Qualitative Hermeneutic Phenomenological Study: The Lived Experiences of School Leaders Who Have Worked Through a Merger

This qualitative hermeneutic phenomenological study describes the lived experiences of school leaders who worked through the processes of school mergers in New York State. The central research question that guided the study was: What are the lived experiences of school leaders who worked through the processes of a school merger? In addition, guiding questions were implemented to understand the phenomenon of school mergers. The guiding questions are: How do school leaders maneuver and manage the organizational structures impacted by the processes of a school merger? What role do school leaders play in the environmental demands influencing the processes of a school merger? Organizational theory guided the study. Organizational theory is the study of how organizations operate and how they impact and are impacted by the environment in which they operate. Utilizing the three principles of organizational theory: organizational structure, culture, and design and change the study describes the lived experiences of school leaders who worked through the processes of school mergers. Study participants were selected through a participant survey screener. The study was conducted through purposeful criterion sampling and data collection methods using individual interviews, focus groups, and questionnaires. The transcendental phenomenological reduction process was used for data analysis. Keywords: merger, organizational theory, school leadershi

Epigenetic Regulation of B Lymphocyte Differentiation, Transdifferentiation, and Reprogramming

B cell development is a multistep process that is tightly regulated at the transcriptional level. In recent years, investigators have shed light on the transcription factor networks involved in all the differentiation steps comprising B lymphopoiesis. The interplay between transcription factors and the epigenetic machinery involved in establishing the correct genomic landscape characteristic of each cellular state is beginning to be dissected. The participation of "epigenetic regulator-transcription factor" complexes is also crucial for directing cells during reprogramming into pluripotency or lineage conversion. In this context, greater knowledge of epigenetic regulation during B cell development, transdifferentiation, and reprogramming will enable us to understand better how epigenetics can control cell lineage commitment and identity. Herein, we review the current knowledge about the epigenetic events that contribute to B cell development and reprogramming

Validación de instrumento de medición para el diagnóstico del proceso de formación de pregrado

El presente artículo revela el proceder realizado por los autores en el diseño y elaboración del instrumento de medición Cuestionario de encuesta a estudiantes para el diagnóstico del proceso de formación de pregrado, todo lo cual emana del proyecto de investigación “Modelo pedagógico acorde con las demandas del siglo XXI para la formación de profesionales en la Universidad de Artemisa”. Se consideran los procedimientos que permitieron adjudicar validez y confiabilidad al instrumento de medición y se exponen los análisis estadísticos que evalúan la consistencia interna del cuestionario a partir de la aplicación del Coeficiente de Correlación Multidimensional rpj, un novedoso y reconocido procedimiento lógico aceptado por la Teoría Clásica de los Test. El pilotaje se realizó a una muestra intencional de 13 estudiantes de la carrera de Lenguas Extranjeras de la Facultad de Ciencias de la Educación, por constituir un grupo homogéneo con una apropiada motivación por sus estudios. Al aplicar el coeficiente a los resultados que se registraron en cada una de las preguntas del instrumento se obtuvieron valores oscilantes entre 0,58 y 0,64 lo cual infiere que el instrumento tiene consistencia y por tanto es confiable.   Palabras clave: validez, confiabilidad,  instrumento de medición.   Abstract The present article reveals the procedure carried out by the authors in the design and elaboration of the survey questionnaire applied to the students as measuring instrument for the diagnosis of the undergraduate training process, all of which arises from the research project "Pedagogical model according to the demands of the 21st century for the training of professionals at the University of Artemisa”. The procedures granting validity and reliability to the measurement instrument were also considered and presented as well as the statistical analysis evaluating the internal consistency of the questionnaire as result of the application of the Multidimensional Correlation Coefficient rpj, a novel and recognized logical procedure accepted by the Classical Theory of Tests. The piloting was done to an intentional sample of 13 students of the Foreign Languages majoring at the School of Sciences of the Education for constituting a homogenous group with an appropriate motivation by their studies. When applying the coefficient to the results that were registered in each one of the questions of the instrument, oscillating values between 0.58 and 0.64 were obtained, which implies that the instrument has consistency and, therefore, it is reliable.   Keywords: validity, reliability, measuring instrument

Validación de instrumento de medición para el diagnóstico del proceso de formación de pregrado

