular Characterization of the PhoP-PhoQ Two-Component System in Escherichia coli K-12: Identification of Extracellular Mg2+-Responsive Promoters." Journal of Bacteriology 181, no. 17 (September 1, 1999): 5516–20. http://dx.doi.org/10.1128/jb.181.17.5516-5520.1999.

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ABSTRACT We identified Mg2+-responsive promoters of thephoPQ, mgtA, and mgrB genes ofEscherichia coli K-12 by S1 nuclease analysis. Expression of these genes was induced by magnesium limitation and depended on PhoP and PhoQ. The transcription start sites were also determined, which allowed us to find a (T/G)GTTTA direct repeat in their corresponding promoter regions.
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20

Solley, David, and Keith Barr. "Optimise what you have first! Low cost upgrading of plants for improved nutrient removal." Water Science and Technology 39, no. 6 (March 1, 1999): 127–34. http://dx.doi.org/10.2166/wst.1999.0279.

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Brisbane Water has undertaken an investigation into low cost options to imprrove the removal of nitrogen and phosphorus for two of its wastewater treatment plants. Luggage Point Stage 2 (300,000 e.p.) is a conventional activated sludge plant designed for nitrification. Gibson Island (150,000 e.p.) is an extended aeration activated sludge plant designed for nitrogen removal to less than 10 mgTN/l. Extensive modelling and plant simulation were carried out to evaluate the potential of various modified operational modes before the most promising modes were trialed on the full scale plants. Operational trials are proceeding well and improved nitrogen removal to less than 3 mgTN/l for Gibson Island and to less than 10 mgTN/l for Luggage Point have been achieved. Improved phosphorus removal has also been achieved for periods at both plants (less than 4 mgTP/L for Luggage Point and less than 2.5 mgTP/l at Gibson Island). However, phosphorus removal has not been consistent and trials are ongoing to determine the sustainable level of phosphorus removal for these plants. The conclusion of the trials to date is that operational strategies can be implemented for these plants to effect the removal of substantial quantities of nitrogen and phosphorus for a minimum of capital cost. This paper presents the results of the various operational strategies that have been trialed and implemented for both plants. When considering the upgrading of a plant for improved nutrient removal, the principle of “Optimise What You Have First” can sometimes produce surprisingly high nutrient removal levels for a very modest capital expenditure.
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21

Minagawa, Shu, Hiroshi Ogasawara, Akinori Kato, Kaneyoshi Yamamoto, Yoko Eguchi, Taku Oshima, Hirotada Mori, Akira Ishihama, and Ryutaro Utsumi. "Identification and Molecular Characterization of the Mg2+ Stimulon of Escherichia coli." Journal of Bacteriology 185, no. 13 (July 1, 2003): 3696–702. http://dx.doi.org/10.1128/jb.185.13.3696-3702.2003.

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ABSTRACT Transcription profile microarray analysis in Escherichia coli was performed to identify the member genes of the Mg2+ stimulon that respond to the availability of external Mg2+ in a PhoP/PhoQ two-component system-dependent manner. The mRNA levels of W3110 in the presence of 30 mM MgCl2, WP3022 (phoP defective), and WQ3007 (phoQ defective) were compared with those of W3110 in the absence of MgCl2. The expression ratios of a total of 232 genes were <0.75 in all three strains (the supplemental data are shown at http://www.nara.kindai.ac.jp/nogei/seiken/array.html ), suggesting that the PhoP/PhoQ system is involved directly or indirectly in the transcription of these genes. Of those, 26 contained the PhoP box-like sequences with the direct repeats of (T/G)GTTTA within 500 bp upstream of the initiation codon. Furthermore, S1 nuclease assays of 26 promoters were performed to verify six new Mg2+ stimulon genes, hemL, nagA, rstAB, slyB, vboR, and yrbL, in addition to the phoPQ, mgrB, and mgtA genes reported previously. In gel shift and DNase I footprinting assays, all of these genes were found to be regulated directly by PhoP. Thus, we concluded that the phoPQ, mgrB, mgtA, hemL, nagA, rstAB, slyB, vboR, and yrbL genes make up the Mg2+ stimulon in E. coli.
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KUMAR, NITU, KRISHNA MOHAN, KARLA GEORGES, FRANCIS DZIVA, and ABIODUN A. ADESIYUN. "Occurrence of Virulence and Resistance Genes in Salmonella in Cloacae of Slaughtered Chickens and Ducks at Pluck Shops in Trinidad." Journal of Food Protection 84, no. 1 (August 20, 2020): 39–46. http://dx.doi.org/10.4315/jfp-20-203.

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ABSTRACT The study used PCR to determine the molecular basis of the antibiotic resistance and virulence profiles of isolates of Salmonella by targeting genes encoding for carriage and persistence in the poultry. Of a total 1,503 cecal samples collected from poultry, 91 (6.1%) were positive for Salmonella. Ten different serotypes were detected from Salmonella isolates. The study was also conducted to determine the occurrence of 13 virulence and 12 resistance genes in isolates of Salmonella. All 46 isolates of Salmonella tested were positive for one or more of the 12 virulence genes detected, ranging from 0.0% (viaB) to 100.0% (invA, mgtB, pipA, and spi4D) (P &lt; 0.05). Occurrence of virulence genes varied significantly (P &lt; 0.05) by serotype but not by animal species. Only 4 (33.3%) of 12 resistance genes assayed were detected: strA, ampC, cmy2, and qnrB. Overall, the occurrence of detected resistance genes was 71.7% (33 of 46), and 87.1 and 40.0% of the isolates from chickens and ducks, respectively, were positive (P = 0.0009). The occurrence of resistance genes ranged from 2.2% (cmy2) to 50.0% (qnrB) in isolates positive for resistance gene. The findings provide evidence that poultry from “pluck shops” are colonized by Salmonella pathogens that harbor virulence and antimicrobial resistance genes; this may have clinical and therapeutic consequences, if the genes detected are expressed. Although there is a need for prudent use of antimicrobial agents in poultry production systems, there should be constant monitoring for the prevalence of resistance in Salmonella isolates using phenotypic methods. The importance of monitoring the occurrence of resistance genes in the pathogens in Trinidad cannot be ignored. HIGHLIGHTS
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23

Park, Sun-Yang, Mauricio H. Pontes, and Eduardo A. Groisman. "Flagella-independent surface motility inSalmonella entericaserovar Typhimurium." Proceedings of the National Academy of Sciences 112, no. 6 (January 26, 2015): 1850–55. http://dx.doi.org/10.1073/pnas.1422938112.

