@article{GiampaoloWojcikSerflingetal.2017,
  author    = {Giampaolo, Sabrina and W{\´o}jcik, Gabriela and Serfling, Edgar and Patra, Amiya K.},
  title     = {Interleukin-2-regulatory T cell axis critically regulates maintenance of hematopoietic stem cells},
  series = {Oncotarget},
  volume    = {8},
  journal   = {Oncotarget},
  number    = {18},
  doi       = {10.18632/oncotarget.16377},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170947},
  pages     = {29625-29642},
  year      = {2017},
  abstract  = {The role of IL-2 in HSC maintenance is unknown. Here we show that Il2\(^{-/-}\) mice develop severe anomalies in HSC maintenance leading to defective hematopoiesis. Whereas, lack of IL-2 signaling was detrimental for lympho- and erythropoiesis, myelopoiesis was enhanced in Il2\(^{-/-}\) mice. Investigation of the underlying mechanisms of dysregulated hematopoiesis in Il2\(^{-/-}\) mice shows that the IL-2-T\(_{reg}\) cell axis is indispensable for HSC maintenance and normal hematopoiesis. Lack of T\(_{reg}\) activity resulted in increased IFN-γ production by activated T cells and an expansion of the HSCs in the bone marrow (BM). Though, restoring T\(_{reg}\) population successfully rescued HSC maintenance in Il2\(^{-/-}\) mice, preventing IFN-γ activity could do the same even in the absence of T\(_{reg}\) cells. Our study suggests that equilibrium in IL-2 and IFN-γ activity is critical for steady state hematopoiesis, and in clinical conditions of BM failure, IL-2 or anti-IFN-γ treatment might help to restore hematopoiesis.},
  language  = {en}
}
@article{MartratMaxwellTominagaetal.2011,
  author    = {Martrat, Griselda and Maxwell, Christopher A. and Tominaga, Emiko and Porta-de-la-Riva, Montserrat and Bonifaci, N{\´u}ria and G{\´o}mez-Bald{\´o}, Laia and Bogliolo, Massimo and L{\´a}zaro, Conxi and Blanco, Ignacio and Brunet, Joan and Neveling, Kornelia and et al,},
  title     = {Exploring the link between MORF4L1 and risk of breast cancer},
  series = {Breast Cancer Research},
  volume    = {13},
  journal   = {Breast Cancer Research},
  number    = {R40},
  doi       = {10.1186/bcr2862},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169119},
  pages     = {1-14},
  year      = {2011},
  abstract  = {Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, Ptrend = 0.45 and 0.05, P2df = 0.51 and 0.14, respectively; and rs10519219, Ptrend = 0.92 and 0.72, P2df = 0.76 and 0.07, respectively. Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.},
  language  = {en}
}
@article{ArltBiehlTayloretal.2011,
  author    = {Arlt, Wiebke and Biehl, Michael and Taylor, Angela E. and Hahner, Stefanie and Lib{\´e}, Rossella and Hughes, Beverly A. and Schneider, Petra and Smith, David J. and Stiekema, Han and Krone, Nils and Porfiri, Emilio and Opocher, Giuseppe and Bertherat, Jer{\^o}me and Mantero, Franco and Allolio, Bruno and Terzolo, Massimo and Nightingale, Peter and Shackleton, Cedric H. L. and Bertagna, Xavier and Fassnacht, Martin and Stewart, Paul M.},
  title     = {Urine Steroid Metabolomics as a Biomarker Tool for Detecting Malignancy in Adrenal Tumors},
  series = {The Journal of Clinical Endocrinology \& Metabolism},
  volume    = {96},
  journal   = {The Journal of Clinical Endocrinology \& Metabolism},
  number    = {12},
  doi       = {10.1210/jc.2011-1565},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154682},
  pages     = {3775 -- 3784},
  year      = {2011},
  abstract  = {Context: Adrenal tumors have a prevalence of around 2\% in the general population. Adrenocortical carcinoma (ACC) is rare but accounts for 2-11\% of incidentally discovered adrenal masses. Differentiating ACC from adrenocortical adenoma (ACA) represents a diagnostic challenge in patients with adrenal incidentalomas, with tumor size, imaging, and even histology all providing unsatisfactory predictive values. Objective: Here we developed a novel steroid metabolomic approach, mass spectrometry-based steroid profiling followed by machine learning analysis, and examined its diagnostic value for the detection of adrenal malignancy. Design: Quantification of 32 distinct adrenal derived steroids was carried out by gas chromatography/mass spectrometry in 24-h urine samples from 102 ACA patients (age range 19-84 yr) and 45 ACC patients (20-80 yr). Underlying diagnosis was ascertained by histology and metastasis in ACC and by clinical follow-up [median duration 52 (range 26-201) months] without evidence of metastasis in ACA. Steroid excretion data were subjected to generalized matrix learning vector quantization (GMLVQ) to identify the most discriminative steroids. Results: Steroid profiling revealed a pattern of predominantly immature, early-stage steroidogenesis in ACC. GMLVQ analysis identified a subset of nine steroids that performed best in differentiating ACA from ACC. Receiver-operating characteristics analysis of GMLVQ results demonstrated sensitivity = specificity = 90\% (area under the curve = 0.97) employing all 32 steroids and sensitivity = specificity = 88\% (area under the curve = 0.96) when using only the nine most differentiating markers. Conclusions: Urine steroid metabolomics is a novel, highly sensitive, and specific biomarker tool for discriminating benign from malignant adrenal tumors, with obvious promise for the diagnostic work-up of patients with adrenal incidentalomas.},
