@article{vandeKerkhofvanderHeijdenSchneideretal.2012, author = {van de Kerkhof, Noortje W. A. and van der Heijden, Frank M. M. A. and Schneider, Marc K. F. and Pfuhlmann, Bruno and St{\"o}ber, Gerald and Egger, Jos I. M. and Verhoeven, Willem M. A.}, title = {Cycloid psychoses: Leonhard's descriptions revisited}, series = {European Journal of Psychiatry}, volume = {26}, journal = {European Journal of Psychiatry}, number = {4}, doi = {10.4321/S0213-61632012000400006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134779}, pages = {266-278}, year = {2012}, abstract = {Background and Objectives: Cycloid psychoses are characterized by polymorphic symptomatology with intraphasic bipolarity, a remitting and recurrent course and favourable prognosis. Perris and Brocicington (P\&B) described the first set of operational criteria that were partly incorporated in ICD-10. The present study investigates psychopathological profiles according to the P\&B criteria and the original descriptions by Leonhard, both against the background of the criteria from the prevailing international classification systems. Methods: Eighty patients with psychotic disorders were recruited and assessed with various psychometric instruments at baseline and after six weeks of antipsychotic treatment in order to investigate the presence of cycloid psychoses according to Leonhard (LCP) and the effect of treatment with antipsychotics. The overlap between LCP and DSM-IV Brief Psychotic Disorder (BPD), ICD Acute Polymorphic Psychotic Disorder (APP) and P\&B criteria was calculated. Results: Using P\&B criteria and a symptom checklist adapted from the original descriptions by Leonhard, 14 and 12 cases of cycloid psychosis were identified respectively reflecting a prevalence of 15-18\%. Small though significant concordance rates were found between LCP and both DSM-BPD and ICD-APP. Concordance between LCP and P\&B criteria was also significant, but modest. Conclusions: This study demonstrates that LCP can be identified in a substantial number of patients with psychotic disorders. Cycloid psychoses are not adequately covered in current classification systems and criteria. Since they are demonstrated to have a specific psychopathological profile, relapsing course and favourable prognosis, it is advocated to include these psychoses in daily differential diagnostic procedures.}, language = {en} } @article{VandeKerkhofFeenstravanderHeijdenetal.2012, author = {Van de Kerkhof, Noortje W. A. and Feenstra, Ilse and van der Heijden, Frank M. M. A. and de Leeuw, Nicole and Pfundt, Rolph and St{\"o}ber, Gerald and Egger, Jos I. M. and Verhoeven, Willem M. A.}, title = {Copy number variants in a sample of patients with psychotic disorders: is standard screening relevant for actual clinical practice?}, series = {Neuropsychiatric Disease and Treatment}, volume = {8}, journal = {Neuropsychiatric Disease and Treatment}, doi = {10.2147/NDT.S32903}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134769}, pages = {295-300}, year = {2012}, abstract = {With the introduction of new genetic techniques such as genome-wide array comparative genomic hybridization, studies on the putative genetic etiology of schizophrenia have focused on the detection of copy number variants (CNVs), ie, microdeletions and/or microduplications, that are estimated to be present in up to 3\% of patients with schizophrenia. In this study, out of a sample of 100 patients with psychotic disorders, 80 were investigated by array for the presence of CNVs. The assessment of the severity of psychiatric symptoms was performed using standardized instruments and ICD-10 was applied for diagnostic classification. In three patients, a submicroscopic CNV was demonstrated, one with a loss in 1q21.1 and two with a gain in 1p13.3 and 7q11.2, respectively. The association between these or other CNVs and schizophrenia or schizophrenia-like psychoses and their clinical implications still remain equivocal. While the CNV affected genes may enhance the vulnerability for psychiatric disorders via effects on neuronal architecture, these insights have not resulted in major changes in clinical practice as yet. Therefore, genome-wide array analysis should presently be restricted to those patients in whom psychotic symptoms are paired with other signs, particularly dysmorphisms and intellectual impairment.