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Flagella are multiprotein complexes necessary for swimming and swarming motility. InSalmonella entericaserovar Typhimurium, flagella-mediated motility is repressed by the PhoP/PhoQ regulatory system. We now report thatSalmonellacan move on 0.3% agarose media in a flagella-independent manner when experiencing the PhoP/PhoQ-inducing signal low Mg2+. This motility requires the PhoP-activatedmgtA,mgtC, andpagMgenes, which specify a Mg2+transporter, an inhibitor ofSalmonella’s own F1FoATPase, and a small protein of unknown function, respectively. The MgtA and MgtC proteins are necessary forpagMexpression becausepagMmRNA levels were lower inmgtAandmgtCmutants than in wild-typeSalmonella, and also becausepagMexpression from a heterologous promoter rescued motility inmgtAandmgtCmutants. PagM promotes group motility by a surface protein(s), as apagM-expressing strain conferred motility upon apagMnull mutant, and proteinase K treatment eliminated motility. ThepagMgene is rarely found outside subspecies I ofS. entericaand often present in nonfunctional allelic forms in organisms lacking the identified motility. Deletion of thepagMgene reduced bacterial replication on 0.3% agarose low Mg2+media but not in low Mg2+liquid media. Our findings define a form of motility that allowsSalmonellato scavenge nutrients and to escape toxic compounds in low Mg2+semisolid environments.
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Eguchi, Yoko, Tadashi Okada, Shu Minagawa, Taku Oshima, Hirotada Mori, Kaneyoshi Yamamoto, Akira Ishihama, and Ryutaro Utsumi. "Signal Transduction Cascade between EvgA/EvgS and PhoP/PhoQ Two-Component Systems of Escherichia coli." Journal of Bacteriology 186, no. 10 (May 15, 2004): 3006–14. http://dx.doi.org/10.1128/jb.186.10.3006-3014.2004.

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ABSTRACT Transcriptional analysis of a constitutively active mutant of the EvgA/EvgS two-component system of Escherichia coli resulted in enhanced expression of 13 PhoP/PhoQ-regulated genes, crcA, hemL, mgtA, ompT, phoP, phoQ, proP, rstA, rstB, slyB, ybjG, yrbL, and mgrB. This regulatory network between the two systems also occurred as a result of overproduction of the EvgA regulator; however, enhanced transcription of the phoPQ genes did not further activate expression of the PhoP/PhoQ-regulated genes. These results demonstrated signal transduction from the EvgA/EvgS system to the PhoP/PhoQ system in E. coli and also identified the genes that required the two systems for enhanced expression. This is one example of the intricate signal transduction networks that are posited to exist in E. coli.
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Jean-Francois, Frantz L., Alissa Myrick, Likai Song, Eric Rubin, and Timothy A. Cross. "Heterooligomerization of Membrane Peptides Involved in Tuberculosis: MgtC and MgtR." Biophysical Journal 102, no. 3 (January 2012): 422a. http://dx.doi.org/10.1016/j.bpj.2011.11.2309.

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26

Дологлонян, А. В., В. Т. Матвеенко, and А. Г. Клименко. "Efficiency of the combined gas turbine plants at partial loads." MORSKIE INTELLEKTUAL`NYE TEHNOLOGII)</msg>, no. 3(57) (August 7, 2022): 109–17. http://dx.doi.org/10.37220/mit.2022.57.3.014.

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Комбинированные установки на базе газотурбинных двигателей (ГТД) и установок органического цикла Ренкина (ОЦР) морского, подводного и наземного базирования часто работают на переменных нагрузках в зависимости от условий эксплуатации. Поэтому необходимо оценить их энергоэффективность для различных схем ГТД, ОЦР и рабочих тел на частичных нагрузках. Предметом рассмотрения в статье является исследование влияния схем ГТД, ОЦР и рода рабочего тела на эффективность комбинированных микрогазотурбинных установок при работе на частичных нагрузках. Установлено, что наиболее эффективной схемой комбинированной микрогазотурбинной установки (МГТУ) во всем диапазоне мощностей является комбинация микрогазотурбинного двигателя (МГТД) на базе простого цикла с турбокомпрессорным утилизатором и регенерацией и регенеративной установки ОЦР. Показано, что характер изменения относительных параметров комбинированной МГТУ определяется в большей степени базовой схемой МГТД, а также родом рабочего тела установки ОЦР. Определено, что наиболее предпочтительным рабочим телом ОЦР в составе МГТУ для большинства схем ГТД является хладагент R-123. Combined based based on gas turbine engines (GTE) and organic Rankine cycle plants (ORC) of marine, underwater and land-based often operate at variable loads depending on operating conditions. Therefore, it is necessary to evaluate their energy efficiency for various schemes of GTE, ORC and working fluids at partial loads. The subject of consideration in the article is the study of the influence of GTE schemes, ORC and the type of working fluid on the efficiency of combined microgas turbine plants when operating at partial loads. It has been established that the most efficient scheme of a combined microgas turbine plant (MGTP) in the entire power range is a combination of a microgas turbine engine (MGTE) based on a simple cycle with a turbocharge utilizer and regeneration and an ORC regenerative unit. It is shown that the nature of the change in the relative parameters of the combined MGTP is determined to a greater extent by the basic scheme of the MGTE, as well as by the type of the working fluid of the ORC unit. It has been determined that the most preferred working fluid of the ORC as part of the MSTP for most gas turbine engine schemes is the R-123 refrigerant.
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27

Jean-Francois, Frantz L., and Timothy A. Cross. "Understanding the Potential Interaction of Transmembrane Helices from MgtC and MgtR." Biophysical Journal 100, no. 3 (February 2011): 384a—385a. http://dx.doi.org/10.1016/j.bpj.2010.12.2287.

