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| 1 | Lrp1 in osteoblasts controls osteoclast activity and protects against osteoporosis by limiting PDGF–RANKL signaling显示文摘Skeletal health relies on architectural integrity and sufficient bone mass, which are maintained through a tightly regulated equilibrium of bone resorption by osteoclasts and bone formation by osteoblasts. Genetic studies have linked the gene coding for low-density lipoprotein receptor-related protein1(Lrp1) to bone traits but whether these associations are based on a causal molecular relationship is unknown. Here, we show that Lrp1 in osteoblasts is a novel regulator of osteoclast activity and bone mass.Mice lacking Lrp1 specifically in the osteoblast lineage displayed normal osteoblast function but severe osteoporosis due to highly increased osteoclast numbers and bone resorption. Osteoblast Lrp1 limited receptor activator of NF-κB ligand(RANKL) expression in vivo and in vitro through attenuation of platelet-derived growth factor(PDGF-BB) signaling. In co-culture, Lrp1-deficient osteoblasts stimulated osteoclastogenesis in a PDGFRβ-dependent manner and in vivo treatment with the PDGFR tyrosine kinase inhibitor imatinib mesylate limited RANKL production and led to complete remission of the osteoporotic phenotype. These results identify osteoblast Lrp1 as a key regulator of osteoblast-to-osteoclast communication and bone mass through a PDGF–RANKL signaling axis in osteoblasts and open perspectives to further explore the potential of PDGF signaling inhibitors in counteracting bone loss as well as to evaluate the importance of functional LRP1 gene variants in the control of bone mass in humans. | Alexander Bartelt Friederike Behler-Janbeck F.Timo Beil Till Koehne Brigitte Müller Tobias Schmidt Markus Heine Laura Ochs Tayfun Yilmaz Martin Dietrich Jan P.Tuckermann Michael Amling Joachim Herz Thorsten Schinke Joerg Heeren Andreas Niemeier | 2018 | Bone Research2018，6，1： | 5 |
| 2 | 面向可持续的渔业补贴:共同渔业政策进入新一轮改革显示文摘本文为德国不来梅大学欧洲环境法规研究中心Till Markus发表在Marine Policy 2010年第34卷1117-1124页文章的中译文。2009年4月22日,欧洲委员会发布了'共同渔业政策改革绿皮书',指出该政策的一个矛盾,一方面对渔业领域的公共财政资助是重要的,另一方面这些资助常常与其他共同渔业政策(Common Fishery Policy,CFP)目标,特别是减少生产能力过剩的目标相冲突。文章提供了一种更好理解补贴影响的分析框架,以及对CFP下的基金计划总体评述,旨在解答欧洲委员会在绿皮书中提出的一些问题。问题的解答基于2种观点:海洋捕捞资源的开发最终依赖于可获得的鱼类种群水平,大量的补贴通过刺激投资动机使鱼类资源压力增大。忽视这种趋势的政策导致了无效和不可持续的捕捞以及公共基金的不公分配。虽然近年来CFP下的援助计划有所改观,但仍存在一些问题。未来对渔业的资助必需朝着可持续和有效利用的方向改革。文章对于了解欧盟的渔业补贴政策、增强渔业补贴经济学评价以及促进我国'强渔惠渔'政策的制定与实施等具有一定的参考意义。 | 林锡坤 Till Markus | 2010 | 中国渔业经济2010，，6： | 4 |
| 3 | Reduced anoctamin 7(ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer显示文摘Objective:Anoctamin 7(ANO7)is a calcium2+-dependent chloride ion channel protein.Its expression is restricted to prostate epithelial cells.The exact function is unknown.This study aimed to analyze ANO7 expression and its clinical significance in prostate cancer(PCa).Methods:ANO7 expression was assessed by immunohistochemistry in 17,747 clinical PCa specimens.Results:ANO7 was strongly expressed in normal prostate glandular cells but often less abundant in cancer cells.ANO7 staining was interpretable in 13,594 cancer tissues and considered strong in 34.4%,moderate in 48.7%,weak in 9.3%,and negative in 7.6%.Reduced staining was tightly linked to adverse tumor features[high classical and quantitative Gleason grade,lymph node metastasis,advanced tumor stage,high Ki67 labeling index,positive surgical margin,and early biochemical recurrence(P<0.0001 each)].The univariate Cox hazard ratio for prostate-specific antigen(PSA)recurrence after prostatectomy in patients with negative vs.strong ANO7 expression was 2.98(95%confidence interval 2.61–3.38).The prognostic impact was independent of established pre-or postoperatively available parameters(P<0.0001).Analysis of annotated molecular data showed that low ANO7 expression was linked to TMPRSS2:ERG fusions(P<0.0001),elevated androgen receptor expression(P<0.0001),as well as presence of 9 of 11 chromosomal deletions(P<0.05 each).A particularly strong association of low ANO7 expression with phosphatase and tensin homolog(PTEN)deletion may indicate a functional relationship with the PTEN/AKT pathway.Conclusions:These data identify reduced ANO7 protein expression as a strong and independent predictor of poor prognosis in PCa.ANO7 measurement,either alone or in combination,might provide clinically useful prognostic information in PCa. | Andreas Marx Lena Koopmann Doris Hoflmayer Franziska Büscheck Claudia Hube-Magg Stefan Steurer Till Eichenauer Till S.Clauditz Waldemar Wilczak Ronald Simon Guido Sauter Jakob R.Izbicki Hartwig Huland Hans Heinzer Markus Graefen Alexander Haese Thorsten Schlomm Christian Bernreuther Patrick Lebok Sarah Bonk | 2021 | Cancer Biology & Medicine2021，18，1： | 3 |
| 4 | Legal Implementation of Integrated Ocean Policies: The EU's Marine Strategy Framework Directive显示文摘 | Till Markus Sabine Schlacke Nina Maier | 2011 | Marine and Coastal Law2011，26，： | 1 |
| 5 | Genetic dissection of Pax6 dosage requirements in the developing mouse eye显示文摘 | Noa DS Tomer K Varda OK Till M Markus K Ernst RT | 2005 | Hum Mol Genet2005，14，15： | 1 |
