The phosphoproteome of toll-like receptor-activated macrophages

First global and quantitative analysis of phosphorylation cascades induced by toll-like receptor (TLR) stimulation in macrophages identifies nearly 7000 phosphorylation sites and shows extensive and dynamic up-regulation and down-regulation after lipopolysaccharide (LPS).In addition to the canonical TLR-associated pathways, mining of the phosphorylation data suggests an involvement of ATM/ATR kinases in signalling and shows that the cytoskeleton is a hotspot of TLR-induced phosphorylation.Intersecting transcription factor phosphorylation with bioinformatic promoter analysis of genes induced by LPS identified several candidate transcriptional regulators that were previously not implicated in TLR-induced transcriptional control

Three Metachronous Osteosarcomas within 22 Years without Pulmonary Metastases: A Case Report and Review of the Literature

Introduction. We present the extremely rare case of a patient with three metachronous osteosarcomas within 22 years without evident pulmonary manifestation of disease 30 years after first diagnosis. Case Presentation. In 1983, a high-grade osteosarcoma of the left distal femur was diagnosed in an 18-year-old Caucasian male. He received rotationplasty accompanied by pre- and postoperative chemotherapy. Ten years later, an osteoblastic osteosarcoma occurred in TH12. En bloc resection and pre- and postoperative chemotherapy followed. In 2005, the patient developed another high-grade osteosarcoma in his right distal femur. Treatment included a wide resection and reconstruction with a tumour endoprosthesis as well as (neo)adjuvant chemotherapy. After the third tumour occurrence, cytogenetic and molecular genetic examinations (p53, rb1) were performed, showing a normal genetic pattern. Screening for metastases never showed clinical evidence of extraskeletal tumour manifestation. Discussion. In patients presenting metachronous osteosarcoma, identification of their lesions clonality (second primary tumour or metastases) could lead to a better understanding of tumour development and help to filter patients who need extended long-term followup due to a higher risk of late occurring sarcoma recurrence

Conductive Geopolymers as Low-Cost Electrode Materials for Microbial Fuel Cells

Geopolymer (GP) inorganic binders have a superior acid resistance compared to conventional cement (e.g., Portland cement, PC) binders, have better microbial compatibility, and are suitable for introducing electrically conductive additives to improve electron and ion transfer properties. In this study, GP–graphite (GPG) composites and PC–graphite (PCG) composites with a graphite content of 1–10 vol % were prepared and characterized. The electrical conductivity percolation threshold of the GPG and PCG composites was around 7 and 8 vol %, respectively. GPG and PCG composites with a graphite content of 8 to 10 vol % were selected as anode electrodes for the electrochemical analysis in two-chamber polarized microbial fuel cells (MFCs). Graphite electrodes were used as the positive control reference material. Geobacter sulfurreducens was used as a biofilm-forming and electroactive model organism for MFC experiments. Compared to the conventional graphite anodes, the anode-respiring biofilms resulted in equal current production on GPG composite anodes, whereas the PCG composites showed a very poor performance. The largest mean value of the measured current densities of a GPG composite used as anodes in MFCs was 380.4 μA cm⁻² with a standard deviation of 129.5 μA cm⁻². Overall, the best results were obtained with electrodes having a relatively low Ohmic resistance, that is, GPG composites and graphite. The very first approach employing sustainable GPs as a low-cost electrode binder material in an MFC showed promising results with the potential to greatly reduce the production costs of MFCs, which would also increase the feasibility of MFC large-scale applications

Agrarrelevante Extremwetterlagen und Möglichkeiten von Risikomanagementsystemen: Studie im Auftrag des Bundesministeriums für Ernährung und Landwirtschaft (BMEL)

