Immune Maturation Effects on Viral Neutralization and Avidity of Hyperimmunized Equine Anti-SARS-CoV-2 Sera

Mass-vaccination against COVID-19 is still a distant goal for most low-to-middle income countries. The experience gained through decades producing polyclonal immunotherapeutics (such as antivenoms) in many of those countries is being redirected to develop similar products able to neutralize SARS-CoV-2 infection. In this study we analyzed the biological activity (viral neutralization or NtAb) and immunochemical properties of hyperimmune horses’ sera (HHS) obtained during initial immunization (I) and posterior re-immunization (R) cycles using the RBD domain of the SARS-CoV-2 spike protein as antigen. HHS at the end of the R cycle showed higher NtAb titers when compared to those after the I cycle (35,585 vs. 7000 mean NtAb, respectively). Moreover, this increase paralleled an increase in avidity (95.2% to 65.2% mean avidity units, respectively). The results presented herein are relevant for manufacturers of these therapeutic tools against COVID-19.Fil: Gonzalez Viacava, Myriam Belen. Ministerio de Salud de la Nación. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Doctor Carlos G. Malbrán". Instituto Nacional de Producción de Biológicos; ArgentinaFil: Varese, Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Mazzitelli, Ignacio Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Lanari, Laura Cecilia. Ministerio de Salud de la Nación. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Doctor Carlos G. Malbrán". Instituto Nacional de Producción de Biológicos; ArgentinaFil: Avila, Lucía. Ministerio de Salud de la Nación. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Doctor Carlos G. Malbrán". Instituto Nacional de Producción de Biológicos; ArgentinaFil: Garcia Vampa, Maria Julia. Ministerio de Salud de la Nación. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Doctor Carlos G. Malbrán". Instituto Nacional de Producción de Biológicos; ArgentinaFil: Geffner, Jorge Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Cascone, Osvaldo. Ministerio de Salud de la Nación. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Doctor Carlos G. Malbrán". Instituto Nacional de Producción de Biológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Dokmetjian, Jose Christian. Ministerio de Salud de la Nación. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Doctor Carlos G. Malbrán". Instituto Nacional de Producción de Biológicos; ArgentinaFil: de Roodt, Adolfo Rafael. Ministerio de Salud de la Nación. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Doctor Carlos G. Malbrán". Instituto Nacional de Producción de Biológicos; ArgentinaFil: Fingermann, Matias. Ministerio de Salud de la Nación. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Doctor Carlos G. Malbrán". Instituto Nacional de Producción de Biológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

BRCA1 loss activates cathepsin L–mediated degradation of 53BP1 in breast cancer cells

Loss of 53BP1 rescues BRCA1 deficiency and is associated with BRCA1-deficient and triple-negative breast cancers (TNBC) and with resistance to genotoxic drugs. The mechanisms responsible for decreased 53BP1 transcript and protein levels in tumors remain unknown. Here, we demonstrate that BRCA1 loss activates cathepsin L (CTSL)–mediated degradation of 53BP1. Activation of this pathway rescued homologous recombination repair and allowed BRCA1-deficient cells to bypass growth arrest. Importantly, depletion or inhibition of CTSL with vitamin D or specific inhibitors stabilized 53BP1 and increased genomic instability in response to radiation and poly(adenosine diphosphate–ribose) polymerase inhibitors, compromising proliferation. Analysis of human breast tumors identified nuclear CTSL as a positive biomarker for TNBC, which correlated inversely with 53BP1. Importantly, nuclear levels of CTSL, vitamin D receptor, and 53BP1 emerged as a novel triple biomarker signature for stratification of patients with BRCA1-mutated tumors and TNBC, with potential predictive value for drug response. We identify here a novel pathway with prospective relevance for diagnosis and customization of breast cancer therapy

Soil organic carbon stocks in native forest of Argentina: a useful surrogate for mitigation and conservation planning under climate variability

