Information Feedback and Mass Media Effects in Cultural Dynamics

We study the effects of different forms of information feedback associated with mass media on an agent-agent based model of the dynamics of cultural dissemination. In addition to some processes previously considered, we also examine a model of local mass media influence in cultural dynamics. Two mechanisms of information feedback are investigated: (i) direct mass media influence, where local or global mass media act as an additional element in the network of interactions of each agent, and (ii) indirect mass media influence, where global media acts as a filter of the influence of the existing network of interactions of each agent. Our results generalize substantiate previous findings showing that cultural diversity builds-up by increasing the strength of the mass media influence. We find that this occurs independently of the mechanisms of action (direct or indirect) of the mass media message. However, through an analysis of the full range of parameters measuring cultural diversity, we establish that the enhancement of cultural diversity produced by interaction with mass media only occurs for strong enough mass media messages. In comparison with previous studies a main different result is that weak mass media messages, in combination with agent-agent interaction, are efficient in producing cultural homogeneity. Moreover, the homogenizing effect of weak mass media messages are more efficient for direct local mass media messages than for global mass media messages or indirect global mass media influences.Agent Based Model, Culture, Dissemination, Mass Media

Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study

More than 20 years have passed since the identification of SLC3A1 and SLC7A9 as causative genes for cystinuria. However, cystinuria patients exhibit significant variability in the age of lithiasis onset, recurrence, and response to treatment, suggesting the presence of modulatory factors influencing cystinuria severity. In 2016, a second renal cystine transporter, AGT1, encoded by the SLC7A13 gene, was discovered. Although it was discarded as a causative gene for cystinuria, its possible effect as a modulatory gene remains unexplored. Thus, we analyzed its function in mouse models of cystinuria, screened the SLC7A13 gene in 34 patients with different lithiasic phenotypes, and functionally characterized the identified variants. Mice results showed that AGT1/rBAT may have a protective role against cystine lithiasis. In addition, among the four missense variants detected in patients, two exhibited a 25% impairment in AGT1/rBAT transport. However, no correlation between SLC7A13 genotypes and lithiasis phenotypes was observed in patients, probably because these variants were found in heterozygous states. In conclusion, our results, consistent with a previous study, suggest that AGT1/rBAT does not have a relevant effect on cystinuria patients, although an impact in patients carrying homozygous pathogenic variants cannot be discarded

Circulating clonotypic B cells in multiple myeloma and monoclonal gammopathy of undetermined significance

This is an open-access paper.The B-cell compartment in which multiple myeloma stem cells reside remains unclear. We investigated the potential presence of mature, surface-membrane immunoglobulin-positive B lymphocytes clonally related to the tumor bone marrow plasma cells among different subsets of peripheral blood B cells from ten patients (7 with multiple myeloma and 3 with monoclonal gammopathies of undetermined significance). The presence of clonotypic immunoglobulin heavy chain gene rearrangements was determined in multiple highly-purified fractions of peripheral blood B-lymphocytes including surface-membrane IgM+ CD27- naïve B-lymphocytes, plus surface-membrane IgG+, IgA+ and IgM+ memory CD27+ B cells, and normal circulating plasma cells, in addition to (mono)clonal plasma cells, by a highly-specific and sensitive allele-specific oligonucleotide polymerase chain reaction directed to the CDR3 sequence of the rearranged IGH gene of tumor plasma cells from individual patients. Our results showed systematic absence of clonotypic rearrangements in all the different B-cell subsets analyzed, including M-compo-nent isotype-matched memory B-lymphocytes, at frequencies <0.03 cells/mL (range: 0.0003-0.08 cells/mL); the only exception were the myeloma plasma cells detected and purified from the peripheral blood of four of the seven myeloma patients. These results indicate that circulating B cells from patients with multiple myeloma and monoclonal gammopathies of undetermined significance are usually devoid of clonotypic B cells while the presence of immunophenotypically aberrant myeloma plasma cells in peripheral blood of myeloma patients is a relatively frequent finding.This work was supported by grants from European Union FP6 STREP MSCNet (N. E06005FF), Cooperative Research Thematic Network on Cancer (RTICs; RTICC RD06/0020/0035-FEDER, RD06/0020/0006, RD12/0036/0048, RD12/0036/0069 and G03/136), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria Ministerio de Sanidad y Consumo (FIS: PI060339; 02/0905; 01/0089/01-02;PS09/01897, and PI06/0824-FEDER), Asociacion Española Contra el Cancer AECC (GCB120981SAN) and Gerencia Regional de Salud de Castilla y León; Ayuda de Excelencia de Castilla y León, Consejería de Educación (EDU/894/2009, GR37) Junta de Castilla y León, Valladolid, Spain. LST received a CAPES/Ministério da Educação scholarship from the Brazilian Government.Peer Reviewe

