TY  - JOUR
A1  - Kleinert, Stefan
A1  - Roll, Petra
A1  - Baumgaertner, Christian
A1  - Himsel, Andrea
A1  - Burkhardt, Harald
A1  - Mueller, Adelheid
A1  - Fleck, Martin
A1  - Feuchtenberger, Martin
A1  - Janett, Manfred
A1  - Tony, Hans-Peter
T1  - Renal Perfusion in Scleroderma Patients Assessed by Microbubble-Based Contrast-Enhanced Ultrasound
N2  - Abstract: Objectives: Renal damage is common in scleroderma. It can occur acutely or chronically. Renal reserve might already be impaired before it can be detected by laboratory findings. Microbubble-based contrast-enhanced ultrasound has been demonstrated to improve blood perfusion imaging in organs. Therefore, we conducted a study to assess renal perfusion in scleroderma patients utilizing this novel technique. Materials and Methodology: Microbubble-based contrast agent was infused and destroyed by using high mechanical index by Siemens Sequoia (curved array, 4.5 MHz). Replenishment was recorded for 8 seconds. Regions of interests (ROI) were analyzed in renal parenchyma, interlobular artery and renal pyramid with quantitative contrast software (CUSQ 1.4, Siemens Acuson, Mountain View, California). Time to maximal Enhancement (TmE), maximal enhancement (mE) and maximal enhancement relative to maximal enhancement of the interlobular artery (mE%A) were calculated for different ROIs. Results: There was a linear correlation between the time to maximal enhancement in the parenchyma and the glomerular filtration rate. However, the other parameters did not reveal significant differences between scleroderma patients and healthy controls. Conclusion: Renal perfusion of scleroderma patients including the glomerular filtration rate can be assessed using microbubble-based contrast media.
KW  - Medizin
KW  - Scleroderma
KW  - renal perfusion
KW  - contrast-enhanced ultrasound.
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75207
ER  - 
TY  - JOUR
A1  - Warnock, David G.
A1  - Ortiz, Alberto
A1  - Mauer, Michael
A1  - Linthorst, Gabor E.
A1  - Oliveira, João P.
A1  - Serra, Andreas L.
A1  - Maródi, László
A1  - Mignani, Renzo
A1  - Vujkovac, Bojan
A1  - Beitner-Johnson, Dana
A1  - Lemay, Roberta
A1  - Cole, J. Alexander
A1  - Svarstad, Einar
A1  - Waldek, Stephen
A1  - Germain, Dominique P.
A1  - Wanner, Christoph
T1  - Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation
JF  - Nephrology Dialysis Transplantation
N2  - Background. The purpose of this study was to identify determinants of renal disease progression in adults with Fabry disease during treatment with agalsidase beta.

Methods. Renal function was evaluated in 151 men and 62 women from the Fabry Registry who received agalsidase beta at an average dose of 1 mg/kg/2 weeks for at least 2 years. Patients were categorized into quartiles based on slopes of estimated glomerular filtration rate (eGFR) during treatment. Multivariate logistic regression analyses were used to identify factors associated with renal disease progression.

Results. Men within the first quartile had a mean eGFR slope of –0.1 mL/min/1.73m2/year, whereas men with the most rapid renal disease progression (Quartile 4) had a mean eGFR slope of –6.7 mL/min/1.73m2/year. The risk factor most strongly associated with renal disease progression was averaged urinary protein:creatinine ratio (UP/Cr) ≥1 g/g (odds ratio 112, 95% confidence interval (95% CI) 4–3109, P = 0.0054). Longer time from symptom onset to treatment was also associated with renal disease progression (odds ratio 19, 95% CI 2–184, P = 0.0098). Women in Quartile 4 had the highest averaged UP/Cr (mean 1.8 g/g) and the most rapid renal disease progression: (mean slope –4.4 mL/min/1.73m2/year).

Conclusions. Adults with Fabry disease are at risk for progressive loss of eGFR despite enzyme replacement therapy, particularly if proteinuria is ≥1 g/g. Men with little urinary protein excretion and those who began receiving agalsidase beta sooner after the onset of symptoms had stable renal function. These findings suggest that early intervention may lead to optimal renal outcomes.
KW  - proteinuria
KW  - enzyme replacement therapy
KW  - alpha galactosidase
KW  - Fabry disease
KW  - genetic renal disease
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124697
VL  - 27
IS  - 3
ER  - 
TY  - JOUR
A1  - Brevoord, Daniel
A1  - Kranke, Peter
A1  - Kuijpers, Marijn
A1  - Weber, Nina
A1  - Hollmann, Markus
A1  - Preckel, Benedikt
T1  - Remote Ischemic Conditioning to Protect against Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis
JF  - PLoS One
N2  - Background: Remote ischemic conditioning is gaining interest as potential method to induce resistance against ischemia reperfusion injury in a variety of clinical settings. We performed a systematic review and meta-analysis to investigate whether remote ischemic conditioning reduces mortality, major adverse cardiovascular events, length of stay in hospital and in the intensive care unit and biomarker release in patients who suffer from or are at risk for ischemia reperfusion injury. 
Methods and Results: Medline, EMBASE and Cochrane databases were searched for randomized clinical trials comparing remote ischemic conditioning, regardless of timing, with no conditioning. Two investigators independently selected suitable trials, assessed trial quality and extracted data. 23 studies in patients undergoing cardiac surgery (15 studies), percutaneous coronary intervention (four studies) and vascular surgery (four studies), comprising in total 1878 patients, were included in this review. Compared to no conditioning, remote ischemic conditioning did not reduce mortality (odds ratio 1.22 [95% confidence interval 0.48, 3.07]) or major adverse cardiovascular events (0.65 [0.38, 1.14]). However, the incidence of myocardial infarction was reduced with remote ischemic conditioning (0.50 [0.31, 0.82]), as was peak troponin release (standardized mean difference -0.28 [-0.47, -0.09]). 
Conclusion: There is no evidence that remote ischemic conditioning reduces mortality associated with ischemic events; nor does it reduce major adverse cardiovascular events. However, remote ischemic conditioning did reduce the incidence of peri-procedural myocardial infarctions, as well as the release of troponin.
KW  - cardiac protection
KW  - stent
KW  - acute kidney injury
KW  - coronary artery bypass
KW  - randomized controlled trial
KW  - myocardial-infarction
KW  - aneurysm repair
KW  - graft surgery
KW  - humans
KW  - angioplasty
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134471
VL  - 7
IS  - 7
ER  - 
TY  - JOUR
A1  - Roeser, Karolin
A1  - Eichholz, Ruth
A1  - Schwerdtle, Barbara
A1  - Schlarb, Angelika A.
A1  - Kübler, Andrea
T1  - Relationship of sleep quality and health-related quality of life in adolescents according to self- and proxy ratings: a questionnaire survey
N2  - Introduction: Sleep disturbances are common in adolescents and adversely affect performance, social contact, and susceptibility to stress. We investigated the hypothesis of a relationship between sleep and health-related quality of life (HRQoL), and applied self- and proxy ratings. Materials and Methods: The sample comprised 92 adolescents aged 11–17 years. All participants and their parents completed a HRQoL measure and the Sleep Disturbance Scale for Children (SDSC ). Children with SDSC T -scores above the normal range (above 60) were classified as poor sleepers. Results: According to self- and proxy ratings, good sleepers reported significantly higher HRQoL than poor sleep- ers. Sleep disturbances were significantly higher and HRQoL significantly lower in self- as compared to parental ratings. Parent-child agreement was higher for subscales measuring observable aspects. Girls experienced significantly stronger sleep disturbances and lower self-rated HRQoL than boys. Discussion: Our findings support the positive relationship of sleep and HRQoL. Furthermore, parents significantly underestimate sleep disturbances and overestimate HRQoL in their children.
KW  - Psychiatrie
KW  - quality of life
KW  - sleep
KW  - adolescence
KW  - parent-child agreement
KW  - sleep disorders
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75953
ER  - 
TY  - JOUR
A1  - Pandurangan, Sudhakar
A1  - Pajak, Agnieszka
A1  - Molnar, Stephen J.
A1  - Cober, Elroy R.
A1  - Dhaubhadel, Sangeeta
A1  - Hernández-Sebastià, Cinta
A1  - Kaiser, Werner M.
A1  - Nelson, Randall L.
A1  - Huber, Steven C.
A1  - Marsolais, Frédéric
T1  - Relationship between asparagine metabolism and protein concentration in soybean seed
JF  - Journal of Experimental Botany
N2  - The relationship between asparagine metabolism and protein concentration was investigated in soybean seed. Phenotyping of a population of recombinant inbred lines adapted to Illinois confirmed a positive correlation between free asparagine levels in developing seeds and protein concentration at maturity. Analysis of a second population of recombinant inbred lines adapted to Ontario associated the elevated free asparagine trait with two of four quantitative trait loci determining population variation for protein concentration, including a major one on chromosome 20 (linkage group I) which has been reported in multiple populations. In the seed coat, levels of asparagine synthetase were high at 50 mg and progressively declined until 150 mg seed weight, suggesting that nitrogenous assimilates are pre-conditioned at early developmental stages to enable a high concentration of asparagine in the embryo. The levels of asparaginase B1 showed an opposite pattern, being low at 50 mg and progressively increased until 150 mg, coinciding with an active phase of storage reserve accumulation. In a pair of genetically related cultivars, ∼2-fold higher levels of asparaginase B1 protein and activity in seed coat, were associated with high protein concentration, reflecting enhanced flux of nitrogen. Transcript expression analyses attributed this difference to a specific asparaginase gene, ASPGB1a. These results contribute to our understanding of the processes determining protein concentration in soybean seed.
KW  - soybean
KW  - seed protein concentration
KW  - quantitative trait locus
KW  - asparagine synthetase
KW  - asparagine
KW  - asparaginase
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126900
VL  - 63
IS  - 8
ER  - 
TY  - JOUR
A1  - Wu, Lingdan
A1  - Pu, Jie
A1  - Allen, John J. B.
A1  - Pauli, Paul
T1  - Recognition of facial expressions in individuals with elevated levels of depressive symptoms: an eye-movement study
JF  - Depression Research and Treatment
N2  - Previous studies consistently reported abnormal recognition of facial expressions in depression. However, it is still not clear whether this abnormality is due to an enhanced or impaired ability to recognize facial expressions, and what underlying cognitive systems are involved. The present study aimed to examine how individuals with elevated levels of depressive symptoms differ from controls on facial expression recognition and to assess attention and information processing using eye tracking. Forty participants (18 with elevated depressive symptoms) were instructed to label facial expressions depicting one of seven emotions. Results showed that the high-depression group, in comparison with the low-depression group, recognized facial expressions faster and with comparable accuracy. Furthermore, the high-depression group demonstrated greater leftwards attention bias which has been argued to be an indicator of hyperactivation of right hemisphere during facial expression recognition.
