The severe restrictions on public life in many countries following the spread of the COVID-19 pandemic specifically affected Holocaust memorials and museums in all parts of the world, especially in ...Europe and in Israel. These measures posed a significant challenge, because contemporary forms of Holocaust commemoration are particularly based on the personal experience of presence at museums and historical sites. In contrast to the experience of distancing in face of the COVID-19 pandemic, establishing the presence of the past is thus a crucial element of contemporary Holocaust commemoration. This article explores the relationship between presence and absence, proximity and distance, guided commemoration and online engagement by critically analyzing digital activities of Holocaust memorials and museums in response to the pandemic. It argues that in the wake of the COVID-19 pandemic, Holocaust memorials began experimenting with the potential of social media for Holocaust memory. These experiments finally accepted the ongoing generational change and reacted to significant previous shifts in media consumption that were already affecting Holocaust commemoration.
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The formate dehydrogenase from Rhodobacter capsulatus (RcFDH) is an oxygen‐tolerant protein with an (αβγ)2 subunit composition that is localized in the cytoplasm. It belongs to the group of metal and ...NAD+‐dependent FDHs with the coordination of a molybdenum cofactor, four Fe4S4 clusters and one Fe2S2 cluster associated with the α‐subunit, one Fe4S4 cluster and one FMN bound to the β‐subunit, and one Fe2S2 cluster bound to the γ‐subunit. RcFDH was heterologously expressed in Escherichia coli and characterized. Cofactor analysis showed that the bis‐molybdopterin guanine dinucleotide cofactor is bound to the FdsA subunit containing a cysteine ligand at the active site. A turnover rate of 2189 min−1 with formate as substrate was determined. The back reaction for the reduction of CO2 was catalyzed with a kcat of 89 min−1. The preference for formate oxidation shows an energy barrier for CO2 reduction of the enzyme. Furthermore, the FMN‐containing and Fe4S4‐containing β‐subunit together with the Fe2S2‐containing γ‐subunit forms a diaphorase unit with activities for both NAD+ reduction and NADH oxidation. In addition to the structural genes fdsG, fdsB, and fdsA, the fds operon in R. capsulatus contains the fdsC and fdsD genes. Expression studies showed that RcFDH is only active when both FdsC and FdsD are present. Both proteins are proposed to be involved in bis‐molybdopterin guanine dinucleotide modification and insertion into RcFDH.
The NAD+ dependent formate dehydrogenase from Rhodobacter capsulatus is an oxygen‐tolerant protein with a (αβγ)2 subunit composition. The purified enzyme expressed in Escherichia coli is able to catalyze the reduction of CO2 to formate in the presence of NADH. The FMN and Fe4S4 containing β‐subunit and the Fe2S2 containing γ‐subunit form a diaphorase unit catalyzing the reversible regeneration of NAD+/NADH.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The global carbon cycle depends on the biological transformations of C1 compounds, which include the reductive incorporation of CO2 into organic molecules (e.g. in photosynthesis and other ...autotrophic pathways), in addition to the production of CO2 from formate, a reaction that is catalyzed by formate dehydrogenases (FDHs). FDHs catalyze, in general, the oxidation of formate to CO2 and H+. However, selected enzymes were identified to act as CO2 reductases, which are able to reduce CO2 to formate under physiological conditions. This reaction is of interest for the generation of formate as a convenient storage form of H2 for future applications. Cofactor-containing FDHs are found in anaerobic bacteria and archaea, in addition to facultative anaerobic or aerobic bacteria. These enzymes are highly diverse and employ different cofactors such as the molybdenum cofactor (Moco), FeS clusters and flavins, or cytochromes. Some enzymes include tungsten (W) in place of molybdenum (Mo) at the active site. For catalytic activity, a selenocysteine (SeCys) or cysteine (Cys) ligand at the Mo atom in the active site is essential for the reaction. This review will focus on the characterization of Mo- and W-containing FDHs from bacteria, their active site structure, subunit compositions and its proposed catalytic mechanism. We will give an overview on the different mechanisms of substrate conversion available so far, in addition to providing an outlook on bio-applications of FDHs. This article is part of a Special Issue entitled: Cofactor-dependent proteins: evolution, chemical diversity and bio-applications.
