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- E-Finance Lab e.V. (1)
Liebers, Nora ; Düll, Johannes ; Fitzgerald, Donnacha ; Kerkhoff, Andrea ; Nörenberg, Daniel ; Käbisch, Eva ; Acker, Fabian ; Fuhrmann, Stephan ; Leng, Corinna ; Welslau, Manfred ; Chemnitz, Jens ; Middeke, Jan Moritz ; Weber, Thomas ; Holtick, Udo ; Trappe, Ralf Ulrich ; Pfannes, Roald ; Liersch, Rüdiger ; Spoer, Christian ; Fuxius, Stefan ; Gebauer, Niklas ; Caillé, Léandra ; Geer, Thomas ; Könecke, Christian ; Keller, Ulrich ; Claus, Rainer ; Mougiakakos, Dimitrios ; Mayer, Stephanie ; Hüttmann, Andreas ; Pott, Christiane ; Trummer, Arne ; Wulf, Gerald ; Brunnberg, Uta ; Bullinger, Lars ; Heß, Georg ; Müller-Tidow, Carsten ; Glaß, Bertram ; Lenz, Georg ; Dreger, Peter ; Dietrich, Sascha
The antibody-drug conjugate polatuzumab vedotin (pola) has recently been approved in combination with bendamustine and rituximab (pola-BR) for patients with refractory or relapsed (r/r) large B-cell lymphoma (LBCL). To investigate the efficacy of pola-BR in a real-world setting, we retrospectively analyzed 105 patients with LBCL who were treated in 26 German centers under the national compassionate use program. Fifty-four patients received pola as a salvage treatment and 51 patients were treated with pola with the intention to bridge to chimeric antigen receptor (CAR) T-cell therapy (n = 41) or allogeneic hematopoietic cell transplantation (n = 10). Notably, patients in the salvage and bridging cohort had received a median of 3 prior treatment lines. In the salvage cohort, the best overall response rate was 48.1%. The 6-month progression-free survival and overall survival (OS) was 27.7% and 49.6%, respectively. In the bridging cohort, 51.2% of patients could be successfully bridged with pola to the intended CAR T-cell therapy. The combination of pola bridging and successful CAR T-cell therapy resulted in a 6-month OS of 77.9% calculated from pola initiation. Pola vedotin-rituximab without a chemotherapy backbone demonstrated encouraging overall response rates up to 40%, highlighting both an appropriate alternative for patients unsuitable for chemotherapy and a new treatment option for bridging before leukapheresis in patients intended for CAR T-cell therapy. Furthermore, 7 of 12 patients with previous failure of CAR T-cell therapy responded to a pola-containing regimen. These findings suggest that pola may serve as effective salvage and bridging treatment of r/r LBCL patients.