KW  - Depression
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123153
VL  - 2012
IS  - 249030
ER  - 
TY  - JOUR
A1  - Haeusler, Karl Georg
A1  - Herm, Juliane
A1  - Kunze, Claudia
A1  - Krüll, Matthias
A1  - Brechtel, Lars
A1  - Lock, Jürgen
A1  - Hohenhaus, Marc
A1  - Heuschmann, Peter U.
A1  - Fiebach, Jochen B.
A1  - Haverkamp, Wilhelm
A1  - Endres, Matthias
A1  - Jungehulsing, Gerhard Jan
T1  - Rate of cardiac arrhythmias and silent brain lesions in experienced marathon runners: rationale, design and baseline data of the Berlin Beat of Running study
JF  - BMC Cardiovascular Disorders
N2  - Background: Regular exercise is beneficial for cardiovascular health but a recent meta-analysis indicated a relationship between extensive endurance sport and a higher risk of atrial fibrillation, an independent risk factor for stroke. However, data on the frequency of cardiac arrhythmias or (clinically silent) brain lesions during and after marathon running are missing. 
Methods/Design: In the prospective observational "Berlin Beat of Running" study experienced endurance athletes underwent clinical examination (CE), 3 Tesla brain magnetic resonance imaging (MRI), carotid ultrasound imaging (CUI) and serial blood sampling (BS) within 2-3 days prior (CE, MRI, CUI, BS), directly after (CE, BS) and within 2 days after (CE, MRI, BS) the 38\(^{th}\) BMW BERLIN-MARATHON 2011. All participants wore a portable electrocardiogram (ECG)-recorder throughout the 4 to 5 days baseline study period. Participants with pathological MRI findings after the marathon, troponin elevations or detected cardiac arrhythmias will be asked to undergo cardiac MRI to rule out structural abnormalities. A follow-up is scheduled after one year. 
Results: Here we report the baseline data of the enrolled 110 athletes aged 36-61 years. Their mean age was 48.8 \(\pm\) 6.0 years, 24.5% were female, 8.2% had hypertension and 2.7% had hyperlipidaemia. Participants have attended a mean of 7.5 \(\pm\) 6.6 marathon races within the last 5 years and a mean of 16 \(\pm\) 36 marathon races in total. Their weekly running distance prior to the 38\(^{th}\) BMW BERLIN-MARATHON was 65 \(\pm\) 17 km. Finally, 108 (98.2%) Berlin Beat-Study participants successfully completed the 38\(^{th}\) BMW BERLIN-MARATHON 2011. 
Discussion: Findings from the "Berlin Beats of Running" study will help to balance the benefits and risks of extensive endurance sport. ECG-recording during the marathon might contribute to identify athletes at risk for cardiovascular events. MRI results will give new insights into the link between physical stress and brain damage.
KW  - marathon running
KW  - cardiac arrhythmia
KW  - atrial fibrillation
KW  - physical activity
KW  - cardiovascular events
KW  - carotid artery
KW  - risk factor
KW  - stroke
KW  - exercise
KW  - death
KW  - metaanalysis
KW  - mechanisms
KW  - ECG-recording
KW  - magnetic resonance imaging
KW  - blood sampling
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133677
VL  - 12
IS  - 69
ER  - 
TY  - JOUR
T1  - Rapidity gap cross sections measured with the ATLAS detector in pp collisions at √s=7TeV
JF  - The European Physical Journal C
N2  - Pseudorapidity gap distributions in proton-proton collisions at √s=7 TeV are studied using a minimum bias data sample with an integrated luminosity of 7.1 μb\(^{−1}\). Cross sections are measured differentially in terms of Δη\(^F\), the larger of the pseudorapidity regions extending to the limits of the ATLAS sensitivity, at η=±4.9, in which no final state particles are produced above a transverse momentum threshold pcutT. The measurements span the region 0<Δη\(^F\)<8 for 200MeV<p\(^{cut}_T\)<800MeV. At small Δη\(^F\) , the data test the reliability of hadronisation models in describing rapidity and transverse momentum fluctuations in final state particle production. The measurements at larger gap sizes are dominated by contributions from the single diffractive dissociation process (pp→Xp), enhanced by double dissociation (pp→XY) where the invariant mass of the lighter of the two dissociation systems satisfies M\(_Y\) ≲7 GeV. The resulting cross section is dσ/dΔη\(^F\) ≈1 mb for Δη\(^F\) ≳3. The large rapidity gap data are used to constrain the value of the Pomeron intercept appropriate to triple Regge models of soft diffraction. The cross section integrated over all gap sizes is compared with other LHC inelastic cross section measurements.
KW  - dissociation process,
KW  - transverse momentum
KW  - large rapidity gap
KW  - cross section measurement
KW  - invariant mass
KW  - diffractive dissociation
KW  - hadronisation model
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127629
VL  - 72
IS  - 1926
ER  - 
TY  - JOUR
A1  - Sanges, C.
A1  - Scheuermann, C.
A1  - Zahedi, R. P.
A1  - Sickmann, A.
A1  - Lamberti, A.
A1  - Migliaccio, N.
A1  - Baljuls, A.
A1  - Marra, M.
A1  - Zappavigna, S.
A1  - Reinders, J.
A1  - Rapp, U.
A1  - Abbruzzese, A.
A1  - Caraglia, M.
A1  - Arcari, P.
T1  - Raf kinases mediate the phosphorylation of eukaryotic translation elongation factor 1A and regulate its stability in eukaryotic cells
JF  - Cell Death and Disease
N2  - 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.
KW  - EF-1A
KW  - Raf kinases
KW  - signal transduction
KW  - apoptosis
KW  - ubiquitin
KW  - mass spectrometry
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124149
VL  - 3
IS  - e276
ER  - 
TY  - JOUR
A1  - Sanges, C.
A1  - Scheuermann, C.
A1  - Zahedi, R. P.
A1  - Sickmann, A.
A1  - Lamberti, A.
A1  - Migliaccio, N.
A1  - Baljuls, A.
A1  - Marra, M.
A1  - Zappavigna, S.
A1  - Rapp, U.
A1  - Abbruzzese, A.
A1  - Caraglia, M.
A1  - Arcari, P.
T1  - Raf kinases mediate the phosphorylation of eukaryotic translation elongation factor 1A and regulate its stability in eukaryotic cells
JF  - Cell Death & Disease
N2  - 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.
KW  - signal transduction
KW  - mass spectrometry
KW  - elongation
KW  - protein docking
KW  - factor EEF1A2
KW  - cancer-cells
KW  - lung cancer
KW  - EF-1A
KW  - Raf kinases
KW  - aminoacyl-transfer-RNA
KW  - tyrosine phosphorylation
KW  - factor 1-alpha
KW  - nucleotide exchange
KW  - polyarcylamide gels
KW  - chain
KW  - apoptosis
KW  - ubiquitin
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134673
VL  - 3
IS  - e276
ER  - 
TY  - JOUR
A1  - Guckenberger, Matthias
A1  - Alexandrow, Nikolaus
A1  - Flentje, Michael
T1  - Radiotherapy alone for stage I-III low grade follicular lymphoma: long-term outcome and comparison of extended field and total nodal irradiation
N2  - Background: To analyze long-term results of radiotherapy alone for stage I-III low grade follicular lymphoma and to compare outcome after extended field irradiation (EFI) and total nodal irradiation (TNI). Methods and materials: Between 1982 and 2007, 107 patients were treated with radiotherapy alone for low grade follicular lymphoma at Ann Arbor stage I (n = 50), II (n = 36) and III (n = 21); 48 and 59 patients were treated with EFI and TNI, respectively. The median total dose in the first treatment series of the diaphragmatic side with larger lymphoma burden was 38 Gy (25 Gy – 50 Gy) and after an interval of median 30 days, a total dose of 28 Gy (12.6 Gy – 45 Gy) was given in the second treatment series completing TNI. Results: After a median follow-up of 14 years for living patients, 10-years and 15-years overall survival (OS) were 64% and 50%, respectively. Survival was not significantly different between stages I, II and III. TNI and EFI resulted in 15-years OS of 65% and 34% but patients treated with TNI were younger, had better performance status and higher stage of disease compared to patients treated with EFI. In multivariate analysis, only age at diagnosis (p<0.001, relative risk [RR] 1.06) and Karnofsky performance status (p = 0.04, RR = 0.96) were significantly correlated with OS. Freedom from progression (FFP) was 58% and 56% after 10-years and 15-years, respectively. Recurrences outside the irradiated volume were significantly reduced after TNI compared to EFI; however, increased rates of in-field recurrences and extra-nodal out-of-field recurrence counterbalanced this effect resulting in no significant difference in FFP between TNI and EFI. In univariate analysis, FFP was significantly improved in stage I compared to stage II but no differences were observed between stages I/II and stage III. In multivariate analysis no patient or treatment parameter was correlated with FFP. Acute toxicity was significantly increased after TNI compared to EFI with a trend to increased late toxicity as well. Conclusions: Radiotherapy alone for stage I and II follicular lymphoma resulted in long-term OS with high rates of disease control; no benefit of TNI over EFI was observed. For stage III follicular lymphoma, TNI achieved promising OS and FFP and should be considered as a potentially curative treatment option.
KW  - Medizin
KW  - Follicular lymphoma
KW  - Total nodal irradiation
KW  - Extended field irradiation
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75702
ER  - 
TY  - JOUR
A1  - Lando, David
A1  - Endesfelder, Ulrike
A1  - Berger, Harald
A1  - Subramanian, Lakxmi
A1  - Dunne, Paul D.
A1  - McColl, James
A1  - Klenerman, David
A1  - Carr, Antony M.
A1  - Sauer, Markus
A1  - Allshire, Robin C.
A1  - Heilemann, Mike
A1  - Laue, Ernest D.
T1  - Quantitative single-molecule microscopy reveals that CENP-A\(^{Cnp1}\) deposition occurs during G2 in fission yeast
JF  - Open Biology
N2  - 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.
KW  - nucleosome
KW  - fission yeast
KW  - identification
KW  - propagation
KW  - CSE4, CENP-A
KW  - CENP-A
KW  - schizosaccaromyces-pombe
KW  - fluorescent protein
KW  - centomeres
KW  - superresolution
KW  - chromatin
KW  - centromere
KW  - ingle-molecule microscopy
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134682
VL  - 2
IS  - 120078
ER  - 
TY  - JOUR
A1  - d'Alquen, Daniela
A1  - De Boeck, Kris
A1  - Bradley, Judy
A1  - Vávrová, Věra
A1  - Dembski, Brigit
A1  - Wagner, Thomas O.F.