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28

Lejona, Sergio, Andrés Aguirre, María Laura Cabeza, Eleonora García Véscovi, and Fernando C. Soncini. "Molecular Characterization of the Mg2+-Responsive PhoP-PhoQ Regulon in Salmonella enterica." Journal of Bacteriology 185, no. 21 (November 1, 2003): 6287–94. http://dx.doi.org/10.1128/jb.185.21.6287-6294.2003.

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ABSTRACT The PhoP/PhoQ two-component system controls the extracellular magnesium deprivation response in Salmonella enterica. In addition, several virulence-associated genes that are mainly required for intramacrophage survival during the infection process are under the control of its transcriptional regulation. Despite shared Mg2+ modulation of the expression of the PhoP-activated genes, no consensus sequence common to all of them could be detected in their promoter regions. We have investigated the transcriptional regulation and the interaction of the response regulator PhoP with the promoter regions of the PhoP-activated loci phoPQ, mgtA, slyB, pmrD, pcgL, phoN, pagC, and mgtCB. A direct repeat of the heptanucleotide sequence (G/T)GTTTA(A/T) was identified as the conserved motif recognized by PhoP to directly control the gene expression of the first five loci, among which the first four are ancestral to enterobacteria. On the other hand, no direct interaction of the response regulator with the promoter of phoN, pagC, or mgtCB was apparent by either in vitro or in vivo assays. These loci are Salmonella specific and were probably acquired by horizontal DNA transfer. Besides, sequence analysis of pag promoters revealed the presence of a conserved PhoP box in 6 out of the 12 genes analyzed. Our results strongly suggest that the expression of a set of Mg2+-controlled genes is driven by PhoP via unknown intermediate regulatory mechanisms that could also involve ancillary factors.
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29

Zweifel, S. G., and W. L. Fangman. "A nuclear mutation reversing a biased transmission of yeast mitochondrial DNA." Genetics 128, no. 2 (June 1, 1991): 241–49. http://dx.doi.org/10.1093/genetics/128.2.241.

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Abstract The highly biased transmission of p- mitochondrial DNA that occurs in hypersuppressive matings between p- and p+ cells of the yeast Saccharomyces cerevisiae is thought to be a consequence of the replication advantage of the p- mtDNA. A nuclear gene, MGT1, that is required for this displacement of p+ mtDNA from zygotic clones has been identified through mutation. When one haploid parent carries the mgt1 allele, transmission of p- mtDNA is substantially reduced. When both haploid parents carry the mgt1 allele, p- mtDNA is essentially eliminated from the zygotic progeny. Thus in the absence of the MGT1 gene there is a switch in the transmission bias; p+ mtDNA rather than the hypersuppressive p- mtDNA is inherited by most zygotic clones. In contrast to its semi-dominant behavior in haploid matings, mgt1 behaves as a recessive allele in diploid matings since the p+ genome in MGT1/mgt1 diploids is efficiently displaced when mated with a MGT1/mgt1 hypersuppressive p- diploid strain. We find that p+ genomes can be comaintained along with hypersuppressive p- mtDNA for extended periods in clonal lines derived from MGT1 x mgt1 matings. However, as expected from the recessive nature of the mgt1 mutation, these p+ genomes are eventually eliminated. Our work indicates that MGT1 plays a crucial role in the competition for inheritance between hypersuppressive p- mtDNAs and the p+ mitochondrial genome. The MGT1 gene product may be a component of a mtDNA replication system that acts preferentially at the rep sequences found in hypersuppressive mtDNAs.
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30

Jin, Fei, Minxuan Sun, Takashi Fujii, Yurika Yamada, Jin Wang, Andrés D. Maturana, Miki Wada, et al. "The structure of MgtE in the absence of magnesium provides new insights into channel gating." PLOS Biology 19, no. 4 (April 27, 2021): e3001231. http://dx.doi.org/10.1371/journal.pbio.3001231.

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MgtE is a Mg2+ channel conserved in organisms ranging from prokaryotes to eukaryotes, including humans, and plays an important role in Mg2+ homeostasis. The previously determined MgtE structures in the Mg2+-bound, closed-state, and structure-based functional analyses of MgtE revealed that the binding of Mg2+ ions to the MgtE cytoplasmic domain induces channel inactivation to maintain Mg2+ homeostasis. There are no structures of the transmembrane (TM) domain for MgtE in Mg2+-free conditions, and the pore-opening mechanism has thus remained unclear. Here, we determined the cryo-electron microscopy (cryo-EM) structure of the MgtE-Fab complex in the absence of Mg2+ ions. The Mg2+-free MgtE TM domain structure and its comparison with the Mg2+-bound, closed-state structure, together with functional analyses, showed the Mg2+-dependent pore opening of MgtE on the cytoplasmic side and revealed the kink motions of the TM2 and TM5 helices at the glycine residues, which are important for channel activity. Overall, our work provides structure-based mechanistic insights into the channel gating of MgtE.
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31

DOLOGLONYAN, A. V., and V. T. MATVEENKO. "THERMODYNAMIC CHARACTERISTICS OF MICROGAS TURBINE ENGINES COMBINED CYCLES FOR DISTRIBUTED ENERGY." Fundamental and Applied Problems of Engineering and Technology 4, no. 1 (2020): 28–41. http://dx.doi.org/10.33979/2073-7408-2020-342-4-1-28-41.

