Registro de contribuyente municipal de Tipitapa Gestión del Registro Municipal de Contribuyente

En la presente Monografía de Graduación, abordamos el tema de sistema de recaudación en el municipio de Tipitapa y lo demás Municipio al nivel Nacional, con el fin de Implementar estrategias de Control en Actualizar la Información de los Contribuyente, Sistema de Actualización de Registro a Contribuyente en la Circunscripción del Municipio de Tipitapa, y manuales que sirven como guía y control e incrementar los ingresos. Es de gran importancia que las municipalidades a nivel general cuenten con esta herramienta ya que en la actualidad la alcaldía municipal de Tipitapa no cuenta con esta guía que vienen a fortalecer las recaudaciones y brindar, mejor atención a la población

CRISPR-ERA for Switching Off (Onco) Genes

Genome-editing nucleases like the popular CRISPR/Cas9 enable the generation of knockout cell lines and null zygotes by inducing site-specific double-stranded breaks (DSBs) within a genome. In most cases, when a DNA template is not present, the DSB is repaired by nonhomologous end joining (NHEJ), resulting in small nucleotide insertions or deletions that can be used to construct knockout alleles. However, for several reasons, these mutations do not produce the desired null result in all cases, instead generating a similar protein with functional activity. This undesirable effect could limit the therapeutic efficiency of gene therapy strategies focused on abrogating oncogene expression by CRISPR/Cas9 and should be taken into account. This chapter reviews the irruption of CRISPR technology for gene silencing and its application in gene therapy

Plan de negocio para la constitución de una despensa familiar para los empleados de la Alcaldía municipal de Mejicanos en el departamento de San Salvador.

El tema del trabajo de graduación surgió porque un miembro del equipo de investigación consideró que un plan de negocios es necesario para la Alcaldía Municipal de Mejicanos, porque la gerencia estaba considerando el implementar una Despensa para los empleados y ofrecer productos de primera necesidad y al alcance de sus bolsillos, es por esto que se estableció el tema: “Plan de Negocio para la Constitución de una Despensa Familiar para los empleados de la Alcaldía Municipal de Mejicanos en el departamento de San Salvador”, con el objetivo de poder brindar a los empleados un lugar donde encuentren lo que necesitan; para sus hogares, y sobre todo en lugar cercano de su lugar de trabajo, con precios competitivos. Al realizar la investigación, se implementó el método científico que se entiende como el conjunto de postulados, reglas y normas para el estudio y la solución de los problemas de investigación, también por medio de los métodos auxiliares como el analítico y el sintético se encontró una alternativa para el plan de negocios para la constitución de una despensa, por medio de técnicas de recolección de información como la entrevista, encuesta, se logró obtener información relevante acerca de la necesidad que existe de que exista una despensa familiar en la Alcaldía de Mejicanos, se elaboró un cuestionario y guía de entrevista. Para la investigación se recurrió a fuentes primarias que la constituyen la encuesta y la entrevista, también se utilizaron fuentes secundarias: libros, trabajos de investigación, revistas, leyes, sitios virtuales, documentos de las instituciones que regulan el funcionamiento de los municipios. Se establecieron las unidades de análisis, el ámbito de estudio y se determinó la muestra. Se interpretó las respuestas al cuestionario y se realizó el diagnostico de los resultados. De acuerdo al diagnóstico se concluye lo siguiente:• Un Plan de Negocios, constituirá en la Alcaldía, una herramienta fundamental para la implementación de la Despensa ya que se establecerá una guía, para que el nuevo establecimiento funcione en óptimas condiciones. • Se brindarán precios al alcance de los empleados ya que se buscarán proveedores que ofrezcan precios bajos, pero sobre todo que los productos sean de calidad. • Al pagar sus productos, los empleados lo harán al contado porque esta es la mejor manera para que la Despensa obtenga sus ingresos diarios y sobre todo que las operaciones no se detengan. • La Despensa contará con un espacio, físico en las cercanías de las alcaldías, esto con el motivo de que los empleados cuenten con un lugar donde puedan realizar sus compras, ya sea a la hora del almuerzo como la hora de salida de su trabajo. Recomendaciones • La Alcaldía al contar con el Plan de Negocios deberá tomar en cuenta los resultados que se plantean en este trabajo de investigación, para que las operaciones de la nueva Despensa sean las indicadas y produzcan ganancias. • Se debe procurar con el establecimiento de la nueva Despensa ser competitivos con los precios de los otros establecimientos, para poder contar con la demanda de los empleados. • La forma de pago de los productos es importante en los negocios, en el caso de la Despensa será al contado lo que proporcionará dinero líquido al establecimiento, pero se debe vigilar de cerca esto ya que si se amerita que el pago sea al crédito se debería evaluar esta opción. • Se debe procurar siempre que el espacio físico de la Despensa, este en óptimas condiciones tanto para el empleado como para los clientes