A1  - Pfalz, Annette
A1  - Hebestreit, Helge
T1  - Quality assessment of expert answers to lay questions about cystic fibrosis from various language zones in Europe: the ECORN-CF project
N2  - Background: The European Centres of Reference Network for Cystic Fibrosis (ECORN-CF) established an Internet forum which provides the opportunity for CF patients and other interested people to ask experts questions about CF in their mother language. The objectives of this study were to: 1) develop a detailed quality assessment tool to analyze quality of expert answers, 2) evaluate the intra- and inter-rater agreement of this tool, and 3) explore changes in the quality of expert answers over the time frame of the project. Methods: The quality assessment tool was developed by an expert panel. Five experts within the ECORN-CF project used the quality assessment tool to analyze the quality of 108 expert answers published on ECORN-CF from six language zones. 25 expert answers were scored at two time points, one year apart. Quality of answers was also assessed at an early and later period of the project. Individual rater scores and group mean scores were analyzed for each expert answer. Results: A scoring system and training manual were developed analyzing two quality categories of answers: content and formal quality. For content quality, the grades based on group mean scores for all raters showed substantial agreement between two time points, however this was not the case for the grades based on individual rater scores. For formal quality the grades based on group mean scores showed only slight agreement between two time points and there was also poor agreement between time points for the individual grades. The inter-rater agreement for content quality was fair (mean kappa value 0.232 ± 0.036, p < 0.001) while only slight agreement was observed for the grades of the formal quality (mean kappa value 0.105 ± 0.024, p < 0.001). The quality of expert answers was rated high (four language zones) or satisfactory (two language zones) and did not change over time. Conclusions: The quality assessment tool described in this study was feasible and reliable when content quality was assessed by a group of raters. Within ECORN-CF, the tool will help ensure that CF patients all over Europe have equal possibility of access to high quality expert advice on their illness.
KW  - ECORN-CF Projekt
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75072
ER  - 
TY  - JOUR
A1  - Langenfeld, Ulrich
A1  - Moch, Sven-Olaf
A1  - Pfoh, Torsten
T1  - QCD threshold corrections for gluino pair production at hadron colliders
JF  - Journal of High Energy Physics
N2  - We present the complete threshold enhanced predictions in QCD for the total cross section of gluino pair production at hadron colliders at next-to-next-to-leading order. Thanks to the computation of the required one-loop hard matching coefficients our results are accurate to the next-to-next-to-leading logarithm. In a brief phenomenological study we provide predictions for the total hadronic cross sections at the LHC and we discuss the uncertainties arising from scale variations and the parton distribution functions.
KW  - resummation
KW  - supersymmetric standard model
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129609
VL  - 11
IS  - 070
ER  - 
TY  - JOUR
A1  - Kilian, W.
A1  - Ohl, T.
A1  - Reuter, J.
A1  - Speckner, C.
T1  - QCD in the color-flow representation
JF  - Journal of High Energy Physics
N2  - For many practical purposes, it is convenient to formulate unbroken non-abelian gauge theories like QCD in a color-flow basis. We present a new derivation of SU(N) interactions in the color-flow basis by extending the gauge group to U(N) × U(1)′ in such a way that the two U(1) factors cancel each other. We use the quantum action principles to show the equivalence to the usual basis to all orders in perturbation theory. We extend the known Feynman rules to exotic color representations (e.g. sextets) and discuss practical applications as they occur in automatic computation programs.
KW  - QCD
KW  - scattering amplitudes
KW  - 1/N expansion
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129583
VL  - 10
IS  - 022
ER  - 
TY  - JOUR
A1  - Steinmann, Diana
A1  - Paelecke-Habermann, Yvonne
A1  - Geinitz, Hans
A1  - Aschoff, Raimund
A1  - Bayerl, Anja
A1  - Bölling, Tobias
A1  - Bosch, Elisabeth
A1  - Bruns, Frank
A1  - Eichenseder-Seiss, Ute
A1  - Gerstein, Johanna
A1  - Gharbi, Nadine
A1  - Hagg, Juliane
A1  - Hipp, Matthias
A1  - Kleff, Irmgard
A1  - Müller, Axel
A1  - Schäfer, Christof
A1  - Schleicher, Ursula
A1  - Sehlen, Susanne
A1  - Theodorou, Marilena
A1  - Wypior, Hans-Joachim
A1  - Zehentmayr, Franz
A1  - van Oorschot, Birgitt
A1  - Vordermark, Dirk
T1  - Prospective evaluation of quality of life effects in patients undergoing palliative radiotherapy for brain metastases
JF  - BMC Cancer
N2  - Background: Recently published results of quality of life (QoL) studies indicated different outcomes of palliative radiotherapy for brain metastases. This prospective multi-center QoL study of patients with brain metastases was designed to investigate which QoL domains improve or worsen after palliative radiotherapy and which might provide prognostic information. 
Methods: From 01/2007-01/2009, n=151 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. Most patients (82 %) received whole-brain radiotherapy. QoL was measured with the EORTC-QLQ-C15-PAL and brain module BN20 before the start of radiotherapy and after 3 months. 
Results: At 3 months, 88/142 (62 %) survived. Nine patients were not able to be followed up. 62 patients (70.5 % of 3-month survivors) completed the second set of questionnaires. Three months after the start of radiotherapy QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs. Although the use of corticosteroid at 3 months could be reduced compared to pre-treatment (63 % vs. 37 %), the score for headaches remained stable. Initial QoL at the start of treatment was better in those alive than in those deceased at 3 months, significantly for physical function, motor dysfunction and the symptom scales fatigue, pain, appetite loss and weakness of legs. In a multivariate model, lower Karnofsky performance score, higher age and higher pain ratings before radiotherapy were prognostic of 3-month survival. 
Conclusions: Moderate deterioration in several QoL domains was predominantly observed three months after start of palliative radiotherapy for brain metastases. Future studies will need to address the individual subjective benefit or burden from such treatment. Baseline QoL scores before palliative radiotherapy for brain metastases may contain prognostic information.
KW  - breast cancer
KW  - brain tumours
KW  - survival
KW  - validation
KW  - symptoms
KW  - EORTC-QLQ-C15-PAL
KW  - EORTC-BN20
KW  - whole-brain radiotherapy
KW  - partitioning analysis RPA
KW  - cancer patients
KW  - lung cancer
KW  - prognostic index
KW  - radiation oncology
KW  - clinical trials
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135254
VL  - 12
IS  - 283
ER  - 
TY  - JOUR
A1  - Galimberti, Daniela
A1  - Dell'Osso, Bernardo
A1  - Fenoglio, Chiara
A1  - Villa, Chiara
A1  - Cortini, Francesca
A1  - Serpente, Maria
A1  - Kittel-Schneider, Sarah
A1  - Weigl, Johannes
A1  - Neuner, Maria
A1  - Volkert, Juliane
A1  - Leonhard, C.
A1  - Olmes, David G.
A1  - Kopf, Juliane
A1  - Cantoni, Claudia
A1  - Ridolfi, Elisa
A1  - Palazzo, Carlotta
A1  - Ghezzi, Laura
A1  - Bresolin, Nereo
A1  - Altamura, A.C.
A1  - Scarpini, Elio
A1  - Reif, Andreas
T1  - Progranulin Gene Variability and Plasma Levels in Bipolar Disorder and Schizophrenia
JF  - PLoS One
N2  - Basing on the assumption that frontotemporal lobar degeneration (FTLD), schizophrenia and bipolar disorder (BPD) might share common aetiological mechanisms, we analyzed genetic variation in the FTLD risk gene progranulin (GRN) in a German population of patients with schizophrenia (n=271) or BPD (n=237) as compared with 574 age-, gender-and ethnicity-matched controls. Furthermore, we measured plasma progranulin levels in 26 German BPD patients as well as in 61 Italian BPD patients and 29 matched controls. A significantly decreased allelic frequency of the minor versus the wild-type allele was observed for rs2879096 (23.2 versus 34.2%, P<0.001, OR: 0.63, 95% CI: 0.49-0.80), rs4792938 (30.7 versus 39.7%, P=0.005, OR: 0.70, 95% CI: 0.55-0.89) and rs5848 (30.3 versus 36.8, P=0.007, OR: 0.71, 95% CI: 0.56-0.91). Mean +/- SEM progranulin plasma levels were significantly decreased in BPD patients, either Germans or Italians, as compared with controls (89.69 +/- 3.97 and 116.14 +/- 5.80 ng/ml, respectively, versus 180.81 +/- 18.39 ng/ml P<0.001) and were not correlated with age. In conclusion, GRN variability decreases the risk to develop BPD and schizophrenia, and progranulin plasma levels are significantly lower in BPD patients than in controls. Nevertheless, a larger replication analysis would be needed to confirm these preliminary results.
KW  - people
KW  - frontotemporal lobar degeneration
KW  - genome-wide association
KW  - Alzheimers disease
KW  - risk genes
KW  - dementia
KW  - GRN
KW  - mutation
KW  - families
KW  - linkage
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131910
VL  - 7
IS  - 4
ER  - 
TY  - JOUR
A1  - Mehnert, Anja
A1  - Koch, Uwe
A1  - Schulz, Holger
A1  - Wegscheider, Karl
A1  - Weis, Joachim
A1  - Faller, Hermann
A1  - Keller, Monika
A1  - Brähler, Elmar
A1  - Härter, Martin
T1  - Prevalence of mental disorders, psychosocial distress and need for psychosocial support in cancer patients – study protocol of an epidemiological multi-center study
N2  - 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 Würzburg. 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.
KW  - metaanalysis
KW  - depression
KW  - survivors
KW  - care
KW  - sample
KW  - instrument
KW  - quality-of-life
KW  - generalized anxiety disorder
KW  - cooperative-oncology-group
KW  - decision making
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-153296
VL  - 12
IS  - 70
ER  - 
TY  - JOUR
A1  - Messi, Bernadette Biloa
A1  - Ndjoko-Ioset, Karine
A1  - Hertlein-Amslinger, Barbara
A1  - Lannang, Alain Meli
A1  - Nkengfack, Augustin E.
A1  - Wolfender, Jean-Luc
A1  - Hostettmann, Kurt
A1  - Bringmann, Gerhard
T1  - Preussianone, a New Flavanone-Chromone Biflavonoid from Garcinia preussii Engl.
JF  - Molecules
N2  - A new flavanone-chromone biflavonoid, preussianone (1), has been isolated from the leaves of Garcinia preussii, along with four known biflavonoids. The absolute stereostructures were elucidated by chemical, spectroscopic, and chiroptical methods. The biological properties of the new biflavonoid against several bacterial strains were evaluated.
KW  - multiflora
KW  - minimal inhibitory concentration
KW  - absolute configuration
KW  - circular dichroism
KW  - C-13 NMR
KW  - guttiferae
KW  - flavenoids
KW  - extractives
KW  - biflavanoids
KW  - livingstonei
KW  - high-temperature NMR
KW  - antibacterial activity
KW  - Garcinia biflavonoids
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130881
VL  - 17
IS  - 5
ER  - 
TY  - JOUR
A1  - Parker, H. E.