Background The nationally determined contribution (NDC) presented by Argentina within the framework of the Paris Agreement is aligned with the decisions made in the context of the United Nations Framework Convention on Climate Change (UNFCCC) on the reduction of emissions derived from deforestation and forest degradation, as well as forest carbon conservation (REDD+). In addition, climate change constitutes one of the greatest threats to forest biodiversity and ecosystem services. However, the soil organic carbon (SOC) stocks of native forests have not been incorporated into the Forest Reference Emission Levels calculations and for conservation planning under climate variability due to a lack of information. The objectives of this study were: (i) to model SOC stocks to 30 cm of native forests at a national scale using climatic, topographic and vegetation as predictor variables, and (ii) to relate SOC stocks with spatial–temporal remotely sensed indices to determine biodiversity conservation concerns due to threats from high inter‑annual climate variability. Methods We used 1040 forest soil samples (0–30 cm) to generate spatially explicit estimates of SOC native forests in Argentina at a spatial resolution of approximately 200 m. We selected 52 potential predictive environmental covariates, which represent key factors for the spatial distribution of SOC. All covariate maps were uploaded to the Google Earth Engine cloud‑based computing platform for subsequent modelling. To determine the biodiversity threats from high inter‑annual climate variability, we employed the spatial–temporal satellite‑derived indices based on Enhanced Vegetation Index (EVI) and land surface temperature (LST) images from Landsat imagery. Results SOC model (0–30 cm depth) prediction accounted for 69% of the variation of this soil property across the whole native forest coverage in Argentina. Total mean SOC stock reached 2.81 Pg C (2.71–2.84 Pg C with a probability of 90%) for a total area of 460,790 km2, where Chaco forests represented 58.4% of total SOC stored, followed by Andean Patagonian forests (16.7%) and Espinal forests (10.0%). SOC stock model was fitted as a function of regional climate, which greatly influenced forest ecosystems, including precipitation (annual mean precipitation and precipitation of warmest quarter) and temperature (day land surface temperature, seasonality, maximum temperature of warmest month, month of maximum temperature, night land surface temperature, and monthly minimum temperature). Biodiversity was influenced by the SOC levels and the forest regions. Conclusions In the framework of the Kyoto Protocol and REDD+, information derived in the present work from the estimate of SOC in native forests can be incorporated into the annual National Inventory Report of Argentina to assist forest management proposals. It also gives insight into how native forests can be more resilient to reduce the impact of biodiversity loss.EEA Santa CruzFil: Peri, Pablo Luis. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz; Argentina.Fil: Peri, Pablo Luis. Universidad Nacional de la Patagonia Austral; Argentina.Fil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Gaitan, Juan José. Universidad Nacional de Luján. Buenos Aires; Argentina.Fil: Gaitan, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Mastrangelo, Matias Enrique. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias. Grupo de Estudio de Agroecosistemas y Paisajes Rurales; Argentina.Fil: Mastrangelo, Matias Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Nosetto, Marcelo Daniel. Universidad Nacional de San Luis. Instituto de Matemática Aplicada San Luis. Grupo de Estudios Ambientales; Argentina.Fil: Nosetto, Marcelo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Villagra, Pablo Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales (IANIGLA); Argentina.Fil: Villagra, Pablo Eugenio. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; Argentina.Fil: Balducci, Ezequiel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Yuto; Argentina.Fil: Pinazo, Martín Alcides. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Montecarlo; Argentina.Fil: Eclesia, Roxana Paola. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Paraná; Argentina.Fil: Von Wallis, Alejandra. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Montecarlo; Argentina.Fil: Villarino, Sebastián. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias. Grupo de Estudio de Agroecosistemas y Paisajes Rurales; Argentina.Fil: Villarino, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Alaggia, Francisco Guillermo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Manfredi. Campo Anexo Villa Dolores; Argentina.Fil: Alaggia, Francisco Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Gonzalez-Polo, Marina. Universidad Nacional del Comahue; Argentina.Fil: Gonzalez-Polo, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. INIBIOMA; Argentina.Fil: Manrique, Silvana M. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Energía No Convencional. CCT Salta‑Jujuy; Argentina.Fil: Meglioli, Pablo A. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales (IANIGLA); Argentina.Fil: Meglioli, Pablo A. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; Argentina.Fil: Rodríguez‑Souilla, Julián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas (CADIC); Argentina.Fil: Mónaco, Martín H. Ministerio de Ambiente y Desarrollo Sostenible. Dirección Nacional de Bosques; Argentina.Fil: Chaves, Jimena Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas (CADIC); Argentina.Fil: Medina, Ariel. Ministerio de Ambiente y Desarrollo Sostenible. Dirección Nacional de Bosques; Argentina.Fil: Gasparri, Ignacio. Universidad Nacional de Tucumán. Instituto de Ecología Regional; Argentina.Fil: Gasparri, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Alvarez Arnesi, Eugenio. Universidad Nacional de Rosario. Instituto de Investigaciones en Ciencias Agrarias de Rosario; Argentina.Fil: Alvarez Arnesi, Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe; Argentina.Fil: Barral, María Paula. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias. Grupo de Estudio de Agroecosistemas y Paisajes Rurales; Argentina.Fil: Barral, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Von Müller, Axel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Esquel Argentina.Fil: Pahr, Norberto Manuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Montecarlo; Argentina.Fil: Uribe Echevarría, Josefina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Quimilí; Argentina.Fil: Fernandez, Pedro Sebastian. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Famaillá; Argentina.Fil: Fernandez, Pedro Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ecología Regional; Argentina.Fil: Morsucci, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales (IANIGLA); Argentina.Fil: Morsucci, Marina. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; Argentina.Fil: Lopez, Dardo Ruben. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Manfredi. Campo Anexo Villa Dolores; Argentina.Fil: Lopez, Dardo Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Cellini, Juan Manuel. Universidad Nacional de la Plata (UNLP). Facultad de Ciencias Naturales y Museo. Laboratorio de Investigaciones en Maderas; Argentina.Fil: Alvarez, Leandro M. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales (IANIGLA); Argentina.Fil: Alvarez, Leandro M. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; Argentina.Fil: Barberis, Ignacio Martín. Universidad Nacional de Rosario. Instituto de Investigaciones en Ciencias Agrarias de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe; Argentina.Fil: Barberis, Ignacio Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe; Argentina.Fil: Colomb, Hernán Pablo. Ministerio de Ambiente y Desarrollo Sostenible. Dirección Nacional de Bosques; Argentina.Fil: Colomb, Hernán. Administración de Parques Nacionales (APN). Parque Nacional Los Alerces; Argentina.Fil: La Manna, Ludmila. Universidad Nacional de la Patagonia San Juan Bosco. Centro de Estudios Ambientales Integrados (CEAI); Argentina.Fil: La Manna, Ludmila. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Barbaro, Sebastian Ernesto. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Cerro Azul; Argentina.Fil: Blundo, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ecología Regional; Argentina.Fil: Blundo, Cecilia. Universidad Nacional de Tucumán. Tucumán; Argentina.Fil: Sirimarco, Marina Ximena. Universidad Nacional de Mar del Plata. Grupo de Estudio de Agroecosistemas y Paisajes Rurales (GEAP); Argentina.Fil: Sirimarco, Marina Ximena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Cavallero, Laura. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Manfredi. Campo Anexo Villa Dolores; Argentina.Fil: Zalazar, Gualberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales (IANIGLA); Argentina.Fil: Zalazar, Gualberto. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; Argentina.Fil: Martínez Pastur, Guillermo José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas (CADIC); Argentina

Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations

Background: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes. Objective: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations. Methods: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-kappa B) signaling. Results: We classified 56 of the 105 distinct NFKB1 variants in 157 individuals from 68 unrelated families as pathogenic. Incomplete clinical penetrance (70%) and age-dependent severity of NFKB1-related phenotypes were observed. The phenotype included hypogammaglobulinemia (88.9%), reduced switched memory B cells (60.3%), and respiratory (83%) and gastrointestinal (28.6%) infections, thus characterizing the disorder as primary immunodeficiency. However, the high frequency of autoimmunity (57.4%), lymphoproliferation (52.4%), noninfectious enteropathy (23.1%), opportunistic infections (15.7%), autoinflammation (29.6%), and malignancy (16.8%) identified NF-kappa B1-related disease as an inborn error of immunity with immune dysregulation, rather than a mere primary immunodeficiency. Current treatment includes immunoglobulin replacement and immunosuppressive agents. Conclusions: We present a comprehensive clinical overview of the NF-kappa B1-related phenotype, which includes immunodeficiency, autoimmunity, autoinflammation, and cancer. Because of its multisystem involvement, clinicians from each and every medical discipline need to be made aware of this autosomal-dominant disease. Hematopoietic stem cell transplantation and NF-kappa B1 pathway-targeted therapeutic strategies should be considered in the future.Peer reviewe

