TY  - JOUR
A1  - Kraft, Stephan
T1  - Zwischen anverwandt und anverwandelt: Familienkonzepte in Grimmelshausens "Simplicissimus Teutsch"
JF  - Simpliciana
N2  - Kein Abstract verfügbar.
KW  - Familie <Motiv>
KW  - Grimmelshausen; Hans Jakob Christoffel von / Simplizissimus
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252805
VL  - XXXIV
ER  - 
TY  - JOUR
A1  - Pfister, Roland
A1  - Pohl, Carsten
A1  - Kiesel, Andrea
A1  - Kunde, Wilfried
T1  - Your Unconscious Knows Your Name
N2  - One’s own name constitutes a unique part of conscious awareness – but does this also hold true for unconscious processing? The present study shows that the own name has the power to bias a person’s actions unconsciously even in conditions that render any other name ineffective. Participants judged whether a letter string on the screen was a name or a non-word while this target stimulus was preceded by a masked prime stimulus. Crucially, the participant’s own name was among these prime stimuli and facilitated reactions to following name targets whereas the name of another, yoked participant did not. Signal detection results confirmed that participants were not aware of any of the prime stimuli, including their own name. These results extend traditional findings on ‘‘breakthrough’’ phenomena of personally relevant stimuli to the domain of unconscious processing. Thus, the brain seems to possess adroit mechanisms to identify and process such stimuli even in the absence of conscious awareness.
KW  - Psychologie
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75304
ER  - 
TY  - JOUR
A1  - Hämmer, Viola
T1  - Wo suchen die Profis? Elektronische Informationsmittel jenseits von Google
N2  - Fast zu jedem Thema liefert Google auf Knopfdruck eine Vielzahl von Informationen. Aber ist die Suchmaschine auch ein Werkzeug, mit dem wissenschaftliche Fragen zufriedenstellend beantwortet werden können? Und welche Alternativen gibt es für die wissenschaftliche Recherche?
KW  - Online-Recherche
KW  - Wissenschaftliche Literatur
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-72776
ER  - 
TY  - JOUR
A1  - Berthold, Norbert
A1  - Brunner, Alexander
T1  - Wie ungleich ist die Welt? Eine empirische Analyse
JF  - Perspektiven der Wirtschaftspolitik
N2  - Kein Abstract verfügbar.
KW  - Ungleichheit
KW  - empirische Analyse
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-194171
SN  - 1468-2516
SN  - 1465-6493
N1  - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
VL  - 12
IS  - 4
ER  - 
TY  - JOUR
A1  - Zhang, Shaowu
A1  - Si, Aung
A1  - Pahl, Mario
T1  - Visually guided decision making in foraging honeybees
JF  - Frontiers in Neuroscience
N2  - Honeybees can easily be trained to perform different types of discrimination tasks under controlled laboratory conditions. This review describes a range of experiments carried out with free-flying forager honeybees under such conditions. The research done over the past 30 or so years suggests that cognitive abilities (learning and perception) in insects are more intricate and flexible than was originally imagined. It has become apparent that honeybees are capable of a variety of visually guided tasks, involving decision making under challenging situations: this includes simultaneously making use of different sensory modalities, such as vision and olfaction, and learning to use abstract concepts such as “sameness” and “difference.” Many studies have shown that decision making in foraging honeybees is highly flexible. The trained animals learn how to solve a task, and do so with a high accuracy, but when they are presented with a new variation of the task, they apply the learnt rules from the earlier setup to the new situation, and solve the new task as well. Honeybees therefore not only feature a rich behavioral repertoire to choose from, but also make decisions most apt to the current situation. The experiments in this review give an insight into the environmental cues and cognitive resources that are probably highly significant for a forager bee that must continually make decisions regarding patches of resources to be exploited.
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124228
VL  - 6
IS  - 88
ER  - 
TY  - JOUR
A1  - Patil, Sandeep S.
A1  - Gentschev, Ivaylo
A1  - Adelfinger, Marion
A1  - Donat, Ulrike
A1  - Hess, Michael
A1  - Weibel, Stephanie
A1  - Nolte, Ingo
A1  - Frentzen, Alexa
A1  - Szalay, Aladar A.
T1  - Virotherapy of Canine Tumors with Oncolytic Vaccinia Virus GLV-1h109 Expressing an Anti-VEGF Single-Chain Antibody
JF  - PLoS One
N2  - Virotherapy using oncolytic vaccinia virus (VACV) strains is one promising new strategy for cancer therapy. We have previously reported that oncolytic vaccinia virus strains expressing an anti-VEGF (Vascular Endothelial Growth Factor) single-chain antibody (scAb) GLAF-1 exhibited significant therapeutic efficacy for treatment of human tumor xenografts. Here, we describe the use of oncolytic vaccinia virus GLV-1h109 encoding GLAF-1 for canine cancer therapy. In this study we analyzed the virus-mediated delivery and production of scAb GLAF-1 and the oncolytic and immunological effects of the GLV-1h109 vaccinia virus strain against canine soft tissue sarcoma and canine prostate carcinoma in xenograft models. Cell culture data demonstrated that the GLV-1h109 virus efficiently infect, replicate in and destroy both tested canine cancer cell lines. In addition, successful expression of GLAF-1 was demonstrated in virus-infected canine cancer cells and the antibody specifically recognized canine VEGF. In two different xenograft models, the systemic administration of the GLV-1h109 virus was found to be safe and led to anti-tumor and immunological effects resulting in the significant reduction of tumor growth in comparison to untreated control mice. Furthermore, tumor-specific virus infection led to a continued production of functional scAb GLAF-1, resulting in inhibition of angiogenesis. Overall, the GLV-1h109-mediated cancer therapy and production of immunotherapeutic anti-VEGF scAb may open the way for combination therapy concept i.e. vaccinia virus mediated oncolysis and intratumoral production of therapeutic drugs in canine cancer patients.
KW  - angiogenesis
KW  - microenvironment
KW  - model
KW  - cancer
KW  - therapy
KW  - pet dogs
KW  - nude-mice
KW  - breast-tumors
KW  - microvascular density
KW  - endothelial growth-factor
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130039
VL  - 7
IS  - 10
ER  - 
TY  - JOUR
A1  - Kunze, Ekkehard
A1  - Pham, Mirko
A1  - Raslan, Furat
A1  - Stetter, Christian
A1  - Lee, Jin-Yul
A1  - Solymosi, Laszlo
A1  - Ernestus, Ralf-Ingo
A1  - Hamilton Vince, Giles
A1  - Westermaier, Thomas
T1  - Value of Perfusion CT, Transcranial Doppler Sonography and Neurological Examination to detect delayed Vasospasm after aneurysmal Subarachnoid Hemorrhage [Research Article]
N2  - Background If detected in time, delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) may be treated by balloon angioplasty or chemical vasospasmolysis in order to enhance cerebral blood flow (CBF) and protect the brain from ischemic damage. This study was conceived to compare the diagnostic accuracy of detailed neurological examination, Transcranial Doppler Sonography (TCD), and Perfusion-CT (PCT) to detect angiographic vasospasm. Methods The sensitivity, specificity, positive and negative predictive values of delayed ischemic neurological deterioration (DIND), pathological findings on PCT- maps, and accelerations of the mean flow velocity (MVF) were calculated. Results The accuracy of DIND to predict angiographic vasospasm was 0.88. An acceleration of MFV in TCD (>140 cm/s) had an accuracy of 0.64, positive PCT-findings of 0.69 with a higher sensitivity, and negative predictive value than TCD. Interpretation Neurological assessment at close intervals is the most sensitive and specific parameter for cerebral vasospasm. PCT has a higher accuracy, sensitivity and negative predictive value than TCD. If detailed neurological evaluation is possible, it should be the leading parameter in the management and treatment decisions. If patients are not amenable to detailed neurological examination, PCT at regular intervals is a helpful tool to diagnose secondary vasospasm after aneurysmal SAH.
KW  - Medizin
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76241
ER  - 
TY  - JOUR
A1  - Ruf, Katharina C.
A1  - Fehn, Sonja
A1  - Bachmann, Michèle
A1  - Moeller, Alexander
A1  - Roht, Kristina
A1  - Kriemler, Susi
A1  - Hebestreit, Helge
T1  - Validation of activity questionnaires in patients with cystic fibrosis by accelerometry and cycle ergometry
N2  - Background: The objective of this study was to validate physical activity questionnaires for cystic fibrosis (CF) against accelerometry and cycle ergometry. Methods: 41 patients with CF (12-42 years) completed the Habitual Activity Estimation Scale (HAES), the 7-Day Physical Activity Recall questionnaire (7D-PAR) and the Lipid Research Clinics questionnaire (LRC) and performed an incremental exercise test according to the Godfrey protocol up to volitional fatigue. Time spent in moderate and vigorous physical activity (MVPA) assessed objectively by accelerometry was related to the time spent in the respective activity categories by correlation analyses and calculating intraclass correlation coefficients (ICC). Furthermore, the results of the exercise test were correlated with the results of the questionnaires. Results: Time spent in the categories ‘hard’,’very hard’ and ‘hard & very hard’ of the 7D-PAR (0.41 < r < 0.56) and ‘active’ (r = 0.33) of the HAES correlated significantly with MVPA. The activity levels of the LRC were not related to objectively determined physical activity. Significant ICCs were only observed between the 7D-PAR activitiy categories and MVPA (ICC = 0.40-0.44). Only the LRC showed moderate correlations with the exercise test (Wmax: r = 0.46, p = 0.002; VO2peak: r = 0.32, p = 0.041). Conclusions: In conclusion, the activity categories ‘hard’ and ‘very hard’ of the 7D-PAR best reflected objectively measured MVPA. Since the association was at most moderate, the 7D-PAR may be selected to describe physical activity within a population. None of the evaluated questionnaires was able to generate valid physical activity data exercise performance data at the individual level. Neither did any of the questionnaires provide a valid assessment of aerobic fitness on an invidual level.
KW  - Medizin
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75083
ER  - 
TY  - JOUR
A1  - Schäfer, Simon
A1  - Weibel, Stephanie
A1  - Donat, Ulrike
A1  - Zhang, Quian
A1  - Aguilar, Richard J.
A1  - Chen, Nanhai G.
A1  - Szalay, Aladar A.
T1  - Vaccinia virus-mediated intra-tumoral expression of matrix metalloproteinase 9 enhances oncolysis of PC-3 xenograft tumors
JF  - BMC Cancer
N2  - Background
Oncolytic viruses, including vaccinia virus (VACV), are a promising alternative to classical mono-cancer treatment methods such as surgery, chemo- or radiotherapy. However, combined therapeutic modalities may be more effective than mono-therapies. In this study, we enhanced the effectiveness of oncolytic virotherapy by matrix metalloproteinase (MMP-9)-mediated degradation of proteins of the tumoral extracellular matrix (ECM), leading to increased viral distribution within the tumors.

Methods
For this study, the oncolytic vaccinia virus GLV-1h255, containing the mmp-9 gene, was constructed and used to treat PC-3 tumor-bearing mice, achieving an intra-tumoral over-expression of MMP-9. The intra-tumoral MMP-9 content was quantified by immunohistochemistry in tumor sections. Therapeutic efficacy of GLV-1h255 was evaluated by monitoring tumor growth kinetics and intra-tumoral virus titers. Microenvironmental changes mediated by the intra-tumoral MMP-9 over-expression were investigated by microscopic quantification of the collagen IV content, the blood vessel density (BVD) and the analysis of lymph node metastasis formation.