  language  = {en}
}
@article{IsaiasTrujilloSummersetal.2016,
  author    = {Isaias, Ioannis U. and Trujillo, Paula and Summers, Paul and Marotta, Giorgio and Mainardi, Luca and Pezzoli, Gianni and Zecca, Luigi and Costa, Antonella},
  title     = {Neuromelanin Imaging and Dopaminergic Loss in Parkinson's Disease},
  series = {Frontiers in Aging Neuroscience},
  volume    = {8},
  journal   = {Frontiers in Aging Neuroscience},
  number    = {196},
  doi       = {10.3389/fnagi.2016.00196},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164046},
  year      = {2016},
  abstract  = {Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the major pathologic substrate is a loss of dopaminergic neurons from the substantia nigra. Our main objective was to determine the correspondence between changes in the substantia nigra, evident in neuromelanin and iron sensitive magnetic resonance imaging (MRI), and dopaminergic striatal innervation loss in patients with PD. Eighteen patients and 18 healthy control subjects were included in the study. Using neuromelanin-MRI, we measured the volume of the substantia nigra and the contrast-to-noise-ratio between substantia nigra and a background region. The apparent transverse relaxation rate and magnetic susceptibility of the substantia nigra were calculated from dual-echo MRI. Striatal dopaminergic innervation was measured as density of dopamine transporter (DAT) by means of single-photon emission computed tomography and [123I] N-ω-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) tropane. Patients showed a reduced volume of the substantia nigra and contrast-to-noise-ratio and both positively correlated with the corresponding striatal DAT density. The apparent transverse relaxation rate and magnetic susceptibility values of the substantia nigra did not differ between patients and healthy controls. The best predictor of DAT reduction was the volume of the substantia nigra. Clinical and imaging correlations were also investigated for the locus coeruleus. Our results suggest that neuromelanin-MRI can be used for quantifying substantia nigra pathology in PD where it closely correlates with dopaminergic striatal innervation loss. Longitudinal studies should further explore the role of Neuromelanin-MRI as an imaging biomarker of PD, especially for subjects at risk of developing the disease.},
  language  = {en}
}
@article{LapaAriasLozaHayakawaetal.2017,
  author    = {Lapa, Constantin and Arias-Loza, Paula and Hayakawa, Nobuyuki and Wakabayashi, Hiroshi and Werner, Rudolf A. and Chen, Xinyu and Shinaji, Tetsuya and Herrmann, Ken and Pelzer, Theo and Higuchi, Takahiro},
  title     = {Whitening and impaired glucose utilization of brown adipose tissue in a rat model of type 2 diabetes mellitus},
  series = {Scientific Reports},
  volume    = {7},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-017-17148-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159066},
  pages     = {16795},
  year      = {2017},
  abstract  = {Brown adipose tissue (BAT) is an attractive therapeutic target to combat diabetes and obesity due to its ability to increase glucose expenditure. In a genetic rat model (ZDF fa/fa) of type-2 diabetes and obesity, we aimed to investigate glucose utilization of BAT by \(^{18}\)F-FDG PET imaging. Male Zucker diabetic fatty (ZDF) and Male Zucker lean (ZL) control rats were studied at 13 weeks. Three weeks prior to imaging, ZDF rats were randomized into a no-restriction (ZDF-ND) and a mild calorie restriction (ZDF-CR) group. Dynamic \(^{18}\)F-FDG PET using a dedicated small animal PET system was performed under hyperinsulinemic-euglycemic clamp. \(^{18}\)F-FDG PET identified intense inter-scapular BAT glucose uptake in all ZL control rats, while no focally increased \(^{18}\)F-FDG uptake was detected in all ZDF-ND rats. Mild but significant improved BAT tracer uptake was identified after calorie restriction in diabetic rats (ZDF-CR). The weight of BAT tissue and fat deposits were significantly increased in ZDF-CR and ZDF-ND rats as compared to ZL controls, while UCP-1 and mitochondrial concentrations were significantly decreased. Whitening and severely impaired insulin-stimulated glucose uptake in BAT was confirmed in a rat model of type-2 diabetes. Additionally, calorie restriction partially restored the impaired BAT glucose uptake.},
  language  = {en}
}
@article{HefnerBerberichLanversetal.2017,
  author    = {Hefner, Jochen and Berberich, Sara and Lanvers, Elena and Sanning, Maria and Steimer, Ann-Kathrin and Kunzmann, Volker},
  title     = {New insights into frequency and contents of fear of cancer progression/recurrence (FOP/FCR) in outpatients with colorectal carcinoma (CRC) receiving oral capecitabine: a pilot study at a comprehensive cancer center},
  series = {Patient Preference and Adherence},
  volume    = {11},
