@article{WildMarshallBocketal.2012, author = {Wild, J. M. and Marshall, H. and Bock, M. and Schad, L. R. and Jakob, P. M. and Puderbach, M. and Molinari, F. and Van Beek, E. J. R. and Biederer, J.}, title = {MRI of the lung (1/3): methods}, series = {Insights into Imaging}, volume = {3}, journal = {Insights into Imaging}, number = {4}, doi = {10.1007/s13244-012-0176-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124238}, pages = {345-353}, year = {2012}, abstract = {Proton magnetic resonance imaging (MRI) has recently emerged as a clinical tool to image the lungs. This paper outlines the current technical aspects of MRI pulse sequences, radiofrequency (RF) coils and MRI system requirements needed for imaging the pulmonary parenchyma and vasculature. Lung MRI techniques are presented as a "technical toolkit", from which MR protocols will be composed in the subsequent papers for comprehensive imaging of lung disease and function (parts 2 and 3). This paper is pitched at MR scientists, technicians and radiologists who are interested in understanding and establishing lung MRI methods. Images from a 1.5 T scanner are used for illustration of the sequences and methods that are highlighted. Main Messages • Outline of the hardware and pulse sequence requirements for proton lung MRI • Overview of pulse sequences for lung parenchyma, vascular and functional imaging with protons • Demonstration of the pulse-sequence building blocks for clinical lung MRI protocols}, language = {en} } @article{TappeHaeuplerSchaeferetal.2013, author = {Tappe, Dennis and Haeupler, Alexandra and Sch{\"a}fer, Hansj{\"o}rg and Racz, Paul and Cramer, Jakob P. and Poppert, Sven}, title = {Armillifer armillatus Pentastomiasis in African Immigrant, Germany}, series = {Emerging Infectious Diseases}, volume = {19}, journal = {Emerging Infectious Diseases}, number = {3}, doi = {10.3201/eid1903.121508}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129054}, pages = {507-508}, year = {2013}, abstract = {No abstract available.}, language = {en} } @article{SchrautJakobWeidneretal.2014, author = {Schraut, K. G. and Jakob, S. B. and Weidner, M. T. and Schmitt, A. G. and Scholz, C. J. and Strekalova, T. and El Hajj, N. and Eijssen, L. M. T. and Domschke, K. and Reif, A. and Haaf, T. and Ortega, G. and Steinbusch, H. W. M. and Lesch, K. P. and Van den Hove, D. L.}, title = {Prenatal stress-induced programming of genome-wide promoter DNA methylation in 5-HTT-deficient mice}, series = {Translational Psychiatry}, volume = {4}, journal = {Translational Psychiatry}, doi = {10.1038/tp.2014.107}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119199}, pages = {e473}, year = {2014}, abstract = {The serotonin transporter gene (5-HTT/SLC6A4)-linked polymorphic region has been suggested to have a modulatory role in mediating effects of early-life stress exposure on psychopathology rendering carriers of the low-expression short (s)-variant more vulnerable to environmental adversity in later life. The underlying molecular mechanisms of this gene-by-environment interaction are not well understood, but epigenetic regulation including differential DNA methylation has been postulated to have a critical role. Recently, we used a maternal restraint stress paradigm of prenatal stress (PS) in 5-HTT-deficient mice and showed that the effects on behavior and gene expression were particularly marked in the hippocampus of female 5-Htt+/- offspring. Here, we examined to which extent these effects are mediated by differential methylation of DNA. For this purpose, we performed a genome-wide hippocampal DNA methylation screening using methylated-DNA immunoprecipitation (MeDIP) on Affymetrix GeneChip Mouse Promoter 1.0 R arrays. Using hippocampal DNA from the same mice as assessed before enabled us to correlate gene-specific DNA methylation, mRNA expression and behavior. We found that 5-Htt genotype, PS and their interaction differentially affected the DNA methylation signature of numerous genes, a subset of which showed overlap with the expression profiles of the corresponding transcripts. For example, a differentially methylated region in the gene encoding myelin basic protein (Mbp) was associated with its expression in a 5-Htt-, PS- and 5-Htt × PS-dependent manner. Subsequent fine-mapping of this Mbp locus linked the methylation status of two specific CpG sites to Mbp expression and anxiety-related behavior. In conclusion, hippocampal DNA methylation patterns and expression profiles of female prenatally stressed 5-Htt+/- mice suggest that distinct molecular mechanisms, some of which are promoter methylation-dependent, contribute to the behavioral effects of the 5-Htt genotype, PS exposure and their interaction.