A1  - Adriaenssens, A.
A1  - Rogers, G.
A1  - Richards, P.
A1  - Koepsell, H.
A1  - Reimann, F.
A1  - Gribble, F. M.
T1  - Predominant role of active versus facilitative glucose transport for glucagon-like peptide-1 secretion
JF  - Diabetologia
N2  - Aims/hypothesis
Several glucose-sensing pathways have been implicated in glucose-triggered secretion of glucagon-like peptide-1 (GLP-1) from intestinal L cells. One involves glucose metabolism and closure of ATP-sensitive K\(^+\) channels, and another exploits the electrogenic nature of Na\(^+\)-coupled glucose transporters (SGLTs). This study aimed to elucidate the role of these distinct mechanisms in glucose-stimulated GLP-1 secretion.

Methods
Glucose uptake into L cells (either GLUTag cells or cells in primary cultures, using a new transgenic mouse model combining proglucagon promoter-driven Cre recombinase with a ROSA26tdRFP reporter) was monitored with the FLII\(_{12}\)Pglu-700μδ6 glucose sensor. Effects of pharmacological and genetic interference with SGLT1 or facilitative glucose transport (GLUT) on intracellular glucose accumulation and metabolism (measured by NAD(P)H autofluorescence), cytosolic Ca\(^{2+}\) (monitored with Fura2) and GLP-1 secretion (assayed by ELISA) were assessed.

Results
L cell glucose uptake was dominated by GLUT-mediated transport, being abolished by phloretin but not phloridzin. NAD(P)H autofluorescence was glucose dependent and enhanced by a glucokinase activator. In GLUTag cells, but not primary L cells, phloretin partially impaired glucose-dependent secretion, and suppressed an amplifying effect of glucose under depolarising high K\(^+\) conditions. The key importance of SGLT1 in GLUTag and primary cells was evident from the impairment of secretion by phloridzin or Sglt1 knockdown and failure of glucose to trigger cytosolic Ca\(^{2+}\) elevation in primary L cells from Sglt1 knockout mice.

Conclusions/interpretation
SGLT1 acts as the luminal glucose sensor in L cells, but intracellular glucose concentrations are largely determined by GLUT activity. Although L cell glucose metabolism depends partially on glucokinase activity, this plays only a minor role in glucose-stimulated GLP-1 secretion.
KW  - KATP channel
KW  - glucokinase
KW  - glucagon-like peptide-1 (GLP-1)
KW  - SGLT1
KW  - L cells
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125927
VL  - 55
IS  - 9
ER  - 
TY  - JOUR
A1  - Moremi, Nyambura
A1  - Mshana, Stephen E.
A1  - Kamugisha, Erasmus
A1  - Kataraihya, Johannes B.
A1  - Tappe, Dennis
A1  - Vogel, Ulrich
A1  - Lyamuya, Eligius F.
A1  - Claus, Heike
T1  - Predominance of methicillin resistant Staphylococcus aureus-ST88 and new ST1797 causing wound infection and abscesses
JF  - Journal of Infection in Developing Countries
N2  - 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.
KW  - Tanzania
KW  - panton-valentine leukocidin
KW  - field gel-electrophoreresis
KW  - molecular epidemiology
KW  - aureus infections
KW  - MRSA
KW  - ST88
KW  - ST1797
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134746
VL  - 6
IS  - 8
ER  - 
TY  - JOUR
A1  - Gentschev, Ivaylo
A1  - Adelfinger, Marion
A1  - Josupeit, Rafael
A1  - Rudolph, Stephan
A1  - Ehrig, Klaas
A1  - Donat, Ulrike
A1  - Weibel, Stephanie
A1  - Chen, Nanhai G.
A1  - Yu, Yong A.
A1  - Zhang, Qian
A1  - Heisig, Martin
A1  - Thamm, Douglas
A1  - Stritzker, Jochen
A1  - MacNeill, Amy
A1  - Szalay, Aladar A.
T1  - Preclinical Evaluation of Oncolytic Vaccinia Virus for Therapy of Canine Soft Tissue Sarcoma
JF  - PLoS One
N2  - Virotherapy using oncolytic vaccinia virus (VACV) strains is one promising new strategy for canine cancer therapy. In this study we describe the establishment of an in vivo model of canine soft tissue sarcoma (CSTS) using the new isolated cell line STSA-1 and the analysis of the virus-mediated oncolytic and immunological effects of two different Lister VACV LIVP1.1.1 and GLV-1h68 strains against CSTS. Cell culture data demonstrated that both tested VACV strains efficiently infected and destroyed cells of the canine soft tissue sarcoma line STSA-1. In addition, in our new canine sarcoma tumor xenograft mouse model, systemic administration of LIVP1.1.1 or GLV-1h68 viruses led to significant inhibition of tumor growth compared to control mice. Furthermore, LIVP1.1.1 mediated therapy resulted in almost complete tumor regression and resulted in long-term survival of sarcoma-bearing mice. The replication of the tested VACV strains in tumor tissues led to strong oncolytic effects accompanied by an intense intratumoral infiltration of host immune cells, mainly neutrophils. These findings suggest that the direct viral oncolysis of tumor cells and the virus-dependent activation of tumor-associated host immune cells could be crucial parts of anti-tumor mechanism in STSA-1 xenografts. In summary, the data showed that both tested vaccinia virus strains and especially LIVP1.1.1 have great potential for effective treatment of CSTS.
KW  - breast-tumors
KW  - animal-model
KW  - nude-mice
KW  - cell-line
KW  - in-vitro
KW  - glv-1h68
KW  - cancer
KW  - virotherapy
KW  - dogs
KW  - neutrophils
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129998
VL  - 7
IS  - 5
ER  - 
TY  - JOUR
A1  - Steinbacher, Andreas
A1  - Buback, Johannes
A1  - Nürnberger, Patrick
A1  - Brixner, Tobias
T1  - Precise and rapid detection of optical activity for accumulative femtosecond spectroscopy
JF  - Optics Express
N2  - We present polarimetry, i.e. the detection of optical rotation of light polarization, in a configuration suitable for femtosecond spectroscopy. The polarimeter is based on common-path optical heterodyne interferometry and provides fast and highly sensitive detection of rotatory power. Femtosecond pump and polarimeter probe beams are integrated into a recently developed accumulative technique that further enhances sensitivity with respect to single-pulse methods. The high speed of the polarimeter affords optical rotation detection during the pump-pulse illumination period of a few seconds. We illustrate the concept on the photodissociation of the enantiomers of methyl p-tolyl sulfoxide. The sensitivity of rotatory detection, i.e. the minimum rotation angle that can be measured, is determined experimentally including all noise sources to be 0.10 milli-degrees for a measurement time of only one second and an interaction length of 250 μm. The suitability of the presented setup for femtosecond studies is demonstrated in a non-resonant two-photon photodissociation experiment.
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85913
UR  - http://www.opticsinfobase.org/oe/fulltext.cfm?uri=oe-20-11-11838&id=233249
ER  - 
TY  - JOUR
A1  - Willems, Coen H. M. P.
A1  - Urlichs, Florian
A1  - Seidenspinner, Silvia
A1  - Kunzmann, Steffen
A1  - Speer, Christian P.
A1  - Kramer, Boris W.
T1  - Poractant alfa (Curosurf (R)) increases phagocytosis of apoptotic neutrophils by alveolar macrophages in vivo
JF  - Respiratory Research
N2  - Background: Clearance of apoptotic neutrophils in the lung is an essential process to limit inflammation, since they could become a pro-inflammatory stimulus themselves. The clearance is partially mediated by alveolar macrophages, which phagocytose these apoptotic cells. The phagocytosis of apoptotic immune cells by monocytes in vitro has been shown to be augmented by several constituents of pulmonary surfactant, e. g. phospholipids and hydrophobic surfactant proteins. In this study, we assessed the influence of exogenous poractant alfa (Curosurf (R)) instillation on the in vivo phagocytosis of apoptotic neutrophils by alveolar macrophages. 
Methods: Poractant alfa (200 mg/kg) was instilled intratracheally in the lungs of three months old adult male C57/Black 6 mice, followed by apoptotic neutrophil instillation. Bronchoalveloar lavage was performed and alveolar macrophages and neutrophils were counted. Phagocytosis of apoptotic neutrophils was quantified by determining the number of apoptotic neutrophils per alveolar macrophages. 
Results: Exogenous surfactant increased the number of alveolar macrophages engulfing apoptotic neutrophils 2.6 fold. The phagocytosis of apoptotic neutrophils was increased in the presence of exogenous surfactant by a 4.7 fold increase in phagocytosed apoptotic neutrophils per alveolar macrophage. 
Conclusions: We conclude that the anti-inflammatory properties of surfactant therapy may be mediated in part by increased numbers of alveolar macrophages and increased phagocytosis of apoptotic neutrophils by alveolar macrophages.
KW  - preterm
KW  - surfactant protein-A
KW  - respiratory-distress-syndrome
KW  - synthetic surfactant
KW  - human monocytes
KW  - SIRP-alpha
KW  - lung
KW  - cells
KW  - inflammation
KW  - resolution
KW  - anti inflammation
KW  - drug therapy
KW  - surfactant
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130721
VL  - 13
IS  - 17
ER  - 
TY  - JOUR
A1  - Schwerk, Christian
A1  - Papandreou, Thalia
A1  - Schuhmann, Daniel
A1  - Nickol, Laura
A1  - Borkowski, Julia
A1  - Steinmann, Ulrike
A1  - Quednau, Natascha
A1  - Stump, Carolin
A1  - Weiss, Christel
A1  - Berger, Jürgen
A1  - Wolburg, Hartwig
A1  - Claus, Heike
A1  - Vogel, Ulrich
A1  - Ishikawa, Hiroshi
A1  - Tenenbaum, Tobias
A1  - Schroten, Horst
T1  - Polar Invasion and Translocation of Neisseria meningitidis and Streptococcus suis in a Novel Human Model of the Blood-Cerebrospinal Fluid Barrier
JF  - PLoS One
N2  - Acute bacterial meningitis is a life-threatening disease in humans. Discussed as entry sites for pathogens into the brain are the blood-brain and the blood-cerebrospinal fluid barrier (BCSFB). Although human brain microvascular endothelial cells (HBMEC) constitute a well established human in vitro model for the blood-brain barrier, until now no reliable human system presenting the BCSFB has been developed. Here, we describe for the first time a functional human BCSFB model based on human choroid plexus papilloma cells (HIBCPP), which display typical hallmarks of a BCSFB as the expression of junctional proteins and formation of tight junctions, a high electrical resistance and minimal levels of macromolecular flux when grown on transwell filters. Importantly, when challenged with the zoonotic pathogen Streptococcus suis or the human pathogenic bacterium Neisseria meningitidis the HIBCPP show polar bacterial invasion only from the physiologically relevant basolateral side. Meningococcal invasion is attenuated by the presence of a capsule and translocated N. meningitidis form microcolonies on the apical side of HIBCPP opposite of sites of entry. As a functionally relevant human model of the BCSFB the HIBCPP offer a wide range of options for analysis of disease-related mechanisms at the choroid plexus epithelium, especially involving human pathogens.
