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The magnetite-based receptors in the beak of birds and their role in avian navigation (2012)

Roswitha Wiltschko Wolfgang Wiltschko

Iron-rich structures have been described in the beak of homing pigeons, chickens and several species of migratory birds and interpreted as magnetoreceptors. Here, we will briefly review findings associated with these receptors that throw light on their nature, their function and their role in avian navigation. Electrophysiological recordings from the ophthalmic nerve, behavioral studies and a ZENK-study indicate that the trigeminal system, the nerves innervating the beak, mediate information on magnetic changes, with the electrophysiological study suggesting that these are changes in intensity. Behavioral studies support the involvement of magnetite and the trigeminal system in magnetoreception, but clearly show that the inclination compass normally used by birds represents a separate system. However, if this compass is disrupted by certain light conditions, migrating birds show 'fixed direction' responses to the magnetic field, which originate in the receptors in the beak. Together, these findings point out that there are magnetite-based magnetoreceptors located in the upper beak close to the skin. Their natural function appears to be recording magnetic intensity and thus providing one component of the multi-factorial 'navigational map' of birds.

The role of recombinant epidermal growth factor and serotonin in the stimulation of tumor growth in a SCCHN xenograft model (2012)

Christin Geissler Markus Hambek Anne Eckardt Christoph Arnoldner Marc Diensthuber Timo Stöver Jens Wagenblast

One challenge of squamous cell carcinoma of the head and neck (SCCHN) chemotherapy is a small percentage of tumor cells that arrest in the G0 phase of the cell cycle and are thus not affected by chemotherapy. This could be one reason for tumor recurrence at a later date. The recruitment of these G0-arresting cells into the active cell cycle and thus, proliferation, may increase the efficacy of chemotherapeutic agents. The aim of this study was to investigate whether stimulation with recombinant epidermal growth factor (EGF) or serotonin leads to an increased tumor cell proliferation in xenografts. Detroit 562 cells were injected into NMRI-Foxn1nu mice. Treatment was performed with 15 µg murine or human EGF, or 200 µg serotonin. The control mice were treated with Lactated Ringer's solution (5 mice/group). Tumor size was measured on days 4, 8 and 12 after tumor cell injection. The EGF stimulated mice showed a significantly higher tumor growth compared to the serotonin-stimulated mice and the untreated controls. In the present study, we show that it is possible to stimulate tumor cells in xenografts by EGF and thus, enhance cell proliferation, resulting in a higher tumor growth compared to the untreated control group. In our future investigations, we plan to include a higher number of mice, an adjustment of the EGF dosage and cell subanalysis, considering the heterogeneity of SCCHN tumors.

First human study in treatment of unresectable liver metastases from colorectal cancer with irinotecan-loaded beads (DEBIRI) (2012)

Katrin Eichler Stephan Zangos Martin G. Mack Renate Maria Hammerstingl Tatjana Gruber-Rouh Christof Gallus Thomas J. Vogl

The objective of this pilot clinical study was to assess the safety, technical feasibility, pharmacokinetic (PK) profile and tumour response of DC Bead™ with irinotecan (DEBIRI™) delivered by intra-arterial embolisation for the treatment of metastatic colorectal cancer. Eleven patients with unresectable liver metastases from CRC, tumour burden <30% of liver volume, adequate haematological, liver and renal function, performance status of <2 were included in this study. Patients received up to 4 sessions of TACE with DEBIRI at 3-week intervals. Feasibility of the procedure, safety and tumour response were assessed after each cycle. PK was measured after the first cycle. Patients were followed up to 24 weeks. Only mild to moderate adverse events were observed. DEBIRI is a technically feasibile procedure; no technical complications were observed. Average Cmax for irinotecan and SN-38 was 194 ng/ml and 16.7 ng/ml, respectively, with average t½ of 4.6 h and 12.4 h following administration of DEBIRI. Best overall response during the study showed disease control in 9 patients (2 patients with partial response and 7 with stable disease, overall response rate of 18%). Our study shows that transarterial chemoembolisation with irinotecan-loaded DC beads (DEBIRI) is safe, technically feasible and effective with a good PK profile.

Static stretching of the hamstrings muscle for injury prevention in football codes: a systematic review (2012)

Slavko Rogan Dirk Wüst Thomas Schwitter Dietmar Schmidtbleicher

Purpose: Hamstring injuries are common among football players. There is still disagreement regarding prevention. The aim of this review is to determine whether static stretching reduces hamstring injuries in football codes. Methods: A systematic literature search was conducted on the online databases PubMed, PEDro, Cochrane, Web of Science, Bisp and Clinical Trial register. Study results were presented descriptively and the quality of the studies assessed were based on Cochrane’s ‘risk of bias’ tool. Results: The review identified 35 studies, including four analysis studies. These studies show deficiencies in the quality of study designs. Conclusion: The study protocols are varied in terms of the length of intervention and follow-up. No RCT studies are available, however, RCT studies should be conducted in the near future.

