Structural and functional map of a bacterial nucleoid

Mapping global protein binding in the E. coli genome reveals extended domains of high protein occupancy

Diabetes mellitus y sus diferentes manifestaciones dermatológicas. Revisión de la literatura

Extracto Se presenta el caso de una paciente de 45 años de edad que consulta al servicio de dermatología por aparición de lesión en miembro inferior izquierdo de crecimiento progresivo, ocasionalmente dolorosa. Como antecedentes importantes presenta diabetes mellitus tipo 2 mal controlada, hipertensión arterial crónica, obesidad grado III e hipotiroidismo en suplencia. En manejo actual con metformina 2 veces día, insulina glargina 12 unidades día, losartán 50 mg día y levotiroxina 50 mcg al día. Al examen físico se evidenciaba una placa de bordes bien definidos con centro atrófico de borde eritematoso con centro pálido mal definida con múltiples vasos en su superficie, que ocupaba el 70% de la región anterior del miembro inferior izquierdo

Dopamine D4 receptor counteracts morphine-induced changes in M opioid receptor signaling in the striosomes of the rat caudate putamen.

Morphine is one of the most potent analgesic drugs used to relieve moderate to severe pain. After long-term use of morphine, neuroadaptive changes in the brain promotes tolerance, which result in a reduced sensitivity to most of its effects with attenuation of analgesic efficacy, and dependence, revealed by drug craving and physical or psychological manifestations of drug withdrawal. The mu opioid receptor (MOR) is critical, not only in mediating morphine analgesia, but also in addictive behaviors by the induction of a strong rewarding effect. We have previously shown that dopamine D4 receptor (D4R) stimulation counteracts morphine-induced activation of dopaminergic nigrostriatal pathway and accumulation of Fos family transcription factors in the caudate putamen (CPu). In the present work, we have studied the effect of D4R activation on MOR changes induced by morphine in the rat CPu on a continuous drug treatment paradigm, by analyzing MOR protein level, pharmacological profile, and functional coupling to G proteins. Furthermore, using conditioned place preference and withdrawal syndrome test, we have investigated the role of D4R activation on morphine-related behavioural effects. MOR immunoreactivity, agonist binding density and its coupling to G proteins are up-regulated in the striosomes by continuous morphine treatment. Interestingly, co-treatment of morphine with the dopamine D4 receptor (D4R) agonist PD168,077 fully counteracts these adaptive changes in MOR, in spite of the fact that continuous PD168,077 treatment increases the [3H]DAMGO Bmax values to the same degree as seen after continuous morphine treatment. In addition, the administration of the D4R agonist counteracts the rewarding effects of morphine, as well as the development of physical dependence. The present results give support for the existence of antagonistic functional D4R-MOR receptor-receptor interactions in the adaptive changes occurring in MOR of striosomes on continuous administration of morphine and preventing morphine-related behaviour.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Campaña Publicitaria de Relanzamiento, para la Marca “La Capricciosa – Gelatería"

La campaña de relanzamiento consta de volver a conectar con el consumidor cuando, por cualquier circunstancia, el producto está llegando a una fase de declive. Las razones pueden ser muy variadas, desde la simple evolución del ciclo de vida del producto, hasta un cambio de gustos del público objetivo, el advenimiento de nuevas modas o incluso cambios en la industria o la tecnología. Luego del realizar un estudio de mercado se consideraron las siguientes razones para proponer el relanzamiento de marca: - Cuando se decidió abrir el nuevo local La Capricciosa – Gelatería, no se realizó una campaña de lanzamiento, tal como se realiza con una marca nueva ni tampoco se comunicó y reforzó la relación que mantiene con la existente marca Capriccio. - No se realizaron, ni se realizan en la actualidad campañas de promoción planificadas durante el año y no cuentan con un plan de medios ni cronograma de difusión. - Se detectó que la marca presenta un problema de identidad visual. Entonces, al escoger desarrollar una campaña de relanzamiento, buscamos resolver los puntos detallados anteriormente, a través de un call to action, teniendo un mensaje claro, que permita una singularidad en la marca frente a la competencia con una imagen fresca y renovada del local, además de un constante impulso en la campaña digital y la colaboración de una influencer que cubra el perfil que se busca según el segmento de mercado. Con esto se espera tener un alza en las ventas y la acogida de nuevos clientes, que escojan a La Capricciosa – Gelatería como la mejor heladería artesanal de Arequipa. Palabras clave: La Capricciosa – Gelatería, Campaña de Relanzamiento, promoción, marca, call to action, influencer, campaña digital.Tesi

Dopamine D4 receptor activation counteracts nigrostriatal pathway activation by morphine: relevance in drug addiction.