Results
GLV-1h255-treatment of PC-3 tumors led to a significant over-expression of intra-tumoral MMP-9, accompanied by a marked decrease in collagen IV content in infected tumor areas, when compared to GLV-1h68-infected tumor areas. This led to considerably elevated virus titers in GLV-1h255 infected tumors, and to enhanced tumor regression. The analysis of the BVD, as well as the lumbar and renal lymph node volumes, revealed lower BVD and significantly smaller lymph nodes in both GLV-1h68- and GLV-1h255- injected mice compared to those injected with PBS, indicating that MMP-9 over-expression does not alter the metastasis-reducing effect of oncolytic VACV.

Conclusions
Taken together, these results indicate that a GLV-1h255-mediated intra-tumoral over-expression of MMP-9 leads to a degradation of collagen IV, facilitating intra-tumoral viral dissemination, and resulting in accelerated tumor regression. We propose that approaches which enhance the oncolytic effect by increasing the intra-tumoral viral load, may be an effective way to improve therapeutic outcome.
KW  - microenvironment
KW  - angiogenesis
KW  - therapy
KW  - cancer
KW  - breast-tumors
KW  - matrix metalloproteinases
KW  - adenovirus
KW  - carcinoma
KW  - prostate
KW  - mice
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-140800
VL  - 12
IS  - 366
ER  - 
TY  - JOUR
A1  - Schäfer, Simon
A1  - Weibel, Stephanie
A1  - Donat, Ulrike
A1  - Zhang, Qian
A1  - Aguilar, Richard J.
A1  - Chen, Nanhai G.
A1  - Szalay, Aladar A.
T1  - Vaccinia virus-mediated intra-tumoral expression of matrix metalloproteinase 9 enhances oncolysis of PC-3 xenograft tumors
N2  - Background: Oncolytic viruses, including vaccinia virus (VACV), are a promising alternative to classical mono-cancer treatment methods such as surgery, chemo- or radiotherapy. However, combined therapeutic modalities may be more effective than mono-therapies. In this study, we enhanced the effectiveness of oncolytic virotherapy by matrix metalloproteinase (MMP-9)-mediated degradation of proteins of the tumoral extracellular matrix (ECM), leading to increased viral distribution within the tumors. Methods: For this study, the oncolytic vaccinia virus GLV-1h255, containing the mmp-9 gene, was constructed and used to treat PC-3 tumor-bearing mice, achieving an intra-tumoral over-expression of MMP-9. The intra-tumoral MMP-9 content was quantified by immunohistochemistry in tumor sections. Therapeutic efficacy of GLV-1h255 was evaluated by monitoring tumor growth kinetics and intra-tumoral virus titers. Microenvironmental changes mediated by the intra-tumoral MMP-9 over-expression were investigated by microscopic quantification of the collagen IV content, the blood vessel density (BVD) and the analysis of lymph node metastasis formation. Results: GLV-1h255-treatment of PC-3 tumors led to a significant over-expression of intra-tumoral MMP-9, accompanied by a marked decrease in collagen IV content in infected tumor areas, when compared to GLV-1h68-infected tumor areas. This led to considerably elevated virus titers in GLV-1h255 infected tumors, and to enhanced tumor regression. The analysis of the BVD, as well as the lumbar and renal lymph node volumes, revealed lower BVD and significantly smaller lymph nodes in both GLV-1h68- and GLV-1h255- injected mice compared to those injected with PBS, indicating that MMP-9 over-expression does not alter the metastasis-reducing effect of oncolytic VACV. Conclusions: Taken together, these results indicate that a GLV-1h255-mediated intra-tumoral over-expression of MMP-9 leads to a degradation of collagen IV, facilitating intra-tumoral viral dissemination, and resulting in accelerated tumor regression. We propose that approaches which enhance the oncolytic effect by increasing the intra-tumoral viral load, may be an effective way to improve therapeutic outcome.
KW  - Biochemie
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-78220
ER  - 
TY  - JOUR
A1  - Vandenberg, Laura N.
A1  - Chahoud, Ibrahim
A1  - Heindel, Jerrold J.
A1  - Padmanabhan, Vasantha
A1  - Paumgartten, Francisco J. R.
A1  - Schönfelder, Gilbert
T1  - Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A
T1  - Estudos de biomonitoração do sistema urinário, circulatório e tecidos indicam grande exposição ao Bisfenol A
JF  - Ciência & Saúde Coletiva
N2  - Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. We examined many possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions. More than 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism were examined. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes.
N2  - Bisfenol A (BPA) é um dos produtos químicos mais produzido em todo o mundo, e a exposição humana a ele é considerada onipresente. Assim, há preocupações de que a quantidade de BPA para o qual os seres humanos estão expostos podem causar efeitos adversos à saúde. Nós examinamos muitas possibilidades sobre o porquê estudos de biomonitorização e toxicocinética podem chegar a conclusões aparentemente conflitantes. Mais de 80 estudos publicados de biomonitorização humana que mediram a concentração de BPA em tecidos humanos, urina, sangue e outros fluidos, juntamente com dois estudos de toxicocinética do metabolismo humano BPA foram examinados. BPA não conjugado foi detectado no sangue (nonanogramas por mililitro gama), e BPA conjugado foi detectado na grande maioria das amostras de urina. Em contraste, estudos de toxico-cinética propuseram que os seres humanos não são internamente expostos ao BPA. Dados disponíveis de estudos de biomonitorização indicam que a população em geral está exposta ao BPA e em risco de exposição interna ao BPA não conjugado. Os dois estudos de toxicocinética, que sugeriram a exposição humana ao BPA é insignificante, têm deficiências significativas e estão diretamente refutados por outros estudos e, portanto não são confiáveis para fins de avaliação de risco.
KW  - human
KW  - performance liquid-chromatography
KW  - toxicocinética
KW  - serum
KW  - fluorescence detection
KW  - disrupting chemicals
KW  - endocrine disruptor
KW  - human exposure
KW  - PBPK/PBTK model
KW  - pregnancy
KW  - risk assessment
KW  - toxicokinetics
KW  - solid-phase extraction
KW  - tandem mass-spectrometry
KW  - HPLC-MS/MS method
KW  - environmental phenols
KW  - estrogen receptor
KW  - adipose tissue
KW  - disruptor endócrino
KW  - exposição humana
KW  - modelo PBPK/PBTK
KW  - gravidez
KW  - avaliação de risco
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134332
VL  - 17
IS  - 2
ER  - 
TY  - JOUR
A1  - Montelius, Mikael
A1  - Ljungberg, Maria
A1  - Horn, Michael
A1  - Forssell-Aronsson, Eva
T1  - Tumour size measurement in a mouse model using high resolution MRI
JF  - BMC Medical Imaging
N2  - Background
Animal models are frequently used to assess new treatment methods in cancer research. MRI offers a non-invasive in vivo monitoring of tumour tissue and thus allows longitudinal measurements of treatment effects, without the need for large cohorts of animals. Tumour size is an important biomarker of the disease development, but to our knowledge, MRI based size measurements have not yet been verified for small tumours (10−2–10−1 g). The aim of this study was to assess the accuracy of MRI based tumour size measurements of small tumours on mice.
Methods
2D and 3D T2-weighted RARE images of tumour bearing mice were acquired in vivo using a 7 T dedicated animal MR system. For the 3D images the acquired image resolution was varied. The images were exported to a PC workstation where the tumour mass was determined assuming a density of 1 g/cm3, using an in-house developed tool for segmentation and delineation. The resulting data were compared to the weight of the resected tumours after sacrifice of the animal using regression analysis.
Results
Strong correlations were demonstrated between MRI- and necropsy determined masses. In general, 3D acquisition was not a prerequisite for high accuracy. However, it was slightly more accurate than 2D when small (<0.2 g) tumours were assessed for inter- and intraobserver variation. In 3D images, the voxel sizes could be increased from 1603 μm3 to 2403 μm3 without affecting the results significantly, thus reducing acquisition time substantially.
Conclusions
2D MRI was sufficient for accurate tumour size measurement, except for small tumours (<0.2 g) where 3D acquisition was necessary to reduce interobserver variation. Acquisition times between 15 and 50 minutes, depending on tumour size, were sufficient for accurate tumour volume measurement. Hence, it is possible to include further MR investigations of the tumour, such as tissue perfusion, diffusion or metabolic composition in the same MR session.
KW  - cancer
KW  - magnetic resonance
KW  - animal model
KW  - volume determination
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124049
VL  - 12
IS  - 12
ER  - 
TY  - JOUR
A1  - Vergho, Daniel Claudius
A1  - Loeser, Andreas
A1  - Kocot, Arkadius
A1  - Spahn, Martin
A1  - Riedmüller, Hubertus
T1  - Tumor thrombus of inferior vena cava in patients with renal cell carcinoma - Clinical and oncological outcome of 50 patients after surgery
N2  - Background: To evaluate oncological and clinical outcome in patients with renal cell carcinoma (RCC) and tumor thrombus involving inferior vena cava (IVC) treated with nephrectomy and thrombectomy. Methods: We identified 50 patients with a median age of 65 years, who underwent radical surgical treatment for RCC and tumor thrombus of the IVC between 1997 and 2010. The charts were reviewed for pathological and surgical parameters, as well as complications and oncological outcome. Results: The median follow-up was 26 months. In 21 patients (42%) distant metastases were already present at the time of surgery. All patients underwent radical nephrectomy, thrombectomy and lymph node dissection through a flank (15 patients/30%), thoracoabdominal (14 patients/28%) or midline abdominal approach (21 patients/42%), depending upon surgeon preference and upon the characteristics of tumor and associated thrombus. Extracorporal circulation with cardiopulmonary bypass (CPB) was performed in 10 patients (20%) with supradiaphragmal thrombus of IVC. Cancer-specific survival for the whole cohort at 5 years was 33.1%. Survival for the patients without distant metastasis at 5 years was 50.7%, whereas survival rate in the metastatic group at 5 years was 7.4%. Median survival of patients with metastatic disease was 16.4 months. On multivariate analysis lymph node invasion, distant metastasis and grading were independent prognostic factors. There was no statistically significant influence of level of the tumor thrombus on survival rate. Indeed, patients with supradiaphragmal tumor thrombus (n = 10) even had a better outcome (overall survival at 5 years of 58.33%) than the entire cohort. Conclusions: An aggressive surgical approach is the most effective therapeutic option in patients with RCC and any level of tumor thrombus and offers a reasonable longterm survival. Due to good clinical and oncological outcome we prefer the use of CPB with extracorporal circulation in patients with supradiaphragmal tumor thrombus. Cytoreductive surgery appears to be beneficial for patients with metastatic disease, especially when consecutive therapy is performed. Although sample size of our study cohort is limited consistent with some other studies lymph node invasion, distant metastasis and grading seem to have prognostic value.