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The subject of this article is methods of complicating the cycles of microgas turbine plants (MGTP) in order to further increase their efficiency. The direction of a deeper utilization of the heat of exhaust gases from MGTP was chosen, turning it into work in the organic Rankine cycle (OCR) plant. It has been established that the costeffectiveness of MGTP with OCR is dependent on the configuration of MGTP, OCR and the type of refrigerant and is higher than the basic configuration of MGTP by 4... 15%. It is shown that to increase the versatility of combined MGTP, it is possible to use plants with a switching heat flow, supplemented by renewable energy sources, to conduct separate optimization of the basic MGTP and the OCR plant.
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32

Cromie, Michael J., and Eduardo A. Groisman. "Promoter and Riboswitch Control of the Mg2+ Transporter MgtA from Salmonella enterica." Journal of Bacteriology 192, no. 2 (November 6, 2009): 604–7. http://dx.doi.org/10.1128/jb.01239-09.

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ABSTRACT The MgtA protein from Salmonella enterica serovar Typhimurium mediates Mg2+ uptake from the periplasm into the cytoplasm. Here we report that the PhoP/PhoQ two-component regulatory system, which responds to periplasmic Mg2+, governs mgtA transcription initiation at all investigated Mg2+ concentrations and that the Mg2+-sensing 5′ leader region of the mgtA gene controls transcription elongation into the mgtA coding region when Salmonella is grown in media with <50 μM Mg2+. Overexpression of the Mg2+ transporter CorA, which is believed to increase cytoplasmic Mg2+ levels, decreased mgtA transcription in a manner dependent on a functional mgtA 5′ leader.
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33

Belon, Claudine, Mariana Rosas Olvera, Eric Vives, Laurent Kremer, Laila Gannoun-Zaki, and Anne-Béatrice Blanc-Potard. "Use of the Salmonella MgtR peptide as an antagonist of the Mycobacterium MgtC virulence factor." Future Microbiology 11, no. 2 (February 2016): 215–25. http://dx.doi.org/10.2217/fmb.15.134.

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34

Coffey, Barbara M., Saeed S. Akhand, and Gregory G. Anderson. "MgtE is a dual-function protein in Pseudomonas aeruginosa." Microbiology 160, no. 6 (June 1, 2014): 1200–1213. http://dx.doi.org/10.1099/mic.0.075275-0.

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The opportunistic pathogen Pseudomonas aeruginosa causes a wide range of infections, including chronic biofilm infections in the lungs of individuals with cystic fibrosis. We previously found that the inner-membrane protein MgtE can function both as a magnesium transporter and a virulence modulator, although the exact mechanism governing these activities is unclear. To address this issue, we carried out an experimental characterization of P. aeruginosa MgtE and generated a computer-rendered model. Our in silico analysis demonstrated the structural similarity of P. aeruginosa MgtE to that of the crystal structure of MgtE in Thermus thermophilus. Experimentally, we verified that MgtE is not essential for growth and found that it may not be involved directly in biofilm formation, even under low-magnesium conditions. We demonstrated both magnesium transport and cytotoxicity-regulating functions, and showed that magnesium-binding sites in the connecting helix region of MgtE are vital in coupling these two functions. Furthermore, limiting magnesium environments stimulated mgtE transcriptional responses. Our results suggested that MgtE might play an important role in linking magnesium availability to P. aeruginosa pathogenesis.
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Iverson-Cabral, Stefanie L., Sabina G. Astete, Craig R. Cohen, Eduardo P. C. Rocha, and Patricia A. Totten. "Intrastrain Heterogeneity of the mgpB Gene in Mycoplasma genitalium Is Extensive In Vitro and In Vivo and Suggests that Variation Is Generated via Recombination with Repetitive Chromosomal Sequences." Infection and Immunity 74, no. 7 (July 2006): 3715–26. http://dx.doi.org/10.1128/iai.00239-06.

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ABSTRACT Mycoplasma genitalium is associated with reproductive tract disease in women and may persist in the lower genital tract for months, potentially increasing the risk of upper tract infection and transmission to uninfected partners. Despite its exceptionally small genome (580 kb), approximately 4% is composed of repeated elements known as MgPar sequences (MgPa repeats) based on their homology to the mgpB gene that encodes the immunodominant MgPa adhesin protein. The presence of these MgPar sequences, as well as mgpB variability between M. genitalium strains, suggests that mgpB and MgPar sequences recombine to produce variant MgPa proteins. To examine the extent and generation of diversity within single strains of the organism, we examined mgpB variation within M. genitalium strain G-37 and observed sequence heterogeneity that could be explained by recombination between the mgpB expression site and putative donor MgPar sequences. Similarly, we analyzed mgpB sequences from cervical specimens from a persistently infected woman (21 months) and identified 17 different mgpB variants within a single infecting M. genitalium strain, confirming that mgpB heterogeneity occurs over the course of a natural infection. These observations support the hypothesis that recombination occurs between the mgpB gene and MgPar sequences and that the resulting antigenically distinct MgPa variants may contribute to immune evasion and persistence of infection.
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Redelman, Carly V., Shubham Chakravarty, and Gregory G. Anderson. "Antibiotic treatment of Pseudomonas aeruginosa biofilms stimulates expression of the magnesium transporter gene mgtE." Microbiology 160, no. 1 (January 1, 2014): 165–78. http://dx.doi.org/10.1099/mic.0.070144-0.