The bHLH transcription factor SPATULA enables cytokinin signaling, and both activate auxin biosynthesis and transport genes at the medial domain of the gynoecium

[EN] Fruits and seeds are the major food source on earth. Both derive from the gynoecium and, therefore, it is crucial to understand the mechanisms that guide the development of this organ of angiosperm species. In Arabidopsis, the gynoecium is composed of two congenitally fused carpels, where two domains: medial and lateral, can be distinguished. The medial domain includes the carpel margin meristem (CMM) that is key for the production of the internal tissues involved in fertilization, such as septum, ovules, and transmitting tract. Interestingly, the medial domain shows a high cytokinin signaling output, in contrast to the lateral domain, where it is hardly detected. While it is known that cytokinin provides meristematic properties, understanding on the mechanisms that underlie the cytokinin signaling pattern in the young gynoecium is lacking. Moreover, in other tissues, the cytokinin pathway is often connected to the auxin pathway, but we also lack knowledge about these connections in the young gynoecium. Our results reveal that cytokinin signaling, that can provide meristematic properties required for CMM activity and growth, is enabled by the transcription factor SPATULA (SPT) in the medial domain. Meanwhile, cytokinin signaling is confined to the medial domain by the cytokinin response repressor ARABIDOPSIS HISTIDINE PHOSPHOTRANSFERASE 6 (AHP6), and perhaps by ARR16 (a type-A ARR) as well, both present in the lateral domains (presumptive valves) of the developing gynoecia. Moreover, SPT and cytokinin, probably together, promote the expression of the auxin biosynthetic gene TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS 1 (TAA1) and the gene encoding the auxin efflux transporter PIN-FORMED 3 (PIN3), likely creating auxin drainage important for gynoecium growth. This study provides novel insights in the spatiotemporal determination of the cytokinin signaling pattern and its connection to the auxin pathway in the young gynoecium.IRO, VMZM, HHU and PLS were supported by the Mexican National Council of Science and Technology (CONACyT) with a PhD fellowship (210085, 210100, 243380 and 219883, respectively). Work in the SDF laboratory was financed by the CONACyT grants CB-2012-177739, FC-2015-2/1061, and INFR-2015-253504, and NMM by the CONACyT grant CB-2011-165986. SDF, CF and LC acknowledge the support of the European Union FP7-PEOPLE-2009-IRSES project EVOCODE (grant no. 247587) and H2020-MSCARISE-2015 project ExpoSEED (grant no. 691109). SDF also acknowledges the Marine Biological Laboratory (MBL) in Woods Hole for a scholarship for the Gene Regulatory Networks for Development Course 2015 (GERN2015). IE acknowledges the International European Fellowship-METMADS project and the Universita degli Studi di Milano (RTD-A; 2016). Research in the laboratory of MFY was funded by NSF (grant IOS-1121055), NIH (grant 1R01GM112976-01A1) and the Paul D. Saltman Endowed Chair in Science Education (MFY). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Reyes Olalde, J.; Zuñiga, V.; Serwatowska, J.; Chávez Montes, R.; Lozano-Sotomayor, P.; Herrera-Ubaldo, H.; Gonzalez Aguilera, K.... (2017). The bHLH transcription factor SPATULA enables cytokinin signaling, and both activate auxin biosynthesis and transport genes at the medial domain of the gynoecium. PLoS Genetics. 13(4):1-31. https://doi.org/10.1371/journal.pgen.1006726S131134Reyes-Olalde, J. I., Zuñiga-Mayo, V. M., Chávez Montes, R. A., Marsch-Martínez, N., & de Folter, S. (2013). Inside the gynoecium: at the carpel margin. Trends in Plant Science, 18(11), 644-655. doi:10.1016/j.tplants.2013.08.002Alvarez-Buylla, E. 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The role of cytokinin during Arabidopsis gynoecia and fruit morphogenesis and patterning. The Plant Journal, 72(2), 222-234. doi:10.1111/j.1365-313x.2012.05062.xZhao, Z., Andersen, S. U., Ljung, K., Dolezal, K., Miotk, A., Schultheiss, S. J., & Lohmann, J. U. (2010). Hormonal control of the shoot stem-cell niche. Nature, 465(7301), 1089-1092. doi:10.1038/nature09126Ashikari, M. (2005). Cytokinin Oxidase Regulates Rice Grain Production. Science, 309(5735), 741-745. doi:10.1126/science.1113373Bartrina, I., Otto, E., Strnad, M., Werner, T., & Schmülling, T. (2011). Cytokinin Regulates the Activity of Reproductive Meristems, Flower Organ Size, Ovule Formation, and Thus Seed Yield in Arabidopsis thaliana. The Plant Cell, 23(1), 69-80. doi:10.1105/tpc.110.079079Hwang, I., Sheen, J., & Müller, B. (2012). Cytokinin Signaling Networks. Annual Review of Plant Biology, 63(1), 353-380. doi:10.1146/annurev-arplant-042811-105503Schaller, G. E., Bishopp, A., & Kieber, J. J. (2015). The Yin-Yang of Hormones: Cytokinin and Auxin Interactions in Plant Development. The Plant Cell, 27(1), 44-63. doi:10.1105/tpc.114.133595Kieber, J. J., & Schaller, G. E. (2010). The Perception of Cytokinin: A Story 50 Years in the Making: Figure 1. Plant Physiology, 154(2), 487-492. doi:10.1104/pp.110.161596Long, J. A., Moan, E. I., Medford, J. I., & Barton, M. K. (1996). A member of the KNOTTED class of homeodomain proteins encoded by the STM gene of Arabidopsis. Nature, 379(6560), 66-69. doi:10.1038/379066a0Jasinski, S., Piazza, P., Craft, J., Hay, A., Woolley, L., Rieu, I., … Tsiantis, M. (2005). KNOX Action in Arabidopsis Is Mediated by Coordinate Regulation of Cytokinin and Gibberellin Activities. Current Biology, 15(17), 1560-1565. doi:10.1016/j.cub.2005.07.023Yanai, O., Shani, E., Dolezal, K., Tarkowski, P., Sablowski, R., Sandberg, G., … Ori, N. (2005). Arabidopsis KNOXI Proteins Activate Cytokinin Biosynthesis. 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Impact of COVID-19 Pandemic on TAVR Activity: A Worldwide Registry