The present article reveals the procedure carried out by the authors in the design and elaboration of the survey questionnaire applied to the students as measuring instrument for the diagnosis of the undergraduate training process, all of which arises from the research project "Pedagogical model according to the demands of the 21st century for the training of professionals at the University of Artemisa”. The procedures granting validity and reliability to the measurement instrument were also considered and presented as well as the statistical analysis evaluating the internal consistency of the questionnaire as result of the application of the Multidimensional Correlation Coefficient rpj, a novel and recognized logical procedure accepted by the Classical Theory of Tests. The piloting was done to an intentional sample of 13 students of the Foreign Languages majoring at the School of Sciences of the Education for constituting a homogenous group with an appropriate motivation by their studies. When applying the coefficient to the results that were registered in each one of the questions of the instrument, oscillating values between 0.58 and 0.64 were obtained, which implies that the instrument has consistency and, therefore, it is reliable.El presente artículo revela el proceder realizado por los autores en el diseño y elaboración del instrumento de medición Cuestionario de encuesta a estudiantes para el diagnóstico del proceso de formación de pregrado, todo lo cual emana del proyecto de investigación “Modelo pedagógico acorde con las demandas del siglo XXI para la formación de profesionales en la Universidad de Artemisa”. Se consideran los procedimientos que permitieron adjudicar validez y confiabilidad al instrumento de medición y se exponen los análisis estadísticos que evalúan la consistencia interna del cuestionario a partir de la aplicación del Coeficiente de Correlación Multidimensional rpj, un novedoso y reconocido procedimiento lógico aceptado por la Teoría Clásica de los Test. El pilotaje se realizó a una muestra intencional de 13 estudiantes de la carrera de Lenguas Extranjeras de la Facultad de Ciencias de la Educación, por constituir un grupo homogéneo con una apropiada motivación por sus estudios. Al aplicar el coeficiente a los resultados que se registraron en cada una de las preguntas del instrumento se obtuvieron valores oscilantes entre 0,58 y 0,64 lo cual infiere que el instrumento tiene consistencia y por tanto es confiable

HDAC7 is a major contributor in the pathogenesis of infant t(4;11) proB acute lymphoblastic leukemia

This paper was funded by grants to MP by the Spanish Ministry of Science, Innovation and Universities (SAF2017-87990-R and EUR2019-103835) and elaborated at the Josep Carreras Leukaemia Research Institute (IJC, Badalona, Barcelona) and IDIBELL Research Institute (L’Hospitalet de Llobregat, Barcelona). OdB is funded by a Juan de la Cierva—Formación fellowship from the Spanish Ministry of Science, Innovation and Universities (FJCI-2017-32430). AM is funded by the Spanish Ministry of Science, Innovation and Universities, which is part of the Agencia Estatal de Investigación (AEI), through grant PRE2018-083183 (cofunded by the European Social Fund). Work in PM and CB’s lab was supported by the European Research Council (CoG-2014646903), the Spanish Ministry of Economy and Competitiveness (SAF-2016-80481-R), Uno entre Cien Mil Foundation, the Leo Messi Foundation, the Asociación Española Contra el Cáncer (AECC-CI-2015), and the ISCIII/FEDER (PI17/01028).

The HDAC7-TET2 epigenetic axis is essential during early B lymphocyte development

