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  • 1
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    Sedimentological processes and environmental variability at Lake Ohrid (Macedonia, Albania) between 637 ka and the present
    Copernicus GmbH ; 2016
    In:  Biogeosciences Vol. 13, No. 4 ( 2016-02-26), p. 1179-1196
    Details
    In: Biogeosciences, Copernicus GmbH, Vol. 13, No. 4 ( 2016-02-26), p. 1179-1196
    Abstract: Abstract. Lake Ohrid (Macedonia, Albania) is thought to be more than 1.2 million years old and host more than 300 endemic species. As a target of the International Continental scientific Drilling Program (ICDP), a successful deep drilling campaign was carried out within the scope of the Scientific Collaboration on Past Speciation Conditions in Lake Ohrid (SCOPSCO) project in 2013. Here, we present lithological, sedimentological, and (bio-)geochemical data from the upper 247.8 m composite depth of the overall 569 m long DEEP site sediment succession from the central part of the lake. According to an age model, which is based on 11 tephra layers (first-order tie points) and on tuning of bio-geochemical proxy data to orbital parameters (second-order tie points), the analyzed sediment sequence covers the last 637 kyr. The DEEP site sediment succession consists of hemipelagic sediments, which are interspersed by several tephra layers and infrequent, thin (〈 5 cm) mass wasting deposits. The hemipelagic sediments can be classified into three different lithotypes. Lithotype 1 and 2 deposits comprise calcareous and slightly calcareous silty clay and are predominantly attributed to interglacial periods with high primary productivity in the lake during summer and reduced mixing during winter. The data suggest that high ion and nutrient concentrations in the lake water promoted calcite precipitation and diatom growth in the epilimnion during MIS15, 13, and 5. Following a strong primary productivity, highest interglacial temperatures can be reported for marine isotope stages (MIS) 11 and 5, whereas MIS15, 13, 9, and 7 were comparably cooler. Lithotype 3 deposits consist of clastic, silty clayey material and predominantly represent glacial periods with low primary productivity during summer and longer and intensified mixing during winter. The data imply that the most severe glacial conditions at Lake Ohrid persisted during MIS16, 12, 10, and 6, whereas somewhat warmer temperatures can be inferred for MIS14, 8, 4, and 2. Interglacial-like conditions occurred during parts of MIS14 and 8.
    Type of Medium: Online Resource
    ISSN: 1726-4189
    URL: Article
    URL: Article
    DOI: 10.5194/bg-13-1179-2016
    DOI: 10.5194/bg-13-1179-2016-supplement
    Language: English
    Publisher: Copernicus GmbH
    Publication Date: 2016
    detail.hit.zdb_id: 2158181-2
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  • 2
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    Targeting TGFβ-activated kinase-1 activation in microglia reduces CAR T immune effector cell-associated neurotoxicity syndrome
    Springer Science and Business Media LLC ; 2024
    In:  Nature Cancer
    Details
    In: Nature Cancer, Springer Science and Business Media LLC
    Type of Medium: Online Resource
    ISSN: 2662-1347
    URL: Article
    DOI: 10.1038/s43018-024-00764-7
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
    detail.hit.zdb_id: 3005299-3
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  • 3
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    The environmental and evolutionary history of Lake Ohrid (FYROM/Albania): interim results from the SCOPSCO deep drilling project
    Copernicus GmbH ; 2017
    In:  Biogeosciences Vol. 14, No. 8 ( 2017-04-20), p. 2033-2054
    Details
    In: Biogeosciences, Copernicus GmbH, Vol. 14, No. 8 ( 2017-04-20), p. 2033-2054
    Abstract: Abstract. This study reviews and synthesises existing information generated within the SCOPSCO (Scientific Collaboration on Past Speciation Conditions in Lake Ohrid) deep drilling project. The four main aims of the project are to infer (i) the age and origin of Lake Ohrid (Former Yugoslav Republic of Macedonia/Republic of Albania), (ii) its regional seismotectonic history, (iii) volcanic activity and climate change in the central northern Mediterranean region, and (iv) the influence of major geological events on the evolution of its endemic species. The Ohrid basin formed by transtension during the Miocene, opened during the Pliocene and Pleistocene, and the lake established de novo in the still relatively narrow valley