Background: The COVID-19 pandemic had a considerable impact on the provision of structural heart intervention worldwide. Our objectives were: 1) to assess the impact of the COVID-19 pandemic on transcatheter aortic valve replacement (TAVR) activity globally; and 2) to determine the differences in the impact according to geographic region and the demographic, development, and economic status of diverse international health care systems. Methods: We developed a multinational registry of global TAVR activity and invited individual TAVR sites to submit TAVR implant data before and during the COVID-19 pandemic. Specifically, the number of TAVR procedures performed monthly from January 2019 to December 2021 was collected. The adaptive measures to maintain TAVR activity by each site were recorded, as was a variety of indices relating to type of health care system and national economic indices. The primary subject of interest was the impact on TAVR activity during each of the pandemic waves (2020 and 2021) compared with the same period pre–COVID-19 (2019). Results: Data were received from 130 centers from 61 countries, with 14 subcontinents and 5 continents participating in the study. Overall, TAVR activity increased by 16.7% (2,337 procedures) between 2018 and 2019 (ie, before the pandemic), but between 2019 and 2020 (ie, first year of the pandemic), there was no significant growth (–0.1%; –10 procedures). In contrast, activity again increased by 18.9% (3,085 procedures) between 2020 and 2021 (ie, second year of the pandemic). During the first pandemic wave, there was a reduction of 18.9% (945 procedures) in TAVR activity among participating sites, while during the second and third waves, there was an increase of 6.7% (489 procedures) and 15.9% (1,042 procedures), respectively. Further analysis and results of this study are ongoing and will be available at the time of the congress. Conclusion: The COVID-19 pandemic initially led to a reduction in the number of patients undergoing TAVR worldwide, although health care systems subsequently adapted, and the number of TAVR recipients continued to grow in subsequent COVID-19 pandemic waves. Categories: STRUCTURAL: Valvular Disease: Aorti