KW  - Medizin
KW  - Renal cell carcinoma
KW  - Inferior vena cava
KW  - Thrombectomy
KW  - Tumor thrombus
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75230
ER  - 
TY  - JOUR
A1  - Heddergott, Nico
A1  - Krüger, Timothy
A1  - Babu, Sujin B.
A1  - Wei, Ai
A1  - Stellamanns, Erik
A1  - Uppaluri, Sravanti
A1  - Pfohl, Thomas
A1  - Stark, Holger
A1  - Engstler, Markus
T1  - Trypanosome Motion Represents an Adaptation to the Crowded Environment ofthe Vertebrate Bloodstream
N2  - Blood is a remarkable habitat: it is highly viscous, contains a dense packaging of cells and perpetually flows at velocities varying over three orders of magnitude. Only few pathogens endure the harsh physical conditions within the vertebrate bloodstream and prosper despite being constantly attacked by host antibodies. African trypanosomes are strictly extracellular blood parasites, which evade the immune response through a system of antigenic variation and incessant motility. How the flagellates actually swim in blood remains to be elucidated. Here, we show that the mode and dynamics of trypanosome locomotion are a trait of life within a crowded environment. Using high-speed fluorescence microscopy and ordered micro-pillar arrays we show that the parasites mode of motility is adapted to the density of cells in blood. Trypanosomes are pulled forward by the planar beat of the single flagellum. Hydrodynamic flow across the asymmetrically shaped cell body translates into its rotational movement. Importantly, the presence of particles with the shape, size and spacing of blood cells is required and sufficient for trypanosomes to reach maximum forward velocity. If the density of obstacles, however, is further increased to resemble collagen networks or tissue spaces, the parasites reverse their flagellar beat and consequently swim backwards, in this way avoiding getting trapped. In the absence of obstacles, this flagellar beat reversal occurs randomly resulting in irregular waveforms and apparent cell tumbling. Thus, the swimming behavior of trypanosomes is a surprising example of micro-adaptation to life at low Reynolds numbers. For a precise physical interpretation, we compare our high-resolution microscopic data to results from a simulation technique that combines the method of multi-particle collision dynamics with a triangulated surface model. The simulation produces a rotating cell body and a helical swimming path, providing a functioning simulation method for a microorganism with a complex swimming strategy
KW  - Biologie
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-78421
ER  - 
TY  - JOUR
A1  - Heddergott, Niko
A1  - Krüger, Timothy
A1  - Babu, Sujin B.
A1  - Wei, Ai
A1  - Stellamanns, Erik
A1  - Uppaluri, Sravanti
A1  - Pfohl, Thomas
A1  - Stark, Holger
A1  - Engstler, Markus
T1  - Trypanosome Motion Represents an Adaptation to the Crowded Environment of the Vertebrate Bloodstream
JF  - PLoS Pathogens
N2  - Blood is a remarkable habitat: it is highly viscous, contains a dense packaging of cells and perpetually flows at velocities varying over three orders of magnitude. Only few pathogens endure the harsh physical conditions within the vertebrate bloodstream and prosper despite being constantly attacked by host antibodies. African trypanosomes are strictly extracellular blood parasites, which evade the immune response through a system of antigenic variation and incessant motility. How the flagellates actually swim in blood remains to be elucidated. Here, we show that the mode and dynamics of trypanosome locomotion are a trait of life within a crowded environment. Using high-speed fluorescence microscopy and ordered micro-pillar arrays we show that the parasites mode of motility is adapted to the density of cells in blood. Trypanosomes are pulled forward by the planar beat of the single flagellum. Hydrodynamic flow across the asymmetrically shaped cell body translates into its rotational movement. Importantly, the presence of particles with the shape, size and spacing of blood cells is required and sufficient for trypanosomes to reach maximum forward velocity. If the density of obstacles, however, is further increased to resemble collagen networks or tissue spaces, the parasites reverse their flagellar beat and consequently swim backwards, in this way avoiding getting trapped. In the absence of obstacles, this flagellar beat reversal occurs randomly resulting in irregular waveforms and apparent cell tumbling. Thus, the swimming behavior of trypanosomes is a surprising example of micro-adaptation to life at low Reynolds numbers. For a precise physical interpretation, we compare our high-resolution microscopic data to results from a simulation technique that combines the method of multi-particle collision dynamics with a triangulated surface model. The simulation produces a rotating cell body and a helical swimming path, providing a functioning simulation method for a microorganism with a complex swimming strategy.
KW  - simulation
KW  - multiparticle collision dynamics
KW  - propulsion
KW  - viscosity
KW  - flagellar
KW  - motility
KW  - solvent
KW  - model
KW  - hydrodynamics
KW  - spiroplasma
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134595
VL  - 8
IS  - 11
ER  - 
TY  - JOUR
A1  - Finze, Maik
A1  - Reiss, Guido J.
T1  - Trimethyl­sulfonium 1-amino-6-fluoro-2,3,4,5,7,8,9,10,11,12-decaiodo-1-carba-closo-dodeca­borate
N2  - no abstract available
KW  - Chemie
KW  - single-crystal X-ray study
KW  - T = 100 K
KW  - wR factor = 0.052
KW  - data-to-parameter ratio = 20.8
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75397
ER  - 
TY  - JOUR
A1  - Prugger, Christof
A1  - Heidrich, Jan
A1  - Wellmann, Jürgen
A1  - Dittrich, Ralf
A1  - Brand, Stefan-Martin
A1  - Telgmann, Ralph
A1  - Breithardt, Günter
A1  - Reinecke, Holger
A1  - Scheld, Hans
A1  - Kleine-Katthöfer, Peter
A1  - Heuschmann, Peter U.
A1  - Keil, Ulrich
T1  - Trends in Cardiovascular Risk Factors Among Patients With Coronary Heart Disease : Results From the EUROASPIRE I, II, and III Surveys in the Münster Region
JF  - Deutsches Ärzteblatt International
N2  - Background: Target values for cardiovascular risk factors in patients with coronary heart disease (CHD) are stated in guidelines for the prevention of cardiovascular disease. We studied secular trends in risk factors over a 12-year period among CHD patients in the region of Munster, Germany.
Methods: The cross-sectional EUROASPIRE I, II and III surveys were performed in multiple centers across Europe. For all three, the Munster region was the participating German region. In the three periods 1995/96, 1999/2000, and 2006/07, the surveys included (respectively) 392, 402 and 457 <= 70-year-old patients with CHD in Munster who had sustained a coronary event at least 6 months earlier. 
Results: The prevalence of smoking remained unchanged, with 16.8% in EUROASPIRE I and II and 18.4% in EUROASPIRE III (p=0.898). On the other hand, high blood pressure and high cholesterol both became less common across the three EUROASPIRE studies (60.7% to 69.4% to 55.3%, and 94.3% to 83.4% to 48.1%, respectively; p<0.001 for both). Obesity became more common (23.0% to 30.6% to 43.1%, p<0.001), as did treatment with antihypertensive and lipid-lowering drugs (80.4% to 88.6% to 94.3%, and 35.0% to 67.4% to 87.0%, respectively; p<0.001 for both). 
Conclusion: The observed trends in cardiovascular risk factors under-score the vital need for better preventive strategies in patients with CHD.
KW  - smoking-cessation
KW  - follow up
KW  - primary-care physicians
KW  - myocardial infarction
KW  - secondary prevention
KW  - clinical practice
KW  - European countries
KW  - drug therapies
KW  - life style
KW  - task force
Y1  - 2012
U6  - https://doi.org/10.3238/arztebl.2012.0303
VL  - 109
IS  - 17
ER  - 
TY  - JOUR
A1  - Schmitt, Jana
A1  - Backes, Christina
A1  - Nourkami-Tutdibi, Nasenien
A1  - Leidinger, Petra
A1  - Deutscher, Stephanie
A1  - Beier, Markus
A1  - Gessler, Manfred
A1  - Graf, Norbert
A1  - Lenhof, Hans-Peter
A1  - Keller, Andreas
A1  - Meese, Eckart
T1  - Treatment-independent miRNA signature in blood of wilms tumor patients
JF  - BMC Genomics
N2  - Background
Blood-born miRNA signatures have recently been reported for various tumor diseases. Here, we compared the miRNA signature in Wilms tumor patients prior and after preoperative chemotherapy according to SIOP protocol 2001.
Results
We did not find a significant difference between miRNA signature of both groups. However both, Wilms tumor patients prior and after chemotherapy showed a miRNA signature different from healthy controls. The signature of Wilms tumor patients prior to chemotherapy showed an accuracy of 97.5% and of patients after chemotherapy an accuracy of 97.0%, each as compared to healthy controls.
Conclusion
Our results provide evidence for a blood-born Wilms tumor miRNA signature largely independent of four weeks preoperative chemotherapy treatment.
KW  - miRNA
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124034
VL  - 13
IS  - 379
ER  - 
TY  - JOUR
A1  - Hickey, Scott F.
A1  - Sridhar, Malathy
A1  - Westermann, Alexander J.
A1  - Qin, Qian
A1  - Vijayendra, Pooja
A1  - Liou, Geoffrey
A1  - Hammond, Ming C.
T1  - Transgene regulation in plants by alternative splicing of a suicide exon
JF  - Nucleic Acids Research
N2  - Compared to transcriptional activation, other mechanisms of gene regulation have not been widely exploited for the control of transgenes. One barrier to the general use and application of alternative splicing is that splicing-regulated transgenes have not been shown to be reliably and simply designed. Here, we demonstrate that a cassette bearing a suicide exon can be inserted into a variety of open reading frames (ORFs), generating transgenes whose expression is activated by exon skipping in response to a specific protein inducer. The surprisingly minimal sequence requirements for the maintenance of splicing fidelity and regulation indicate that this splicing cassette can be used to regulate any ORF containing one of the amino acids Glu, Gln or Lys. Furthermore, a single copy of the splicing cassette was optimized by rational design to confer robust gene activation with no background expression in plants. Thus, conditional splicing has the potential to be generally useful for transgene regulation.
KW  - kingdom
KW  - pre-messenger RNA
KW  - gene expression
KW  - elements
KW  - decay
KW  - arabidopsis
KW  - eukaryotes
KW  - mechanisms
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134724
VL  - 40
IS  - 10
ER  - 
TY  - JOUR
A1  - Pernitzsch, Sandy R.
A1  - Sharma, Cynthia M.
T1  - Transcriptome Complexity and Riboregulation in the Human Pathogen Helicobacter pylori
KW  - Medizin
KW  - RNA-seq
KW  - sRNA
KW  - Helicobacterpylori
KW  - post-transcriptionalregulation
KW  - transcriptomeanalysis
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75096
ER  - 
TY  - JOUR
A1  - Förster, Frank
A1  - Beisser, Daniela
A1  - Grohme, Markus A.
A1  - Liang, Chunguang
A1  - Mali, Brahim
A1  - Siegl, Alexander Matthias
A1  - Engelmann, Julia C.
A1  - Shkumatov, Alexander V.
A1  - Schokraie, Elham
A1  - Müller, Tobias
A1  - Schnölzer, Martina
A1  - Schill, Ralph O.
