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Based on correlated magnetosphere‐ionosphere (M‐I) conjugate observations of seven events, we study the hot zone developed under short‐circuiting conditions leading (a) to the development of outward Subauroral Polarization Streams (SAPS) or Subauroral Ion Drifts (SAID) electric (E) field and (b) to the various subauroral arcs' absence or presence. Results show (a) the close relations of the hot zone earthward extent and peak ion temperature (Ti) to the magnitude of outward SAPS/SAID E field and (b) the hot zone's high Ti (∼11,000 eV) developed under enhanced plasma turbulence that was (c) generated by the amplified narrow hot ion and electron plasma density peaks, (d) sometimes in plasmaspheric plumes, and that was (e) sometimes further enhanced by the strong auroral kilometric radiation (AKR) waves (f) leading to the development of enhanced SAPS/SAID E field. From these (a–f) findings we conclude for the seven events investigated that (a) the hot zone's development under short‐circuiting conditions was regulated by the kinetic energy of mesoscale plasma flows and that (b) the hot zone created the favorable inner‐magnetosphere conditions during short circuiting (c) for stable auroral red (SAR) arc development by plasma turbulence, which is the common source of heat/suprathermal particles accelerated downward, and (d) in the plasmaspheric plume scenario for SAR arc and Strong Thermal Emission Velocity Enhancement (STEVE) arc development by the plumes' enhanced cold plasma populations leading to strong shear flows and thus shear‐flow instabilities well‐known associated with the SAPS/SAR arc and recently regarded as a potential driver mechanism of the STEVE arc. Key Points: The hot zone's development under short‐circuiting conditions was regulated by the kinetic energy of mesoscale plasma flowsThe hot zone created favorable inner‐magnetosphere conditions for the development of stable auroral red arc by plasma turbulenceStrong Thermal Emission Velocity Enhancement arc development was favored by the plasmaspheric plume related shear flows [ABSTRACT FROM AUTHOR]

Previous studies have shown that auroral kilometric radiation (AKR) can play an important role in the magnetosphere‐atmosphere coupling and has the right‐handed extraordinary (R‐X), left‐handed ordinary (L‐O) and left‐handed extraordinary (L‐X) modes. However, the L‐X mode has not been directly observed in the lower latitude magnetosphere yet, probably because of its very limited frequency range. Here, using observations of the Arase satellite on 6 September 2018, we present an AKR event with two distinct bands (8–20 and 300–1000 kHz) around the location: L = 8 and latitude = −37°. The low (high) band is identified as the L‐X (R‐X) mode based on the polarization and frequency ranges. Simulations of 3‐D ray tracing show that most of ray paths with 14 (11 and 18) kHz pass (miss) the location of Arase, basically consistent with observations. Our study provides direct evidence that the L‐X mode can propagate from high latitudes downward to lower latitudes. Plain Language Summary: Auroral kilometric radiation (AKR) is a widely existing radio emission with kilometric wavelength at the Earth, contributing to the magnetosphere‐atmosphere coupling. Similar emissions have been observed on all magnetic planets of the solar system. Previous studies have shown that AKR primarily occurs in the R‐X mode, with a small contribution in the L‐O and L‐X modes. The L‐X mode at lower latitudes has not been directly observed so far, most likely due to its extremely limited frequency range. Here, we present an L‐X mode (peak frequency ∼14 kHz) in the lower latitude magnetosphere observed by the Arase satellite. Using the 3‐D ray tracing method, we simulate ray paths with different initial wave parameters and source locations. Simulations show that ray paths with 14 (11 and 18) kHz pass (miss) the location of the Arase satellite and are highly dependent on initial wave parameters and the location of source. Our results provide a direct evidence that the L‐X mode from high latitude source regions can propagate downward to lower latitudes under suitable conditions. This study enriches the understanding of AKR propagation characteristics in the magnetosphere. Key Points: An auroral kilometric radiation (AKR) event with two distinct bands (8–20 kHz and 300–1000 kHz) is observed around the location: L = 8 and latitude = −37°Based on the polarization and frequency ranges, the low (high) band AKR is identified as the L‐X (R‐X) mode3‐D ray tracing simulations show that L‐X mode can propagate downward to lower latitudes, basically consistent with observations [ABSTRACT FROM AUTHOR]

The most important dose-limiting factor of the anthracycline idarubicin is the high risk of cardiotoxicity, in which the secondary alcohol metabolite idarubicinol plays an important role. It is not yet clear which enzymes are most important for the formation of idarubicinol and which inhibitors might be suitable to suppress this metabolic step and thus would be promising concomitant drugs to reduce idarubicin-associated cardiotoxicity. We, therefore, established and validated a mass spectrometry method for intracellular quantification of idarubicin and idarubicinol and investigated idarubicinol formation in different cell lines and its inhibition by known inhibitors of the aldo–keto reductases AKR1A1, AKR1B1, and AKR1C3 and the carbonyl reductases CBR1/3. The enzyme expression pattern differed among the cell lines with dominant expression of CBR1/3 in HEK293 and MCF-7 and very high expression of AKR1C3 in HepG2 cells. In HEK293 and MCF-7 cells, menadione was the most potent inhibitor (IC50 = 1.6 and 9.8 µM), while in HepG2 cells, ranirestat was most potent (IC50 = 0.4 µM), suggesting that ranirestat is not a selective AKR1B1 inhibitor, but also an AKR1C3 inhibitor. Over-expression of AKR1C3 verified the importance of AKR1C3 for idarubicinol formation and showed that ranirestat is also a potent inhibitor of this enzyme. Taken together, our study underlines the importance of AKR1C3 and CBR1 for the reduction of idarubicin and identifies potent inhibitors of metabolic formation of the cardiotoxic idarubicinol, which should now be tested in vivo to evaluate whether such combinations can increase the cardiac safety of idarubicin therapies while preserving its efficacy. [ABSTRACT FROM AUTHOR]

Aldo-keto reductases (AKRs), a superfamily of NADP(H)-dependent oxidoreductases, catalyze the oxidoreduction of a wide variety of eobiotic and xenobiotic aldehydes and ketones. In mammals, AKRs play essential roles in hormone and xenobiotic metabolism, oxidative stress, and drug resistance, but little is known about these enzymes in the parasitic nematode Haemonchus contortus. In the present study, 22 AKR genes existing in the H. contortus genome were investigated and a phylogenetic analysis with comparison to AKRs in Caenorhabditis elegans, sheep and humans was conducted. The constitutive transcription levels of all AKRs were measured in eggs, larvae, and adults of H. contortus, and their expression was compared in a drug-sensitive strain (ISE) and a benzimidazole-resistant strain (IRE) previously derived from the sensitive strain by imposing benzimidazole selection pressure. In addition, the inducibility of AKRs by exposure of H. contortus adults to benzimidazole anthelmintic flubendazole in vitro was tested. Phylogenetic analysis demonstrated that the majority of AKR genes in H. contortus lack orthologues in the sheep genome, which is a favorable finding for considering AKRs as potential drug targets. Large differences in the expression levels of individual AKRs were observed, with AKR1, AKR3, AKR8, and AKR10 being the most highly expressed at most developmental stages. Significant changes in the expression of AKRs during the life cycle and pronounced sex differences were found. Comparing the IRE and ISE strains, three AKRs were upregulated, and seven AKRs were downregulated in adults. In addition, the expression of three AKRs was induced by flubendazole exposure in adults of the ISE strain. Based on these results, AKR1, AKR2, AKR3, AKR5, AKR10 and AKR19 in particular merit further investigation and functional characterization with respect to their potential involvement in drug biotransformation and anthelmintic resistance in H. contortus.

