Multiple Myeloma Includes Phenotypically Defined Subsets of Clonotypic CD20+ B Cells that Persist During Treatment with Rituximab

Potential progenitor B cell compartments in multiple myeloma (MM) are clinically important. MM B cells and some circulating MM plasma cells express CD20, predicting their clearance by treatment with anti-CD20. Here we describe two types of clonotypic CD20+ B cell in peripheral blood of myeloma patients, identified by their expression of CD19 and CD20 epitopes, their expression of CD45RA and their light scatter properties. Thus, the circulating component of the MM clone includes at least two distinct CD19+ CD20+ B cell compartments, as well as CD138+ CD20+ plasma cells. To determine whether either or both B cell subsets and the CD20+ plasma cell subset were depleted by anti-CD20 therapy, they were evaluated before, during and after treatment of patients with rituximab (anti-CD20), followed by quantifying B cell subsets over a 5 month period during and after treatment. Overall, all three types of circulating B lineage cells persist despite treatment with rituximab. The inability of rituximab to prolong survival in MM may result from this failure to deplete CD20+ B and plasma cells in MM

Root ABA and H+-ATPase are key players in the root and shoot growth-promoting action of humic acids

Although the ability of humic (HA) and fulvic acids (FA) to improve plant growth has been demonstrated, knowledge about the mechanisms responsible for the direct effects of HA and FA on the promotion of plant growth is scarce and fragmentary. Our study investigated the causal role of both root PM H+-ATPase activity and ABA in the SHA-promoting action on both root and shoot growth. The involvement of these processes in the regulation of shoot cytokinin concentration and activity was also studied. Our aim was to integrate such plant responses for providing new insights to the current model on the mode of action of HA for promoting root and shoot growth. Experiments employing specific inhibitors and using Cucumis sativus L. plants show that both the root PM H+-ATPase activity and root ABA play a crucial role in the root growth-promoting action of SHA. With regard to the HA-promoting effects on shoot growth, two pathways of events triggered by the interaction of SHA with plant roots are essential for the increase in root PM H+-ATPase activity—which also mediates an increase in cytokinin concentration and action in the shoot—and the ABA-mediated increase in hydraulic conductivity (Lpr).Fil: Olaetxea, Maite. Universidad de Navarra; EspañaFil: Mora, Maria Veronica. Universidad Nacional de Rio Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones Agrobiotecnológicas - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Agrobiotecnológicas; ArgentinaFil: Bacaicoa, Eva. Universidad de Navarra; EspañaFil: Baigorri, Roberto. Timac Agro. Technical and Development Department; EspañaFil: Garnica, Maria. Universidad de Navarra; EspañaFil: Fuentes, Marta. Universidad de Navarra; EspañaFil: Zamarreño, Angel Maria. Universidad de Navarra; EspañaFil: Spíchal, Lukáš. Palacký University Olomouc; República ChecaFil: García-Mina, José María. Universidad de Navarra; Españ

Root ABA and H+-ATPase are key players in the root and shoot growth-promoting action of humic acids

Although the ability of humic (HA) and fulvic acids (FA) to improve plant growth has been demonstrated, knowledge about the mechanisms responsible for the direct effects of HA and FA on the promotion of plant growth is scarce and fragmentary. Our study investigated the causal role of both root PM H+-ATPase activity and ABA in the SHA-promoting action on both root and shoot growth. The involvement of these processes in the regulation of shoot cytokinin concentration and activity was also studied. Our aim was to integrate such plant responses for providing new insights to the current model on the mode of action of HA for promoting root and shoot growth. Experiments employing specific inhibitors and using Cucumis sativus L. plants show that both the root PM H+-ATPase activity and root ABA play a crucial role in the root growth-promoting action of SHA. With regard to the HA-promoting effects on shoot growth, two pathways of events triggered by the interaction of SHA with plant roots are essential for the increase in root PM H+-ATPase activity-which also mediates an increase in cytokinin concentration and action in the shoot-and the ABA-mediated increase in hydraulic conductivity (Lp(r))