Correct B cell identity at each stage of cellular differentiation during B lymphocyte development is critically dependent on a tightly controlled epigenomic landscape. We previously identified HDAC7 as an essential regulator of early B cell development and its absence leads to a drastic block at the pro-B to pre-B cell transition. More recently, we demonstrated that HDAC7 loss in pro-B-ALL in infants associates with a worse prognosis. Here we delineate the molecular mechanisms by which HDAC7 modulates early B cell development. We find that HDAC7 deficiency drives global chromatin de-condensation, histone marks deposition and deregulates other epigenetic regulators and mobile elements. Specifically, the absence of HDAC7 induces TET2 expression, which promotes DNA 5-hydroxymethylation and chromatin de-condensation. HDAC7 deficiency also results in the aberrant expression of microRNAs and LINE-1 transposable elements. These findings shed light on the mechanisms by which HDAC7 loss or misregulation may lead to B cell-based hematological malignancies.FUNDING: Spanish Ministry of Economy and Competitiveness (MINECO) [SAF2017-87990-R]; Spanish Ministry of Science and Innovation (MICINN) [EUR2019-103835]; Josep Carreras Leukaemia Research Institute (IJC, Badalona, Barcelona); IDIBELL Research Institute (L’Hospitalet de Llobregat, Barcelona); A.M. is funded by the Spanish Ministry of Science, Innovation and Universities, which is part of the Agencia Estatal de Investigacion (AEI) [PRE2018-083183] (cofunded by the European Social Fund]; OdB. was funded by a Juan de la Cierva Formacion Fellowship from the Spanish Ministry of Science, Innovation and Universities [FJCI-2017-32430]; Postdoctoral Fellowship from the Asociacion Española Contra el Cáncer (AECC) ´ Foundation [POSTD20024DEBA]; B.M. is awardee of the Ayudas para la formacion del profesorado universitario [FPU18/00755, Ministerio de Universidades]; B.M.J. is funded by La Caixa Banking Foundation Junior Leader project [LCF/BQ/PI19/11690001]; FEDER/Spanish Ministry of Science and Innovation [RTI2018-094788-A-I00]; L.T.-D. is funded by the FPI Fellowship [PRE2019- 088005]; L.R. is funded by an AGAUR FI fellowship [2019FI-B00017]; J.L.S. is funded by ISCIII [CP19/00176], co-funded by ESF, ‘Investing in your future’ and the Spanish Ministry of Science, Innovation and Universities [PID2019-111243RA-I00]. CRG acknowledge the support of the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049- S, MCIN/AEI /10.13039/501100011033). Funding for open access charge: Spanish Ministry of Science, Innovation and Universities (MICIU) [SAF2017-87990-R, EUR2019-103835].ACKNOWLEDGEMENTS: We thank CERCA Programme/Generalitat de Catalunya and the Josep Carreras Foundation for institutional support. We thank Dr Eric Olson (UT Southwestern Medical Center, Dallas, TX, USA) and Dr Michael Reth (Max Planck Institute of Immunology and Epigenetics, Freiburg, Germany) for kindly providing the Hdac7loxp/- and mb1- Cre mice, respectively. We thank Luc´ıa Fanlo for her assistance in technical issues and bioinformatics analysis of ChIP-seq and ATAC-seq experiments. We thank Alberto Bueno for deep analysis of our RNA-seq and hMeDIP-seq data, in order to assess the presence of differentially expressed dsRNA species. We also thank Drs Pura Munoz ˜ Canoves and Tokameh Mahmoudi for helpful comments on ´ the manuscript

In vivo conditional deletion of HDAC7 reveals its requirement to establish proper B lymphocyte identity and development

Class IIa histone deacetylase (HDAC) subfamily members are tissue-specific gene repressors with crucial roles in development and differentiation processes. A prominent example is HDAC7, a class IIa HDAC that shows a lymphoid-specific expression pattern within the hematopoietic system. In this study, we explored its potential role in B cell development by generating a conditional knockout mouse model. Our study demonstrates for the first time that HDAC7 deletion dramatically blocks early B cell development and gives rise to a severe lymphopenia in peripheral organs, while also leading to pro-B cell lineage promiscuity. We find that HDAC7 represses myeloid and T lymphocyte genes in B cell progenitors through interaction with myocyte enhancer factor 2C (MEFC2). In B cell progenitors, HDAC7 is recruited to promoters and enhancers of target genes, and its absence leads to increased enrichment of histone active marks. Our results prove that HDAC7 is a bona fide transcriptional repressor essential for B cell development

Obesity attenuates the effect of sleep apnea on active TGF-ss 1 levels and tumor aggressiveness in patients with melanoma

Active transforming growth factor-β1 (TGF-β1), a cytokine partially regulated by hypoxia and obesity, has been related with poor prognosis in several tumors. We determine whether obstructive sleep apnea (OSA) increases serum levels of active TGF-β1 in patients with cutaneous melanoma (CM), assess their relationship with melanoma aggressiveness and analyze the factors related to TGF-β1 levels in obese and non-obese OSA patients. In a multicenter observational study, 290 patients with CM were underwent sleep studies. TGF-β1 was increased in moderate-severe OSA patients vs. non-OSA or mild OSA patients with CM. In OSA patients, TGF-β1 levels correlated with mitotic index, Breslow index and melanoma growth rate, and were increased in presence of ulceration or higher Clark levels. In CM patients, OSA was associated with higher TGF-β1 levels and greater melanoma aggressiveness only in non-obese subjects. An in vitro model showed that IH-induced increases of TGF-β1 expression in melanoma cells is attenuated in the presence of high leptin levels. In conclusion, TGF-β1 levels are associated with melanoma aggressiveness in CM patients and increased in moderate-severe OSA. Moreover, in non-obese patients with OSA, TGF-β1 levels correlate with OSA severity and leptin levels, whereas only associate with leptin levels in obese OSA patients