Splice donor site sgRNAs enhance CRISPR/Cas9-mediated knockout efficiency

[EN]CRISPR/Cas9 allows the generation of knockout cell lines and null zygotes by inducing site-specific double-stranded breaks. In most cases the DSB is repaired by non-homologous end joining, resulting in small nucleotide insertions or deletions that can be used to construct knockout alleles. However, these mutations do not produce the desired null result in all cases, but instead generate a similar, functionally active protein. This effect could limit the therapeutic efficiency of gene therapy strategies based on abrogating oncogene expression, and therefore needs to be considered carefully. If there is an acceptable degree of efficiency of CRISPR/Cas9 delivery to cells, the key step for success lies in the effectiveness of a specific sgRNA at knocking out the oncogene, when only one sgRNA can be used. This study shows that the null effect could be increased with an sgRNA targeting the splice donor site (SDS) of the chosen exon. Following this strategy, the generation of null alleles would be facilitated in two independent ways: the probability of producing a frameshift mutation and the probability of interrupting the canonical mechanism of pre-mRNA splicing. In these contexts, we propose to improve the loss-of-function yield driving the CRISPR system at the SDS of critical exons

Does Confinement Affect Treatment Dropout Rates in Patients With Gambling Disorder? A Nine-Month Observational Study

Background and Aims: COVID-19 pandemic and confinement have represented a challenge for patients with gambling disorder (GD). Regarding treatment outcome, dropout may have been influenced by these adverse circumstances. The aims of this study were: (a) to analyze treatment dropout rates in patients with GD throughout two periods: during and after the lockdown and (b) to assess clinical features that could represent vulnerability factors for treatment dropout. Methods: The sample consisted of n=86 adults, mostly men (n=79, 91.9%) and with a mean age of 45years old (SD=16.85). Patients were diagnosed with GD according to DSM-5 criteria and were undergoing therapy at a Behavioral Addiction Unit when confinement started. Clinical data were collected through a semi-structured interview and protocolized psychometric assessment. A brief telephone survey related to COVID-19 concerns was also administered at the beginning of the lockdown. Dropout data were evaluated at two moments throughout a nine-month observational period (T1: during the lockdown, and T2: after the lockdown). Results: The risk of dropout during the complete observational period was R=32/86=0.372 (37.2%), the Incidence Density Rate (IDR) ratio T2/T1 being equal to 0.052/0.033=1.60 (p=0.252). Shorter treatment duration (p=0.007), lower anxiety (p=0.025), depressive symptoms (p=0.045) and lower use of adaptive coping strategies (p=0.046) characterized patients who abandoned treatment during the lockdown. Briefer duration of treatment Baenas et al. Lockdown and GD: Treatment Dropout Frontiers in Psychology | www.frontiersin.org 2 December 2021 | Volume 12 | Article 761802 (p=0.001) and higher employment concerns (p=0.044) were highlighted in the individuals who dropped out after the lockdown. Treatment duration was a predictor of dropout in both periods (p=0.005 and p<0.001, respectively). Conclusion: The present results suggest an impact of the COVID-19 pandemic on treatment dropout among patients with GD during and after the lockdown, being treatment duration a predictor of dropout. Assessing vulnerability features in GD may help clinicians identify high-risk individuals and enhance prevention and treatment approaches in future similar situations