A1  - Frohme, Marcus
A1  - Dandekar, Thomas
T1  - Transcriptome analysis in tardigrade species reveals specific molecular pathways for stress adaptations
JF  - Bioinformatics and biology insights
N2  - Tardigrades have unique stress-adaptations that allow them to survive extremes of cold, heat, radiation and vacuum. To study this, encoded protein clusters and pathways from an ongoing transcriptome study on the tardigrade \(Milnesium\) \(tardigradum\) were analyzed using bioinformatics tools and compared to expressed sequence tags (ESTs) from \(Hypsibius\) \(dujardini\), revealing major pathways involved in resistance against extreme environmental conditions. ESTs are available on the Tardigrade Workbench along with software and databank updates. Our analysis reveals that RNA stability motifs for \(M.\) \(tardigradum\) are different from typical motifs known from higher animals. \(M.\) \(tardigradum\) and \(H.\) \(dujardini\) protein clusters and conserved domains imply metabolic storage pathways for glycogen, glycolipids and specific secondary metabolism as well as stress response pathways (including heat shock proteins, bmh2, and specific repair pathways). Redox-, DNA-, stress- and protein protection pathways complement specific repair capabilities to achieve the strong robustness of \(M.\) \(tardigradum\). These pathways are partly conserved in other animals and their manipulation could boost stress adaptation even in human cells. However, the unique combination of resistance and repair pathways make tardigrades and \(M.\) \(tardigradum\) in particular so highly stress resistant.
KW  - RNA
KW  - expressed sequence tag
KW  - cluster
KW  - protein familiy
KW  - adaption
KW  - tardigrada
KW  - transcriptome
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123089
N1  - This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited.
VL  - 6
ER  - 
TY  - JOUR
A1  - Herbort, Oliver
A1  - Butz, Martin V.
T1  - Too good to be true? Ideomotor theory from a computational perspective
N2  - In recent years, Ideomotor Theory has regained widespread attention and sparked the development of a number of theories on goal-directed behavior and learning. However, there are two issues with previous studies’ use of Ideomotor Theory. Although Ideomotor Theory is seen as very general, it is often studied in settings that are considerably more simplistic than most natural situations. Moreover, Ideomotor Theory’s claim that effect anticipations directly trigger actions and that action-effect learning is based on the formation of direct action-effect associations is hard to address empirically. We address these points from a computational perspective. A simple computational model of Ideomotor Theory was tested in tasks with different degrees of complexity.The model evaluation showed that Ideomotor Theory is a computationally feasible approach for understanding efficient action-effect learning for goal-directed behavior if the following preconditions are met: (1) The range of potential actions and effects has to be restricted. (2) Effects have to follow actions within a short time window. (3) Actions have to be simple and may not require sequencing. The first two preconditions also limit human performance and thus support Ideomotor Theory. The last precondition can be circumvented by extending the model with more complex, indirect action generation processes. In conclusion, we suggest that IdeomotorTheory offers a comprehensive framework to understand action-effect learning. However, we also suggest that additional processes may mediate the conversion of effect anticipations into actions in many situations.
KW  - Psychologie
KW  - ideomotor theory
KW  - associative learning
KW  - computational model
KW  - planning
KW  - consolidation
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76383
ER  - 
TY  - JOUR
T1  - Time-dependent angular analysis of the decay B\(^0_s\)→J/ψϕ and extraction of ΔΓ\(_s\) and the CP-violating weak phase ϕ\(_s\) by ATLAS
JF  - Journal of High Energy Physics
N2  - A measurement of B\(^0_s\)→J/ψϕ decay parameters, including the CP -violating weak phase ϕ\(_s\) and the decay width difference ΔΓ\(_s\) is reported, using 4.9 fb\(^{−1}\) of integrated luminosity collected in 2011 by the ATLAS detector from LHC pp collisions at a centre-of-mass energy √s=7 TeV. The mean decay width Γ\(_s\) and the transversity amplitudes |A\(_0\)(0)|\(^2\) and |A\(_∥\)(0)|\(^2\) are also measured. The values reported for these parameters are:

ϕ\(_s\)=0.22±0.41 (stat.)±0.10 (syst.) rad
ΔΓ\(_s\)=0.053±0.021 (stat.)±0.010 (syst.)ps\(^{−1}\) 
Γ\(_s\)=0.677±0.007 (stat.)±0.004 (syst.) ps\(^{−1}\)  
|A\(_0\)(0)|\(^2\)=0.528±0.006 (stat.)±0.009 (syst.)
|A\(_∥\)(0)|\(^2\)=0.220±0.008 (stat.)±0.007 (syst.)

where the values quoted for ϕ\(_s\) and ΔΓ\(_s\) correspond to the solution compatible with the external measurements to which the strong phase δ\(_⊥\) is constrained and where ΔΓ\(_s\) is constrained to be positive. The fraction of S-wave KK or f\(_0\) contamination through the decays B\(^0_s\)→J/ψK\(^+\)K\(^−\)(f\(_0\)) is measured as well and is found to be consistent with zero. Results for ϕ\(_s\) and ΔΓ\(_s\) are also presented as 68%, 90% and 95% likelihood contours, which show agreement with Standard Model expectations.
KW  - hadron-hadron scattering
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128125
VL  - 12
IS  - 072
ER  - 
TY  - JOUR
A1  - Langhauser, Friederike L.
A1  - Heiler, Patrick M.
A1  - Grudzenski, Saskia
A1  - Lemke, Andreas
A1  - Alonso, Angelika
A1  - Schad, Lothar R.
A1  - Hennerici, Michael G.
A1  - Meairs, Stephen
A1  - Fata, Marc
T1  - Thromboembolic stroke in C57BL/6 mice monitored by 9.4 T MRI using a 1H cryo probe
JF  - Experimental and Translational Stroke Medicine
N2  - Background
A new thromboembolic animal model showed beneficial effects of t-PA with an infarct volume reduction of 36.8% in swiss mice. Because knock-out animal experiments for stroke frequently used C57BL76 mice we evaluated t-PA effects in this mouse strain and measured infarct volume and vascular recanalisation in-vivo by using high-field 9.4 T MRI and a 1H surface cryo coil.
Methods
Clot formation was triggered by microinjection of murine thrombin into the right middle cerebral artery (MCA). Animals (n = 28) were treated with 10 mg/kg, 5 mg/kg or no tissue plasminogen activator (t-PA) 40 min after MCA occlusion. For MR-imaging a Bruker 9.4 T animal system with a 1H surface cryo probe was used and a T2-weighted RARE sequence, a diffusion weighted multishot EPI sequence and a 3D flow-compensated gradient echo TOF angiography were performed.
Results
The infarct volume in animals treated with t-PA was significantly reduced (0.67 ± 1.38 mm3 for 10 mg/kg and 10.9 ± 8.79 mm3 for 5 mg/kg vs. 19.76 ± 2.72 mm3 ; p < 0.001) compared to untreated mice. An additional group was reperfused with t-PA inside the MRI. Already ten minutes after beginning of t-PA treatment, reperfusion flow was re-established in the right MCA. However, signal intensity was lower than in the contralateral MCA. This reduction in cerebral blood flow was attenuated during the first 60 minutes after reperfusion. 24 h after MCA occlusion and reperfusion, no difference in signal intensity of the contralateral and ipsilateral MCAs was observed.
Conclusions
We confirm a t-Pa effect using this stroke model in the C57BL76 mouse strain and demonstrate a chronological sequence MRI imaging after t-PA using a 1H surface cryo coil in a 9.4 T MRI. This setting will allow testing of new thrombolytic strategies for stroke treatment in-vivo in C57BL76 knock-out mice.
KW  - animal models
KW  - MRI
KW  - experimental
KW  - embolic stroke
KW  - T-PA
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124218
VL  - 4
IS  - 18
ER  - 
TY  - JOUR
A1  - Nanguneri, Siddharth
A1  - Flottmann, Benjamin
A1  - Horstmann, Heinz
A1  - Heilemann, Mike
A1  - Kuner, Thomas
T1  - Three-Dimensional, Tomographic Super-Resolution Fluorescence Imaging of Serially Sectioned Thick Samples
JF  - PLoS One
N2  - Three-dimensional fluorescence imaging of thick tissue samples with near-molecular resolution remains a fundamental challenge in the life sciences. To tackle this, we developed tomoSTORM, an approach combining single-molecule localization-based super-resolution microscopy with array tomography of structurally intact brain tissue. Consecutive sections organized in a ribbon were serially imaged with a lateral resolution of 28 nm and an axial resolution of 40 nm in tissue volumes of up to 50 \(\mu\)mx50\(\mu\)mx2.5\(\mu\)m. Using targeted expression of membrane bound (m)GFP and immunohistochemistry at the calyx of Held, a model synapse for central glutamatergic neurotransmission, we delineated the course of the membrane and fine-structure of mitochondria. This method allows multiplexed super-resolution imaging in large tissue volumes with a resolution three orders of magnitude better than confocal microscopy.
KW  - architecture
KW  - rat calyx
KW  - in-vivo
KW  - microscopy
KW  - resolution
KW  - proteins
KW  - transmission
KW  - ultrastructure
KW  - reconstruction
KW  - localization
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134434
VL  - 7
IS  - 5
ER  - 
TY  - JOUR
A1  - Aso, Yoshinori
A1  - Herb, Andrea
A1  - Ogueta, Maite
A1  - Siwanowicz, Igor
A1  - Templier, Thomas
A1  - Friedrich, Anja B.
A1  - Ito, Kei
A1  - Scholz, Henrike
A1  - Tanimoto, Hiromu
T1  - Three Dopamine Pathways Induce Aversive Odor Memories with Different Stability
JF  - PLoS Genetics
N2  - Animals acquire predictive values of sensory stimuli through reinforcement. In the brain of Drosophila melanogaster, activation of two types of dopamine neurons in the PAM and PPL1 clusters has been shown to induce aversive odor memory. Here, we identified the third cell type and characterized aversive memories induced by these dopamine neurons. These three dopamine pathways all project to the mushroom body but terminate in the spatially segregated subdomains. To understand the functional difference of these dopamine pathways in electric shock reinforcement, we blocked each one of them during memory acquisition. We found that all three pathways partially contribute to electric shock memory. Notably, the memories mediated by these neurons differed in temporal stability. Furthermore, combinatorial activation of two of these pathways revealed significant interaction of individual memory components rather than their simple summation. These results cast light on a cellular mechanism by which a noxious event induces different dopamine signals to a single brain structure to synthesize an aversive memory.
KW  - dynamics
KW  - serotonin
KW  - expression
KW  - melanogaster
KW  - neurons form
KW  - olfactory memory
KW  - long-term-memory
KW  - drosophila mushroom body
KW  - sensitization
KW  - localization
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130631
VL  - 8
IS  - 7
ER  - 
TY  - JOUR
A1  - Yamakawa, Hisanori
A1  - Fukushima, Yoshimasa
A1  - Itoh, Shigeru
A1  - Heber, Ulrich
T1  - Three different mechanisms of energy dissipation of a desiccation-tolerant moss serve one common purpose: to protect reaction centres against photo-oxidation
JF  - Journal of Experimental Botany
N2  - Three different types of non-photochemical de-excitation of absorbed light energy protect photosystem II of the sun- and desiccation-tolerant moss Rhytidium rugosum against photo-oxidation. The first mechanism, which is light-induced in hydrated thalli, is sensitive to inhibition by dithiothreitol. It is controlled by the protonation of a thylakoid protein. Other mechanisms are activated by desiccation. One of them permits exciton migration towards a far-red band in the antenna pigments where fast thermal deactivation takes place. This mechanism appears to be similar to a mechanism detected before in desiccated lichens. A third mechanism is based on the reversible photo-accumulation of a radical that acts as a quencher of excitation energy in reaction centres of photosystem II. On the basis of absorption changes around 800 nm, the quencher is suggested to be an oxidized chlorophyll. The data show that desiccated moss is better protected against photo-oxidative damage than hydrated moss. Slow drying of moss thalli in the light increases photo-protection more than slow drying in darkness.