between 1.9 and 1.3 Ma. The lake history is recorded in a 584 m long sediment sequence, which was recovered within the framework of the International Continental Scientific Drilling Program (ICDP) from the central part (DEEP site) of the lake in spring 2013. To date, 54 tephra and cryptotephra horizons have been found in the upper 460 m of this sequence. Tephrochronology and tuning biogeochemical proxy data to orbital parameters revealed that the upper 247.8 m represent the last 637 kyr. The multi-proxy data set covering these 637 kyr indicates long-term variability. Some proxies show a change from generally cooler and wetter to drier and warmer glacial and interglacial periods around 300 ka. Short-term environmental change caused, for example, by tephra deposition or the climatic impact of millennial-scale Dansgaard–Oeschger and Heinrich events are superimposed on the long-term trends. Evolutionary studies on the extant fauna indicate that Lake Ohrid was not a refugial area for regional freshwater animals. This differs from the surrounding catchment, where the mountainous setting with relatively high water availability provided a refuge for temperate and montane trees during the relatively cold and dry glacial periods. Although Lake Ohrid experienced significant environmental change over the last 637 kyr, preliminary molecular data from extant microgastropod species do not indicate significant changes in diversification rate during this period. The reasons for this constant rate remain largely unknown, but a possible lack of environmentally induced extinction events in Lake Ohrid and/or the high resilience of the ecosystems may have played a role.
    Type of Medium: Online Resource
    ISSN: 1726-4189
    URL: Article
    DOI: 10.5194/bg-14-2033-2017
    Language: English
    Publisher: Copernicus GmbH
    Publication Date: 2017
    detail.hit.zdb_id: 2158181-2
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  • 4
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    Northern Mediterranean climate since the Middle Pleistocene: a 637 ka stable isotope record from Lake Ohrid (Albania/Macedonia)
    Copernicus GmbH ; 2016
    In:  Biogeosciences Vol. 13, No. 6 ( 2016-03-24), p. 1801-1820
    Details
    In: Biogeosciences, Copernicus GmbH, Vol. 13, No. 6 ( 2016-03-24), p. 1801-1820
    Abstract: Abstract. Lake Ohrid (Macedonia/Albania) is an ancient lake with unique biodiversity and a site of global significance for investigating the influence of climate, geological, and tectonic events on the generation of endemic populations. Here, we present oxygen (δ18O) and carbon (δ13C) isotope data from carbonate over the upper 243 m of a composite core profile recovered as part of the Scientific Collaboration on Past Speciation Conditions in Lake Ohrid (SCOPSCO) project. The investigated sediment succession covers the past ca. 637 ka. Previous studies on short cores from the lake (up to 15 m, 〈 140 ka) have indicated the total inorganic carbon (TIC) content of sediments to be highly sensitive to climate change over the last glacial–interglacial cycle. Sediments corresponding to warmer periods contain abundant endogenic calcite; however, an overall low TIC content in glacial sediments is punctuated by discrete bands of early diagenetic authigenic siderite. Isotope measurements on endogenic calcite (δ18Oc and δ13Cc) reveal variations both between and within interglacials that suggest the lake has been subject to palaeoenvironmental change on orbital and millennial timescales. We also measured isotope ratios from authigenic siderite (δ18Os and δ13Cs) and, with the oxygen isotope composition of calcite and siderite, reconstruct δ18O of lake water (δ18Olw) over the last 637 ka. Interglacials have higher δ18Olw values when compared to glacial periods most likely due to changes in evaporation, summer temperature, the proportion of winter precipitation (snowfall), and inflow from adjacent Lake Prespa. The isotope stratigraphy suggests Lake Ohrid experienced a period of general stability from marine isotope stage (MIS) 15 to MIS 13, highlighting MIS 14 as a particularly warm glacial. Climate conditions became progressively wetter during MIS 11 and MIS 9. Interglacial periods after MIS 9 are characterised by increasingly evaporated and drier conditions through MIS 7, MIS 5, and the Holocene. Our results provide new evidence for long-term climate change in the northern Mediterranean region, which will form the basis to better understand the influence of major environmental events on biological evolution within Lake Ohrid.