Efecto de Azospirillum brasilense sobre la cosecha y el desarrollo radical de plantas de caña de azúcar variedad C86-456 obtenidas por cultivo in vitro, en condiciones normales y bajo sobrehumedecimiento del suelo

In order to know the influence of the bacteria Azospirillum brasilense on plants of sugar cane, cultivar C86-456, from tissue culture under normal conditions and flooded soil in a Vertisol from El Valle del Cauto, an experiment was carried out using an at random blocks design. The main crop variables (pol in cane, t. caña.ha-1 and t. pol.ha-1) at the twelve months of age were taken, as stump of spring of the year and the development reached by the radical system in its more active area to achieve this experiment. The best results in the crop variables and development of the radical system were obtained it the treatments where the bacteria was present, although non significant under both conditions, evidencing that the stress due to excess of water in the soil affects the normal development of the sugar cane in general by modifying the kindness that the rhizospheric microorganism provides.Key words: biofertilizer, radical system, Saccharum, yieldPara conocer la influencia que ejerce la bacteria Azospirillum brasilense sobre plantas caña de azúcar, variedad C86-456 obtenidas por cultivo in vitro en un Vertisol del Valle del Cauto, en condiciones normales y bajo sobrehumedecimiento, se realizó un experimento con un diseño de bloques al azar. Para esto se tomaron las principales variables de cosecha (pol en caña, t. caña.ha-1 y t. pol.ha-1) y el desarrollo alcanzado por el sistema radical en su área más activa en ciclo de caña planta a los doce meses de cultivo. Los mejores resultados de las variables de cosecha y desarrollo del sistema radical, se obtuvieron en los tratamientos donde la bacteria estuvo presente, aunque no significativos en ambas condiciones, evidenciando que el estrés por exceso de agua en el suelo provoca disminuciones del normal desarrollo de la caña de azúcar en general y modifica las bondades que aporta el microorganismo rizosférico.Palabras clave: biofertilizante, rendimiento, Saccharum, sistema radica

Mesenchymal stromal cells (MSC) from JAK2+ myeloproliferative neoplasms differ from normal MSC and contribute to the maintenance of neoplastic hematopoiesis

[EN]There is evidence of continuous bidirectional cross-talk between malignant cells and bone marrow-derived mesenchymal stromal cells (BM-MSC), which favors the emergence and progression of myeloproliferative neoplastic (MPN) diseases. In the current work we have compared the function and gene expression profile of BM-MSC from healthy donors (HDMSC) and patients with MPN (JAK2V617F), showing no differences in the morphology, proliferation and differentiation capacity between both groups. However, BM-MSC from MPN expressed higher mean fluorescence intensity (MIF) of CD73, CD44 and CD90, whereas CD105 was lower when compared to controls. Gene expression profile of BM-MSC showed a total of 169 genes that were differentially expressed in BM-MSC from MPN patients compared to HD-MSC. In addition, we studied the ability of BM-MSC to support the growth and survival of hematopoietic stem/progenitor cells (HSPC), showing a significant increase in the number of CFU-GM colonies when MPN-HSPC were co-cultured with MPN-MSC. Furthermore, MPN-MSC showed alteration in the expression of genes associated to the maintenance of hematopoiesis, with an overexpression of SPP1 and NF-kB, and a downregulation of ANGPT1 and THPO. Our results suggest that BM-MSC from JAK2+ patients differ from their normal counterparts and favor the maintenance of malignant clonal hematopoietic cell

TRAF3 alterations are frequent in del-3′IGH chronic lymphocytic leukemia patients and define a specific subgroup with adverse clinical features

