ALBERT

Description: Biomaterials employed for neural stimulation, as well as brain/machine interfaces, offer great perspectives to combat neurodegenerative diseases, while application of lab-on-a-chip devices such as multielectrode arrays is a promising alternative to assess neural function in vitro. For bioelectronic monitoring, nanostructured microelectrodes are required, which exhibit an increased surface area where the detection sensitivity is not reduced by the self-impedance of the electrode. In our study, we investigated the interaction of neurons (SH-SY5Y) and glial cells (U-87 MG) with nanocolumnar titanium nitride (TiN) electrode materials in comparison to TiN with larger surface grains, gold, and indium tin oxide (ITO) substrates. Glial cells showed an enhanced proliferation on TiN materials; however, these cells spread evenly distributed over all the substrate surfaces. By contrast, neurons proliferated fastest on nanocolumnar TiN and formed large cell agglomerations. We implemented a radial autocorrelation function of cellular positions combined with various clustering algorithms. These combined analyses allowed us to quantify the largest cluster on nanocolumnar TiN; however, on ITO and gold, neurons spread more homogeneously across the substrates. As SH-SY5Y cells tend to grow in clusters under physiologic conditions, our study proves nanocolumnar TiN as a potential bioactive material candidate for the application of microelectrodes in contact with neurons. To this end, the employed K-means clustering algorithm together with radial autocorrelation analysis is a valuable tool to quantify cell-surface interaction and cell organization to evaluate biomaterials’ performance in vitro.

Description: Outer shelf sedimentary records are promising for determining the recurrence intervals of tsunamis. However, compared to onshore deposits, offshore deposits are more difficult to access, and so far, studies of outer shelf tsunami deposits are scarce. Here, an example of studying these deposits is presented to infer implications for tsunami-related signatures in similar environments and potentially contribute to pre-historic tsunami event detections. A multidisciplinary approach was performed to detect the sedimentary imprints left by the 1755 CE tsunami in two cores, located in the southern Portuguese continental shelf at water depths of 58 and 91 m. Age models based on 14C and 210Pbxs allowed a probable correspondence with the 1755 CE tsunami event. A multi-proxy approach, including sand composition, grain-size, inorganic geochemistry, magnetic susceptibility, and microtextural features on quartz grain surfaces, yielded evidence for a tsunami depositional signature, although only a subtle terrestrial signal is present. A low contribution of terrestrial material to outer shelf tsunami deposits calls for methodologies that reveal sedimentary structures linked to tsunami event hydrodynamics. Finally, a change in general sedimentation after the tsunami event might have influenced the signature of the 1755 CE tsunami in the outer shelf environment.

Description: Viktoria Blumenberg and Maria-Luisa Schubert contributed equally. Introduction: The CD19 specific chimeric antigen receptor (CAR) T-cell products Axicabtagene-Ciloleucel and Tisagenlecleucel are approved for the treatment of refractory/relapsed B-cell precursor ALL (BCP-ALL) and Diffuse Large B-cell lymphoma (DLBCL). Despite high response rates, long term remission is only achieved in a subgroup if patients. In addition, CAR T cell therapy is accompanied by potentially severe immune related toxicities including cytokine release syndrome (CRS) or neurotoxicity (ICANS). Therefore, we need to identify biological mechanisms of treatment resistance and toxicity occurring in the host in addition to improve the CAR T product itself. The impact of the gut microbiome on T-cell based immunotherapies such as checkpoint inhibition or allogeneic hematopoietic stem cell transplant has been shown, but it´s role in mediating anti-tumor responses and the occurrence of immunotoxicities of CAR T-cell therapy has not yet been reported so far. Methods: Patients with r/r BCP-ALL and DLBCL were treated with the commercially available CD19 specific CAR T-cell products Axicabtagene-Ciloleucel or Tisagenlecleucel or in-house manufactured CD19-targeted CD28-4-1BB-CD3ζ CAR T-cells at both our institutions. Fecal biospecimens from 33 patients were collected sequentially before, during and after CAR T transfusion (specific time points: before lymphodepleting chemotherapy, day of CAR T-cell transfusion and in 7 day intervals up to day 28). 16S rRNA sequencing and shotgun metagenome sequencing has been performed on 137 stool samples. Sequencing results and clinical metadata are integrated into a patient-centered "hospitalome" including infections and immunotoxicities as well as concomitant anti-infective, immunosuppressive agents and treatment response. Patients having received any type of anti-infective medication exceeding prophylaxis on the day of CAR T cell transfusion or up to two weeks prior were distinguished from patients without prior anti-infective medication or only receiving anti-infective drugs from day 1 after CAR T-cell transfusion. Results: Patients receiving anti-infectives up to two weeks prior to CAR T-cell transfusion display a significantly lower response rate compared to patients, who have been treated with antibiotic and / or -mycotic treatment after day 0 (Tab. 1). Before CAR T-cell transfusion patients showed a heterogeneous, but largely diverse gut microbial taxa (Shannon index median: 4.2.). After CAR T-cell transfusion the alpha diversity (i.e. within-sample diversity) decreases with the nadir at day 14 (Shannon index, median 2.4), which depended significantly on broad-spectrum antibiotic administration (Fig. 1-2). Furthermore, loss of diversity correlated significantly with the occurrence of CRS (p 30% per sample). The expansion of enterococci was again found in samples of patients, who received antibiotic treatment. Conclusion: The gut microbiome of CAR T-cell patients undergoes large and diverse compositional changes, whereas altered diversity is significantly associated with administration of anti-infectives prior to CAR T-cell transfusion and the occurrence of CRS. The assessment of the gut microbial taxa of CAR T-cell patients might serve as a predictive biomarker for immunotoxicity and, eventually, treatment response. Disclosures Blumenberg: Gilead: Consultancy, Research Funding; Novartis: Research Funding; Celgene: Research Funding. Schubert:Kite / Gilead: Consultancy; Takeda: Consultancy. Buecklein:Amgen: Consultancy; Pfizer: Consultancy; Celgene: Research Funding; Novartis: Research Funding; Gilead: Consultancy, Research Funding. Müller-Tidow:Pfizer: Research Funding, Speakers Bureau; Daiichi Sankyo: Research Funding; BiolineRx: Research Funding; Janssen-Cilag GmbH: Speakers Bureau. Dreger:Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; AstraZeneca: Consultancy; Roche: Consultancy, Speakers Bureau; Neovii: Research Funding; Riemser: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy; Novartis: Consultancy, Speakers Bureau. Schmitt:Apogenix: Research Funding; Hexal: Other: Travel grants , Research Funding; Novartis: Other: educational activities and conferences, Research Funding; Kite: Other: Travel grants, educational activities and conferences; MSD: Membership on an entity's Board of Directors or advisory committees, Other: PI of clinical trials on letermovir; TolerogenixX Ltd: Other: Co-Founder and shareholder. Subklewe:Roche AG: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; AMGEN: Consultancy, Honoraria, Research Funding; Janssen: Consultancy; Pfizer: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria, Research Funding; Seattle Genetics: Research Funding; Morphosys: Research Funding; Celgene: Consultancy, Honoraria.