}, language = {en} } @article{SchmidtHaywardCoelhoetal.2019, author = {Schmidt, Thomas S. B. and Hayward, Matthew R. and Coelho, Luiis P. and Li, Simone S. and Costea, Paul I. and Voigt, Anita Y. and Wirbel, Jakob and Maistrenko, Oleksandr M. and Alves, Renato J. C. and Bergsten, Emma and de Beaufort, Carine and Sobhani, Iradj and Heintz-Buschart, Anna and Sunagawa, Shinichi and Zeller, Georg and Wilmes, Paul and Bork, Peer}, title = {Extensive transmission of microbes along the gastrointestinal tract}, series = {eLife}, volume = {8}, journal = {eLife}, doi = {10.7554/eLife.42693}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228954}, pages = {e42693, 1-18}, year = {2019}, abstract = {The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 individuals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy individuals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens. This establishes the oral cavity as an endogenous reservoir for gut microbial strains, and oral-fecal transmission as an important process that shapes the gastrointestinal microbiome in health and disease.}, subject = {Barrier}, language = {en} } @article{SchmalzlPlumhoffGilbertetal.2019, author = {Schmalzl, J. and Plumhoff, P. and Gilbert, F. and Gohlke, F. and Konrads, C. and Brunner, U. and Jakob, F. and Ebert, R. and Steinert, AF}, title = {The inflamed biceps tendon as a pain generator in the shoulder: A histological and biomolecular analysis}, series = {Journal of Orthopaedic Surgery}, volume = {27}, journal = {Journal of Orthopaedic Surgery}, number = {1}, doi = {10.1177/2309499018820349}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228611}, pages = {1-10}, year = {2019}, abstract = {Introduction: The long head of the biceps (LHB) is often resected in shoulder surgery. However, its contribution to inflammatory processes in the shoulder remains unclear. In the present study, inflamed and noninflamed human LHBs were comparatively characterized for features of inflammation. Materials and methods: Twenty-two resected LHB tendons were classified into inflamed (n = 11) and noninflamed (n = 11) samples. For histological examination, samples were stained with hematoxylin eosin, Azan, van Gieson, and Masson Goldner trichrome. Neuronal tissue was immunohistochemically visualized. In addition, specific inflammatory marker gene expression of primary LHB-derived cell cultures were analyzed. Results: Features of tendinopathy, such as collagen disorganization, infiltration by inflammatory cells, neovascularization, and extensive neuronal innervation were found in the tendinitis group. Compared to noninflamed samples, inflamed LHBs showed a significantly increased inflammatory marker gene expression Conclusion: Structural and biomolecular differences of both groups suggest that the LHB tendon acts as an important pain generator in the shoulder joint. These findings can, on the one hand, contribute to the understanding of the biomolecular genesis of LHB tendinitis and, on the other hand, provide possibilities for new therapeutic approaches.}, language = {en} } @article{PhamHelluyBraeuningeretal.2010, author = {Pham, Mirko and Helluy, X. and Braeuninger, S. and Jakob, P. and Stoll, G. and Kleinschnitz, Christoph and Bendszus, M.