Ablikim, Medina ; Achasov, Mikhail N. ; Adlarson, Patrik ; Ahmed, Samer ; Albrecht, Malte ; Aliberti, Riccardo ; Amoroso, Antonio ; An, M. R. ; An, Q. ; Bai, X. H. ; Bai, Yu ; Bakina, Olga ; Baldini Ferroli, Rinaldo ; Balossino, Ilaria ; Ban, Yong ; Begzsuren, Khurelbaatar ; Berger, Niklaus ; Bertani, Monica ; Bettoni, Diego ; Bianchi, Fabrizio ; Bloms, Johannes ; Bortone, Alberto ; Boyko, Igor R. ; Briere, Roy A. ; Cai, H. ; Cai, X. ; Calcaterra, Alessandro ; Cao, G. F. ; Cao, N. ; Çetin, Serkant Ali ; Chang, Jinfan ; Chang, W. L. ; Chelkov, Gueorgui A. ; Chen, D. Y. ; Chen, G. ; Chen, Hesheng ; Chen, M. L. ; Chen, S. J. ; Chen, X. R. ; Chen, Yuanbo ; Chen, Z. J. ; Cheng, W. S. ; Cibinetto, Gianluigi ; Cossio, Fabio ; Cui, X. F. ; Dai, Hongliang ; Dai, Xinchen ; Dbeyssi, Alaa ; Boer, Remco E. de ; Dedovich, Dmitri V. ; Deng, Ziyan ; Denig, Achim ; Denysenko, Igor ; Destefanis, Marco Giovanni Maria ; De Mori, Francesca ; Ding, Y. ; Dong, C. ; Dong, J. ; Dong, Liaoyuan ; Dong, Mingyi ; Dong, X. ; Du, Shuxian ; Fan, Y. L. ; Fang, J. ; Fang, Shuangshi ; Fang, Y. ; Farinelli, Riccardo ; Fava, Luciano ; Feldbauer, Florian ; Felici, Giulietto ; Feng, C. Q. ; Feng, J. H. ; Fritsch, Miriam ; Fu, Chengdong ; Gao, Y. ; Gao, Y. ; Gao, Y. ; Gao, Y. G. ; Garzia, I. ; Ge, P. T. ; Geng, C. ; Gersabeck, Evelina ; Gilman, A. ; Goetzen, Klaus ; Gong, L. ; Gong, Wenxuan ; Gradl, Wolfgang ; Greco, M. ; Gu, L. M. ; Gu, Minhao ; Gu, S. ; Gu, Y. T. ; Guan, C. Y. ; Guo, Aiqiang ; Guo, L. B. ; Guo, R. P. ; Guo, Yuping ; Guskov, Alexey ; Han, T. T. ; Han, W. Y. ; Hao, Xiqing ; Harris, F. A. ; Hüsken, Nils ; He, K. L. ; Heinsius, Fritz-Herbert ; Heinz, C. H. ; Held, T. ; Heng, Yuekun ; Herold, Christoph ; Himmelreich, Mathilde ; Holtmann, Tobias ; Hou, G. Y. ; Hou, Y. R. ; Hou, Zhilong ; Hu, Haiming ; Hu, J. F. ; Hu, T. ; Hu, Y. ; Huang, G. S. ; Huang, L. Q. ; Huang, X. T. ; Huang, Y. P. ; Huang, Z. ; Hussain, Tahir ; Ikegami Andersson, Walter ; Imoehl, William ; Irshad, M. ; Jaeger, S. ; Janchiv, S. ; Ji, Quan ; Ji, Qingping ; Ji, X. B. ; Ji, X. L. ; Ji, Y. Y. ; Jiang, H. B. ; Jiang, Xiaoshan ; Jiao, J. B. ; Jiao, Z. ; Jin, Shan ; Jin, Y. ; Jing, M. Q. ; Johansson, Tord ; Kalantar-Nayestanaki, Nasser ; Kang, X. S. ; Kappert, Rosa ; Kavatsyuk, Myroslav O. ; Ke, B. C. ; Keshk, I. K. ; Khoukaz, Alfons ; Kiese, P. ; Kiuchi, R. ; Kliemt, Ralf ; Koch, L. ; Kolcu, O. B. ; Kopf, Bertram ; Kuemmel, M. ; Kuessner, M. ; Kupsc, Andrzej ; Kurth, M. G. ; Kühn, Wolfgang ; Lane, John Jake ; Lange, Jens Sören ; Larin, P. ; Lavania, Anita ; Lavezzi, Lia ; Lei, Z. H. ; Leithoff, H. ; Lellmann, Max ; Lenz, Thomas ; Li, C. ; Li, C. H. ; Li, C. ; Li, D. M. ; Li, F. ; Li, G. ; Li, H. ; Li, H. ; Li, Haibo ; Li, H. J. ; Li, J. L. ; Li, J. Q. ; Li, J. S. ; Li, K. ; Li, L. K. ; Li, L. ; Li, P. R. ; Li, S. Y. ; Li, Weidong ; Li, Weiguo ; Li, X. H. ; Li, X. L. ; Li, X. ; Li, Z. Y. ; Liang, H. ; Liang, H. ; Liang, H. ; Liang, Y. F. ; Liang, Y. T. ; Liao, G. R. ; Liao, L. Z. ; Libby, J. ; Lin, C. X. ; Liu, B. J. ; Liu, C. X. ; Liu, D. ; Liu, Fu-Hu ; Liu, F. ; Liu, F. ; Liu, H. B. ; Liu, H. M. ; Liu, H. ; Liu, H. ; Liu, J. B. ; Liu, J. L. ; Liu, J. Y. ; Liu, K. ; Liu, K. Y. ; Liu, L. ; Liu, M. H. ; Liu, P. L. ; Liu, Q. ; Liu, Q. ; Liu, S. B. ; Liu, S. ; Liu, T. ; Liu, W. M. ; Liu, X. ; Liu, Y. ; Liu, Y. B. ; Liu, Zhen-An ; Liu, Z. Q. ; Lou, Xinchou ; Lu, F. X. ; Lu, H. J. ; Lu, J. D. ; Lu, Junguang ; Lu, X. L. ; Lu, Y. ; Lu, Yunpeng ; Luo, Chenglin ; Luo, M. X. ; Luo, P. W. ; Luo, T. ; Luo, X. L. ; Lyu, Xiao-Rui ; Ma, Fengcai ; Ma, H. L. ; Ma, Lianliang ; Ma, M. M. ; Ma, Qiumei ; Ma, R. Q. ; Ma, R. T. ; Ma, X. X. ; Ma, Xiaoyan ; Maas, Frank E. ; Maggiora, Marco ; Maldaner, Stephan ; Malde, Sneha ; Malik, Qadeer Afzal ; Mangoni, Alessio ; Mao, Yajun ; Mao, Zepu ; Marcello, Simonetta ; Meng, Z. X. ; Messchendorp, Johannes Gerhardus ; Mezzadri, Giulio ; Min, T. J. ; Mitchell, Ryan Edward ; Mo, Xiaohu ; Mo, Y. J. ; Muchnoi, Nikolai Yu. ; Muramatsu, H. ; Nakhoul, S. ; Nefedov, Yury ; Nerling, Frank ; Nikolaev, Ivan Borisovich ; Ning, Z. ; Nisar, Shabana ; Olsen, Stephen L. ; Ouyang, Qun ; Pacetti, Simone ; Pan, X. ; Pan, Y. ; Pathak, A. ; Patteri, P. ; Pelizäus, Marc ; Peng, H. P. ; Peters, Klaus ; Pettersson, J. ; Ping, J. L. ; Ping, R. G. ; Poling, Ronald ; Prasad, Vindhyawasini ; Qi, H. ; Qi, H. R. ; Qi, K. H. ; Qi, Ming ; Qi, T. Y. ; Qian, S. ; Qian, W.B. ; Qian, Z. ; Qiao, Congfeng ; Qin, L.Q. ; Qin, X.P. ; Qin, X.S. ; Qin, Zhonghua ; Qiu, Jinfa ; Qu, S.Q. ; Rashid, K.H. ; Ravindran, Krishnakumar ; Redmer, Christoph Florian ; Rivetti, Angelo ; Rodin, Viktor ; Da Rocha Rolo, Manuel Dionisio ; Rong, Gang ; Rosner, Christoph ; Rump, Marcel Andre ; Sang, H.S. ; Sarantsev, Andrei V. ; Schelhaas, Yasemin ; Schnier, Claudius ; Schönning, Karin ; Scodeggio, Marco ; Shan, D.C. ; Shan, Wei ; Shan, Xinyu ; Shangguan, J.F. ; Shao, M. ; Shen, C.P. ; Shen, H.F. ; Shen, P.X. ; Shen, X.Y. ; Shi, H.C. ; Shi, R.S. ; Shi, X. ; Shi, X.D. ; Song, J.J. ; Song, W.M. ; Song, Y.X. ; Sosio, Stefano ; Spataro, Stefano ; Su, K.X. ; Su, P.P. ; Sui, F.F. ; Sun, Gongxing ; Sun, H.K. ; Sun, J.F. ; Sun, L. ; Sun, S.S. ; Sun, T. ; Sun, W.Y. ; Sun, W.Y. ; Sun, X. ; Sun, Y.J. ; Sun, Y.K. ; Sun, Y.Z. ; Sun, Z.T. ; Tan, Y.H. ; Tan, Y.X. ; Tang, C.J. ; Tang, G.Y. ; Tang, J. ; Teng, J.X. ; Thoren, Viktor ; Tian, W.H. ; Tian, Y.T. ; Uman, Ismail ; Wang, B. ; Wang, C.W. ; Wang, D.Y. ; Wang, H.J. ; Wang, H.P. ; Wang, K. ; Wang, L.L. ; Wang, M. ; Wang, M.Z. ; Wang, M. ; Wang, W. ; Wang, W.H. ; Wang, W.P. ; Wang, X. ; Wang, X.F. ; Wang, X.L. ; Wang, Y. ; Wang, Y. ; Wang, Y.D. ; Wang, Y.F. ; Wang, Y.Q. ; Wang, Y.Y. ; Wang, Z. ; Wang, Zongyuan ; Wang, Z. ; Wang, Z. ; Wei, D.H. ; Weidner, Frederik ; Wen, Shuopin ; White, D.J. ; Wiedner, Ulrich ; Wilkinson, G. ; Wolke, Magnus ; Wollenberg, Leonard ; Wu, J.F. ; Wu, L.H. ; Wu, L.J. ; Wu, X. ; Wu, Z. ; Xia, Lei ; Xiao, H. ; Xiao, S.Y. ; Xiao, Zhenjun ; Xie, X.H. ; Xie, Y.G. ; Xie, Y.H. ; Xing, T.Y. ; Xu, Guofa ; Xu, Q.J. ; Xu, W. ; Xu, Xinping ; Xu, Y.C. ; Yan, F. ; Yan, L. ; Yan, W.B. ; Yan, W.C. ; Yan, X. ; Yang, H.J. ; Yang, Hongxun ; Yang, L. ; Yang, S.L. ; Yang, Yongxu ; Yang, Y. ; Yang, Z. ; Ye, M. ; Ye, Minghan ; Yin, J.H. ; You, Z.Y. ; Yu, Boxiang ; Yu, C.X. ; Yu, G. ; Yu, J.S. ; Yu, T. ; Yuan, Chang-Zheng ; Yuan, L. ; Yuan, X.Q. ; Yuan, Y. ; Yuan, Z.Y. ; Yue, C.X. ; Yuncu, A. ; Zafar, A.A. ; Zeng, X. ; Zeng, Y. ; Zhang, A. Q. ; Zhang, B. X. ; Zhang, G. ; Zhang, H. ; Zhang, H.H. ; Zhang, H.H. ; Zhang, Hongyu ; Zhang, J.J. ; Zhang, J.L. ; Zhang, J.Q. ; Zhang, J.W. ; Zhang, Jianyong ; Zhang, J.Z. ; Zhang, J. ; Zhang, J. ; Zhang, L.M. ; Zhang, L.Q. ; Zhang, L. ; Zhang, S. ; Zhang, S.F. ; Zhang, S. ; Zhang, X.D. ; Zhang, X.Y. ; Zhang, Y. ; Zhang, Y.H. ; Zhang, Y.T. ; Zhang, Y. ; Zhang, Y. ; Zhang, Y. ; Zhang, Z.H. ; Zhang, Z.Y. ; Zhao, G. ; Zhao, J. ; Zhao, J.Y. ; Zhao, J.Z. ; Zhao, L. ; Zhao, L. ; Zhao, Ming-Gang ; Zhao, Q. ; Zhao, Shujun ; Zhao, Yubin ; Zhao, Y.X. ; Zhao, Zhengguo ; Zhemchugov, Alexey ; Zheng, B. ; Zheng, Jianping ; Zheng, Y. ; Zheng, Y.H. ; Zhong, B. ; Zhong, C. ; Zhou, L.P. ; Zhou, Q. ; Zhou, X. ; Zhou, X.K. ; Zhou, X.R. ; Zhou, X.Y. ; Zhu, A.N. ; Zhu, J. ; Zhu, K. ; Zhu, Kejun ; Zhu, S.H. ; Zhu, T.J. ; Zhu, W.J. ; Zhu, W.J. ; Zhu, Y.C. ; Zhu, Zian ; Zou, B.S. ; Zou, Jiaheng
Using 10.1 × 109 J/ψ events produced by the Beijing Electron Positron Collider (BEPCII) at a center-of-mass energy √s = 3.097 GeV and collected with the BESIII detector, we present a search for the rare semi-leptonic decay J/ψ → D−e+νe + c.c. No excess of signal above background is observed, and an upper limit on the branching fraction ℬ(J/ψ → D−e+νe + c. c.) < 7.1 × 10−8 is obtained at 90% confidence level. This is an improvement of more than two orders of magnitude over the previous best limit.