The Role of MMP7 and Its Cross-Talk with the FAS/FASL System during the Acquisition of Chemoresistance to Oxaliplatin

Background: The efficacy of oxaliplatin in cancer chemotherapy is limited by the development of drug resistance. MMP7 has been related to the loss of tumor cell response to cytotoxic agents although the exact mechanism is not fully understood. Moreover, MMP7 is an independent prognosis factor for survival in patients with colorectal cancer. The aim of the present study was to analyze the role of MMP7 and its cross-talk with the Fas/FasL system during the acquisition of oxaliplatin resistance in colon cancer cells. Principal Findings: For this purpose we have developed three different oxaliplatin-resistant cell lines (RHT29, RHCT116 p53+/+, RHCT116 p53−/−) from the parental HT29, HCT116 p53+/+ and HCT116 p53−/− colon cancer cells. MMP7 basal expression was higher in the resistant compared to the parental cell lines. MMP7 was also upregulated by oxaliplatin in both HT29 (p53 mutant) and RHCT116 p53−/− but not in the RHCT116 p53+/+. Inhibition of MMP by 1,10-phenantroline monohydrate or siRNA of MMP7 restores cell sensitivity to oxaliplatin-induced apoptosis in both HT29 and RHCT116 p53−/− but not in the RHCT116 p53+/+. Some of these effects are caused by alterations in Fas receptor. Fas is upregulated by oxaliplatin in colon cancer cells, however the RHT29 cells treated with oxaliplatin showed a 3.8-fold lower Fas expression at the cell surface than the HT29 cells. Decrease of Fas at the plasma membrane seems to be caused by MMP7 since its inhibition restores Fas levels. Moreover, functional analysis of Fas demonstrates that this receptor was less potent in inducing apoptosis in RHT29 cells and that its activation induces MAPK signaling in resistant cells. Conclusions: Taking together, these results suggest that MMP7 is related to the acquisition of oxaliplatin-resistance and that its inhibition restores drug sensitivity by increasing Fas receptor. Furthermore, Fas undergoes a change in its functionality in oxaliplatin-resistant cells inducing survival pathways instead of apoptotic signals

HDAC7 Is a Repressor of Myeloid Genes Whose Downregulation Is Required for Transdifferentiation of Pre-B Cells into Macrophages

B lymphopoiesis is the result of several cell-commitment, lineage-choice, and differentiation processes. Every differentiation step is characterized by the activation of a new, lineage-specific, genetic program and the extinction of the previous one. To date, the central role of specific transcription factors in positively regulating these distinct differentiation processes to acquire a B cell-specific genetic program is well established. However, the existence of specific transcriptional repressors responsible for the silencing of lineage inappropriate genes remains elusive. Here we addressed the molecular mechanism behind repression of non-lymphoid genes in B cells. We report that the histone deacetylase HDAC7 was highly expressed in pre-B cells but dramatically down-regulated during cellular lineage conversion to macrophages. Microarray analysis demonstrated that HDAC7 re-expression interfered with the acquisition of the gene transcriptional program characteristic of macrophages during cell transdifferentiation; the presence of HDAC7 blocked the induction of key genes for macrophage function, such as immune, inflammatory, and defense response, cellular response to infections, positive regulation of cytokines production, and phagocytosis. Moreover, re-introduction of HDAC7 suppressed crucial functions of macrophages, such as the ability to phagocytose bacteria and to respond to endotoxin by expressing major pro-inflammatory cytokines. To gain insight into the molecular mechanisms mediating HDAC7 repression in pre-B cells, we undertook co-immunoprecipitation and chromatin immunoprecipitation experimental approaches. We found that HDAC7 specifically interacted with the transcription factor MEF2C in pre-B cells and was recruited to MEF2 binding sites located at the promoters of genes critical for macrophage function. Thus, in B cells HDAC7 is a transcriptional repressor of undesirable genes. Our findings uncover a novel role for HDAC7 in maintaining the identity of a particular cell type by silencing lineage-inappropriate genes