| 6 | Loss of PSP94 expression is associated with early PSA recurrence and deteriorates outcome of PTEN deleted prostate cancers显示文摘Objective: Prostate secretory protein of 94 amino acids(PSP94) is a target gene of the EZH2 transcriptional repressor and is often downregulated in prostate cancer;however, its prognostic value is disputed.Methods: Immunohistochemical analysis of a tissue microarray of 12, 432 prostate cancer specimens was performed to evaluate PSP94 expression. Correlation of PSP94 expression with tumor phenotype, patient prognosis, TMPRSS2:ERG fusion status, EZH2 expression and PTEN deletion was studied.Results: PSP94 expression was increased in benign prostatic hyperplasia;however, it was downregulated in 48% and negative in42% of the 9, 881 interpretable prostate cancer specimens. The loss of PSP94 expression was inversely correlated to EZH2 expression(P < 0.0001) and largely unrelated to the ERG status, but strongly correlated with high Gleason grade, advanced tumor stage, and nodal metastasis(P <0.0001 each). The fraction of PSP94-negative cancer specimens increased from 40% in pT2 to 52%in pT3 b-pT4(P < 0.0001) and from 40% in Gleason 3+3 = 6 to 46% in Gleason 4+3 = 7 and 60% in Gleason ≥4+4 = 8(P <0.0001). Loss of PSP94 was linked to early prostate-specific antigen recurrence, but with little absolute effect(P < 0.0001).However, it provided additional prognostic impact in cancer specimens with PTEN deletion. Loss of PSP94 deteriorated prognosis of cancer patients with PTEN deletion by more than 10%(P < 0.0001). The combination of PTEN deletion and PSP94 loss provided independent prognostic information that was observed in several subgroups defined by classical and quantitative Gleason grade.Conclusions: The results of our study suggest that combined PSP94/PTEN analysis can be potentially used in the clinical prognosis of prostate cancer. | Andreas M. Luebke Ali Attarchi-Tehrani Jan Meiners Claudia Hube-Magg Dagmar S. Lang Martina Kluth Maria Christina Tsourlakis Sarah Minner Ronald Simon Guido Sauter Franziska Buscheck Frank Jacobsen Andrea Hinsch Stefan Steurer Thorsten Schlomm Hartwig Huland Markus Graefen Alexander Haese Hans Heinzer Till S. Clauditz Eike Burandt Waldemar Wilczak Doris Hoflmayer | 2019 | Cancer Biology & Medicine2019，16，2： | 1 |
| 7 | Enriching plant diversity in grasslands by large-scale experimental sward disturbance and seed addition along gradients of land-use intensity显示文摘Aims The relationship between biodiversity and ecosystem functioning is among the most active areas of ecological research.Furthermore,enhancing the diversity of degraded ecosystems is a major goal in applied restoration ecology.In grasslands,many species may be locally absent due to dispersal or microsite limitation and may therefore profit from mechanical disturbance of the resident vegeta-tion.We established a seed addition and disturbance experiment across several grassland sites of different land use to test whether plant diversity can be increased in these grasslands.Additionally,the experiment will allow us testing the consequences of increased plant diversity for ecosystem processes and for the diversity of other taxa in real-world ecosystems.Here,we present details of the experimen-tal design and report results from the first vegetation survey 1 year after disturbance and seed addition.Moreover,we tested whether the effects of seed addition and disturbance varied among grassland depending on their land use or pre-disturbance plant diversity.Methods A full-factorial experiment was installed in 73 grasslands in three regions across Germany.Grasslands were under regular agricul-tural use,but varied in the type and the intensity of management,thereby representing the range of management typical for large parts of Central Europe.The disturbance treatment consisted of disturbing the top 10 cm of the sward using a rotavator or rotary harrow.Seed addition consisted of sowing a high-diversity seed mixture of regional plant species.These species were all regionally present,but often locally absent,depending on the resident vegetation composi-tion and richness of each grassland.Important Findings Seven months after sward disturbance,respective plots had significantly increased in bare soil,seedling species richness and number of seed-lings.Seed addition had increased plant species richness,but only in combination with sward disturbance.The increase in species richness,when both seed addition and disturbance was applied,was higher at high land-use intensity and low resident diversity.Thus,we show that at least the early recruitment of many species is possible also at high land-use intensity,indicating the potential to restore and enhance bio-diversity of species-poor agricultural grasslands.Our newly established experiment provides a unique platform for broad-scale research on the land-use dependence of future trajectories of vegetation diversity and composition and their effects on ecosystem functioning. | Valentin H.Klaus Deborah Schäfer Till Kleinebecker Markus Fischer Daniel Prati Norbert Hölzel | 2017 | Journal of Plant Ecology2017，10，4： | 0 |
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