@article{BaeumerKarthaKumarAllampallyetal.2019, author = {B{\"a}umer, Nils and Kartha, Kalathil K. and Kumar Allampally, Naveen and Yagai, Shiki and Albuquerque, Rodrigo Q. and Fern{\´a}ndez, Gustavo}, title = {Exploiting Coordination Isomerism for Controlled Self-Assembly}, series = {Angewandte Chemie International Edition}, volume = {58}, journal = {Angewandte Chemie International Edition}, doi = {10.1002/anie.201908002}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221362}, pages = {15626-15630}, year = {2019}, abstract = {We exploited the inherent geometrical isomerism of a PtII complex as a new tool to control supramolecular assembly processes. UV irradiation and careful selection of solvent, temperature, and concentration leads to tunable coordination isomerism, which in turn allows fully reversible switching between two distinct aggregate species (1D fibers↔2D lamellae) with different photoresponsive behavior. Our findings not only broaden the scope of coordination isomerism, but also open up exciting possibilities for the development of novel stimuli-responsive nanomaterials.}, language = {en} } @article{SolDehmHechtetal.2018, author = {Sol, Jeroen A. H. P. and Dehm, Volker and Hecht, Reinhard and W{\"u}rthner, Frank and Schenning, Albertus P. H. J. and Debije, Michael G.}, title = {Temperature-Responsive Luminescent Solar Concentrators: Tuning Energy Transfer in a Liquid Crystalline Matrix}, series = {Angewandte Chemie International Edition}, volume = {57}, journal = {Angewandte Chemie International Edition}, doi = {10.1002/anie.201710487}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-238778}, pages = {1030-1033}, year = {2018}, abstract = {Temperature-responsive luminescent solar concentrators (LSCs) have been fabricated in which the F{\"o}rster resonance energy transfer (FRET) between a donor-acceptor pair in a liquid crystalline solvent can be tuned. At room temperatures, the perylene bisimide (PBI) acceptor is aggregated and FRET is inactive; while after heating to a temperature above the isotropic phase of the liquid crystal solvent, the acceptor PBI completely dissolves and FRET is activated. This unusual temperature control over FRET was used to design a color-tunable LSC. The device has been shown to be highly stable towards consecutive heating and cooling cycles, making it an appealing device for harvesting otherwise unused solar energy.}, language = {en} } @article{CounsellKardaDiazetal.2018, author = {Counsell, John R. and Karda, Rajvinder and Diaz, Juan Antiano and Carey, Louise and Wiktorowicz, Tatiana and Buckley, Suzanne M. K. and Ameri, Shima and Ng, Joanne and Baruteau, Julien and Almeida, Filipa and de Silva, Rohan and Simone, Roberto and Lugar{\`a}, Eleonora and Lignani, Gabriele and Lindemann, Dirk and Rethwilm, Axel and Rahim, Ahad A. and Waddington, Simon N. and Howe, Steven J.}, title = {Foamy Virus Vectors Transduce Visceral Organs and Hippocampal Structures following In Vivo Delivery to Neonatal Mice}, series = {Molecular Therapy: Nucleic Acids}, volume = {12}, journal = {Molecular Therapy: Nucleic Acids}, doi = {10.1016/j.omtn.2018.07.006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223379}, pages = {626-634}, year = {2018}, abstract = {Viral vectors are rapidly being developed for a range of applications in research and gene therapy. Prototype foamy virus (PFV) vectors have been described for gene therapy, although their use has mainly been restricted to ex vivo stem cell modification. Here we report direct in vivo transgene delivery with PFV vectors carrying reporter gene constructs. In our investigations, systemic PFV vector delivery to neonatal mice gave transgene expression in the heart, xiphisternum, liver, pancreas, and gut, whereas intracranial administration produced brain expression until animals were euthanized 49 days post-transduction. Immunostaining and confocal microscopy analysis of injected brains showed that transgene expression was highly localized to hippocampal architecture despite vector delivery being administered to the lateral ventricle. This was compared with intracranial biodistribution of lentiviral vectors and adeno-associated virus vectors, which gave a broad, non-specific spread through the neonatal mouse brain without regional localization, even when administered at lower copy numbers. Our work demonstrates that PFV can be used for neonatal gene delivery with an intracranial expression profile that localizes to hippocampal neurons, potentially because of the mitotic status of the targeted cells, which could be of use for research applications and gene therapy of neurological disorders.}, language = {en} } @article{GriemertSchwarzmaierHummeletal.2019, author = {Griemert, Eva-Verena and Schwarzmaier, Susanne M. and Hummel, Regina and G{\"o}lz, Christina and Yang, Dong and Neuhaus, Winfried and Burek, Malgorzata and F{\"o}rster, Carola Y. and Petkovic, Ivan and Trabold, Raimund and Plesnila, Nikolaus and Engelhard, Kristin and Sch{\"a}fer, Michael K. and Thal, Serge C.