Did increasing seasonality and fire frequency cause the c4 grassland transition in South America (SA)? Investigations from two paleosol sites in NW Argentina using δ13c isotopes, molecular biomarkers, phytoliths, and X-ray fluorescence (XRF)

Recent advances in molecular biomarkers along with traditional bulk δ13C isotopic analysis, phytolith assemblages, and XRF analysis allow for the detailed reconstruction of continental paleoecological and paleoclimatic conditions. We use these methods to reconstruct conditions during the expansion of C4 grasses, considered one of the most important biological events during the Cenozoic. We hypothesize that in SA, the spread of C4 grasses was driven by the intensification of the SA Summer Monsoon and that this increase in C4 vegetation caused an intensification of fire regimes, due to both seasonality fire and fireC4 expansion feedbacks, that has long been suspected but poorly documented and never studied in this context in SA. This study presents resultsfrom welldated paleosols from two sites in N.W. Argentina: La Viña (LV) and Palo Pintado (PP) in the Salta Province. The LV site includes the Jesus Maria Formations, Guanaco and Piquete (~15 4Ma), while the PP site includes the Palo Pintado Formation (~7.5 6 Ma). Previous studies have interpreted these sites as foreland basin sediments deposited in a meandering stream tolacustrine environment. Shifts in the δ13C obtained from bulk organic matter and phytolith assemblages in these paleosols are used to identify vegetation transitions from C3dominatedgrasslands and forests, to C4dominated grasslands. Leaf wax biomarkers include higher order nalkanes (C20 to C36), and are used to independently determine vegetation composition and changes to aridity and seasonality. XRF analysis is carried out to determine the chemical index of alteration in paleosols, which is a comparable proxy for precipitation seasonality. Polycyclic aromatic hydrocarbons (PAH) are used to determine fire regimes, in order to verify whether C4 expansion promoted fires. δ13C analysis of LV reveals a steady change from a C3dominatedecosystem at 15 Ma to a C3C4 intermediary ecosystem by 7.5 Ma. The PP site does not show any directional change in vegetation type during the investigated period between 7.2 Ma to 6 Ma, though δ13C values indicate a mixed C3C4 ecosystem throughout this period. However, results from the PP site show that increasing C4 cover, determined from bulk organic matter δ13C, is positively correlated with an increased fire frequency, determined from increasing PAH concentrations. Ultimately, these data contribute to constraining the causes of C4 expansion in NW Argentina, including the most important climatic controls and feedbacks from fire regimes, in continental SA.Fil: Ghosh, Adit. California State University; Estados UnidosFil: Cotton, Jennifer M.. California State University; Estados UnidosFil: Hyland, Ethan G.. North Carolina State University; Estados UnidosFil: Hauswirth, Scott C.. California State University; Estados UnidosFil: Raigemborn, María Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Tineo, David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaThe Geological Society of America Connects 2021PasadenaEstados UnidosGeological Society of Americ

Late Miocene expansion of grasslands in northwest Argentina linked to shifting hydroclimate: A complex interaction among tectonics, climate, and ecology

Factors driving the late Miocene expansion of C4 grasses remain widely debated. Here, we explored the role of climate and fire in controlling the abundance of C4 vegetation in the Angastaco Basin (Palo Pintado area) and La Viña Basin, NW Argentina, during the late Miocene (ca. 14−5.33 Ma). From paleosol horizons, we reconstructed paleoclimate and paleovegetation conditions using phytolith assemblages, geochemical and isotopic proxies, and polycyclic aromatic hydrocarbons (PAHs) to determine fire input. Our paleoclimate reconstructions suggest a stable mean annual temperature (MAT) of ∼10 °C and a gradual decline in mean annual precipitation (MAP) from 1100 mm yr−1 to 850 mm yr−1. Paleovegetation reconstructions from carbon isotopic composition and phytolith assemblages show a maximum of ∼15% C4 vegetation by 6 Ma. No significant increases in fire occurrence or establishment of fire feedbacks were identified from the PAH data. Though low in abundance (∼3% on average), our data identified the presence of C4 grass by the late Miocene. The lack of significant C4 expansion in this region was likely controlled by the changing hydroclimatic conditions associated with the Andes mountain range—increasing aridity and elevation constraints along with the lack of a fire feedback might have limited the distribution of C4 vegetation.Fil: Azmi, Iffat. North Carolina State University; Estados UnidosFil: Hyland, Ethan. North Carolina State University; Estados UnidosFil: Cotton, Jennifer. California State University Northridge;Fil: Ghosh, Adit. University of Southern California; Estados UnidosFil: Raigemborn, María Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Tineo, David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Hauswirth, Scott. California State University Northridge;Fil: Insel, Nadja. Northeastern Illinois University (northeastern Illinois)

Late Miocene-Pliocene vegetation, fire and hydroclimate dynamics in the Río Iruya basin, Northwest Argentina