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Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen with the capacity to cause serious disease, including chronic biofilm infections in the lungs of cystic fibrosis (CF) patients. These infections are treated with high concentrations of antibiotics. Virulence modulation is an important tool utilized by P. aeruginosa to propagate infection and biofilm formation in the CF airway. Many different virulence modulatory pathways and proteins have been identified, including the magnesium transporter protein MgtE. We have recently found that isogenic deletion of mgtE leads to increased cytotoxicity through effects on the type III secretion system. To explore the role of the CF lung environment in MgtE activity, we investigated mgtE transcriptional regulation following antibiotic treatment. Utilizing quantitative real-time-PCR, we have demonstrated an increase in mgtE transcript levels following antibiotic treatment with most of the 12 antibiotics tested. To begin to determine the regulatory network governing mgtE expression, we screened a transposon-mutant library of P. aeruginosa to look for mutants with potentially altered mgtE activity, using cytotoxicity as a readout. In this screen, we observed that AlgR, which regulates production of the biofilm polysaccharide alginate, alters MgtE-mediated cytotoxicity. This cross-talk between MgtE and AlgR suggests that AlgR is involved in linking external inducing signals (e.g. antibiotics) to mgtE transcription and downstream virulence and biofilm activities. Analysing such interactions may lead to a better understanding of how the CF lung environment shapes P. aeruginosa biofilm infections.
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Barchiesi, Julieta, María E. Castelli, Fernando C. Soncini, and Eleonora García Véscovi. "mgtA Expression Is Induced by Rob Overexpression and Mediates a Salmonella enterica Resistance Phenotype." Journal of Bacteriology 190, no. 14 (May 16, 2008): 4951–58. http://dx.doi.org/10.1128/jb.00195-08.

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ABSTRACT Rob is a member of the Sox/Mar subfamily of AraC/XylS-type transcriptional regulators implicated in bacterial multidrug, heavy metal, superoxide, and organic solvent resistance phenotypes. We demonstrate that, in Salmonella enterica, Rob overexpression upregulates the transcription of mgtA, which codes for the MgtA Mg2+ transporter. mgtA was previously characterized as a member of the Mg2+-modulated PhoPQ regulon. Here we demonstrate that Rob (but not its paralog protein SoxS or MarA) is able to induce mgtA transcription in a PhoP-independent fashion by binding to a conserved Mar/Sox/Rob motif localized downstream of the PhoP-box and overlapping the PhoP-dependent transcriptional start site. We found that Rob-induced mgtA expression confers low-level cyclohexane resistance on Salmonella. Because mgtA intactness is required for Rob-induced cyclohexane resistance, provided the AcrAB multidrug efflux pump can be expressed, we postulate that MgtA is involved in the AcrAB-mediated cyclohexane detoxification mechanism promoted by Rob in Salmonella.
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38

Szadkowski, Dobromir, Luís António Menezes Carreira, and Lotte Søgaard-Andersen. "A bipartite, low-affinity roadblock domain-containing GAP complex regulates bacterial front-rear polarity." PLOS Genetics 18, no. 9 (September 6, 2022): e1010384. http://dx.doi.org/10.1371/journal.pgen.1010384.

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The Ras-like GTPase MglA is a key regulator of front-rear polarity in the rod-shaped Myxococcus xanthus cells. MglA-GTP localizes to the leading cell pole and stimulates assembly of the two machineries for type IV pili-dependent motility and gliding motility. MglA-GTP localization is spatially constrained by its cognate GEF, the RomR/RomX complex, and GAP, the MglB Roadblock-domain protein. Paradoxically, RomR/RomX and MglB localize similarly with low and high concentrations at the leading and lagging poles, respectively. Yet, GEF activity dominates at the leading and GAP activity at the lagging pole by unknown mechanisms. Here, we identify RomY and show that it stimulates MglB GAP activity. The MglB/RomY interaction is low affinity, restricting formation of the bipartite MglB/RomY GAP complex almost exclusively to the lagging pole with the high MglB concentration. Our data support a model wherein RomY, by forming a low-affinity complex with MglB, ensures that the high MglB/RomY GAP activity is confined to the lagging pole where it dominates and outcompetes the GEF activity of the RomR/RomX complex. Thereby, MglA-GTP localization is constrained to the leading pole establishing front-rear polarity.
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39

DOLOGLONYAN, A. V., and V. T. MATVIIENKO. "USE OF LOCAL COLD CLIMATE RESOURCES IN COMBINED CYCLES OF MICROGAS TURBINE ENGINES FOR DISTRIBUTED POWER ENGINEERING." Fundamental and Applied Problems of Engineering and Technology 4, no. 2 (2020): 124–35. http://dx.doi.org/10.33979/2073-7408-2020-342-4-2-124-135.

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The subject of this article is methods of complicating of microgas turbine plants (MGTP) cycles in order to further increase their efficiency. The direction of a deeper utilization of the heat of exhaust gases of MGTP was chosen, turning it into work in the organic Rankine cycle (OCR) plant, as well as the use of local climatic cold resources. It has been established that the use of an additional steam turbine as part of the OCR combined MGTP allows to increase its efficiency from October to March on 2... 4% depending on the configuration of the basic MGTP, which ensures an increase in the average annual efficiency on 1... 2%. It is shown that the OCR plant on R-134a does not allow the full use of the temperature potential of the gases of the base MGTP, since the decomposition temperature is lower than the temperature of the gases of the base MGTP, therefore the efficiency of all configurations of combined MGTP using R- 134a is lower than the analogous ones using ammonia on 2... 5%.
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40

Esposito, Gabriele, René van Bavel, Tom Baranowski, and Néstor Duch-Brown. "Applying the Model of Goal-Directed Behavior, Including Descriptive Norms, to Physical Activity Intentions." Psychological Reports 119, no. 1 (July 22, 2016): 5–26. http://dx.doi.org/10.1177/0033294116649576.

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The theory of planned behavior (TPB) has received its fair share of criticism lately, including calls for it to retire. We contribute to improving the theory by testing extensions such as the model of goal-directed behavior (MGDB, which adds desire and anticipated positive and negative emotions) applied to physical activity (PA) intention. We also test the inclusion of a descriptive norms construct as an addition to the subjective norms construct, also applied to PA, resulting in two additional models: TPB including descriptive norms (TPB + DN) and MGDB including descriptive norms (MGDB + DN). The study is based on an online survey of 400 young adult Internet users, previously enrolled in a subject pool. Confirmatory factor analysis (CFA) showed that TPB and TPB + DN were not fit for purpose, while MGDB and MGDB + DN were. Structural equation modelling (SEM) conducted on MGDB and MGDB + DN showed that the inclusion of descriptive norms took over the significance of injunctive norms, and increased the model's account of total variance in intention to be physically active.
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41

Munday, John, Harsha Ariyarathna, Danielle Aberdein, and Neroli Thomson. "Immunostaining for p53 and p16CDKN2A Protein Is Not Predictive of Prognosis for Dogs with Malignant Mammary Gland Neoplasms." Veterinary Sciences 6, no. 1 (March 25, 2019): 34. http://dx.doi.org/10.3390/vetsci6010034.