}, title = {Outcome of experimental stroke in C57Bl/6 and Sv/129 mice assessed by multimodal ultra-high field MRI}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68115}, year = {2010}, abstract = {Transgenic mice bred on C57Bl/6 or Sv/129 genetic background are frequently used in stroke research. It is well established that variations in cerebrovascular anatomy and hemodynamics can influence stroke outcome in different inbred mouse lines. We compared stroke development in C57Bl/6 and Sv/129 mice in the widely used model of transient middle cerebral artery occlusion (tMCAO) by multimodal ultra-high field magnetic resonance imaging (MRI). C57Bl/6 and Sv/129 mice underwent 60 min of tMCAO and were analyzed by MRI 2 h and 24 h afterwards. Structural and functional images were registered to a standard anatomical template. Probability maps of infarction were rendered by automated segmentation from quantitative T2-relaxometric images. Whole-brain segmentation of infarction was accomplished manually on high-resolution T2-weighted (T2-w) RARE images. Cerebral perfusion (cerebral blood flow, CBF) was measured quantitatively by modified continuous arterial-spin-labeling (CASL) and apparent diffusion coefficients (ADC) by spin-echo diffusion-weighted imaging (DWI). Probabilities of cortical (95.1\% ± 3.1 vs. 92.1\% ± 2.5; p > 0.05) and subcortical (100\% vs. 100\%; p > 0.05) infarctions at 24 h were similar in both groups as was the whole-brain volumetric extent of cerebral infarction. In addition, CBF and ADC values did not differ between C57Bl/6 and Sv/129 mice at any time point or region of interest. The C57Bl/6 and Sv/129 genetic background is no major confounding factor of infarct size and cerebral perfusion in the tMCAO model.}, subject = {NMR-Tomographie}, language = {en} } @article{JendeKenderRotheretal.2020, author = {Jende, Johann M. E. and Kender, Zoltan and Rother, Christian and Alvarez-Ramos, Lucia and Groener, Jan B. and Pham, Mirko and Morgenstern, Jakob and Oikonomou, Dimitrios and Hahn, Artur and Juerchott, Alexander and Kollmer, Jennifer and Heiland, Sabine and Kopf, Stefan and Nawroth, Peter P. and Bendszus, Martin and Kurz, Felix T.}, title = {Diabetic Polyneuropathy Is Associated With Pathomorphological Changes in Human Dorsal Root Ganglia: A Study Using 3T MR Neurography}, series = {Frontiers in Neuroscience}, volume = {14}, journal = {Frontiers in Neuroscience}, doi = {10.3389/fnins.2020.570744}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212459}, year = {2020}, abstract = {Diabetic neuropathy (DPN) is one of the most severe and yet most poorly understood complications of diabetes mellitus. In vivo imaging of dorsal root ganglia (DRG), a key structure for the understanding of DPN, has been restricted to animal studies. These have shown a correlation of decreased DRG volume with neuropathic symptom severity. Our objective was to investigate correlations of DRG morphology and signal characteristics at 3 Tesla (3T) magnetic resonance neurography (MRN) with clinical and serological data in diabetic patients with and without DPN. In this cross-sectional study, participants underwent 3T MRN of both L5 DRG using an isotropic 3D T2-weighted, fat-suppressed sequence with subsequent segmentation of DRG volume and analysis of normalized signal properties. Overall, 55 diabetes patients (66 ± 9 years; 32 men; 30 with DPN) took part in this study. DRG volume was smaller in patients with severe DPN when compared to patients with mild or moderate DPN (134.7 ± 21.86 vs 170.1 ± 49.22; p = 0.040). In DPN patients, DRG volume was negatively correlated with the neuropathy disability score (r = -0.43; 95\%CI = -0.66 to -0.14; p = 0.02), a measure of neuropathy severity. DRG volume showed negative correlations with triglycerides (r = -0.40; 95\%CI = -0.57 to -0.19; p = 0.006), and LDL cholesterol (r = -0.33; 95\%CI = -0.51 to -0.11; p = 0.04). There was a strong positive correlation of normalized MR signal intensity (SI) with the neuropathy symptom score in the subgroup of patients with painful DPN (r = 0.80; 95\%CI = 0.46 to 0.93; p = 0.005). DRG SI was positively correlated with HbA1c levels (r = 0.30; 95\%CI = 0.09 to 0.50; p = 0.03) and the triglyceride/HDL ratio (r = 0.40; 95\%CI = 0.19 to 0.57; p = 0.007). In this first in vivo study, we found DRG morphological degeneration and signal increase in correlation with neuropathy severity. This elucidates the potential importance of MR-based DRG assessments in studying structural and functional changes in DPN.}, language = {en} } @article{GramAlbertovaSchirmeretal.2022, author = {Gram, Maximilian and Albertova, P. and Schirmer, V. and Blaimer, M. and Gamer, M. and Herrmann, M. J. and Nordbeck, P. and Jakob, P. M.