}, title = {Plasminogen activator inhibitor-1 augments damage by impairing fibrinolysis after traumatic brain injury}, series = {Annals of Neurology}, volume = {85}, journal = {Annals of Neurology}, doi = {10.1002/ana.25458}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228682}, pages = {667-680}, year = {2019}, abstract = {Objective Plasminogen activator inhibitor-1 (PAI-1) is the key endogenous inhibitor of fibrinolysis, and enhances clot formation after injury. In traumatic brain injury, dysregulation of fibrinolysis may lead to sustained microthrombosis and accelerated lesion expansion. In the present study, we hypothesized that PAI-1 mediates post-traumatic malfunction of coagulation, with inhibition or genetic depletion of PAI-1 attenuating clot formation and lesion expansion after brain trauma. Methods We evaluated PAI-1 as a possible new target in a mouse controlled cortical impact (CCI) model of traumatic brain injury. We performed the pharmacological inhibition of PAI-1 with PAI-039 and stimulation by tranexamic acid, and we confirmed our results in PAI-1-deficient animals. Results PAI-1 mRNA was time-dependently upregulated, with a 305-fold peak 12 hours after CCI, which effectively counteracted the 2- to 3-fold increase in cerebral tissue-type/urokinase plasminogen activator expression. PAI-039 reduced brain lesion volume by 26\% at 24 hours and 43\% at 5 days after insult. This treatment also attenuated neuronal apoptosis and improved neurofunctional outcome. Moreover, intravital microscopy demonstrated reduced post-traumatic thrombus formation in the pericontusional cortical microvasculature. In PAI-1-deficient mice, the therapeutic effect of PAI-039 was absent. These mice also displayed 13\% reduced brain damage compared with wild type. In contrast, inhibition of fibrinolysis with tranexamic acid increased lesion volume by 25\% compared with vehicle. Interpretation This study identifies impaired fibrinolysis as a critical process in post-traumatic secondary brain damage and suggests that PAI-1 may be a central endogenous inhibitor of the fibrinolytic pathway, promoting a procoagulatory state and clot formation in the cerebral microvasculature. Ann Neurol 2019;85:667-680}, language = {en} } @article{FigelBrinkmannBuffetal.2019, author = {Figel, Benedikt and Brinkmann, Leonie and Buff, Christine and Heitmann, Carina Y. and Hofmann, David and Bruchmann, Maximilian and Becker, Michael P. I. and Herrmann, Martin J. and Straube, Thomas}, title = {Phasic amygdala and BNST activation during the anticipation of temporally unpredictable social observation in social anxiety disorder patients}, series = {NeuroImage: Clinical}, volume = {22}, journal = {NeuroImage: Clinical}, doi = {10.1016/j.nicl.2019.101735}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228071}, year = {2019}, abstract = {Anticipation of potentially threatening social situations is a key process in social anxiety disorder (SAD). In other anxiety disorders, recent research of neural correlates of anticipation of temporally unpredictable threat suggests a temporally dissociable involvement of amygdala and bed nucleus of the stria terminalis (BNST) with phasic amygdala responses and sustained BNST activation. However, the temporal profile of amygdala and BNST responses during temporal unpredictability of threat has not been investigated in patients suffering from SAD. We used functional magnetic resonance imaging (fMRI) to investigate neural activation in the central nucleus of the amygdala (CeA) and the BNST during anticipation of temporally unpredictable aversive (video camera observation) relative to neutral (no camera observation) events in SAD patients compared to healthy controls (HC). For the analysis of fMRI data, we applied two regressors (phasic/sustained) within the same model to detect temporally dissociable brain responses. The aversive condition induced increased anxiety in patients compared to HC. SAD patients compared to HC showed increased phasic activation in the CeA and the BNST for anticipation of aversive relative to neutral events. SAD patients as well as HC showed sustained activity alterations in the BNST for aversive relative to neutral anticipation. No differential activity during sustained threat anticipation in SAD patients compared to HC was found. Taken together, our study reveals both CeA and BNST involvement during threat anticipation in SAD patients. The present results point towards potentially SAD-specific threat processing marked by elevated phasic but not sustained CeA and BNST responses when compared to HC.}, language = {en} } @article{FazziniLaminaFendtetal.2019, author = {Fazzini, Federica and Lamina, Claudia and Fendt, Liane and Schultheiss, Ulla T. and Kotsis, Fruzsina and Hicks, Andrew A. and Meiselbach, Heike and Weissensteiner, Hansi and Forer, Lukas and Krane, Vera and Eckardt, Kai-Uwe and K{\"o}ttgen, Anna and Kronenberg, Florian}, title = {Mitochondrial DNA copy number is associated with mortality and infections in a large cohort of patients with chronic kidney disease}, series = {Kidney International}, volume = {96}, journal = {Kidney International}, organization = {GCKD Investigators}, doi = {10.1016/j.kint.2019.04.021}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227662}, pages = {480-488}, year = {2019}, abstract = {Damage of mitochondrial DNA (mtDNA) with reduction in copy number has been proposed as a biomarker for mitochondrial dysfunction and oxidative stress. Chronic kidney disease (CKD) is associated with increased mortality and risk of cardiovascular disease, but the underlying mechanisms remain incompletely understood. Here we investigated the prognostic role of mtDNA copy number for cause-specific mortality in 4812 patients from the German Chronic Kidney Disease study, an ongoing prospective observational national cohort study of patients with CKD stage G3 and A1-3 or G1-2 with overt proteinuria (A3) at enrollment. MtDNA was quantified in whole blood using a plasmid-normalized PCR-based assay. At baseline, 1235 patients had prevalent cardiovascular disease. These patients had a significantly lower mtDNA copy number than patients without cardiovascular disease (fully-adjusted model: odds ratio 1.03, 95\% confidence interval [CI] 1.01-1.05 per 10 mtDNA