Red Argentina de Parcelas Permanentes de Bosques Nativos para promover colaboraciones científicas en estudios de largo plazo

Las parcelas forestales permanentes son áreas de muestreo donde se registran periódicamente la identidad, abundancia y tamaño de los árboles, para estudiar cómo cambian los bosques en relación con el clima, los disturbios naturales y los usos y manejos. Hasta hoy, los patrones de cambio observados con parcelas permanentes en la Argentina tuvieron alcance local o regional. Para potenciar los vínculos entre los diferentes grupos de trabajo que promuevan colaboraciones a escalas intra- e inter-regionales creamos la Red Argentina de Parcelas Permanentes de Bosques Nativos (RAPP), abarcando las regiones forestales de los Bosques Andino-Patagónicos, Chaco Seco, Chaco Húmedo, Monte de Sierras y Bolsones, Monte de Llanuras y Mesetas, Selva Paranaense y Yungas. Aquí sintetizamos y caracterizamos la información de 317 parcelas permanentes (328.9 ha) incluidas en la RAPP, describiendo su distribución geográfica, objetivos, principales aspectos metodológicos y características de los bosques donde están establecidas (e.g., disturbios, tenencia de la tierra, estructura, riqueza de especies). Asimismo, se discute la complementariedad entre la RAPP y los inventarios nacionales de bosques nativos. Las parcelas se distribuyen entre 22.02° y 54.89° S y entre 19 y 2304 m s. n. m., aunque están concentradas principalmente en el Subtrópico (Chaco Seco, Chaco Húmedo, Selva Paranaense y Yungas) y en los Bosques Andino-Patagónicos. En todas las parcelas se identifica la taxonomía de los árboles y se miden diferentes variables dasométricas, fundamentales para responder preguntas ecológicas a una mayor escala mediante colaboraciones. Esperamos continuar incorporando grupos de trabajo a la RAPP e incentivar el establecimiento de nuevas parcelas permanentes en regiones poco representadas (e.g., Monte, Espinal y Delta e Islas del Paraná). La meta es que la RAPP permita avanzar en el estudio a largo plazo de todos los bosques nativos de la Argentina, aumentando la cobertura nacional y las interacciones entre los grupos de trabajo.Permanent forest plots are sampling areas where tree identity, abundance and size are recorded periodically, in order to study how forests change with climate, natural disturbances, uses and management. So far, patterns of change observed with permanent plots in Argentina have been local or regional. To promote scientific collaborations between different research groups within and among regions of Argentina, we created the Network of Permanent Plots of Native Argentinian Forests (RAPP), which includes the regions of Bosques Andino-Patagónicos, Chaco Seco, Chaco Húmedo, Monte de Sierras y Bolsones, Monte de Llanuras y Mesetas, Selva Paranaense and Yungas. Here we synthesize and characterize the information of 317 permanent plots (328.9 ha) included in the RAPP, describing their geographic distribution, objectives, main methodological aspects, and characteristics of the forests where they are established (e.g., disturbance, land tenure, structure, species richness), and after that, discuss the complementarity between the RAPP and the national inventories of native forests. Permanent plots are established over a wide range of latitude (22.02-54.89° S) and elevation (19 a 2304 m a. s. l.), but they are mainly concentrated in Subtropics (Chaco Seco, Chaco Húmedo, Selva Paranaense, and Yungas) and in Bosques Andino-Patagónicos. In all plots, trees are taxonomically identified and different dasometric variables are remeasured, which are the basis for potential collaborations to answer ecological questions at a larger scale. We hope to continue incorporating working groups in the RAPP and encouraging the establishment of plots, mainly in regions with a low number of permanent plots such as Monte, Espinal, and Delta e Islas del Paraná. The goal is that the RAPP advances in the long-term study of all native forests in Argentina, achieving a greater national cover and more interactions among research teams.Estación Experimental Agropecuaria BarilocheFil: Ceballos, Sergio Javier. Universidad Nacional de Tucuman. Instituto de Ecologia Regional; ArgentinaFil: Blundo, Cecilia. Universidad Nacional de Tucuman. Instituto de Ecologia Regional; ArgentinaFil: Malizia, Agustina. Universidad Nacional de Tucuman. Instituto de Ecologia Regional; ArgentinaFil: Osinaga Acosta, Oriana. Universidad Nacional de Tucuman. Instituto de Ecologia Regional; ArgentinaFil: Carilla, Julieta. Universidad Nacional de Tucuman. Instituto de Ecologia Regional; ArgentinaFil: Grau, Hector Ricardo. Universidad Nacional de Tucuman. Instituto de Ecologia Regional; ArgentinaFil: Cuchietti, Anibal. Ministerio de Ambiente y Desarrollo Sostenible de la Nación. Dirección Nacional de Bosques; ArgentinaFil: Campanello, Paula Inés. Universidad Nacional de la Patagonia San Juan Bosco. Facultad de Ingeniería; ArgentinaFil: Gasparri, Ignacio. Universidad Nacional de Tucuman. Instituto de Ecologia