@article{CuiSchlesingerSchoenhalsetal.2016, author = {Cui, Huanhuan and Schlesinger, Jenny and Schoenhals, Sophia and Toenjes, Martje and Dunkel, Ilona and Meierhofer, David and Cano, Elena and Schulz, Kerstin and Berger, Michael F. and Haack, Timm and Abdelilah-Seyfried, Salim and Bulyk, Martha L. and Sauer, Sascha and Sperling, Silke R.}, title = {Phosphorylation of the chromatin remodeling factor DPF3a induces cardiac hypertrophy through releasing HEY repressors from DNA}, series = {Nucleic acids research}, volume = {44}, journal = {Nucleic acids research}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0305-1048}, doi = {10.1093/nar/gkv1244}, pages = {2538 -- 2553}, year = {2016}, abstract = {DPF3 (BAF45c) is a member of the BAF chromatin remodeling complex. Two isoforms have been described, namely DPF3a and DPF3b. The latter binds to acetylated and methylated lysine residues of histones. Here, we elaborate on the role of DPF3a and describe a novel pathway of cardiac gene transcription leading to pathological cardiac hypertrophy. Upon hypertrophic stimuli, casein kinase 2 phosphorylates DPF3a at serine 348. This initiates the interaction of DPF3a with the transcriptional repressors HEY, followed by the release of HEY from the DNA. Moreover, BRG1 is bound by DPF3a, and is thus recruited to HEY genomic targets upon interaction of the two components. Consequently, the transcription of downstream targets such as NPPA and GATA4 is initiated and pathological cardiac hypertrophy is established. In human, DPF3a is significantly up-regulated in hypertrophic hearts of patients with hypertrophic cardiomyopathy or aortic stenosis. Taken together, we show that activation of DPF3a upon hypertrophic stimuli switches cardiac fetal gene expression from being silenced by HEY to being activated by BRG1. Thus, we present a novel pathway for pathological cardiac hypertrophy, whose inhibition is a long-term therapeutic goal for the treatment of the course of heart failure.}, language = {en} } @misc{VolckmarHanPuetteretal.2016, author = {Volckmar, Anna-Lena and Han, Chung-Ting and P{\"u}tter, Carolin and Haas, Stefan and Vogel, Carla I. G. and Knoll, Nadja and Struve, Christoph and G{\"o}bel, Maria and Haas, Katharina and Herrfurth, Nikolas and Jarick, Ivonne and Grallert, Harald and Sch{\"u}rmann, Annette and Al- Hasani, Hadi and Hebebrand, Johannes and Sauer, Sascha and Hinney, Anke}, title = {Analysis of genes involved in body weight regulation by targeted re-sequencing}, series = {PLoS ONE}, journal = {PLoS ONE}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-410289}, pages = {16}, year = {2016}, abstract = {Introduction Genes involved in body weight regulation that were previously investigated in genome-wide association studies (GWAS) and in animal models were target-enriched followed by massive parallel next generation sequencing. Methods We enriched and re-sequenced continuous genomic regions comprising FTO, MC4R, TMEM18, SDCCAG8, TKNS, MSRA and TBC1D1 in a screening sample of 196 extremely obese children and adolescents with age and sex specific body mass index (BMI) >= 99th percentile and 176 lean adults (BMI <= 15th percentile). 22 variants were confirmed by Sanger sequencing. Genotyping was performed in up to 705 independent obesity trios (extremely obese child and both parents), 243 extremely obese cases and 261 lean adults. Results and Conclusion We detected 20 different non-synonymous variants, one frame shift and one nonsense mutation in the 7 continuous genomic regions in study groups of different weight extremes. For SNP Arg695Cys (rs58983546) in TBC1D1 we detected nominal association with obesity (p(TDT) = 0.03 in 705 trios). Eleven of the variants were rare, thus were only detected heterozygously in up to ten individual(s) of the complete screening sample of 372 individuals. Two of them (in FTO and MSRA) were found in lean individuals, nine in extremely obese. In silico analyses of the 11 variants did not reveal functional implications for the mutations. Concordant with our hypothesis we detected a rare variant that potentially leads to loss of FTO function in a lean individual. For TBC1D1, in contrary to our hypothesis, the loss of function variant (Arg443Stop) was found in an obese individual. Functional in vitro studies are warranted.