@article{VogelKamitzHallahanetal.2018,
  author    = {Vogel, Heike and Kamitz, Anne and Hallahan, Nicole and Lebek, Sandra and Schallschmidt, Tanja and Jonas, Wenke and J{\"a}hnert, Markus and Gottmann, Pascal and Zellner, Lisa and Kanzleiter, Timo and Damen, Mareike and Altenhofen, Delsi and Burkhardt, Ralph and Renner, Simone and Dahlhoff, Maik and Wolf, Eckhard and M{\"u}ller, Timo Dirk and Bl{\"u}her, Matthias and Joost, Hans-Georg and Chadt, Alexandra and Al-Hasani, Hadi and Sch{\"u}rmann, Annette},
  title     = {A collective diabetes cross in combination with a computational framework to dissect the genetics of human obesity and Type 2 diabetes},
  series = {Human molecular genetics},
  volume    = {27},
  journal   = {Human molecular genetics},
  number    = {17},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0964-6906},
  doi       = {10.1093/hmg/ddy217},
  pages     = {3099 -- 3112},
  year      = {2018},
  abstract  = {To explore the genetic determinants of obesity and Type 2 diabetes (T2D), the German Center for Diabetes Research (DZD) conducted crossbreedings of the obese and diabetes-prone New Zealand Obese mouse strain with four different lean strains (B6, DBA, C3H, 129P2) that vary in their susceptibility to develop T2D. Genome-wide linkage analyses localized more than 290 quantitative trait loci (QTL) for obesity, 190 QTL for diabetes-related traits and 100 QTL for plasma metabolites in the out-cross populations. A computational framework was developed that allowed to refine critical regions and to nominate a small number of candidate genes by integrating reciprocal haplotype mapping and transcriptome data. The efficiency of the complex procedure was demonstrated for one obesity QTL. The genomic interval of 35 Mb with 502 annotated candidate genes was narrowed down to six candidates. Accordingly, congenic mice retained the obesity phenotype owing to an interval that contains three of the six candidate genes. Among these the phospholipase PLA2G4A exhibited an elevated expression in adipose tissue of obese human subjects and is therefore a critical regulator of the obesity locus. Together, our broad and complex approach demonstrates that combined- and comparative-cross analysis exhibits improved mapping resolution and represents a valid tool for the identification of disease genes.},
  language  = {en}
}
@article{MuellerWindhofMaximovetal.2013,
  author    = {M{\"u}ller, Sara and Windhof, Indra M. and Maximov, Vladimir and Jurkowski, Tomasz and Jeltsch, Albert and F{\"o}rstner, Konrad U. and Sharma, Cynthia M. and Gr{\"a}f, Ralph and Nellen, Wolfgang},
  title     = {Target recognition, RNA methylation activity and transcriptional regulation of the dictyostelium discoideum Dnmt2-homologue (DnmA)},
  series = {Nucleic acids research},
  volume    = {41},
  journal   = {Nucleic acids research},
  number    = {18},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0305-1048},
  doi       = {10.1093/nar/gkt634},
  pages     = {8615 -- 8627},
  year      = {2013},
  abstract  = {Although the DNA methyltransferase 2 family is highly conserved during evolution and recent reports suggested a dual specificity with stronger activity on transfer RNA (tRNA) than DNA substrates, the biological function is still obscure. We show that the Dictyostelium discoideum Dnmt2-homologue DnmA is an active tRNA methyltransferase that modifies C38 in tRNA(Asp(GUC)) in vitro and in vivo. By an ultraviolet-crosslinking and immunoprecipitation approach, we identified further DnmA targets. This revealed specific tRNA fragments bound by the enzyme and identified tRNA(Glu(CUC/UUC)) and tRNA(Gly(GCC)) as new but weaker substrates for both human Dnmt2 and DnmA in vitro but apparently not in vivo. Dnmt2 enzymes form transient covalent complexes with their substrates. The dynamics of complex formation and complex resolution reflect methylation efficiency in vitro. Quantitative PCR analyses revealed alterations in dnmA expression during development, cell cycle and in response to temperature stress. However, dnmA expression only partially correlated with tRNA methylation in vivo. Strikingly, dnmA expression in the laboratory strain AX2 was significantly lower than in the NC4 parent strain. As expression levels and binding of DnmA to a target in vivo are apparently not necessarily accompanied by methylation, we propose an additional biological function of DnmA apart from methylation.},