Classical activated sludge systems have been used for over a century in domestic wastewater treatment. However, in recent years, not only carbon removal but also nitrogen and phosphorus removal have become essential for preserving water resources. In this context, scientists are searching for effective and sustainable solutions. In this study, the integrated biological activated sludge (IFAS) process, which is created by integrating fixed biofilm into the classical activated sludge process, was applied by combining it with a sequential batch reactor SBR). The IFAS-SBR system was applied in the sequencing batch reactor with a 40% volume fill ratio of moving support material, utilizing anaerobic (An)/aerobic (Ox)/anoxic (Ox) cycles, with a 36 hour hydraulic retention time (HRT) and an 11.8-day sludge retention time (SRT). During the operational phases, average removal efficiencies of 92.7% for chemical oxygen demand (COD), 79.5% for total nitrogen (TN), and 59.3% for phosphate phosphorus (PO4-P) were achieved. Considering discharge criteria, the reactor achieved successful COD and TN removal, but fell short in terms of phosphorus removal. The IFAS-SBR reactor, has the potential to meet wastewater standards under optimized conditions. [ABSTRACT FROM AUTHOR]

Die Alkalikieselsäure Reaktion (AKR) führt zu schweren bis irreparablen Schäden in Bauwerken und kann nur durch präventives Testen der Gesteinskörnung vermieden werden, allerdings haben die angewandten Testverfahren noch Potential zur Optimierung, welches auf schnellere und präzisere Verfahren hoffen lässt. Am Institut für Baustoffe, Bauphysik und Bauchemie der Technischen Universität Hamburg wird ein neues Testverfahren entwickelt, welches den chemischen Testverfahren ähnelt. Anders als bei den üblichen chemischen Verfahren wird die Reaktivität der Gesteinskörnung nicht von dem Masseverlust oder Konzentration einzelner Komponenten bestimmt. In diesem Ansatz wird die Reaktivität der Gesteinskörnung aus der Veränderung chemischer Parameter, die infolge der Lösung von Gesteinsmehl in hochkonzentrierter heißer Lauge hervorgerufen werden, abgeleitet. Während des Versuchs werden der pH‐Wert, das Redoxpotential und die elektrische Leitfähigkeit aufgezeichnet. Die Zeitverläufe dieser Parameter haben mathematisch quantifizierbare Eigenschaften, wie Geschwindigkeitskonstanten, stationäre Zustände oder Extrempunkte anhand derer die Reaktivität der Gesteinskörnung gefolgert werden soll. Dies basiert auf der Annahme, dass sich das Lösungsverhalten verschieden reaktiver Materialien unterscheidet. Die bisherigen Ergebnisse zeigen sich wiederholende Ergebnisse und eine Differenzierbarkeit der quantifizierbaren Punkte bezüglich der jeweiligen Proben. [ABSTRACT FROM AUTHOR]

Kurzfassung: Ein besonders hohes Risiko für das Auftreten einer schädigenden Alkali‐Kieselsäure‐Reaktion im Beton (AKR) besteht bei Meerwasserbauwerken, da über die im Wasserbau sehr langen Nutzungszeiträume eine permanente Alkalizufuhr von außen erfolgt. Es hat sich gezeigt, dass unter diesen Randbedingungen trotz Einhaltung bestehender Regelungen eine AKR nicht in allen Fällen sicher vermieden werden kann. Für laufende und künftige Baumaßnahmen vor allem im Meerwasserbereich wurde daher ein umfangreiches Forschungsvorhaben gemeinsam von der Bundesanstalt für Wasserbau und der Bauhaus‐Universität Weimar durchgeführt. Ziel der Untersuchungen war insbesondere die Entwicklung einer geeigneten Performance‐Prüfung mit praxisrelevanten Einwirkungen zur Beurteilung der Dauerhaftigkeit von Betonen für Wasser‐ und Meerwasserbauwerke. Begleitend wurden Untersuchungen zur Charakterisierung der Alkaliempfindlichkeit der verwendeten Gesteinskörnungen durchgeführt. Aus den Ergebnissen wurden Erkenntnisse für die zukünftige Vorgehensweise zur Schadensvermeidung solcher langlebigen Infrastrukturbauwerke abgeleitet. [ABSTRACT FROM AUTHOR]

We investigate the Abnormal Sub‐Auroral Ion Drifts (ASAID) developed in the postmidnight (1–4) magnetic local time sector in 2013. Shown by the Defense Meteorological Satellite Program F15 horizontal ion velocity measurements, we specified 21 antisunward (eastward) ASAID flow channels (FCs) based on their respective underlying polar convections. Overall, the polar convection formed a two‐cell pattern with its convection axis tilted in the morning‐evening direction because of the underlying BY < 0 conditions. Its dawn cell intruded into the duskside from the dawnside where the eastward ASAID flows were streaming antisunward, opposite to the dawn cell sunward convection flows. Mostly, the ASAID FC appeared in the coinciding ring‐current–related ionospheric trough and flow‐stagnation–related main ionospheric trough in the South American sector because of the favorable conditions created by the South Atlantic Magnetic Anomaly promoting also the development of Stable Auroral Red (SAR) arc. Rarely observed, the ASAID FC was associated with the SAR arc detected over Rothera. Detected in the Mid Pacific longitude sector, a pair of northern‐southern ASAID FCs demonstrated northern‐southern conjugacy. With correlated observations, demonstrating magnetosphere‐ionosphere conjugacy, the inward (earthward) ASAID electric (E) field could also be investigated. These reveal the ASAID E field's fast‐time development by short‐circuiting when the hot‐ring‐current—cold‐plasmasphere interface developed and became impacted by finite Larmor radius effects because of the earthward intrusion of hot ring current protons. The ASAID E field's inner‐magnetosphere environment was characterized by the hot zone where heating was generated by low‐frequency waves and auroral kilometric radiations. Key Points: The postmidnight eastward Abnormal Sub‐Auroral Ion Drifts (ASAID) flows streamed antisunward: opposite to the dawn cell's sunward flowsThe ASAID flows were associated mostly with the ring ionospheric trough and sometimes with the SAR arcThe inward (earthward) ASAID E field developed by short‐circuiting when finite Larmor radius effects dominated [ABSTRACT FROM AUTHOR]

In this study, we have surveyed the Defense Meteorological Satellite Program F15 plots of horizontal ion velocity measurements for the calendar year of 2013 and specified 15 antisunward (westward) sub‐auroral ion drifts (SAID) detections taken in the 1–4 magnetic local time (MLT) sector based on their respective underlying polar convections. We find that during these 15 SAID events, the strong duskside westward polar plasma convection extended across the midnight meridian into the postmidnight 1–4 MLT sector making there the westward SAID flows streaming antisunward. These antisunward (westward) SAID flows were observed only once as a northern‐southern conjugate pair over the Mid Pacific and repeatedly in the South American longitude sector's wider region. We could correlate six antisunward (westward) SAID flows with their respective nearby outward SAID E fields observed by one of the Van Allen Probe (VAP) satellites in the inner magnetosphere. These provided two strong correlations depicting inner‐magnetosphere—topside‐ionosphere conjugate observations and four weak correlations. The VAP observations illustrate (a) the newly‐formed outward SAID E field and (b) its plasma environment still showing (c) the signatures of short‐circuiting across (d) the newly‐formed plasmapause appearing with (e) the hot zone on the earthward/tailward side and sometimes with (f) a localized heat source. Implying different underlying heating mechanisms, the hot zone and the heat source were associated with energetic plasma particles accelerated by plasma turbulence, low‐frequency waves including electromagnetic ion cyclotron waves, and/or auroral kilometric radiation bursts. Key Points: Antisunward (westward) sub‐auroral ion drifts (SAID) flows were observed in the 1–4 magnetic local time sector near South America 14 times in 2013In the inner magnetosphere, the outward SAID E field developed via short‐circuiting near the newly‐formed plasmapauseThe hot zone and heat source were heated by the enhanced energetic e−/i+ population, electromagnetic ion cyclotron waves and/or auroral kilometric radiation bursts [ABSTRACT FROM AUTHOR]

Low‐frequency radio signals of natural origins have been registered in the heliosphere for more than 50 years, mainly being a product of interaction between the solar wind and the planetary magnetospheres. Withing these signals, series of man‐made transmissions have been detected, coming from the LORAN‐C navigation system and the terrestrial longwave broadcasting stations. The paper compares these two types of signals in the terms of their power distribution, which affects their readability and achieved effective range in space, as well as their possible usability in future research basing on the type of information they deliver. It is indicated that the less‐investigated longwave signals are more efficient, spectrum‐powerful and information‐rich that the LORAN‐C system, offering more possibilities for heliospheric and near‐Earth space research. Plain Language Summary: Space around the Earth and our Solar System is rich in radio signals which are generated naturally—as an effect of interaction between the solar wind and the celestial bodies' magnetospheres. These natural signals have been studied for more than 50 years by various spacecraft. Within these signals, man‐made emissions have been recorded—the navigation system LORAN‐C transmissions and terrestrial longwave radio. This paper compares the ability to carry power and information by these two diffferent transmissions, defining that the one more resistant to weakening and more information‐rich is the longwave radio broadcasting signal. It can be used by spacecraft for technical reasons, or as a mean of probing the space around Earth to deliver information of its composition and properties. Key Points: Introduction to low frequency radio signals in spaceComparison between the longwave A3E system and the LORAN‐C navigation systemDefinition of basic signal properties and frequency proposed for future research [ABSTRACT FROM AUTHOR]

