Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas

Esta publicación detalla los experimentos realizados para la clonación de un ADNc que codifica una nueva metaloproteasa de matriz extracelular a partir de una biblioteca de ADNc procedente de un carcinoma mamario. Este trabajo es de gran interés en la investigación del cáncer, ya que describe la identificación de una nueva colagenasa en los carcinomas mamarios proponiendo un posible papel en el proceso tumoral. Hay evidencia de que las metaloproteasas participan en el proceso de degradación proteolítica de los diferentes componentes de la membrana basal, favoreciendo así la invasión tumoral y las metástasis. El ADNc de la colagenasa-3 se expresó en un sistema de virus vaccinia, y la proteína recombinante fue capaz de degradar los colágenos fibrilares, lo que apoya la hipótesis de que el ADNc aislado codifica para una colagenasa auténtica. El análisis por Northern blot del ARN de tejidos normales y patológicos demostró la existencia de tres especies diferentes de ARNm en los tumores de mama, que parecen ser el resultado de la utilización de distintos sitios de poliadenilación presentes en la región 3'-no codificante del gen. Por el contrario, no se detectó ARNm de la colalagenasa-3 por Northern blot ni por PCR en otros tejidos humanos como mama normal, fibroadenomas mamarios, hígado, placenta, ovario, útero, próstata y glándula parótida. Sobre la base del aumento de la expresión de la colagenasa-3 en los carcinomas de mama y la ausencia de expresión detectable en los tejidos normales, se propone un posible papel de esta metaloproteinasa en el proceso tumoral

CUTLL1, a novel human T-cell lymphoma cell line with t(7;9) rearrangement, aberrant NOTCH1 activation and high sensitivity to c-secretase inhibitors

Activating mutations in NOTCH1 are present in over 50% of human T-cell lymphoblastic leukemia (T-ALL) samples and inhibition of NOTCH1 signaling with c-secretase inhibitors (GSI) has emerged as a potential therapeutic strategy for the treatment of this disease. Here, we report a new human T-cell lymphoma line CUTLL1, which expresses high levels of activated NOTCH1 and is extremely sensitive to c-secretase inhibitors treatment. CUTLL1 cells harbor a t(7;9)(q34;q34) translocation which induces the expression of a TCRB-NOTCH1 fusion transcript encoding a membrane-bound truncated form of the NOTCH1 receptor. GSI treatment of CUTLL1 cells blocked NOTCH1 processing and caused rapid clearance of activated intracellular NOTCH1. Loss of NOTCH1 activity induced a gene expression signature characterized by the downregulation of NOTCH1 target genes such as HES1 and NOTCH3. In contrast with most human T-ALL cell lines with activating mutations in NOTCH1, CUTLL1 cells showed a robust cellular phenotype upon GSI treatment characterized by G1 cell cycle arrest and increased apoptosis. These results show that the CUTLL1 cell line has a strong dependence on NOTCH1 signaling for proliferation and survival and supports that T-ALL patients whose tumors harbor t(7;9) should be included in clinical trials testing the therapeutic efficacy NOTCH1 inhibition with GSIs. Leukemia (2006) 20, 1279–1287. doi:10.1038/sj.leu.2404258; published online 11 May 200

Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP

As cancer cells traverse collagen-rich extracellular matrix (ECM) barriers and intravasate, they adopt a fibroblast-like phenotype and engage undefined proteolytic cascades that mediate invasive activity. Herein, we find that fibroblasts and cancer cells express an indistinguishable pericellular collagenolytic activity that allows them to traverse the ECM. Using fibroblasts isolated from gene-targeted mice, a matrix metalloproteinase (MMP)–dependent activity is identified that drives invasion independently of plasminogen, the gelatinase A/TIMP-2 axis, gelatinase B, collagenase-3, collagenase-2, or stromelysin-1. In contrast, deleting or suppressing expression of the membrane-tethered MMP, MT1-MMP, in fibroblasts or tumor cells results in a loss of collagenolytic and invasive activity in vitro or in vivo. Thus, MT1-MMP serves as the major cell-associated proteinase necessary to confer normal or neoplastic cells with invasive activity

Pleiotropic functions of the tumor- and metastasis-suppressing Matrix Metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice

Matrix metalloproteinase-8 (MMP-8; neutrophil collagenase) is an important regulator of innate immunity which has onco-suppressive actions in numerous tumor types

Marketing digital y fidelización de clientes en el desarrollo de la sostenibilidad comercial de la región Junín