    Type of Medium: Online Resource
    ISSN: 1726-4189
    URL: Article
    DOI: 10.5194/bg-13-1801-2016
    Language: English
    Publisher: Copernicus GmbH
    Publication Date: 2016
    detail.hit.zdb_id: 2158181-2
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  • 5
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    Periodic 1.5 ka climate variations during MIS 2 in the belt of Southern Hemispheric westerlies
    Cambridge University Press (CUP) ; 2017
    In:  Quaternary Research Vol. 88, No. 1 ( 2017-07), p. 110-120
    Details
    In: Quaternary Research, Cambridge University Press (CUP), Vol. 88, No. 1 ( 2017-07), p. 110-120
    Abstract: Lacustrine sediments retrieved from Laguna Potrok Aike in the framework of the Potrok Aike Maar Lake Sediment Archive Drilling Project (PASADO) offer the possibility to investigate climate variations of the past ~51 cal ka BP in Southern Hemispheric midlatitudes, Argentinean Patagonia. This study focuses on short-term cyclicities in the Ca and magnetic susceptibility data sets between 51 and 15 cal ka BP. The record yields a climate pattern with a periodicity of 1.5 ka during Marine Oxygen Isotope Stage 2 (MIS 2) detected in the Southern Hemisphere from 31 to 17 cal ka BP for the first time. MIS 2 is known for constantly cold temperatures, whereas prominent climate variations paced by a 1.5 ka periodicity occurred during MIS 3. Our study documents that minor latitudinal oscillations of the Southern Hemispheric westerlies and the polar easterlies with a 1.5 ka periodicity also took place during MIS 2. However, we assume that because of a major northward displacement of the Southern Hemispheric westerlies, these oscillations did not sufficiently affect the zone of Circumpolar Deep Waters and an increased greenhouse effect by upwelling of CO 2 -rich deep waters did not occur. This mechanism illustrates why prominent climate events fail to appear during MIS 2.
    Type of Medium: Online Resource
    ISSN: 0033-5894 , 1096-0287
    URL: Article
    DOI: 10.1017/qua.2017.13
    RVK:
    RA 1000
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2017
    detail.hit.zdb_id: 1471589-2
    detail.hit.zdb_id: 205711-6
    SSG: 13
    SSG: 14
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  • 6
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    Petrophysical and sedimentary petrographic characterisation of the Bückeburg Formation (German Wealden) in the geothermal well Groß Buchholz Gt-1 (Hanover, Germany)
    Schweizerbart ; 2012
    In:  Zeitschrift der Deutschen Gesellschaft für Geowissenschaften Vol. 163, No. 4 ( 2012-12-01), p. 483-492
    Details
    In: Zeitschrift der Deutschen Gesellschaft für Geowissenschaften, Schweizerbart, Vol. 163, No. 4 ( 2012-12-01), p. 483-492
    Type of Medium: Online Resource
    ISSN: 1860-1804
    Uniform Title: Petrophysical and sedimentary petrographic characterisation of the Bückeburg Formation (German Wealden) in the geothermal well Groß Buchholz Gt-1 (Hanover, Germany)
    URL: Article
    DOI: 10.1127/1860-1804/2012/0163-0483
    RVK:
    TE 1000
    Language: English , English
    Publisher: Schweizerbart
    Publication Date: 2012
    detail.hit.zdb_id: 2186032-4
    SSG: 13
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  • 7
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    Immune-Effector-Cell-Associated-Neurotoxicity-Syndrome (ICANS) Pathophysiology Is Mediated By Microglia TGF-β-Activated Kinase-1 Signaling
    American Society of Hematology ; 2023
    In:  Blood Vol. 142, No. Supplement 1 ( 2023-11-02), p. 100-100
    Details
    In: Blood, American Society of Hematology, Vol. 142, No. Supplement 1 ( 2023-11-02), p. 100-100