copies decrease). After four years of follow-up, we observed a significant inverse association between mtDNA copy number and all-cause mortality, adjusted for kidney function and cardiovascular disease risk factors (hazard ratio 1.37, 95\% CI 1.09-1.73 for quartile 1 compared to quartiles 2-4). When grouped by causes of death, estimates pointed in the same direction for all causes but in a fully-adjusted model decreased copy numbers were significantly lower only in infection-related death (hazard ratio 1.82, 95\% CI 1.08-3.08). A similar association was observed for hospitalizations due to infections in 644 patients (hazard ratio 1.19, 95\% CI 1.00-1.42 in the fully-adjusted model). Thus, our data support a role of mitochondrial dysfunction in increased cardiovascular disease and mortality risks as well as susceptibility to infections in patients with CKD.}, language = {en} } @article{LummaValkBoeckleretal.2018, author = {Lumma, Anna-Lena and Valk, Sofie L. and B{\"o}ckler, Anne and Vrtička, Pascal and Singer, Tania}, title = {Change in emotional self-concept following socio-cognitive training relates to structural plasticity of the prefrontal cortex}, series = {Brain and Behavior}, volume = {8}, journal = {Brain and Behavior}, doi = {10.1002/brb3.940}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-237395}, year = {2018}, abstract = {Introduction Self-referential processing is a key component of the emotional self-concept. Previous studies have shown that emotional self-referential processing is related to structure and function of cortical midline areas such as medial prefrontal cortex (mPFC), and that it can be altered on a behavioral level by specific mental training practices. However, it remains unknown how behavioral training-related change in emotional self-concept content relates to structural plasticity. Methods To address this issue, we examined the relationship between training-induced change in participant's emotional self-concept measured through emotional word use in the Twenty Statement Test and change in cortical thickness in the context of a large-scale longitudinal mental training study called the ReSource Project. Results Based on prior behavioral findings showing increased emotional word use particularly after socio-cognitive training targeting perspective-taking capacities, this study extended these results by revealing that individual differences in the degree to which participants changed their emotional self-concept after training was positively related to cortical thickness change in right mPFC extending to dorsolateral PFC (dlPFC). Furthermore, increased self-related negative emotional word use after training was positively associated with cortical thickness change in left pars orbitalis and bilateral dlPFC. Conclusions Our findings reveal training-related structural brain change in regions known to be involved in self-referential processing and cognitive control, and could indicate a relationship between restructuring of the emotional self-concept content as well as reappraisal of negative aspects and cortical thickness change. As such, our findings can guide the development of psychological interventions targeted to alter specific facets of the self-concept.}, language = {en} } @article{KiserPoppSchmittBoehreretal.2019, author = {Kiser, Dominik P. and Popp, Sandy and Schmitt-B{\"o}hrer, Angelika G. and Strekalova, Tatyana and van den Hove, Daniel L. and Lesch, Klaus-Peter and Rivero, Olga}, title = {Early-life stress impairs developmental programming in Cadherin 13 (CDH13)-deficient mice}, series = {Progress in Neuropsychopharmacology \& Biological Psychiatry}, volume = {89}, journal = {Progress in Neuropsychopharmacology \& Biological Psychiatry}, doi = {10.1016/j.pnpbp.2018.08.010}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325859}, pages = {158-168}, year = {2019}, abstract = {Objective Cadherin-13 (CDH13), a member of the calcium-dependent cell adhesion molecule family, has been linked to neurodevelopmental disorders, including autism spectrum (ASD) and attention-deficit/hyperactivity (ADHD) disorders, but also to depression. In the adult brain, CDH13 expression is restricted e.g. to the presynaptic compartment of inhibitory GABAergic synapses in the hippocampus and Cdh13 knockout mice show an increased inhibitory drive onto hippocampal CA1 pyramidal neurons, leading to a shift in excitatory/inhibitory balance. CDH13 is also moderating migration of serotonergic neurons in the dorsal raphe nucleus, establishing projections preferentially to the thalamus and cerebellum during brain development. Furthermore, CDH13 is upregulated by chronic stress as well as in depression, suggesting a role in early-life adaptation to stressful experience. Here, we therefore investigated the interaction between Cdh13 variation and neonatal maternal separation (MS) in mice. Methods Male and female wild-type (Cdh13+/+), heterozygous (Cdh13+/-) and homozygous (Cdh13-/-) knockout mice exposed to MS, or daily handling as control, were subjected to a battery of behavioural tests to assess motor activity, learning and memory as well as anxiety-like behaviour. A transcriptome analysis of the hippocampus was performed in an independent cohort of mice which was exposed to MS or handling, but remained na{\"i}ve for behavioural testing. Results MS lead to increased anxiety-like behaviour in Cdh13-/- mice compared to the other two MS groups. Cdh13-/- mice showed a context-dependent effect on stress- and anxiety-related behaviour, impaired extinction learning following contextual fear conditioning and decreased impulsivity, as well as a mild decrease in errors in the