  journal   = {Patient Preference and Adherence},
  doi       = {10.2147/PPA.S142784},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158476},
  pages     = {1907-1914},
  year      = {2017},
  abstract  = {Background: Fear of cancer progression/recurrence (FOP/FCR) is considered one of the most prevalent sources of distress in cancer survivors and associated with lower quality of life and functional impairment. Detailed measures of FOP/FCR are needed because little is known about the knowledge of FOP/FCR, its associations with the patient-doctor relationship, and the rate of adequate therapy. Colorectal cancer (CRC) is one of the most prevalent cancer entities, and oral capecitabine is widely prescribed as treatment. Therefore, we initiated a pilot study to expand the literature on FOP/FCR in CRC outpatients receiving capecitabine and to generate hypotheses for future investigations. Methods: This study included 58 patients treated at a comprehensive cancer center. FOP/FCR was assessed with the Fear of Progression Questionnaire (FOP-Q-SF). Satisfaction with the relationships with doctors was assessed with the Patient-Doctor Relationship Questionnaire-9 (PRDQ-9). Levels of side effects were rated by the patients on a visual analog scale. Clinical data were extracted from the charts. Results: A total of 19 out of 58 patients (36\%) suffered from FOP/FCR according to our assessment. Levels of FOP/FCR seemed to be mostly moderate to high. Only four out of the 19 distressed patients (21\%) were treated accordingly. Typical side effects of oncological treatment were associated with higher FOP/FCR. Satisfaction with doctor-patient relationships was not associated with FOP/FCR. Regarding single items of FOP/FCR, three out of the five most prevalent fears were associated with close relatives. Discussion: FOP/FCR occurred frequently in more than one in three patients, but was mostly untreated in this sample of consecutive outpatients with CRC receiving oral capecitabine. In detail, most fears were related to family and friends. In addition to an unmet need of patients, our data indicate sources of distress not considered thus far. If replicated in larger studies, results may help to inform intervention development and improve patient care.},
  language  = {en}
}
@article{HerrmannBeierSimonsetal.2016,
  author    = {Herrmann, Martin J. and Beier, Jennifer S. and Simons, Bibiane and Polak, Thomas},
  title     = {Transcranial Direct Current Stimulation (tDCS) of the Right Inferior Frontal Gyrus Attenuates Skin Conductance Responses to Unpredictable Threat Conditions},
  series = {Frontiers in Human Neuroscience},
  volume    = {10},
  journal   = {Frontiers in Human Neuroscience},
  number    = {352},
  doi       = {10.3389/fnhum.2016.00352},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146486},
  year      = {2016},
  abstract  = {Patients with panic and post-traumatic stress disorders seem to show increased psychophysiological reactions to conditions of unpredictable (U) threat, which has been discussed as a neurobiological marker of elevated levels of sustained fear in these disorders. Interestingly, a recent study found that the right inferior frontal gyrus (rIFG) is correlated to the successful regulation of sustained fear during U threat. Therefore this study aimed to examine the potential use of non-invasive brain stimulation to foster the rIFG by means of anodal transcranial direct current stimulation (tDCS) in order to reduce psychophysiological reactions to U threat. Twenty six participants were randomly assigned into an anodal and sham stimulation group in a double-blinded manner. Anodal and cathodal electrodes (7 * 5 cm) were positioned right frontal to target the rIFG. Stimulation intensity was I = 2 mA applied for 20 min during a task including U threat conditions (NPU-task). The effects of the NPU paradigm were measured by assessing the emotional startle modulation and the skin conductance response (SCR) at the outset of the different conditions. We found a significant interaction effect of condition × tDCS for the SCR (F(2,48) = 6.3, p < 0.01) without main effects of condition and tDCS. Post hoc tests revealed that the increase in SCR from neutral (N) to U condition was significantly reduced in verum compared to the sham tDCS group (t(24) = 3.84, p < 0.001). Our results emphasize the causal role of rIFG for emotional regulation and the potential use of tDCS to reduce apprehension during U threat conditions and therefore as a treatment for anxiety disorders.},
  language  = {en}
}
@article{WunschHohmannMillesetal.2016,
  author    = {Wunsch, Marie and Hohmann, Christopher and Milles, Bianca and Rostermund, Christina and Lehmann, Paul V. and Schroeter, Michael and Bayas, Antonios and Ulzheimer, Jochen and M{\"a}urer, Mathias and Erg{\"u}n, S{\"u}leyman and Kuerten, Stefanie},
  title     = {The Correlation between the Virus- and Brain Antigen-Specific B Cell Response in the Blood of Patients with Multiple Sclerosis},
  series = {Viruses},
  volume    = {8},
  journal   = {Viruses},
  number    = {4},