The spread of C4 grasses and fire history through the Late Miocene-Pliocene in South America has remained a mystery due to sparse terrestrial archives and lack of corresponding geochemical vegetation and fire proxies. We hypothesize that the increased seasonality of precipitation associated with a strengthening summer monsoon enabled the spread of C4 grasses in the Río Iruya basin and this increase in C4 vegetation resulted in a positive feedback with fire frequency. To test this hypothesis, the carbon isotopic ratio of bulk organic carbon (δ13CBOM) and specific Polycyclic Aromatic Hydrocarbon (PAH) biomarkers were used as proxies for vegetation type, concentrations of PAHs were used to reconstruct fire regimes and bulk geochemistry of paleosol clay minerals were used to reconstruct climatic changes. We observe the appearance of ~50% C4 cover in the basin by 5.13 Ma from δ13CBOM values. PAH vegetation provenance from the retene, DMP-x and DMP-y proxy indicated a mixed gymnosperm forest with a grassy understory across the studied period. Thus, we conclude that C4 grasses were replacing C3 grasses in a gymnosperm dominated forest in Río Iruya. Fire frequency reconstructed from total PAH concentrations normalized to the concentration of C31 alkane, appears relatively stable throughout the investigated period. We observe an increase in mean annual precipitation derived from the CIA-K proxy from 6.6 to 5.4 Ma. We conclude that the increase in C4 cover did not drive an increase in fire frequency at Río Iruya. This lack of increase in fire frequency is likely due to the presence of fire resistant C3 taxa, to the lack of threshold C4 grass cover, or increased precipitation. Thus, we conclude that significant changes in vegetation but not fire regimes, took place in Río Iruya during the investigated period, and precipitation estimates suggest that these vegetation changes may be linked to the strengthening of the South American summer monsoon.Fil: Ghosh, Adit. University of Southern California; Estados UnidosFil: Cotton, Jennifer. California State University; Estados UnidosFil: Hauswirth, Scott. California State University; Estados UnidosFil: Hyland, Ethan. North Carolina State University; Estados UnidosFil: Azmi, Iffat. North Carolina State University; Estados UnidosFil: Raigemborn, María Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Tineo, David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Hayduk, Tyler. Canoga Park; Estados UnidosFil: Insel, Nadja. North Carolina State University; Estados UnidosThe Geological Society of America Connects 2021PortlandEstados UnidosGeological Society of Americ

The rise of C4 grasses in South America: Linking grassland transition to the South American summer monsoon

The expansion of C4 grasses is one of the most dramatic ecological changes in the past 65 million years. Beginning in the late Miocene (~7 million years ago), these tropical and subtropical grasses began to spread and now cover roughly 25% of the Earth's surface. C4 grasses include economically important crops such as corn, sugarcane and sorghum, but the environmental conditions that drove this global expansion are poorly understood. In this study, we aim to determine the drivers of C4 grass expansion in South America. We hypothesize that this expansion was driven by the strengthening of the South American Summer Monsoon (SASM), which occurred as a result of regional climatic change due to local tectonic and global climatic changes. Using carbon isotopes of bulk organic matter preserved in paleosols, we reconstruct the abundance of C4 grasses across 7 sites in Argentina to assess the timing of this ecological transition in South America. We pair this C4 grass reconstruction with phytolith and biomarker analysis to gain a more detailed perspective of vegetation and fire history, and we use soil geochemistry proxies to assess changes in hydroclimate across the region from the late Miocene-Pliocene. We find that in the absence of temperature and atmospheric CO2 changes, hydrologic change is likely the driver of C4 grass abundances in the Miocene. In far northwest Argentina, our data suggests that increased seasonality brought about by the intensification of the South American Monsoon drove the expansion of C4 grasses, at least in the more humid regions. These results are supported by Community Earth System Model simulations that suggest an increase in summer precipitation along the eastern foothills of the Andes in Northern Argentina between 8 and 3Ma. Our data does not show a correlation between fire frequency and C4 grass abundance in Argentina, unlike in the Siwaliks of South Asia. We also note that we only find moderate to high abundances of C4 grasses in areas where proxy-based precipitation estimates exceed ~500mm/yr. We also do not observe C4 grasses at sites with modern elevations higher than ~3,000 feet or behind rain shadows, showing that tectonically-driven climate changes are important controls on the distribution and spread of C4 grasses. This work will allow us to better predict changes to modern grasslands in the future.Fil: Cotton, Jennifer M.. Departament Of Geological Sciences ; College Of Science And Mathematics ; California State University Northridge;Fil: Ghosh, Adit. University of Southern California; Estados UnidosFil: Hyland, Ethan. North Carolina State University; Estados UnidosFil: Hauswirth, Scott. Departament Of Geological Sciences ; College Of Science And Mathematics ; California State University Northridge;Fil: Littleton, Shelby. Departament Of Geological Sciences ; College Of Science And Mathematics ; California State University Northridge;Fil: Azmi, Iffat. North Carolina State University; Estados UnidosFil: Insel, Nadja. Northeastern Illinois University (northeastern Illinois);Fil: Raigemborn, María Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Tineo, David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; Argentina73rd Annual Meeting of the Rocky Mountain SectionFort CollinsEstados UnidosThe Geological Society of Americ