Barnes maze and reduced risk-taking in the light-dark transition test after MS. We also show sex differences, with increased locomotor activity in female Cdh13-/- mice, but unaltered impulsivity and activity in male Cdh13-/- mice. Transcriptome analysis revealed several pathways associated with cell surface/adhesion molecules to be altered following Cdh13 deficiency, together with an influence on endoplasmic reticulum function. Conclusion MS resulted in increased stress resilience, increased exploration and an overall anxiolytic behavioural phenotype in male Cdh13+/+ and Cdh13+/- mice. Cdh13 deficiency, however, obliterated most of the effects caused by early-life stress, with Cdh13-/- mice exhibiting delayed habituation, no reduction of anxiety-like behaviour and decreased fear extinction. Our behavioural findings indicate a role of CDH13 in the programming of and adaptation to early-life stress. Finally, our transcriptomic data support the view of CDH13 as a neuroprotective factor as well as a mediator in cell-cell interactions, with an impact on synaptic plasticity.}, language = {en} } @techreport{Gessner2024, type = {Working Paper}, author = {Geßner, Daniel}, title = {Rethinking renewable energy policies for hydrogen - How the intercept of electricity and hydrogen markets can be addressed}, doi = {10.25972/OPUS-37097}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-370973}, pages = {30}, year = {2024}, abstract = {A lot of countries have recently published updated hydrogen strategies, often including more ambitious targets for hydrogen production. In parallel, accompanying ramp-up mechanisms are increasingly coming into focus with the first ones already being released. However, these proposals usually translate mechanisms from renewable energy (RE) policy without considering the specific uncertainties, spillovers, and externalities of integrating hydrogen electrolysis into electricity grids. This article details how different aspects of a policy can address the specific issues, namely funding, risk-mitigation, and the complex relation with electricity markets. It shows that, compared to RE policy, subsidies need to emphasize the input side more strongly as price risks and intermittency from electricity markets are more prominent than from hydrogen markets. Also, it proposes a targeted mechanism to capture the positive externality of mitigating excess electricity in the grid while keeping investment security high. Economic policy should consider such approaches before massively scaling support and avoid the design shortcomings experienced with early RE policy.}, subject = {Wasserstoff}, language = {en} } @article{TaubenboeckWeigandEschetal.2019, author = {Taubenb{\"o}ck, H. and Weigand, M. and Esch, T. and Staab, J. and Wurm, M. and Mast, J. and Dech, S.}, title = {A new ranking of the world's largest cities—Do administrative units obscure morphological realities?}, series = {Remote Sensing of Environment}, volume = {232}, journal = {Remote Sensing of Environment}, doi = {10.1016/j.rse.2019.111353}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240634}, year = {2019}, abstract = {With 37 million inhabitants, Tokyo is the world's largest city in UN statistics. With this work we call this ranking into question. Usually, global city rankings are based on nationally collected population figures, which rely on administrative units. Sprawling urban growth, however, leads to morphological city extents that may surpass conventional administrative units. In order to detect spatial discrepancies between the physical and the administrative city, we present a methodology for delimiting Morphological Urban Areas (MUAs). We understand MUAs as a territorially contiguous settlement area that can be distinguished from low-density peripheral and rural hinterlands. We design a settlement index composed of three indicators (settlement area, settlement area proportion and density within the settlements) describing a gradient of built-up density from the urban center to the periphery applying a sectoral monocentric city model. We assume that the urban-rural transition can be defined along this gradient. With it, we re-territorialize the conventional administrative units. Our data basis are recent mapping products derived from multi-sensoral Earth observation (EO) data - namely the Global Urban Footprint (GUF) and the GUF Density (GUF-DenS) - providing globally consistent knowledge about settlement locations and densities. For the re-territorialized MUAs we calculate population numbers using WorldPop data. Overall, we cover the 1692 cities with >300,000 inhabitants on our planet. In our results we compare the consistently re-territorialized MUAs and the administrative units as well as their related population figures. We find the MUA in the Pearl River Delta the largest morphologically contiguous urban agglomeration in the world with a calculated population of 42.6 million. Tokyo, in this new list ranked number 2, loses its top position. In rank-size distributions we present the resulting deviations from previous city rankings. Although many MUAs outperform administrative units by area, we find that, contrary to what we assumed, in most cases MUAs are considerably smaller than administrative units. Only in Europe we find MUAs largely outweighing administrative units in extent.