ALBERT

Description: Background: A regional-scale sensitivity study has been carried out to investigate the climatic effects of forest cover change in Europe. Applying REMO (regional climate model of the Max Planck Institute for Meteorology), the projected temperature and precipitation tendencies have been analysed for summer, based on the results of the A2 IPCC-SRES emission scenario simulation. For the end of the 21st century it has been studied, whether the assumed forest cover increase could reduce the effects of the greenhouse gas concentration change. Results: Based on the simulation results, biogeophysical effects of the hypothetic potential afforestation may lead to cooler and moister conditions during summer in most parts of the temperate zone. The largest relative effects of forest cover increase can be expected in northern Germany, Poland and Ukraine, which is 15--20% of the climate change signal for temperature and more than 50% for precipitation. In northern Germany and France, potential afforestation may enhance the effects of emission change, resulting in more severe heavy precipitation events. The probability of dry days and warm temperature extremes would decrease. Conclusions: Large contiguous forest blocks can have distinctive biogeophysical effect on the climate on regional and local scale. In certain regions of the temperate zone, climate change signal due to greenhouse gas emission can be reduced by afforestation due to the dominant evaporative cooling effect during summer. Results of this case study with a hypothetical land cover change can contribute to the assessment of the role of forests in adapting to climate change. Thus they can build an important basis of the future forest policy.

Description: Background: The human endogenous retrovirus K (HERV-K) has been acquired by the genome of human ancestors million years ago. It is the most complete of the HERVs with transcriptionally active gag, pol and env genes. Splice variants of env, which are rec, 1.5 kb transcript and Np9 have been suggested to be tumorigenic. Transcripts of HERV-K have been detected in a multitude of human cancers. However, no such reports are available concerning glioblastomas (GBM), the most common malignant brain tumor in adults. Patients have a limited prognosis of 14.6 months in median, despite standard treatment. Therefore, we elucidated whether HERV-K transcripts could be detected in these tumors and serve as new molecular target for treatment.FindingsWe analyzed human GBM cell lines, tissue samples from patients and primary cell cultures of different passages for HERV-K full length mRNA and env, rec and 1.5 kb transcripts. While the GBM cell lines U138, U251, U343 and GaMG displayed weak and U87 strong expression of the full length HERV-K, the splice products could not be detected, despite a weak expression of env mRNA in U87 cells. Very few tissue samples from patients showed weak expression of env mRNA, but none of the rec or 1.5 kb transcripts. Primary cells expressed the 1.5 kb transcript weakly in early passages, but lost HERV-K expression with extended culture time. Conclusions: These data suggest that HERV-K splice products do not play a role in human malignant gliomas and therefore, are not suitable as targets for new therapy regimen.

Description: Background: The human endogenous retrovirus K (HERV-K) has been acquired by the genome of human ancestors million years ago. It is the most complete of the HERVs with transcriptionally active gag, pol and env genes. Splice variants of env, which are rec, 1.5 kb transcript and Np9 have been suggested to be tumorigenic. Transcripts of HERV-K have been detected in a multitude of human cancers. However, no such reports are available concerning glioblastomas (GBM), the most common malignant brain tumor in adults. Patients have a limited prognosis of 14.6 months in median, despite standard treatment. Therefore, we elucidated whether HERV-K transcripts could be detected in these tumors and serve as new molecular target for treatment.FindingsWe analyzed human GBM cell lines, tissue samples from patients and primary cell cultures of different passages for HERV-K full length mRNA and env, rec and 1.5 kb transcripts. While the GBM cell lines U138, U251, U343 and GaMG displayed weak and U87 strong expression of the full length HERV-K, the splice products could not be detected, despite a weak expression of env mRNA in U87 cells. Very few tissue samples from patients showed weak expression of env mRNA, but none of the rec or 1.5 kb transcripts. Primary cells expressed the 1.5 kb transcript weakly in early passages, but lost HERV-K expression with extended culture time. Conclusions: These data suggest that HERV-K splice products do not play a role in human malignant gliomas and therefore, are not suitable as targets for new therapy regimen.

Description: Background: Aberrant DNA methylation is a hallmark of many cancers. Classically there are two types of endometrial cancer, endometrioid adenocarcinoma (EAC), or Type I, and uterine papillary serous carcinoma (UPSC), or Type II. However, the whole genome DNA methylation changes in these two classical types of endometrial cancer is still unknown. Results: Here we described complete genome-wide DNA methylome maps of EAC, UPSC, and normal endometrium by applying a combined strategy of methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme digestion sequencing (MRE-seq). We discovered distinct genome-wide DNA methylation patterns in EAC and UPSC: 27,009 and 15,676 recurrent differentially methylated regions (DMRs) were identified respectively, compared with normal endometrium. Over 80% of DMRs were in intergenic and intronic regions. The majority of these DMRs were not interrogated on the commonly used Infinium 450K array platform. Large-scale demethylation of chromosome X was detected in UPSC, accompanied by decreased XIST expression. Importantly, we discovered that the majority of the DMRs harbored promoter or enhancer functions and are specifically associated with genes related to uterine development and disease. Among these, abnormal methylation of transposable elements (TEs) may provide a novel mechanism to deregulate normal endometrium-specific enhancers derived from specific TEs. Conclusions: DNA methylation changes are an important signature of endometrial cancer and regulate gene expression by affecting not only proximal promoters but also distal enhancers.