KW  - gene expression
KW  - plexus epithelial-cells
KW  - central-nervous-system
KW  - microvascular endothelial-cells
KW  - choroid-plexus
KW  - in vitro
KW  - brain barrier
KW  - tight junctions
KW  - meningococcal disease
KW  - bacterial meningitis
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131459
VL  - 7
IS  - 1
ER  - 
TY  - JOUR
A1  - Tu, Xiaolin
A1  - Chen, Jianquan
A1  - Lim, Joohyun
A1  - Karner, Courtney M.
A1  - Lee, Seung-Yon
A1  - Heisig, Julia
A1  - Wiese, Cornelia
A1  - Surendran, Kameswaran
A1  - Kopan, Raphael
A1  - Gessler, Manfred
A1  - Long, Fanxin
T1  - Physiological Notch Signaling Maintains Bone Homeostasis via RBPjk and Hey Upstream of NFATc1
JF  - PLoS Genetics
N2  - Notch signaling between neighboring cells controls many cell fate decisions in metazoans both during embryogenesis and in postnatal life. Previously, we uncovered a critical role for physiological Notch signaling in suppressing osteoblast differentiation in vivo. However, the contribution of individual Notch receptors and the downstream signaling mechanism have not been elucidated. Here we report that removal of Notch2, but not Notch1, from the embryonic limb mesenchyme markedly increased trabecular bone mass in adolescent mice. Deletion of the transcription factor RBPjk, a mediator of all canonical Notch signaling, in the mesenchymal progenitors but not the more mature osteoblast-lineage cells, caused a dramatic high-bone-mass phenotype characterized by increased osteoblast numbers, diminished bone marrow mesenchymal progenitor pool, and rapid age-dependent bone loss. Moreover, mice deficient in Hey1 and HeyL, two target genes of Notch-RBPjk signaling, exhibited high bone mass. Interestingly, Hey1 bound to and suppressed the NFATc1 promoter, and RBPjk deletion increased NFATc1 expression in bone. Finally, pharmacological inhibition of NFAT alleviated the high-bone-mass phenotype caused by RBPjk deletion. Thus, Notch-RBPjk signaling functions in part through Hey1-mediated inhibition of NFATc1 to suppress osteoblastogenesis, contributing to bone homeostasis in vivo.
KW  - expression
KW  - axial skeletal defects
KW  - transcription factor
KW  - alagille syndrome
KW  - osteoblast differentiation
KW  - human jagged1
KW  - aortic-valve
KW  - T cells
KW  - mutations
KW  - mice
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133490
VL  - 8
IS  - 3
ER  - 
TY  - JOUR
A1  - Cornelius, C.
A1  - Leingärtner, A.
A1  - Hoiss, B.
A1  - Krauss, J.
A1  - Steffan-Dewenter, I.
A1  - Menzel, A.
T1  - Phenological response of grassland species to manipulative snowmelt and drought along an altitudinal gradient
N2  - Plant communities in the European Alps are assumed to be highly affected by climate change since temperature rise in this region is above the global average. It is predicted that higher temperatures will lead to advanced snowmelt dates and that the number of extreme weather events will increase. The aims of this study were to determine the impacts of extreme climatic events on flower phenology and to assess whether those impacts differed between lower and higher altitudes. In 2010 an experiment simulating advanced and delayed snowmelt as well as drought event was conducted along an altitudinal transect ca. every 250m (600-2000 m a.s.l.) in the Berchtesgaden National Park, Germany. The study showed that flower phenology is strongly affected by altitude; however there were few effects of the manipulative treatments on flowering. The effects of advanced snowmelt were significantly greater at higher than at lower sites, but no significant difference was found between both altitudinal bands for the other treatments. The response of flower phenology to temperature declined through the season and the length of flowering duration was not significantly influenced by treatments. The stronger effect of advanced snowmelt at higher altitudes might be a response to differences in treatment intensity across the gradient. Consequently, shifts in the date of snowmelt due to global warming may affect species more at higher than at lower altitudes since changes may be more pronounced at higher altitudes. Our data indicate a rather low risk of drought events on flowering phenology in the Bavarian Alps.
KW  - Biologie
KW  - Advanced snowmelt
KW  - Alps
KW  - BBCH
KW  - Climate change
KW  - Delayed snowmelt
KW  - Flowering
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-77969
N1  - ist zugleich: IV. Kapitel der Dissertation von Bernhard Hoiß
ER  - 
TY  - JOUR
A1  - Bohnenkamp, Anne
A1  - Brüning, Gerrit
A1  - Henke, Silke
A1  - Henzel, Katrin
A1  - Jannidis, Fotis
A1  - Middel, Gregor
A1  - Pravida, Dietmar
A1  - Wissenbach, Moritz
T1  - Perspektiven auf Goethes ›Faust‹ Werkstattbericht der historisch-kritischen Hybridedition
N2  - Werkstattbericht Hybridedition zu Goethes Faust. Es handelt sich dabei um ein Gemeinschaftsprojekt des Freien deutsche Hochstifts, des Goethe- und Schiller Archivs Weimar und der Universität Würzburg. Der Aufsatz befasst sich mit dem derzeitigen Entwicklungsstand der Edition, deren Konzeption als Hybridedition und verschiedenen Aspekten der Datenmodellierung.
KW  - Historische Kritik
KW  - Goethe
KW  - Johann Wolfgang von
KW  - Entstehung
KW  - Digitale Edition
KW  - Faust
KW  - Archiv
KW  - Werkstattbericht
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76823
ER  - 
TY  - JOUR
A1  - Aad, G.
A1  - Abbott, B.
A1  - Abdallah, J.
A1  - Abdelalim, A. A.
A1  - Abdesselam, A.
T1  - Performance of the ATLAS Trigger System in 2010
JF  - The European Physical Journal C
N2  - Proton–proton collisions at √s=7 TeV and heavy ion collisions at \(\sqrt{sNN}\)=2.76 TeV were produced by the LHC and recorded using the ATLAS experiment’s trigger system in 2010. The LHC is designed with a maximum bunch crossing rate of 40 MHz and the ATLAS trigger system is designed to record approximately 200 of these per second. The trigger system selects events by rapidly identifying signatures of muon, electron, photon, tau lepton, jet, and B meson candidates, as well as using global event signatures, such as missing transverse energy. An overview of the ATLAS trigger system, the evolution of the system during 2010 and the performance of the trigger system components and selections based on the 2010 collision data are shown. A brief outline of plans for the trigger system in 2011 is presented.
KW  - ATLAS
KW  - Trigger System
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127321
VL  - 72
IS  - 1849
ER  - 
TY  - JOUR
T1  - Performance of missing transverse momentum reconstruction in proton-proton collisions at  √s=7 TeV with ATLAS
JF  - The European Physical Journal C
N2  - The measurement of missing transverse momentum in the ATLAS detector, described in this paper, makes use of the full event reconstruction and a calibration based on reconstructed physics objects. The performance of the missing transverse momentum reconstruction is evaluated using data collected in pp collisions at a centre-of-mass energy of 7 TeV in 2010. Minimum bias events and events with jets of hadrons are used from data samples corresponding to an integrated luminosity of about 0.3 nb\(^{−1}\) and 600 nb\(^{−1}\) respectively, together with events containing a Z boson decaying to two leptons (electrons or muons) or a W boson decaying to a lepton (electron or muon) and a neutrino, from a data sample corresponding to an integrated luminosity of about 36 pb\(^{−1}\). An estimate of the systematic uncertainty on the missing transverse momentum scale is presented
KW  - momentum scale
KW  - Atlas detector
KW  - pp collision
KW  - systematic uncertainty
KW  - transverse momentum
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127530
VL  - 72
IS  - 1844
ER  - 
TY  - JOUR
A1  - Zoephel, Judith
A1  - Reiher, Wencke
A1  - Rexer, Karl-Heinz
A1  - Kahnt, Jörg
A1  - Wegener, Christian
T1  - Peptidomics of the Agriculturally Damaging Larval Stage of the Cabbage Root Fly Delia radicum (Diptera: Anthomyiidae)
JF  - PLoS One
N2  - The larvae of the cabbage root fly induce serious damage to cultivated crops of the family Brassicaceae. We here report the biochemical characterisation of neuropeptides from the central nervous system and neurohemal organs, as well as regulatory peptides from enteroendocrine midgut cells of the cabbage maggot. By LC-MALDI-TOF/TOF and chemical labelling with 4-sulfophenyl isothiocyanate, 38 peptides could be identified, representing major insect peptide families: allatostatin A, allatostatin C, FMRFamide-like peptides, kinin, CAPA peptides, pyrokinins, sNPF, myosuppressin, corazonin, SIFamide, sulfakinins, tachykinins, NPLP1-peptides, adipokinetic hormone and CCHamide 1. We also report a new peptide (Yamide) which appears to be homolog to an amidated eclosion hormone-associated peptide in several Drosophila species. Immunocytochemical characterisation of the distribution of several classes of peptide-immunoreactive neurons and enteroendocrine cells shows a very similar but not identical peptide distribution to Drosophila. Since peptides regulate many vital physiological and behavioural processes such as moulting or feeding, our data may initiate the pharmacological testing and development of new specific peptide-based protection methods against the cabbage root fly and its larva.
KW  - adult drosophila
KW  - central-nervous-system
KW  - blowfly calliphora-vomitoria
KW  - drosophila melanogaster
KW  - mass spectometry
KW  - feeding behavior
KW  - fruit fly
KW  - functional characterization
KW  - immunoreactive neurons
KW  - neobellieria bullata
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131727
VL  - 7
IS  - 7
ER  - 
TY  - JOUR
A1  - Brandt, Alexander U.