Description: The spatial distributions of (1) surface sediment characteristics (D0.5, Sediment Surface Area (SSA), Particulate Organic Carbon (POC), Chlorophyll-a (Chl-a), Phaeophytin-a (Phaeo-a), Total and Enzymatically Hydrolyzable Amino Acids (THAA, EHAA), δ13C) and (2) sediment profile image (apparent Redox Potential Discontinuity (aRPD), numbers and depths of biological traces) characteristics were quantified based on the sampling of 32 stations located within the West Gironde Mud Patch (Bay of Biscay, NE Atlantic) in view of (1) assessing the spatial structuration of a temperate river-dominated ocean margin located in a high-energy area, (2) disentangling the impacts of hydrodynamics and bottom trawling on this structuration, and (3) comparing the West Gironde Mud Patch with the Rhône River Prodelta (located in a low-energy area). Results support the subdivision of the West Gironde Mud Patch in a proximal and a distal part and show (1) the existence of depth gradients in surface sedimentary organics characteristics and bioturbation within the distal part; (2) no evidence for a significant effect of bottom trawling, as opposed to Bottom Shear Stress, on the West Gironde Mud Patch spatial structuration; and (3) major discrepancies between spatial structuration in the West Gironde Mud Patch and the Rhône River Prodelta, which were attributed to differences in tidal regimes, sedimentation processes, and local hydrodynamics, which is in agreement with current river-dominated ocean margin typologies.

Description: Paleolimnological reconstructions from the mid and high latitudes in the Southern Hemisphere are still relatively scarce. Anthropogenic impacts have evidenced trophic state changes and an increase in cyanobacterial blooms in the lacustrine system of San Pedro de la Paz in the last decades. Here, we reconstructed primary production and sedimentological changes spanning the past 2500 years in two coastal lakes in Mediterranean Chile. A multiproxy approach including sedimentological, biogenic silica, carbon and nitrogen isotopes and fossil pigments analysis in sediment cores was performed in Laguna Grande (LGSP) and Laguna Chica de San Pedro (LCSP). A marked change in the sedimentology of the lakes, likely related to the terrigenous sediment inputs derived by a transition from an arid condition in the mid-Holocene to a more humid condition in the late Holocene that favoured arboreal forest establishment at 100 BC–AD 150. A period of low primary production was identified between 850 to 1050 AC for LCSP, suggesting moist and cold conditions that were possibly related to La Niña events. In recent decades, there have been increases in primary production, probably resulting from anthropogenic disturbances. These likely include the clearance of native vegetation, the introduction of exotic tree species, and urbanisation, which in turn, resulted in nutrient inputs and hence eutrophication. We conclude that an integrated management program for both lakes is urgently needed.