ALBERT

Description: Stearoyl-CoA desaturase 1 (SCD1) desaturates long chain fatty acids and is therefore a key enzyme in fat catabolism. Its synthesis is downregulated in liver during illnesses caused by high levels of circulatin...

Description: Mutations in enhancer-associated chromatin-modifying components and genomic alterations in non-coding regions of the genome occur frequently in cancer, and other diseases pointing to the importance of enhancer fidelity to ensure proper tissue homeostasis. In this review, I will use specific examples to discuss how mutations in chromatin-modifying factors might affect enhancer activity of disease-relevant genes. I will then consider direct evidence from single nucleotide polymorphisms, small insertions, or deletions but also larger genomic rearrangements such as duplications, deletions, translocations, and inversions of specific enhancers to demonstrate how they have the ability to impact enhancer activity of disease genes including oncogenes and tumor suppressor genes. Considering that the scientific community only fairly recently has begun to focus its attention on “enhancer malfunction” in disease, I propose that multiple new enhancer-regulated and disease-relevant processes will be uncovered in the near future that will constitute the mechanistic basis for novel therapeutic avenues. Enhancer deregulation underlies various diseases. It can be caused by mutations in enhancer-associated chromatin-modifying factors such as UTX/KDM6A, MLL3/KMT2C, and MLL4/KMT2D or alternatively by mutations or genomic alterations of disease, or cancer gene enhancers. Both cases result in altered enhancer activity of disease-relevant genes such as tumor suppressor or oncogenes.

Description: Differential RNA-sequencing (dRNA-seq) is indispensable for determination of primary transcriptomes. However, using dRNA-seq data to map transcriptional start sites (TSSs) and promoters genome-wide is a bioinf...

Description: Background: The enzyme acetyl-CoA carboxylase-alpha (ACC-alpha) is rate limiting for de novo fatty acid synthesis. Among the four promoters expressing the bovine gene, promoter IA (PIA) is dominantly active in lipogenic tissues. This promoter is in principal repressed but activated under favorable nutritional conditions. Previous analyses already coarsely delineated the repressive elements on the distal promoter but did not resolve the molecular nature of the repressor. Knowledge about the molecular functioning of this repressor is fundamental to understanding the nutrition mediated regulation of PIA activity. We analyzed here the molecular mechanism calibrating PIA activity. Results: We finely mapped the repressor binding sites in reporter gene assays and demonstrate together with Electrophoretic Mobility Shift Assays that nuclear factor-Y (NF-Y) and CCAAT/enhancer binding protein- (C/EBP-beta) each separately repress PIA activity by binding to their cognate low affinity sites, located on distal elements of the promoter. Simultaneous binding of both factors results in strongest repression. Paradoxically, over expression of NFY factors, but also - and even more so - of C/EBP-beta significantly activated the promoter when bound to high affinity sites on the proximal promoter. However, co-transfection experiments revealed that NF-Y may eventually diminish the strong stimulatory effect of C/EBP at the proximal PIA in a dose dependent fashion. We validated by chromatin immunoprecipitation, that NF-Y and C/EBP factors may physically interact. ConclusionsThe proximal promoter segment of PIA appears to be principally in an active state, since even minute concentrations of both, NF-Y and C/EBP-beta factors can saturate the high affinity activator sites. Higher factor concentrations will saturate the low affinity repressive sites on the distal promoter resulting in reduced and calibrated promoter activity. Based on measurements of the mRNA concentrations of those factors in different tissues we propose that the interplay of both factors may set tissue-specific limits for PIA activity.

Description: How temperate forests will respond to climate change is uncertain; projections range from severe decline to increased growth. We conducted field tests of sessile oak ( Quercus petraea), a widespread keystone European forest tree species, including more than 150,000 trees sourced from 116 geographically diverse populations. The tests were planted on 23 field sites in six European countries, in order to expose them to a wide range of climates, including sites reflecting future warmer and drier climates. By assessing tree height and survival, our objectives were twofold: (1) to identify the source of differential population responses to climate (genetic differentiation due to past divergent climatic selection versus plastic responses to ongoing climate change), (2) to explore which climatic variables (temperature or precipitation) trigger the population responses. Tree growth and survival were modeled for contemporary climate and then projected using data from four regional climate models for years 2071-2100, using two greenhouse gas concentration trajectory scenarios each. Overall results indicated a moderate response of tree height and survival to climate variation, with changes in dryness (either annual or during the growing season) explaining the major part of the response. Whilst, on average, populations exhibited local adaptation, there was significant clinal population differentiation for height growth with winter temperature at the site of origin. The most moderate climate model (HIRHAM5-EC; rcp4.5) predicted minor decreases in height and survival, whilst the most extreme model (CCLM4-GEM2-ES; rcp8.5) predicted large decreases in survival and growth for southern and southeastern edge populations (Hungary and Turkey). Other non-marginal populations with continental climates were predicted to be severely and negatively affected (Bercé, France), while populations at the contemporary northern limit (colder and humid maritime regions; Denmark and Norway) will probably not show large changes in growth and survival in response to climate change. This article is protected by copyright. All rights reserved.