A1  - Zimmermann, Hanna
A1  - Kaufhold, Falko
A1  - Promesberger, Julia
A1  - Schippling, Sven
A1  - Finis, David
A1  - Aktas, Orhan
A1  - Geis, Christian
A1  - Ringelstein, Marius
A1  - Ringelstein, E. Bernd
A1  - Hartung, Hans-Peter
A1  - Paul, Friedemann
A1  - Kleffner, Ilka
A1  - Dörr, Jan
T1  - Patterns of Retinal Damage Facilitate Differential Diagnosis between Susac Syndrome and MS
JF  - PLoS One
N2  - Susac syndrome, a rare but probably underdiagnosed combination of encephalopathy, hearing loss, and visual deficits due to branch retinal artery occlusion of unknown aetiology has to be considered as differential diagnosis in various conditions. Particularly, differentiation from multiple sclerosis is often challenging since both clinical presentation and diagnostic findings may overlap. Optical coherence tomography is a powerful and easy to perform diagnostic tool to analyse the morphological integrity of retinal structures and is increasingly established to depict characteristic patterns of retinal pathology in multiple sclerosis. Against this background we hypothesised that differential patterns of retinal pathology facilitate a reliable differentiation between Susac syndrome and multiple sclerosis. In this multicenter cross-sectional observational study optical coherence tomography was performed in nine patients with a definite diagnosis of Susac syndrome. Data were compared with age-, sex-, and disease duration-matched relapsing remitting multiple sclerosis patients with and without a history of optic neuritis, and with healthy controls. Using generalised estimating equation models, Susac patients showed a significant reduction in either or both retinal nerve fibre layer thickness and total macular volume in comparison to both healthy controls and relapsing remitting multiple sclerosis patients. However, in contrast to the multiple sclerosis patients this reduction was not distributed over the entire scanning area but showed a distinct sectorial loss especially in the macular measurements. We therefore conclude that patients with Susac syndrome show distinct abnormalities in optical coherence tomography in comparison to multiple sclerosis patients. These findings recommend optical coherence tomography as a promising tool for differentiating Susac syndrome from MS.
KW  - optical coherence tomography
KW  - vasculopathy
KW  - artery occlusion
KW  - hearing loss
KW  - microangiopathy
KW  - brain
KW  - endotheliopathy
KW  - antibodies
KW  - multiple-sclerosis
KW  - retinocochleocerebral
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134013
VL  - 7
IS  - 6
ER  - 
TY  - JOUR
A1  - Matlach, Juliane
A1  - Slobodda, Joerg
A1  - Grehn, Franz
A1  - Klink, Thomas
T1  - Pars plana vitrectomy for malignant glaucoma in non-glaucomatous and in filtered glaucomatous eyes
N2  - Purpose: To assess the outcomes of pars plana vitrectomy for the treatment of malignant glaucoma in patients with and without previous filtration surgery. Patients and methods: Data of 15 patients developing malignant glaucoma after trabeculectomy (60%) or following ophthalmic interventions other than filtration surgery (40%) were recorded retrospectively. Pars plana vitrectomy was performed in case of failed medical or laser treatment recreating the normal pathway of aqueous humor. The main outcome measures were the postoperative intraocular pressure (IOP), the frequency of complications, and success rate based on the following criteria: IOP reduction by $20% and to #21 mmHg (definition one) or an IOP , 18 mmHg (definition two) with (qualified success) and without (complete success) glaucoma medication. Results: Vitrectomy reduced IOP from baseline in eyes with and without previous trabeculectomy during a median follow-up of 16.4 months (range 7 days to 58 months); although the majority of patients required glaucoma medication to reach desired IOP. The complete success rates were 11% (both definitions) for patients with filtering blebs and none of the patients without previous trabeculectomy had complete success at the 12-month visit. Complications were few and included transient shallowing of the anterior chamber, choroidal detachment, corneal decompensation, filtering bleb failure, and need for further IOP-lowering procedures. Conclusion: Pars plana vitrectomy is equally effective for malignant glaucoma caused by trabeculectomy or interventions other than filtration surgery, although IOP-lowering medication is necessary in nearly all cases to maintain target IOP.
KW  - Medizin
KW  - ciliolenticular block glaucoma
KW  - malignant glaucoma
KW  - pars plana vitrectomy
KW  - trabeculectomy
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76375
ER  - 
TY  - JOUR
A1  - Margapoti, E.
A1  - Alves, F. M.
A1  - Mahapatra, S.
A1  - Lopez-Richard, V.
A1  - Worschech, L.
A1  - Brunner, K.
A1  - Qu, F.
A1  - Destefani, C.
A1  - Menendez-Proupin, E.
A1  - Bougerol, C.
A1  - Forchel, A.
A1  - Marques, G. E.
T1  - Paramagnetic shift in thermally annealed Cd\(_x\)Zn\(_{1-x}\)Se quantum dots
JF  - New Journal of Physics
N2  - The photoluminescence of annealed Cd\(_x\)Zn\(_{1-x}\)Se quantum dots (QDs) under the influence of an external magnetic field has been studied in this paper. Post-growth annealing was performed for different annealing times. Above a critical annealing time, the QD luminescence shows a pronounced red-shift of the Zeeman split magnetic subcomponents. This observation is in contrast to the blue-shift caused by the diamagnetic behavior that is usually observed in non-magnetic QDs. We attribute our finding to the paramagnetism caused by the mixing of heavy and light hole states. Hence, post-growth thermal annealing treatment might be employed to render undoped epitaxial QDs intrinsically magnetic in a controlled manner. Two theoretical models were developed: a few-particle model to account for excitonic complex effects and a multiband calculation that describes the valence band hybridization. Contrasting the two models allowed us to unambiguously elucidate the nature of such an effect.
KW  - semiconductors
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133294
VL  - 14
IS  - 043038
ER  - 
TY  - JOUR
A1  - Jakubietz, Michael G.
A1  - Gruenert, Joerg G.
A1  - Jakubietz, Rafael G.
T1  - Palmar and dorsal fixed-angle plates in AO C-type fractures of the distal radius: is there an advantage of palmar plates in the long term?
JF  - Journal of Orthopedic Surgery and Research
N2  - Background: Current surgical approaches to the distal radius include dorsal and palmar plate fixation. While palmar plates have gained widespread popularity, few reports have provided data on long term clinical outcomes in comparison. This paper reports the result of a randomised clinical study comparing dorsal Pi plates and palmar, angle-stable plates for treatment of comminuted, intraarticular fractures of the distal radius over the course of twelve months. 
Methods: 42 patients with unilateral, intraarticular fractures of the distal radius were included and randomised to 2 groups, 22 were treated with a palmar plate, 20 received a dorsal Pi-plate. Results were evaluated after 6 weeks, 3, 6 and 12 months postoperatively focussing on functional recovery as well as radiological results. 
Results: The palmar plate group demonstrated significantly better results regarding range of motion and grip strength over the course of 12 months. While a comparable increase in function was observed in both groups, the better results from the early postoperative period in the palmar plate group prevailed over the whole course. Radiological results showed a significantly increased palmar tilt and carpal sag in dorsal plates, with other radiological parameters being comparable. Pain levels were decreased in dorsal plates after hardware removal and failed to show significant differences after 12 months. However, complications such as tendon ruptures were more frequent in the dorsal plate group. 
Conclusions: Functional advantage of palmar plates gained within the first 6 weeks prevails over the course of a year. Both groups demonstrate further gradual increase of function after 6 months, although dorsal plates did not catch up completely. Improved early postoperative function seems to be the cornerstone for the best possible results. Patients with dorsal plates benefit from hardware removal more than palmar plates in terms of reduction of pain levels. The advantage of palmar plates is a faster functional recovery with lower complication rates. This is especially important in the elderly population. Radiological results did not show a superiority of palmar plates over dorsal plates.
KW  - internal fixation
KW  - intraarticular fractures
KW  - percutaneous fixation
KW  - open reduction
KW  - trial
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133987
VL  - 7
IS  - 8
ER  - 
TY  - JOUR
A1  - Roesler, Joachim
A1  - Segerer, Florian
A1  - Morbach, Henner
A1  - Kleinert, Stefan
A1  - Thieme, Sebastian
A1  - Rösen-Wolff, Angela
A1  - Liese, Johannes G.
T1  - P67-phox (NCF2) Lacking Exons 11 and 12 Is Functionally Active and Leads to an Extremely Late Diagnosis of Chronic Granulomatous Disease (CGD)
JF  - PLoS One
N2  - Two brothers in their fifties presented with a medical history of suspected fungal allergy, allergic bronchopulmonary aspergillosis, alveolitis, and invasive aspergillosis and pulmonary fistula, respectively. Eventually, after a delay of 50 years, chronic granulomatous disease (CGD) was diagnosed in the index patient. We found a new splice mutation in the NCF2 (p67-phox) gene, c.1000+2T -> G, that led to several splice products one of which lacked exons 11 and 12. This deletion was in frame and allowed for remarkable residual NADPH oxidase activity as determined by transduction experiments using a retroviral vector. We conclude that p67-phox which lacks the 34 amino acids encoded by the two exons can still exert considerable functional activity. This activity can partially explain the long-term survival of the patients without adequate diagnosis and treatment, but could not prevent progressing lung damage.
KW  - P67(PHOX)
KW  - NADPH oxidase
KW  - European experience
KW  - interferon gamma
KW  - gene
KW  - region
KW  - prophylaxis
KW  - infection
KW  - mutation
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134948
VL  - 7
IS  - 4
ER  - 
TY  - JOUR
A1  - Kotte, K.
A1  - Löw, F.
A1  - Huber, S. G.
A1  - Krause, T.
A1  - Mulder, I.
A1  - Schöler, H. F.
T1  - Organohalogen emissions from saline environments - spatial extrapolation using remote sensing as most promising tool
JF  - Biogeosciences
N2  - Due to their negative water budget most recent semi-/arid regions are characterized by vast evaporates (salt lakes and salty soils). We recently identified those hyper-saline environments as additional sources for a multitude of volatile halogenated organohalogens (VOX). These compounds can affect the ozone layer of the stratosphere and play a key role in the production of aerosols. A remote sensing based analysis was performed in the Southern Aral Sea basin, providing information of major soil types as well as their extent and spatial and temporal evolution. VOX production has been determined in dry and moist soil samples after 24 h. Several C1- and C2 organohalogens have been found in hyper-saline topsoil profiles, including CH3Cl, CH3Br, CHBr3 and CHCl3. The range of organohalogens also includes trans-1,2-dichloroethene (DCE), which is reported here to be produced naturally for the first time. Using MODIS time series and supervised image classification a daily production rate for DCE has been calculated for the 15 000 km\(^2\) ranging research area in the southern Aralkum. The applied laboratory setup simulates a short-term change in climatic conditions, starting from dried-out saline soil that is instantly humidified during rain events or flooding. It describes the general VOX production potential, but allows only for a rough estimation of resulting emission loads. VOX emissions are expected to increase in the future since the area of salt affected soils is expanding due to the regressing Aral Sea. Opportunities, limits and requirements of satellite based rapid change detection and salt classification are discussed.
KW  - aral sea basin
KW  - methyl-bromide
KW  - methane emissions
KW  - abiotic formation
KW  - time series
KW  - salt lakes
KW  - land
KW  - Uzbekistan
KW  - soils/sediments
KW  - classifiaction
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134265
VL  - 9
IS  - 3
ER  - 
TY  - JOUR
A1  - Aeschlimann, Martin
A1  - Bauer, Michael
A1  - Bayer, Daniela
A1  - Brixner, Tobias
A1  - Cunovic, Stefan
A1  - Fischer, Alexander
A1  - Melchior, Pascal
A1  - Pfeiffer, Walter
A1  - Rohmer, Martin
A1  - Schneider, Christian
A1  - Strüber, Christian
A1  - Tuchscherer, Philip
A1  - Voronine, Dimitri V.