}, language = {en} } @article{GermainElliottFalissardetal.2019, author = {Germain, Dominique P. and Elliott, Perry M. and Falissard, Bruno and Fomin, Victor V. and Hilz, Max J. and Jovanovic, Ana and Kantola, Ilkka and Linhart, Aleš and Renzo, Mignani and Namdar, Mehdi and Nowak, Albina and Oliveira, Jo{\~a}o-Paulo and Pieroni, Maurizio and Viana-Baptista, Miguel and Wanner, Christoph and Spada, Marco}, title = {The effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: A systematic literature review by a European panel of experts}, series = {Molecular Genetics and Metabolism Reports}, volume = {19}, journal = {Molecular Genetics and Metabolism Reports}, doi = {10.1016/j.ymgmr.2019.100454}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232987}, year = {2019}, abstract = {Background Enzyme replacement therapy (ERT) with recombinant human α-galactosidase has been available for the treatment of Fabry disease since 2001 in Europe and 2003 in the USA. Treatment outcomes with ERT are dependent on baseline patient characteristics, and published data are derived from heterogeneous study populations. Methods We conducted a comprehensive systematic literature review of all original articles on ERT in the treatment of Fabry disease published up until January 2017. This article presents the findings in adult male patients. Results Clinical evidence for the efficacy of ERT in adult male patients was available from 166 publications including 36 clinical trial publications. ERT significantly decreases globotriaosylceramide levels in plasma, urine, and in different kidney, heart, and skin cell types, slows the decline in estimated glomerular filtration rate, and reduces/stabilizes left ventricular mass and cardiac wall thickness. ERT also improves nervous system, gastrointestinal, pain, and quality of life outcomes. Conclusions ERT is a disease-specific treatment for patients with Fabry disease that may provide clinical benefits on several outcomes and organ systems. Better outcomes may be observed when treatment is started at an early age prior to the development of organ damage such as chronic kidney disease or cardiac fibrosis. Consolidated evidence suggests a dose effect. Data described in male patients, together with female and paediatric data, informs clinical practice and therapeutic goals for individualized treatment.}, language = {en} } @article{FlunkertMaierhoferDittrichetal.2018, author = {Flunkert, Julia and Maierhofer, Anna and Dittrich, Marcus and M{\"u}ller, Tobias and Horvath, Steve and Nanda, Indrajit and Haaf, Thomas}, title = {Genetic and epigenetic changes in clonal descendants of irradiated human fibroblasts}, series = {Experimental Cell Research}, volume = {370}, journal = {Experimental Cell Research}, doi = {10.1016/j.yexcr.2018.06.034}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228177}, pages = {322-332}, year = {2018}, abstract = {To study delayed genetic and epigenetic radiation effects, which may trigger radiation-induced carcinogenesis, we have established single-cell clones from irradiated and non-irradiated primary human fibroblasts. Stable clones were endowed with the same karyotype in all analyzed metaphases after 20 population doublings (PDs), whereas unstable clones displayed mosaics of normal and abnormal karyotypes. To account for variation in radiation sensitivity, all experiments were performed with two different fibroblast strains. After a single X-ray dose of 2 Gy more than half of the irradiated clones exhibited radiation-induced genome instability (RIGI). Irradiated clones displayed an increased rate of loss of chromosome Y (LOY) and copy number variations (CNVs), compared to controls. CNV breakpoints clustered in specific chromosome regions, in particular 3p14.2 and 7q11.21, coinciding with common fragile sites. CNVs affecting the FHIT gene in FRA3B were observed in independent unstable clones and may drive RIGI. Bisulfite pyrosequencing of control clones and the respective primary culture revealed global hypomethylation of ALU, LINE-1, and alpha-satellite repeats as well as rDNA hypermethylation during in vitro ageing. Irradiated clones showed further reduced ALU and alpha-satellite methylation and increased rDNA methylation, compared to controls. Methylation arrays identified several hundred differentially methylated genes and several enriched pathways associated with in vitro ageing. Methylation changes in 259 genes and the MAP kinase signaling pathway were associated with delayed radiation effects (after 20 PDs). Collectively, our results suggest that both genetic (LOY and CNVs) and epigenetic changes occur in the progeny of exposed cells that were not damaged directly by irradiation, likely contributing to radiation-induced carcinogenesis. We did not observe epigenetic differences between stable and unstable irradiated clones. The fact that the DNA methylation (DNAm) age of clones derived from the same primary culture varied greatly suggests that DNAm age of a single cell (represented by a clone) can be quite different from the DNAm age of a tissue. We propose that DNAm age reflects the emergent property of a large number of individual cells whose respective DNAm ages can be highly variable.