}, title = {Towards robust in vivo quantification of oscillating biomagnetic fields using Rotary Excitation based MRI}, series = {Scientific Reports}, volume = {12}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-022-19275-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300862}, year = {2022}, abstract = {Spin-lock based functional magnetic resonance imaging (fMRI) has the potential for direct spatially-resolved detection of neuronal activity and thus may represent an important step for basic research in neuroscience. In this work, the corresponding fundamental effect of Rotary EXcitation (REX) is investigated both in simulations as well as in phantom and in vivo experiments. An empirical law for predicting optimal spin-lock pulse durations for maximum magnetic field sensitivity was found. Experimental conditions were established that allow robust detection of ultra-weak magnetic field oscillations with simultaneous compensation of static field inhomogeneities. Furthermore, this work presents a novel concept for the emulation of brain activity utilizing the built-in MRI gradient system, which allows REX sequences to be validated in vivo under controlled and reproducible conditions. Via transmission of Rotary EXcitation (tREX), we successfully detected magnetic field oscillations in the lower nano-Tesla range in brain tissue. Moreover, tREX paves the way for the quantification of biomagnetic fields.}, language = {en} } @article{BenischSchillingKleinHitpassetal.2012, author = {Benisch, Peggy and Schilling, Tatjana and Klein-Hitpass, Ludger and Frey, S{\"o}nke P. and Seefried, Lothar and Raaijmakers, Nadja and Krug, Melanie and Regensburger, Martina and Zeck, Sabine and Schinke, Thorsten and Amling, Michael and Ebert, Amling and Jakob, Franz}, title = {The Transcriptional Profile of Mesenchymal Stem Cell Populations in Primary Osteoporosis Is Distinct and Shows Overexpression of Osteogenic Inhibitors}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {9}, doi = {10.1371/journal.pone.0045142}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133379}, pages = {e45142}, year = {2012}, abstract = {Primary osteoporosis is an age-related disease characterized by an imbalance in bone homeostasis. While the resorptive aspect of the disease has been studied intensely, less is known about the anabolic part of the syndrome or presumptive deficiencies in bone regeneration. Multipotent mesenchymal stem cells (MSC) are the primary source of osteogenic regeneration. In the present study we aimed to unravel whether MSC biology is directly involved in the pathophysiology of the disease and therefore performed microarray analyses of hMSC of elderly patients (79-94 years old) suffering from osteoporosis (hMSC-OP). In comparison to age-matched controls we detected profound changes in the transcriptome in hMSC-OP, e.g. enhanced mRNA expression of known osteoporosis-associated genes (LRP5, RUNX2, COL1A1) and of genes involved in osteoclastogenesis (CSF1, PTH1R), but most notably of genes coding for inhibitors of WNT and BMP signaling, such as Sclerostin and MAB21L2. These candidate genes indicate intrinsic deficiencies in self-renewal and differentiation potential in osteoporotic stem cells. We also compared both hMSC-OP and non-osteoporotic hMSC-old of elderly donors to hMSC of similar to 30 years younger donors and found that the transcriptional changes acquired between the sixth and the ninth decade of life differed widely between osteoporotic and non-osteoporotic stem cells. In addition, we compared the osteoporotic transcriptome to long term-cultivated, senescent hMSC and detected some signs for pre-senescence in hMSC-OP. Our results suggest that in primary osteoporosis the transcriptomes of hMSC populations show distinct signatures and little overlap with non-osteoporotic aging, although we detected some hints for senescence-associated changes. While there are remarkable inter-individual variations as expected for polygenetic diseases, we could identify many susceptibility genes for osteoporosis known from genetic studies. We also found new candidates, e.g. MAB21L2, a novel repressor of BMP-induced transcription. Such transcriptional changes may reflect epigenetic changes, which are part of a specific osteoporosis-associated aging process.}, language = {en} }