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Mammary gland tumors (MGTs) are common in dogs and show a variable clinical behavior that is difficult to predict. Currently, few immunohistochemical markers have been established to predict the prognosis of a canine MGT. However, p53 immunostaining has been variably reported to be prognostic for canine MGTs. Additionally, while p16CDK2NA protein (p16) immunostaining has been found to be prognostic for human breast cancers, this marker has never been evaluated as a prognostic marker for canine neoplasms. In the present study, the prognostic utility of p53 and p16 was evaluated in 35 canine malignant MGTs. It was observed that 19 (54%) dogs died due to their MGTs with an overall mean survival time (MST) of 882 days. Seven MGTs showed p53 immunostaining, but this was not significantly associated with death (4 of 7 vs. 15 of 28; p = 0.6) or MST (670 vs. 934 days; p = 0.57). Five dogs had MGTs with no p16 immunostaining, 28 MGTs had intermediate p16 immunostaining, and two MGTs had increased p16 immunostaining. Neither death due to MGT (4 of 5, 14 of 28, or 1 of 2; p = 0.28) nor MST (683, 927, and 307 days; p = 0.31) were significantly associated with p16 immunostaining. Interestingly, p53 immunostaining was significantly associated with an increase or loss of p16 immunostaining. This is the first time that p16 has been evaluated as a prognostic marker for canine neoplasms. While these results suggest that a proportion of canine MGTs develop by cellular mechanisms that alter both p53 and p16 expression, there was no evidence that defects in p53 or p16 alter the behavior of a MGT. Neither p53 nor p16 was found to significantly predict prognosis, although this could reflect the limited number of MGTs included in the study.
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DOLOGLONYAN, A. V., D. S. STREBKOV, V. T. MATVIIENKO, and I. N. STACENKO. "USE OF VACUUM MICROGAS TURBINE PLANTS FOR HEATPOWER SUPPLY OF LOCAL OBJECTS." Fundamental and Applied Problems of Engineering and Technology 4, no. 1 (2020): 42–48. http://dx.doi.org/10.33979/2073-7408-2020-342-4-1-42-48.

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Consideration subject in article are vacuum cycles of microgas turbine plants (MGTP) for the purpose of studying of their profitability and perspectives of use for heatpower supply of local objects. Vacuum MGTP of a simple cycle and with warmth regeneration is investigated. Optimum parameters of cycles – ratio of turbine expansion and regeneration ratio are found. It is established that profitability of MGTP with regeneration of warmth is higher in comparison with MGTP of a simple cycle almost twice, specific power decreases approximately by 1,35 times. By virtue of profitability and smaller values of compressor pressure ratio increase of the microturbine it is reasonable to apply in MGTP of a vacuum cycle with warmth regeneration.
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43

Anderson, Gregory G., Timothy L. Yahr, Rustin R. Lovewell, and George A. O'Toole. "The Pseudomonas aeruginosa Magnesium Transporter MgtE Inhibits Transcription of the Type III Secretion System." Infection and Immunity 78, no. 3 (December 22, 2009): 1239–49. http://dx.doi.org/10.1128/iai.00865-09.

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ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that causes life-long pneumonia in individuals with cystic fibrosis (CF). These long-term infections are maintained by bacterial biofilm formation in the CF lung. We have recently developed a model of P. aeruginosa biofilm formation on cultured CF airway epithelial cells. Using this model, we discovered that mutation of a putative magnesium transporter gene, called mgtE, led to increased cytotoxicity of P. aeruginosa toward epithelial cells. This altered toxicity appeared to be dependent upon expression of the type III secretion system (T3SS). In this study, we found that mutation of mgtE results in increased T3SS gene transcription. Through epistasis analyses, we discovered that MgtE influences the ExsE-ExsC-ExsD-ExsA gene regulatory system of T3SS by either directly or indirectly inhibiting ExsA activity. While variations in calcium levels modulate T3SS gene expression in P. aeruginosa, we found that addition of exogenous magnesium did not inhibit T3SS activity. Furthermore, mgtE variants that were defective for magnesium transport could still complement the cytotoxicity effect. Thus, the magnesium transport function of MgtE does not fully explain the regulatory effects of MgtE on cytotoxicity. Overall, our results indicate that MgtE modulates expression of T3SS genes.
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44

Pohland, Anne-Christin, and Dirk Schneider. "Mg2+ homeostasis and transport in cyanobacteria – at the crossroads of bacterial and chloroplast Mg2+ import." Biological Chemistry 400, no. 10 (October 25, 2019): 1289–301. http://dx.doi.org/10.1515/hsz-2018-0476.

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AbstractMagnesium cation (Mg2+) is the most abundant divalent cation in living cells, where it is required for various intracellular functions. In chloroplasts and cyanobacteria, established photosynthetic model systems, Mg2+is the central ion in chlorophylls, and Mg2+flux across the thylakoid membrane is required for counterbalancing the light-induced generation of a ΔpH across the thylakoid membrane. Yet, not much is known about Mg2+homoeostasis, transport and distribution within cyanobacteria. However, Mg2+transport across membranes has been studied in non-photosynthetic bacteria, and first observations and findings are reported for chloroplasts. Cyanobacterial cytoplasmic membranes appear to contain the well-characterized Mg2+channels CorA and/or MgtE, which both facilitate transmembrane Mg2+flux down the electrochemical gradient. Both Mg2+channels are typical for non-photosynthetic bacteria. Furthermore, Mg2+transporters of the MgtA/B family are also present in the cytoplasmic membrane to mediate active Mg2+import into the bacterial cell. While the cytoplasmic membrane of cyanobacteria resembles a ‘classical’ bacterial membrane, essentially nothing is known about Mg2+channels and/or transporters in thylakoid membranes of cyanobacteria or chloroplasts. As discussed here, at least one Mg2+channelling protein must be localized within thylakoid membranes. Thus, either one of the ‘typical’ bacterial Mg2+channels has a dual localization in the cytoplasmic plus the thylakoid membrane, or another, yet unidentified channel is present in cyanobacterial thylakoid membranes.
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45

Hood, Graham, Ramakrishnan Karunakaran, J. Allan Downie, and Philip Poole. "MgtE From Rhizobium leguminosarum Is a Mg2+ Channel Essential for Growth at Low pH and N2 Fixation on Specific Plants." Molecular Plant-Microbe Interactions® 28, no. 12 (December 2015): 1281–87. http://dx.doi.org/10.1094/mpmi-07-15-0166-r.