•Cofactor-containing FDHs catalyze the reversible oxidation of formate to CO2 and protons.•An overview on the available data on Mo- and W-containing FDHs is presented.•Different catalytic mechanisms for substrate conversion are compared.•We propose evidence for the presence of a sulfur ligand at the Mo active site.•The mechanism of sulfur insertion by the help of molecular chaperones is discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This work aims to give an overview of wireless communication technologies (WCT) for underground applications. Difficulties regarding the harsh mining environment and operational constraints for WCT ...implementation and use are discussed. Selected technologies are then classified regarding underground mining-specific use cases in advanced mining operations. Use-case-based application categories such as 'automation and teleoperation', 'tracking and tracing' and 'Long-Range Underground Monitoring (LUM)' are defined. The use cases determine requirements for the operational suitability and also quantify evaluation criteria for the evaluation of WCT. The result is a comparison by category of the wireless technologies, which underlines potentials of different technologies for defined use cases, but it can be concluded that the technology always has to be evaluated within the use case and operational constraints.
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The regulation of physiological gut functions such as peristalsis or secretion of digestive enzymes by the central nervous system via the Nervus vagus is well known. Recent investigations highlight ...that pathological conditions of neurological or psychiatric disorders might directly interfere with the autonomous neuronal network of the gut - the enteric nervous system, or even derive from there. By using a murine Alzheimer's disease model, we investigated a potential influence of disease-associated changes on gastrointestinal properties. 5xFAD mice at three different ages were compared to wild type littermates in regard to metabolic parameters and enzymes of the gut by fluorimetric enzyme assay and western blotting. Overexpression of human amyloid-β protein precursor (AβPP) within the gut was assessed by qPCR and IHC; fecal microbiome analysis was conducted by 16SrRNA quantitation of selected phyla and species. While general composition of fecal samples, locomotion, and food consumption of male 5xFAD animals were not changed, we observed a reduced body weight occurring at early pathological stages. Human AβPP was not only expressed within the brain of these mice but also in gut tissue. Analysis of fecal proteins revealed a reduced trypsin amount in the 5xFAD model mice as compared to the wild type. In addition, we observed changes in fecal microbiota composition along with age. We therefore suggest that the presence of the mutated transgenes (AβPP and PS1), which are per se the basis for the genetic form of Alzheimer's disease in humans, directly interferes with gut function as shown here for the disease model mice.
Silicon (Si) is a beneficial element that alleviates the effects of stress factors including drought (D). Strawberry is a Si-accumulator species sensitive to D; however, the function of Si in this ...species is obscure. This study was conducted to examine the effect of Si and inoculation with an arbuscular mycorrhizal fungus (AMF) on physiological and biochemical responses of strawberry plants under D. Plants were grown for six weeks in perlite and irrigated with a nutrient solution. The effect of Si (3 mmol L‒1), AMF (Rhizophagus clarus) and D (mild and severe D) was studied on growth, water relations, mycorrhization, antioxidative defense, osmolytes concentration, and micronutrients status. Si and AMF significantly enhanced plant biomass production by increasing photosynthesis rate, water content and use efficiency, antioxidant enzyme defense, and the nutritional status of particularly Zn. In contrast to the roots, osmotic adjustment did not contribute to the increase of leaf water content suggesting a different strategy of both Si and AMF for improving water status in the leaves and roots. Our results demonstrated a synergistic effect of AMF and Si on improving the growth of strawberry not only under D but also under control conditions.