    Abstract: Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the field of immune therapy in treating relapsed and refractory B cell malignancies. Despite remarkable progress, CD19 CAR-T cell therapy is associated with major side effects, most significantly are cytokine-release syndrome and neurotoxicity. Of note, 40-60% of patients receiving CD19 CAR-T cells suffer from severe neurotoxicity termed immune cell-associated-neurotoxicity-syndrome (ICANS), which remains a major obstacle limiting their therapeutic efficacy. Several pre-clinical reports using xenograft mouse models have been published to address ICANS, however, they do not fully recapitulate the clinical scenario. Identifying and targeting the molecular mediators of neurotoxicity could help ameliorate ICANS induced by CD19 CAR-T cells. In order to understand the molecular mechanisms leading to CD19 CAR-T cell-induced ICANS, we established syngeneic ICANS mouse models for B-cell malignancies including non-Hodgkin's Lymphoma (B-NHL) and Acute Lymphoblastic Leukemia (B-ALL). Micro-array and single-nuclei RNA sequencing analyses were performed to unveil key signaling pathways in microglia leading to ICANS pathophysiology. Cognitive impairment resulting from the transfer of CD19 CAR-T cells was assessed with behavior studies in murine models. Imaging mass cytometry was performed on autopsied ICANS and control patient cohorts to study the relevance of microglial activation in patients. We previously demonstrated that microglial upregulation of tumor necrosis factor-alpha (TNFα) results in graft versus host disease of the central nervous system (Mathew and Vinnakota et al. JCI 2020). Similarly, our ICANS mouse models exhibit morphological and functional signs of microglial activation with increased expression of TNFα and GM-CSF along with endothelial damage in lymphoma-bearing mice that received CD19 CAR-T cells when compared to non-transduced controls. Behavioral studies revealed that mice receiving CD19 CAR-T cells exhibit cognitive deficits and increased anxiety. The behavior deficits were however rescued by microglia depletion indicating an important role for microglia in mediating CD19 CAR-T cells induced ICANS. Mechanistically, we identified the activation of p-38 mitogen-activated protein kinase (MAPK) in microglia isolated from mice receiving CD19 CAR-T cells. Furthermore, pharmacological inhibition of TGF-β-activated kinase-1 (TAK1), an upstream target for p-38 MAPK significantly reduced microglial activation, lowered microglia production of TNF and GM-CSF, and improved cognitive function in these mice. In line with these results, microglia-specific knockdown of TAK1 using Cx3cr1 creER:Tak1 fl/fl mice revealed reduced microglial activation and improved cognitive function when compared to littermate controls. Moreover, TAK1 inhibition combined with CD19 CAR-T cell therapy synergistically improved anti-lymphoma/leukemia effects leading to better survival in B-cell malignancy-bearing mice. Translocator-protein-positron-emission-tomography (TSPO-PET) on ICANS patients revealed signs of microglial activation. In addition, Imaging-mass cytometry analysis on post-mortem ICANS patient cohort revealed upregulation of myeloid cell markers further confirming the in vivo findings. In summary, our results identify TAK1/p38 MAPK-pathway as a key mediator of CAR19 CAR-T cell-induced neurotoxicity. Targeting this axis diminished the neurotoxicity associated with this therapy. This study provides a rationale for testing TAK1-inhibition in a clinical trial for treating CD19 CAR-T cell-induced neurotoxicity.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2023-184867
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2023
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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