Lenz, Maximilian ; Galanis, Christos ; Müller-Dahlhaus, Florian ; Opitz, Alexander ; Wierenga, Corette ; Szabó, Gábor ; Ziemann, Ulf ; Deller, Thomas ; Funke, Klaus ; Vlachos, Andreas
Repetitive transcranial magnetic stimulation (rTMS) is used as a therapeutic tool in neurology and psychiatry. While repetitive magnetic stimulation (rMS) has been shown to induce plasticity of excitatory synapses, it is unclear whether rMS can also modify structural and functional properties of inhibitory inputs. Here we employed 10-Hz rMS of entorhinohippocampal slice cultures to study plasticity of inhibitory neurotransmission on CA1 pyramidal neurons. Our experiments reveal a rMS-induced reduction in GABAergic synaptic strength (2–4 h after stimulation), which is Ca2+-dependent and accompanied by the remodelling of postsynaptic gephyrin scaffolds. Furthermore, we present evidence that 10-Hz rMS predominantly acts on dendritic, but not somatic inhibition. Consistent with this finding, a reduction in clustered gephyrin is detected in CA1 stratum radiatum of rTMS-treated anaesthetized mice. These results disclose that rTMS induces coordinated Ca2+-dependent structural and functional changes of specific inhibitory postsynapses on principal neurons.
Epilepsy is a complex neurological disorder which can severely affect neuronal function. Some patients may experience status epilepticus, a life-threatening state of ongoing seizure activity associated with postictal cognitive dysfunction. However, the molecular mechanisms by which status epilepticus influences brain function beyond seizure activity remain not well understood. Here, we addressed the question of whether pilocarpine-induced status epilepticus affects synaptopodin (SP), an actin-binding protein, which regulates the ability of neurons to express synaptic plasticity. This makes SP an interesting marker for epilepsy-associated alterations in synaptic function. Indeed, single dose intraperitoneal pilocarpine injection (250 mg/kg) in three-month-old male C57BL/6J mice leads to a rapid reduction in hippocampal SP-cluster sizes and numbers (in CA1 stratum radiatum of the dorsal hippocampus; 90 min after injection). In line with this observation (and previous work using SP-deficient mice), a defect in the ability to induce long-term potentiation (LTP) of Schaffer collateral-CA1 synapses is observed. Based on these findings we propose that status epilepticus could exert its aftereffects on cognition at least in part by perturbing SP-dependent mechanisms of synaptic plasticity.
Dummann, Wolf ; Steinig, Sebastian ; Hofmann, Peter ; Lenz, Matthias ; Kusch, Stephanie ; Flögel, Sascha ; Herrle, Jens Olaf ; Hallmann, Christian ; Rethemeyer, Janet ; Kasper, Haino Uwe ; Wagner, Thomas
Extensive black shale deposits formed in the Early Cretaceous South Atlantic, supporting the notion that this emerging ocean basin was a globally important site of organic carbon burial. The magnitude of organic carbon burial in marine basins is known to be controlled by various tectonic, oceanographic, hydrological, and climatic processes acting on different temporal and spatial scales, the nature and relative importance of which are poorly understood for the young South Atlantic. Here we present new bulk and molecular geochemical data from an Aptian–Albian sediment record recovered from the deep Cape Basin at Deep Sea Drilling Project (DSDP) Site 361, which we combine with general circulation model results to identify driving mechanisms of organic carbon burial. A multimillion-year decrease (i.e., Early Aptian–Albian) in organic carbon burial, reflected in a lithological succession of black shale, gray shale, and red beds, was caused by increasing bottom water oxygenation due to abating hydrographic restriction via South Atlantic–Southern Ocean gateways. These results emphasize basin evolution and ocean gateway development as a decisive primary control on enhanced organic carbon preservation in the Cape Basin at geological timescales (> 1 Myr). The Early Aptian black shale sequence comprises alternations of shales with high (> 6 %) and relatively low (∼ 3.5 %) organic carbon content of marine sources, the former being deposited during the global Oceanic Anoxic Event (OAE) 1a, as well as during repetitive intervals before and after OAE 1a. In all cases, these short-term intervals of enhanced organic carbon burial coincided with strong influxes of sediments derived from the proximal African continent, indicating closely coupled climate–land–ocean interactions. Supported by our model results, we show that fluctuations in weathering-derived nutrient input from the southern African continent, linked to changes in orbitally driven humidity and aridity, were the underlying drivers of repetitive episodes of enhanced organic carbon burial in the deep Cape Basin. These results suggest that deep marine environments of emerging ocean basins responded sensitively and directly to short-term fluctuations in riverine nutrient fluxes. We explain this relationship using the lack of wide and mature continental shelf seas that could have acted as a barrier or filter for nutrient transfer from the continent into the deep ocean.