  doi       = {10.3390/v8040105},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146946},
  pages     = {105},
  year      = {2016},
  abstract  = {There is a largely divergent body of literature regarding the relationship between Epstein-Barr virus (EBV) infection and brain inflammation in multiple sclerosis (MS). Here, we tested MS patients during relapse (n = 11) and in remission (n = 19) in addition to n = 22 healthy controls to study the correlation between the EBV- and brain-specific B cell response in the blood by enzyme-linked immunospot (ELISPOT) and enzyme-linked immunosorbent assay (ELISA). Cytomegalovirus (CMV) was used as a control antigen tested in n = 16 MS patients during relapse and in n = 35 patients in remission. Over the course of the study, n = 16 patients were untreated, while n = 33 patients received immunomodulatory therapy. The data show that there was a moderate correlation between the frequencies of EBV- and brain-reactive B cells in MS patients in remission. In addition we could detect a correlation between the B cell response to EBV and disease activity. There was no evidence of an EBV reactivation. Interestingly, there was also a correlation between the frequencies of CMV- and brain-specific B cells in MS patients experiencing an acute relapse and an elevated B cell response to CMV was associated with higher disease activity. The trend remained when excluding seronegative subjects but was non-significant. These data underline that viral infections might impact the immunopathology of MS, but the exact link between the two entities remains subject of controversy.},
  language  = {en}
}
@article{WernerLueckerathSchmidetal.2016,
  author    = {Werner, R. A. and L{\"u}ckerath, K. and Schmid, J. S. and Higuchi, T. and Kreissl, M. C. and Grelle, I. and Reiners, C. and Buck, A. K. and Lapa, C.},
  title     = {Thyroglobulin fluctuations in patients with iodine-refractory differentiated thyroid carcinoma on lenvatinib treatment - initial experience},
  series = {Scientific Reports},
  volume    = {6},
  journal   = {Scientific Reports},
  doi       = {10.1038/srep28081},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147407},
  pages     = {28081},
  year      = {2016},
  abstract  = {Tyrosine kinase inhibitors (TKI) have shown clinical effectiveness in iodine-refractory differentiated thyroid cancer (DTC). The corresponding role of serum thyroglobulin (Tg) in iodine-refractory DTC has not been investigated yet. 9 patients (3 female, 61 ± 8y) with progressive iodine-refractory DTC starting on lenvatinib were considered. Tumor restaging was performed every 2-3 months including contrast-enhanced computed tomography (CT, RECIST 1.1). Serum Tg was measured and compared to imaging findings. After treatment initiation, serum Tg levels dropped in all patients with a median reduction of 86.2\%. During long-term follow-up (median, 25.2 months), fluctuations in Tg could be observed in 8/9 subjects. According to RECIST, 6/9 subjects achieved a partial response or stable disease with the remaining 3/9 experiencing progressive disease (2/3 with Tg levels rising above baseline). All of the patients with disease progression presented with a preceding continuous rise in serum Tg, whereas tumor marker oscillations in the subjects with controlled disease were only intermittent. Initiation of lenvatinib in iodine-refractory DTC patients is associated with a significant reduction in serum Tg levels as a marker of treatment response. In the course of treatment, transient Tg oscillations are a frequent phenomenon that may not necessarily reflect morphologic tumor progression.},
  language  = {en}
}
@article{UeceylerBikoHoseetal.2016,
  author    = {{\"U}{\c{c}}eyler, Nurcan and Biko, Lydia and Hose, Dorothea and Hoffmann, Lukas and Sommer, Claudia},
  title     = {Comprehensive and differential long-term characterization of the alpha-galactosidase A deficient mouse model of Fabry disease focusing on the sensory system and pain development},
  series = {Molecular Pain},
  volume    = {12},
  journal   = {Molecular Pain},
  number    = {1744806916646370},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147562},
  year      = {2016},
  abstract  = {Fabry disease is an X-linked lysosomal storage disorder due to impaired activity of alpha-galactosidase A with intracellular accumulation of globotriaosylceramide. Associated small fiber pathology leads to characteristic pain in Fabry disease. We systematically assessed sensory system, physical activity, metabolic parameters, and morphology of male and female mice with alpha-galactosidase A deficiency (Fabry ko) from 2 to 27 months of age and compared results with those of age- and gender-matched wild-type littermates of C57Bl/6J background. Results From the age of two months, male and female Fabry mice showed mechanical hypersensitivity (p < 0.001 each) compared to wild-type littermates. Young Fabry ko mice of both genders were hypersensitive to heat stimulation (p < 0.01) and developed heat hyposensitivity with aging (p < 0.05), while cold hyposensitivity was present constantly in young (p < 0.01) and old (p < 0.05) Fabry ko mice compared to wild-type littermates. Stride angle increased only in male Fabry ko mice with aging (p < 0.01) in comparison to wild-type littermates. Except for young female mice, male (p < 0.05) and female (p < 0.01) Fabry ko mice had a higher body weight than wild-type littermates. Old male Fabry ko mice were physically less active than their wild-type littermates (p < 0.05), had lower chow intake (p < 0.001), and lost more weight (p < 0.001) in a one-week treadmill experiment than wild-type littermates. Also, Fabry ko mice showed spontaneous pain protective behavior and developed orofacial dysmorphism resembling patients with Fabry disease. Conclusions. Mice with alpha-galactosidase A deficiency show age-dependent and distinct deficits of the sensory system. alpha-galactosidase A-deficient mice seem to model human Fabry disease and may be helpful when studying the pathophysiology of Fabry-associated pain.},
  language  = {en}
}
@article{PhamHelluyKleinschnitzetal.2011,
  author    = {Pham, Mirko and Helluy, Xavier and Kleinschnitz, Christoph and Kraft, Peter and Bartsch, Andreas J. and Jakob, Peter and Nieswandt, Bernhard and Bendszus, Martin and Guido, Stoll},
  title     = {Sustained Reperfusion after Blockade of Glycoprotein-Receptor-Ib in Focal Cerebral Ischemia: An MRI Study at 17.6 Tesla},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {4},
  doi       = {10.1371/journal.pone.0018386},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142608},
  pages     = {e18386},
  year      = {2011},
  abstract  = {Background: Inhibition of early platelet adhesion by blockade of glycoprotein-IB (GPIb) protects mice from ischemic stroke. To elucidate underlying mechanisms in-vivo, infarct development was followed by ultra-high field MRI at 17.6 Tesla. Methods: Cerebral infarction was induced by transient-middle-cerebral-artery-occlusion (tMCAO) for 1 hour in C57/BL6 control mice (N = 10) and mice treated with 100 mg Fab-fragments of the GPIb blocking antibody p0p/B 1 h after tMCAO (N = 10). To control for the effect of reperfusion, additional mice underwent permanent occlusion and received anti-GPIb treatment (N = 6; pMCAO) or remained without treatment (N = 3; pMCAO). MRI 2 h and 24 h after MCAO measured cerebral-blood-flow (CBF) by continuous arterial-spin labelling, the apparent-diffusion-coefficient (ADC), quantitative-T2 and T2-weighted imaging. All images were registered to a standard mouse brain MRI atlas and statistically analysed voxel-wise, and by cortico-subcortical ROI analysis. Results: Anti-GPIb treatment led to a relative increase of postischemic CBF vs. controls in the cortical territory of the MCA (2 h: 44.2 +/- 6.9 ml/100g/min versus 24 h: 60.5 +/- 8.4; p = 0.0012, F((1,18)) = 14.63) after tMCAO. Subcortical CBF 2 h after tMCAO was higher in anti-GPIb treated animals (45.3 +/- 5.9 vs. controls: 33.6 +/- 4.3; p = 0.04). In both regions, CBF findings were clearly related to a lower probability of infarction (Cortex/Subcortex of treated group: 35\%/65\% vs. controls: 95\%/100\%) and improved quantitative-T2 and ADC. After pMCAO, anti-GPIb treated mice developed similar infarcts preceded by severe irreversible hypoperfusion as controls after tMCAO indicating dependency of stroke protection on reperfusion. Conclusion: Blockade of platelet adhesion by anti-GPIb-Fab-fragments results in substantially improved CBF early during reperfusion. This finding was in exact spatial correspondence with the prevention of cerebral infarction and indicates in-vivo an increased patency of the microcirculation. Thus, progression of infarction during early ischemia and reperfusion can be mitigated by anti-platelet treatment.},
  language  = {en}
}
@article{GulbertiMollHameletal.2015,
  author    = {Gulberti, A. and Moll, C.K.E. and Hamel, W. and Buhmann, C. and Koeppen, J.A. and Boelmans, K. and Zittel, S. and Gerloff, C. and Westphal, M. and Schneider, T.R. and Engel, A.K.},
  title     = {Predictive timing functions of cortical beta oscillations are impaired in Parkinson's disease and influenced by L-DOPA and deep brain stimulation of the subthalamic nucleus Impaired beta-band timing functions in PD},
  series = {NeuroImage: Clinical},
  volume    = {9},
  journal   = {NeuroImage: Clinical},
  doi       = {10.1016/j.nicl.2015.09.013},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150049},
  pages     = {436-449},
  year      = {2015},