Auroral kilometric radiation (AKR) is the paradigm of intense radio emission from planetary magnetospheres. Being close to the electron gyro frequency and/or its lower harmonics, its observation indicates the non-thermal state of the source plasma. Emission is produced when the plasma enters a state of energetic excitation which results in deformation of the electron distribution function. Under certain conditions this leads to “quasi-coherent” emission. It is believed that the weakly-relativistic electron-cyclotron-maser instability is responsible for this kind of radiation. Since energetically radio radiation normally is not of primary importance in the large-scale magnetospheric phenomena, AKR as such has, for the purposes of large-scale magnetospheric physics, become considered a marginal problem. Here this notion is questioned. AKR while applying to the auroral region mainly during magnetospherically disturbed times carries just a fraction of the total substorm energy. It is, however, of diagnostic power in the physics of the upper auroral ionosphere and Space Weather research. As a fundamental physical problem of generation of radiation in non-thermal plasmas it remains not resolved yet. Many questions have been left open even when dealing only with the electron-cyclotron-maser. These can advantageously be studied in the magnetosphere proper both by observation and theory, the only continuously accessible place in space. The most important are listet here with hint on how they should be attacked. Its value is to be sought in the role it should play in application to the other magnetized planets, extra-solar planets, and to strongly magnetized astronomical objects as an important tool to diagnose the matter state responsible for radiation in the radio frequency range beyond thermal, shock or synchrotron radiation.

Strawberry (Fragaria × ananassa) fruits are rich in ascorbic acid (AsA) and anthocyanin, which are essential antioxidants for human health. However, the underlying regulatory mechanism of these antioxidant accumulation, especially AsA accumulation in strawberry fruits, remains largely unknown. In this study, we identified FaAKR23 was a regulator of AsA and anthocyanin accumulation. We transiently expressed FaAKR23 in strawberry fruits and conducted metabolic and molecular analyses to explore the role of FaAKR23 in AsA and anthocyanin accumulation. Transient silencing of FaAKR23 (FaAKR23-RNAi) in strawberry fruits significantly decreased the AsA and anthocyanin contents compared with control (empty vector-RNAi, EV-RNAi). Correspondingly, expression of some structural genes and regulatory factors involved in these two antioxidants' accumulation was dramatically repressed. In addition, transcriptome analysis of EV-RNAi and FaAKR23-RNAi fruits suggested that FaAKR23 was also involved in starch and sucrose metabolism as well as plant–pathogen interaction. Overall, these results not only provide the coordinated regulatory function of FaAKR23 on AsA and anthocyanin accumulation but also offer a promising candidate gene for strawberry breeding with high antioxidants. [ABSTRACT FROM AUTHOR]

Main conclusion: A novel gene belonging to the aldo–keto reductase 13 family is involved in isoliquiritigenin biosynthesis in dahlia. The yellow pigments of dahlia flowers are derived from 6′-deoxychalcones, which are synthesized via a two-step process, involving the conversion of 3-malonyl-CoA and 4-coumaloyl-CoA into isoliquiritigenin in the first step, and the subsequent generation of butein from isoliquiritigenin. The first step reaction is catalyzed by chalcone synthase (CHS) and aldo–keto reductase (AKR). AKR has been implicated in the isoflavone biosynthesis in legumes, however, isolation of butein biosynthesis related AKR members are yet to be reported. A comparative RNA-seq analysis between two dahlia cultivars, 'Shukuhai' and its butein-deficient lateral mutant 'Rinka', was used in this study to identify a novel AKR gene involved in 6'-deoxychalcone biosynthesis. DvAKR1 encoded a AKR 13 sub-family protein with significant differential expression levels, and was phylogenetically distinct from the chalcone reductases, which belongs to the AKR 4A sub-family in legumes. DNA sequence variation and expression profiles of DvAKR1 gene were correlated with 6′-deoxychalcone accumulation in the tested dahlia cultivars. A single over-expression analysis of DvAKR1 was not sufficient to initiate the accumulation of isoliquiritigenin in tobacco, in contrast, its co-overexpression with a chalcone 4′-O-glucosyltransferase (Am4′CGT) from Antirrhinum majus and a MYB transcription factor, CaMYBA from Capsicum annuum successfully induced isoliquiritigenin accumulation. In addition, DvAKR1 homologous gene expression was detected in Coreopsideae species accumulating 6′-deoxychalcone, but not in Asteraceae species lacking 6′-deoxychalcone production. These results not only demonstrate the involvement of DvAKR1 in the biosynthesis of 6'-deoxychalcone in dahlia, but also show that 6′-deoxychalcone occurrence in Coreopsideae species developed evolutionarily independent from legume species. [ABSTRACT FROM AUTHOR]

Auroral kilometric radiation (AKR) is generated at high latitudes and can propagate down to low latitudes. Due to the lack of direct observations, the characteristics of AKR in the middle and low latitudes of two hemispheres have not been studied so far. Here, using observations of the Arase satellite from 23 March 2017 to 31 July 2019, we present the first statistical study of AKR distribution in the northern (Magnetic latitude Mlat = 0°–40°) and southern (Mlat = −40°–0°) hemispheres. Results (totally 30,353 samples) show that relatively high occurrence rates (>30%) of AKR in the northern (southern) hemisphere primarily stay in the region of magnetic local time MLT = 17–24 (MLT = 21–05). About 60% of wave samples in the northern (southern) hemisphere are observed in the frequency range of ≤300 kHz (>300 kHz). The asymmetric distribution in two hemispheres can further enrich our understanding of AKR. Plain Language Summary: Auroral kilometric radiation (AKR) is a strong radio emission with kilometric wavelength at the Earth. They have a potential for accelerating electrons to relativistic energies or scattering electrons into the atmosphere, leading to serious damage to spacecrafts or ozone destruction. Because the parallel electric field contributing to AKR generation should be different in the northern and southern hemispheres, it is necessary to study the distribution characteristics of AKR in two hemispheres. Here, we examine the data of Arase satellite from 23 March 2017 to 31 July 2019, and find that the distributions of AKR samples in two hemispheres are asymmetric. The occurrence rate in the southern hemisphere is greater than that in the northern hemisphere. More AKR samples in the northern (southern) hemisphere occur from dusk to midnight (pre‐midnight to dawn). More AKR samples in the northern (southern) hemisphere are observed in the frequency range of ≤300 kHz (>300 kHz). This study provides more information about AKR in the magnetosphere. Key Points: The distribution characteristics of Auroral kilometric radiation (AKR) in two hemispheres are presented for the first time based on observations from Arase satelliteAKR samples in the northern (southern) hemisphere are observed relatively frequently in the region of magnetic local time = 17–24 (MLT = 21–05)More AKR samples in the northern (southern) hemisphere stay in the low (high) frequency range [ABSTRACT FROM AUTHOR]

Ascorbic acid (AsA) is an important antioxidant for scavenging reactive oxygen species and it is essential for human health. Strawberry (Fragaria ) ananassa) fruits are rich in AsA. In recent years, strawberry has been regarded as a model for non-climacteric fruit ripening. However, in contrast to climacteric fruits, such as tomato, the regulatory mechanism of AsA accumulation in strawberry fruits remains largely unknown. In this study, we first identified 125 AsA metabolism-related genes from the cultivated strawberry “Camarosa” genome. The expression pattern analysis using an available RNA-seq data showed that the AsA biosynthetic-related genes in the D-mannose/Lgalactose pathway were downregulated remarkably during fruit ripening which was opposite to the increasing AsA content in fruits. The D-galacturonate reductase gene (GalUR) in the D-Galacturonic acid pathway was extremely upregulated in strawberry receptacles during fruit ripening. The FaGalUR gene above belongs to the aldo-keto reductases (AKR) superfamily and has been proposed to participate in AsA biosynthesis in strawberry fruits. To explore whether there are other genes in the AKR superfamily involved in regulating AsA accumulation during strawberry fruit ripening, we further implemented a genome-wide analysis of the AKR superfamily using the octoploid strawberry genome. A total of 80 FaAKR genes were identified from the genome and divided into 20 subgroups based on phylogenetic analysis. These FaAKR genes were unevenly distributed on 23 chromosomes. Among them, nine genes showed increased expression in receptacles as the fruit ripened, and notably, FaAKR23 was the most dramatically upregulated FaAKR gene in receptacles. Compared with fruits at green stage, its expression level increased by 142-fold at red stage. The qRT-PCR results supported that the expression of FaAKR23 was increased significantly during fruit ripening. In particular, the FaAKR23 was the only FaAKR gene that was significantly upregulated by abscisic acid (ABA) and suppressed by nordihydroguaiaretic acid (NDGA, an ABA biosynthesis blocker), indicating FaAKR23 might play important roles in ABA-mediated strawberry fruit ripening. In a word, our study provides useful information on the AsA metabolism during strawberry fruit ripening and will help understand the mechanism of AsA accumulation in strawberry fruits [ABSTRACT FROM AUTHOR]

