732 research outputs found

    Metabolite transport and its impact on metabolic engineering approaches

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    Cells are the structural units of life and are separated from the environment by at least one cellular membrane consisting of a lipid bilayer. Thus, metabolite transport across cellular membranes is a key feature of living organisms. Specialized proteins or protein complexes mediate transport processes and are accessible to metabolic engineering approaches. Genetic modifications in metabolic engineering has mostly involved the deletion or overexpression of genes encoding for enzymes. The role of transporters has received much less attention, but as this special issue shows, it is a key factor to consider when rationally designing microbial cell factories. Transporters have been employed in metabolic engineering endeavors to target three fundamental aspects: Import of substrates , Export of products , Modification of intracellular fluxes

    The fungal sexual revolution continues: indications of sexuality in the citric acid producing fungus Aspergillus niger

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    Sexual reproduction is an important proliferation mechanism which provides advantages to a species by promoting genetic variation. Interestingly, for a large group of fungal species, including the industrially relevant Aspergillus niger, this mode of reproduction has not been described yet. In recent years, strong indications of the sexual potential of A. niger have accumulated 1. These include the ability of certain strains to produce pre-mature sexual structures (sclerotia) and the presence of a mating type MAT1-1 locus in the commonly used A. niger strains, such as ATCC 1015 and CBS 513.88. Here we show additional evidence of the sexual potential of A. niger. Formation of sclerotia could be induced in the progenitor of the industrial citric acid producing strains of A. niger, ATCC 1015, and in pyrG mutants derived from it 2. The capability of ATCC 1015 to form sclerotia, known to act as sexual structures in related organisms, represents a step forward towards the discovery of a sexual cycle in this important industrial species. To find the second mating type locus, we performed genome sequencing of the A. niger neotype strain CBS 554.65 and identified the missing MAT1-2 locus 3. A nucleotide alignment showed a different orientation of the MAT1-1 locus of ATCC 1015 compared to the MAT1-2 locus of CBS 554.65. While the genomic context of the MAT1-2 locus in CBS 554.65 is similar to the one of other MAT1-2 A. niger strains and other Aspergillus species, the region comprising the MAT1-1 locus is inverted in all sequenced strains of A. niger. These observations suggest the occurrence of genetic flipping or switching events at the MAT1-1 locus of A. niger, which might have a direct impact on its sexuality. These results provide new insights in the mating system of A. niger and pave the way for the discovery of a sexual cycle in a species long thought to be asexual. 1. Ellena, V., Sauer, M. & Steiger, M. G. Fungal Biol. Biotechnol. 7, 17 (2020). 2. Ellena, V., Bucchieri, D., Arcalis, E., Sauer, M. & Steiger, M. G. Fungal Biol. 125, 485–494 (2021). 3. Ellena, V., Seekles, S. J., Ram, A. F. J. & Steiger, M. G. BMC Genomics 1–17 (2021)

    cexA and its regulatory processes - the manganese mistery of A. niger

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    cexA and its regulatory processes – a closer look into the citric acid production mechanisms of Aspergillus niger Authors: Aline Reinfurt, Valeria Ellena, Matthias G. Steiger Aspergillus niger is an important filamentous fungus used for the industrial production of citric acid. One of the main contributors to high citric acid accumulation by the fungus is the citrate transporter CexA. It belongs to the major faciliatory superfamily subclass DHA1 which act as drug-H+ antiporters1. Since cexA and its regulators are essential within the citric acid production process, it is important to study their regulatory mechanism, which is the focus of this work. LaeA for one is known to be a major regulator of the cexA gene. It regulates the expression via methylation levels of the histones H3K4 and H3K92. There are indications that other transcriptional regulators such as AmyR and XlnR are also involved in the regulation of cexA on a transcriptional level. Another factor that affects citric acid production is the amount of manganese that is present during the production process. Observations showed that the fungus develops a certain pellet-like morphology under manganese limitation conditions and that this limitation is decisive for high citric acid accumulation by A. niger3,4. However, the exact mode of action of manganese in the cell is not clear. The transcriptional influence of manganese on cexA and laeA is investigated in order to find out more about the connection between manganese limitation and citric acid production

    cexA and its regulatory processes - the manganese mistery of A. niger

    No full text
    cexA and its regulatory processes – a closer look into the citric acid production mechanisms of Aspergillus niger Authors: Aline Reinfurt, Valeria Ellena, Matthias G. Steiger Aspergillus niger is an important filamentous fungus used for the industrial production of citric acid. One of the main contributors to high citric acid accumulation by the fungus is the citrate transporter CexA. It belongs to the major faciliatory superfamily subclass DHA1 which act as drug-H+ antiporters1. Since cexA and its regulators are essential within the citric acid production process, it is important to study their regulatory mechanism, which is the focus of this work. LaeA for one is known to be a major regulator of the cexA gene. It regulates the expression via methylation levels of the histones H3K4 and H3K92. There are indications that other transcriptional regulators such as AmyR and XlnR are also involved in the regulation of cexA on a transcriptional level. Another factor that affects citric acid production is the amount of manganese that is present during the production process. Observations showed that the fungus develops a certain pellet-like morphology under manganese limitation conditions and that this limitation is decisive for high citric acid accumulation by A. niger3,4. However, the exact mode of action of manganese in the cell is not clear. The transcriptional influence of manganese on cexA and laeA is investigated in order to find out more about the connection between manganese limitation and citric acid production