Regional; ArgentinaFil: Gatti, Genoveva. Universidad Nacional de Misiones. Instituto de Biología Subtropical; ArgentinaFil: Loto, Dante. Universidad Nacional de Santiago del Estero. Instituto de Biología Subtropical; ArgentinaFil: Martinez Pastur, Guillermo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Austral de Investigaciones Cientificas. Laboratorio de recursos agroforestales; ArgentinaFil: Saucedo Miranda, Jimena. Ministerio de Ambiente y Desarrollo Sostenible de la Nación. Dirección Nacional de Bosques; ArgentinaFil: Amoroso, Mariano. Universidad Nacional de Río Negro. Instituto de Investigaciones en Recursos Naturales, Agroecología y Desarrollo Rural; ArgentinaFil: Andino, Natalia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro de Investigaciones de la Geosfera y Biosfera; ArgentinaFil: Arpigiani, Daniela. Universidad Nacional de Río Negro. Instituto de Investigaciones en Recursos Naturales, Agroecología y Desarrollo Rural; ArgentinaFil: Aschero, Valeria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto Argentino de Nivologia, Glaciologia y Ciencias Ambientales; ArgentinaFil: Barberis, Ignacio Martin. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias. Instituto de Investigaciones en Ciencias Agrarias de Rosario; ArgentinaFil: Bedrij, Natalia Alejandra. Universidad Nacional de Misiones. Instituto de Biología Subtropical; ArgentinaFil: Nicora Chequin, Renata. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botanica del Nordeste; ArgentinaFil: Chillo, María Verónica. Instituto Nacional de Tecnologia Agropecuaria (INTA). Estacion Experimental Agropecuaria Bariloche. Agencia de Extension Rural El Bolson; ArgentinaFil: Chillo, María Verónica. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Investigaciones Forestales y Agropecuarias Bariloche; ArgentinaFil: Eibl, Beatriz. Universidad Nacional de Misiones. Facultad de Ciencias Forestales; ArgentinaFil: Eliano, Pablo. Asociación Forestal Industrial de Jujuy; ArgentinaFil: Fernandez, Romina Daiana. Universidad Nacional de Tucuman. Instituto de Ecologia Regional; ArgentinaFil: Garibaldi, Lucas Alejandro. Universidad Nacional de Río Negro. Instituto de Investigaciones en Recursos Naturales, Agroecología y Desarrollo Rural; ArgentinaFil: Giannoni, Stella. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro de Investigaciones de la Geosfera y Biosfera; ArgentinaFil: Goldenberg, Matias Guillermo. Universidad Nacional de Río Negro. Instituto de Investigaciones en Recursos Naturales, Agroecología y Desarrollo Rural; ArgentinaFil: Gonzalez Peñalba, Marcelo. Administracion Nacional de Parques Nacionales. Parque Nacional Lanin; ArgentinaFil: Jimenez, Yohana Gisell. Universidad Nacional de Tucuman. Instituto de Ecologia Regional; ArgentinaFil: Kees, Sebastian. Instituto Nacional de Tecnologia Agropecuaria (INTA). Estacion Experimental Agropecuaria Saenz Peña. Campo Anexo Estacion Forestal Plaza; ArgentinaFil: Klekailo, Graciela Noemi. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias; ArgentinaFil: Lara, Martin. Administracion Nacional de Parques Nacionales. Parque Nacional Lanin; ArgentinaFil: Mac Donagh, Patricio. Universidad Nacional de Misiones. Facultad de Ciencias Forestales; ArgentinaFil: Malizia, Lucio Ricardo. Universidad Nacional de Jujuy. Centro de Estudios Territoriales Ambientales y Sociales; ArgentinaFil: Mazzini, Flavia. Universidad Nacional de Jujuy. Centro de Estudios Territoriales Ambientales y Sociales; ArgentinaFil: Medina, Walter Adrian. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias. Instituto de Investigaciones en Ciencias Agrarias de Rosario; ArgentinaFil: Oddi, Facundo Jose.Universidad Nacional de Río Negro. Instituto de Investigaciones en Recursos Naturales, Agroecología y Desarrollo Rural; ArgentinaFil: Paredes, Dardo. Ministerio de Agricultura, Ganadería y Pesca de Tierra del Fuego. Dirección General de Desarrollo Forestal; ArgentinaFil: Peri, Pablo Luis. Instituto Nacional de Tecnologia Agropecuaria (INTA). Estacion Experimental Agropecuaria Santa Cruz; ArgentinaFil: Peri, Pablo Luis. Universidad Nacional de la Patagonia Austral; ArgentinaFil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Persini, Carlos. Fundación Huellas para un Futuro, Reserva, Refugio y Estación Biológica Aponapó. ArgentinaFil: Prado, Darien Eros. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias. Instituto de Investigaciones en Ciencias Agrarias de Rosario; ArgentinaFil: Salas, Roberto Manuel. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botanica del Nordeste; ArgentinaFil: Srur, Ana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto Argentino de Nivologia, Glaciologia y Ciencias Ambientales; ArgentinaFil: Villagra, Mariana. Universidad Nacional de Misiones. Instituto de Biología Subtropical; ArgentinaFil: Zelaya, Patricia. Universidad Nacional de Santiago del Estero. Facultad de Humanidades, Ciencias Sociales y de la Salud. Instituto de Estudios para el Desarrollo Social; ArgentinaFil: Villagra, Pablo Eugenio. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; Argentin