Normally, auroral kilometric radiation (AKR) which is emitted in the auroral zones escapes from the Earth. But since a few decades very similar radiations are observed by ground‐based receivers and by satellites at altitudes below the AKR generation area. They are called leaked AKR or AKR‐like emissions because it is expected that there are linked to AKR. This paper deals with observations of such AKR‐like emissions observed in the auroral zones (in the North and in the South) by the low‐altitude satellite DEMETER. In total, 2,526 events have been recorded during 6.5 years. These events are not very rare as they occur at least 2% of the time. Although this data set has a severe flaw due to a latitudinal constraint, it was possible to draw interesting properties of these emissions. In fact they are very similar to usual AKR observed at much higher altitudes during auroral activities (the same frequency range, magnetic local time (MLT) sector, and invariant latitude). The main difference concerns a strong asymmetry between the Northern and the Southern hemispheres: (a) the number of AKR‐like emissions in the Northern hemisphere is 32% larger than in the Southern hemisphere but this percentage decreases when the auroral activity increases, and (b) there is an important seasonal effect because the number of events decreases during the winter season both in the North and in the South. Plain Language Summary: Auroral kilometric radiation (AKR) is the strongest terrestrial radio emission generated between 30 and 800 kHz along the auroral field lines and associated with a discrete auroral arc. This emission is generated by superthermal electrons (several keV) which are injected from the magnetotail when the solar activity increases. Typical location of the source is ∼22 hr of magnetic local time (MLT), ∼70° of invariant latitude, and (2–10)103 km of altitude. AKR propagates from the Earth and should not be able to reach low altitudes because of the ionospheric frequency cutoff. But a few decades ago, AKR‐like emissions have been recorded by low orbiting satellites and even by ground‐based receivers. It was explained by a mode conversion of the wave propagating in inhomogeneous plasma. Up to now, only studies of some AKR‐like events have been reported, and this paper presents the statistical properties of such emissions recorded by the low altitude satellite DEMETER during 6.5 years. AKR‐like emissions display similar characteristics of AKR in terms of frequency, MLT, and invariant latitude. It is shown that more events are observed in the North than in the South, and that there is a seasonal effect (the number of events decreases in winter hemispheres). Key Points: Numerous auroral kilometric radiation‐like events have been recorded by the low‐altitude satellite DEMETER during moderate and high magnetic activityThere are more events in the Northern than in the Southern hemisphere but this difference decreases when the auroral activity increasesThe number of events decreases in winter in each hemisphere [ABSTRACT FROM AUTHOR]

Ascorbic acid (AsA) is an important antioxidant for scavenging reactive oxygen species and it is essential for human health. Strawberry (Fragaria × ananassa) fruits are rich in AsA. In recent years, strawberry has been regarded as a model for non-climacteric fruit ripening. However, in contrast to climacteric fruits, such as tomato, the regulatory mechanism of AsA accumulation in strawberry fruits remains largely unknown. In this study, we first identified 125 AsA metabolism-related genes from the cultivated strawberry “Camarosa” genome. The expression pattern analysis using an available RNA-seq data showed that the AsA biosynthetic-related genes in the D-mannose/L-galactose pathway were downregulated remarkably during fruit ripening which was opposite to the increasing AsA content in fruits. The D-galacturonate reductase gene (GalUR) in the D-Galacturonic acid pathway was extremely upregulated in strawberry receptacles during fruit ripening. The FaGalUR gene above belongs to the aldo-keto reductases (AKR) superfamily and has been proposed to participate in AsA biosynthesis in strawberry fruits. To explore whether there are other genes in the AKR superfamily involved in regulating AsA accumulation during strawberry fruit ripening, we further implemented a genome-wide analysis of the AKR superfamily using the octoploid strawberry genome. A total of 80 FaAKR genes were identified from the genome and divided into 20 subgroups based on phylogenetic analysis. These FaAKR genes were unevenly distributed on 23 chromosomes. Among them, nine genes showed increased expression in receptacles as the fruit ripened, and notably, FaAKR23 was the most dramatically upregulated FaAKR gene in receptacles. Compared with fruits at green stage, its expression level increased by 142-fold at red stage. The qRT-PCR results supported that the expression of FaAKR23 was increased significantly during fruit ripening. In particular, the FaAKR23 was the only FaAKR gene that was significantly upregulated by abscisic acid (ABA) and suppressed by nordihydroguaiaretic acid (NDGA, an ABA biosynthesis blocker), indicating FaAKR23 might play important roles in ABA-mediated strawberry fruit ripening. In a word, our study provides useful information on the AsA metabolism during strawberry fruit ripening and will help understand the mechanism of AsA accumulation in strawberry fruits.

Aldo-keto reductases (AKRs), a superfamily of NADP(H)-dependent oxidoreductases, catalyze the oxidoreduction of a wide variety of eobiotic and xenobiotic aldehydes and ketones. In mammals, AKRs play essential roles in hormone and xenobiotic metabolism, oxidative stress, and drug resistance, but little is known about these enzymes in the parasitic nematode Haemonchus contortus. In the present study, 22 AKR genes existing in the H. contortus genome were investigated and a phylogenetic analysis with comparison to AKRs in Caenorhabditis elegans , sheep and humans was conducted. The constitutive transcription levels of all AKRs were measured in eggs, larvae, and adults of H. contortus , and their expression was compared in a drug-sensitive strain (ISE) and a benzimidazole-resistant strain (IRE) previously derived from the sensitive strain by imposing benzimidazole selection pressure. In addition, the inducibility of AKRs by exposure of H. contortus adults to benzimidazole anthelmintic flubendazole in vitro was tested. Phylogenetic analysis demonstrated that the majority of AKR genes in H. contortus lack orthologues in the sheep genome, which is a favorable finding for considering AKRs as potential drug targets. Large differences in the expression levels of individual AKRs were observed, with AKR1, AKR3, AKR8, and AKR10 being the most highly expressed at most developmental stages. Significant changes in the expression of AKRs during the life cycle and pronounced sex differences were found. Comparing the IRE and ISE strains, three AKRs were upregulated, and seven AKRs were downregulated in adults. In addition, the expression of three AKRs was induced by flubendazole exposure in adults of the ISE strain. Based on these results, AKR1, AKR2, AKR3, AKR5, AKR10 and AKR19 in particular merit further investigation and functional characterization with respect to their potential involvement in drug biotransformation and anthelmintic resistance in H. contortus. [Display omitted] [ABSTRACT FROM AUTHOR]

Strawberry (Fragaria × ananassa) fruits are rich in ascorbic acid (AsA) and anthocyanin, which are essential antioxidants for human health. However, the underlying regulatory mechanism of these antioxidant accumulation, especially AsA accumulation in strawberry fruits, remains largely unknown. In this study, we identified FaAKR23 was a regulator of AsA and anthocyanin accumulation. We transiently expressed FaAKR23 in strawberry fruits and conducted metabolic and molecular analyses to explore the role of FaAKR23 in AsA and anthocyanin accumulation. Transient silencing of FaAKR23 (FaAKR23-RNAi) in strawberry fruits significantly decreased the AsA and anthocyanin contents compared with control (empty vector-RNAi, EV-RNAi). Correspondingly, expression of some structural genes and regulatory factors involved in these two antioxidants’ accumulation was dramatically repressed. In addition, transcriptome analysis of EV-RNAi and FaAKR23-RNAi fruits suggested that FaAKR23 was also involved in starch and sucrose metabolism as well as plant–pathogen interaction. Overall, these results not only provide the coordinated regulatory function of FaAKR23 on AsA and anthocyanin accumulation but also offer a promising candidate gene for strawberry breeding with high antioxidants.