KW  - reaction centre
KW  - photoprotection
KW  - energy dissipation
KW  - energy conservation
KW  - chlorophyll fluorescence
KW  - photosystem II
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126897
VL  - 63
IS  - 10
ER  - 
TY  - JOUR
A1  - Lutz, Manfred B.
T1  - Therapeutic Potential of Semi-Mature Dendritic Cells for Tolerance Induction
N2  - Dendritic cells (DCs) are major players in the control of adaptive tolerance and immunity. Therefore, their specific generation and adoptive transfer into patients or their in vivo targeting is attractive for clinical applications. While injections of mature immunogenic DCs are tested in clinical trials, tolerogenic DCs still are awaiting this step. Besides the tolerogenic potential of immature DCs, also semi-mature DCs can show tolerogenic activity but both types also bear unfavorable features. Optimal tolerogenic DCs, their molecular tool bar, and their use for specific diseases still have to be defined. Here, the usefulness of in vitro generated and adoptively transferred semi-mature DCs for tolerance induction is outlined. The in vivo targeting of semi-mature DCs as represented by steady state migratory DCs are discussed for treatment of autoimmune diseases and allergies. First clinical trials with transcutaneous allergen application may point to their therapeutic use in the future.
KW  - Medizin
KW  - dendritic cells
KW  - tolerance
KW  - epicutaneous
KW  - transcutaneous
KW  - steady state
KW  - migration
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75535
ER  - 
TY  - JOUR
A1  - Meule, Adrian
A1  - Kübler, Andrea
T1  - The translation of substance dependence criteria to food-related behaviors: different views and interpretations.
JF  - Frontiers in psychiatry
N2  - No abstract available.
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123092
ER  - 
TY  - JOUR
A1  - Benisch, Peggy
A1  - Schilling, Tatjana
A1  - Klein-Hitpass, Ludger
A1  - Frey, Sönke P.
A1  - Seefried, Lothar
A1  - Raaijmakers, Nadja
A1  - Krug, Melanie
A1  - Regensburger, Martina
A1  - Zeck, Sabine
A1  - Schinke, Thorsten
A1  - Amling, Michael
A1  - Ebert, Amling
A1  - Jakob, Franz
T1  - The Transcriptional Profile of Mesenchymal Stem Cell Populations in Primary Osteoporosis Is Distinct and Shows Overexpression of Osteogenic Inhibitors
JF  - PLoS One
N2  - Primary osteoporosis is an age-related disease characterized by an imbalance in bone homeostasis. While the resorptive aspect of the disease has been studied intensely, less is known about the anabolic part of the syndrome or presumptive deficiencies in bone regeneration. Multipotent mesenchymal stem cells (MSC) are the primary source of osteogenic regeneration. In the present study we aimed to unravel whether MSC biology is directly involved in the pathophysiology of the disease and therefore performed microarray analyses of hMSC of elderly patients (79-94 years old) suffering from osteoporosis (hMSC-OP). In comparison to age-matched controls we detected profound changes in the transcriptome in hMSC-OP, e.g. enhanced mRNA expression of known osteoporosis-associated genes (LRP5, RUNX2, COL1A1) and of genes involved in osteoclastogenesis (CSF1, PTH1R), but most notably of genes coding for inhibitors of WNT and BMP signaling, such as Sclerostin and MAB21L2. These candidate genes indicate intrinsic deficiencies in self-renewal and differentiation potential in osteoporotic stem cells. We also compared both hMSC-OP and non-osteoporotic hMSC-old of elderly donors to hMSC of similar to 30 years younger donors and found that the transcriptional changes acquired between the sixth and the ninth decade of life differed widely between osteoporotic and non-osteoporotic stem cells. In addition, we compared the osteoporotic transcriptome to long term-cultivated, senescent hMSC and detected some signs for pre-senescence in hMSC-OP. Our results suggest that in primary osteoporosis the transcriptomes of hMSC populations show distinct signatures and little overlap with non-osteoporotic aging, although we detected some hints for senescence-associated changes. While there are remarkable inter-individual variations as expected for polygenetic diseases, we could identify many susceptibility genes for osteoporosis known from genetic studies. We also found new candidates, e.g. MAB21L2, a novel repressor of BMP-induced transcription. Such transcriptional changes may reflect epigenetic changes, which are part of a specific osteoporosis-associated aging process.
KW  - alkaline-phosphatase
KW  - in vitro
KW  - bone-mineral density
KW  - age-related osteoporosis
KW  - WNT signaling pathway
KW  - replicative senescence
KW  - morphogenetic protein
KW  - parathyroid-hormone
KW  - growth factor
KW  - skeletal overexpression
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133379
VL  - 7
IS  - 9
ER  - 
TY  - JOUR
A1  - Spivey, Tara L.
A1  - De Giorgi, Valeria
A1  - Zhao, Yingdong
A1  - Bedognetti, Davide
A1  - Pos, Zoltan
A1  - Liu, Qiuzhen
A1  - Tomei, Sara
A1  - Ascierto, Maria Libera
A1  - Uccellini, Lorenzo
A1  - Reinboth, Jennifer
A1  - Chouchane, Lotfi
A1  - Stroncek, David F.
A1  - Wang, Ena
A1  - Marincola, Francesco M.
T1  - The stable traits of melanoma genetics: an alternate approach to target discovery
JF  - BMC Genomics
N2  - Background: The weight that gene copy number plays in transcription remains controversial; although in specific cases gene expression correlates with copy number, the relationship cannot be inferred at the global level. We hypothesized that genes steadily expressed by 15 melanoma cell lines (CMs) and their parental tissues (TMs) should be critical for oncogenesis and their expression most frequently influenced by their respective copy number. 
Results: Functional interpretation of 3,030 transcripts concordantly expressed (Pearson's correlation coefficient p-value < 0.05) by CMs and TMs confirmed an enrichment of functions crucial to oncogenesis. Among them, 968 were expressed according to the transcriptional efficiency predicted by copy number analysis (Pearson's correlation coefficient p-value < 0.05). We named these genes, "genomic delegates" as they represent at the transcriptional level the genetic footprint of individual cancers. We then tested whether the genes could categorize 112 melanoma metastases. Two divergent phenotypes were observed: one with prevalent expression of cancer testis antigens, enhanced cyclin activity, WNT signaling, and a Th17 immune phenotype (Class A). This phenotype expressed, therefore, transcripts previously associated to more aggressive cancer. The second class (B) prevalently expressed genes associated with melanoma signaling including MITF, melanoma differentiation antigens, and displayed a Th1 immune phenotype associated with better prognosis and likelihood to respond to immunotherapy. An intermediate third class (C) was further identified. The three phenotypes were confirmed by unsupervised principal component analysis. 
Conclusions: This study suggests that clinically relevant phenotypes of melanoma can be retraced to stable oncogenic properties of cancer cells linked to their genetic back bone, and offers a roadmap for uncovering novel targets for tailored anti-cancer therapy.
KW  - tumors
KW  - comparative genomic hybridization
KW  - coloteral cancer
KW  - prognostic relevance
KW  - aquired resistance
KW  - malignant melanoma
KW  - antigen expression
KW  - tissue microarray
KW  - cell carcinoma
KW  - T cells
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131992
VL  - 13
IS  - 156
ER  - 
TY  - JOUR
A1  - Huser, Annina
A1  - Rohwedder, Astrid
A1  - Apostolopoulou, Anthi A.
A1  - Widmann, Annekathrin
A1  - Pfitzenmaier, Johanna E.
A1  - Maiolo, Elena M.
A1  - Selcho, Mareike
A1  - Pauls, Dennis
A1  - von Essen, Alina
A1  - Gupta, Tript
A1  - Sprecher, Simon G.
A1  - Birman, Serge
A1  - Riemensperger, Thomas
A1  - Stocker, Reinhard F.
A1  - Thum, Andreas S.
T1  - The Serotonergic Central Nervous System of the Drosophila Larva: Anatomy and Behavioral Function
JF  - PLoS One
N2  - The Drosophila larva has turned into a particularly simple model system for studying the neuronal basis of innate behaviors and higher brain functions. Neuronal networks involved in olfaction, gustation, vision and learning and memory have been described during the last decade, often up to the single-cell level. Thus, most of these sensory networks are substantially defined, from the sensory level up to third-order neurons. This is especially true for the olfactory system of the larva. Given the wealth of genetic tools in Drosophila it is now possible to address the question how modulatory systems interfere with sensory systems and affect learning and memory. Here we focus on the serotonergic system that was shown to be involved in mammalian and insect sensory perception as well as learning and memory. Larval studies suggested that the serotonergic system is involved in the modulation of olfaction, feeding, vision and heart rate regulation. In a dual anatomical and behavioral approach we describe the basic anatomy of the larval serotonergic system, down to the single-cell level. In parallel, by expressing apoptosis-inducing genes during embryonic and larval development, we ablate most of the serotonergic neurons within the larval central nervous system. When testing these animals for naive odor, sugar, salt and light perception, no profound phenotype was detectable; even appetitive and aversive learning was normal. Our results provide the first comprehensive description of the neuronal network of the larval serotonergic system. Moreover, they suggest that serotonin per se is not necessary for any of the behaviors tested. However, our data do not exclude that this system may modulate or fine-tune a wide set of behaviors, similar to its reported function in other insect species or in mammals. Based on our observations and the availability of a wide variety of genetic tools, this issue can now be addressed.
KW  - term memory
KW  - light avoidance
KW  - decision making
KW  - olfactory memory
KW  - immunoreactive neurons
KW  - containing neurons
KW  - moth manduca sexta
KW  - head involution
KW  - mushroom bodies
KW  - biogenic amines
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130437
VL  - 7
IS  - 10
ER  - 
TY  - JOUR
A1  - Bandyra, Katarzyna J.
A1  - Said, Nelly
A1  - Pfeiffer, Verena
A1  - Górna, Maria W.
A1  - Vogel, Jörg
A1  - Luisi, Ben F.
T1  - The Seed Region of a Small RNA Drives the Controlled Destruction of the Target mRNA by the Endoribonuclease RNase E
JF  - Molecular Cell
N2  - Numerous small non-coding RNAs (sRNAs) in bacteria modulate rates of translation initiation and degradation of target mRNAs, which they recognize through base-pairing facilitated by the RNA chaperone Hfq. Recent evidence indicates that the ternary complex of Hfq, sRNA and mRNA guides endoribonuclease RNase E to initiate turnover of both the RNAs. We show that a sRNA not only guides RNase E to a defined site in a target RNA, but also allosterically activates the enzyme by presenting a monophosphate group at the 5′-end of the cognate-pairing “seed.” Moreover, in the absence of the target the 5′-monophosphate makes the sRNA seed region vulnerable to an attack by RNase E against which Hfq confers no protection. These results suggest that the chemical signature and pairing status of the sRNA seed region may help to both ‘proofread’ recognition and activate mRNA cleavage, as part of a dynamic process involving cooperation of RNA, Hfq and RNase E.