Dummann, Wolf ; Steinig, Sebastian ; Hofmann, Peter ; Lenz, Matthias ; Kusch, Stephanie ; Flögel, Sascha ; Herrle, Jens Olaf ; Hallmann, Christian ; Rethemeyer, Janet ; Kasper, Haino Uwe ; Wagner, Thomas
Extensive black shale deposits formed in the Early Cretaceous South Atlantic, supporting the notion that this emerging ocean basin was a globally important site of organic carbon burial. The magnitude of organic carbon burial in marine basins is known to be controlled by various tectonic, oceanographic, hydrological, and climatic processes acting on different temporal and spatial scales, the nature and relative importance of which are poorly understood for the young South Atlantic. Here we present new bulk and molecular geochemical data from an Aptian–Albian sediment record recovered from the deep Cape Basin at Deep Sea Drilling Project (DSDP) Site 361, which we combine with general circulation model results to identify driving mechanisms of organic carbon burial. A multi-million year decrease (i.e. Early Aptian–Albian) in organic carbon burial, reflected in a lithological succession of black shale, gray shale, and red beds, was caused by increasing bottom water oxygenation due to abating tectonic restriction via South Atlantic-Southern Ocean gateways. These results emphasize basin evolution and ocean gateway development as a decisive primary control on enhanced organic carbon preservation in the Cape Basin at geological time scales (>1 Myr). The Early Aptian black shale sequence comprises alternations of shales with high (>5%) and relatively low (~3%) organic carbon content of marine sources, the former being deposited during the global Oceanic Anoxic Event (OAE) 1a, as well as during repetitive events before and after OAE 1a. In all cases, these short-term events of enhanced organic carbon burial coincided with strong influxes of sediments derived from the proximal African continent, indicating closely coupled climate–land–ocean interactions. Supported by our model results, we propose that fluctuations in weathering-derived nutrient input from the southern African continent, linked to fluctuations in pCO2 and/or orbitally driven humidity/aridity, were the underlying drivers of short-term organic carbon burial in the deep Cape Basin. These results suggest that deep marine environments of emerging ocean basins responded sensitively and directly to short term fluctuations in riverine nutrient fluxes. We explain this relationship by the lack of wide and mature continental shelf seas that could have acted as a barrier or filter for nutrient transfer from the continent into the deep ocean.
Lenz, Maximilian ; Eichler, Amelie ; Kruse, Pia ; Strehl, Andreas ; Rodriguez-Rozada, Silvia ; Goren, Itamar ; Yogev, Nir ; Frank, Stefan ; Waisman, Ari ; Deller, Thomas ; Jung, Steffen ; Maggio, Nicola ; Vlachos, Andreas
Systemic inflammation is associated with alterations in complex brain functions such as learning and memory. However, diagnostic approaches to functionally assess and quantify inflammation-associated alterations in synaptic plasticity are not well-established. In previous work, we demonstrated that bacterial lipopolysaccharide (LPS)-induced systemic inflammation alters the ability of hippocampal neurons to express synaptic plasticity, i.e., the long-term potentiation (LTP) of excitatory neurotransmission. Here, we tested whether synaptic plasticity induced by repetitive magnetic stimulation (rMS), a non-invasive brain stimulation technique used in clinical practice, is affected by LPS-induced inflammation. Specifically, we explored brain tissue cultures to learn more about the direct effects of LPS on neural tissue, and we tested for the plasticity-restoring effects of the anti-inflammatory cytokine interleukin 10 (IL10). As shown previously, 10 Hz repetitive magnetic stimulation (rMS) of organotypic entorhino-hippocampal tissue cultures induced a robust increase in excitatory neurotransmission onto CA1 pyramidal neurons. Furthermore, LPS-treated tissue cultures did not express rMS-induced synaptic plasticity. Live-cell microscopy in tissue cultures prepared from a novel transgenic reporter mouse line [C57BL/6-Tg(TNFa-eGFP)] confirms that ex vivo LPS administration triggers microglial tumor necrosis factor alpha (TNFα) expression, which is ameliorated in the presence of IL10. Consistent with this observation, IL10 hampers the LPS-induced increase in TNFα, IL6, IL1β, and IFNγ and restores the ability of neurons to express rMS-induced synaptic plasticity in the presence of LPS. These findings establish organotypic tissue cultures as a suitable model for studying inflammation-induced alterations in synaptic plasticity, thus providing a biological basis for the diagnostic use of transcranial magnetic stimulation in the context of brain inflammation.
