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1

Cs�k�ny, B. "Magari via Malcev." Algebra Universalis 36, no. 3 (September 1996): 421–22. http://dx.doi.org/10.1007/bf01236767.

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2

Heller, Tamar. "Sex in Mind: The Gendered Brain in Nineteenth-Century Literature and Mental Sciences, by Rachel Malane." Victorian Studies 49, no. 4 (July 2007): 687–89. http://dx.doi.org/10.2979/vic.2007.49.4.687.

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3

Ribot, Wilson J., and Ricky L. Ulrich. "The Animal Pathogen-Like Type III Secretion System Is Required for the Intracellular Survival of Burkholderia mallei within J774.2 Macrophages." Infection and Immunity 74, no. 7 (July 2006): 4349–53. http://dx.doi.org/10.1128/iai.01939-05.

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ABSTRACT Burkholderia mallei is a highly infectious gram-negative pathogen and is the causative agent of human and animal glanders. By generating polar mutations (disruption of bsaQ and bsaZ) in the B. mallei ATCC 23344 animal pathogen-like type III secretion system (TTS), we demonstrate that this bacterial protein delivery system is required for intracellular growth of B. mallei in J774.2 cells, formation of macrophage membrane protrusions, actin polymerization, and phagosomal escape. These findings suggest that TTS plays a role in the intracellular trafficking of B. mallei and may facilitate cell-to-cell spread via actin-based motility.
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4

Zimmerman, Shawn M., Mackenzie E. Long, Jeremy S. Dyke, Tomislav P. Jelesijevic, Frank Michel, Eric R. Lafontaine, and Robert J. Hogan. "Use of Immunohistochemistry to Demonstrate In Vivo Expression of the Burkholderia mallei Virulence Factor BpaB During Experimental Glanders." Veterinary Pathology 55, no. 2 (November 16, 2017): 258–67. http://dx.doi.org/10.1177/0300985817736113.

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Burkholderia mallei causes the highly contagious and debilitating zoonosis glanders, which infects via inhalation or percutaneous inoculation and often culminates in life-threatening pneumonia and sepsis. In humans, glanders is difficult to diagnose and requires prolonged antibiotic therapy with low success rates. No vaccine exists to protect against B. mallei, and there is concern regarding its use as a bioweapon. The authors previously identified the protein BpaB as a potential target for devising therapies due to its role in adherence to host cells and the formation of biofilms in vitro and its contribution to pathogenicity in a mouse model of glanders. In the present study, the authors developed an immunostaining approach to probe tissues of experimentally infected animals and demonstrated that BpaB is produced exclusively in vivo by wild-type B. mallei in target organs from mice and marmosets. They detected the expression of BpaB by B. mallei both extracellularly and within macrophages, neutrophils, and epithelial cells in respiratory tissues (7/10 marmoset; 2/2 mouse). The authors also noted the intracellular expression of BpaB by B. mallei in macrophages in the regional lymph nodes of mice (2/2 tissues) and MALT of marmosets (4/5 tissues). It is interesting that B. mallei bacteria infecting distal organs did not express BpaB (2/2 mice; 3/3 marmosets), suggesting that the protein is not necessary for bacterial fitness in these anatomic locations. These findings underscore the value of BpaB as a target for developing medical countermeasures and provide insight into its role in pathogenesis.
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Schell, Mark A., Lyla Lipscomb, and David DeShazer. "Comparative Genomics and an Insect Model Rapidly Identify Novel Virulence Genes of Burkholderia mallei." Journal of Bacteriology 190, no. 7 (January 25, 2008): 2306–13. http://dx.doi.org/10.1128/jb.01735-07.

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ABSTRACT Burkholderia pseudomallei and its host-adapted deletion clone Burkholderia mallei cause the potentially fatal human diseases melioidosis and glanders, respectively. The antibiotic resistance profile and ability to infect via aerosol of these organisms and the absence of protective vaccines have led to their classification as major biothreats and select agents. Although documented infections by these bacteria date back over 100 years, relatively little is known about their virulence and pathogenicity mechanisms. We used in silico genomic subtraction to generate their virulome, a set of 650 putative virulence-related genes shared by B. pseudomallei and B. mallei but not present in five closely related nonpathogenic Burkholderia species. Although most of these genes are clustered in putative operons, the number of targets for mutant construction and verification of reduced virulence in animal models is formidable. Therefore, Galleria mellonella (wax moth) larvae were evaluated as a surrogate host; we found that B. pseudomallei and B. mallei, but not other phylogenetically related bacteria, were highly pathogenic for this insect. More importantly, four previously characterized B. mallei mutants with reduced virulence in hamsters or mice had similarly reduced virulence in G. mellonella larvae. Site-specific inactivation of selected genes in the computationally derived virulome identified three new potential virulence genes, each of which was required for rapid and efficient killing of larvae. Thus, this approach may provide a means to quickly identify high-probability virulence genes in B. pseudomallei, B. mallei, and other pathogens.
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6

Narmatha S, Janani K,. "MALLET-Privacy Preserving Influencer Mining in Social Media Networks via Hypergraph." International Journal of Innovative Research in Computer and Communication Engineering 03, no. 02 (February 28, 2015): 767–71. http://dx.doi.org/10.15680/ijircce.2015.0302025.

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7

Landete, José María, Sergi Ferrer, Vicente Monedero, and Manuel Zúñiga. "Malic Enzyme and Malolactic Enzyme Pathways Are Functionally Linked but Independently Regulated in Lactobacillus casei BL23." Applied and Environmental Microbiology 79, no. 18 (July 8, 2013): 5509–18. http://dx.doi.org/10.1128/aem.01177-13.

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ABSTRACTLactobacillus caseiis the only lactic acid bacterium in which two pathways forl-malate degradation have been described: the malolactic enzyme (MLE) and the malic enzyme (ME) pathways. Whereas the ME pathway enablesL. caseito grow onl-malate, MLE does not support growth. Themlegene cluster consists of three genes encoding MLE (mleS), the putativel-malate transporter MleT, and the putative regulator MleR. Themaegene cluster consists of four genes encoding ME (maeE), the putative transporter MaeP, and the two-component system MaeKR. Since both pathways compete for the same substrate, we sought to determine whether they are coordinately regulated and their role inl-malate utilization as a carbon source. Transcriptional analyses revealed that themleandmaegenes are independently regulated and showed that MleR acts as an activator and requires internalization ofl-malate to induce the expression ofmlegenes. Notwithstanding, bothl-malate transporters were required for maximall-malate uptake, although only anmleTmutation caused a growth defect onl-malate, indicating its crucial role inl-malate metabolism. However, inactivation of MLE resulted in higher growth rates and higher final optical densities onl-malate. The limited growth onl-malate of the wild-type strain was correlated to a rapid degradation of the availablel-malate tol-lactate, which cannot be further metabolized. Taken together, our results indicate thatL. caseil-malate metabolism is not optimized for utilization ofl-malate as a carbon source but for deacidification of the medium by conversion ofl-malate intol-lactate via MLE.
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8

Avasthi, Prachee. "Can microtubule motors use every available track?" Journal of Cell Biology 217, no. 12 (November 7, 2018): 4055–56. http://dx.doi.org/10.1083/jcb.201810083.

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Flagellar assembly and function depend on cargo traveling via motors on microtubule doublets. Bertiaux, Mallet et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201805030) find that only a subset of available doublets are used for this transport in trypanosomes, leading to questions about how and why this is achieved.
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9

Doyle, Ruben, Richard J. van Arkel, Sarah Muirhead-Allwood, and Jonathan R. T. Jeffers. "Impaction technique influences implant stability in low-density bone model." Bone & Joint Research 9, no. 7 (July 2020): 386–93. http://dx.doi.org/10.1302/2046-3758.97.bjr-2019-0303.r1.

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Aims Cementless acetabular components rely on press-fit fixation for initial stability. In certain cases, initial stability is more difficult to obtain (such as during revision). No current study evaluates how a surgeon’s impaction technique (mallet mass, mallet velocity, and number of strikes) may affect component fixation. This study seeks to answer the following research questions: 1) how does impaction technique affect a) bone strain generation and deterioration (and hence implant stability) and b) seating in different density bones?; and 2) can an impaction technique be recommended to minimize risk of implant loosening while ensuring seating of the acetabular component? Methods A custom drop tower was used to simulate surgical strikes seating acetabular components into synthetic bone. Strike velocity and drop mass were varied. Synthetic bone strain was measured using strain gauges and stability was assessed via push-out tests. Polar gap was measured using optical trackers. Results A phenomenon of strain deterioration was identified if an excessive number of strikes was used to seat a component. This effect was most pronounced in low-density bone at high strike velocities. Polar gap was reduced with increasing strike mass and velocity. Conclusion A high mallet mass with low strike velocity resulted in satisfactory implant stability and polar gap, while minimizing the risk of losing stability due to over-striking. Extreme caution not to over-strike must be exercised when using high velocity strikes in low-density bone for any mallet mass. Cite this article: Bone Joint Res 2020;9(7):386–393.
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10

Burtnick, Mary N., David DeShazer, Vinod Nair, Frank C. Gherardini, and Paul J. Brett. "Burkholderia mallei Cluster 1 Type VI Secretion Mutants Exhibit Growth and Actin Polymerization Defects in RAW 264.7 Murine Macrophages." Infection and Immunity 78, no. 1 (November 2, 2009): 88–99. http://dx.doi.org/10.1128/iai.00985-09.