KW  - medicine
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126202
VL  - 47
IS  - 6
ER  - 
TY  - JOUR
A1  - Naseem, Muhammad
A1  - Dandekar, Thomas
T1  - The Role of Auxin-Cytokinin Antagonism in Plant-Pathogen Interactions
JF  - PLOS Pathogens
N2  - No abstract available.
KW  - disease
KW  - pseudomas-syringae
KW  - arabidpsis thaliana
KW  - immunity
KW  - organogenesis
KW  - transcription
KW  - resistance
KW  - crosstalk
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131901
VL  - 8
IS  - 11
ER  - 
TY  - JOUR
A1  - Schubert, Maria
A1  - Joniau, Steven
A1  - Gontero, Paolo
A1  - Kneitz, Susanne
A1  - Scholz, Claus-Jürgen
A1  - Kneitz, Burkhard
A1  - Briganti, Alberto
A1  - Karnes, R. Jeffery
A1  - Tombal, Bertrand
A1  - Walz, Jochen
A1  - Hsu, Chao-Yu
A1  - Marchioro, Giansilvio
A1  - Bader, Pia
A1  - Bangma, Chris
A1  - Frohneberg, Detlef
A1  - Graefen, Markus
A1  - Schröder, Fritz
A1  - van Cangh, Paul
A1  - van Poppel, Hein
A1  - Spahn, Martin
T1  - The Role of Adjuvant Hormonal Treatment after Surgery for Localized High-Risk Prostate Cancer: Results of a Matched Multiinstitutional Analysis
JF  - Advances in Urology
N2  - Introduction. To assess the role of adjuvant androgen deprivation therapy (ADT) in high-risk prostate cancer patients (PCa) after surgery. Materials and Methods. The analysis case matched 172 high-risk PCa patients with positive section margins or non-organ confined disease and negative lymph nodes to receive adjuvant ADT (group 1, n=86 ) or no adjuvant ADT (group 2, n=86). Results. Only 11.6% of the patients died, 2.3% PCa related. Estimated 5–10-year clinical progression-free survival was 96.9% (94.3%) for group 1 and 73.7% (67.0%) for group 2, respectively. Subgroup analysis identified men with T2/T3a tumors at low-risk and T3b margins positive disease at higher risk for progression. Conclusion. Patients with T2/T3a tumors are at low-risk for metastatic disease and cancer-related death and do not need adjuvant ADT. We identified men with T3b margin positive disease at highest risk for clinical progression. These patients benefit from immediate adjuvant ADT.
KW  - prostate cancer
KW  - adjuvant hormonal treatment
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137712
VL  - 2012
ER  - 
TY  - JOUR
A1  - Rhiem, Kerstin
A1  - Engel, Christoph
A1  - Graeser, Monika
A1  - Zachariae, Silke
A1  - Kast, Karin
A1  - Kiechle, Marion
A1  - Ditsch, Nina
A1  - Janni, Wolfgang
A1  - Mundhenke, Christoph
A1  - Golatta, Michael
A1  - Varga, Dominic
A1  - Preisler-Adams, Sabine
A1  - Heinrich, Tilman
A1  - Bick, Ulrich
A1  - Gadzicki, Dorothea
A1  - Briest, Susanne
A1  - Meindl, Alfons
A1  - Schmutzler, Rita K.
T1  - The risk of contralateral breast cancer in patients from BRCA1/2 negative high risk families as compared to patients from BRCA1 or BRCA2 positive families: a retrospective cohort study
JF  - Breast Cancer Research
N2  - Introduction: While it has been reported that the risk of contralateral breast cancer in patients from BRCA1 or BRCA2 positive families is elevated, little is known about contralateral breast cancer risk in patients from high risk families that tested negative for BRCA1/2 mutations.
Methods: A retrospective, multicenter cohort study was performed from 1996 to 2011 and comprised 6,235 women with unilateral breast cancer from 6,230 high risk families that had tested positive for BRCA1 (n = 1,154) or BRCA2 (n = 575) mutations or tested negative (n = 4,501). Cumulative contralateral breast cancer risks were calculated using the Kaplan-Meier product-limit method and were compared between groups using the log-rank test. Cox regression analysis was applied to assess the impact of the age at first breast cancer and the familial history stratified by mutation status.
Results: The cumulative risk of contralateral breast cancer 25 years after first breast cancer was 44.1% (95%CI, 37.6% to 50.6%) for patients from BRCA1 positive families, 33.5% (95%CI, 22.4% to 44.7%) for patients from BRCA2 positive families and 17.2% (95%CI, 14.5% to 19.9%) for patients from families that tested negative for BRCA1/2 mutations. Younger age at first breast cancer was associated with a higher risk of contralateral breast cancer. For women who had their first breast cancer before the age of 40 years, the cumulative risk of contralateral breast cancer after 25 years was 55.1% for BRCA1, 38.4% for BRCA2, and 28.4% for patients from BRCA1/2 negative families. If the first breast cancer was diagnosed at the age of 50 or later, 25-year cumulative risks were 21.6% for BRCA1, 15.5% for BRCA2, and 12.9% for BRCA1/2 negative families.
Conclusions: Contralateral breast cancer risk in patients from high risk families that tested negative for BRCA1/2 mutations is similar to the risk in patients with sporadic breast cancer. Thus, the mutation status should guide decision making for contralateral mastectomy.
KW  - contralateral breast cancer
KW  - BRCA1/2 negative
KW  - BRCA1 positive
KW  - BRCA2 positive
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135715
VL  - 14
IS  - 6
ER  - 
TY  - JOUR
A1  - Spannaus, Ralf
A1  - Hartl, Maximilian J.
A1  - Wöhrl, Birgitta M.
A1  - Rethwilm, Axel
A1  - Bodem, Jochen
T1  - The prototype foamy virus protease is active independently of the integrase domain
N2  - Background: Recently, contradictory results on foamy virus protease activity were published. While our own results indicated that protease activity is regulated by the viral RNA, others suggested that the integrase is involved in the regulation of the protease. Results: To solve this discrepancy we performed additional experiments showing that the protease-reverse transcriptase (PR-RT) exhibits protease activity in vitro and in vivo, which is independent of the integrase domain. In contrast, Pol incorporation, and therefore PR activity in the viral context, is dependent on the integrase domain. To further analyse the regulation of the protease, we incorporated Pol in viruses by expressing a GagPol fusion protein, which supported near wild-type like infectivity. A GagPR-RT fusion, lacking the integrase domain, also resulted in wild-type like Gag processing, indicating that the integrase is dispensable for viral Gag maturation. Furthermore, we demonstrate with a trans-complementation assays that the PR in the context of the PR-RT protein supports in trans both, viral maturation and infectivity. Conclusion: We provide evidence that the FV integrase is required for Pol encapsidation and that the FV PR activity is integrase independent. We show that an active PR can be encapsidated in trans as a GagPR-RT fusion protein.
KW  - Medizin
KW  - Foamy virus
KW  - Regulation of protease activity
KW  - PARM
KW  - Integrase
KW  - GagPol fusion protein
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75370
ER  - 
TY  - JOUR
A1  - Makoah Nigel, Animake
A1  - Arndt, Hans-Dieter
A1  - Pradel, Gabriele
T1  - The proteasome of malaria parasites: A multi-stage drug target for chemotherapeutic intervention?
JF  - International Journal for Parasitology: Drugs and Drug Resistance
N2  - The ubiquitin/proteasome system serves as a regulated protein degradation pathway in eukaryotes, and is involved in many cellular processes featuring high protein turnover rates, such as cell cycle control, stress response and signal transduction. In malaria parasites, protein quality control is potentially important because of the high replication rate and the rapid transformations of the parasite during life cycle progression. The proteasome is the core of the degradation pathway, and is a major proteolytic complex responsible for the degradation and recycling of non-functional ubiquitinated proteins. Annotation of the genome for Plasmodium falciparum, the causative agent of malaria tropica, revealed proteins with similarity to human 26S proteasome subunits. In addition, a bacterial ClpQ/hslV threonine peptidase-like protein was identified. In recent years several independent studies indicated an essential function of the parasite proteasome for the liver, blood and transmission stages. In this review, we compile evidence for protein recycling in Plasmodium parasites and discuss the role of the 26S proteasome as a prospective multi-stage target for antimalarial drug discovery programs.
KW  - plasmodium falciparum
KW  - proteasome
KW  - ubiquitin
KW  - inhibitor
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137777
VL  - 2
ER  - 
TY  - JOUR
A1  - Merget, Benjamin
A1  - Koetschan, Christian
A1  - Hackl, Thomas
A1  - Förster, Frank
A1  - Dandekar, Thomas
A1  - Müller, Tobias
A1  - Schultz, Jörg
A1  - Wolf, Matthias
T1  - The ITS2 Database
JF  - Journal of Visual Expression
N2  - The internal transcribed spacer 2 (ITS2) has been used as a phylogenetic marker for more than two decades. As ITS2 research mainly focused on the very variable ITS2 sequence, it confined this marker to low-level phylogenetics only. However, the combination of the ITS2 sequence and its highly conserved secondary structure improves the phylogenetic resolution1 and allows phylogenetic inference at multiple taxonomic ranks, including species delimitation.

The ITS2 Database presents an exhaustive dataset of internal transcribed spacer 2 sequences from NCBI GenBank accurately reannotated. Following an annotation by profile Hidden Markov Models (HMMs), the secondary structure of each sequence is predicted. First, it is tested whether a minimum energy based fold (direct fold) results in a correct, four helix conformation. If this is not the case, the structure is predicted by homology modeling. In homology modeling, an already known secondary structure is transferred to another ITS2 sequence, whose secondary structure was not able to fold correctly in a direct fold.

The ITS2 Database is not only a database for storage and retrieval of ITS2 sequence-structures. It also provides several tools to process your own ITS2 sequences, including annotation, structural prediction, motif detection and BLAST search on the combined sequence-structure information. Moreover, it integrates trimmed versions of 4SALE and ProfDistS for multiple sequence-structure alignment calculation and Neighbor Joining tree reconstruction. Together they form a coherent analysis pipeline from an initial set of sequences to a phylogeny based on sequence and secondary structure.

In a nutshell, this workbench simplifies first phylogenetic analyses to only a few mouse-clicks, while additionally providing tools and data for comprehensive large-scale analyses.
KW  - homology modeling
KW  - molecular systematics
KW  - internal transcribed spacer 2
KW  - alignment
KW  - genetics
KW  - secondary structure
KW  - ribosomal RNA
KW  - phylogenetic tree
KW  - phylogeny
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124600
VL  - 61
IS  - e3806
ER  - 
TY  - JOUR
A1  - Isaias, Ioannis U.