}, language = {en} } @article{HardcastleTomeCannonetal.2012, author = {Hardcastle, Nicholas and Tom{\´e}, Wolfgang A. and Cannon, Donald M. and Brouwer, Charlotte L. and Wittendorp, Paul W. H. and Dogan, Nesrin and Guckenberger, Matthias and Allaire, St{\´e}phane and Mallya, Yogish and Kumar, Prashant and Oechsner, Markus and Richter, Anne and Song, Shiyu and Myers, Michael and Polat, B{\"u}lent and Bzdusek, Karl}, title = {A multi-institution evaluation of deformable image registration algorithms for automatic organ delineation in adaptive head and neck radiotherapy}, series = {Radiation Oncology}, volume = {7}, journal = {Radiation Oncology}, number = {90}, doi = {10.1186/1748-717X-7-90}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134756}, year = {2012}, abstract = {Background: Adaptive Radiotherapy aims to identify anatomical deviations during a radiotherapy course and modify the treatment plan to maintain treatment objectives. This requires regions of interest (ROIs) to be defined using the most recent imaging data. This study investigates the clinical utility of using deformable image registration (DIR) to automatically propagate ROIs. Methods: Target (GTV) and organ-at-risk (OAR) ROIs were non-rigidly propagated from a planning CT scan to a per-treatment CT scan for 22 patients. Propagated ROIs were quantitatively compared with expert physician-drawn ROIs on the per-treatment scan using Dice scores and mean slicewise Hausdorff distances, and center of mass distances for GTVs. The propagated ROIs were qualitatively examined by experts and scored based on their clinical utility. Results: Good agreement between the DIR-propagated ROIs and expert-drawn ROIs was observed based on the metrics used. 94\% of all ROIs generated using DIR were scored as being clinically useful, requiring minimal or no edits. However, 27\% (12/44) of the GTVs required major edits. Conclusion: DIR was successfully used on 22 patients to propagate target and OAR structures for ART with good anatomical agreement for OARs. It is recommended that propagated target structures be thoroughly reviewed by the treating physician.}, language = {en} } @article{MoremiMshanaKamugishaetal.2012, author = {Moremi, Nyambura and Mshana, Stephen E. and Kamugisha, Erasmus and Kataraihya, Johannes B. and Tappe, Dennis and Vogel, Ulrich and Lyamuya, Eligius F. and Claus, Heike}, title = {Predominance of methicillin resistant Staphylococcus aureus-ST88 and new ST1797 causing wound infection and abscesses}, series = {Journal of Infection in Developing Countries}, volume = {6}, journal = {Journal of Infection in Developing Countries}, number = {8}, doi = {10.3855/jidc.2093}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134746}, pages = {620-625}, year = {2012}, abstract = {Introduction: Although there has been a worldwide emergence and spread of methicillin-resistant Staphylococcus aureus (MRSA), little is known about the molecular epidemiology of MRSA in Tanzania. Methodology: In this study, we characterized MRSA strains isolated from clinical specimens at the Bugando Medical Centre, Tanzania, between January and December 2008. Of 160 S. aureus isolates from 600 clinical specimens, 24 (15\%) were found to be MRSA. Besides molecular screening for the Panton Valentine leukocidin (PVL) genes by PCR, MRSA strains were further characterized by Multi-Locus Sequence Typing (MLST) and spa typing. Results: Despite considerable genetic diversity, the spa types t690 (29.1\%) and t7231 (41.6\%), as well as the sequence types (ST) 88 (54.2\%) and 1797 (29.1\%), were dominant among clinical isolates. The PVL genes were detected in 4 isolates; of these, 3 were found in ST 88 and one in ST1820. Resistance to erythromycin, clindamicin, gentamicin, tetracycline and co-trimoxazole was found in 45.8\%, 62.5\%, 41.6\%, 45.8\% and 50\% of the strains, respectively. Conclusion: We present the first thorough typing of MRSA at a Tanzanian hospital. Despite considerable genetic diversity, ST88 was dominant among clinical isolates at the Bugando Medical Centre. Active and standardized surveillance of nosocomial MRSA infection should be conducted in the future to analyse the infection and transmission rates and implement effective control measures.