}, language = {en} } @article{NumbergerGanzertZoccaratoetal.2019, author = {Numberger, Daniela and Ganzert, Lars and Zoccarato, Luca and M{\"u}hldorfer, Kristin and Sauer, Sascha and Grossart, Hans-Peter and Greenwood, Alex D.}, title = {Characterization of bacterial communities in wastewater with enhanced taxonomic resolution by full-length 16S rRNA sequencing}, series = {Scientific reports}, volume = {9}, journal = {Scientific reports}, publisher = {Nature Publ. Group}, address = {London}, issn = {2045-2322}, doi = {10.1038/s41598-019-46015-z}, pages = {14}, year = {2019}, abstract = {Wastewater treatment is crucial to environmental hygiene in urban environments. However, wastewater treatment plants (WWTPs) collect chemicals, organic matter, and microorganisms including pathogens and multi-resistant bacteria from various sources which may be potentially released into the environment via WWTP effluent. To better understand microbial dynamics in WWTPs, we characterized and compared the bacterial community of the inflow and effluent of a WWTP in Berlin, Germany using full-length 16S rRNA gene sequences, which allowed for species level determination in many cases and generally resolved bacterial taxa. Significantly distinct bacterial communities were identified in the wastewater inflow and effluent samples. Dominant operational taxonomic units (OTUs) varied both temporally and spatially. Disease associated bacterial groups were efficiently reduced in their relative abundance from the effluent by the WWTP treatment process, except for Legionella and Leptospira species which demonstrated an increase in relative proportion from inflow to effluent. This indicates that WWTPs, while effective against enteric bacteria, may enrich and release other potentially pathogenic bacteria into the environment. The taxonomic resolution of full-length 16S rRNA genes allows for improved characterization of potential pathogenic taxa and other harmful bacteria which is required to reliably assess health risk.}, language = {en} } @article{NumbergerZoccaratoWoodhouseetal.2022, author = {Numberger, Daniela and Zoccarato, Luca and Woodhouse, Jason Nicholas and Ganzert, Lars and Sauer, Sascha and Garc{\´i}a M{\´a}rquez, Jaime Ricardo and Domisch, Sami and Grossart, Hans-Peter and Greenwood, Alex}, title = {Urbanization promotes specific bacteria in freshwater microbiomes including potential pathogens}, series = {The science of the total environment : an international journal for scientific research into the environment and its relationship with man}, volume = {845}, journal = {The science of the total environment : an international journal for scientific research into the environment and its relationship with man}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0048-9697}, doi = {10.1016/j.scitotenv.2022.157321}, pages = {13}, year = {2022}, abstract = {Freshwater ecosystems are characterized by complex and highly dynamic microbial communities that are strongly structured by their local environment and biota. Accelerating urbanization and growing city populations detrimentally alter freshwater environments. To determine differences in freshwater microbial communities associated with urban-ization, full-length 16S rRNA gene PacBio sequencing was performed in a case study from surface waters and sedi-ments from a wastewater treatment plant, urban and rural lakes in the Berlin-Brandenburg region, Northeast Germany. Water samples exhibited highly habitat specific bacterial communities with multiple genera showing clear urban signatures. We identified potentially harmful bacterial groups associated with environmental parameters specific to urban habitats such as Alistipes, Escherichia/Shigella, Rickettsia and Streptococcus. We demonstrate that urban-ization alters natural microbial communities in lakes and, via simultaneous warming and eutrophication and creates favourable conditions that promote specific bacterial genera including potential pathogens. Our findings are evidence to suggest an increased potential for long-term health risk in urbanized waterbodies, at a time of rapidly expanding global urbanization. The results highlight the urgency for undertaking mitigation measures such as targeted lake restoration projects and sustainable water management efforts.}, language = {en} }