Interstitial 14q32 deletions involving IGH gene are infrequent events in chronic lymphocytic leukemia (CLL), affecting less than 5% of patients. To date, little is known about their clinical impact and molecular underpinnings, and its mutational landscape is currently unknown. In this work, a total of 871 CLLs were tested for the IGH break-apart probe, and 54 (6.2%) had a 300 kb deletion of 3′IGH (del-3′IGH CLLs), which contributed to a shorter time to first treatment (TFT). The mutational analysis by next-generation sequencing of 317 untreated CLLs (54 del-3′IGH and 263 as the control group) showed high mutational frequencies of NOTCH1 (30%), ATM (20%), genes involved in the RAS signaling pathway (BRAF, KRAS, NRAS, and MAP2K1) (15%), and TRAF3 (13%) within del-3′IGH CLLs. Notably, the incidence of TRAF3 mutations was significantly higher in del-3′IGH CLLs than in the control group (p < .001). Copy number analysis also revealed that TRAF3 loss was highly enriched in CLLs with 14q deletion (p < .001), indicating a complete biallelic inactivation of this gene through deletion and mutation. Interestingly, the presence of mutations in the aforementioned genes negatively refined the prognosis of del-3′IGH CLLs in terms of overall survival (NOTCH1, ATM, and RAS signaling pathway genes) and TFT (TRAF3). Furthermore, TRAF3 biallelic inactivation constituted an independent risk factor for TFT in the entire CLL cohort. Altogether, our work demonstrates the distinct genetic landscape of del-3′IGH CLL with multiple molecular pathways affected, characterized by a TRAF3 biallelic inactivation that contributes to a marked poor outcome in this subgroup of patients.Funding information: Universidad de Salamanca; Fundación Española de Hematología y Hemoterapia (FEHH); Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Grant/Award Number: CB16/12/00233; Red Temática de Investigación Cooperativa en Cáncer (RTICC); “Fundación Memoria Don Samuel Solórzano Barruso”: FS/33–2020, Grant/Award Number: RD12/0036/0069; “Gerencia Regional de Salud, SACYL”:, Grant/Award Numbers: GRS2385/A/21, GRS2140/A/20; Consejería de Educación, Junta de Castilla y León, Grant/Award Number: SA118P20; European Regional Development Fund and Instituto de Salud Carlos III, Grant/Award Numbers: CD19/00222, FI19/00191; Spanish Fondo de Investigaciones Sanitarias, Grant/Award Numbers: PI21/00983, PI18/0150

Dissecting the role of TP53 alterations in del(11q) chronic lymphocytic leukemia

© 2021 The Authors.[Background]: Several genetic alterations have been identified as driver events in chronic lymphocytic leukemia (CLL) pathogenesis and oncogenic evolution. Concurrent driver alterations usually coexist within the same tumoral clone, but how the cooperation of multiple genomic abnormalities contributes to disease progression remains poorly understood. Specifically, the biological and clinical consequences of concurrent high-risk alterations such as del(11q)/ATM-mutations and del(17p)/TP53-mutations have not been established.[Methods]: We integrated next-generation sequencing (NGS) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 techniques to characterize the in vitro and in vivo effects of concurrent monoallelic or biallelic ATM and/or TP53 alterations in CLL prognosis, clonal evolution, and therapy response.[Results]: Targeted sequencing analysis of the co-occurrence of high-risk alterations in 271 CLLs revealed that biallelic inactivation of both ATM and TP53 was mutually exclusive, whereas monoallelic del(11q) and TP53 alterations significantly co-occurred in a subset of CLL patients with a highly adverse clinical outcome. We determined the biological effects of combined del(11q), ATM and/or TP53 mutations in CRISPR/Cas9-edited CLL cell lines. Our results showed that the combination of monoallelic del(11q) and TP53 mutations in CLL cells led to a clonal advantage in vitro and in in vivo clonal competition experiments, whereas CLL cells harboring biallelic ATM and TP53 loss failed to compete in in vivo xenotransplants. Furthermore, we demonstrated that CLL cell lines harboring del(11q) and TP53 mutations show only partial responses to B cell receptor signaling inhibitors, but may potentially benefit from ATR inhibition.[Conclusions]: Our work highlights that combined monoallelic del(11q) and TP53 alterations coordinately contribute to clonal advantage and shorter overall survival in CLL.Spanish Fondo de Investigaciones Sanitarias, Grant/Award Numbers: PI15/01471, PI18/01500); Fundación Memoria Don Samuel Solórzano Barruso, Grant/Award Number: RD12/0036/006