  abstract  = {Cortex-basal ganglia circuits participate in motor timing and temporal perception, and are important for the dynamic configuration of sensorimotor networks in response to exogenous demands. In Parkinson's disease (PD) patients, rhythmic auditory stimulation (RAS) induces motor performance benefits. Hitherto, little is known concerning contributions of the basal ganglia to sensory facilitation and cortical responses to RAS in PD. Therefore, we conducted an EEG study in 12 PD patients before and after surgery for subthalamic nucleus deep brain stimulation (STN-DBS) and in 12 age-matched controls. Here we investigated the effects of levodopa and STN-DBS on resting-state EEG and on the cortical-response profile to slow and fast RAS in a passive-listening paradigm focusing on beta-band oscillations, which are important for auditory-motor coupling. The beta-modulation profile to RAS in healthy participants was characterized by local peaks preceding and following auditory stimuli. In PD patients RAS failed to induce pre-stimulus beta increases. The absence of pre-stimulus beta-band modulation may contribute to impaired rhythm perception in PD. Moreover, post-stimulus beta-band responses were highly abnormal during fast RAS in PD patients. Treatment with levodopa and STN-DBS reinstated a post-stimulus beta-modulation profile similar to controls, while STN-DBS reduced beta-band power in the resting-state. The treatment-sensitivity of beta oscillations suggests that STN-DBS may specifically improve timekeeping functions of cortical beta oscillations during fast auditory pacing.},
  language  = {en}
}
@article{YilmazRoeschKlingeletal.2011,
  author    = {Yilmaz, Ali and R{\"o}sch, Sabine and Klingel, Karin and Kandolf, Reinhard and Helluy, Xavier and Hiller, Karl-Heinz and Jakob, Peter M and Sechtem, Udo},
  title     = {Molecular magnetic resonance imaging (MRI) of inflamed myocardium using ferucarbotran in patients with acute myocardial infarction},
  series = {Journal of Cardiovascular Magnetic Resonance},
  volume    = {13},
  journal   = {Journal of Cardiovascular Magnetic Resonance},
  number    = {Suppl. 1},
  doi       = {10.1186/1532-429X-13-S1-P149},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140991},
  pages     = {P149},
  year      = {2011},
  abstract  = {Introduction: Superparamagnetic iron oxide nanoparticle (SPIO)-based molecular imaging agents targeting macrophages have been developed and successfully applied in animal models of myocardial infarction.},
  language  = {en}
}
@article{HartlBodemJochheimetal.2011,
  author    = {Hartl, Maximilian J. and Bodem, Jochen and Jochheim, Fabian and Rethwilm, Axel and R{\"o}sch, Paul and W{\"o}hrl, Birgitta M.},
  title     = {Regulation of foamy virus protease activity by viral RNA},
  series = {Retrovirology},
  volume    = {8},
  journal   = {Retrovirology},
  number    = {Suppl. 1},
  doi       = {10.1186/1742-4690-8-S1-A228},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142248},
  pages     = {A228},
  year      = {2011},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{HopfnerSchormairKnaufetal.2011,
  author    = {Hopfner, Franziska and Schormair, Barbara and Knauf, Franziska and Berthele, Achim and T{\"o}lle, Thomas R. and Baron, Ralf and Maier, Christoph and Treede, Rolf-Detlef and Binder, Andreas and Sommer, Claudia and Maih{\"o}fner, Christian and Kunz, Wolfram and Zimprich, Friedrich and Heemann, Uwe and Pfeufer, Arne and N{\"a}bauer, Michael and K{\"a}{\"a}b, Stefan and Nowak, Barbara and Gieger, Christian and Lichtner, Peter and Trenkwalder, Claudia and Oexle, Konrad and Winkelmann, Juliane},
  title     = {Novel SCARB2 mutation in Action Myoclonus-Renal Failure syndrome and evaluation of SCARB2 mutations in isolated AMRF features},
  series = {BMC Neurology},
  volume    = {11},
  journal   = {BMC Neurology},
  number    = {134},
  doi       = {10.1186/1471-2377-11-134},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141209},
  pages     = {1-8},
  year      = {2011},
  abstract  = {Background: Action myoclonus-renal failure syndrome is a hereditary form of progressive myoclonus epilepsy associated with renal failure. It is considered to be an autosomal-recessive disease related to loss-of-function mutations in SCARB2. We studied a German AMRF family, additionally showing signs of demyelinating polyneuropathy and dilated cardiomyopathy. To test the hypothesis whether isolated appearance of individual AMRF syndrome features could be related to heterozygote SCARB2 mutations, we screened for SCARB2 mutations in unrelated patients showing isolated AMRF features. Methods: In the AMRF family all exons of SCARB2 were analyzed by Sanger sequencing. The mutation screening of unrelated patients with isolated AMRF features affected by either epilepsy (n = 103, progressive myoclonus epilepsy or generalized epilepsy), demyelinating polyneuropathy (n = 103), renal failure (n = 192) or dilated cardiomyopathy (n = 85) was performed as high resolution melting curve analysis of the SCARB2 exons. Results: A novel homozygous 1 bp deletion (c.111delC) in SCARB2 was found by sequencing three affected homozygous siblings of the affected family. A heterozygous sister showed generalized seizures and reduction of nerve conduction velocity in her legs. No mutations were found in the epilepsy, renal failure or dilated cardiomyopathy samples. In the polyneuropathy sample two individuals with demyelinating disease were found to be carriers of a SCARB2 frameshift mutation (c.666delCCTTA). Conclusions: Our findings indicate that demyelinating polyneuropathy and dilated cardiomyopathy are part of the action myoclonus-renal failure syndrome. Moreover, they raise the possibility that in rare cases heterozygous SCARB2 mutations may be associated with PNP features.},