}, language = {en} } @article{GermainAradBurlinaetal.2019, author = {Germain, Dominique P. and Arad, Michael and Burlina, Alessandro and Elliott, Perry M. and Falissard, Bruno and Feldt-Rasmussen, Ulla and Hilz, Max J. and Hughes, Derralynn A. and Ortiz, Alberto and Wanner, Christoph and Weidemann, Frank and Spada, Marco}, title = {The effect of enzyme replacement therapy on clinical outcomes in female patients with Fabry disease - A systematic literature review by a European panel of experts}, series = {Molecular Genetics and Metabolism}, volume = {126}, journal = {Molecular Genetics and Metabolism}, doi = {10.1016/j.ymgme.2018.09.007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232963}, pages = {224-235}, year = {2019}, abstract = {Background Heterozygous females with Fabry disease have a wide range of clinical phenotypes depending on the nature of their mutation and their X-chromosome inactivation pattern; it is therefore important to examine outcomes of enzyme replacement therapy (ERT) in the female patient population specifically. This paper presents the findings of a systematic literature review of treatment outcomes with ERT in adult female patients. Methods A comprehensive systematic literature review was conducted through January 2017 to retrieve published papers with original data on ERT in the treatment of Fabry disease. The review included all original articles that presented ERT outcomes data on patients with Fabry disease, irrespective of the study type. Results Clinical evidence for the efficacy of ERT in female patients was available from 67 publications including six clinical trial publications, and indicates significant reductions in plasma and urine globotriaosylceramide (GL-3) accumulation (in female patients with elevated pre-treatment levels) and improvements in cardiac parameters and quality of life (QoL). To date, data are insufficient to conclude on the effects of ERT on the nervous system, gastrointestinal manifestations, and pain in female patients with Fabry disease. Conclusions This review of available literature data demonstrates that ERT in adult female patients with Fabry disease has a beneficial effect on GL-3 levels and cardiac outcomes. The current evidence also suggests that ERT may improve QoL in this patient population, though further studies are needed to examine these results.}, language = {en} } @article{OmenacaVazquezGarciaCorbeiraetal.2018, author = {Ome{\~n}aca, Felix and V{\´a}zquez, Liliana and Garcia-Corbeira, Pilar and Mesaros, Narcisa and Hanssens, Linda and Dolhain, Jan and Puente G{\´o}mez, Ivonne and Liese, Johannes and Knuf, Markus}, title = {Immunization of preterm infants with GSK's hexavalent combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine: A review of safety and immunogenicity}, series = {Vaccine}, volume = {36}, journal = {Vaccine}, doi = {10.1016/j.vaccine.2018.01.005}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234450}, pages = {986-996}, year = {2018}, abstract = {Background Infants with history of prematurity (<37 weeks gestation) and low birth weight (LBW, <2500 g) are at high risk of infection due to functional immaturity of normal physical and immunological defense mechanisms. Despite current recommendations that infants with history of prematurity/LBW should receive routine immunization according to the same schedule and chronological age as full-term infants, immunization is often delayed. Methods Here we summarize 10 clinical studies and 15 years of post-marketing safety surveillance of GSK's hexavalent vaccine (DTPa-HBV-IPV/Hib), a combined diphtheria-tetanus-acellular-pertussis-hepatitis-B-inactivated-poliovirus-Haemophilus influenzae-type-b (Hib) conjugate vaccine, when administered alone, or co-administered with pneumococcal conjugate, rotavirus, and meningococcal vaccines and respiratory syncytial virus IgG to infants with history of prematurity/LBW in clinical trials. Results At least 92.5\% of infants with history of prematurity/LBW as young as 24 weeks gestation in clinical studies were seropositive to all vaccine antigens after 3-dose primary vaccination with GSK's hexavalent DTPa-HBV-IPV/Hib vaccine, with robust immune responses to booster vaccination. Seropositivity rates and antibody concentrations to hepatitis B and Hib appeared lower in infants with history of prematurity/LBW than term infants. Between 13-30\% of medically stable infants with history of prematurity developed apnea after vaccination with GSK's hexavalent DTPa-HBV-IPV/Hib vaccine; usually after dose 1. The occurrence of post-immunization cardiorespiratory events appears to be influenced by the severity of any underlying neonatal condition. Most cardiorespiratory events resolve spontaneously or require minimal intervention. GSK's hexavalent DTPa-HBV-IPV/Hib vaccine was well tolerated in co-administration regimens. Conclusion GSK's hexavalent DTPa-HBV-IPV/Hib vaccine alone or co-administered with other pediatric vaccines has a clinically acceptable safety and immunogenicity profile when used in infants with history of prematurity/LBW for primary and booster vaccination. Additional studies are needed in very premature and very LBW infants. However, currently available data support using GSK's hexavalent DTPa-HBV-IPV/Hib vaccine to immunize infants with history of prematurity/LBW according to chronological age.}, language = {en} } @article{SpadaBaronElliottetal.2019, author = {Spada, Marco and Baron, Ralf and Elliott, Perry M. and Falissard, Bruno and Hilz, Max J. and Monserrat, Lorenzo and T{\o}ndel, Camilla and Tylki-Szymańska, Anna and Wanner, Christoph and Germain, Dominique P.}, title = {The effect of enzyme replacement therapy on clinical outcomes in paediatric patients with Fabry disease - A systematic literature review by a European panel of experts}, series = {Molecular Genetics and Metabolism}, volume = {126}, journal = {Molecular Genetics and Metabolism}, doi = {10.1016/j.ymgme.2018.04.007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239287}, pages = {212-223}, year = {2019}, abstract = {Background Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL-3). The disease can manifest early during childhood and adolescence. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase is the first specific treatment for Fabry disease and has been available in Europe since 2001. This paper presents the findings of a systematic literature review of clinical outcomes with ERT in paediatric patients with Fabry disease. Methods A comprehensive systematic review of published literature on ERT in Fabry disease was conducted in January 2017. The literature analysis included all original articles reporting outcomes of ERT in paediatric patients. Results Treatment-related outcomes in the paediatric population were reported in six publications derived from open-label clinical trials and in 10 publications derived from observational or registry-based studies. ERT was shown to significantly reduce plasma and urine GL-3 levels in paediatric patients with Fabry disease. The effect of ERT on GL-3 clearance from renal podocytes appeared to be agalsidase dose-dependent. ERT relieved pain and improved gastrointestinal symptoms and quality of life. Conclusions Based on the published literature, the use of ERT in paediatric patients can significantly clear GL-3 accumulation, ameliorate the early symptoms of Fabry disease, and improve quality of life. Treatment with ERT in paediatric patients with Fabry disease may be important to prevent further disease progression and overt organ damage.}, language = {en} } @article{ArgyrousideNijsLagattaetal.2019, author = {Argyrousi, Elentina K. and de Nijs, Laurence and Lagatta, Davi C. and Schl{\"u}tter, Anna and Weidner, Magdalena T. and Z{\"o}ller, Johanna and van Goethem, Nick P. and Joca, S{\^a}mia R. L. and van den Hove, Daniel L. A. and Prickaerts, Jos}, title = {Effects of DNA methyltransferase inhibition on pattern separation performance in mice}, series = {Neurobiology of Learning and Memory}, volume = {159}, journal = {Neurobiology of Learning and Memory}, doi = {https://doi.org/10.1016/j.nlm.2019.02.003}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221226}, pages = {6-15}, year = {2019}, abstract = {Enhancement of synaptic plasticity through changes in neuronal gene expression is a prerequisite for improved cognitive performance. Moreover, several studies have shown that DNA methylation is able to affect the expression of (e.g. plasticity) genes that are important for several cognitive functions. In this study, the effect of the DNA methyltransferase (DNMT) inhibitor RG108 was assessed on object pattern separation (OPS) task in mice. In addition, its effect on the expression of target genes was monitored. Administration of RG108 before the test led to a short-lasting, dose-dependent increase in pattern separation memory that was not present anymore after 48 h. Furthermore, treatment with RG108 did not enhance long-term memory of the animals when tested after a 24 h inter-trial interval in the same task. At the transcriptomic level, acute treatment with RG108 was accompanied by increased expression of Bdnf1, while expression of Bdnf4, Bdnf9, Gria1 and Hdac2 was not altered within 1 h after treatment. Methylation analysis of 14 loci in the promoter region of Bdnf1 revealed a counterintuitive increase in the levels of DNA methylation at three CpG sites. Taken together, these results indicate that acute administration of RG108 has a short-lasting pro-cognitive effect on object pattern separation that could be explained by increased Bdnf1 expression. The observed increase in Bdnf1 methylation suggests a complex interplay between Bdnf methylation-demethylation that promotes Bdnf1 expression and associated cognitive performance. Considering that impaired pattern separation could constitute the underlying problem of a wide range of mental and cognitive disorders, pharmacological agents including DNA methylation inhibitors that improve pattern separation could be compelling targets for the treatment of these disorders. In that respect, future studies are needed in order to determine the effect of chronic administration of such agents.}, language = {en} } @article{FeistauerRichter2018, author = {Feistauer, Daniela and Richter, Tobias}, title = {Validity of students' evaluations of teaching: Biasing effects of likability and prior subject interest}, series = {Studies in Educational Evaluation}, volume = {59}, journal = {Studies in Educational Evaluation}, doi = {10.1016/j.stueduc.2018.07.009}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228005}, pages = {168-178}, year = {2018}, abstract = {This study examined the validity of students' evaluations of teaching as an instrument for measuring teaching quality by examining the effects of likability and prior subject interest as potential biasing effects, measured at the beginning of the course and at the time of evaluation. University students (N = 260) evaluated psychology courses in one semester at a German university with a standardized questionnaire, yielding 517 data points. Cross-classified multilevel analyses revealed fixed effects of likability at both times of measurement and fixed effects of prior subject interest measured at the beginning of the course. Likability seems to exert a substantial bias on student evaluations of teaching, albeit one that is overestimated when measured at the time of evaluation. In contrast, prior subject interest seems to introduce a weak bias. Considering that likability bears no conceptual relationship to teaching quality, these findings point to a compromised validity of students' evaluations of teaching.