Das Verbundforschungsvorhaben untersuchte regional differenzierte Änderungen agrarrelevanter Extremwetterlagen in Deutschland und deren Auswirkungen auf die Landwirtschaft einschließlich Sonderkulturen und Forstwirtschaft. Auswertungen der Stationsdaten von 1961 bis 2013 des Deutschen Wetterdienstes sowie Daten aus 21 Klimamodellläufen bis zum Jahr 2100 zeigten unter anderem einen Anstieg extremer Hitzetage, die auch in Zukunft häufiger werden sollen. Ferner wurde in den letzten 20 Jahren eine Zunahme der Tage ohne Niederschlag im März und April sowie eine Zunahme extrem trockener Tage im Sommer beobachtet, wobei letztere zukünftig weiter zunehmen sollen. Zunehmende Hitze und Trockenheit beeinträchtigen vor allem die Ertragsbildung bei einigen Ackerkulturen, wie z.B. beim Weizen. Im Wald ist die Verjüngungsfähigkeit vor allem unter Fichte und Kiefer gefährdet. Bei einigen Extremwetterlagen, die insbesondere im Acker- und Sonderkulturanbau hohe Schäden verursachen, wie z. B. Hagel, Starkniederschläge und Spätfröste, besteht wegen fehlender Beobachtungsdaten bzw. nicht eindeutiger Wechselwirkungen weiterer Forschungsbedarf. Nach den Ergebnissen besteht angesichts vielfältiger Anpassungsoptionen in der Land- und Forstwirtschaft keine unmittelbare Notwendigkeit, Risikomanagementsysteme staatlich verstärkt zu unterstützen.The collaborative project analysed regional differentiated changes of extreme weather events in Germany and their impacts on agriculture including specialised crops and forestry. Analyses of weather station data from 1961 to 2013 of the German Weather Service as well as results of 21 climate model runs until 2100 show i. a. an increase of days with extreme heat which are expected to become more frequent in the future. Furthermore, an increase of days without precipitation in March and April as well as an increase of days with extreme drought in summer were observed. The latter are expected to increase in the future. Increasing heat and drought adversely affect in particular growth and crop harvest of arable cultures e. g. winter wheat. Extreme drought impairs especially the regeneration capacity in spruce and pine forests. For some extreme weather events that cause severe damages in particular in arable and specialised crops such as hail, extreme precipitation and late frosts further research need was identified due to missing observation data or unclear interactions between weather and vegetation. According to the results and in the light of various adaptation options there is currently no further necessity for governmental support of risk management systems

Hypofractionated stereotactic radiotherapy of limited brain metastases: a single-centre individualized treatment approach

<p>Abstract</p> <p>Background</p> <p>We retrospectively report treatment results of our single-centre experience with hypofractionated stereotactic radiotherapy (hfSRT) of limited brain metastases in primary and recurrence disease situations. Our aim was to find the most effective and safe dose concept.</p> <p>Methods</p> <p>From 04/2006 to 12/2010, 75 patients, with 108 intracranial metastases, were treated with hfSRT. 52 newly diagnosed metastases (48%), without up-front whole brain radiotherapy (WBRT), received hfSRT as a primary treatment. 56 metastases (52%) received a prior WBRT and were treated in this study in a recurrence situation. Main fractionation concepts used for primary hfSRT were 6-7x5 Gy (61.5%) and 5x6 Gy (19.2%), for recurrent hfSRT 7-10x4 Gy (33.9%) and 5-6x5 Gy (33.9%).</p> <p>Results</p> <p>Median overall survival (OS) of all patients summed up to 9.1 months, actuarial 6-and 12-month-OS was 59% and 35%, respectively. Median local brain control (LC) was 11.9 months, median distant brain control (DC) 3.9 months and intracranial control (IC) 3.4 months, respectively. Variables with significant influence on OS were Gross Tumour Volume (GTV) (p = 0.019), the biological eqivalent dose (calculated on a 2 Gy single dose, EQD2, α/β = 10) < and ≥ median of 39 Gy (p = 0.012), extracerebral activity of the primary tumour (p < 0.001) and the steroid uptake during hfSRT (p = 0.03). LC was significantly influenced by the EQD2, ≤ and > 35 Gy (p = 0.004) in both uni- and multivariate Cox regression analysis. Median LC was 14.9 months for EQD2 >35 Gy and 3.4 months for doses ≤35 Gy, respectively. Early treatment related side effects were usually mild. Nevertheless, patients with a EQD2 >35 Gy had higher rates of toxicity (31%) than ≤35 Gy (8.3%, p=0.026).</p> <p>Conclusion</p> <p>Comparing different dose concepts in hfSRT, a cumulative EQD2 of ≥35 Gy seems to be the most effective concept in patients with primary or recurrent limited brain metastases. Despite higher rates of only mild toxicity, this concept represents a safe treatment option.</p

Correction: High-risk additional chromosomal abnormalities at low blast counts herald death by CML (Leukemia, (2020), 34, 8, (2074-2086), 10.1038/s41375-020-0826-9)

An amendment to this paper has been published and can be accessed via a link at the top of the paper