Auroral kilometric radiations (AKR) are strong radio emission phenomena, and can produce significant acceleration or scattering of radiation belt electrons. The variation of AKR wave amplitude with the latitude (λ) has not been reported so far owing to lack of measurements. Here, using observations of the Arase satellite and Van Allen Probes from March 23, 2017 to July 31, 2019, we present the first statistical study on the AKR electric field amplitude (Et) in the radiation belts for |λ| = 0° − 40° and L‐shell L = 3.0–6.2. Results (totally 14,770 samples) show that Et can be described by a concise formula: Et(λ) = E0 exp(ξ sin |λ|), decreasing with decreasing latitude. Fitting parameters E0 and ξ are limited in the ranges: E0 = 0.054–0.340 mV/m and ξ = 3.0–4.2. Wave amplitudes are greater (smaller) under intense (weak) geomagnetic conditions. This study helps to better quantify the gyroresonance between AKR and radiation belt electrons. Plain Language Summary: Auroral kilometric radiation (AKR) is a strong radio emission phenomenon which is generated in the low density polar cavity. They can propagate downward into radiation belts and produce significant acceleration or pitch angle scattering of energetic electrons. Those electrons can yield serious damage to spacecraft or ozone destruction. Because wave‐particle interaction generally occurs at each point along the field line and diffusion coefficients are directly proportional to the square of wave amplitude, it is necessary to specify the field‐aligned wave amplitude. However, previous calculations of AKR‐electron interaction were based on the assumption of the constant field‐aligned wave amplitude. Here, using observations of the Arase satellite and Van Allen Probes from March 23, 2017 to July 31, 2019, we report a field‐aligned distribution of AKR wave amplitude for the first time. Gaussian fitting for the electric field power spectral density is performed to obtain the wave amplitude of each AKR sample. We calculate averaged wave amplitudes of total 14,770 samples on the dayside and nightside. Results show that wave amplitude can be described by a concise formula, decreasing obviously with decreasing latitude. Wave amplitudes are greater (smaller) under intense (weak) geomagnetic condition. This paper provides the further understanding of AKR‐electron interaction. Key Points: The field‐aligned distribution of AKR wave amplitude is presented for the first time based on Arase satellite and Van Allen ProbesWave amplitudes can be approximately described by a concise exponential formula and decrease obviously with decreasing latitudeThe AKR sample and amplitude are roughly symmetric around the equator, wave amplitudes increase with increasing geomagnetic activities [ABSTRACT FROM AUTHOR]

Influence of cyclic compressive loading induced degradation of road pavement concrete on harmful AAR In recent years the German motorway network has seen an increase in the occurrence of damage to concrete road surfaces built before 2005, which can be attributed to the alkali‐silica reaction (ASR). In addition to exposure to ASR‐stimulating alkali‐rich deicing‐agents, road surfaces are also subjected to cyclical mechanical loading resulting from traffic and induced stresses due to climatic impact. Such mechanical loadings are not considered in any of the previously developed ASR testing procedures. This cyclical loading could, however, lead to a degradation of the concrete microstructure and, in turn, stimulate the ASR‐process. This article presents investigations that contribute to answering the question of whether a mechanically induced degradation influences the ASR‐process. The hypothesis that the mechanically induced degradation leads to an increase in mass transport is examined. The mass transport is important for the ASR process because the reactants need to be transported to the reaction location before the reaction can take place. Therefore, it is assumed that increased mass transport also leads to increased ASR damage. Concrete specimens made of typical pavement concretes are subjected to a pre‐damaging cyclic compressive loading. The degradation is characterized simultaneously during the pre‐damaging process using non‐destructive testing (NDT) techniques. Then the effects of the cyclical pre‐damage on the mass transport as well as on the ASR are determined by comparing results from test specimens with and without pre‐damage. The results lead to the conclusion that the cyclical pre‐damage increases both the mass transport and the ASR. [ABSTRACT FROM AUTHOR]

Human skin melanoma is one of the most aggressive and difficult to treat human malignancies, with an increasing incidence over the years. While the resection of the early diagnosed primary tumor remains the best clinical approach, advanced/metastatic melanoma still remains with a poor prognosis. Indeed, although enormous progress in the therapeutic treatment of human tumors has been made in recent years, patients affected by metastatic melanoma are still poorly affected by these clinical advances. Therefore, new valuable therapeutic approaches are urgently needed, to design and define effective treatments to consistently increase the overall survival rate of patients affected by this malignancy. In this review we summarize the main signaling pathways studied to kill human skin melanoma, and introduce the ferroptotic cell death as a new pathway to be explored to eradicate this tumor. [ABSTRACT FROM AUTHOR]

Auroral kilometric radiations (AKR) are widely existing superluminous waves in the magnetosphere. Due to rarely available measurements of AKR magnetic field components, we derive the explicit expression of diffusion coefficients in terms of electric field components, which can be applied to various space plasma waves. Using Van Allen Probes data, we calculate diffusion coefficients with different harmonic orders for two AKR events. It is found that the first (higher) harmonic order contributes to diffusion coefficients at small (larger) pitch angles. The effect of higher harmonic orders becomes more significant as the electron energy increases. These results are contrary to the case of chorus wave, in which the first order usually contributes much to wave‐particle interactions. Estimations show that the phase space density of 0.5 MeV electrons can increase ∼10 times within 6 hr by AKR. This study is important for better modeling of AKR‐induced radiation belt electron dynamics. Key Points: The expressions of diffusion coefficients in terms of the electric field component are derived for the first timeThe bounce‐averaged diffusion rates are calculated using realistic wave data from Van Allen ProbesThe higher (lower) harmonic orders play dominant roles in diffusion rates at higher (lower) pitch angles [ABSTRACT FROM AUTHOR]

Following oral administration, the bioavailability of progesterone is low and highly variable. As a result, no clinically relevant, natural progesterone oral formulation is available. After oral delivery, first-pass metabolism initially occurs in the intestines; however, very little information on progesterone metabolism in this organ currently exists. The aim of this study is to investigate the contributions of liver and intestine to progesterone clearance. In the presence of NADPH, a rapid clearance of progesterone was observed in human and rat liver samples (t1/2 2.7 and 2.72 min, respectively). The rate of progesterone depletion in intestine was statistically similar between rat and human (t1/2 197.6 min in rat and 157.2 min in human). However, in the absence of NADPH, progesterone was depleted at a significantly lower rate in rat intestine compared to human. The roles of aldo keto reductases (AKR), xanthine oxidase (XAO) and aldehyde oxidase (AOX) in progesterone metabolism were also investigated. The rate of progesterone depletion was found to be significantly reduced by AKR1C, 1D1 and 1B1 in human liver and by AKR1B1 in human intestine. The inhibition of AOX also caused a significant reduction in progesterone degradation in human liver, whereas no change was observed in the presence of an XAO inhibitor. Understanding the kinetics of intestinal as well as liver metabolism is important for the future development of progesterone oral formulations. This novel information can inform decisions on the development of targeted formulations and help predict dosage regimens.

