The Immunophilin-Like Protein XAP2 Is a Negative Regulator of Estrogen Signaling through Interaction with Estrogen Receptor α

XAP2 (also known as aryl hydrocarbon receptor interacting protein, AIP) is originally identified as a negative regulator of the hepatitis B virus X-associated protein. Recent studies have expanded the range of XAP2 client proteins to include the nuclear receptor family of transcription factors. In this study, we show that XAP2 is recruited to the promoter of ERα regulated genes like the breast cancer marker gene pS2 or GREB1 and negatively regulate the expression of these genes in MCF-7 cells. Interestingly, we show that XAP2 downregulates the E2-dependent transcriptional activation in an estrogen receptor (ER) isoform-specific manner: XAP2 inhibits ERα but not ERβ-mediated transcription. Thus, knockdown of intracellular XAP2 levels leads to increased ERα activity. XAP2 proteins, carrying mutations in their primary structures, loose the ability of interacting with ERα and can no longer regulate ER target gene transcription. Taken together, this study shows that XAP2 exerts a negative effect on ERα transcriptional activity and may thus prevent ERα-dependent events

Induction of Erythroid Differentiation in Human Erythroleukemia Cells by Depletion of Malic Enzyme 2

Malic enzyme 2 (ME2) is a mitochondrial enzyme that catalyzes the conversion of malate to pyruvate and CO2 and uses NAD as a cofactor. Higher expression of this enzyme correlates with the degree of cell de-differentiation. We found that ME2 is expressed in K562 erythroleukemia cells, in which a number of agents have been found to induce differentiation either along the erythroid or the myeloid lineage. We found that knockdown of ME2 led to diminished proliferation of tumor cells and increased apoptosis in vitro. These findings were accompanied by differentiation of K562 cells along the erythroid lineage, as confirmed by staining for glycophorin A and hemoglobin production. ME2 knockdown also totally abolished growth of K562 cells in nude mice. Increased ROS levels, likely reflecting increased mitochondrial production, and a decreased NADPH/NADP+ ratio were noted but use of a free radical scavenger to decrease inhibition of ROS levels did not reverse the differentiation or apoptotic phenotype, suggesting that ROS production is not causally involved in the resultant phenotype. As might be expected, depletion of ME2 induced an increase in the NAD+/NADH ratio and ATP levels fell significantly. Inhibition of the malate-aspartate shuttle was insufficient to induce K562 differentiation. We also examined several intracellular signaling pathways and expression of transcription factors and intermediate filament proteins whose expression is known to be modulated during erythroid differentiation in K562 cells. We found that silencing of ME2 leads to phospho-ERK1/2 inhibition, phospho-AKT activation, increased GATA-1 expression and diminished vimentin expression. Metabolomic analysis, conducted to gain insight into intermediary metabolic pathways that ME2 knockdown might affect, showed that ME2 depletion resulted in high orotate levels, suggesting potential impairment of pyrimidine metabolism. Collectively our data point to ME2 as a potentially novel metabolic target for leukemia therapy

A review of trends and drivers of greenhouse gas emissions by sector from 1990 to 2018

Global greenhouse gas (GHG) emissions can be traced to five economic sectors: energy, industry, buildings, transport and AFOLU (agriculture, forestry and other land uses). In this topical review, we synthesise the literature to explain recent trends in global and regional emissions in each of these sectors. To contextualise our review, we present estimates of GHG emissions trends by sector from 1990 to 2018, describing the major sources of emissions growth, stability and decline across ten global regions. Overall, the literature and data emphasise that progress towards reducing GHG emissions has been limited. The prominent global pattern is a continuation of underlying drivers with few signs of emerging limits to demand, nor of a deep shift towards the delivery of low and zero carbon services across sectors. We observe a moderate decarbonisation of energy systems in Europe and North America, driven by fuel switching and the increasing penetration of renewables. By contrast, in rapidly industrialising regions, fossil-based energy systems have continuously expanded, only very recently slowing down in their growth. Strong demand for materials, floor area, energy services and travel have driven emissions growth in the industry, buildings and transport sectors, particularly in Eastern Asia, Southern Asia and South-East Asia. An expansion of agriculture into carbon-dense tropical forest areas has driven recent increases in AFOLU emissions in Latin America, South-East Asia and Africa. Identifying, understanding, and tackling the most persistent and climate-damaging trends across sectors is a fundamental concern for research and policy as humanity treads deeper into the Anthropocene

Barbara Thimm / Gottfried Kößler / Susanne Ulrich (Hrsg.): Verunsichernde Orte. Selbstverständnis und Weiterbildung in der Gedenkstättenpädagogik. Frankfurt am Main: Brandes und Apsel 2010 (207 S.) [Rezension]

Rezension von: Barbara Thimm / Gottfried Kößler / Susanne Ulrich (Hrsg.): Verunsichernde Orte. Selbstverständnis und Weiterbildung in der Gedenkstättenpädagogik. Frankfurt am Main: Brandes und Apsel 2010 (207 S.; ISBN 978-3-86099-630-0; 19,90 EUR)

Enhanced chemical weathering as a geoengineering strategy to reduce atmospheric carbon dioxide, supply nutrients, and mitigate ocean acidification

Chemical weathering is an integral part of both the rock and carbon cycles and is being affected by changes in land use, particularly as a result of agricultural practices such as tilling, mineral fertilization, or liming to adjust soil pH. These human activities have already altered the chemical terrestrial cycles and land-ocean flux of major elements, although the extent remains difficult to quantify. When deployed on a grand scale, Enhanced Weathering (a form of mineral fertilization), the application of finely ground minerals over the land surface, could be used to remove CO2 from the atmosphere. The release of cations during the dissolution of such silicate minerals would convert dissolved CO2 to bicarbonate, increasing the alkalinity and pH of natural waters. Some products of mineral dissolution would precipitate in soils or taken up by ecosystems, but a significant portion would be transported to the coastal zone and the open ocean, where the increase in alkalinity would partially counteract “ocean acidification” associated with the current marked increase in atmospheric CO2. Other elements released during this mineral dissolution, like Si, P or K, could stimulate biological productivity, further helping to remove CO2 from the atmosphere. On land, the terrestrial carbon-pool would likely increase in response to Enhanced Weathering in areas where ecosystem growth rates are currently limited by one of the nutrients that would be released during mineral dissolution. In the ocean, the biological carbon pumps (which export organic matter and CaCO3 to the deep ocean) may be altered by the resulting influx of nutrients and alkalinity to the ocean. This review merges current interdisciplinary knowledge about Enhanced Weathering, the processes involved, and the applicability as well as some of the consequences and risks of applying the method