In the last decade, it has become obvious that Alzheimer's disease (AD) is closely linked to changes in lipids or lipid metabolism. One of the main pathological hallmarks of AD is amyloid-β (Aβ) ...deposition. Aβ is derived from sequential proteolytic processing of the amyloid precursor protein (APP). Interestingly, both, the APP and all APP secretases are transmembrane proteins that cleave APP close to and in the lipid bilayer. Moreover, apoE4 has been identified as the most prevalent genetic risk factor for AD. ApoE is the main lipoprotein in the brain, which has an abundant role in the transport of lipids and brain lipid metabolism. Several lipidomic approaches revealed changes in the lipid levels of cerebrospinal fluid or in post mortem AD brains. Here, we review the impact of apoE and lipids in AD, focusing on the major brain lipid classes, sphingomyelin, plasmalogens, gangliosides, sulfatides, DHA, and EPA, as well as on lipid signaling molecules, like ceramide and sphingosine-1-phosphate. As nutritional approaches showed limited beneficial effects in clinical studies, the opportunities of combining different supplements in multi-nutritional approaches are discussed and summarized.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Metal-containing formate dehydrogenases (FDH) catalyse the reversible oxidation of formate to carbon dioxide at their molybdenum or tungsten active site. They display a diverse subunit and cofactor ...composition, but structural information on these enzymes is limited. Here we report the cryo-electron microscopic structures of the soluble Rhodobacter capsulatus FDH (RcFDH) as isolated and in the presence of reduced nicotinamide adenine dinucleotide (NADH). RcFDH assembles into a 360 kDa dimer of heterotetramers revealing a putative interconnection of electron pathway chains. In the presence of NADH, the RcFDH structure shows charging of cofactors, indicative of an increased electron load.
Macroautophagy/autophagy failure with the accumulation of autophagosomes is an early neuropathological feature of Alzheimer disease (AD) that directly affects amyloid beta (Aβ) metabolism. Although ...loss of presenilin 1 function has been reported to impair lysosomal function and prevent autophagy flux, the detailed mechanism leading to autophagy dysfunction in AD remains to be elucidated. The resemblance between pathological hallmarks of AD and Niemann-Pick Type C disease, including endosome-lysosome abnormalities and impaired autophagy, suggests cholesterol accumulation as a common link. Using a mouse model of AD (APP-PSEN1-SREBF2 mice), expressing chimeric mouse-human amyloid precursor protein with the familial Alzheimer Swedish mutation (APP695swe) and mutant presenilin 1 (PSEN1-dE9), together with a dominant-positive, truncated and active form of SREBF2/SREBP2 (sterol regulatory element binding factor 2), we demonstrated that high brain cholesterol enhanced autophagosome formation, but disrupted its fusion with endosomal-lysosomal vesicles. The combination of these alterations resulted in impaired degradation of Aβ and endogenous MAPT (microtubule associated protein tau), and stimulated autophagy-dependent Aβ secretion. Exacerbated Aβ-induced oxidative stress in APP-PSEN1-SREBF2 mice, due to cholesterol-mediated depletion of mitochondrial glutathione/mGSH, is critical for autophagy induction. In agreement, in vivo mitochondrial GSH recovery with GSH ethyl ester, inhibited autophagosome synthesis by preventing the oxidative inhibition of ATG4B deconjugation activity exerted by Aβ. Moreover, cholesterol-enrichment within the endosomes-lysosomes modified the levels and membrane distribution of RAB7A and SNAP receptors (SNAREs), which affected its fusogenic ability. Accordingly, in vivo treatment with 2-hydroxypropyl-β-cyclodextrin completely rescued these alterations, making it a potential therapeutic tool for AD.
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Gemfibrozil is a drug that has been used for over 40 years to lower triglycerides in blood. As a ligand for peroxisome proliferative-activated receptor-alpha (PPARα), which is expressed in many ...tissues, it induces the transcription of numerous genes for carbohydrate and lipid-metabolism. However, nothing is known about how intracellular lipid-homeostasis and, in particular, triglycerides are affected. As triglycerides are stored in lipid-droplets, which are known to be associated with many diseases, such as Alzheimer's disease, cancer, fatty liver disease and type-2 diabetes, treatment with gemfibrozil could adversely affect these diseases. To address the question whether gemfibrozil also affects intracellular lipid-levels, SH-SY5Y, HEK and Calu-3 cells, representing three different metabolically active organs (brain, lung and kidney), were incubated with gemfibrozil and subsequently analyzed semi-quantitatively by mass-spectrometry. Importantly, all cells showed a strong increase in intracellular triglycerides (SH-SY5Y: 170.3%; HEK: 272.1%; Calu-3: 448.1%), suggesting that the decreased triglyceride-levels might be due to an enhanced cellular uptake. Besides the common intracellular triglyceride increase, a cell-line specific alteration in acylcarnitines are found, suggesting that especially in neuronal cell lines gemfibrozil increases the transport of fatty acids to mitochondria and therefore increases the turnover of fatty acids for the benefit of additional energy supply, which could be important in diseases, such as Alzheimer's disease.
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