Methods for evaluating concrete pavements for a damaging alkali‐silica reaction It is very difficult to plan the maintenance requirements of concrete pavements with alkali‐silica reaction. Up to now, the necessary assessment has been carried out via visual appearance, AKR‐provoking concrete investigations as well as polarization microscopic investigations on thin sections. With these investigations a forecast for the damage development is not possible. It is only possible to assess whether damage is no longer to be expected or whether there is still further potential for residual damage. The often significant deterioration of concrete pavement can be traced back to an undetected horizontal crack formation. In the context of an alkali‐silica reaction (ASR), horizontal cracks can be found in the area of the joint crosses, the transverse joints and the longitudinal joints, which then extend several centimeters into the carriageway slab. The article illustrates the consequences of a damaging ASR and other loads in a carriageway slab. For the first time, it establishes a systematic relationship between a damaging ASR in a carriageway slab and the horizontal cracks in the area of the joints. [ABSTRACT FROM AUTHOR]

Automated ASR Concrete Prism Testing at 60 °C The Concrete Prism Test at 60 °C (60 °C‐CPT) is a common method to evaluate the susceptibility of concrete and aggregates to the Alkali‐Silica Reaction (ASR). This paper presents a new device for an automated version of the 60 °C‐CPT. The system monitors the expansion of concrete prisms automatically. Compared to the conventional test method, effort and time consumption are notably reduced. The nearly continuous recording of expansion signals allows for studying of ASR‐mechanisms in more detail than the conventional test. In addition, the interruptions of ASR‐provoking storage, necessary for manual measurements, are avoided. The presented study compares results of conventional and automated testing of two types of aggregate. In accordance with previous findings, continuously stored prisms generally expand less than the conventionally tested prisms. To find a possible explanation, differences in leaching of alkali from the concrete prisms were quantified. For verifying the alkali‐reactivity of the two aggregates, they were also classified in the fog chamber test at 40 °C, the German reference method. [ABSTRACT FROM AUTHOR]

Creep and mechanical properties of pavement concretes after ASR‐provocative storage Four pavement concretes were subjected to ASR‐provoking storage with the FIB climate simulation concrete prism test which has been developed on F.A. Finger‐Institute for Building Materials Science of Bauhaus University Weimar. Strains, compressive strength, elastic modulus, creep and shrinkage have been determined. The results show, that the ASR‐induced damage process can be described as follows: ASR‐induced micro‐cracking in the cement matrix is rather negligible for compressive strength of concrete. Dissolution processes and cracking in the aggregate reduce the stiffness of the concrete (modulus of elasticity), but not the compressive strength of concrete. The cracks that originate in the rock grain of slow‐reacting aggregates continue into the matrix. With a larger matrix volume and thus increased crack formation, creep is increased. Undamaged concrete shows marginally larger creep under the influence of salt solution (NaCl solution). This indicates a chemical influence of the matrix. [ABSTRACT FROM AUTHOR]

Highlights • A monoclonal antibody for AKR1C3, 10B10, was developed and characterized. • 10B10 was compared to the commonly used AKR1C3 antibodies. • 10B10 is highly specific and sensitive to AKR1C3 in multiple assay formats. • 10B10 will be a valuable tool in clinic for AKR1C3 precision therapy. Abstract Human aldo-keto reductase AKR1C3 (type 2 3α-hydroxysteroid dehydrogenase/type 5 17β-hydroxysteroid dehydrogenase) is involved in testosterone and estrogen metabolism. AKR1C3 expression is relatively low in most tissues and high in prostate and mammary glands in regulating androgen and estrogen levels. However, in many cancers, overexpression of AKR1C3 was observed, thus prompting the development of therapeutics targeting AKR1C3. To facilitate the development of AKR1C3 targeting therapeutics, evaluating the expression of AKR1C3 is vital. As AKR1C3 is highly homologous with its family proteins, AKR1C1, AKR1C2, AKR1C4 and other AKR1 proteins, reagents that can unambiguously discriminate these enzymes are needed. In this report, a highly specific monoclonal antibody for AKR1C3, 10B10, was developed and characterized. Compared to other AKR1C3 antibodies, 10B10 is highly specific and sensitive to AKR1C3 in multiple assay formats. Thus, 10B10 will be a valuable tool for the clinical development of AKR1C3 targeting therapeutics and the study of AKR1C3 biology. [ABSTRACT FROM AUTHOR]

Tiaprofenic acid is a widely used anti-inflammatory drug; however, the reductive metabolism of tiaprofenic acid is not yet well understood. Here, we compared the reduction of tiaprofenic acid in microsomes and cytosol from the human liver. The microsomes exhibited lower K m value toward tiaprofenic acid than the cytosol (K m = 164 ± 18 μM vs. 569 ± 74 μM, respectively), whereas the cytosol showed higher specific activity during reduction than the microsomes (V max = 728 ± 52 pmol mg of protein −1 min −1 vs. 285 ± 11 pmol mg of protein −1 min −1 , respectively). Next, a panel of recombinant carbonyl reducing enzymes from AKR and SDR superfamilies has been studied to find the enzymes responsible for the cytosolic reduction of tiaprofenic acid. CBR1 was identified as the reductase of tiaprofenic acid with high specific activity (56,965 ± 6741 pmol mg of protein −1 min −1 ). Three other enzymes, AKR1A1, AKR1B10, and AKR1C4, were also able to reduce tiaprofenic acid, but with very low activity. Thus, CBR1 was shown to be a tiaprofenic acid reductase in vitro and was also suggested to be the principal tiaprofenic acid reductase in vivo . [ABSTRACT FROM AUTHOR]

Contamination of water and soil with Pharmaceutical and Personal Care Products (PPCP); although present at very lower concentrations, has raised alarming issues regarding their toxicity to ecosystem. Their mitigation through biological and chemical treatments have been a area of great interest in recent past. One such attempt is made wherein degradation of doxorubicin (DOX); a well known anticancer agent, is explored with Fe-Ni bimetallic nanoparticles (Fe-Ni NP’s). These nanoparticles degrade DOX through chemisorptive exothermic pseudo-multilayer film-diffusion mineralisation process as evident from adsorption and intra-particle mechanisms. The degradation mechanism is established from metabolites formed during its degradation by LC–MS analysis. It is observed that chemical degradation route closely resembles with that of metabolic pathway mediated by aldo-keto reductase (AKR); a family of oxido-reductase enzyme involving ROS and iron-sulphur clusters. The toxicity of degraded DOX solution evaluated against two breast cancer cell lines viz . MCF-7 and MDA-MB-231 and a normal cell line HEK-293 revealed that the metabolites are non-toxic in nature. These findings are further corroborated with chemo-informatics studies using Molinspiration Properties Calculator. Formation of oxide layer on the nanoparticle surface evident from XPS analysis that decreases their recycling capacity. Thus, Fe-Ni NP’s are exhibiting properties like a functional mimic of AKR that degrade DOX in an eco-friendly manner. [ABSTRACT FROM AUTHOR]

Durable concrete pavements using different binders in top and bottom lift It is a matter of common knowledge that ground granulated blast furnace slag and siliceous fly ash can be used to mitigate alkali-silica-reaction (ASR) in concrete. Nonetheless such materials are seldom used for the construction of concrete pavements in Germany, as their application can impair the deicer-scaling resistance of the concrete. In two-lift concrete pavements a possible approach to avoid this problem is to use cements with a higher proportion of blast furnace slag only in the thick bottom lift, thus minimizing its susceptibility to ASR. The thin top lift, which is subjected to a high level of mechanical and freeze-thaw stress, is still produced with Ordinary Portland Cement, hence ensuring a sufficient deicer-scaling resistance. However, this approach is currently hindered by the German technical standards for concrete pavements, which require the use of the same cement in the top and bottom lift. Furthermore the standards do not permit the application of siliceous fly ash to partly substitute cement in concrete pavements. It was therefore the aim of a research project to obtain the necessary knowledge for assessing potential benefits and risks of a more flexible use of binders in concrete pavements. [ABSTRACT FROM AUTHOR]

Cytotoxic compounds like reactive carbonyl compounds such as methylglyoxal (MG), melandialdehyde (MDA), besides the ROS accumulate significantly at higher levels under salinity stress conditions and affect lipids and proteins that inhibit plant growth and productivity. The detoxification of these cytotoxic compounds by overexpression of NADPH-dependent Aldo-ketoreductase (AKR1) enzyme enhances the salinity stress tolerance in tobacco. The PsAKR1 overexpression plants showed higher survival and chlorophyll content and reduced MDA, H2O2, and MG levels under NaCl stress. The transgenic plants showed reduced levels of Na + levels in both root and shoot due to reduced reactive carbonyl compounds (RCCs) and showed enhanced membrane stability resulted in higher root growth and biomass. The increased levels of antioxidant glutathione and enhanced activity of superoxide dismutase (SOD), ascorbate peroxidase (APX) and glutathione reductase (GR) suggest AKR1 could protect these enzymes from the RCC induced protein carbonylation by detoxification process. The transgenics also showed higher activity of delta 1-pyrroline-5- carboxylate synthase (P5CS) enzyme resulted in increasedproline levels to maintain osmotic homeostasis. The results demonstrates that the AKR1 protects proteins or enzymes that are involved in scavenging of cytotoxic compounds by detoxifying RCCs generated under salinity stress. [ABSTRACT FROM AUTHOR]