Description: Background: Glioblastoma multiforme located in the posterior fossa is extremely rare with a frequency up to 3.4%. Compared with glioblastoma of the hemispheres the prognosis of infratentorial glioblastoma seems to be slightly better. Absence of brainstem invasion and low expression rates of epidermal growth factor receptor are described as factors for long-time survival due to the higher radiosensitivity of these tumors.Case presentationIn this case study, we report a German female patient with an exophytic glioblastoma multiforme arising from the cerebellar tonsil and a secondary spinal manifestation. Furthermore, the tumor showed no O (6)-Methylguanine-DNA methyltransferase promotor-hypermethylation and no isocitrate dehydrogenase 1 mutations. All these signs are accompanied by significantly shorter median overall survival. A long-term tumor control of the spinal metastases was achieved by a combined temozolomide/bevacizumab and irradiation therapy, as part of a standard care administered by the treating physician team. Results: To our knowledge this is the first published case of a combined cerebellar exophytic glioblastoma with a subsequent solid spinal manifestation. Furthermore this case demonstrates a benefit undergoing this special adjuvant therapy regime in terms of overall survival. Conclusion: Due to the limited overall prognosis of the disease, spinal manifestations of glioma are rarely clinically relevant. The results of our instructive case, however, with a positive effect on both life quality and survival warrant treating future patients in the frame of a prospective clinical study.

Description: Background: Increased expression of glial fibrillary acidic protein (GFAP) within macroglia is commonly seen as a hallmark of glial activation after damage within the central nervous system, including the retina. The increased expression of GFAP in glia is also considered part of the pathologically inhibitory environment for regeneration of axons from damaged neurons. Recent studies have raised the possibility that reactive gliosis and increased GFAP cannot automatically be assumed to be negative events for the surrounding neurons and that the context of the reactive gliosis is critical to whether neurons benefit or suffer. We utilized transgenic mice expressing a range of Gfap to titrate the amount of GFAP in retinal explants to investigate the relationship between GFAP concentration and the regenerative potential of retinal ganglion cells.FindingsExplants from Gfap-/- and Gfap+/- mice did not have increased neurite outgrowth compared with Gfap+/+ and Gfap over-expressing mice as would be expected if GFAP was detrimental to axon regeneration. In fact, Gfap over-expressing explants had the most neurite outgrowth when treated with a neurite stimulatory media. Transmission electron microscopy revealed that neurites formed bundles, which were surrounded by larger cellular processes that were GFAP positive indicating a close association between growing axons and glial cells in this regeneration paradigm. Conclusions: We postulate that glial cells with increased Gfap expression support the elongation of new neurites from retinal ganglion cells possibly by providing a scaffold for outgrowth.

Description: Background: Altered DNA methylation patterns represent an attractive mechanism for understanding the phenotypic changes associated with human aging. Several studies have described global and complex age-related methylation changes, but their structural and functional significance has remained largely unclear. Results: We have used transcriptome sequencing to characterize age-related gene expression changes in the human epidermis. The results revealed a significant set of 75 differentially expressed genes with a strong functional relationship to skin homeostasis. We then used whole-genome bisulfite sequencing to identify age-related methylation changes at single-base resolution. Data analysis revealed no global aberrations, but rather highly localized methylation changes, particularly in promoter and enhancer regions that were associated with altered transcriptional activity. Conclusions: Our results suggest that the core developmental program of human skin is stably maintained through the aging process and that aging is associated with a limited destabilization of the epigenome and specific gene expression changes.

Description: The Earth System Model Evaluation Tool (ESMValTool) is a community diagnostics and performance metrics tool designed to improve comprehensive and routine evaluation of Earth system models (ESMs) participating in the Coupled Model Intercomparison Project (CMIP). It has undergone rapid development since the first release in 2016 and is now a well-tested tool that provides end-to-end provenance tracking to ensure reproducibility. It consists of (1) an easy-to-install, well-documented Python package providing the core functionalities (ESMValCore) that performs common preprocessing operations and (2) a diagnostic part that includes tailored diagnostics and performance metrics for specific scientific applications. Here we describe large-scale diagnostics of the second major release of the tool that supports the evaluation of ESMs participating in CMIP Phase 6 (CMIP6). ESMValTool v2.0 includes a large collection of diagnostics and performance metrics for atmospheric, oceanic, and terrestrial variables for the mean state, trends, and variability. ESMValTool v2.0 also successfully reproduces figures from the evaluation and projections chapters of the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report (AR5) and incorporates updates from targeted analysis packages, such as the NCAR Climate Variability Diagnostics Package for the evaluation of modes of variability, the Thermodynamic Diagnostic Tool (TheDiaTo) to evaluate the energetics of the climate system, as well as parts of AutoAssess that contains a mix of top–down performance metrics. The tool has been fully integrated into the Earth System Grid Federation (ESGF) infrastructure at the Deutsches Klimarechenzentrum (DKRZ) to provide evaluation results from CMIP6 model simulations shortly after the output is published to the CMIP archive. A result browser has been implemented that enables advanced monitoring of the evaluation results by a broad user community at much faster timescales than what was possible in CMIP5.