    The endogeneity of money and the eurosystem

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    The endogenous theory of money, developed by Basil Moore, argues that the supply of central bank money in modern economies is not under the control of the central bank. According to this view, a central bank typically supplies cash reserves automatically on demand at its minimum lending rate, resulting in a clearly horizontal money supply function. While the paper agrees with Moore that the supply of central bank money cannot be determined exogenously by the central bank, it wonders whether the supply is determined completely by the demand of the commercial banks. The paper suggests that the central bank has some exogenous power to control the quantity of its supply by rationing. More importantly, the central bank is forced to do so! The central bank cannot not merely exist as an automat responding to the wishes of the commercial banks. Part I discusses the cause why the central bank has to restrict its supply, while part II demonstrates how the supply of central bank money can be controlled by looking at the monetary policy operations of the Eurosystem. In accordance with this analysis, the paper offers a modified horizontal or “staircase” supply function of central bank money. --

    The European Central Bank and the eurosystem: An analysis of the missing central monetary institution in European Monetary Union

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    The Eurosystem is the fifth decentralized system in the history of central banks. It consists of the European Central Bank (ECB) and twelve National Central Banks (NCBs) forming the European Monetary Union (EMU). The stark decentrality of this System is so little known that ubiquitous statements by high level Euro experts on its supposed similarity with other decentralized systems, like the former Bundesbank System and the existing Federal Reserve System, are met with no protest. A closer look on European documents and the balance sheet of the ECB reveals, however, that the ECB – far from being the monopoly supplier of central bank money – cannot set the refinancing conditions to credit institutions in EMU. The latter are determined by the Council of Governors of the Eurosystem, while the main refinancing operations are executed by the NCBs leaving to the ECB the role of vicarious agent. The ECB can neither control all types of securities accepted for the NCBs’ credit operations nor is it able to act as lender of last resort. Yet, every possible manoeuvre to make the ECB look like a central bank of the NCBs is relentlessly employed, most obviously in the design of the Euro banknotes which are issued by the NCBs but carry only the imprint of the ECB, as well as by the ECB’s balance sheet as at 31 December 2002. The latter contains for the first time the item “banknotes in circulation” that are, however, issued by the NCBs and only allocated to the ECB. --

    Glutathione from recovered glucose as ingredient in antioxidant nanocapsules for triggered flavor delivery

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    Side streams from modern lignocellulose biorefineries have found value-added applications in various industries ranging from food to medical. Here, bioproduction of glutathione from glucose recovered from man-made cellulose fiber production was investigated. Rayon fibers were enzymatically hydrolyzed and the resulting glucose and Zn in the hydrolysate were successfully used for glutathione (15.5 mg L−1) production by an engineered strain of Saccharomyces cerevisiae. Next, out of reduced glutathione (GSH) in combination with human serum albumin (HSA) and silk fibroin (SF), nanocapsules were developed. Production of HSA/SF/GSH nanocapsules was further optimized by experimental design and the resulting nanocapsules were characterized by particle size, zeta potential, chemical properties (secondary structure ratios, crosslinking, and release kinetics) and thermal stability. An average hydrodynamic radius of 462.72 ± 73.36 nm and average zeta potential of −13.67 ± 0.01 mV were obtained by optimization using an experimental design approach. Increasing secondary structure ratios for HSA/SF/GSH nanocapsules indicated the successful integration of GSH into the nanocapsule shell by ultrasound induced self-assembly. Regarding possible future application as a cosmeceutical, flavor substances were encapsulated, and the release kinetics of flavor substances were studied, resulting in pH- and viscosity-dependent maximum release rates of 40.45 ± 0.35% for menthol and 38.60 ± 2.07% for raspberry ketone. Additionally, the radical scavenging properties of the system were evaluated, showing increased scavenging for produced HSA/SF/GSH nanocapsules compared to controls. Therefore, HSA/SF/GSH nanocapsules are seen as a promising new system in cosmeceutical approaches

    Impatience and uncertainty: Experimental decisions predict adolescents? field behavior

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    We study risk attitudes, ambiguity attitudes, and time preferences of 661 children and adolescents, aged ten to eighteen years, in an incentivized experiment. We relate experimental choices to field behavior. Experimental measures of impatience are found to be significant redictors of health related field behavior and saving decisions. In particular, more impatient children and adolescents are more likely to spend money on alcohol and cigarettes, have a higher body mass index (BMI) and are less likely to save money. Experimental measures for risk and ambiguity attitudes are only weak predictors of field behavior.experiments with children and adolescents; risk; ambiguity; time preferences; health status; savings; external validity; field behavior.

    On the Complexity of Finding a Sparse Connected Spanning Subgraph in a Non-Uniform Failure Model

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    We study a generalization of the classic Spanning Tree problem that allows for a non-uniform failure model. More precisely, edges are either safe or unsafe and we assume that failures only affect unsafe edges. In Unweighted Flexible Graph Connectivity we are given an undirected graph G = (V,E) in which the edge set E is partitioned into a set S of safe edges and a set U of unsafe edges and the task is to find a set T of at most k edges such that T -{u} is connected and spans V for any unsafe edge u ∈ T. Unweighted Flexible Graph Connectivity generalizes both Spanning Tree and Hamiltonian Cycle. We study Unweighted Flexible Graph Connectivity in terms of fixed-parameter tractability (FPT). We show an almost complete dichotomy on which parameters lead to fixed-parameter tractability and which lead to hardness. To this end, we obtain FPT-time algorithms with respect to the vertex deletion distance to cluster graphs and with respect to the treewidth. By exploiting the close relationship to Hamiltonian Cycle, we show that FPT-time algorithms for many smaller parameters are unlikely under standard parameterized complexity assumptions. Regarding problem-specific parameters, we observe that Unweighted Flexible Graph Connectivity admits an FPT-time algorithm when parameterized by the number of unsafe edges. Furthermore, we investigate a below-upper-bound parameter for the number of edges of a solution. We show that this parameter also leads to an FPT-time algorithm.Discrete Mathematics and Optimizatio
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