  language  = {en}
}
@article{LilieBaerKettneretal.2011,
  author    = {Lilie, Hauke and B{\"a}r, Dorit and Kettner, Karina and Weininger, Ulrich and Balbach, Jochen and Naumann, Manfred and M{\"u}ller, Eva-Christina and Otto, Albrecht and Gast, Klaus and Golbik, Ralph},
  title     = {Yeast hexokinase isoenzyme ScHxk2 : stability of a two-domain protein with discontinuous domains},
  issn      = {0269-2139},
  year      = {2011},
  abstract  = {The hexokinase isoenzyme 2 of Saccharomyces cerevisiae (ScHxk2) represents an archetype of a two-domain protein with the active site located in a cleft between the two domains. Binding of the substrate glucose results in a rigid body movement of the two domains leading to a cleft closure of the active site. Both domains of this enzyme are composed of discontinuous peptide sequences. This structural feature is reflected in the stability and folding of the ScHxk2 protein. Structural transitions induced by urea treatment resulted in the population of a thermodynamically stable folding intermediate, which, however, does not correspond to a molecule with one domain folded and the other unfolded. As demonstrated by different spectroscopic techniques, both domains are structurally affected by the partial denaturation. The intermediate possesses only 40\% of the native secondary structural content and a substantial increase in the Stokes radius as judged by circular dichroism and dynamic light scattering analyses. One-dimensional 1H NMR data prove that all tryptophan residues are in a non-native environment in the intermediate, indicating substantial changes in the tertiary structure. Still, the intermediate possesses quite a high stability for a transition intermediate of about ;G = ;22 kJ mol;1.},
  language  = {en}
}
@misc{WuertzKozakRoszkowskiCambriaetal.2020,
  author    = {Wuertz-Kozak, Karin and Roszkowski, Martin and Cambria, Elena and Block, Andrea and Kuhn, Gisela A. and Abele, Thea and Hitzl, Wolfgang and Drießlein, David and M{\"u}ller, Ralph and Rapp, Michael Armin and Mansuy, Isabelle M. and Peters, Eva M. J. and Wippert, Pia-Maria},
  title     = {Effects of Early Life Stress on Bone Homeostasis in Mice and Humans},
  series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe},
  number    = {670},
  issn      = {1866-8364},
  doi       = {10.25932/publishup-48532},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-485324},
  pages     = {26},
  year      = {2020},
  abstract  = {Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (μCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.},
  language  = {en}
}
@article{WuertzKozakRoszkowskiCambriaetal.2020,
  author    = {Wuertz-Kozak, Karin and Roszkowski, Martin and Cambria, Elena and Block, Andrea and Kuhn, Gisela A. and Abele, Thea and Hitzl, Wolfgang and Drießlein, David and M{\"u}ller, Ralph and Rapp, Michael Armin and Mansuy, Isabelle M. and Peters, Eva M. J. and Wippert, Pia-Maria},
  title     = {Effects of Early Life Stress on Bone Homeostasis in Mice and Humans},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {18},
  publisher = {Molecular Diversity Preservation International},
  address   = {Basel},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21186634},
  pages     = {24},
  year      = {2020},
  abstract  = {Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (μCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.},
  language  = {en}
}
@article{SchweigelBatsiosMuellerTaubenbergeretal.2022,
  author    = {Schweigel, Ulrike and Batsios, Petros and M{\"u}ller-Taubenberger, Annette and Gr{\"a}f, Ralph and Grafe, Marianne},
  title     = {Dictyostelium spastin is involved in nuclear envelope dynamics during semi-closed mitosis},