Acute injuries in student circus artists with regard to gender specific differences (2012)

Eileen M. Wanke Moira McCormack Franziska Koch Alice Wanke Jan David Alexander Groneberg

Purpose: Student circus artists train as both artists and athletes with their bodies holding the key to professional success. The daily training load of student circus artists is often associated with maximum physical and psychological stress with injuries posing a threat to a potential professional career. The purpose of this study is the differentiated analysis and evaluation of work accidents in order to initiate the development of injury preventive programs. Methods: The 17 years of data were obtained from standardized anonymous work accident records of the Berlin State Accident Insurance (UKB) as well as a State Artist Educational School (n = 169, Male: 70; Female: 99) from student artists. Evaluation and descriptive statistics were conducted with Excel 2007 and PASW Statistics 18. Results: The injury risk seems to be relatively low (0.3 injuries/1000h). There are gender specific differences as to the location of injuries. Only 7% of the accidents demand a break of more than 3 days. Injury patterns vary depending on the activity and the employment of props/equipment. 75.2% of work accidents have multifactorial and 24.8% exogenous causes. Conclusions: Because physical fitness is all important in the circus arts there are numerous options for injury prevention programs that should be realized subject to gender-specific differences. Follow-ups on chronic complaints and a more individual approach are indispensable due to the very specific activities in the circus arts.

Estrogen-Dependent Dynamic Profile of eNOS-DNA Associations in Prostate Cancer (2012)

Simona Nanni Aurora Aiello Agnese Re Alessandro Guffanti Valentina Benvenuti Claudia Colussi Luis Jaime Castro-Vega Armando Felsani Arturo Londono-Vallejo Maurizio C. Capogrossi Silvia Bacchetti Carlo Gaetano Alfredo Pontecorvi Antonella Farsetti

In previous work we have documented the nuclear translocation of endothelial NOS (eNOS) and its participation in combinatorial complexes with Estrogen Receptor Beta (ERβ) and Hypoxia Inducible Factors (HIFs) that determine localized chromatin remodeling in response to estrogen (E2) and hypoxia stimuli, resulting in transcriptional regulation of genes associated with adverse prognosis in prostate cancer (PCa). To explore the role of nuclear eNOS in the acquisition of aggressive phenotype in PCa, we performed ChIP-Sequencing on chromatin-associated eNOS from cells from a primary tumor with poor outcome and from metastatic LNCaP cells. We found that: 1. the eNOS-bound regions (peaks) are widely distributed across the genome encompassing multiple transcription factors binding sites, including Estrogen Response Elements. 2. E2 increased the number of peaks, indicating hormone-dependent eNOS re-localization. 3. Peak distribution was similar with/without E2 with ≈ 55% of them in extragenic DNA regions and an intriguing involvement of the 5′ domain of several miRs deregulated in PCa. Numerous potentially novel eNOS-targeted genes have been identified suggesting that eNOS participates in the regulation of large gene sets. The parallel finding of downregulation of a cluster of miRs, including miR-34a, in PCa cells associated with poor outcome led us to unveil a molecular link between eNOS and SIRT1, an epigenetic regulator of aging and tumorigenicity, negatively regulated by miR-34a and in turn activating eNOS. E2 potentiates miR-34a downregulation thus enhancing SIRT1 expression, depicting a novel eNOS/SIRT1 interplay fine-tuned by E2-activated ER signaling, and suggesting that eNOS may play an important role in aggressive PCa.

Environmental change impacts on the C- and N-cycle of European forests: a model comparison study (2012)

David R. Cameron Marcel van Oijen Christian Werner Klaus Butterbach-Bahl Edwin Haas Gerardus Bernardus Maria Heuvelink Rüdiger Grote Ralf Kiese Matthias Kuhnert Johannes Kros Adrian Leip Gert Jan Reinds Hannes I. Reuter Mart Jan Schelhaas Wim De Vries Jagadeesh Yeluripati