}, language = {en} } @article{GraystonCzannerElhaddetal.2019, author = {Grayston, Rebecca and Czanner, Gabriela and Elhadd, Kareim and Goebel, Andreas and Frank, Bernhard and {\"U}{\c{c}}eyler, Nurcan and Malik, Rayaz A and Alam, Uazman}, title = {A systematic review and meta-analysis of the prevalence of small fiber pathology in fibromyalgia: Implications for a new paradigm in fibromyalgia etiopathogenesis}, series = {Seminars in Arthritis and Rheumatism}, volume = {48}, journal = {Seminars in Arthritis and Rheumatism}, doi = {10.1016/j.semarthrit.2018.08.003}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227566}, pages = {933-940}, year = {2019}, abstract = {Objectives Fibromyalgia is a condition which exhibits chronic widespread pain with neuropathic pain features and has a major impact on health-related quality of life. The pathophysiology remains unclear, however, there is increasing evidence for involvement of the peripheral nervous system with a high prevalence of small fiber pathology (SFP). The aim of this systematic literature review is to establish the prevalence of SFP in fibromyalgia. Methods An electronic literature search was performed using MEDLINE, EMBASE, PubMed, Web of Science, CINAHL and the Cochrane Library databases. Published full-text, English language articles that provide SFP prevalence data in studies of fibromyalgia of patients over 18years old were included. All articles were screened by two independent reviewers using a priori criteria. Methodological quality and risk of bias were evaluated using the critical appraisal tool by Munn et al. Overall and subgroup pooled prevalence were calculated by random-effects meta-analysis with 95\% CI. Results Database searches found 935 studies; 45 articles were screened of which 8 full text articles satisfied the inclusion criteria, providing data from 222 participants. The meta-analysis demonstrated the pooled prevalence of SFP in fibromyalgia is 49\% (95\% CI: 38-60\%) with a moderate degree of heterogeneity, (I2= 68\%). The prevalence estimate attained by a skin biopsy was 45\% (95\% CI: 32-59\%, I2= 70\%) and for corneal confocal microscopy it was 59\% (95\% CI: 40-78\%, I2= 51\%). Conclusion There is a high prevalence of SFP in fibromyalgia. This study provides compelling evidence of a distinct phenotype involving SFP in fibromyalgia. Identifying SFP will aid in determining its relationship to pain and potentially facilitate the development of future interventions and pharmacotherapy.}, language = {en} } @article{SchubertHagedornYoshiietal.2018, author = {Schubert, Frank K. and Hagedorn, Nicolas and Yoshii, Taishi and Helfrich-F{\"o}rster, Charlotte and Rieger, Dirk}, title = {Neuroanatomical details of the lateral neurons of Drosophila melanogaster support their functional role in the circadian system}, series = {Journal of Comparative Neurology}, volume = {526}, journal = {Journal of Comparative Neurology}, doi = {10.1002/cne.24406}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234477}, pages = {1209-1231}, year = {2018}, abstract = {Drosophila melanogaster is a long-standing model organism in the circadian clock research. A major advantage is the relative small number of about 150 neurons, which built the circadian clock in Drosophila. In our recent work, we focused on the neuroanatomical properties of the lateral neurons of the clock network. By applying the multicolor-labeling technique Flybow we were able to identify the anatomical similarity of the previously described E2 subunit of the evening oscillator of the clock, which is built by the 5th small ventrolateral neuron (5th s-LNv) and one ITP positive dorsolateral neuron (LNd). These two clock neurons share the same spatial and functional properties. We found both neurons innervating the same brain areas with similar pre- and postsynaptic sites in the brain. Here the anatomical findings support their shared function as a main evening oscillator in the clock network like also found in previous studies. A second quite surprising finding addresses the large lateral ventral PDF-neurons (l-LNvs). We could show that the four hardly distinguishable l-LNvs consist of two subgroups with different innervation patterns. While three of the neurons reflect the well-known branching pattern reproduced by PDF immunohistochemistry, one neuron per brain hemisphere has a distinguished innervation profile and is restricted only to the proximal part of the medulla-surface. We named this neuron "extra" l-LNv (l-LNvx). We suggest the anatomical findings reflect different functional properties of the two l-LNv subgroups.}, language = {en} } @article{ChenGehringerLorenz2018, author = {Chen, Dan and Gehringer, Matthias and Lorenz, Sonja}, title = {Developing Small-Molecule Inhibitors of HECT-Type Ubiquitin Ligases for Therapeutic Applications: Challenges and Opportunities}, series = {ChemBioChem}, volume = {19}, journal = {ChemBioChem}, doi = {10.1002/cbic.201800321}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222412}, pages = {2123-2135}, year = {2018}, abstract = {The ubiquitin system regulates countless physiological and disease-associated processes and has emerged as an attractive entryway for therapeutic efforts. With over 600 members in the human proteome, ubiquitin ligases are the most diverse class of ubiquitylation enzymes and pivotal in encoding specificity in ubiquitin signaling. Although considerable progress has been made in the identification of small molecules targeting RING ligases, relatively little is known about the "druggability" of HECT (homologous to E6AP C terminus) ligases, many of which are critically implicated in human pathologies. A major obstacle to optimizing the few available ligands is our incomplete understanding of their inhibitory mechanisms and the structural basis of catalysis in HECT ligases. Here, we survey recent approaches to manipulate the activities of HECT ligases with small molecules to showcase the particular challenges and opportunities these enzymes hold as therapeutic targets.}, language = {en} }