The rise of C4 grasses in Argentina: Linking grassland transition to the South American summer Monsoon using sediments, paleosols, phytoliths and isotopes

The expansion of C4 grasses is one of the most dramatic ecological changes in the past 65 million years. Beginning in the late Miocene (~10-5 Ma), these tropical and subtropical grasses began to spread and now cover roughly 25% of the Earth´s surface. C4 grasses include economically and ecologically important crops, but the environmental conditions that drove this global expansion are poorly understood. In this study, we aim to determine the drivers of C4 grass expansion in central South America (Argentina). We hypothesize that this expansion was driven by the strengthening of the South American Summer Monsoon (SASM), which occurred as a result of regional climatic change related to local tectonic and global climatic processes. Using sedimentology/stratigraphy, paleopedology and geochemistry, phytolith and carbon isotope reconstructions, and biomarkers, we present paired reconstructions of environmental and climatic conditions and the abundance of C4 grasses across 7 sites in northern and central Argentina to assess the timing of this ecological transition in South America during the late Miocene-Pliocene. We find that in the absence of temperature and atmospheric CO2 changes, regional hydrologic change is likely the driver of C4 grass abundances in the Miocene. In northwest and central Argentina, our data suggests that increased precipitation seasonality brought about by the intensification of the South American Monsoon drove the expansion of C4 grasses, at least in the more humid regions. These results are supported by Community Earth System Model simulations that suggest an increase in summer precipitation along the eastern foothills of the Andes in Argentina between 8 and 3 Ma. Our data does not show a correlation between fire frequency and C4 grass abundance in Argentina, unlike other regions where this may drive the expansion. We also note that we only find moderate to high abundances of C4 grasses in areas where proxy-based precipitation estimates exceed ~500 mm/yr, and do not observe C4 grasses at sites with modern elevations higher than ~3,000 feet or behind rain shadows, showing that tectonically driven conditions are important controls on the distribution and spread of C4 grasses.Fil: Hyland, E. G.. North Carolina State University; Estados UnidosFil: Cotton, Jennifer M.. California State University; Estados UnidosFil: Ghosh, Adit. University of Southern California; Estados UnidosFil: Hauswirth, S. C.. California State University; Estados UnidosFil: Littleton, S.. California State University; Estados UnidosFil: Azmi, Iffat. North Carolina State University; Estados UnidosFil: Insel, Nadja. Northeastern Illinois University (northeastern Illinois);Fil: Raigemborn, María Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Tineo, David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaXVIII Reunión Argentina de Sedimentología y IX Congreso Latinoamericano de SedimentologíaLa PlataArgentinaAsociación Sedimentológica Argentin

Abstract LB210: Preclinical development and evaluation of allogeneic CAR T cells targeting CD70 for the treatment of renal cell carcinoma

Abstract CD70 is highly expressed on renal cell carcinoma (RCC), with limited normal tissue expression, making it an attractive CAR T target for an immunogenic solid tumor indication. Here we generated and characterized a panel of anti-CD70 scFv-based CAR T cells. Despite the expression of CD70 on T cells, production of CAR T from a subset of scFvs with potent in vitro activity was achieved. Expression of CD70 CARs was found to mask CD70 detection in cis and provide protection from CD70 CAR T-mediated fratricide. Two unique classes of CAR T cells were identified with differing memory phenotype, activation status, and cytotoxic activity. Epitope mapping revealed CARs binding to the membrane distal region of the CD70 extracellular domain (ECD) fall into the more active and differentiated class, as compared to CARs binding the membrane proximal region of the CD70 ECD. CD70 CAR T cells were evaluated with rituximab-based off switches to provide control over CAR T function and displayed robust antitumor activity against RCC cell lines and patient-derived xenografts in mouse models. Tissue cross reactivity studies to evaluate off-target binding with two lead CARs showed membrane staining in rare tissue-resident lymphocytes, thus matching the known expression pattern of CD70. Expected findings related to T cell activation, and elimination of CD70-expressing cells were observed in a cynomolgus monkey CD3-CD70 bispecific toxicity study and included cytokine release and loss of cellularity in lymphoid tissues. Lastly, highly functional CD70 allogeneic CAR T cells were produced at large scale through elimination of the T cell receptor by TALEN® gene editing. Taken together, these efficacy and safety data support the evaluation of CD70 CAR T cells for the treatment of RCC and led to the advancement of an allogeneic CD70 CAR T candidate into Phase I clinical trials. Citation Format: Siler Panowski, Surabhi Srinivasan, Nguyen Tan, Silvia Tacheva-Grigorova, Bryan Smith, Yvonne Mak, Hongxiu Ning, Jonathan Villanueva, Dinali Wijewarnasuriya, Shanshan Lang, Zea Melton, Adit Ghosh, Mathilde Dusseaux, Roman Galetto, Jonathan Heyen, Tao Sai, Thomas Van Blarcom, Javier Chaparro-Riggers, Barbra Sasu. Preclinical development and evaluation of allogeneic CAR T cells targeting CD70 for the treatment of renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB210.</jats:p