  language  = {en}
}
@article{WalitzaMelfsenJansetal.2011,
  author    = {Walitza, Susanne and Melfsen, Siebke and Jans, Thomas and Zellmann, Henrike and Wewetzer, Christoph and Warnke, Andreas},
  title     = {Obsessive-Compulsive Disorder in Children and Adolescents},
  series = {Deutsches {\"A}rzteblatt International},
  volume    = {108},
  journal   = {Deutsches {\"A}rzteblatt International},
  number    = {11},
  doi       = {10.3238/arztebl.2011.0173},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141214},
  pages     = {173-I},
  year      = {2011},
  abstract  = {Background: Early-onset obsessive-compulsive disorder (OCD) is one of the more common mental illnesses of children and adolescents, with prevalence of 1\% to 3\%. Its manifestations often lead to severe impairment and to conflict in the family. In this review, we summarize the manifestations, comorbidity, pathophysiology, and course of this disease as well as current modes of diagnosis and treatment. Methods: We selectively review the relevant literature and the German-language guidelines for the diagnosis and treatment of mental illnesses in children and adolescents. Results: Obsessive-compulsive manifestations are of many types and cause severe impairment. Comorbid mental disturbances are present in as many as 70\% of patients. The disease takes a chronic course in more than 40\% of patients. Cognitive behavioral therapy is the treatment of first choice, followed by combination pharmacotherapy including selective serotonin reuptake inhibitors (SSRI) and then by SSRI alone. Conclusion: OCD often begins in childhood or adolescence. There are empirically based neurobiological and cognitive-behavioral models of its pathophysiology. Multiaxial diagnostic evaluation permits early diagnosis. Behavioral therapy and medications are highly effective treatments, but the disorder nonetheless takes a chronic course in a large percentage of patients.},
  language  = {en}
}
@article{HillStritzkerScadengetal.2011,
  author    = {Hill, Philip J. and Stritzker, Jochen and Scadeng, Miriam and Geissinger, Ulrike and Haddad, Daniel and Basse-L{\"u}sebrink, Thomas C. and Gbureck, Uwe and Jakob, Peter and Szalay, Aladar A.},
  title     = {Magnetic Resonance Imaging of Tumors Colonized with Bacterial Ferritin-Expressing \(Escherichia\) \(coli\)},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {10},
  doi       = {10.1371/journal.pone.0025409},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140920},
  pages     = {e25409},
  year      = {2011},
  abstract  = {Background: Recent studies have shown that human ferritin can be used as a reporter of gene expression for magnetic resonance imaging (MRI). Bacteria also encode three classes of ferritin-type molecules with iron accumulation properties. Methods and Findings: Here, we investigated whether these bacterial ferritins can also be used as MRI reporter genes and which of the bacterial ferritins is the most suitable reporter. Bacterial ferritins were overexpressed in probiotic E. coli Nissle 1917. Cultures of these bacteria were analyzed and those generating highest MRI contrast were further investigated in tumor bearing mice. Among members of three classes of bacterial ferritin tested, bacterioferritin showed the most promise as a reporter gene. Although all three proteins accumulated similar amounts of iron when overexpressed individually, bacterioferritin showed the highest contrast change. By site-directed mutagenesis we also show that the heme iron, a unique part of the bacterioferritin molecule, is not critical for MRI contrast change. Tumor-specific induction of bacterioferritin-expression in colonized tumors resulted in contrast changes within the bacteria-colonized tumors. Conclusions: Our data suggest that colonization and gene expression by live vectors expressing bacterioferritin can be monitored by MRI due to contrast changes.},
  language  = {en}
}
@article{PeckSchugZhangetal.2016,
  author    = {Peck, Barrie and Schug, Zachary T. and Zhang, Qifeng and Dankworth, Beatrice and Jones, Dylan T. and Smethurst, Elizabeth and Patel, Rachana and Mason, Susan and Jian, Ming and Saunders, Rebecca and Howell, Michael and Mitter, Richard and Spencer-Dene, Bradley and Stamp, Gordon and McGarry, Lynn and James, Daniel and Shanks, Emma and Aboagye, Eric O. and Critchlow, Susan E. and Leung, Hing Y. and Harris, Adrian L. and Wakelam, Michael J. O. and Gottlieb, Eyal and Schulze, Almut},
  title     = {Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments},
  series = {Cancer \& Metabolism},
  volume    = {4},
  journal   = {Cancer \& Metabolism},
  number    = {6},
  doi       = {10.1186/s40170-016-0146-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145905},
  year      = {2016},