  series = {Nucleus},
  volume    = {13},
  journal   = {Nucleus},
  number    = {1},
  publisher = {Taylor \& Francis Group},
  address   = {Philadelphia},
  issn      = {1949-1034},
  doi       = {10.1080/19491034.2022.2047289},
  pages     = {144 -- 154},
  year      = {2022},
  abstract  = {Dictyostelium amoebae perform a semi-closed mitosis, in which the nuclear envelope is fenestrated at the insertion sites of the mitotic centrosomes and around the central spindle during karyokinesis. During late telophase the centrosome relocates to the cytoplasmic side of the nucleus, the central spindle disassembles and the nuclear fenestrae become closed. Our data indicate that Dictyostelium spastin (DdSpastin) is a microtubule-binding and severing type I membrane protein that plays a role in this process. Its mitotic localization is in agreement with a requirement for the removal of microtubules that would hinder closure of the fenestrae. Furthermore, DdSpastin interacts with the HeH/ LEM-family protein Src1 in BioID analyses as well as the inner nuclear membrane protein Sun1, and shows subcellular co-localizations with Src1, Sun1, the ESCRT component CHMP7 and the IST1-like protein filactin, suggesting that the principal pathway of mitotic nuclear envelope remodeling is conserved between animals and Dictyostelium amoebae.},
  language  = {en}
}
@article{MettlerMuehlhausHemmeetal.2014,
  author    = {Mettler, Tabea and M{\"u}hlhaus, Timo and Hemme, Dorothea and Sch{\"o}ttler, Mark Aurel and Rupprecht, Jens and Idoine, Adam and Veyel, Daniel and Pal, Sunil Kumar and Yaneva-Roder, Liliya and Winck, Flavia Vischi and Sommer, Frederik and Vosloh, Daniel and Seiwert, Bettina and Erban, Alexander and Burgos, Asdrubal and Arvidsson, Samuel Janne and Schoenfelder, Stephanie and Arnold, Anne and Guenther, Manuela and Krause, Ursula and Lohse, Marc and Kopka, Joachim and Nikoloski, Zoran and M{\"u}ller-R{\"o}ber, Bernd and Willmitzer, Lothar and Bock, Ralph and Schroda, Michael and Stitt, Mark},
  title     = {Systems analysis of the response of photosynthesis, metabolism, and growth to an increase in irradiance in the photosynthetic model organism chlamydomonas reinhardtii},
  series = {The plant cell},
  volume    = {26},
  journal   = {The plant cell},
  number    = {6},
  publisher = {American Society of Plant Physiologists},
  address   = {Rockville},
  issn      = {1040-4651},
  doi       = {10.1105/tpc.114.124537},
  pages     = {2310 -- 2350},
  year      = {2014},
  abstract  = {We investigated the systems response of metabolism and growth after an increase in irradiance in the nonsaturating range in the algal model Chlamydomonas reinhardtii. In a three-step process, photosynthesis and the levels of metabolites increased immediately, growth increased after 10 to 15 min, and transcript and protein abundance responded by 40 and 120 to 240 min, respectively. In the first phase, starch and metabolites provided a transient buffer for carbon until growth increased. This uncouples photosynthesis from growth in a fluctuating light environment. In the first and second phases, rising metabolite levels and increased polysome loading drove an increase in fluxes. Most Calvin-Benson cycle (CBC) enzymes were substrate-limited in vivo, and strikingly, many were present at higher concentrations than their substrates, explaining how rising metabolite levels stimulate CBC flux. Rubisco, fructose-1,6-biosphosphatase, and seduheptulose-1,7-bisphosphatase were close to substrate saturation in vivo, and flux was increased by posttranslational activation. In the third phase, changes in abundance of particular proteins, including increases in plastidial ATP synthase and some CBC enzymes, relieved potential bottlenecks and readjusted protein allocation between different processes. Despite reasonable overall agreement between changes in transcript and protein abundance (R-2 = 0.24), many proteins, including those in photosynthesis, changed independently of transcript abundance.},
  language  = {en}
}