A1  - Volkmann, Jens
A1  - Marzegan, Alberto
A1  - Marotta, Giorgio
A1  - Cavallari, Paolo
A1  - Pezzoli, Gianni
T1  - The Influence of Dopaminergic Striatal Innervation on Upper Limb Locomotor Synergies
JF  - PLoS One
N2  - To determine the role of striatal dopaminergic innervation on upper limb synergies during walking, we measured arm kinematics in 13 subjects with Parkinson disease. Patients were recruited according to several inclusion criteria to represent the best possible in vivo model of dopaminergic denervation. Of relevance, we included only subjects with normal spatio-temporal parameters of the stride and gait speed to avoid an impairment of upper limbs locomotor synergies as a consequence of gait impairment per se. Dopaminergic innervation of the striatum was measured by FP-CIT and SPECT. All patients showed a reduction of gait-associated arms movement. No linear correlation was found between arm ROM reduction and contralateral dopaminergic putaminal innervation loss. Still, a partition analysis revealed a 80% chance of reduced arm ROM when putaminal dopamine content loss was >47%. A significant correlation was described between the asymmetry indices of the swinging of the two arms and dopaminergic striatal innervation. When arm ROM was reduced, we found a positive correlation between upper-lower limb phase shift modulation ( at different gait velocities) and striatal dopaminergic innervation. These findings are preliminary evidence that dopaminergic striatal tone plays a modulatory role in upper-limb locomotor synergies and upper-lower limb coupling while walking at different velocities.
KW  - pet
KW  - Parkinsons disease
KW  - basal ganglia
KW  - spinal-cord
KW  - walking
KW  - gait
KW  - arm
KW  - coordination
KW  - movements
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133976
VL  - 7
IS  - 12
ER  - 
TY  - JOUR
A1  - Ermert, Volker
A1  - Fink, Andreas H.
A1  - Morse, Andrew P.
A1  - Paeth, Heiko
T1  - The Impact of Regional Climate Change on Malaria Risk due to Greenhouse Forcing and Land-Use Changes in Tropical Africa
JF  - Environmental Health Perspectives
N2  - BACKGROUND: Climate change will probably alter the spread and transmission intensity of malaria in Africa. OBJECTIVES: In this study, we assessed potential changes in the malaria transmission via an integrated weather disease model. 
METHODS: We simulated mosquito biting rates using the Liverpool Malaria Model (LMM). The input data for the LMM were bias-corrected temperature and precipitation data from the regional model (REMO) on a 0.5 degrees latitude longitude grid. A Plasmodium falciparum infection model expands the LMM simulations to incorporate information on the infection rate among children. Malaria projections were carried out with this integrated weather disease model for 2001 to 2050 according to two climate scenarios that include the effect of anthropogenic land-use and land-cover changes on climate. 
RESULTS: Model-based estimates for the present climate (1960 to 2000) are consistent with observed data for the spread of malaria in Africa. In the model domain, the regions where malaria is epidemic are located in the Sahel as well as in various highland territories. A decreased spread of malaria over most parts of tropical Africa is projected because of simulated increased surface temperatures and a significant reduction in annual rainfall. However, the likelihood of malaria epidemics is projected to increase in the southern part of the Sahel. In most of East Africa, the intensity of malaria transmission is expected to increase. Projections indicate that highland areas that were formerly unsuitable for malaria will become epidemic, whereas in the lower-altitude regions of the East African highlands, epidemic risk will decrease. 
CONCLUSIONS: We project that climate changes driven by greenhouse-gas and land-use changes will significantly affect the spread of malaria in tropical Africa well before 2050. The geographic distribution of areas where malaria is epidemic might have to be significantly altered in the coming decades.
KW  - climate change
KW  - West Africa
KW  - highland malaria
KW  - malaria
KW  - malaria model
KW  - malaria projection
KW  - Sahel
KW  - transmission
KW  - model
KW  - highlands
KW  - temperatures
KW  - validation
KW  - resurgence
KW  - scenarios
KW  - epidemic
KW  - deseases
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135562
VL  - 120
IS  - 1
ER  - 
TY  - JOUR
A1  - Jaschke, Alexander
A1  - Chung, Bomee
A1  - Hesse, Deike
A1  - Kluge, Reinhart
A1  - Zahn, Claudia
A1  - Moser, Markus
A1  - Petzke, Klaus-Jürgen
A1  - Brigelius-Flohé, Regina
A1  - Puchkov, Dmytro
A1  - Koepsell, Hermann
A1  - Heeren, Joerg
A1  - Joost, Hans-Georg
A1  - Schürmann, Annette
T1  - The GTPase ARFRP1 controls the lipidation of chylomicrons in the Golgi of the intestinal epithelium
JF  - Human Molecular Genetics
N2  - The uptake and processing of dietary lipids by the small intestine is a multistep process that involves several steps including vesicular and protein transport. The GTPase ADP-ribosylation factor-related protein 1 (ARFRP1) controls the ARF-like 1 (ARL1)-mediated Golgi recruitment of GRIP domain proteins which in turn bind several Rab-GTPases. Here, we describe the essential role of ARFRP1 and its interaction with Rab2 in the assembly and lipidation of chylomicrons in the intestinal epithelium. Mice lacking Arfrp1 specifically in the intestine \((Arfrp1^{vil−/−})\) exhibit an early post-natal growth retardation with reduced plasma triacylglycerol and free fatty acid concentrations. \(Arfrp1^{vil−/−}\) enterocytes as well as Arfrp1 mRNA depleted Caco-2 cells absorbed fatty acids normally but secreted chylomicrons with a markedly reduced triacylglycerol content. In addition, the release of apolipoprotein A-I (ApoA-I) was dramatically decreased, and ApoA-I accumulated in the \(Arfrp1^{vil−/−}\) epithelium, where it predominantly co-localized with Rab2. The release of chylomicrons from Caco-2 was markedly reduced after the suppression of Rab2, ARL1 and Golgin-245. Thus, the GTPase ARFRP1 and its downstream proteins are required for the lipidation of chylo­microns and the assembly of ApoA-I to these particles in the Golgi of intestinal epithelial cells.
KW  - ARF
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125658
VL  - 21
IS  - 14
ER  - 
TY  - JOUR
A1  - Franke, B.
A1  - Faraone, S. V.
A1  - Asherson, P.
A1  - Buitelaar, J.
A1  - Bau, C. H. D.
A1  - Ramos-Quiroga, J. A.
A1  - Mick, E.
A1  - Grevet, E. H.
A1  - Johansson, S.
A1  - Haavik, J.
A1  - Lesch, K.-P.
A1  - Cormand, B.
A1  - Reif, A.
T1  - The genetics of attention deficit/hyperactivity disorder in adults, a review
JF  - Molecular Psychiatry
N2  - The adult form of attention deficit/hyperactivity disorder (aADHD) has a prevalence of up to 5% and is the most severe long-term outcome of this common neurodevelopmental disorder. Family studies in clinical samples suggest an increased familial liability for aADHD compared with childhood ADHD (cADHD), whereas twin studies based on self-rated symptoms in adult population samples show moderate heritability estimates of 30–40%. However, using multiple sources of information, the heritability of clinically diagnosed aADHD and cADHD is very similar. Results of candidate gene as well as genome-wide molecular genetic studies in aADHD samples implicate some of the same genes involved in ADHD in children, although in some cases different alleles and different genes may be responsible for adult versus childhood ADHD. Linkage studies have been successful in identifying loci for aADHD and led to the identification of LPHN3 and CDH13 as novel genes associated with ADHD across the lifespan. In addition, studies of rare genetic variants have identified probable causative mutations for aADHD. Use of endophenotypes based on neuropsychology and neuroimaging, as well as next-generation genome analysis and improved statistical and bioinformatic analysis methods hold the promise of identifying additional genetic variants involved in disease etiology. Large, international collaborations have paved the way for well-powered studies. Progress in identifying aADHD risk genes may provide us with tools for the prediction of disease progression in the clinic and better treatment, and ultimately may help to prevent persistence of ADHD into adulthood.
KW  - IMpACT
KW  - persistent ADHD
KW  - molecular genetics
KW  - heritability
KW  - endophenotype
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124677
VL  - 17
ER  - 
TY  - JOUR
A1  - Jin, Jing
A1  - Allison, Brendan Z.
A1  - Kaufmann, Tobias
A1  - Kübler, Andrea
A1  - Zhang, Yu
A1  - Wang, Xingyu
A1  - Cichocki, Andrzej
T1  - The Changing Face of P300 BCIs: A Comparison of Stimulus Changes in a P300 BCI Involving Faces, Emotion, and Movement
JF  - PLoS One
N2  - Background: One of the most common types of brain-computer interfaces (BCIs) is called a P300 BCI, since it relies on the P300 and other event-related potentials (ERPs). In the canonical P300 BCI approach, items on a monitor flash briefly to elicit the necessary ERPs. Very recent work has shown that this approach may yield lower performance than alternate paradigms in which the items do not flash but instead change in other ways, such as moving, changing colour or changing to characters overlaid with faces. 
Methodology/Principal Findings: The present study sought to extend this research direction by parametrically comparing different ways to change items in a P300 BCI. Healthy subjects used a P300 BCI across six different conditions. Three conditions were similar to our prior work, providing the first direct comparison of characters flashing, moving, and changing to faces. Three new conditions also explored facial motion and emotional expression. The six conditions were compared across objective measures such as classification accuracy and bit rate as well as subjective measures such as perceived difficulty. In line with recent studies, our results indicated that the character flash condition resulted in the lowest accuracy and bit rate. All four face conditions (mean accuracy >91%) yielded significantly better performance than the flash condition (mean accuracy = 75%). 
Conclusions/Significance: Objective results reaffirmed that the face paradigm is superior to the canonical flash approach that has dominated P300 BCIs for over 20 years. The subjective reports indicated that the conditions that yielded better performance were not considered especially burdensome. Therefore, although further work is needed to identify which face paradigm is best, it is clear that the canonical flash approach should be replaced with a face paradigm when aiming at increasing bit rate. However, the face paradigm has to be further explored with practical applications particularly with locked-in patients.
KW  - ERPS
KW  - communication
KW  - TO-target interval
KW  - visual-evoked potentials
KW  - brain-computer-interface
KW  - recognition
KW  - amplitude
KW  - paradigm
KW  - systems
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134173
VL  - 7
IS  - 11
ER  - 
TY  - JOUR
A1  - Ramachandran, Vinoy K.
A1  - Shearer, Neil
A1  - Jacob, Jobin J.
A1  - Sharma, Cynthia M.
A1  - Thompson, Arthur
T1  - The architecture and ppGpp-dependent expression of the primary transcriptome of Salmonella Typhimurium during invasion gene expression
JF  - BMC Genomics
N2  - Background: Invasion of intestinal epithelial cells by Salmonella enterica serovar Typhimurium (S. Typhimurium) requires expression of the extracellular virulence gene expression programme (STEX), activation of which is dependent on the signalling molecule guanosine tetraphosphate (ppGpp). Recently, next-generation transcriptomics (RNA-seq) has revealed the unexpected complexity of bacterial transcriptomes and in this report we use differential RNA sequencing (dRNA-seq) to define the high-resolution transcriptomic architecture of wildtype S. Typhimurium and a ppGpp null strain under growth conditions which model STEX. In doing so we show that ppGpp plays a much wider role in regulating the S. Typhimurium STEX primary transcriptome than previously recognised. 