Fenofibric acid is a hypolipidemic drug that is used as an active ingredient per se or is administered in the form of fenofibrate that releases fenofibric acid after absorption. The metabolism of fenofibric acid is mediated primarily by glucuronidation. However, the other part of fenofibric acid is excreted as reduced fenofibric acid. Enzymes responsible for the formation of reduced fenofibric acid as well as their subcellular localization have remained unknown until now. We have found that the predominant site of fenofibric acid reduction is the human liver cytosol, whereas liver microsomes reduced fenofibric acid to a lower extent and exhibited a lower affinity for this drug (K m > 1000 μM). Of nine carbonyl-reducing enzymes (CREs) tested, CBR1 exhibited the greatest activity for fenofibric acid reduction (CL int = 85.975 μl/mg protein/min). CBR1 predominantly formed (−)-enantiomers of reduced fenofibric acid similar to liver cytosol and in accordance with the in vivo data. AKR1C1, AKR1C2, AKR1C3 and AKR1B1 were also identified as reductases of fenofibric acid but are expected to play only a minor role in fenofibric acid metabolism. [ABSTRACT FROM AUTHOR]

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Im Rahmen des Bewerbungsverfahrens der Materialprüfungsanstalt Universität Stuttgart (MPA Universität Stuttgart) als zugelassener AKR‐Gutachter nach ARS 04/2013 [1] wurde ein breit angelegtes Untersuchungsprogramm an der MPA in Stuttgart und am Finger‐Institut (FIB) in Weimar durchgeführt. Im ersten Teil war es zunächst anhand von Vergleichsversuchen zu beurteilen, ob bei dem an der MPA Universität Stuttgart vorgesehenen Einsatz der FIB‐Klimawechsellagerung als AKR‐Performance‐Prüfung gleichlautende Aussagen bei der Beurteilung des AKR‐Schädigungspotenzials von Betonzusammensetzungen erreicht werden wie bei einer analogen Prüfung der Betonzusammensetzungen am FIB in Weimar. Dazu wurden Vergleichsversuche an insgesamt vier Betonzusammensetzungen sowohl unter Einwirkung von NaCl‐Lösung als auch unter Einwirkung von Wasser durchgeführt. Im zweiten Teil sollte an allen vier Betonzusammensetzungen die zeitliche Entwicklung der Festigkeits‐ und Verformungseigenschaften charakterisiert werden, um daraus Bewertungskriterien für AKR‐Performance‐Prüfungen ableiten zu können. Strength and deformation properties of concrete as evaluation criteria for ASR performance tests Within the scope of the application procedure of the Materials Testing Institute University of Stuttgart (MPA University Stuttgart) as approved ASR consultant according to ARS 04/2013 [1] a comprehensive program of examinations was conducted at the MPA in Stuttgart and the Finger‐Institute (FIB) in Weimar. The first part of the examinations was about to evaluate whether the ASR potential of concrete compositions is evaluated consistently at the MPA University Stuttgart and the FIB in Weimar by using the FIB cyclic climate storage test method as ASR performance test. For that purpose, a round‐robin test with four different concrete compositions tested under exposure of water and NaCl solution respectively was done. The second part of the examinations was about to characterize the temporal development of the strength and deformation properties of the tested concretes to derive additional evaluation criteria for ASR performance tests. [ABSTRACT FROM AUTHOR]

Die Laser induzierte Breakdown Spektroskopie (LIBS) bietet für die Analyse heterogener, mineralischer Baustoffe, wie z. B. Beton, deutliche Vorteile gegenüber konventionellen Methoden. Sie ermöglicht neben der Quantifizierung von Elementgehalten und ‐verteilungen im Baustoff auch die Differenzierung von Elementkonzentrationen innerhalb einzelner Phasen im Baustoff. So können beispielsweise die für die Alkali‐Kieselsäure‐Reaktion (AKR) interessanten Natriumkonzentrationen bestimmt und hinsichtlich ihrer Verteilung aufgelöst werden. Es lassen sich Natriumgehalte, welche sich in der Gesteinskörung befinden, separat von denen der Betonmatrix bestimmen. Der vorliegende Artikel befasst sich mit den Vor‐ und Nachteilen von LIBS als alternative Methode für die chemische Analyse von Baustoffen. Anhand von Beispielen aus der Praxis wird der derzeitige Stand der Technik dargestellt und ein Vergleich mit etablierten Messmethoden vorgenommen. Laser Induced Breakdown Spectroscopy (LIBS) in civil engineering – innovative analysis of building materials Compared to conventional methods the Laser Induced Breakdown Spectroscopy (LIBS) provides significant advantages for analysis of heterogeneous, mineral building materials as e.g. concrete. Besides providing the possibility to quantify element concentrations and distributions in building materials, this technique enables also to differentiate concentrations within different phases of the material. It is possible to determine sodium concentrations and distribution directly, which e.g. is important when regarding Alkali‐Silica‐Reaction (ASR). Sodium contents provided by the aggregates can be distinguished from those provided by the concrete matrix. The present article is concerned with the advantages and disadvantages of LIBS as alternative method for chemical analysis of building materials. On the basis of samples from practice the current state of the art is shown and different measurement techniques will be compared. [ABSTRACT FROM AUTHOR]

In Betonbauteilen unter gleichzeitiger zyklischer Beanspruchung und externer Alkalizufuhr ist die Gefahr von Schäden infolge oder unter Mitwirkung einer Alkali‐Kieselsäure‐Reaktion (AKR) besonders hoch. Dies betrifft insbesondere Fahrbahndecken, bedingt durch den zunehmenden Schwerlastverkehr und den winterlichen Auftrag des Enteisungsmittels NaCl. Speziell die Rolle einer mechanischen Vorschädigung des Betons infolge der Verkehrsbeanspruchungen auf den Ablauf einer AKR ist dabei aber noch nicht in ausreichendem Umfang geklärt. Ein Teil der dazu seit 2012 durchgeführten Untersuchungen im Rahmen der DFG‐Forschergruppe 1498 soll im Folgenden vorgestellt werden. Es zeigte sich, dass eine AKR in definiert mechanisch vorgeschädigten Betonprobekörpern mit alkalireaktiven Gesteinskörnungen und unter äußerer Alkalizufuhr vor allem früher beginnt als in äquivalenten Probekörpern ohne Vorschädigung. Grund dafür ist das schnellere und tiefere Eindringen von Wasser und insbesondere gelöstem NaCl in den Beton, wodurch Na‐Ionen als Reaktionspartner für eine AKR früher und langfristig auch in größerer Menge verfügbar sind. Investigations into alkali‐silica reaction in pre‐damaged pavement concretes In concrete elements, simultaneously subjected to cyclic loadings and external alkalis, the risk for damages caused by or under participation of an alkali‐silica reaction (ASR) is particularly high. This concerns especially concrete pavements due to the increasing heavy load traffic and the wintry application of NaCl deicer. Notably the role of a mechanical pre‐damage of concrete caused by traffic loadings on the course of the ASR is largely unclear. A part of the investigations that has been conducted since 2012 into this issue within the scope of the DFG (German research foundation) funded research group 1498 shall be introduced in the following. It was evident that an ASR in defined mechanically pre‐damaged concrete prisms with alkali‐reactive aggregates and under an external supply of alkalis started earlier than in equal prisms without a pre‐damage. The reason for this is the faster and deeper ingress of water and particularly of dissolved NaCl into the concrete, by what Na ions as reaction partner for an ASR are available earlier and, in the long‐term, in greater amounts too. [ABSTRACT FROM AUTHOR]

Oxcarbazepine, a second generation antiepileptic drug belonging to the family of dibenz[b,f]azepines, is subjected to a rapid and extensive biotransformation. Oxcarbazepine demonstrates a low potential for drug interactions because its biotransformation is mainly mediated by the reduction pathway instead of oxidative pathways, which are very susceptible to drug interactions. The reductive metabolism of oxcarbazepine yields a 10-monohydroxy derivative (10,11-dihydro-10-hydroxy-carbazepine), which is responsible for the pharmacological activity. The identity and localization of enzymes participating in the reduction of oxcarbazepine in response to this active metabolite have remained unknown until now. Thus, we investigated the reductive metabolism of oxcarbazepine in human liver subcellular fractions and using recombinant carbonyl reducing enzymes. The reduction of oxcarbazepine was shown to occur largely in the liver cytosol rather than liver microsomes. Furthermore, the activity and stereospecificity of cytosolic carbonyl reducing enzymes toward oxcarbazepine were assessed. Of the eight tested enzymes, six reductases were identified to contribute to the reduction of oxcarbazepine. The highest activities were demonstrated by AKR1C1, AKR1C2, AKR1C3, and AKR1C4. The contribution of CBR1 and CBR3 to the reduction of oxcarbazepine was also significant, although their role in oxcarbazepine metabolism in vivo is unclear. [ABSTRACT FROM AUTHOR]