Forests are important components of the greenhouse gas balance of Europe. There is considerable uncertainty about how predicted changes to climate and nitrogen deposition will perturb the carbon and nitrogen cycles of European forests and thereby alter forest growth, carbon sequestration and N2O emission. The present study aimed to quantify the carbon and nitrogen balance, including the exchange of greenhouse gases, of European forests over the period 2010–2030, with a particular emphasis on the spatial variability of change. The analysis was carried out for two tree species: European beech and Scots pine. For this purpose, four different dynamic models were used: BASFOR, DailyDayCent, INTEGRATOR and Landscape-DNDC. These models span a range from semi-empirical to complex mechanistic. Comparison of these models allowed assessment of the extent to which model predictions depended on differences in model inputs and structure. We found a European average carbon sink of 0.160 ± 0.020 kgC m−2 yr−1 (pine) and 0.138 ± 0.062 kgC m−2 yr−1 (beech) and N2O source of 0.285 ± 0.125 kgN ha−1 yr−1 (pine) and 0.575 ± 0.105 kgN ha−1 yr−1 (beech). The European average greenhouse gas potential of the carbon source was 18 (pine) and 8 (beech) times that of the N2O source. Carbon sequestration was larger in the trees than in the soil. Carbon sequestration and forest growth were largest in central Europe and lowest in northern Sweden and Finland, N. Poland and S. Spain. No single driver was found to dominate change across Europe. Forests were found to be most sensitive to change in environmental drivers where the drivers were limiting growth, where changes were particularly large or where changes acted in concert. The models disagreed as to which environmental changes were most significant for the geographical variation in forest growth and as to which tree species showed the largest rate of carbon sequestration. Pine and beech forests were found to have differing sensitivities to environmental change, in particular the response to changes in nitrogen and precipitation, with beech forest more vulnerable to drought. There was considerable uncertainty about the geographical location of N2O emissions. Two of the models BASFOR and LandscapeDNDC had largest emissions in central Europe where nitrogen deposition and soil nitrogen were largest whereas the two other models identified different regions with large N2O emission. N2O emissions were found to be larger from beech than pine forests and were found to be particularly sensitive to forest growth.

Corrigendum to ''The relative roles of CO2 and palaeogeography in determining late Miocene climate: results from a terrestrial model-data comparison'' published in Clim. Past, 8, 1257–1285, 2012 (2012)

Catherine D. Bradshaw Daniel J. Lunt Rachel Flecker Ulrich Salzmann Matthew J. Pound Alan M. Haywood Jussi Eronen

In the original manuscript, Figs. 7–16 included fonts which were not correctly embedded in the file. As such, unless certain propriety software (ArcGIS) is installed on the viewing platform, the figures will appear corrupted. In this Corrigendum, Figs. 7–16 and their captions are reproduced with the fonts correctly embedded. Please find the correct figures below.

The relative roles of CO2 and palaeogeography in determining late Miocene climate: results from a terrestrial model–data compariso (2012)

Catherine D. Bradshaw Daniel J. Lunt Rachel Flecker Ulrich Salzmann Matthew J. Pound Alan M. Haywood Jussi Eronen

The late Miocene palaeorecord provides evidence for a warmer and wetter climate than that of today, and there is uncertainty in the palaeo-CO2 record of at least 200 ppm. We present results from fully coupled atmosphere-ocean-vegetation simulations for the late Miocene that examine the relative roles of palaeogeography (topography and ice sheet geometry) and CO2 concentration in the determination of late Miocene climate through comprehensive terrestrial model-data comparisons. Assuming that these data accurately reflect the late Miocene climate, and that the late Miocene palaeogeographic reconstruction used in the model is robust, then results indicate that: 1. Both palaeogeography and atmospheric CO2 contribute to the proxy-derived precipitation differences between the late Miocene and modern reference climates. However these contributions exibit synergy and so do not add linearly. 2. The vast majority of the proxy-derived temperature differences between the late Miocene and modern reference climates can only be accounted for if we assume a palaeo-CO2 concentration towards the higher end of the range of estimates.

The relative roles of CO2 and palaeogeography in determining Late Miocene climate: results from a terrestrial model-data comparison (2012)

Catherine D. Bradshaw Daniel J. Lunt Rachel Flecker Ulrich Salzmann Matthew J. Pound Alan M. Haywood Jussi Eronen

The Late Miocene (∼11.6–5.3 Ma) palaeorecord provides evidence for a warmer and wetter climate than that of today and there is uncertainty in the palaeo-CO2 record of at least 150 ppmv. We present results from fully coupled atmosphere-ocean-vegetation simulations for the Late Miocene that examine the relative roles of palaeogeography (topography and ice sheet geometry) and CO2 concentration in the determination of Late Miocene climate through comprehensive terrestrial model-data comparisons. Assuming that the data accurately reflects the Late Miocene climate, and that the Late Miocene palaeogeographic reconstruction used in the model is robust, then results indicate that the proxy-derived precipitation differences between the Late Miocene and modern can be largely accounted for by the palaeogeographic changes alone. However, the proxy-derived temperatures differences between the Late Miocene and modern can only begin to be accounted for if we assume a palaeo-CO2 concentration towards the higher end of the range of estimates.

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