}, language = {en} } @article{MinnerupSutherlandBuchanetal.2012, author = {Minnerup, Jens and Sutherland, Brad A. and Buchan, Alastair M. and Kleinschnitz, Christoph}, title = {Neuroprotection for Stroke: Current Status and Future Perspectives}, series = {International Journal of Molecular Science}, volume = {13}, journal = {International Journal of Molecular Science}, number = {9}, doi = {10.3390/ijms130911753}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134730}, pages = {11753-11772}, year = {2012}, abstract = {Neuroprotection aims to prevent salvageable neurons from dying. Despite showing efficacy in experimental stroke studies, the concept of neuroprotection has failed in clinical trials. Reasons for the translational difficulties include a lack of methodological agreement between preclinical and clinical studies and the heterogeneity of stroke in humans compared to homogeneous strokes in animal models. Even when the international recommendations for preclinical stroke research, the Stroke Academic Industry Roundtable (STAIR) criteria, were followed, we have still seen limited success in the clinic, examples being NXY-059 and haematopoietic growth factors which fulfilled nearly all the STAIR criteria. However, there are a number of neuroprotective treatments under investigation in clinical trials such as hypothermia and ebselen. Moreover, promising neuroprotective treatments based on a deeper understanding of the complex pathophysiology of ischemic stroke such as inhibitors of NADPH oxidases and PSD-95 are currently evaluated in preclinical studies. Further concepts to improve translation include the investigation of neuroprotectants in multicenter preclinical Phase III-type studies, improved animal models, and close alignment between clinical trial and preclinical methodologies. Future successful translation will require both new concepts for preclinical testing and innovative approaches based on mechanistic insights into the ischemic cascade.}, language = {en} } @article{HickeySridharWestermannetal.2012, author = {Hickey, Scott F. and Sridhar, Malathy and Westermann, Alexander J. and Qin, Qian and Vijayendra, Pooja and Liou, Geoffrey and Hammond, Ming C.}, title = {Transgene regulation in plants by alternative splicing of a suicide exon}, series = {Nucleic Acids Research}, volume = {40}, journal = {Nucleic Acids Research}, number = {10}, doi = {10.1093/nar/gks032}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134724}, pages = {4701-4710}, year = {2012}, abstract = {Compared to transcriptional activation, other mechanisms of gene regulation have not been widely exploited for the control of transgenes. One barrier to the general use and application of alternative splicing is that splicing-regulated transgenes have not been shown to be reliably and simply designed. Here, we demonstrate that a cassette bearing a suicide exon can be inserted into a variety of open reading frames (ORFs), generating transgenes whose expression is activated by exon skipping in response to a specific protein inducer. The surprisingly minimal sequence requirements for the maintenance of splicing fidelity and regulation indicate that this splicing cassette can be used to regulate any ORF containing one of the amino acids Glu, Gln or Lys. Furthermore, a single copy of the splicing cassette was optimized by rational design to confer robust gene activation with no background expression in plants. Thus, conditional splicing has the potential to be generally useful for transgene regulation.}, language = {en} } @article{LandoEndesfelderBergeretal.2012, author = {Lando, David and Endesfelder, Ulrike and Berger, Harald and Subramanian, Lakxmi and Dunne, Paul D. and McColl, James and Klenerman, David and Carr, Antony M. and Sauer, Markus and Allshire, Robin C. and Heilemann, Mike and Laue, Ernest D.