Cytogenetic profiles in multiple myeloma and monoclonal gammopathy of undetermined significance: a study in highly purified aberrant plasma cells

This is an open-access paper.Cytogenetic studies in clonal plasma cell disorders have mainly been done in whole bone marrow or CD138+ microbead-enriched plasma cells and suggest that recurrent immunoglobulin heavy chain translocations - e.g. t(4;14) - are primary oncogenetic events. The aim of this study was to determine cytogenetic patterns of highly purified aberrant plasma cells (median purity ≥98%) in different clonal plasma cell disorders. We analyzed aberrant plasma cells from 208 patients with multiple myeloma (n=148) and monoclonal gammopathy of undetermined significance (n=60) for the presence of del(13q14), del(17p13) and t(14q32) using multicolor interphase fluorescence in situ hybridization. Additionally, immunoglobulin heavy chain gene arrangements were analyzed and complementarity determining region 3 was sequenced in a subset of patients and combined multicolor interphase fluorescence in situ hybridization/immunofluorescent protein staining analyses were performed in selected cases to confirm clonality and cytogenetic findings. At diagnosis, 96% of cases with multiple myeloma versus 77% of monoclonal gammopathy of undetermined significance cases showed at least one cytogenetic alteration and/or hyperdiploidy. The cytogenetic heterogeneity of individual cases reflected coexistence of cytogenetically-defined aberrant plasma cell clones, and led to the assumption that karyotypic alterations were acquired stepwise. Cases of multiple myeloma and monoclonal gammopathy of undetermined significance frequently showed different but related cytogenetic profiles when other cytogenetic alterations such as deletions/gains of the immunoglobulin heavy chain or the fibroblast growth factor receptor 3 were additionally considered. Interestingly, in 24% of multiple myeloma versus 62% of monoclonal gammopathy of undetermined significance patients with an immunoglobulin heavy chain translocation, aberrant plasma cells with and without t(14q32) coexisted in the same patient. Our data suggest that recurrent immunoglobulin heavy chain translocations might be absent in the primordial plasma cell clone in a significant proportion of patients with clonal plasma cell disorders carrying these cytogenetic alterations.This work was partially supported by grants from the Fundacion Memoria de Don Samuel Solorzano Barruso, Salamanca, Spain (FS/4-2010). The authors would also like to thank the Dr. Werner Jackstädt Foundation (Wuppertal, Germany) for grant supporting the work of Martin Schmidt-Hieber. The authors would like to thank the Cooperative Research Thematic Network (RTICs; RTICC RD06/0020/0035, RD06/0020/0006 and G03/136), MM Jevitt, SL firm, Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS: PI060339; 02/0905; 01/0089/01-02; PS09/01897) and Gerencia Regional de Salud de Castilla y León; Ayuda de Excelencia de Castilla y León, Consejeria de Educación (EDU/894/2009, GR37), and Consejería de Sanidad (557/A/10), Junta de Castilla y León, Valladolid, Spain for supporting this study. JMS is supported by a grant (CP05/00321) from the ISCIII, Ministerio de Ciencia e Innovacion, Madrid, Spain.Peer Reviewe

Detailed characterization of multiple myeloma circulating tumor cells shows unique phenotypic, cytogenetic, functional, and circadian distribution profile

[EN]Circulating myeloma tumor cells (CTCs) as defined by the presence of peripheral blood (PB) clonal plasma cells (PCs) are a powerful prognostic marker in multiple myeloma (MM). However, the biological features of CTCs and their pathophysiological role in MM remains unexplored. Here, we investigate the phenotypic, cytogenetic, and functional characteristics as well as the circadian distribution of CTCs vs paired bone marrow (BM) clonal PCs from MM patients. Our results show that CTCs typically represent a unique subpopulation of all BM clonal PCs, characterized by downregulation (P < .05) of integrins (CD11a/CD11c/CD29/CD49d/CD49e), adhesion (CD33/CD56/CD117/CD138), and activation molecules (CD28/CD38/CD81). Fluorescence in situ hybridization analysis of fluorescence-activated cell sorter-sorted CTCs also unraveled different cytogenetic profiles vs paired BM clonal PCs. Moreover, CTCs were mostly quiescent and associated with higher clonogenic potential when cocultured with BM stromal cells. Most interestingly, CTCs showed a circadian distribution which fluctuates in a similar pattern to that of CD34(+) cells, and opposite to stromal cell-derived factor 1 plasma levels and corresponding surface expression of CXC chemokine receptor 4 on clonal PCs, suggesting that in MM, CTCs may egress to PB to colonize/metastasize other sites in the BM during the patients' resting period