Candidate Massive Galaxies at z~4 in the Dark Energy Survey

Using stellar population models, we predicted that the Dark Energy Survey (DES) - due to its special combination of area (5000 deg. sq.) and depth ($i = 24.3$) - would be in the position to detect massive ($\gtrsim 10^{11}$ M$_{\odot}$) galaxies at $z \sim 4$. We confront those theoretical calculations with the first $\sim 150$ deg. sq. of DES data reaching nominal depth. From a catalogue containing $\sim 5$ million sources, $\sim26000$ were found to have observed-frame $g-r$ vs $r-i$ colours within the locus predicted for $z \sim 4$ massive galaxies. We further removed contamination by stars and artefacts, obtaining 606 galaxies lining up by the model selection box. We obtained their photometric redshifts and physical properties by fitting model templates spanning a wide range of star formation histories, reddening and redshift. Key to constrain the models is the addition, to the optical DES bands $g$, $r$, $i$, $z$, and $Y$, of near-IR $J$, $H$, $K_{s}$ data from the Vista Hemisphere Survey. We further applied several quality cuts to the fitting results, including goodness of fit and a unimodal redshift probability distribution. We finally select 233 candidates whose photometric redshift probability distribution function peaks around $z\sim4$, have high stellar masses ($\log($M$^{*}$/M$_{\odot})\sim 11.7$ for a Salpeter IMF) and ages around 0.1 Gyr, i.e. formation redshift around 5. These properties match those of the progenitors of the most massive galaxies in the local universe. This is an ideal sample for spectroscopic follow-up to select the fraction of galaxies which is truly at high redshift. These initial results and those at the survey completion, which we shall push to higher redshifts, will set unprecedented constraints on galaxy formation, evolution, and the re-ionisation epoch

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection