Refine
Document Type
- Article (5)
- Postprint (2)
- Part of Periodical (1)
Is part of the Bibliography
- yes (8)
Keywords
- DNA damage (2)
- DNA damage response (2)
- Lu/Hf dating of garnet (2)
- ageing (2)
- base excision repair (incision activity) (2)
- liver (2)
- maintenance of genomic integrity (2)
- poly(ADP-ribosyl)ation (2)
- sex (2)
- Aphasie (1)
The thermal structure of subduction zones exerts a major influence on deep-seated mechanical and chemical processes controlling arc magmatism, seismicity, and global element cycles. Accretionary complexes exposed inland may comprise tectonic blocks with contrasting pressure-temperature (P-T) histories, making it possible to investigate the dynamics and thermal evolution of former subduction interfaces. With this aim, we present new Lu-Hf geochronological results for mafic rocks of the Halilbagi Complex (Anatolia) that evolved along different thermal gradients. Samples include a lawsonite-epidote blueschist, a lawsonite-epidote eclogite, and an epidote eclogite (all with counter-clockwise P-T paths), a prograde lawsonite blueschist with a "hairpin"-type P-T path, and a garnet amphibolite from the overlying sub-ophiolitic metamorphic sole. Equilibrium phase diagrams suggest that the garnet amphibolite formed at similar to 0.6-0.7 GPa and 800-850 degrees C, whereas the prograde lawsonite blueschist records burial from 2.1 GPa and 420 degrees C to 2.6 GPa and 520 degrees C. Well-defined Lu-Hf isochrons were obtained for the epidote eclogite (92.38 +/- 0.22 Ma) and the lawsonite-epidote blueschist (90.19 +/- 0.54 Ma), suggesting rapid garnet growth. The lawsonite-epidote eclogite (87.30 +/- 0.39 Ma) and the prograde lawsonite blueschist (ca. 86 Ma) are younger, whereas the garnet amphibolite (104.5 +/- 3.5 Ma) is older. Our data reveal a consistent trend of progressively decreasing geothermal gradient from granulite-facies conditions at similar to 104 Ma to the epidote-eclogite facies around 92 Ma, and the lawsonite blueschist-facies between 90 Ma and 86 Ma. Three Lu-Hf garnet dates (between 92 Ma and 87 Ma) weighted toward the growth of post-peak rims (as indicated by Lu distribution in garnet) suggest that the HP/LT rocks were exhumed continuously and not episodically. We infer that HP/LT metamorphic rocks within the Halilbagi Complex were subjected to continuous return flow, with "warm" rocks being exhumed during the tectonic burial of "cold" ones. Our results, combined with regional geological constraints, allow us to speculate that subduction started at a transform fault near a mid-oceanic spreading centre. Following its formation, this ancient subduction interface evolved thermally over more than 15 Myr, most likely as a result of heat dissipation rather than crustal underplating. (C) 2018, China University of Geosciences (Beijing) and Peking University. Production and hosting by Elsevier B.V.
Scope: Trace element (TE) deficiencies often occur accumulated, as nutritional intake is inadequate for several TEs, concurrently. Therefore, the impact of a suboptimal supply of iron, zinc, copper, iodine, and selenium on the TE status, health parameters, epigenetics, and genomic stability in mice are studied. Methods and results: Male mice receive reduced or adequate amounts of TEs for 9 weeks. The TE status is analyzed mass‐spectrometrically in serum and different tissues. Furthermore, gene and protein expression of TE biomarkers are assessed with focus on liver. Iron concentrations are most sensitive toward a reduced supply indicated by increased serum transferrin levels and altered hepatic expression of iron‐related genes. Reduced TE supply results in smaller weight gain but higher spleen and heart weights. Additionally, inflammatory mediators in serum and liver are increased together with hepatic genomic instability. However, global DNA (hydroxy)methylation is unaffected by the TE modulation. Conclusion: Despite homeostatic regulation of most TEs in response to a low intake, this condition still has substantial effects on health parameters. It appears that the liver and immune system react particularly sensitive toward changes in TE intake. The reduced Fe status might be the primary driver for the observed effects.
The thermal structure of subduction zones exerts a major influence on deep-seated mechanical and chemical processes controlling arc magmatism, seismicity, and global element cycles. Accretionary complexes exposed inland may comprise tectonic blocks with contrasting pressure-temperature (P-T) histories, making it possible to investigate the dynamics and thermal evolution of former subduction interfaces. With this aim, we present new Lu-Hf geochronological results for mafic rocks of the Halilbagi Complex (Anatolia) that evolved along different thermal gradients. Samples include a lawsonite-epidote blueschist, a lawsonite-epidote eclogite, and an epidote eclogite (all with counter-clockwise P-T paths), a prograde lawsonite blueschist with a "hairpin"-type P-T path, and a garnet amphibolite from the overlying sub-ophiolitic metamorphic sole. Equilibrium phase diagrams suggest that the garnet amphibolite formed at similar to 0.6-0.7 GPa and 800-850 degrees C, whereas the prograde lawsonite blueschist records burial from 2.1 GPa and 420 degrees C to 2.6 GPa and 520 degrees C. Well-defined Lu-Hf isochrons were obtained for the epidote eclogite (92.38 +/- 0.22 Ma) and the lawsonite-epidote blueschist (90.19 +/- 0.54 Ma), suggesting rapid garnet growth. The lawsonite-epidote eclogite (87.30 +/- 0.39 Ma) and the prograde lawsonite blueschist (ca. 86 Ma) are younger, whereas the garnet amphibolite (104.5 +/- 3.5 Ma) is older. Our data reveal a consistent trend of progressively decreasing geothermal gradient from granulite-facies conditions at similar to 104 Ma to the epidote-eclogite facies around 92 Ma, and the lawsonite blueschist-facies between 90 Ma and 86 Ma. Three Lu-Hf garnet dates (between 92 Ma and 87 Ma) weighted toward the growth of post-peak rims (as indicated by Lu distribution in garnet) suggest that the HP/LT rocks were exhumed continuously and not episodically. We infer that HP/LT metamorphic rocks within the Halilbagi Complex were subjected to continuous return flow, with "warm" rocks being exhumed during the tectonic burial of "cold" ones. Our results, combined with regional geological constraints, allow us to speculate that subduction started at a transform fault near a mid-oceanic spreading centre. Following its formation, this ancient subduction interface evolved thermally over more than 15 Myr, most likely as a result of heat dissipation rather than crustal underplating.
Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery.
Mechanistic studies on the adverse effects of manganese overexposure in differentiated LUHMES cells
(2022)
Manganese (Mn) is an essential trace element, but overexposure is associated with toxicity and neurological dysfunction. Accumulation of Mn can be observed in dopamine-rich regions of the brain in vivo and Mn-induced oxidative stress has been discussed extensively. Nevertheless, Mn-induced DNA damage, adverse effects of DNA repair, and possible resulting consequences for the neurite network are not yet characterized. For this, LUHMES cells were used, as they differentiate into dopaminergic-like neurons and form extensive neurite networks. Experiments were conducted to analyze Mn bioavailability and cytotoxicity of MnCl2, indicating a dose-dependent uptake and substantial cytotoxic effects. DNA damage, analyzed by means of 8-oxo-7,8-dihydro-2'-guanine (8oxodG) and single DNA strand break formation, showed significant dose- and time-dependent increase of DNA damage upon 48 h Mn exposure. Furthermore, the DNA damage response was increased which was assessed by analytical quantification of poly(ADP-ribosyl)ation (PARylation). Gene expression of the respective DNA repair genes was not significantly affected. Degradation of the neuronal network is significantly altered by 48 h Mn exposure. Altogether, this study contributes to the characterization of Mn-induced neurotoxicity, by analyzing the adverse effects of Mn on genome integrity in dopaminergic-like neurons and respective outcomes.
A matter of concern
(2021)
Neurons are post-mitotic cells in the brain and their integrity is of central importance to avoid neurodegeneration. Yet, the inability of self-replenishment of post-mitotic cells results in the need to withstand challenges from numerous stressors during life. Neurons are exposed to oxidative stress due to high oxygen consumption during metabolic activity in the brain. Accordingly, DNA damage can occur and accumulate, resulting in genome instability. In this context, imbalances in brain trace element homeostasis are a matter of concern, especially regarding iron, copper, manganese, zinc, and selenium. Although trace elements are essential for brain physiology, excess and deficient conditions are considered to impair neuronal maintenance. Besides increasing oxidative stress, DNA damage response and repair of oxidative DNA damage are affected by trace elements. Hence, a balanced trace element homeostasis is of particular importance to safeguard neuronal genome integrity and prevent neuronal loss. This review summarises the current state of knowledge on the impact of deficient, as well as excessive iron, copper, manganese, zinc, and selenium levels on neuronal genome stability
Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery.
Das 10. Herbsttreffen Patholinguistik mit dem Schwerpunktthema »Panorama Patholinguistik: Sprachwissenschaft trifft Sprachtherapie« fand am 19.11.2016 in Potsdam statt. Das Herbsttreffen wird seit 2007 jährlich vom Verband für Patholinguistik e.V. (vpl) durchgeführt. Der vorliegende Tagungsband beinhaltet die vier Hauptvorträge zum Schwerpunktthema sowie Beiträge zu den Kurzvorträgen »Patholinguistik im Fokus« und der Posterpräsentationen zu weiteren Themen aus der sprachtherapeutischen Forschung und Praxis.