T1  - Optimal open-loop near-field control of plasmonic nanostructures
N2  - Optimal open-loop control, i.e. the application of an analytically derived control rule, is demonstrated for nanooptical excitations using polarization-shaped laser pulses. Optimal spatial near-field localization in gold nanoprisms and excitation switching is realized by applying a shift to the relative phase of the two polarization components. The achieved near-field switching confirms theoretical predictions, proves the applicability of predefined control rules in nanooptical light–matter interaction and reveals local mode interference to be an important control mechanism.
KW  - Chemie
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75256
ER  - 
TY  - JOUR
A1  - Hubert, Kerstin
A1  - Pawlik, Marie-Christin
A1  - Claus, Heike
A1  - Jarva, Hanna
A1  - Meri, Seppo
A1  - Vogel, Ulrich
T1  - Opc Expression, LPS Immunotype Switch and Pilin Conversion Contribute to Serum Resistance of Unencapsulated Meningococci
JF  - PLoS One
N2  - Neisseria meningitidis employs polysaccharides and outer membrane proteins to cope with human serum complement attack. To screen for factors influencing serum resistance, an assay was developed based on a colorimetric serum bactericidal assay. The screening used a genetically modified sequence type (ST)-41/44 clonal complex (cc) strain lacking LPS sialylation, polysaccharide capsule, the factor H binding protein (fHbp) and MutS, a protein of the DNA repair mechanism. After killing of >99.9% of the bacterial cells by serum treatment, the colorimetric assay was used to screen 1000 colonies, of which 35 showed enhanced serum resistance. Three mutant classes were identified. In the first class of mutants, enhanced expression of Opc was identified. Opc expression was associated with vitronectin binding and reduced membrane attack complex deposition confirming recent observations. Lipopolysaccharide (LPS) immunotype switch from immunotype L3 to L8/L1 by lgtA and lgtC phase variation represented the second class. Isogenic mutant analysis demonstrated that in ST-41/44 cc strains the L8/L1 immunotype was more serum resistant than the L3 immunotype. Consecutive analysis revealed that the immunotypes L8 and L1 were frequently observed in ST-41/44 cc isolates from both carriage and disease. Immunotype switch to L8/L1 is therefore suggested to contribute to the adaptive capacity of this meningococcal lineage. The third mutant class displayed a pilE allelic exchange associated with enhanced autoaggregation. The mutation of the C terminal hypervariable region D of PilE included a residue previously associated with increased pilus bundle formation. We suggest that autoaggregation reduced the surface area accessible to serum complement and protected from killing. The study highlights the ability of meningococci to adapt to environmental stress by phase variation and intrachromosomal recombination affecting subcapsular antigens.
KW  - factor H
KW  - C-reactive protein
KW  - B neisseria meningitidis
KW  - outer membrane protein
KW  - phase variation
KW  - serogroup B
KW  - bactericidal activity
KW  - epithelial cells
KW  - gene conversion
KW  - strain MC58
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135421
VL  - 7
IS  - 9
ER  - 
TY  - JOUR
A1  - Hartung, Andreas
A1  - Seufert, Florian
A1  - Berges, Carsten
A1  - Gessner, Viktoria H.
A1  - Holzgrabe, Ulrike
T1  - One-Pot Ugi/Aza-Michael Synthesis of Highly Substituted 2,5-Diketopiperazines with Anti-Proliferative Properties
JF  - Molecules
N2  - The well-known Ugi reaction of aldehydes with amines, carboxylic acids and isocyanides leads to the formation of acyclic alpha-acylaminocarboxamides. Replacement of the carboxylic acid derivatives with beta-acyl substituted acrylic acids gives access to highly substituted 2,5-diketopiperazines in one single reaction-step without additives or complex reaction procedures. The obtained diketopiperazines show anti-proliferative effects on activated T cells and represent therefore potential candidates for targeting unwanted T cell-mediated immune responses.
KW  - multicomponent Ugi-type reaction
KW  - intramolecular Michael addition
KW  - strategy
KW  - derivates
KW  - diketopiperazines
KW  - chemistry
KW  - T cell
KW  - 2,5-diketopiperazines
KW  - anti-proliferative effects
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130423
VL  - 17
IS  - 12
ER  - 
TY  - JOUR
A1  - Patil, Sandeep S.
A1  - Gentschev, Ivaylo
A1  - Nolte, Ingo
A1  - Ogilvie, Gregory
A1  - Szalay, Aladar A.
T1  - Oncolytic virotherapy in veterinary medicine: current status and future prospects for canine patients
N2  - Oncolytic viruses refer to those that are able to eliminate malignancies by direct targeting and lysis of cancer cells, leaving non-cancerous tissues unharmed. Several oncolytic viruses including adenovirus strains, canine distemper virus and vaccinia virus strains have been used for canine cancer therapy in preclinical studies. However, in contrast to human studies, clinical trials with oncolytic viruses for canine cancer patients have not been reported. An ‘ideal’ virus has yet to be identified. This review is focused on the prospective use of oncolytic viruses in the treatment of canine tumors - a knowledge that will undoubtedly contribute to the development of oncolytic viral agents for canine cancer therapy in the future.
KW  - Medizin
KW  - cancer
KW  - canine cancer therapy
KW  - oncolytic virus
KW  - oncolysis
KW  - target molecule
KW  - combination therapy
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75128
ER  - 
TY  - JOUR
A1  - Wang, Huiqiang
A1  - Chen, Nanhai G.
A1  - Minev, Boris R.
A1  - Szalay, Aladar A.
T1  - Oncolytic vaccinia virus GLV-1h68 strain shows enhanced replication in human breast cancer stem-like cells in comparison to breast cancer cells
JF  - Journal of Translational Medicine
N2  - Background: Recent data suggest that cancer stem cells (CSCs) play an important role in cancer, as these cells possess enhanced tumor-forming capabilities and are responsible for relapses after apparently curative therapies have been undertaken. Hence, novel cancer therapies will be needed to test for both tumor regression and CSC targeting. The use of oncolytic vaccinia virus (VACV) represents an attractive anti-tumor approach and is currently under evaluation in clinical trials. The purpose of this study was to demonstrate whether VACV does kill CSCs that are resistant to irradiation and chemotherapy. 
Methods: Cancer stem-like cells were identified and separated from the human breast cancer cell line GI-101A by virtue of increased aldehyde dehydrogenase 1 (ALDH1) activity as assessed by the ALDEFLUOR assay and cancer stem cell-like features such as chemo-resistance, irradiation-resistance and tumor-initiating were confirmed in cell culture and in animal models. VACV treatments were applied to both ALDEFLUOR-positive cells in cell culture and in xenograft tumors derived from these cells. Moreover, we identified and isolated CD44\(^+\)CD24\(^+\)ESA\(^+\) cells from GI-101A upon an epithelial-mesenchymal transition (EMT). These cells were similarly characterized both in cell culture and in animal models. 
Results: We demonstrated for the first time that the oncolytic VACV GLV-1h68 strain replicated more efficiently in cells with higher ALDH1 activity that possessed stem cell-like features than in cells with lower ALDH1 activity. GLV-1h68 selectively colonized and eventually eradicated xenograft tumors originating from cells with higher ALDH1 activity. Furthermore, GLV-1h68 also showed preferential replication in CD44\(^+\)CD24\(^+\)ESA\(^+\) cells derived from GI-101A upon an EMT induction as well as in xenograft tumors originating from these cells that were more tumorigenic than CD44\(^+\)CD24\(^-\)ESA\(^+\) cells. 
Conclusions: Taken together, our findings indicate that GLV-1h68 efficiently replicates and kills cancer stem-like cells. Thus, GLV-1h68 may become a promising agent for eradicating both primary and metastatic tumors, especially tumors harboring cancer stem-like cells that are resistant to chemo and/or radiotherapy and may be responsible for recurrence of tumors.
KW  - tumors
KW  - therapy
KW  - metastasis
KW  - identification
KW  - lines
KW  - gene expression
KW  - in-vitro propagation
KW  - acute myeloid leukemia
KW  - epithelial-mesenchymal transition
KW  - subpopulation
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130019
VL  - 10
IS  - 167
ER  - 
TY  - JOUR
A1  - Harrington, John M.
A1  - Scelsi, Chris
A1  - Hartel, Andreas
A1  - Jones, Nicola G.
A1  - Engstler, Markus
A1  - Capewell, Paul
A1  - MacLeod, Annette
A1  - Hajduk, Stephen
T1  - Novel African Trypanocidal Agents: Membrane Rigidifying Peptides
JF  - PLoS One
N2  - The bloodstream developmental forms of pathogenic African trypanosomes are uniquely susceptible to killing by small hydrophobic peptides. Trypanocidal activity is conferred by peptide hydrophobicity and charge distribution and results from increased rigidity of the plasma membrane. Structural analysis of lipid-associated peptide suggests a mechanism of phospholipid clamping in which an internal hydrophobic bulge anchors the peptide in the membrane and positively charged moieties at the termini coordinate phosphates of the polar lipid headgroups. This mechanism reveals a necessary phenotype in bloodstream form African trypanosomes, high membrane fluidity, and we suggest that targeting the plasma membrane lipid bilayer as a whole may be a novel strategy for the development of new pharmaceutical agents. Additionally, the peptides we have described may be valuable tools for probing the biosynthetic machinery responsible for the unique composition and characteristics of African trypanosome plasma membranes.
KW  - depth
KW  - trypanosome lytic factor
KW  - signal peptides
KW  - cell surface
KW  - protein
KW  - brucei
KW  - environment
KW  - bilayers
KW  - binding
KW  - probes
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135179
VL  - 7
IS  - 9
ER  - 
TY  - JOUR
A1  - Chenchiah, Isaac
A1  - Schlömerkemper, Anja
T1  - Non-laminate microstructures in monoclinic-I martensite
N2  - We study the symmetrised rank-one convex hull of monoclinic-I martensite (a twelve-variant material) in the context of geometrically-linear elasticity. We construct sets of T3s, which are (non-trivial) symmetrised rank-one convex hulls of 3-tuples of pairwise incompatible strains. Moreover we construct a five-dimensional continuum of T3s and show that its intersection with the boundary of the symmetrised rank-one convex hull is four-dimensional. We also show that there is another kind of monoclinic-I martensite with qualitatively different semi-convex hulls which, so far as we know, has not been experimentally observed. Our strategy is to combine understanding of the algebraic structure of symmetrised rank-one convex cones with knowledge of the faceting structure of the convex polytope formed by the strains.