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MgtE is predicted to be a Rhizobium leguminosarum channel and is essential for growth when both Mg2+ is limiting and the pH is low. N2 was only fixed at 8% of the rate of wild type when the crop legume Pisum sativum was inoculated with an mgtE mutant of R. leguminosarum and, although bacteroids were present, they were few in number and not fully developed. R. leguminosarum MgtE was also essential for N2 fixation on the native legume Vicia hirsuta but not when in symbiosis with Vicia faba. The importance of MgtE and the relevance of the contrasting phenotypes is discussed.
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46

Hall, Michael J., Yana Chertock, Elizabeth Handorf, John M. Kaczmar, Julie Innocent, Yu-Ning Wong, and Mary Beryl Daly. "Remote genomic consultation to support uptake of a multi-gene genomic tumor panel (MGTP) by community oncologists (COs): Results of a pilot study." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 1587. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.1587.

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1587 Background: MGTP use in routine cancer (CA) care is likely to increase w/lower costs for NGS-based testing and growing numbers of actionable targets coupled with targeted therapeutics. Early MGPT uptake has been slow among community oncologists (COs) due to their lower confidence to order, interpret, and act upon results of MGTP. This study evaluated the provision of telephone genomic consultation (GC) via an academic clinician link to an institutional genomic tumor board to support MGTP testing of CA patients (PTs) by COs. Methods: 4 practices of COs participated: 9 COs recruited 25 PTs w/metastatic CA. All PTs/COs completed baseline and follow-up (FU) assessments. Tumor blocks were evaluated at Fox Chase Cancer Center (FCCC) and tested w/a 50-gene MGTP. 12% blocks were inadequate. MGTP results were presented when appropriate at FCCC’s Genomic Tumor Board. All MGTP yielded > 1 variant (Var) [range 1-6]: 13/22 (59%) pts tested had a clinically relevant V; 6 other Vars were potentially actionable w/ approved therapy, while 3 Vars have novel therapies in Phase I/II studies. MGTP were called out to COs (by MJH) < 2 wks of resulting. A tailored summary was provided to COs. Results: At baseline, COs (n = 9) had limited experience w/MGTP (78%, < 5 ordered). Barriers for COs were: poor understanding of MGTPs (67%), cost (89%), uncertain benefit (44%), and poor access to targeted therapies (67%). At FU, 4/8 (50%) COs found GC “very useful”, and 63% reported MGPT paired w/GC would “probably/definitely” increase their use of MGTPs. Most (88%) felt MGPTs should be offered to PTs w/incurable CA. Among PTs at baseline (n = 25), awareness of MGTP was moderate (50%), but 79% reported it would help doctors take better care of their PTs. Valuation of MGTP was mixed—30% would pay $0 out of pocket, yet 30% also said they would travel “any distance” for an MGT-targeted experimental therapy. At FU (n = 14), 86% PTs felt MGPT was valuable, yet only 46% would “definitely” retest, and only 31% would pay > $100 to retest, even for 500+ genes. Conclusions: GC can be effective to support COs to use MGTPs. PTs w/CA have high expectations of MGTPs to improve their care, and yet attribute modest value to retest or to have a larger MGTP.
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47

DiPersio, John F., Jonathan Hoggatt, Steven Devine, Lukasz Biernat, Haley Howell, Veit Schmelmer, Jason R. Neale, et al. "Rapid and Robust Mobilization of CD34+ HSCs without G-CSF Following Administration of Mgta-145 Alone or in Combination with Plerixafor." Blood 134, Supplement_1 (November 13, 2019): 1961. http://dx.doi.org/10.1182/blood-2019-127523.