Description: ABSTRACT During the last decades, the effects of global warming have become apparent also in Europe, causing relevant impacts in many sectors. Under projected future global warming, such a tendency can be expected to persist until the end of this century and beyond. Identifying which climate-related impacts are likely to increase, and by how much, is an important element of any effective strategy for managing future climate risks. This study investigates whether energy demand for cooling and heating buildings can be expected to increase or decrease under climate change. Two indicators of weather-related energy consumption for heating and cooling buildings are considered: heating degree-days (HDD) and cooling degree-days (CDD). The evolution of these indicators has been analysed based on 11 high-resolution bias-adjusted EURO-CORDEX simulations for two emission representative concentration pathways (RCP4.5 and RCP8.5). Both indicators have been validated over the period 1981–2010 using an independent data set that contains more than 4000 station data, showing very high correlation over most of Europe. Trends of HDD and CDD from 1981 to 2100, together with their uncertainties, are analysed. For both RCPs, all simulations project a significant decrease for HDD, especially over Scandinavia and European Russia, and an increase of CDD which peaks over the Mediterranean region and the Balkans. Overall, degree-day trends do not show remarkable differences if population weighting is applied. If a constant population scenario is considered, the decrease in HDD will outbalance the increase in CDD in the 21st century over most of Europe. Thus the related energy demand (expressed as Energy Degree-days, EDD) is expected to decrease. If, however, population projections over the 21st century are included in the calculations, it is shown that despite the persisting warming, EDD will increase over northern Europe, the Baltic countries, Great Britain, Ireland, Benelux, the Alps, Spain, and Cyprus, resulting in an overall increase in EDD over Europe. Using 11 bias-adjusted EURO-CORDEX simulations, we computed heating (HDD) and cooling degree-days (CDD) for 1981–2100 over Europe under RCP4.5 and RCP8.5. A significant projected decrease in HDD under both scenarios is found, especially over Fennoscandia and Russia; the increase of CDD will peak over Mediterranean and Balkans. Under a constant population scenario, energy degree-days (EDD) are expected to decrease almost over the entire Europe. Using population projections, EDD will increase over northern Europe, the Baltic Republics, the British Isles, Benelux, the Alps, Spain, and Cyprus. Ensemble mean linear trends of HDD/year (left) and CDD/year (right) under RCP4.5 (top) and RCP8.5 (bottom). Over grey areas, fewer than 7 out of 11 simulations projected a significant trend at 95%. Population-weighting is not applied in this map.

Description: Early diagenetic processes in Peruvian shelf and slope sediments are numerically reproduced by applying chemical thermodynamics in a complex, universal approach using the PHREEQC (version 2) computer code. The reaction kinetics of organic carbon remineralization are integrated into a set of equilibrium reactions by defining the type and the amount of converted organic matter in a certain time step. We calculate the most intense remineralization of organic carbon for present-day shelf sites, and the final carbon pool is dominated by secondary carbonates. This serves to highlight the influence of organic matter degradation and anaerobic oxidation of methane (AOM) on diagenetic mineral formation. The enrichment of aqueous methane and the formation of methane hydrate only takes place in slope sediments with high sedimentation rates that prevent diffusive loss of methane (e.g., Sites 682 and 688). Moreover, AOM prevents the diffusion of dissolved methane into overlying seawater. Throughout the Miocene period, these sites were located on a former shelf and the total carbon loss from the sediments was significantly higher in comparison with the present-day. Compared with the present-day shelf site, organic matter remineralization is high, and methane is produced but not stored within the sediments. Our model calculations rule out the possibility of present-day and former shelf site sediments off the coast of Peru as methane reservoirs. Remineralized TOC has to be considered, particularly in older sediments, when interpreting TOC profiles and calculating mass accumulation rates of total organic carbon (MARTOC). The more organic matter has been remineralized during the depositional history, the larger the difference between MARTOC calculated from measured TOC data, and from the sum of modeled and measured TOC data. Consequently, most reliable primary productivity calculations are based on the sum of measured relict TOC and the amount of remineralized organic carbon determined by modeling.