Hildebrandt-Einfeldt, Lars ; Yap, Kenrick ; Paul, Mandy H. ; Stoffer, Carolin ; Zahn, Nadine ; Drakew, Alexander ; Lenz, Maximilian ; Vlachos, Andreas ; Deller, Thomas
The entorhino-dentate projection, i.e., the perforant pathway, terminates in a highly ordered and laminated fashion in the rodent dentate gyrus (DG): fibers arising from the medial entorhinal cortex (MEC) terminate in the middle molecular layer, whereas fibers arising from the lateral entorhinal cortex (LEC) terminate in the outer molecular layer of the DG. In rats and rabbits, a crossed entorhino-dentate projection exists, which originates from the entorhinal cortex (EC) and terminates in the contralateral DG. In contrast, in mice, such a crossed projection is reportedly absent. Using single and double mouse organotypic entorhino-hippocampal slice cultures, we studied the ipsi- and crossed entorhino-dentate projections. Viral tracing revealed that entorhino-dentate projections terminate with a high degree of lamina-specificity in single as well as in double cultures. Furthermore, in double cultures, entorhinal axons arising from one slice freely intermingled with entorhinal axons originating from the other slice. In single as well as in double cultures, entorhinal axons exhibited a correct topographical projection to the DG: medial entorhinal axons terminated in the middle and lateral entorhinal axons terminated in the outer molecular layer. Finally, entorhinal neurons were virally transduced with Channelrhodopsin2-YFP and stimulated with light, revealing functional connections between the EC and dentate granule cells. We conclude from our findings that entorhino-dentate projections form bilaterally in the mouse hippocampus in vitro and that the mouse DG provides a permissive environment for crossed entorhinal fibers.
Bohnenberger, Hanibal ; Ströbel, Philipp ; Mohr, Sebastian ; Corso, Jasmin ; Berg, Tobias ; Urlaub, Henning ; Lenz, Christof ; Serve, Hubert ; Oellerich, Thomas
In-depth analyses of cancer cell proteomes are needed to elucidate oncogenic pathomechanisms, as well as to identify potential drug targets and diagnostic biomarkers. However, methods for quantitative proteomic characterization of patient-derived tumors and in particular their cellular subpopulations are largely lacking. Here we describe an experimental set-up that allows quantitative analysis of proteomes of cancer cell subpopulations derived from either liquid or solid tumors. This is achieved by combining cellular enrichment strategies with quantitative Super-SILAC-based mass spectrometry followed by bioinformatic data analysis. To enrich specific cellular subsets, liquid tumors are first immunophenotyped by flow cytometry followed by FACS-sorting; for solid tumors, laser-capture microdissection is used to purify specific cellular subpopulations. In a second step, proteins are extracted from the purified cells and subsequently combined with a tumor-specific, SILAC-labeled spike-in standard that enables protein quantification. The resulting protein mixture is subjected to either gel electrophoresis or Filter Aided Sample Preparation (FASP) followed by tryptic digestion. Finally, tryptic peptides are analyzed using a hybrid quadrupole-orbitrap mass spectrometer, and the data obtained are processed with bioinformatic software suites including MaxQuant. By means of the workflow presented here, up to 8,000 proteins can be identified and quantified in patient-derived samples, and the resulting protein expression profiles can be compared among patients to identify diagnostic proteomic signatures or potential drug targets.