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Background Granulocyte colony-stimulating factor (G-CSF) is the standard of care for mobilization of hematopoietic stem cells (HSCs). G-CSF requires 4-7 days of injections and often multiple aphereses to acquire sufficient CD34+ cells for transplant. The number of CD34+ HSCs mobilized can be variable and patients who fail to mobilize enough CD34+ cells are treated with the combination of G-CSF plus plerixafor. G-CSF use is associated with bone pain, nausea, headaches, fatigue, rare episodes of splenic rupture, and is contraindicated for patients with autoimmune and sickle cell disease. MGTA-145 (GroβT) is a CXCR2 agonist. MGTA-145, in combination with plerixafor, a CXCR4 inhibitor, has the potential to rapidly and reliably mobilize robust numbers of HSCs with a single dose and same-day apheresis for transplant that is free from G-CSF. MGTA-145 plus plerixafor work synergistically to rapidly mobilize HSCs in both mice and non-human primates (Hoggatt, Cell 2018; Goncalves, Blood 2018). Based on these data, Magenta initiated a Phase 1 dose-escalating study to evaluate the safety, PK and PD of MGTA-145 as a single agent and in combination with plerixafor. Methods This study consists of four parts. In Part A, healthy volunteers were dosed with MGTA-145 (0.0075 - 0.3 mg/kg) or placebo. In Part B, MGTA-145 dose levels from Part A were selected for use in combination with a clinically approved dose of plerixafor. In Part C, a single dose MGTA-145 plus plerixafor will be administered on day 1 and day 2. In Part D, MGTA-145 plus plerixafor will be administered followed by apheresis. Results MGTA-145 monotherapy was well tolerated in all subjects dosed (Table 1) with no significant adverse events. Some subjects experienced mild (Grade 1) transient lower back pain that dissipated within minutes. In the ongoing study, the combination of MGTA-145 with plerixafor was well tolerated, with some donors experiencing Grade 1 and 2 gastrointestinal adverse events commonly observed with plerixafor alone. Pharmacokinetic (PK) exposure and maximum plasma concentrations increased dose proportionally and were not affected by plerixafor (Fig 1A). Monotherapy of MGTA-145 resulted in an immediate increase in neutrophils (Fig 1B) and release of plasma MMP-9 (Fig 1C). Neutrophil mobilization plateaued within 1-hour post MGTA-145 at doses greater than 0.03 mg/kg. This plateau was followed by a rebound of neutrophil mobilization which correlated with re-expression of CXCR2 and presence of MGTA-145 at pharmacologically active levels. Markers of neutrophil activation were relatively unchanged (<2-fold vs baseline). A rapid and statistically significant increase in CD34+ cells occurred @ 0.03 and 0.075 mg/kg of MGTA-145 (p < 0.01) relative to placebo with peak mobilization (Fig 1D) 30 minutes post MGTA-145 (7-fold above baseline @ 0.03 mg/kg). To date, the combination of MGTA-145 plus plerixafor mobilized >20/µl CD34s in 92% (11/12) subjects compared to 50% (2/4) subjects receiving plerixafor alone. Preliminary data show that there was a significant increase in fold change relative to baseline in CD34+ cells (27x vs 13x) and phenotypic CD34+CD90+CD45RA- HSCs (38x vs 22x) mobilized by MGTA-145 with plerixafor. Mobilized CD34+ cells were detectable at 15 minutes with peak mobilization shifted 2 - 4 hours earlier for the combination vs plerixafor alone (4 - 6h vs 8 - 12h). Detailed results of single dose administration of MGTA-145 and plerixafor given on one day as well as also on two sequential days will be presented along with fully characterized graft analysis post apheresis from subjects given MGTA-145 and plerixafor. Conclusions MGTA-145 is safe and well tolerated, as a monotherapy and in combination with plerixafor and induced rapid and robust mobilization of significant numbers of HSCs with a single dose in all subjects to date. Kinetics of CD34+ cell mobilization for the combination was immediate (4x increase vs no change for plerixafor alone @ 15 min) suggesting the mechanism of action of MGTA-145 plus plerixafor is different from plerixafor alone. Preliminary data demonstrate that MGTA-145 when combined with plerixafor results in a significant increase in CD34+ fold change relative to plerixafor alone. Magenta Therapeutics intends to develop MGTA-145 as a first line mobilization product for blood cancers, autoimmune and genetic diseases and plans a Phase 2 study in multiple myeloma and non-Hodgkin lymphoma in 2020. Disclosures DiPersio: Magenta Therapeutics: Equity Ownership; NeoImmune Tech: Research Funding; Cellworks Group, Inc.: Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Consultancy; Incyte: Consultancy, Research Funding; RiverVest Venture Partners Arch Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; WUGEN: Equity Ownership, Patents & Royalties, Research Funding; Macrogenics: Research Funding, Speakers Bureau; Bioline Rx: Research Funding, Speakers Bureau; Celgene: Consultancy; Amphivena Therapeutics: Consultancy, Research Funding. Hoggatt:Magenta Therapeutics: Consultancy, Equity Ownership, Research Funding. Devine:Kiadis Pharma: Other: Protocol development (via institution); Bristol Myers: Other: Grant for monitoring support & travel support; Magenta Therapeutics: Other: Travel support for advisory board; My employer (National Marrow Donor Program) has equity interest in Magenta. Biernat:Medpace, Inc.: Employment. Howell:Magenta Therapeutics: Employment, Equity Ownership. Schmelmer:Magenta Therapeutics: Employment, Equity Ownership. Neale:Magenta Therapeutics: Employment, Equity Ownership. Boitano:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Cooke:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Goncalves:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Raffel:Magenta Therapeutics: Employment, Equity Ownership. Falahee:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Morrow:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Davis:Magenta Therapeutics: Employment, Equity Ownership.
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48

Choi, Eunna, Ki-Young Lee, and Dongwoo Shin. "The MgtR regulatory peptide negatively controls expression of the MgtA Mg2+ transporter in Salmonella enterica serovar Typhimurium." Biochemical and Biophysical Research Communications 417, no. 1 (January 2012): 318–23. http://dx.doi.org/10.1016/j.bbrc.2011.11.107.

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49

Smith, R. L., M. T. Kaczmarek, L. M. Kucharski, and M. E. Maguire. "Magnesium transport in Salmonella typhimurium: regulation of mgtA and mgtCB during invasion of epithelial and macrophage cells." Microbiology 144, no. 7 (July 1, 1998): 1835–43. http://dx.doi.org/10.1099/00221287-144-7-1835.

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50

Lavigne, Jean-Philippe, David O'Callaghan, and Anne-Béatrice Blanc-Potard. "Requirement of MgtC for Brucella suis Intramacrophage Growth: a Potential Mechanism Shared by Salmonella enterica and Mycobacterium tuberculosis for Adaptation to a Low-Mg2+ Environment." Infection and Immunity 73, no. 5 (May 2005): 3160–63. http://dx.doi.org/10.1128/iai.73.5.3160-3163.2005.

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ABSTRACT A Brucella suis mgtC mutant is defective for growth within macrophages and in low-Mg2+ medium. These phenotypes are strikingly similar to those observed with mgtC mutants from Salmonella enterica and Mycobacterium tuberculosis, two other pathogens that proliferate within phagosomes. MgtC appears as a remarkable virulence factor that would have been acquired by distantly related intracellular pathogens to contribute to the adaptation to a low-Mg2+ environment in the phagosome.
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