Objective. To determine the relationship between digital marketing and customer loyalty in the development of commercial sustainability in the province of Tarma, Junín region (Peru). Methods. The research had a quantitative approach and was of basic type, correlational level and non-experimental-cross-sectional design; two instruments were used: the digital marketing questionnaire and the customer loyalty questionnaire. The first questionnaire consisted of 12 items referring to the dimensions of digital marketing and the second consisted of 15 items referring to the dimensions of customer loyalty. The sample consisted of 120 customers of commercial establishments in the province of Tarma. Results. 47.5 % of respondents considered that the implementation of digital marketing in commercial establishments is regular, 36.7 % considered that there is a low implementation and only 15.8 % considered that there is a high implementation of digital marketing. Referring to the customer loyalty questionnaire, 63.3 % considered that customer loyalty in commercial establishments occurs regularly, 21.7 % considered that customer loyalty is high and 15 % considered that customer loyalty is low. Conclusion. There is a direct and statistically significant relationship between digital marketing and customer loyalty in the development of sustainability in the province of Tarma, Junín region.Objetivo. Determinar la relación entre marketing digital y fidelización de clientes en el desarrollo de la sostenibilidad comercial de la provincia de Tarma, región Junín (Perú). Métodos. La investigación tuvo un enfoque cuantitativo y fue de tipo básico, nivel correlacional y diseño no experimental-transversal; se emplearon dos instrumentos: el cuestionario de marketing digital y el cuestionario de fidelización de clientes. El primer cuestionario constó de 12 ítems referidos a las dimensiones de marketing digital y el segundo constó de 15 ítems referidos a las dimensiones de la fidelización de clientes. La muestra estuvo conformada por 120 clientes de establecimientos comerciales de la provincia de Tarma. Resultados. El 47,5 % de encuestados consideró que la implementación del marketing digital en los establecimientos comerciales se da de forma regular, el 36,7% consideró que hay una baja implantación y solo el 15,8 % consideró que hay una alta implantación del marketing digital. Referente al cuestionario de fidelización de clientes, el 63,3 % consideró que la fidelización de clientes en los establecimientos comerciales se da de forma regular, el 21,7 % consideró que la fidelización de clientes es alta y el 15% considera que la fidelización de clientes es baja. Conclusión. Existe relación directa y estadísticamente significativa entre marketing digital y fidelización de clientes en el desarrollo de la sostenibilidad de la provincia de Tarma, región Junín

Generating Random Logic Programs Using Constraint Programming

Testing algorithms across a wide range of problem instances is crucial to ensure the validity of any claim about one algorithm's superiority over another. However, when it comes to inference algorithms for probabilistic logic programs, experimental evaluations are limited to only a few programs. Existing methods to generate random logic programs are limited to propositional programs and often impose stringent syntactic restrictions. We present a novel approach to generating random logic programs and random probabilistic logic programs using constraint programming, introducing a new constraint to control the independence structure of the underlying probability distribution. We also provide a combinatorial argument for the correctness of the model, show how the model scales with parameter values, and use the model to compare probabilistic inference algorithms across a range of synthetic problems. Our model allows inference algorithm developers to evaluate and compare the algorithms across a wide range of instances, providing a detailed picture of their (comparative) strengths and weaknesses.Comment: This is an extended version of the paper published in CP 202

Experiencia subjetiva del empleado en colaboradores de establecimientos hoteleros de la región Junín

Objective: To determine the characteristics of the employee experience in employees of hotel establishments in the Junín region. Methods. The type of research was basic, descriptive level, simple descriptive design and non-experimental-transectional. The methods used were observation, analysis and synthesis and inductive-deductive, while the instrument applied was the questionnaire and the technique was the survey. The sample consisted of 320 employees of hotel establishments in the Junín region and the sample selection criterion was non-probabilistic by convenience. Results. The main results were that the levels of employee experience at the subjective level were regular in its physical and technological dimensions, and high in its cultural dimension; which reflects that, despite the adverse conditions due to the covid-19 pandemic, the collaborators performed their tasks with appropriateness and assertiveness. Conclusion. Companies in the hotel sector should implement programs that reinforce and establish the objective conditions of their work environment in order to generate profitable and positive subjective experiences in favor of their employees and the productivity of the organization.Objetivo. Determinar las características del employee experience en colaboradores de establecimientos hoteleros de la región Junín. Métodos. El tipo de investigación fue básica, de nivel descriptivo, diseño descriptivo simple y no experimental-transeccional. Los métodos fueron la observación, el análisis y síntesis y el inductivo-deductivo, mientras que el instrumento aplicado fue el cuestionario y la técnica la encuesta. La muestra estuvo conformada por 320 colaboradores de establecimientos hoteleros de la región Junín y el criterio de selección de la muestra fue no probabilístico por conveniencia. Resultados. Los principales resultados fueron que los niveles de experiencia del empleado a nivel subjetivo fueron regulares en sus dimensiones física y tecnológica, y de nivel alto en su dimensión cultural; lo que refleja que, pese a las condiciones adversas por pandemia de la covid-19, los colaboradores desarrollaron labores con propiedad y asertividad. Conclusión. Las empresas del sector hotelero deben implementar programas que refuercen y establezcan las condiciones objetivas de su entorno laboral a fin de generar experiencias subjetivas redituables y positivas en favor de sus colaboradores y la productividad de la organización

Analysis of the alteration in the optical configuration of Raman spectrometer: Optimization of signal-to-noise ratio (SNR) in a specific wavelength range of clinical interest

Abstract. The present article is focused on the optimization of the optical parameters of a Raman spectrometer in order to obtain a minimum width of its spectral lines. In this way, using as reference the width of a fingerprint band of a calcified biological tissue, a spectral line without distortion or any loss of resolution was identified. This optimization is employed with the aim of improvement of the signal-to-noise ratio (SNR). A great improvement in the efficiency of the spectral collect was obtained, which can reduce significantly the time of diagnosis of target tissues, such as the calcified coronarian tissue. Therefore, the potential application of this new spectroscopic system increases the efficiency and precision, favoring the security of this technique to future in vivo applications. The excellent results obtained in this work become this spectroscopic system a powerful tool to the clinical diagnosis of several diseases