Zur Beurteilung der Alkaliempfindlichkeit der Gesteinskörnung finden normativ der Betonversuch mit Nebelkammerlagerung bei 40 °C und alternativ der 60 °C-Betonversuch Anwendung. Als Beurteilungskriterium für den Schädigungsprozess wird bei beiden Verfahren die an Betonprismen diskontinuierlich ermittelte Dehnung herangezogen. Auch bei den zusätzlich in der Nebelkammer gelagerten Würfeln beschränkt sich die Schadensanalyse auf eine diskontinuierliche Verfolgung der maximalen Breite der Oberflächenrisse. Im Rahmen des Beitrags wird eine neuartige, bereits erfolgreich erprobte zerstörungsfreie Prüfmethodik vorgestellt. Diese ermöglicht durch eine gleichzeitige kontinuierliche Dehnungs-, Schallemissions- und Ultraschallmessung eine kontinuierliche Verfolgung der inneren Gefügeveränderungen in den Betonprüfkörpern während der AKR-provozierenden Lagerung. Dabei wurden drei zeitlich aufeinanderfolgende Phasen der inneren Gefügeveränderung mit einer Dominanz von Hydratation, Rissbildung sowie vermutlicher Rissverfüllung mit Reaktionsprodukten identifiziert. Die ablaufenden Rissbildungsprozesse wurden zusätzlich mit diskontinuierlich durchgeführten röntgentomografischen Untersuchungen zeitlich und räumlich visualisiert. Die CT-Befunde wurden durch mikroskopische Untersuchungen bestätigt. Analysis of ASR-induced damage processes in concrete Application of innovative measurement techniques The alkali-reactive potential of aggregates is assessed according to the German guidelines by two different test methods. These are the 40 °C fog chamber storage and as an alternative method the 60 °C concrete prism test. In both tests, the discontinuously measured expansion of ASR-generating stored concrete prisms is used as criterion for the internal damage process. The damage analysis of the cubes additionally stored in the 40 °C fog chamber is also restricted to the discontinuous measurement of the crack width on the cubes surfaces. This paper describes an innovative, already successfully applied, non-destructive measurement methodology. This methodology enables a continuous monitoring of the internal damage processes in ASR-generating stored concrete specimens due to a continuous recording of expansion, acoustic emission and ultrasonic velocity. Thereby, three sequent phases of internal structural changes dominated by hydration, crack formation and filling of the cracks with ASR-gel and/or other reaction products can be detected. The crack formation was temporally and spatially visualised by discontinuously applied X-ray computed tomography measurements. Microscopic analyses confirm the findings of the X-ray 3D-CT. [ABSTRACT FROM AUTHOR]

Abstract: The stereospecific 5β-reduction of Δ4-3-ketosterols is very difficult to achieve chemically and introduces a 90° bend between ring A and B of the planar steroid. In mammals, the reaction is catalyzed by steroid 5β-reductase, a member of the aldo-keto reductase (AKR) family. The human enzyme, AKR1D1, plays an essential role in bile-acid biosynthesis since the 5β-configuration is required for the emulsifying properties of bile. Deficient 5β-reductase activity can lead to cholestasis and neo-natal liver failure and is often lethal if it remains untreated. In five patients with 5β-reductase deficiency, sequencing revealed individual, non-synonymous point mutations in the AKR1D1 gene: L106F, P133R, G223E, P198L and R261C. However, mapping these mutations to the AKR1D1 crystal structure failed to reveal any obvious involvement in substrate or cofactor binding or catalytic mechanism, and it remained unclear whether these mutations could be causal for the observed disease. We analyzed the positions of the reported mutations and found that they reside in highly conserved portions of AKR1D1 and hypothesized that they would likely lead to changes in protein folding, and hence enzyme activity. Attempts to purify the mutant enzymes for further characterization by over-expression in Escherichia coli yielded sufficient amounts of only one mutant (P133R). This enzyme exhibited reduced K m and k cat values with the bile acid intermediate Δ4-cholesten-7α-ol-3-one as substrate reminiscent of uncompetitive inhibition. In addition, P133R displayed no change in cofactor affinity but was more thermolabile as judged by CD-spectroscopy. When all AKR1D1 mutants were expressed in HEK 293 cells, protein expression levels and enzyme activity were dramatically reduced. Furthermore, cycloheximide treatment revealed decreased stability of several of the mutants compared to wild type. Our data show, that all five mutations identified in patients with functional bile acid deficiency strongly affected AKR1D1 enzyme functionality and therefore may be causal for this disease. [Copyright &y& Elsevier]

The aldo-keto reductase (AKR) superfamily comprises enzymes that catalyze redox transformations involved in biosynthesis, intermediary metabolism, and detoxification. Substrates of AKRs include glucose, steroids, glycosylation end-products, lipid peroxidation products, and environmental pollutants. These proteins adopt a (β /α )8 barrel structural motif interrupted by a number of extraneous loops and helixes that vary between proteins and bring structural identity to individual families. The human AKR family differs from the rodent families. Due to their broad substrate specificity, AKRs play an important role in the phase II detoxification of a large number of pharmaceuticals, drugs, and xenobiotics. [ABSTRACT FROM AUTHOR]

The article presents a study on the polymorphism in MRL and AKR mice sex-determining region on Y (Sry) genes. It notes that the sex of a mammal is ascertained when an ovum that contains a haploid genome with an X chromosome fertilized by a sperm that has a haploid genome with an X or Y chromosome. The anatomical determination of sex happens toward the development as gonads initially grow as bipotential primordia with plasticity to evolve into ovaries or testes wherein the Sry expression is needed. The study used several processes including the light microscopic analysis, and genomic DNA extraction. Sry PCR and nucleotide sequencing, and comparison of Sry nucleotide sequences and corresponding amino acids between M+ and B6 are also applied.

NK cell activity is regulated in part by inhibitory receptors that bind to MHC class I molecules. It is possible to enhance NK cell cytotoxicity against tumor cells by preventing the interaction of these inhibitory receptors with their MHC class I ligands. In this study, we determined that Ly49G2 is an inhibitory receptor in AKR mice for self-MHC class I, and AKR Ly49G2 has an identical sequence to BALB/c Ly49G2. Blockade of Ly49G2 receptors in vivo resulted in decreased growth of BW-Sp3 lymphoma cells when the tumor cells were given i.v. but not when the tumor cells were inoculated into the flank forming a solid tumor. However, NK cells were involved in inhibiting the growth of BW-Sp3 tumor cells in the flank. These data demonstrate that the effectiveness of inhibitory receptor blockade depends upon the tissue location of the tumor cells. [ABSTRACT FROM AUTHOR]

The importance of maternal care in shaping an individual’s phenotype in health and disease is becoming more and more apparent in both human and animal studies. However, in mouse studies using inbred strains or knockout mice to analyze the genetic influences on the development of normal and aberrant behavioral phenotypes, maternal behavior is very poorly characterized and often ignored. This study provides an extensive analysis of spontaneous maternal behavior of inbred mice in three conditions: (1) comparing two commonly used strains, (2) analyzing the impact of adopting pups from the same strain (intrastrain cross-fostering) and (3) analyzing the impact of adopting pups from a different strain (interstrain cross-fostering). For each condition, maternal behavior was analyzed continuously over 23-h periods on postnatal days 2, 4, 6 and 9. We report that (1) the maternal behavior of C57BL/6J and DBA/2J dams toward their biological offspring is highly similar, (2) intrastrain cross-fostering has minimal impact on maternal behavior of C57BL/6J and DBA/2J dams, (3) interstrain cross-fostering does not modify the strain differences in maternal care observed between AKR and C3H/He mothers and (4) the pup strain does influence the amount of maternal behavior shown by both mothers in interstrain cross-fostering. These latter findings demonstrate that both mother strain and pup strain are key determinants of maternal behavior. [ABSTRACT FROM AUTHOR]