}, title = {Quantitative single-molecule microscopy reveals that CENP-A\(^{Cnp1}\) deposition occurs during G2 in fission yeast}, series = {Open Biology}, volume = {2}, journal = {Open Biology}, number = {120078}, doi = {10.1098/rsob.120078}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134682}, year = {2012}, abstract = {The inheritance of the histone H3 variant CENP-A in nucleosomes at centromeres following DNA replication is mediated by an epigenetic mechanism. To understand the process of epigenetic inheritance, or propagation of histones and histone variants, as nucleosomes are disassembled and reassembled in living eukaryotic cells, we have explored the feasibility of exploiting photo-activated localization microscopy (PALM). PALM of single molecules in living cells has the potential to reveal new concepts in cell biology, providing insights into stochastic variation in cellular states. However, thus far, its use has been limited to studies in bacteria or to processes occurring near the surface of eukaryotic cells. With PALM, one literally observes and 'counts' individual molecules in cells one-by-one and this allows the recording of images with a resolution higher than that determined by the diffraction of light (the so-called super-resolution microscopy). Here, we investigate the use of different fluorophores and develop procedures to count the centromere-specific histone H3 variant CENP-A\(^{Cnp1}\) with single-molecule sensitivity in fission yeast (Schizosaccharomyces pombe). The results obtained are validated by and compared with ChIP-seq analyses. Using this approach, CENP-A\(^{Cnp1}\) levels at fission yeast (S. pombe) centromeres were followed as they change during the cell cycle. Our measurements show that CENP-A(Cnp1) is deposited solely during the G2 phase of the cell cycle.}, language = {en} } @article{SangesScheuermannZahedietal.2012, author = {Sanges, C. and Scheuermann, C. and Zahedi, R. P. and Sickmann, A. and Lamberti, A. and Migliaccio, N. and Baljuls, A. and Marra, M. and Zappavigna, S. and Rapp, U. and Abbruzzese, A. and Caraglia, M. and Arcari, P.}, title = {Raf kinases mediate the phosphorylation of eukaryotic translation elongation factor 1A and regulate its stability in eukaryotic cells}, series = {Cell Death \& Disease}, volume = {3}, journal = {Cell Death \& Disease}, number = {e276}, doi = {10.1038/cddis.2012.16}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134673}, year = {2012}, abstract = {We identified eukaryotic translation elongation factor 1A (eEF1A) Raf-mediated phosphorylation sites and defined their role in the regulation of eEF1A half-life and of apoptosis of human cancer cells. Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B-and C-Raf. Interestingly, S21 belongs to the first eEF1A GTP/GDP-binding consensus sequence. Phosphorylation of S21 was strongly enhanced when both eEF1A isoforms were preincubated prior the assay with C-Raf, suggesting that the eEF1A isoforms can heterodimerize thus increasing the accessibility of S21 to the phosphate. Overexpression of eEF1A1 in COS 7 cells confirmed the phosphorylation of T88 also in vivo. Compared with wt, in COS 7 cells overexpressed phosphodeficient (A) and phospho-mimicking (D) mutants of eEF1A1 (S21A/D and T88A/D) and of eEF1A2 (S21A/D), resulted less stable and more rapidly proteasome degraded. Transfection of S21 A/D eEF1A mutants in H1355 cells increased apoptosis in comparison with the wt isoforms. It indicates that the blockage of S21 interferes with or even supports C-Raf induced apoptosis rather than cell survival. Raf-mediated regulation of this site could be a crucial mechanism involved in the functional switching of eEF1A between its role in protein biosynthesis and its participation in other cellular processes.}, language = {en} } @article{GresleAlexandrouWuetal.2012, author = {Gresle, Melissa M. and Alexandrou, Estella and Wu, Qizhu and Egan, Gary and Jokubaitis, Vilija and Ayers, Margaret and Jonas, Anna and Doherty, William and Friedhuber, Anna and Shaw, Gerry and Sendtner, Michael and Emery, Ben and Kilpatrick, Trevor and Butzkueven, Helmut}, title = {Leukemia Inhibitory Factor Protects Axons in Experimental Autoimmune Encephalomyelitis via an Oligodendrocyte-Independent Mechanism}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {10}, doi = {10.1371/journal.pone.0047379}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134617}, pages = {e47379}, year = {2012}, abstract = {Leukemia inhibitory factor (LIF) and Ciliary Neurotrophic factor (CNTF) are members of the