Ablikim, Medina ; Achasov, Mikhail N. ; Adlarson, Patrik ; Ahmed, Samer ; Albrecht, Malte ; Aliberti, Riccardo ; Amoroso, Antonio ; An, M. R. ; An, Q. ; Bai, X. H. ; Bai, Yu ; Bakina, Olga ; Baldini Ferroli, Rinaldo ; Balossino, Ilaria ; Ban, Yong ; Begzsuren, Khurelbaatar ; Berger, Niklaus ; Bertani, Monica ; Bettoni, Diego ; Bianchi, Fabrizio ; Biernat, Jacek ; Bloms, Johannes ; Bortone, Alberto ; Boyko, Igor R. ; Briere, Roy A. ; Cai, H. ; Cai, X. ; Calcaterra, Alessandro ; Cao, G. F. ; Cao, N. ; Çetin, Serkant Ali ; Chang, Jinfan ; Chang, W. L. ; Chelkov, Gueorgui A. ; Chen, D. Y. ; Chen, G. ; Chen, Hesheng ; Chen, M. L. ; Chen, S. J. ; Chen, X. R. ; Chen, Yuanbo ; Chen, Z. J. ; Cheng, W. S. ; Cibinetto, Gianluigi ; Cossio, Fabio ; Cui, X. F. ; Dai, Hongliang ; Dai, Xinchen ; Dbeyssi, Alaa ; Boer, Remco E. de ; Dedovich, Dmitri V. ; Deng, Ziyan ; Denig, Achim ; Denysenko, Igor ; Destefanis, Marco Giovanni Maria ; De Mori, Francesca ; Ding, Y. ; Dong, C. ; Dong, J. ; Dong, Liaoyuan ; Dong, Mingyi ; Dong, X. ; Du, Shuxian ; Fan, Y. L. ; Fang, J. ; Fang, Shuangshi ; Fang, Y. ; Farinelli, Riccardo ; Fava, Luciano ; Feldbauer, Florian ; Felici, Giulietto ; Feng, C. Q. ; Feng, J. H. ; Fritsch, Miriam ; Fu, Chengdong ; Gao, Y. ; Gao, Y. ; Gao, Y. ; Gao, Y. G. ; Garzia, I. ; Ge, P. T. ; Geng, C. ; Gersabeck, Evelina ; Gilman, A. ; Goetzen, Klaus ; Gong, L. ; Gong, Wenxuan ; Gradl, Wolfgang ; Greco, M. ; Gu, L. M. ; Gu, Minhao ; Gu, S. ; Gu, Y. T. ; Guan, C. Y. ; Guo, Aiqiang ; Guo, L. B. ; Guo, R. P. ; Guo, Yuping ; Guskov, Alexey ; Han, T. T. ; Han, W. Y. ; Hansson, J. ; Hao, Xiqing ; Harris, F. A. ; Hüsken, Nils ; He, K. L. ; Heinsius, Fritz-Herbert ; Heinz, C. 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Though immensely successful, the standard model of particle physics does not offer any explanation as to why our Universe contains so much more matter than antimatter. A key to a dynamically generated matter–antimatter asymmetry is the existence of processes that violate the combined charge conjugation and parity (CP) symmetry1. As such, precision tests of CP symmetry may be used to search for physics beyond the standard model. However, hadrons decay through an interplay of strong and weak processes, quantified in terms of relative phases between the amplitudes. Although previous experiments constructed CP observables that depend on both strong and weak phases, we present an approach where sequential two-body decays of entangled multi-strange baryon–antibaryon pairs provide a separation between these phases. Our method, exploiting spin entanglement between the double-strange Ξ− baryon and its antiparticle2 Ξ¯+
, has enabled a direct determination of the weak-phase difference, (ξP − ξS) = (1.2 ± 3.4 ± 0.8) × 10−2 rad. Furthermore, three independent CP observables can be constructed from our measured parameters. The precision in the estimated parameters for a given data sample size is several orders of magnitude greater than achieved with previous methods3. Finally, we provide an independent measurement of the recently debated Λ decay parameter αΛ (refs. 4,5). The ΛΛ¯
asymmetry is in agreement with and compatible in precision to the most precise previous measurement.