KW  - Martensit
KW  - Mehrskalenmodell
KW  - Phasenumwandlung
KW  - Variationsrechnung
KW  - kubisch-monokliner Phasenübergang
KW  - semi-konvexe Hüllen
KW  - geometrisch lineare Elastizitätstheorie
KW  - T3s
KW  - cubic-monoclinic martensites
KW  - semi-convex hulls
KW  - geometrically linear elasticity
KW  - T3s
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-72134
ER  - 
TY  - JOUR
A1  - Riedel, Simone S.
A1  - Mottok, Anja
A1  - Brede, Christian
A1  - Bäuerlein, Carina A.
A1  - Jordán Garrote, Ana Laura
A1  - Ritz, Miriam
A1  - Mattenheimer, Katharina
A1  - Rosenwald, Andreas
A1  - Einsele, Hermann
A1  - Bogen, Bjarne
A1  - Beilhack, Andreas
T1  - Non-Invasive Imaging Provides Spatiotemporal Information on Disease Progression and Response to Therapy in a Murine Model of Multiple Myeloma
N2  - Background: Multiple myeloma (MM) is a B-cell malignancy, where malignant plasma cells clonally expand in the bone marrow of older people, causing significant morbidity and mortality. Typical clinical symptoms include increased serum calcium levels, renal insufficiency, anemia, and bone lesions. With standard therapies, MM remains incurable; therefore, the development of new drugs or immune cell-based therapies is desirable. To advance the goal of finding a more effective treatment for MM, we aimed to develop a reliable preclinical MM mouse model applying sensitive and reproducible methods for monitoring of tumor growth and metastasis in response to therapy. Material and Methods: A mouse model was created by intravenously injecting bone marrow-homing mouse myeloma cells (MOPC-315.BM) that expressed luciferase into BALB/c wild type mice. The luciferase in the myeloma cells allowed in vivo tracking before and after melphalan treatment with bioluminescence imaging (BLI). Homing of MOPC-315.BM luciferase+ myeloma cells to specific tissues was examined by flow cytometry. Idiotype-specific myeloma protein serum levels were measured by ELISA. In vivo measurements were validated with histopathology. Results: Strong bone marrow tropism and subsequent dissemination of MOPC-315.BM luciferase+ cells in vivo closely mimicked the human disease. In vivo BLI and later histopathological analysis revealed that 12 days of melphalan treatment slowed tumor progression and reduced MM dissemination compared to untreated controls. MOPC-315.BM luciferase+ cells expressed CXCR4 and high levels of CD44 and a4b1 in vitro which could explain the strong bone marrow tropism. The results showed that MOPC-315.BM cells dynamically regulated homing receptor expression and depended on interactions with surrounding cells. Conclusions: This study described a novel MM mouse model that facilitated convenient, reliable, and sensitive tracking of myeloma cells with whole body BLI in living animals. This model is highly suitable for monitoring the effects of different treatment regimens.
KW  - Medizin
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-77978
ER  - 
TY  - JOUR
A1  - Votteler, Miriam
A1  - Carvajal Berrio, Daniel A.
A1  - Pudlas, Marieke
A1  - Walles, Heike
A1  - Schenke-Layland, Katja
T1  - Non-contact, Label-free Monitoring of Cells and Extracellular Matrix using Raman Spectroscopy
JF  - Journal of Visual Expression
N2  - Non-destructive, non-contact and label-free technologies to monitor cell and tissue cultures are needed in the field of biomedical research.1-5 However, currently available routine methods require processing steps and alter sample integrity. Raman spectroscopy is a fast method that enables the measurement of biological samples without the need for further processing steps. This laser-based technology detects the inelastic scattering of monochromatic light.6 As every chemical vibration is assigned to a specific Raman band (wavenumber in cm-1), each biological sample features a typical spectral pattern due to their inherent biochemical composition.7-9 Within Raman spectra, the peak intensities correlate with the amount of the present molecular bonds.1 Similarities and differences of the spectral data sets can be detected by employing a multivariate analysis (e.g. principal component analysis (PCA)).10

Here, we perform Raman spectroscopy of living cells and native tissues. Cells are either seeded on glass bottom dishes or kept in suspension under normal cell culture conditions (37 °C, 5% CO2) before measurement. Native tissues are dissected and stored in phosphate buffered saline (PBS) at 4 °C prior measurements. Depending on our experimental set up, we then either focused on the cell nucleus or extracellular matrix (ECM) proteins such as elastin and collagen. For all studies, a minimum of 30 cells or 30 random points of interest within the ECM are measured. Data processing steps included background subtraction and normalization.
KW  - tissue engineering
KW  - label-free analysis
KW  - raman spectroscopy
KW  - bioengineering
KW  - living cells
KW  - extracellular matrix
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124569
VL  - 63
IS  - e3977
ER  - 
TY  - JOUR
A1  - Kraft, Peter
A1  - De Meyer, Simon F.
A1  - Kleinschnitz, Christoph
T1  - Next-Generation Antithrombotics in Ischemic Stroke: Preclinical Perspective on ‘Bleeding-Free Antithrombosis’
JF  - Journal of Cerebral Blood Flow and Metabolism
N2  - The present antithrombotic drugs used to treat or prevent ischemic stroke have significant limitations: either they show only moderate efficacy (platelet inhibitors), or they significantly increase the risk for hemorrhages (thrombolytics, anticoagulants). Although most strokes are caused by thrombotic or embolic vessel occlusions, the pathophysiological role of platelets and coagulation is largely unclear. The introduction of novel transgenic mouse models and specific coagulation inhibitors facilitated a detailed analysis of molecular pathways mediating thrombus formation in models of acute ischemic stroke. Prevention of early platelet adhesion to the damaged vessel wall by blocking platelet surface receptors glycoprotein Ib alpha (GPIbα) or glycoprotein VI (GPVI) protects from stroke without provoking bleeding complications. In addition, downstream signaling of GPIbα and GPVI has a key role in platelet calcium homeostasis and activation. Finally, the intrinsic coagulation cascade, activated by coagulation factor XII (FXII), has only recently been identified as another important mediator of thrombosis in cerebrovascular disease, thereby disproving established concepts. This review summarizes the latest insights into the pathophysiology of thrombus formation in the ischemic brain. Potential clinical merits of novel platelet inhibitors and anticoagulants as powerful and safe tools to combat ischemic stroke are discussed.
KW  - von Willebrand factor
KW  - platelets
KW  - glycoprotein Ib
KW  - FXII
KW  - coagulation
KW  - Stim
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126538
VL  - 32
IS  - 10
ER  - 
TY  - JOUR
A1  - Darwish, Hany W.
A1  - Attia, Mohamed I.
T1  - New spectrofluorimetric methods for determination of melatonin in the presence of N-{2-[1-({3-[2-(acetylamino)ethyl]-5-methoxy-1H-indol-2-yl}methyl)-5-methoxy-1H-indol-3-yl]ethyl} acetamide: a contaminant in commercial melatonin preparations
JF  - Chemistry Central Journal
N2  - Background: Melatonin (MLT) has many health implications, therefore it is of valuable importance to develop specific analytical methods for determination of MLT in the presence of its main contaminant, N-{2-[1-({3-[2(acetylamino)ethyl]-5-methoxy-1H-indol-2-yl}methyl)-5-methoxy-1H-indol-3-yl]ethyl}acetamide (10). For development of these analytical methods, compound 10 had to be prepared in an adequate amount. 
Results: Compound 10 was synthesized in six steps starting from 5-methoxyindole-2-carboxylic acid (1). Analytical performance of the proposed spectrofluorimetric methods was statistically validated with respect to linearity, accuracy, precision and specificity. The proposed methods were successfully applied for the assay of MLT in laboratory prepared mixtures containing up to 60 % of compound 10 and in commercial MLT tablets with recoveries not less than 99.00 %. No interference was observed from common pharmaceutical additives and the results were favorably compared with those obtained by a reference method. 
Conclusions: This work describes simple, sensitive, and reliable second derivative spectrofluorimetric method in addition to two multivariate calibration methods, principal component regression (PCR) and partial least square (PLS), for the determination of MLT in the presence of compound 10.
KW  - melatonin
KW  - commercial preparations
KW  - spectrofluorimetry
KW  - synthesis
KW  - contaminants
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134606
VL  - 6
IS  - 36
ER  - 
TY  - JOUR
A1  - Darwish, Hany W.
A1  - Attia, Mohamed I.
T1  - New spectrofluorimetric methods for determination of melatonin in the presence of N-{2-[1-({3-[2-(acetylamino)ethyl]-5-methoxy-1H-indol-2-yl}methyl)-5-methoxy-1H-indol-3-yl]- ethyl}acetamide: a contaminant in commercial melatonin preparations
N2  - Background: Melatonin (MLT) has many health implications, therefore it is of valuable importance to develop specific analytical methods for determination of MLT in the presence of its main contaminant, N-{2-[1-({3-[2-(acetylamino)ethyl]-5-methoxy-1H-indol-2-yl}methyl)-5-methoxy-1H-indol-3-yl]ethyl}acetamide (10). For development of these analytical methods, compound 10 had to be prepared in an adequate amount. Results: Compound 10 was synthesized in six steps starting from 5-methoxyindole-2-carboxylic acid (1). Analytical performance of the proposed spectrofluorimetric methods was statistically validated with respect to linearity, accuracy, precision and specificity. The proposed methods were successfully applied for the assay of MLT in laboratory prepared mixtures containing up to 60 % of compound 10 and in commercial MLT tablets with recoveries not less than 99.00 %. No interference was observed from common pharmaceutical additives and the results were favorably compared with those obtained by a reference method. Conclusions: This work describes simple, sensitive, and reliable second derivative spectrofluorimetric method in addition to two multivariate calibration methods, principal component regression (PCR) and partial least square (PLS), for the determination of MLT in the presence of compound 10.
KW  - Chemie
KW  - Melatonin
KW  - Contaminants
KW  - Synthesis
KW  - Spectrofluorimetry
KW  - Commercial preparations
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-78234
ER  - 
TY  - JOUR
A1  - Winter, Walter
T1  - Neutrinos from Cosmic Accelerators Including Magnetic Field and Flavor Effects
N2  - We review the particle physics ingredients affecting the normalization, shape, and flavor composition of astrophysical neutrinos fluxes, such as different production modes, magnetic field effects on the secondaries muons, pions, and kaons, and flavor mixing, where we focus on p? interactions. We also discuss the interplay with neutrino propagation and detection, including the possibility to detect flavor and its application in particle physics, and the use of the Glashow resonance to discriminate p? from pp interactions in the source. We illustrate the implications on fluxes and flavor composition with two different models: 1 the target photon spectrum is dominated by synchrotron emission of coaccelerated electrons and 2 the target photon spectrum follows the observed photon spectrum of gamma-ray bursts. In the latter case, the multimessenger extrapolation from the gamma-ray fluence to the expected neutrino flux is highlighted.
KW  - Magnetfeld
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75290
ER  -