interleukin-6 family of cytokines, defined by use of the gp130 molecule as an obligate receptor. In the murine experimental autoimmune encephalomyelitis (EAE) model, antagonism of LIF and genetic deletion of CNTF worsen disease. The potential mechanism of action of these cytokines in EAE is complex, as gp130 is expressed by all neural cells, and could involve immuno-modulation, reduction of oligodendrocyte injury, neuronal protection, or a combination of these actions. In this study we aim to investigate whether the beneficial effects of CNTF/LIF signalling in EAE are associated with axonal protection; and whether this requires signalling through oligodendrocytes. We induced MOG\(_{35-55}\) EAE in CNTF, LIF and double knockout mice. On a CNTF null background, LIF knockout was associated with increased EAE severity (EAE grade 2.1\(\pm\)0.14 vs 2.6\(\pm\)0.19; P<0.05). These mice also showed increased axonal damage relative to LIF heterozygous mice, as indicated by decreased optic nerve parallel diffusivity on MRI (1540\(\pm\)207 \(\mu\)m\(^2\)-/s vs 1310\(\pm\)175 \(\mu\)m\(^2\)-/s; P<0.05), and optic nerve (-12.5\%) and spinal cord (-16\%) axon densities; and increased serum neurofilament-H levels (2.5 fold increase). No differences in inflammatory cell numbers or peripheral auto-immune T-cell priming were evident. Oligodendrocyte-targeted gp130 knockout mice showed that disruption of CNTF/LIF signalling in these cells has no effect on acute EAE severity. These studies demonstrate that endogenous CNTF and LIF act centrally to protect axons from acute inflammatory destruction via an oligodendrocyte-independent mechanism.}, language = {en} } @article{MehnertKochSchulzetal.2012, author = {Mehnert, Anja and Koch, Uwe and Schulz, Holger and Wegscheider, Karl and Weis, Joachim and Faller, Hermann and Keller, Monika and Br{\"a}hler, Elmar and H{\"a}rter, Martin}, title = {Prevalence of mental disorders, psychosocial distress and need for psychosocial support in cancer patients - study protocol of an epidemiological multi-center study}, volume = {12}, number = {70}, doi = {10.1186/1471-244X-12-70}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153296}, year = {2012}, abstract = {Background Empirical studies investigating the prevalence of mental disorders and psychological distress in cancer patients have gained increasing importance during recent years, particularly with the objective to develop and implement psychosocial interventions within the cancer care system. Primary purpose of this epidemiological cross-sectional multi-center study is to detect the 4-week-, 12-month-, and lifetime prevalence rates of comorbid mental disorders and to further assess psychological distress and psychosocial support needs in cancer patients across all major tumor entities within the in- and outpatient oncological health care and rehabilitation settings in Germany. Methods/Design In this multicenter, epidemiological cross-sectional study, cancer patients across all major tumor entities will be enrolled from acute care hospitals, outpatient cancer care facilities, and rehabilitation centers in five major study centers in Germany: Freiburg, Hamburg, Heidelberg, Leipzig and W{\"u}rzburg. A proportional stratified random sample based on the nationwide incidence of all cancer diagnoses in Germany is used. Patients are consecutively recruited in all centers. On the basis of a depression screener (PHQ-9) 50\% of the participants that score below the cutoff point of 9 and all patients scoring above are assessed using the Composite International Diagnostic Interview for Oncology (CIDI-O). In addition, all patients complete validated questionnaires measuring emotional distress, information and psychosocial support needs as well as quality of life. Discussion Epidemiological data on the prevalence of mental disorders and distress provide detailed and valid information for the estimation of the demands for the type and extent of psychosocial support interventions. The data will provide information about specific demographic, functional, cancer- and treatment-related risk factors for mental comorbidity and psychosocial distress, specific supportive care needs and use of psychosocial support offers.}, language = {en} }