Results: Here we report the precise mapping of transcriptional start sites (TSSs) for 78% of the S. Typhimurium open reading frames (ORFs). The TSS mapping enabled a genome-wide promoter analysis resulting in the prediction of 169 alternative sigma factor binding sites, and the prediction of the structure of 625 operons. We also report the discovery of 55 new candidate small RNAs (sRNAs) and 302 candidate antisense RNAs (asRNAs). We discovered 32 ppGpp-dependent alternative TSSs and determined the extent and level of ppGpp-dependent coding and non-coding transcription. We found that 34% and 20% of coding and non-coding RNA transcription respectively was ppGpp-dependent under these growth conditions, adding a further dimension to the role of this remarkable small regulatory molecule in enabling rapid adaptation to the infective environment. 
Conclusions: The transcriptional architecture of S. Typhimurium and finer definition of the key role ppGpp plays in regulating Salmonella coding and non-coding transcription should promote the understanding of gene regulation in this important food borne pathogen and act as a resource for future research.
KW  - legionella pneumophila
KW  - growth rate control
KW  - escherichia coli K-12
KW  - pathogenicity island 2
KW  - bacterial signal molecule
KW  - enterica serovar typhimurium
KW  - messenger RNA
KW  - protein synthesis
KW  - sationary phase
KW  - environmental regulation
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130625
VL  - 13
IS  - 25
ER  - 
TY  - JOUR
A1  - Pils, Stefan
A1  - Kopp, Kathrin
A1  - Peterson, Lisa
A1  - Tascon, Julia Delgado
A1  - Nyffenegger-Jann, Naja J.
A1  - Hauck, Christof R.
T1  - The Adaptor Molecule Nck Localizes the WAVE Complex to Promote Actin Polymerization during CEACAM3-Mediated Phagocytosis of Bacteria
JF  - PLoS One
N2  - Background: CEACAM3 is a granulocyte receptor mediating the opsonin-independent recognition and phagocytosis of human-restricted CEACAM-binding bacteria. CEACAM3 function depends on an intracellular immunoreceptor tyrosine-based activation motif (ITAM)-like sequence that is tyrosine phosphorylated by Src family kinases upon receptor engagement. The phosphorylated ITAM-like sequence triggers GTP-loading of Rac by directly associating with the guanine nucleotide exchange factor (GEF) Vav. Rac stimulation in turn is critical for actin cytoskeleton rearrangements that generate lamellipodial protrusions and lead to bacterial uptake. 
Principal Findings: In our present study we provide biochemical and microscopic evidence that the adaptor proteins Nck1 and Nck2, but not CrkL, Grb2 or SLP-76, bind to tyrosine phosphorylated CEACAM3. The association is phosphorylation-dependent and requires the Nck SH2 domain. Overexpression of the isolated Nck1 SH2 domain, RNAi-mediated knock-down of Nck1, or genetic deletion of Nck1 and Nck2 interfere with CEACAM3-mediated bacterial internalization and with the formation of lamellipodial protrusions. Nck is constitutively associated with WAVE2 and directs the actin nucleation promoting WAVE complex to tyrosine phosphorylated CEACAM3. In turn, dominant-negative WAVE2 as well as shRNA-mediated knock-down of WAVE2 or the WAVE-complex component Nap1 reduce internalization of bacteria. 
Conclusions: Our results provide novel mechanistic insight into CEACAM3-initiated phagocytosis. We suggest that the CEACAM3 ITAM-like sequence is optimized to co-ordinate a minimal set of cellular factors needed to efficiently trigger actin-based lamellipodial protrusions and rapid pathogen engulfment.
KW  - activation
KW  - neisseria gonorrhoeae
KW  - human pathogens
KW  - T cell
KW  - signal transduction
KW  - escherichia coli
KW  - epithelial cells
KW  - tyrosine kinase
KW  - receptor
KW  - adhesion
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131747
VL  - 7
IS  - 3
ER  - 
TY  - JOUR
A1  - Samimi, C.
A1  - Fink, A. H.
A1  - Paeth, H.
T1  - The 2007 flood in the Sahel: causes, characteristics and its presentation in the media and FEWS NET
JF  - Natural Hazards and Earth System Sciences
N2  - During the rainy season in 2007, reports about exceptional rains and floodings in the Sahel were published in the media, especially in August and September. Institutions and organizations like the World Food Programme (WFP) and FEWS NET put the events on the agenda and released alerts and requested help. The partly controversial picture was that most of the Sahel faced a crisis caused by widespread floodings. Our study shows that the rainy season in 2007 was exceptional with regard to rainfall amount and return periods. In many areas the event had a return period between 1 and 50 yr with high spatial heterogeneity, with the exception of the Upper Volta basin, which yielded return periods of up to 1200 yr. Despite the strong rainfall, the interpretation of satellite images show that the floods were mainly confined to lakes and river beds. However, the study also proves the difficulties in assessing the meteorological processes and the demarcation of flooded areas in satellite images without ground truthing. These facts and the somewhat vague and controversial reports in the media and FEWS NET demonstrate that it is crucial to thoroughly analyze such events at a regional and local scale involving the local population.
KW  - prediction
KW  - satellite rainfall products
KW  - tropical North-Africa
KW  - West-Africa
KW  - climate change
KW  - summer rainfall
KW  - variability
KW  - SST
KW  - teleconnection
KW  - validation
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131790
VL  - 12
IS  - 2
SP  - 313
EP  - 325
ER  - 
TY  - JOUR
A1  - Radermacher, Kim A.
A1  - Wingler, Kirstin
A1  - Kleikers, Pamela
A1  - Altenhöfer, Sebastian
A1  - Hermans, Johannes J. R.
A1  - Kleinschnitz, Christoph
A1  - Schmidt, Harald H. H. W.
T1  - The 1027th target candidate in stroke: Will NADPH oxidase hold up?
JF  - Experimental and Translational Stroke Medicine
N2  - As recently reviewed, 1026 neuroprotective drug candidates in stroke research have all failed on their road towards validation and clinical translation, reasons being quality issues in preclinical research and publication bias. Quality control guidelines for preclinical stroke studies have now been established. However, sufficient understanding of the underlying mechanisms of neuronal death after stroke that could be possibly translated into new therapies is lacking. One exception is the hypothesis that cellular death is mediated by oxidative stress. Oxidative stress is defined as an excess of reactive oxygen species (ROS) derived from different possible enzymatic sources. Among these, NADPH oxidases (NOX1-5) stand out as they represent the only known enzyme family that has no other function than to produce ROS. Based on data from different NOX knockout mouse models in ischemic stroke, the most relevant isoform appears to be NOX4. Here we discuss the state-of-the-art of this target with respect to stroke and open questions that need to be addressed on the path towards clinical translation.
KW  - NADPH oxidases (NOX)
KW  - stroke therapy
KW  - oxidative stress
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124197
VL  - 4
IS  - 11
ER  - 
TY  - JOUR
A1  - Jain, Preetesh
A1  - Javdan, Mohammad
A1  - Feger, Franziska K.
A1  - Chiu, Pui Yan
A1  - Sison, Cristina
A1  - Damle, Rajendra N.
A1  - Bhuiya, Tawfiqul A.
A1  - Sen, Filiz
A1  - Abruzzo, Lynne V.
A1  - Burger, Jan A.
A1  - Rosenwald, Andreas
A1  - Allen, Steven L.
A1  - Kolitz, Jonathan E.
A1  - Rai, Kanti R.
A1  - Chiorazzi, Nicholas
A1  - Sherry, Barbara
T1  - Th17 and non-Th17 interleukin-17-expressing cells in chronic lymphocytic leukemia: delineation, distribution, and clinical relevance
JF  - Haematologica
N2  - Background The levels and clinical relevance of Th17 cells and other interleukin-17-producing cells have not been analyzed in chronic lymphocytic leukemia. The objective of this study was to quantify blood and tissue levels of Th17 and other interleukin-17-producing cells in patients with this disease and correlate blood levels with clinical outcome. 
Design and Methods: Intracellular interleukin-17A was assessed in blood and splenic mononuclear cells from patients with chronic lymphocytic leukemia and healthy subjects using flow cytometry. Interleukin-17A-producing cells were analyzed in formalin-fixed, paraffin-embedded spleen and lymph node sections using immunohistochemistry and immunofluorescence. 
Results: The absolute numbers of Th17 cells in peripheral blood mononuclear cells and the percentages of Th17 cells in spleen cell suspensions were higher in patients with chronic lymphocytic leukemia than in healthy subjects; in six out of eight paired chronic lymphocytic leukemia blood and spleen sample comparisons, Th17 cells were enriched in spleen suspensions. Circulating Th17 levels correlated with better prognostic markers and longer overall survival of the patients. Two "non-Th17" interleukin-17-expressing cells were identified in chronic lymphocytic leukemia spleens: proliferating cells of the granulocytic lineage and mature mast cells. Granulocytes and mast cells in normal spleens did not express interleukin-17. Conversely, both chronic lymphocytic leukemia and healthy lymph nodes contained similar numbers of interleukin-17+ mast cells as well as Th17 cells. 
Conclusions: Th17 cells are elevated in chronic lymphocytic leukemia patients with better prognostic markers and correlate with longer survival. Furthermore, non-Th17 interleukin-17A-expressing cells exist in chronic lymphocytic leukemia spleens as maturing granulocytes and mature mast cells, suggesting that the microenvironmental milieu in leukemic spleens promotes the recruitment and/or expansion of Th17 and other IL-17-expressing cells. The pathophysiology of Th17 and non-Th17-interleukin-producing cells in chronic lymphocytic leukemia and their distributions and roles in this disease merit further study.
KW  - disease
KW  - helper T cells
KW  - T(H)17 cells
KW  - tumor microenvironment
KW  - multiple myeloma
KW  - up regulation
KW  - mast cells
KW  - lineage
KW  - pathway
KW  - IL-17
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131290
VL  - 97
IS  - 4
ER  - 
TY  - JOUR
A1  - Hommers, Wilfried
A1  - Lewand, Martin
A1  - Ehrmann, Dominic
T1  - Testing the moral algebra of two Kohlbergian informers
JF  - Psícologica
N2  - This paper seeks to unify two major theories of moral judgment: Kohlberg's stage theory and Anderson's moral information integration theory. Subjects were told about thoughts of actors in Kohlberg's classic altruistic Heinz dilemma and in a new egoistical dilemma. These actors's thoughts represented Kohlberg's stages I (Personal Risk) and IV (Societal Risk) and had three levels, High, Medium, and Low. They were presented singly and in a 3 x 3 integration design. Subjects judged how many months of prison the actor deserved. The data supported the averaging model of moral integration theory, whereas Kohlberg's theory has no way to handle the integration problem. Following this, subjects ranked statements related to Kohlberg's first four stages in a procedure similar to that of Rest (1975). Higher score went with larger effect of Societal Risk as predicted by Kohlberg's theory. But contrary to Kohlberg's theory, no age trends were found. Also strongly contrary to Kohlberg's theory, effects of Personal Risk (Stage I) and Societal Risk (Stage IV) correlated positively.
KW  - integration
KW  - information
KW  - judgements
KW  - intent
KW  - damage
KW  - rules
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133917
VL  - 33
IS  - 3
ER  -