  abstract  = {Background Enhanced macromolecule biosynthesis is integral to growth and proliferation of cancer cells. Lipid biosynthesis has been predicted to be an essential process in cancer cells. However, it is unclear which enzymes within this pathway offer the best selectivity for cancer cells and could be suitable therapeutic targets. Results Using functional genomics, we identified stearoyl-CoA desaturase (SCD), an enzyme that controls synthesis of unsaturated fatty acids, as essential in breast and prostate cancer cells. SCD inhibition altered cellular lipid composition and impeded cell viability in the absence of exogenous lipids. SCD inhibition also altered cardiolipin composition, leading to the release of cytochrome C and induction of apoptosis. Furthermore, SCD was required for the generation of poly-unsaturated lipids in cancer cells grown in spheroid cultures, which resemble those found in tumour tissue. We also found that SCD mRNA and protein expression is elevated in human breast cancers and predicts poor survival in high-grade tumours. Finally, silencing of SCD in prostate orthografts efficiently blocked tumour growth and significantly increased animal survival. Conclusions Our data implicate lipid desaturation as an essential process for cancer cell survival and suggest that targeting SCD could efficiently limit tumour expansion, especially under the metabolically compromised conditions of the tumour microenvironment.},
  language  = {en}
}
@article{ShityakovDandekarFoerster2015,
  author    = {Shityakov, Sergey and Dandekar, Thomas and F{\"o}rster, Carola},
  title     = {Gene expression profiles and protein-protein interaction network analysis in AIDS patients with HIV-associated encephalitis and dementia},
  series = {HIV/AIDS: Research and Palliative Care},
  volume    = {7},
  journal   = {HIV/AIDS: Research and Palliative Care},
  doi       = {10.2147/HIV.S88438},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149494},
  pages     = {265-276},
  year      = {2015},
  abstract  = {Central nervous system dysfunction is an important cause of morbidity and mortality in patients with human immunodeficiency virus type 1 (HIV-1) infection and acquired immunodeficiency virus syndrome (AIDS). Patients with AIDS are usually affected by HIV-associated encephalitis (HIVE) with viral replication limited to cells of monocyte origin. To examine the molecular mechanisms underlying HIVE-induced dementia, the GSE4755 Affymetrix data were obtained from the Gene Expression Omnibus database and the differentially expressed genes (DEGs) between the samples from AIDS patients with and without apparent features of HIVE-induced dementia were identified. In addition, protein-protein interaction networks were constructed by mapping DEGs into protein-protein interaction data to identify the pathways that these DEGs are involved in. The results revealed that the expression of 1,528 DEGs is mainly involved in the immune response, regulation of cell proliferation, cellular response to inflammation, signal transduction, and viral replication cycle. Heat-shock protein alpha, class A member 1 (HSP90AA1), and fibronectin 1 were detected as hub nodes with degree values >130. In conclusion, the results indicate that HSP90A and fibronectin 1 play important roles in HIVE pathogenesis.},
  language  = {en}
}
@article{HertleinSturmKircheretal.2011,
  author    = {Hertlein, Tobias and Sturm, Volker and Kircher, Stefan and Basse-L{\"u}sebrink, Thomas and Haddad, Daniel and Ohlsen, Knut and Jakob, Peter},
  title     = {Visualization of Abscess Formation in a Murine Thigh Infection Model of \(Staphylococcus\) \(aureus\) by (19)F-Magnetic Resonance Imaging (MRI)},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {3},
  doi       = {10.1371/journal.pone.0018246},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142846},
  pages     = {e18246},
  year      = {2011},
  abstract  = {Background: During the last years, (19)F-MRI and perfluorocarbon nanoemulsion (PFC) emerged as a powerful contrast agent methodology to track cells and to visualize inflammation. We applied this new modality to visualize deep tissue abscesses during acute and chronic phase of inflammation caused by Staphylococcus aureus infection. Methodology and Principal Findings: In this study, a murine thigh infection model was used to induce abscess formation and PFC or CLIO (cross linked ironoxides) was administered during acute or chronic phase of inflammation. 24 h after inoculation, the contrast agent accumulation was imaged at the site of infection by MRI. Measurements revealed a strong accumulation of PFC at the abscess rim at acute and chronic phase of infection. The pattern was similar to CLIO accumulation at chronic phase and formed a hollow sphere around the edema area. Histology revealed strong influx of neutrophils at the site of infection and to a smaller extend macrophages during acute phase and strong influx of macrophages at chronic phase of inflammation. Conclusion and Significance: We introduce (19)F-MRI in combination with PFC nanoemulsions as a new platform to visualize abscess formation in a murine thigh infection model of S. aureus. The possibility to track immune cells in vivo by this modality offers new opportunities to investigate host immune response, the efficacy of antibacterial therapies and the influence of virulence factors for pathogenesis.},
  language  = {en}
}