Explorando saberes: la etnobotánica a través del registro audiovisual como instrumento de innovación docente para el aprendizaje significativo y la acción social del desarrollo sostenible

Memoria ID-170. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2019-2020

The cellular origin and malignant transformation of Waldenström macroglobulinemia

Although information about the molecular pathogenesis of Waldenström macroglobulinemia (WM) has significantly advanced, the precise cell of origin and the mechanisms behind WM transformation from immunoglobulin-M (IgM) monoclonal gammopathy of undetermined significance (MGUS) remain undetermined. Here, we undertook an integrative phenotypic, molecular, and genomic approach to study clonal B cells from newly diagnosed patients with IgM MGUS (n = 22), smoldering (n = 16), and symptomatic WM (n = 11). Through principal component analysis of multidimensional flow cytometry data, we demonstrated highly overlapping phenotypic profiles for clonal B cells from IgM MGUS, smoldering, and symptomatic WM patients. Similarly, virtually no genes were significantly deregulated between fluorescence-activated cell sorter-sorted clonal B cells from the 3 disease groups. Interestingly, the transcriptome of the Waldenström B-cell clone was highly different than that of normal CD25-CD22+ B cells, whereas significantly less genes were differentially expressed and specific WM pathways normalized once the transcriptome of the Waldenström B-cell clone was compared with its normal phenotypic (CD25+CD22+low) B-cell counterpart. The frequency of specific copy number abnormalities [+4, del(6q23.3-6q25.3), +12, and +18q11-18q23] progressively increased from IgM MGUS and smoldering WM vs symptomatic WM (18% vs 20% and 73%, respectively; P = .008), suggesting a multistep transformation of clonal B cells that, albeit benign (ie, IgM MGUS and smoldering WM), already harbor the phenotypic and molecular signatures of the malignant Waldenström clone.This study was supported by Cooperative Research Thematic Network grants RD12/0036/0058 and RD12/0036/0048 of the Red de Cancer (Cancer Network of Excellence), Consejería de Sanidad, Junta de Castilla y Leon, Valladolid, Spain (557/A/10).Peer Reviewe

Etnobotánica, aprovechamiento tradicional de plantas y patrimonio cultural como instrumento de innovación para el desarrollo sostenible

Memoria ID-0147. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2017-2018

Percepción, valores y actitudes sobre el medio ambiente y el tratamiento de la problemática ambiental en los medios de comunicación

Memoria ID-0142. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2014-2015

Impact of measurable residual disease by decentralized flow cytometry: a PETHEMA real-world study in 1076 patients with acute myeloid leukemia

The role of decentralized assessment of measurable residual disease (MRD) for risk stratification in acute myeloid leukemia (AML) remains largely unknown, and so it does which methodological aspects are critical to empower the evaluation of MRD with prognostic significance, particularly if using multiparameter flow cytometry (MFC). We analyzed 1076 AML patients in first remission after induction chemotherapy, in whom MRD was evaluated by MFC in local laboratories of 60 Hospitals participating in the PETHEMA registry. We also conducted a survey on technical aspects of MRD testing to determine the impact of methodological heterogeneity in the prognostic value of MFC. Our results confirmed the recommended cutoff of 0.1% to discriminate patients with significantly different cumulative-incidence of relapse (-CIR- HR:0.71, P < 0.001) and overall survival (HR: 0.73, P = 0.001), but uncovered the limited prognostic value of MFC based MRD in multivariate and recursive partitioning models including other clinical, genetic and treatment related factors. Virtually all aspects related with methodological, interpretation, and reporting of MFC based MRD testing impacted in its ability to discriminate patients with different CIR. Thus, this study demonstrated that “real-world” assessment of MRD using MFC is prognostic in patients at first remission, and urges greater standardization for improved risk-stratification toward clinical decisions in AML.This study was supported by the Centro de Investigación Biomédica en Red – Área de Oncología - del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369, CB16/12/00233, CB16/12/00284 and CB16/12/00400), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS No. PI16/01661, PI16/00517 and PI18/01946), Gerencia Regional de Salud de CyL (GRS 1346/A/16) and the Plan de Investigación de la Universidad de Navarra (PIUNA 2014-18). This study was supported internationally by the Cancer Research UK, FCAECC and AIRC under the Accelerator Award Program EDITOR