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ABSTRACT Burkholderia mallei is a facultative intracellular pathogen that causes severe disease in animals and humans. Recent studies have shown that the cluster 1 type VI secretion system (T6SS-1) expressed by this organism is essential for survival in a hamster model of glanders. To better understand the role of T6SS-1 in the pathogenesis of disease, studies were initiated to examine the interactions of B. mallei tssE mutants with RAW 264.7 murine macrophages. Results obtained by utilizing modified gentamicin protection assays indicated that although the tssE mutants were able to survive within RAW 264.7 cells, significant growth defects were observed in comparison to controls. In addition, analysis of infected monolayers by differential interference contrast and fluorescence microscopy demonstrated that the tssE mutants lacked the ability to induce multinucleated giant cell formation. Via the use of fluorescence microscopy, tssE mutants were shown to undergo escape from lysosome-associated membrane protein 1-positive vacuoles. Curiously, however, following entry into the cytosol, the mutants exhibited actin polymerization defects resulting in inefficient intra- and intercellular spread characteristics. Importantly, all mutant phenotypes observed in this study could be restored by complementation. Based upon these findings, it appears that T6SS-1 plays a critical role in growth and actin-based motility following uptake of B. mallei by RAW 264.7 cells.
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11

Yu, JW, and KC Woo. "Ammonia Assimilation and Metabolite Transport in Isolated Chloroplasts. II. Malate Stimulates Ammonia Assimilation in Chloroplasts Isolated From Leaves of Dicotyledonous but Not Monocotyledonous Species." Functional Plant Biology 19, no. 6 (1992): 659. http://dx.doi.org/10.1071/pp9920659.

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Malate stimulated NH3 assimilation, as determined by a (2-oxoglutarate, NH3)-dependent O2 evolution system, by up to 3-fold in chloroplasts isolated from leaves of dicot but not monocot species. This difference was apparently correlated with the endogenous metabolite pools present in these chloroplast preparations. During NH3 assimilation the glutamate and glutamine pools were large in spinach (dicot) but small in oat chloroplasts. The reverse was the case for the 2-oxoglutarate (2-OG) pool. The addition of malate substantially increased the glutamate, glutamine and 2-OG pools in spinach chloroplasts but had little effect in oat chloroplasts. This suggests that the supply of 2-OG was apparently limiting NH3 assimilation in spinach chloroplasts. Malate increased this supply and, consequently, stimulated NH3 assimilation. On the other hand, NH3 assimilation in oat chloroplasts seemed to be limited by the supply of glutamate and glutamine which could not be overcome by the addition of malate. Chloroplasts were also isolated from oat seedlings watered with high nutrient solution. The rates of NH3 assimilation in these organelles exceeded those obtained in spinach chloroplasts. But the addition of malate had little effect on (2-OG, NH3)-dependent O2 evolution in these oat chloroplasts. Since malate did not inhibit this activity it is conceivable that it still might play a role, albeit a 'passive' role, in serving as a counter-ion for 2-OG uptake via the 2-OG translocator and glutamate export via the Dct translocator during NH3 assimilation.
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12

Wright, Ian J., and Pauline Y. Ladiges. "Geographic Variation in Eucalyptus diversifolia (Myrtaceae) and the Recognition of New Subspecies E. diversifolia subsp. hesperia and E. diversifolia subsp. megacarpa." Australian Systematic Botany 10, no. 5 (1997): 651. http://dx.doi.org/10.1071/sb96019.

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Patterns of geographic variation in morphological and chemical characters are documented in Eucalyptus diversifolia Bonpl. (soap mallee, white coastal mallee). This species is found in coastal and subcoastal Australia from southern Western Australia to Cape Nelson (western Victoria), with a number of disjunctions in the intervening region. Morphological data from adult plants collected at field localities and seedlings grown under uniform conditions were analysed using univariate and multivariate methods, including oneway ANOVA, multiple comparison tests, non-metric multidimensional scaling (NMDS), nearest neighbour networks, and minimum spanning trees. Seedling material was tested for isozyme polymorphism, and adult leaf flavonoids were analysed using liquid chromatography. Morphological and chemical characters are also documented in E. aff. diversifolia, a closely related but unnamed taxon restricted to ironstone outcrops near Norseman (WA), and putative E. diversifolia- E. baxteri hybrids from Cape Nelson. Congruent patterns in data sets distinguish three groups of E. diversifolia adults and progeny: (1) those to the west of the Nullarbor disjunction; (2) South Australian populations to the east of this disjunction; and (3) those from Cape Nelson. Formal taxonomic recognition of the three forms at subspecific level is established, namely E. diversifolia subsp. diversifolia, E. diversifolia subsp. hesperia, and E. diversifolia subsp. megacarpa. Patterns of geographic affinity between populations are consistent with a hypothesis of genetic exchange between normally disjunct regional populations of E. diversifolia via coastal land-bridges exposed during periodic times of low sea level since the mid Tertiary.
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13

Zelle, Rintze M., Erik de Hulster, Wouter A. van Winden, Pieter de Waard, Cor Dijkema, Aaron A. Winkler, Jan-Maarten A. Geertman, Johannes P. van Dijken, Jack T. Pronk, and Antonius J. A. van Maris. "Malic Acid Production by Saccharomyces cerevisiae: Engineering of Pyruvate Carboxylation, Oxaloacetate Reduction, and Malate Export." Applied and Environmental Microbiology 74, no. 9 (March 14, 2008): 2766–77. http://dx.doi.org/10.1128/aem.02591-07.

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ABSTRACT Malic acid is a potential biomass-derivable “building block” for chemical synthesis. Since wild-type Saccharomyces cerevisiae strains produce only low levels of malate, metabolic engineering is required to achieve efficient malate production with this yeast. A promising pathway for malate production from glucose proceeds via carboxylation of pyruvate, followed by reduction of oxaloacetate to malate. This redox- and ATP-neutral, CO2-fixing pathway has a theoretical maximum yield of 2 mol malate (mol glucose)−1. A previously engineered glucose-tolerant, C2-independent pyruvate decarboxylase-negative S. cerevisiae strain was used as the platform to evaluate the impact of individual and combined introduction of three genetic modifications: (i) overexpression of the native pyruvate carboxylase encoded by PYC2, (ii) high-level expression of an allele of the MDH3 gene, of which the encoded malate dehydrogenase was retargeted to the cytosol by deletion of the C-terminal peroxisomal targeting sequence, and (iii) functional expression of the Schizosaccharomyces pombe malate transporter gene SpMAE1. While single or double modifications improved malate production, the highest malate yields and titers were obtained with the simultaneous introduction of all three modifications. In glucose-grown batch cultures, the resulting engineered strain produced malate at titers of up to 59 g liter−1 at a malate yield of 0.42 mol (mol glucose)−1. Metabolic flux analysis showed that metabolite labeling patterns observed upon nuclear magnetic resonance analyses of cultures grown on 13C-labeled glucose were consistent with the envisaged nonoxidative, fermentative pathway for malate production. The engineered strains still produced substantial amounts of pyruvate, indicating that the pathway efficiency can be further improved.
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Muthu, Magesh, Ranjeet Kumar, Azharuddin Sajid Syed Khaja, Jonathan D. Gilthorpe, Jenny L. Persson, and Anders Nordström. "GLUL Ablation Can Confer Drug Resistance to Cancer Cells via a Malate-Aspartate Shuttle-Mediated Mechanism." Cancers 11, no. 12 (December 5, 2019): 1945. http://dx.doi.org/10.3390/cancers11121945.