Shoot iron status and auxin are involved in iron deficiency-induced phytosiderophores release in wheat

Background: The release of phytosiderephores (PS) to the rhizosphere is the main root response to iron (Fe) deficiency in graminaceous plants. We have investigated the role of the Fe status in the shoot as well as of the signaling pathways controlled by three relevant phytoregulators-indolacetic acid (IAA), ethylene and nitric oxide (NO) - in the regulation of this root response in Fe-starved wheat plants. To this end, the PS accumulation in the nutrient solution and the root expression of the genes encoding the nicotianamine aminotransferase (TaNAAT) and ferritin (TaFER) have been evaluated in plants subjected to different treatments. Results: The application of Fe to leaves of Fe-deficient plants prevented the increase in both PS root release and TaNAAT gene expression thus showing the relevant role of the shoot to root communication in the regulation of PS root release and some steps of PS biosynthesis. Experiments with specific hormone inhibitors showed that while ethylene and NO did not positively regulate Fe deficiency induced PS root release, auxin plays an essential role in the regulation of this process. Moreover, the application of IM to Fe-sufficient plants promoted both PS root release and TaNAAT gene expression thus indicating that auxin might be involved in the shoot to root signaling network regulating Fe-deficiency root responses in wheat Conclusions: These results therefore indicate that PS root release in Fe-deficient wheat plants is directly modulated by the shoot Fe status through signaling pathways involving, among other possible effectors, auxin

COVID-19 patients display changes in lymphocyte subsets with a higher frequency of dysfunctional CD8lo T cells associated with disease severity

This work examines cellular immunity against SARS-CoV-2 in patients from Córdoba, Argentina, during two major waves characterized by different circulating viral variants and different social behavior. Using flow cytometry, we evaluated the main lymphocyte populations of peripheral blood from hospitalized patients with moderate and severe COVID-19 disease. Our results show disturbances in the cellular immune compartment, as previously reported in different cohorts worldwide. We observed an increased frequency of B cells and a significant decrease in the frequency of CD3+ T cells in COVID-19 patients compared to healthy donors (HD). We also found a reduction in Tregs, which was more pronounced in severe patients. During the first wave, the frequency of GZMB, CD107a, CD39, and PD-1-expressing conventional CD4+ T (T conv) cells was significantly higher in moderate and severe patients than in HD. During the second wave, only the GZMB+ T conv cells of moderate and severe patients increased significantly. In addition, these patients showed a decreased frequency in IL-2-producing T conv cells. Interestingly, we identified two subsets of circulating CD8+ T cells with low and high CD8 surface expression in both HD and COVID-19 patients. While the percentages of CD8hi and CD8lo T cells within the CD8+ population in HD are similar, a significant increase was observed in CD8lo T cell frequency in COVID-19 patients. CD8lo T cell populations from HD as well as from SARS-CoV-2 infected patients exhibited lower frequencies of the effector cytokine-producing cells, TNF, IL-2, and IFN-γ, than CD8hi T cells. Interestingly, the frequency of CD8lo T cells increased with disease severity, suggesting that this parameter could be a potential marker for disease progression. Indeed, the CD8hi/CD8lo index helped to significantly improve the patient’s clinical stratification and disease outcome prediction. Our data support the addition of, at least, a CD8hi/CD8lo index into the panel of biomarkers commonly used in clinical labs, since its determination may be a useful tool with impact on the therapeutic management of the patients

Shoot iron status and auxin are involved in iron deficiency-induced phytosiderophores release in wheat

Background: The release of phytosiderephores (PS) to the rhizosphere is the main root response to iron (Fe) deficiency in graminaceous plants. We have investigated the role of the Fe status in the shoot as well as of the signaling pathways controlled by three relevant phytoregulators-indolacetic acid (IAA), ethylene and nitric oxide (NO) - in the regulation of this root response in Fe-starved wheat plants. To this end, the PS accumulation in the nutrient solution and the root expression of the genes encoding the nicotianamine aminotransferase (TaNAAT) and ferritin (TaFER) have been evaluated in plants subjected to different treatments. Results: The application of Fe to leaves of Fe-deficient plants prevented the increase in both PS root release and TaNAAT gene expression thus showing the relevant role of the shoot to root communication in the regulation of PS root release and some steps of PS biosynthesis. Experiments with specific hormone inhibitors showed that while ethylene and NO did not positively regulate Fe deficiency induced PS root release, auxin plays an essential role in the regulation of this process. Moreover, the application of IM to Fe-sufficient plants promoted both PS root release and TaNAAT gene expression thus indicating that auxin might be involved in the shoot to root signaling network regulating Fe-deficiency root responses in wheat Conclusions: These results therefore indicate that PS root release in Fe-deficient wheat plants is directly modulated by the shoot Fe status through signaling pathways involving, among other possible effectors, auxin

Responsabilidad Social Organizacional en la Gestión Humana: análisis teórico

Este documento propone elaborar un análisis sobre la responsabilidad social organizacional (RSO). Partiendo de su evolución terminológica hasta desarrollar uno de sus principios, el cual se destaca por la participación del capital humano como parte de los grupos primarios de interés, además abordar el concepto de gestión del talento humano. El propósito del documento es conocer cómo desde la visión de la gestión humana es posible aplicar la RSO en la organización con el fin de mantener el beneficio de las partes interesadas.//Abstract:This document proposes to elaborate an analysis on organizational social responsibility (OSR). Starting from its terminological evolution to develop one of its principles, which is stand out by the participation of human capital as part of the primary groups of interest, also address the concept of human talent management. The purpose of the document is to know how from the perspective of human management it is possible to apply the RSO in the organization in order to maintain the benefit of the interested parts

Single-Cell Analysis and Next-Generation Immuno-Sequencing Show That Multiple Clones Persist in Patients with Chronic Lymphocytic Leukemia

<div><p>The immunoglobulin heavy chain (<i>IGH)</i> gene rearrangement in chronic lymphocytic leukemia (CLL) provides a unique molecular signature; however, we demonstrate that 26/198 CLL patients (13%) had more than one <i>IGH</i> rearrangement, indicating the power of molecular technology over phenotypic analysis. Single-cell PCR analysis and next-generation immuno-sequencing identified <i>IGH</i>-defined clones. In 23% (18/79) of cases whose clones carried unmutated immunoglobulin heavy chain variable (<i>IGHV</i>) genes (U-CLL), <i>IGH</i> rearrangements were bialleic with one productive (P) and one non-productive (NP) allele. Two U-CLL were biclonal, each clone being monoallelic (P). In 119 <i>IGHV</i>-mutated (M-CLL) cases, one had biallelic rearrangements in their CLL (P/NP) and five had 2–4 distinct clones. Allelic exclusion was maintained in all B-clones analyzed. Based on single-cell PCR analysis, 5/11 partner clones (45%) reached levels of >5x10⁹ cells/L, suggesting second CLL clones. Partner clones persisted over years. Conventional <i>IGH</i> characterization and next-generation sequencing of 13 CLL, 3 multiple myeloma, 2 Waldenstrom’s macroglobulinemia and 3 age-matched healthy donors consistently identified the same rearranged <i>IGH</i> sequences. Most multiple clones occurred in M-CLL, perhaps indicative of weak clonal dominance, thereby associating with a good prognosis. In contrast, biallelic CLL occurred primarily in U-CLL thus being associated with poor prognosis. Extending beyond intra-clonal diversity, molecular analysis of clonal evolution and apparent subclones in CLL may also reflect <i>inter</i>-clonal diversity.</p></div

Comparison of clonal frequencies estimated by SCA and ImmunoSEQ NGS.

<p>^a Frequencies calculated as percentage of total productive <i>IGH</i> rearrangements</p><p>^<b>b</b> 66% had complete sequence homology, 8% comprised intraclonal heterogeneity outside of the CDR3 region.</p><p>Comparison of clonal frequencies estimated by SCA and ImmunoSEQ NGS.</p