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Glutamate-ammonia ligase (GLUL) is important for acid-base homeostasis, ammonia detoxification, cell signaling, and proliferation. Here, we reported that GLUL ablation conferred resistance to several anticancer drugs in specific cancer cell lines while leaving other cell lines non-resistant to the same drugs. To understand the biochemical mechanics supporting this drug resistance, we compared drug-resistant GLUL knockout (KO) A549 non-small-cell lung carcinoma (NSCLC) cells with non-resistant GLUL KO H1299 NSCLC cells and found that the resistant A549 cells, to a larger extent, depended on exogenous glucose for proliferation. As GLUL activity is linked to the tricarboxylic acid (TCA) cycle via reversed glutaminolysis, we probed carbon flux through both glycolysis and TCA pathways by means of 13C5 glutamine, 13C5 glutamate, and 13C6 glucose tracing. We observed increased labeling of malate and aspartate in A549 GLUL KO cells, whereas the non-resistant GLUL KO H1299 cells displayed decreased 13C-labeling. The malate and aspartate shuttle supported cellular NADH production and was associated with cellular metabolic fitness. Inhibition of the malate-aspartate shuttle with aminooxyacetic acid significantly impacted upon cell viability with an IC50 of 11.5 μM in resistant GLUL KO A549 cells compared to 28 μM in control A549 cells, linking resistance to the malate-aspartate shuttle. Additionally, rescuing GLUL expression in A549 KO cells increased drug sensitivity. We proposed a novel metabolic mechanism in cancer drug resistance where the increased capacity of the malate-aspartate shuttle increased metabolic fitness, thereby facilitating cancer cells to escape drug pressure.
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Taillefer, M., T. Rydzak, D. B. Levin, I. J. Oresnik, and R. Sparling. "Reassessment of the Transhydrogenase/Malate Shunt Pathway in Clostridium thermocellum ATCC 27405 through Kinetic Characterization of Malic Enzyme and Malate Dehydrogenase." Applied and Environmental Microbiology 81, no. 7 (January 23, 2015): 2423–32. http://dx.doi.org/10.1128/aem.03360-14.

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ABSTRACTClostridium thermocellumproduces ethanol as one of its major end products from direct fermentation of cellulosic biomass. Therefore, it is viewed as an attractive model for the production of biofuels via consolidated bioprocessing. However, a better understanding of the metabolic pathways, along with their putative regulation, could lead to improved strategies for increasing the production of ethanol. In the absence of an annotated pyruvate kinase in the genome, alternate means of generating pyruvate have been sought. Previous proteomic and transcriptomic work detected high levels of a malate dehydrogenase and malic enzyme, which may be used as part of a malate shunt for the generation of pyruvate from phosphoenolpyruvate. The purification and characterization of the malate dehydrogenase and malic enzyme are described in order to elucidate their putative roles in malate shunt and their potential role inC. thermocellummetabolism. The malate dehydrogenase catalyzed the reduction of oxaloacetate to malate utilizing NADH or NADPH with akcatof 45.8 s−1or 14.9 s−1, respectively, resulting in a 12-fold increase in catalytic efficiency when using NADH over NADPH. The malic enzyme displayed reversible malate decarboxylation activity with akcatof 520.8 s−1. The malic enzyme used NADP+as a cofactor along with NH4+and Mn2+as activators. Pyrophosphate was found to be a potent inhibitor of malic enzyme activity, with aKiof 0.036 mM. We propose a putative regulatory mechanism of the malate shunt by pyrophosphate and NH4+based on the characterization of the malate dehydrogenase and malic enzyme.
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16

Waters, James K., Thomas P. Mawhinney, and David W. Emerich. "Nitrogen Assimilation and Transport by Ex Planta Nitrogen-Fixing Bradyrhizobium diazoefficiens Bacteroids Is Modulated by Oxygen, Bacteroid Density and l-Malate." International Journal of Molecular Sciences 21, no. 20 (October 13, 2020): 7542. http://dx.doi.org/10.3390/ijms21207542.

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Symbiotic nitrogen fixation requires the transfer of fixed organic nitrogen compounds from the symbiotic bacteria to a host plant, yet the chemical nature of the compounds is in question. Bradyrhizobium diazoefficiens bacteroids were isolated anaerobically from soybean nodules and assayed at varying densities, varying partial pressures of oxygen, and varying levels of l-malate. Ammonium was released at low bacteroid densities and high partial pressures of oxygen, but was apparently taken up at high bacteroid densities and low partial pressures of oxygen in the presence of l-malate; these later conditions were optimal for amino acid excretion. The ratio of partial pressure of oxygen/bacteroid density of apparent ammonium uptake and of alanine excretion displayed an inverse relationship. Ammonium uptake, alanine and branch chain amino acid release were all dependent on the concentration of l-malate displaying similar K0.5 values of 0.5 mM demonstrating concerted regulation. The hyperbolic kinetics of ammonium uptake and amino acid excretion suggests transport via a membrane carrier and also suggested that transport was rate limiting. Glutamate uptake displayed exponential kinetics implying transport via a channel. The chemical nature of the compounds released were dependent upon bacteroid density, partial pressure of oxygen and concentration of l-malate demonstrating an integrated metabolism.
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17

Heart, Emma, Gary W. Cline, Leon P. Collis, Rebecca L. Pongratz, Joshua P. Gray, and Peter J. S. Smith. "Role for malic enzyme, pyruvate carboxylation, and mitochondrial malate import in glucose-stimulated insulin secretion." American Journal of Physiology-Endocrinology and Metabolism 296, no. 6 (June 2009): E1354—E1362. http://dx.doi.org/10.1152/ajpendo.90836.2008.

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Pyruvate cycling has been implicated in glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. The operation of some pyruvate cycling pathways is proposed to necessitate malate export from the mitochondria and NADP+-dependent decarboxylation of malate to pyruvate by cytosolic malic enzyme (ME1). Evidence in favor of and against a role of ME1 in GSIS has been presented by others using small interfering RNA-mediated suppression of ME1. ME1 was also proposed to account for methyl succinate-stimulated insulin secretion (MSSIS), which has been hypothesized to occur via succinate entry into the mitochondria in exchange for malate and subsequent malate conversion to pyruvate. In contrast to rat, mouse β-cells lack ME1 activity, which was suggested to explain their lack of MSSIS. However, this hypothesis was not tested. In this report, we demonstrate that although adenoviral-mediated overexpression of ME1 greatly augments GSIS in rat insulinoma INS-1 832/13 cells, it does not restore MSSIS, nor does it significantly affect GSIS in mouse islets. The increase in GSIS following ME1 overexpression in INS-1 832/13 cells did not alter the ATP-to-ADP ratio but was accompanied by increases in malate and citrate levels. Increased malate and citrate levels were also observed after INS-1 832/13 cells were treated with the malate-permeable analog dimethyl malate. These data suggest that although ME1 overexpression augments anaplerosis and GSIS in INS-1 832/13 cells, it is not likely involved in MSSIS and GSIS in pancreatic islets.
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Paluscio, Elyse, and Michael G. Caparon. "Streptococcus pyogenes Malate Degradation Pathway Links pH Regulation and Virulence." Infection and Immunity 83, no. 3 (January 12, 2015): 1162–71. http://dx.doi.org/10.1128/iai.02814-14.

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The ability ofStreptococcus pyogenesto infect different niches within its human host most likely relies on its ability to utilize alternative carbon sources. In examining this question, we discovered that all sequencedS. pyogenesstrains possess the genes for the malic enzyme (ME) pathway, which allows malate to be used as a supplemental carbon source for growth. ME is comprised of four genes in two adjacent operons, with the regulatory two-component MaeKR required for expression of genes encoding a malate permease (maeP) and malic enzyme (maeE). Analysis of transcription indicated that expression ofmaePandmaeEis induced by both malate and low pH, and induction in response to both cues is dependent on the MaeK sensor kinase. Furthermore, bothmaePEandmaeKRare repressed by glucose, which occurs via a CcpA-independent mechanism. Additionally, malate utilization requires the PTS transporter EI enzyme (PtsI), as a PtsI–mutant fails to express the ME genes and is unable to utilize malate. Virulence of selected ME mutants was assessed in a murine model of soft tissue infection. MaeP–, MaeK–, and MaeR–mutants were attenuated for virulence, whereas a MaeE–mutant showed enhanced virulence compared to that of the wild type. Taken together, these data show that ME contributes toS. pyogenes' carbon source repertory, that malate utilization is a highly regulated process, and that a single regulator controls ME expression in response to diverse signals. Furthermore, malate uptake and utilization contribute to the adaptive pH response, and ME can influence the outcome of infection.
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Russell, R. R., and H. Taegtmeyer. "Pyruvate carboxylation prevents the decline in contractile function of rat hearts oxidizing acetoacetate." American Journal of Physiology-Heart and Circulatory Physiology 261, no. 6 (December 1, 1991): H1756—H1762. http://dx.doi.org/10.1152/ajpheart.1991.261.6.h1756.

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Acetoacetate, when present as the only fuel for respiration in rat hearts, causes an impairment in contractile function that is reversible with the addition of substrates that can contribute to anaplerosis. To determine the importance of pyruvate carboxylation via NADP(+)-dependent malic enzyme on metabolism and function in hearts oxidizing acetoacetate, isolated working rat hearts were perfused with [1-14C]pyruvate and acetoacetate. While the cardiac power output after 60 min of perfusion in hearts utilizing acetoacetate alone had fallen to 44% of the initial value, the addition of pyruvate resulted in a stable performance with no fall in the work output. When hydroxymalonate, an inhibitor of NADP(+)-dependent malic enzyme and malate dehydrogenase, was added to the two substrates, function at 60 min was similar to the value for hearts oxidizing acetoacetate alone. Measurements of the specific activities of malate, aspartate, and citrate confirm inhibition of both pyruvate carboxylation and malate oxidation. The findings are consistent with a mechanism in which the enrichment of malate by pyruvate improves function by increasing the production of reducing equivalents by the malate dehydrogenase and the isocitrate dehydrogenase reactions increase flux through the span of the tricarboxylic acid cycle from malate to 2-oxoglutarate. The present study demonstrates the physiological importance of anaplerotic pathways in maintaining contractile function in the heart.
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Yu, JW, and KC Woo. "Ammonia Assimilation and Metabolite Transport in Isolated Chloroplasts. I. Kinetic Measurement of 2-Oxoglutarate and Malate Uptake Via the 2-Oxoglutarate Translocator in Oat and Spinach Chloroplasts." Functional Plant Biology 19, no. 6 (1992): 653. http://dx.doi.org/10.1071/pp9920653.

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The stable double-layer silicone centrifugation system was used to determine the kinetic properties of the 2-oxoglutarate (2-OG) translocator in isolated oat and spinach chloroplasts. The uptake of [14C]2-OG and [14C]malate via the 2-OG translocator were measured in the presence of 20 mM glutamate in chloroplasts preloaded with unlabelled 2-OG. The characteristics of the general dicarboxylate (Dct) translocator were also determined using chloroplasts preloaded with glutamate. The Vmax values obtained for transport activity via the 2-OG translocator in oat and spinach chloroplasts exceeded 150 μmol mg-1 Chl h-1 and for the Dct translocator less than 100 μmol mg-1 Chl h-1. The K� (malate) values of the 2-OG and Dct translocators also showed large differences in the two species. In spinach chloroplasts they were 2.7 and 0.6 mM for the 2-OG and Dct translocators respectively whereas, in oat chloroplasts the corresponding values were 2.7 and 1.4 mM. This suggests that, in spinach, malate would be transported into the chloroplasts preferentially via the Dct translocator, thus providing a kinetic basis for the 'push and pull' mechanism proposed for dicarboxylate transport during photorespiratory NH3 recycling in the 2-translocator model.
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21

Patron, L., O. Carp, I. Mindru, Gabriela Marinescu, L. Diamandescu, and Armin Reller. "Synthesis of Y3Fe5O12 via Thermal Decomposition of Polynuclear Coordination Compounds." Materials Science Forum 587-588 (June 2008): 278–82. http://dx.doi.org/10.4028/www.scientific.net/msf.587-588.278.

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The possibility of obtaining yttrium iron garnet (Y3Fe5O12, YIG) through thermal decomposition of two coordination compounds with malate and gluconate anions as ligands, (NH4)6[Y3Fe5(C4O5H4)6(C4O5H3)6]·12H2O and (NH4)6[Y3Fe5(C6O7H10)6(C6O7H9)6]·8H2O. A mixture of simple oxides, namely Y2O3 and α-Fe2O3, orthorhombic ferrite YFeO3 and small amounts Y3Fe5O12, is generated from the thermolysis of malate compound, while a clean Y3Fe5O12 is obtained from gluconate compound.
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Dry, IB, and JT Wiskich. "Characteristics of Glycine and Malate Oxidation by Pea Leaf Mitochondria: Evidence of Differential Access to NAD and Respiratory Chains." Functional Plant Biology 12, no. 4 (1985): 329. http://dx.doi.org/10.1071/pp9850329.

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The addition of glycine to pea leaf mitochondria oxidizing malate in either state 3 or state 4 led to a marked increase in the rate of O2 uptake. Malate was also found to stimulate the state 3 and state 4 rates of O2 uptake with glycine. The increases in state 4 rates were not due to increases in the rate of O2 uptake via the alternative pathway, as the state 4 rate in the presence of malate or glycine, or both, was not limited by the rate of electron flow between ubiquinone and O2. The rotenone-insensitive state 3 rates of O2 uptake in the presence of malate or glycine, in freshly isolated mitochondria, could be stimulated by the addition of NAD. However, these NAD-limited, rotenone-insensitive, rates could also be stimulated by the addition of a second NAD-linked substrate. Mitochondria could be further depleted of NAD such that the rotenone-insensitive state 3 rate of glycine oxidation was stimulated threefold by added NAD. Even in these NAD-depleted mitochondria, the rate of O2 uptake in the presence of glycine was found to be markedly stimulated by malate, indicating that the malate-oxidizing enzymes had access to NAD, within these mitochondria, which was unavailable to glycine decarboxylase. These results are not consistent with a uniform distribution of enzymes within mitochondria with access to a common pool of NAD, and suggest that glycine decarboxylase and the malate-oxidizing enzymes may have differential access, both in terms of size and location, to NAD within pea leaf mitochondria.
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Kim, Eun Young, Baek Soo Han, Won Kon Kim, Sang Chul Lee, and Kwang-Hee Bae. "Acceleration of adipogenic differentiation via acetylation of malate dehydrogenase 2." Biochemical and Biophysical Research Communications 441, no. 1 (November 2013): 77–82. http://dx.doi.org/10.1016/j.bbrc.2013.10.016.

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Irfan, Muhammad, Saifullah Khan, Alaa R. Hameed, Alhanouf I. Al-Harbi, Syed Ainul Abideen, Saba Ismail, Asad Ullah, Sumra Wajid Abbasi, and Sajjad Ahmad. "Computational Based Designing of a Multi-Epitopes Vaccine against Burkholderia mallei." Vaccines 10, no. 10 (September 21, 2022): 1580. http://dx.doi.org/10.3390/vaccines10101580.

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The emergence of antibiotic resistance in bacterial species is a major threat to public health and has resulted in high mortality as well as high health care costs. Burkholderia mallei is one of the etiological agents of health care-associated infections. As no licensed vaccine is available against the pathogen herein, using reverse vaccinology, bioinformatics, and immunoinformatics approaches, a multi-epitope-based vaccine against B. mallei was designed. In completely sequenced proteomes of B. mallei, 18,405 core, 3671 non-redundant, and 14,734 redundant proteins were predicted. Among the 3671 non-redundant proteins, 3 proteins were predicted in the extracellular matrix, 11 were predicted as outer membrane proteins, and 11 proteins were predicted in the periplasmic membrane. Only two proteins, type VI secretion system tube protein (Hcp) and type IV pilus secretin proteins, were selected for epitope prediction. Six epitopes, EAMPERMPAA, RSSPPAAGA, DNRPISINL, RQRFDAHAR, AERERQRFDA, and HARAAQLEPL, were shortlisted for multi-epitopes vaccine design. The predicted epitopes were linked to each other via a specific GPGPG linker and the epitopes peptide was then linked to an adjuvant molecule through an EAAAK linker to make the designed vaccine more immunologically potent. The designed vaccine was also found to have favorable physicochemical properties with a low molecular weight and fewer transmembrane helices. Molecular docking studies revealed vaccine construct stable binding with MHC-I, MHC-II, and TLR-4 with energy scores of −944.1 kcal/mol, −975.5 kcal/mol, and −1067.3 kcal/mol, respectively. Molecular dynamic simulation assay noticed stable dynamics of the docked vaccine-receptors complexes and no drastic changes were observed. Binding free energies estimation revealed a net value of −283.74 kcal/mol for the vaccine-MHC-I complex, −296.88 kcal/mol for the vaccine-MHC-II complex, and −586.38 kcal/mol for the vaccine-TLR-4 complex. These findings validate that the designed vaccine construct showed promising ability in terms of binding to immune receptors and may be capable of eliciting strong immune responses once administered to the host. Further evidence from experimentations in mice models is required to validate real immune protection of the designed vaccine construct against B. mallei.
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Cronholm, T. "Incorporation of the 1-pro-R and 1-pro-S hydrogen atoms of ethanol in the reduction of acids in the liver of intact rats and in isolated hepatocytes." Biochemical Journal 229, no. 2 (July 15, 1985): 323–31. http://dx.doi.org/10.1042/bj2290323.

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Ethanol oxidation causes redox effects. The coupling of this oxidation via NADH to intermediary metabolism was studied in order to reveal the underlying mechanisms. Isolated rat hepatocytes were incubated with [1,1-2H2]-, (1R)-[1-2H]- and (1S)-[1-2H]-ethanol and the 2H incorporation was measured in lactate, beta-hydroxybutyrate, fumarate, malate, succinate, alpha-oxoglutarate and citrate. The results differed in the following ways from results obtained in intact rats. Lactate became labelled to an increasing extent, and in more than one position, indicating labelling of pyruvate. A small and constant fraction of malate and fumarate was formed without access to [2H]coenzyme. Addition of aspartate increased this fraction, which was concluded to be formed in the mitochondria. Citrate was essentially unlabelled. The 2H from (1R)-[1-2H]ethanol contributed to malate to a larger extent and to beta-hydroxybutyrate to a smaller extent, and 2H from (1S)-[1-2H]ethanol contributed to lactate to a smaller extent. These results indicate that the exchange via shuttle system was less efficient in isolated hepatocytes than in intact rats. The 2H incorporation was independent of concentration of [1,1-2H2]ethanol when this was above 5mM. Additions known to increase ethanol elimination, and cyanamide, which decreases it, had no marked effect on the 2H incorporation. This indicates equilibration of the NADH bound to alcohol dehydrogenase with free NADH. Disulfiram and cyanamide caused a decrease in the relative incorporation from (1S)-[1-2H]ethanol into malate in liver of intact rats. Addition of cyanamide to incubations with hepatocytes resulted in a decrease of the contribution of 2H from (1S)-[1-2H]ethanol in lactate, beta-hydroxybutyrate and malate. This indicates that acetaldehyde was only oxidized in the mitochondrial compartment.
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Yang, Hang, Linlin Du, and Zhaocai Zhang. "Potential biomarkers in septic shock besides lactate." Experimental Biology and Medicine 245, no. 12 (April 10, 2020): 1066–72. http://dx.doi.org/10.1177/1535370220919076.

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Septic shock can be defined as sepsis with persisting hypotension and is required for vasopressors after initial unsuccessful fluid resuscitation. Elevated lactate is a biomarker of tissue perfusion and oxygenation and a useful prognostic tool for resuscitation in septic shock, as it is a byproduct of anaerobic glycolysis due to inadequate oxygen delivery and tissue hypoxia. Early and serial systematic lactate measurement will prompt physician more rapid intervention and lactate normalization, which is associated with better outcome. However, lactate formation during septic shock is neither entirely related to tissue hypoxia, nor reversible by increasing oxygen delivery. Meanwhile, lactate can be oxidized via tricarboxylic acid cycle after being transferred into mitochondria via lactate shuttle, which indicates elevated lactate can be used rather than only accumulation. Glycolysis and elevated lactate can be initiated by hypoxia, but persistent hyperlactatemia may not only represent persistent hypoxia. Some other potential biomarkers have been reviewed in the article including intermediates of tricarboxylic acid cycle, malate-aspartate shuttle, the nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide (NAD+/NADH) ratio, NAD+, NADH, malate, and malate dehydrogenase from the point of view of energy metabolism. Among them, malate dehydrogenase participates in both malate-aspartate shuttle and tricarboxylic acid cycle, and it can also indirectly reflex the NAD+/NADH ratio. It is reasonable to hypothesize that the combination of lactate and malate dehydrogenase will be more comprehensive to reflex hypoxia in septic shock. Impact statement Elevated lactate has been commonly considered as a biomarker and a useful prognostic tool for resuscitation in septic shock, facilitating physician more rapid intervention and treatment. However, it can be initiated by hypoxia, but persistent hyperlactatemia may not represent persistent hypoxia only. In the article, it is the first time to review potential biomarkers in septic shock from the point of view of energy metabolism including intermediates of TCA cycle, MAS, the NAD+/NADH ratio, NAD+, NADH, malate, and MDH. And the combination of lactate and MDH is also proposed in septic shock for the first time, as MDH in cytoplasm and mitochondria participates in both MAS and TCA cycle for ATP generation. Its feasibility in clinic has been analyzed at the end, although related research is still limited. It is reasonable the combination of lactate and MDH will be more comprehensive to reflex hypoxia in septic shock.
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Hesse, Friederike, Vencel Somai, Felix Kreis, Flaviu Bulat, Alan J. Wright, and Kevin M. Brindle. "Monitoring tumor cell death in murine tumor models using deuterium magnetic resonance spectroscopy and spectroscopic imaging." Proceedings of the National Academy of Sciences 118, no. 12 (March 16, 2021): e2014631118. http://dx.doi.org/10.1073/pnas.2014631118.

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2H magnetic resonance spectroscopic imaging has been shown recently to be a viable technique for metabolic imaging in the clinic. We show here that 2H MR spectroscopy and spectroscopic imaging measurements of [2,3-2H2]malate production from [2,3-2H2]fumarate can be used to detect tumor cell death in vivo via the production of labeled malate. Production of [2,3-2H2]malate, following injection of [2,3-2H2]fumarate (1 g/kg) into tumor-bearing mice, was measured in a murine lymphoma (EL4) treated with etoposide, and in human breast (MDA-MB-231) and colorectal (Colo205) xenografts treated with a TRAILR2 agonist, using surface-coil localized 2H MR spectroscopy at 7 T. Malate production was also imaged in EL4 tumors using a fast 2H chemical shift imaging sequence. The malate/fumarate ratio increased from 0.016 ± 0.02 to 0.16 ± 0.14 in EL4 tumors 48 h after drug treatment (P = 0.0024, n = 3), and from 0.019 ± 0.03 to 0.25 ± 0.23 in MDA-MB-231 tumors (P = 0.0001, n = 5) and from 0.016 ± 0.04 to 0.28 ± 0.26 in Colo205 tumors (P = 0.0002, n = 5) 24 h after drug treatment. These increases were correlated with increased levels of cell death measured in excised tumor sections obtained immediately after imaging. 2H MR measurements of [2,3-2H2]malate production from [2,3-2H2]fumarate provide a potentially less expensive and more sensitive method for detecting cell death in vivo than 13C MR measurements of hyperpolarized [1,4-13C2]fumarate metabolism, which have been used previously for this purpose.
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Takanashi, Kojiro, Takayuki Sasaki, Tomohiro Kan, Yuka Saida, Akifumi Sugiyama, Yoko Yamamoto, and Kazufumi Yazaki. "A Dicarboxylate Transporter, LjALMT4, Mainly Expressed in Nodules of Lotus japonicus." Molecular Plant-Microbe Interactions® 29, no. 7 (July 2016): 584–92. http://dx.doi.org/10.1094/mpmi-04-16-0071-r.

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Legume plants can establish symbiosis with soil bacteria called rhizobia to obtain nitrogen as a nutrient directly from atmospheric N2 via symbiotic nitrogen fixation. Legumes and rhizobia form nodules, symbiotic organs in which fixed-nitrogen and photosynthetic products are exchanged between rhizobia and plant cells. The photosynthetic products supplied to rhizobia are thought to be dicarboxylates but little is known about the movement of dicarboxylates in the nodules. In terms of dicarboxylate transporters, an aluminum-activated malate transporter (ALMT) family is a strong candidate responsible for the membrane transport of carboxylates in nodules. Among the seven ALMT genes in the Lotus japonicus genome, only one, LjALMT4, shows a high expression in the nodules. LjALMT4 showed transport activity in a Xenopus oocyte system, with LjALMT4 mediating the efflux of dicarboxylates including malate, succinate, and fumarate, but not tricarboxylates such as citrate. LjALMT4 also mediated the influx of several inorganic anions. Organ-specific gene expression analysis showed LjALMT4 mRNA mainly in the parenchyma cells of nodule vascular bundles. These results suggest that LjALMT4 may not be involved in the direct supply of dicarboxylates to rhizobia in infected cells but is responsible for supplying malate as well as several anions necessary for symbiotic nitrogen fixation, via nodule vasculatures.
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Kovács, E., P. Tóth, Cs Juhász, and J. TamáS. "Biological agents in potable water." International Review of Applied Sciences and Engineering 5, no. 1 (June 1, 2014): 47–51. http://dx.doi.org/10.1556/irase.5.2014.1.6.

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Abstract There are numerous biological agents including bacteria such as Brucella suis, B. abortus, Francisella tularensis, Burkholderia mallei, Coxiella burnetii, Yersina pestis, Bacillus anthracis and Chlamydia psittaci, viruses such as Variola major and V. minor, Flavivirus and Hantavirus, and toxins such as Botulinum toxin produced by the bacterium Clostridium botulinum, Staphylococcus enterotoxin B and Trichothecene mycotoxin reported to have potential to cause illness via water consumption. In the recent years, biological threat prevention for urban water supply systems has been of special interest worldwide, thus, protection against biological agents requires adequate knowledge, available water treatment technologies and preparedness. In this review, the history of biological threat via public water supply, as well as selected early detection methods, prevention strategies and risk assessment models are detailed.
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30

Hopley, Tara, Linda M. Broadhurst, and Michael G. Gardner. "Isolation via 454 sequencing and characterisation of microsatellites for Acacia montana (Fabaceae), Mallee wattle: an endemic shrub from southeastern Australia." Conservation Genetics Resources 7, no. 1 (August 31, 2014): 171–72. http://dx.doi.org/10.1007/s12686-014-0321-6.

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31

Brett, Paul J., Mary N. Burtnick, Christian Heiss, Parastoo Azadi, David DeShazer, Donald E. Woods, and Frank C. Gherardini. "Burkholderia thailandensis oacAMutants Facilitate the Expression ofBurkholderia mallei-Like O Polysaccharides." Infection and Immunity 79, no. 2 (November 29, 2010): 961–69. http://dx.doi.org/10.1128/iai.01023-10.

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ABSTRACTPrevious studies have shown that the O polysaccharides (OPS) expressed byBurkholderia malleiare similar to those produced byBurkholderia thailandensisexcept that they lack the 4-O-acetyl modifications on their 6-deoxy-α-l-talopyranosyl residues. In the present study, we describe the identification and characterization of an open reading frame, designatedoacA, expressed byB. thailandensisthat accounts for this phenomenon. Utilizing theB. thailandensisandB. malleilipopolysaccharide (LPS)-specific monoclonal antibodies Pp-PS-W and 3D11, Western immunoblot analyses demonstrated that the LPS antigens expressed by theoacAmutant,B. thailandensisZT0715, were antigenically similar to those produced byB. malleiATCC 23344. In addition, immunoblot analyses demonstrated that whenB. malleiATCC 23344 was complemented intranswithoacA, it synthesizedB. thailandensis-like LPS antigens. To elucidate the structure of the OPS moieties expressed by ZT0715, purified samples were analyzed via nuclear magnetic resonance spectroscopy. As predicted, these studies demonstrated that the loss of OacA activity influenced the O acetylation phenotype of the OPS moieties. Unexpectedly, however, the results indicated that the O methylation status of the OPS antigens was also affected by the loss of OacA activity. Nonetheless, it was revealed that the LPS moieties expressed by theoacAmutant reacted strongly with theB. malleiLPS-specific protective monoclonal antibody 9C1-2. Based on these findings, it appears that OacA is required for the 4-Oacetylation and 2-Omethylation ofB. thailandensisOPS antigens and that ZT0715 may provide a safe and cost-effective source ofB. mallei-like OPS to facilitate the synthesis of glanders subunit vaccine candidates.
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Cook, Samantha, Nikki Daniels, and Sarah Woodbridge. "How do hand therapists conservatively manage acute, closed mallet finger? A survey of members of the British Association of Hand Therapists." Hand Therapy 22, no. 1 (August 20, 2016): 13–25. http://dx.doi.org/10.1177/1758998316664822.

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Introduction Previous research concerning the conservative management of mallet finger has focused on splint application, with limited representation of supplementary rehabilitation and best practice. This research sought to investigate the practice and opinions of members of the British Association of Hand Therapists regarding their current treatment and to determine whether any specific exercise prescription or rehabilitation protocols are followed. Methods British Association of Hand Therapists members were contacted via e-mail and requested to complete an online survey. Thirty-five responses (5.7% response rate), 30 (4.8% response rate) of which were fully completed were obtained over the eight-week data collection period. The questionnaire consisted of 30 questions (20 quantitative and 10 qualitative) concerning therapists’ roles and condition management. Responses were analysed in terms of response frequencies, percentages and thematic text analysis. Results The results demonstrated current clinical practices in line with available best-evidenced practice. Conservative therapeutic management is diverse and varied. Therapists believe their role to be significant in optimising outcome success. Discussion Exercises and other interventions supplementary to splinting are commonly utilised in the therapeutic management of acute, closed mallet finger. This research found hand therapists implement a diverse range of clinical skills in order to optimise outcome success. Recommendations for best practice and further research are presented.
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P, Das. "Semen Infection Associated Male Infertility and Role of Assisted Reproductive Techniques: A Review." Virology & Immunology Journal 6, no. 3 (September 8, 2022): 1–9. http://dx.doi.org/10.23880/vij-16000297.

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Recent research has revealed that pathogens in the semen and in the genital tract play a significant role in male infertility. The infection of viruses like Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Human Papilloma Virus (HPV), Herpes-Simplex Virus (HSV), and Human Cytomegalovirus (HCMV) may have a significant impact on male infertility. These infections may lead to temporary or permanent infertility, hormonal impairment, testicular malfunction, or abnormal spermatogenesis. This review is looking into the mechanism of viral infections and their effects on male fertility. The current review also focuses on defining the role of ARTs (Assisted Reproductive Techniques) in the occurrence and management of viral load of the male reproductive system
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Meemongkolkiat, Thitipan, Jane Allison, Frank Seebacher, Julianne Lim, Chanpen Chanchao, and Benjamin P. Oldroyd. "Thermal adaptation in the honeybee (Apis mellifera) via changes to the structure of malate dehydrogenase." Journal of Experimental Biology 223, no. 18 (July 17, 2020): jeb228239. http://dx.doi.org/10.1242/jeb.228239.

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ABSTRACTIn honeybees there are three alleles of cytosolic malate dehydrogenase gene: F, M and S. Allele frequencies are correlated with environmental temperature, suggesting that the alleles have temperature-dependent fitness benefits. We determined the enzyme activity of each allele across a range of temperatures in vitro. The F and S alleles have higher activity and are less sensitive to high temperatures than the M allele, which loses activity after incubation at temperatures found in the thorax of foraging bees in hot climates. Next, we predicted the protein structure of each allele and used molecular dynamics simulations to investigate their molecular flexibility. The M allozyme is more flexible than the S and F allozymes at 50°C, suggesting a plausible explanation for its loss of activity at high temperatures, and has the greatest structural flexibility at 15°C, suggesting that it can retain some enzyme activity at cooler temperatures. MM bees recovered from 2 h of cold narcosis significantly better than all other genotypes. Combined, these results explain clinal variation in malate dehydrogenase allele frequencies in the honeybee at the molecular level.
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Meng, Ge, Chunyan Liu, Shidong Qin, Mengshu Dong, Xiaomi Wei, Meilin Zheng, Liwen Qin, Huihui Wang, Xiaoshuang He, and Zhiguo Zhang. "An improved synthesis of sunitinib malate via a solvent-free decarboxylation process." Research on Chemical Intermediates 41, no. 11 (May 5, 2015): 8941–54. http://dx.doi.org/10.1007/s11164-015-1939-z.

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36

Mora-Macías, Javier, Jonathan Odilón Ojeda-Rivera, Dolores Gutiérrez-Alanís, Lenin Yong-Villalobos, Araceli Oropeza-Aburto, Javier Raya-González, Gabriel Jiménez-Domínguez, Gabriela Chávez-Calvillo, Rubén Rellán-Álvarez, and Luis Herrera-Estrella. "Malate-dependent Fe accumulation is a critical checkpoint in the root developmental response to low phosphate." Proceedings of the National Academy of Sciences 114, no. 17 (April 11, 2017): E3563—E3572. http://dx.doi.org/10.1073/pnas.1701952114.

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Low phosphate (Pi) availability constrains plant development and seed production in both natural and agricultural ecosystems. When Pi is scarce, modifications of root system architecture (RSA) enhance the soil exploration ability of the plant and lead to an increase in Pi uptake. In Arabidopsis, an iron-dependent mechanism reprograms primary root growth in response to low Pi availability. This program is activated upon contact of the root tip with low-Pi media and induces premature cell differentiation and the arrest of mitotic activity in the root apical meristem, resulting in a short-root phenotype. However, the mechanisms that regulate the primary root response to Pi-limiting conditions remain largely unknown. Here we report on the isolation and characterization of two low-Pi insensitive mutants (lpi5 and lpi6), which have a long-root phenotype when grown in low-Pi media. Cellular, genomic, and transcriptomic analysis of low-Pi insensitive mutants revealed that the genes previously shown to underlie Arabidopsis Al tolerance via root malate exudation, known as SENSITIVE TO PROTON RHIZOTOXICITY (STOP1) and ALUMINUM ACTIVATED MALATE TRANSPORTER 1 (ALMT1), represent a critical checkpoint in the root developmental response to Pi starvation in Arabidopsis thaliana. Our results also show that exogenous malate can rescue the long-root phenotype of lpi5 and lpi6. Malate exudation is required for the accumulation of Fe in the apoplast of meristematic cells, triggering the differentiation of meristematic cells in response to Pi deprivation.
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Liu, Kun, Ying Xu, and Ning-Yi Zhou. "Identification of a Specific Maleate Hydratase in the Direct Hydrolysis Route of the Gentisate Pathway." Applied and Environmental Microbiology 81, no. 17 (June 12, 2015): 5753–60. http://dx.doi.org/10.1128/aem.00975-15.

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ABSTRACTIn contrast to the well-characterized and more common maleylpyruvate isomerization route of the gentisate pathway, the direct hydrolysis route occurs rarely and remains unsolved. InPseudomonas alcaligenesNCIMB 9867, two gene clusters,xlnandhbz, were previously proposed to be involved in gentisate catabolism, and HbzF was characterized as a maleylpyruvate hydrolase converting maleylpyruvate to maleate and pyruvate. However, the complete degradation pathway of gentisate through direct hydrolysis has not been characterized. In this study, we obtained from the NCIMB culture collection aPseudomonas alcaligenesspontaneous mutant strain that lacked thexlncluster and designated the mutant strain SponMu. Thehbzcluster in strain SponMu was resequenced, revealing the correct location of the stop codon forhbzIand identifying a new gene,hbzG. HbzIJ was demonstrated to be a maleate hydratase consisting of large and small subunits, stoichiometrically converting maleate to enantiomerically pured-malate. HbzG is a glutathione-dependent maleylpyruvate isomerase, indicating the possible presence of two alternative pathways of maleylpyruvate catabolism. However, thehbzF-disrupted mutant could still grow on gentisate, while disruption ofhbzGprevented this ability, indicating that the direct hydrolysis route was not a complete pathway in strain SponMu. Subsequently, ad-malate dehydrogenase gene was introduced into thehbzG-disrupted mutant, and the engineered strain was able to grow on gentisate via the direct hydrolysis route. This fills a gap in our understanding of the direct hydrolysis route of the gentisate pathway and provides an explanation for the high yield ofd-malate from maleate by thisd-malate dehydrogenase-deficient natural mutant.
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Hung, Hui-Chih, Meng-Wei Kuo, Gu-Gang Chang, and Guang-Yaw Liu. "Characterization of the functional role of allosteric site residue Asp102 in the regulatory mechanism of human mitochondrial NAD(P)+-dependent malate dehydrogenase (malic enzyme)." Biochemical Journal 392, no. 1 (November 8, 2005): 39–45. http://dx.doi.org/10.1042/bj20050641.

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Human mitochondrial NAD(P)+-dependent malate dehydrogenase (decarboxylating) (malic enzyme) can be specifically and allosterically activated by fumarate. X-ray crystal structures have revealed conformational changes in the enzyme in the absence and in the presence of fumarate. Previous studies have indicated that fumarate is bound to the allosteric pocket via Arg67 and Arg91. Mutation of these residues almost abolishes the activating effect of fumarate. However, these amino acid residues are conserved in some enzymes that are not activated by fumarate, suggesting that there may be additional factors controlling the activation mechanism. In the present study, we tried to delineate the detailed molecular mechanism of activation of the enzyme by fumarate. Site-directed mutagenesis was used to replace Asp102, which is one of the charged amino acids in the fumarate binding pocket and is not conserved in other decarboxylating malate dehydrogenases. In order to explore the charge effect of this residue, Asp102 was replaced by alanine, glutamate or lysine. Our experimental data clearly indicate the importance of Asp102 for activation by fumarate. Mutation of Asp102 to Ala or Lys significantly attenuated the activating effect of fumarate on the enzyme. Kinetic parameters indicate that the effect of fumarate was mainly to decrease the Km values for malate, Mg2+ and NAD+, but it did not notably elevate kcat. The apparent substrate Km values were reduced by increasing concentrations of fumarate. Furthermore, the greatest effect of fumarate activation was apparent at low malate, Mg2+ or NAD+ concentrations. The Kact values were reduced with increasing concentrations of malate, Mg2+ and NAD+. The Asp102 mutants, however, are much less sensitive to regulation by fumarate. Mutation of Asp102 leads to the desensitization of the co-operative effect between fumarate and substrates of the enzyme.
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Wijaya, Andy Wiranata, Andreas Ulmer, Lara Hundsdorfer, Natascha Verhagen, Attila Teleki, and Ralf Takors. "Compartment-specific metabolome labeling enables the identification of subcellular fluxes that may serve as promising metabolic engineering targets in CHO cells." Bioprocess and Biosystems Engineering 44, no. 12 (September 30, 2021): 2567–78. http://dx.doi.org/10.1007/s00449-021-02628-1.

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Abstract13C labeling data are used to calculate quantitative intracellular flux patterns reflecting in vivo conditions. Given that approaches for compartment-specific metabolomics exist, the benefits they offer compared to conventional non-compartmented 13C flux studies remain to be determined. Using compartment-specific labeling information of IgG1-producing Chinese hamster ovary cells, this study investigated differences of flux patterns exploiting and ignoring metabolic labeling data of cytosol and mitochondria. Although cellular analysis provided good estimates for the majority of intracellular fluxes, half of the mitochondrial transporters, and NADH and ATP balances, severe differences were found for some reactions. Accurate flux estimations of almost all iso-enzymes heavily depended on the sub-cellular labeling information. Furthermore, key discrepancies were found for the mitochondrial carriers vAGC1 (Aspartate/Glutamate antiporter), vDIC (Malate/H+ symporter), and vOGC (α-ketoglutarate/malate antiporter). Special emphasis is given to the flux of cytosolic malic enzyme (vME): it could not be estimated without the compartment-specific malate labeling information. Interesting enough, cytosolic malic enzyme is an important metabolic engineering target for improving cell-specific IgG1 productivity. Hence, compartment-specific 13C labeling analysis serves as prerequisite for related metabolic engineering studies.
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Fernandes, Paula J., Qin Guo, David M. Waag, and Michael S. Donnenberg. "The Type IV Pilin of Burkholderia mallei Is Highly Immunogenic but Fails To Protect against Lethal Aerosol Challenge in a Murine Model." Infection and Immunity 75, no. 6 (April 2, 2007): 3027–32. http://dx.doi.org/10.1128/iai.00150-07.

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ABSTRACT Burkholderia mallei is the cause of glanders and a proven biological weapon. We identified and purified the type IV pilin protein of this organism to study its potential as a subunit vaccine. We found that purified pilin was highly immunogenic. Furthermore, mice infected via sublethal aerosol challenge developed significant increases in titers of antibody against the pilin, suggesting that it is expressed in vivo. Nevertheless, we found no evidence that high-titer antipilin antisera provided passive protection against a sublethal or lethal aerosol challenge and no evidence of protection afforded by active immunization with purified pilin. These results contrast with the utility of type IV pilin subunit vaccines against other infectious diseases and highlight the need for further efforts to identify protective responses against this pathogen.
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van der Rest, Michel E., Christian Frank, and Douwe Molenaar. "Functions of the Membrane-Associated and Cytoplasmic Malate Dehydrogenases in the Citric Acid Cycle ofEscherichia coli." Journal of Bacteriology 182, no. 24 (December 15, 2000): 6892–99. http://dx.doi.org/10.1128/jb.182.24.6892-6899.2000.

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ABSTRACT Oxidation of malate to oxaloacetate in Escherichia colican be catalyzed by two enzymes: the well-known NAD-dependent malate dehydrogenase (MDH; EC 1.1.1.37 ) and the membrane-associated malate:quinone-oxidoreductase (MQO; EC 1.1.99.16 ), encoded by the genemqo (previously called yojH). Expression of themqo gene and, consequently, MQO activity are regulated by carbon and energy source for growth. In batch cultures, MQO activity was highest during exponential growth and decreased sharply after onset of the stationary phase. Experiments with the β-galactosidase reporter fused to the promoter of the mqo gene indicate that its transcription is regulated by the ArcA-ArcB two-component system. In contrast to earlier reports, MDH did not repressmqo expression. On the contrary, MQO and MDH are active at the same time in E. coli. For Corynebacterium glutamicum, it was found that MQO is the principal enzyme catalyzing the oxidation of malate to oxaloacetate. These observations justified a reinvestigation of the roles of MDH and MQO in the citric acid cycle of E. coli. In this organism, a defined deletion of the mdh gene led to severely decreased rates of growth on several substrates. Deletion of the mqo gene did not produce a distinguishable effect on the growth rate, nor did it affect the fitness of the organism in competition with the wild type. To investigate whether in an mqo mutant the conversion of malate to oxaloacetate could have been taken over by a bypass route via malic enzyme, phosphoenolpyruvate synthase, and phosphenolpyruvate carboxylase, deletion mutants of the malic enzyme genessfcA and b2463 (coding for EC 1.1.1.38 and EC1.1.1.40 , respectively) and of the phosphoenolpyruvate synthase (EC2.7.9.2 ) gene pps were created. They were introduced separately or together with the deletion of mqo. These studies did not reveal a significant role for MQO in malate oxidation in wild-type E. coli. However, comparing growth of themdh single mutant to that of the double mutant containingmdh and mqo deletions did indicate that MQO partly takes over the function of MDH in an mdh mutant.
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42

Kim, Eun Young, Won Kon Kim, Hyo Jin Kang, Jeong-Hoon Kim, Sang J. Chung, Yeon Soo Seo, Sung Goo Park, Sang Chul Lee, and Kwang-Hee Bae. "Acetylation of malate dehydrogenase 1 promotes adipogenic differentiation via activating its enzymatic activity." Journal of Lipid Research 53, no. 9 (June 12, 2012): 1864–76. http://dx.doi.org/10.1194/jlr.m026567.

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43

Katava, M., M. Marchi, D. Madern, M. Sztucki, M. Maccarini, and F. Sterpone. "Temperature Unmasks Allosteric Propensity in a Thermophilic Malate Dehydrogenase via Dewetting and Collapse." Journal of Physical Chemistry B 124, no. 6 (January 21, 2020): 1001–8. http://dx.doi.org/10.1021/acs.jpcb.9b10776.

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44

Shi, Ting, Shan Liu, and Yi-Heng P. Job Zhang. "CO2 fixation for malate synthesis energized by starch via in vitro metabolic engineering." Metabolic Engineering 55 (September 2019): 152–60. http://dx.doi.org/10.1016/j.ymben.2019.07.005.

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45

Oh, Se Jeong, Dong Ryun Gu, Su Hyun Jin, Keun Ha Park, and Seoung Hoon Lee. "Cytosolic malate dehydrogenase regulates RANKL-mediated osteoclastogenesis via AMPK/c-Fos/NFATc1 signaling." Biochemical and Biophysical Research Communications 475, no. 1 (June 2016): 125–32. http://dx.doi.org/10.1016/j.bbrc.2016.05.055.

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46

HA, D. C., J. B. AHN, and Y. E. KWON. "ChemInform Abstract: Synthesis of (-)-Macronecine via Condensation Reaction Between Malate Enolate and Imine." ChemInform 29, no. 43 (June 19, 2010): no. http://dx.doi.org/10.1002/chin.199843248.

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47

Wang, Xin, Yue Han, Xuan Feng, Yun-Zhen Li, Bao-Xiang Qin, Ji-Jing Luo, Zheng Wei, Yong-Fu Qiu, Fang Liu, and Rong-Bai Li. "Breeding of Indica glutinous cytoplasmic male sterile line WX209A via CRISPR/Cas9 mediated genomic editing." Czech Journal of Genetics and Plant Breeding 55, No. 3 (June 17, 2019): 93–100. http://dx.doi.org/10.17221/197/2017-cjgpb.

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Glutinous cytoplasmic male sterile (CMS) line is necessary to select hybrid glutinous rice combination with high yield and quality. To develop glutinous CMS with low amylose content, in this study, we firstly knocked out the granule-bound starch synthase OsWaxy in 209B using CRISPR/Cas9 mediated genome editing technology and successfully obtained a glutinous maintainer line WX209B. Comparing with maintainer line 209B, WX209B showed decreased amylose contents and similar agronomic characters. And then, through one generation of hybridization and two generations of backcrossing with WX209B as the male parent and 209A as the female parent, the glutinous CMS line WX209A was successfully achieved. Our study provides a strategy to efficiently breed for the glutinous cytoplasmic male sterile line by combining CRISPR/Cas9-mediated gene editing technology with conventional backcross breeding method in a short period, which prepares the ground for further breeding of hybrid glutinous rice variety.
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48

Erb, Tobias J., Lena Frerichs-Revermann, Georg Fuchs, and Birgit E. Alber. "The Apparent Malate Synthase Activity of Rhodobacter sphaeroides Is Due to Two Paralogous Enzymes, (3S)-Malyl-Coenzyme A (CoA)/β-Methylmalyl-CoA Lyase and (3S)- Malyl-CoA Thioesterase." Journal of Bacteriology 192, no. 5 (January 4, 2010): 1249–58. http://dx.doi.org/10.1128/jb.01267-09.

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ABSTRACT Assimilation of acetyl coenzyme A (acetyl-CoA) is an essential process in many bacteria that proceeds via the glyoxylate cycle or the ethylmalonyl-CoA pathway. In both assimilation strategies, one of the final products is malate that is formed by the condensation of acetyl-CoA with glyoxylate. In the glyoxylate cycle this reaction is catalyzed by malate synthase, whereas in the ethylmalonyl-CoA pathway the reaction is separated into two proteins: malyl-CoA lyase, a well-known enzyme catalyzing the Claisen condensation of acetyl-CoA with glyoxylate and yielding malyl-CoA, and an unidentified malyl-CoA thioesterase that hydrolyzes malyl-CoA into malate and CoA. In this study the roles of Mcl1 and Mcl2, two malyl-CoA lyase homologs in Rhodobacter sphaeroides, were investigated by gene inactivation and biochemical studies. Mcl1 is a true (3S)-malyl-CoA lyase operating in the ethylmalonyl-CoA pathway. Notably, Mcl1 is a promiscuous enzyme and catalyzes not only the condensation of acetyl-CoA and glyoxylate but also the cleavage of β-methylmalyl-CoA into glyoxylate and propionyl-CoA during acetyl-CoA assimilation. In contrast, Mcl2 was shown to be the sought (3S)-malyl-CoA thioesterase in the ethylmalonyl-CoA pathway, which specifically hydrolyzes (3S)-malyl-CoA but does not use β-methylmalyl-CoA or catalyze a lyase or condensation reaction. The identification of Mcl2 as thioesterase extends the enzyme functions of malyl-CoA lyase homologs that have been known only as “Claisen condensation” enzymes so far. Mcl1 and Mcl2 are both related to malate synthase, an enzyme which catalyzes both a Claisen condensation and thioester hydrolysis reaction.
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49

Gatehouse, Robyn D., I. S. Williams, and B. J. Pillans. "Fingerprinting windblown dust in south-eastern Australian soils by uranium-lead dating of detrital zircon." Soil Research 39, no. 1 (2001): 7. http://dx.doi.org/10.1071/sr99078.

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The U-Pb ages of fine-grained zircon separated from 2 dust-dominated soils in the eastern highlands of south-eastern Australia and measured by ion microprobe (SHRIMP) revealed a characteristic age ‘fingerprint’ from which the source of the dust has been determined and by which it will be possible to assess the contribution of dust to other soil profiles. The 2 soils are dominated by zircon 400–600 and 1000–1200 Ma old, derived from Palaeozoic granites and sediments of the Lachlan Fold Belt, but also contain significant components 100–300 Ma old, characteristic of igneous rocks in the New England Fold Belt in northern New South Wales and Queensland. This pattern closely matches that of sediments of the Murray-Darling Basin, especially the Mallee dunefield, suggesting that weathering of rocks in the eastern highlands has contributed large quantities of sediment to the arid and semi-arid inland basins via internally draining rivers of the present and past Murray–Darling River systems, where it has formed a major source of dust subsequently blown eastwards and deposited in the highland soils of eastern Australia.
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50

Goodger, Jason Q. D., Allison M. Heskes, Drew J. King, Roslyn M. Gleadow, and Ian E. Woodrow. "Research note: Micropropagation of Eucalyptus polybractea selected for key essential oil traits." Functional Plant Biology 35, no. 3 (2008): 247. http://dx.doi.org/10.1071/fp07241.

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A protocol for the micropropagation of Eucalyptus polybractea R.T. Baker (blue mallee) using axillary bud proliferation from lignotuber-derived explants is described. Three different ages of plants were used as explant sources: glasshouse-grown seedlings, field-grown saplings, and coppice of field-grown mature lignotubers. Explants from each source initiated successfully and no significant difference was observed for shoot proliferation, rooting success or hardening success between explant sources. Leaf oil quantity and quality for hardened clones transplanted to a field plantation were assessed after 3 months of growth. Ramets of all clones contained high quality oil with over 80% 1,8-cineole. For seedling-derived clones, foliar oil concentrations of ramets were higher than those of the ortets from which they were derived. For sapling and mature lignotuber derived clones the opposite was the case. This suggests that ontogenetic and physiological constraints may be influencing yield in the young ramets. The age of the explant source did not appear to influence the success of micropropagation, and as a result older plants (for which key oil traits are known) can be selected as elite plants for multiplying selected genotypes via micropropagation.
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