Morphine induces dopamine release in the caudate putamen (CPu), which promotes stereotyped behavior and habit learning for drug-seeking and –taking. Nigrostriatal pathway stimulation by morphine is due to a removal of tonic inhibition arising from SNr GABA interneurons on SNc dopaminergic neurons through the mu opioid receptor (MOR). Long-term morphine exposure produces a series of adaptations in SNc dopamine neurons, which affect neuron excitability and dopamine output to CPu. We have previously shown that dopamine D4 receptor (D4R) stimulation counteracts acute and chronic morphine-induced accumulation of several transcription factors in the CPu (Gago et al., 2011 Brain Res.). Since D4R is expressed in the SNr (Rivera et al., Brain Res. 2003), we postulate that a functional D4R-MOR interaction at the midbrain level could exists. We have investigated the role of D4R in the morphine-induced nigroestriatal dopamine metabolism in the rat brain using biochemical and immunohistochemical techniques. We also have studied the influence of D4R on morphine-induced morphological changes in SNc dopamine neurons using both immunohistochemical and image analysis techniques. Finally, we examined a possible underlying mechanism of the D4R-MOR interaction at the SN level using in vitro quantitative receptor autoradiography. We have found that D4R activation restores dopamine metabolism in the nigroestriatal pathway after acute morphine treatment and prevents morphine-induced rise of tyroxine hydroxylase and dopamine transporter. Rats receiving a continuous treatment of morphine (6 days) showed SNc dopamine neurons with smaller size and higher circularity index compared with the controls animals. These morphine-induced morphological adaptatives changes were prevented when a D4R agonist (PD168,077) was administered at the same time with morphine. Autoradiographic studies demonstrated that the D4R agonist reduce the affinity of MOR. The present study provides evidence for the existence of a fully blocking effect of the D4R on the activation of dopaminergic nigroestriatal pathway by morphine.Financiación: P09-CVI- 4702 (Proyecto de Excelencia de la Junta de Andalucía

Theoretical and empirical quality assessment of transcription factor-binding motifs

Position-specific scoring matrices (PSSMs) are routinely used to predict transcription factor (TF)-binding sites in genome sequences. However, their reliability to predict novel binding sites can be far from optimum, due to the use of a small number of training sites or the inappropriate choice of parameters when building the matrix or when scanning sequences with it. Measures of matrix quality such as E-value and information content rely on theoretical models, and may fail in the context of full genome sequences. We propose a method, implemented in the program ‘matrix-quality’, that combines theoretical and empirical score distributions to assess reliability of PSSMs for predicting TF-binding sites. We applied ‘matrix-quality’ to estimate the predictive capacity of matrices for bacterial, yeast and mouse TFs. The evaluation of matrices from RegulonDB revealed some poorly predictive motifs, and allowed us to quantify the improvements obtained by applying multi-genome motif discovery. Interestingly, the method reveals differences between global and specific regulators. It also highlights the enrichment of binding sites in sequence sets obtained from high-throughput ChIP-chip (bacterial and yeast TFs), and ChIP–seq and experiments (mouse TFs). The method presented here has many applications, including: selecting reliable motifs before scanning sequences; improving motif collections in TFs databases; evaluating motifs discovered using high-throughput data sets

Glibenclamide inhibits cell growth by inducing G0/G1 arrest in the human breast cancer cell line MDA-MB-231

Background: Glibenclamide (Gli) binds to the sulphonylurea receptor (SUR) that is a regulatory subunit of ATP-sensitive potassium channels (KATP channels). Binding of Gli to SUR produces the closure of KATP channels and the inhibition of their activity. This drug is widely used for treatment of type 2-diabetes and it has been signaled as antiproliferative in several tumor cell lines. In previous experiments we demonstrated the antitumoral effect of Gli in mammary tumors induced in rats. The aim of the present work was to investigate the effect of Gli on MDA-MB-231 breast cancer cell proliferation and to examine the possible pathways involved in this action. Results: The mRNA expression of the different subunits that compose the KATP channels was evaluated in MDA-MB-231 cells by reverse transcriptase-polymerase chain reaction. Results showed the expression of mRNA for both pore-forming isoforms Kir6.1 and Kir6.2 and for the regulatory isoform SUR2B in this cell line. Gli inhibited cell proliferation assessed by a clonogenic method in a dose dependent manner, with an increment in the population doubling time. The KATP channel opener minoxidil increased clonogenic proliferation, effect that was counteracted by Gli. When cell cycle analysis was performed by flow cytometry, Gli induced a significant cell-cycle arrest in G0/G1 phase, together with an up-regulation of p27 levels and a diminution in cyclin E expression, both evaluated by immunoblot. However, neither differentiation evaluated by neutral lipid accumulation nor apoptosis assessed by different methodologies were detected. The cytostatic, non toxic effect on cell proliferation was confirmed by removal of the drug. Combination treatment of Gli with tamoxifen or doxorubicin showed an increment in the antiproliferative effect only for doxorubicin. Conclusions: Our data clearly demonstrated a cytostatic effect of Gli in MDA-MB-231 cells that may be mediated through KATP channels, associated to the inhibition of the G1-S phase progression. In addition, an interesting observation about the effect of the combination of Gli with doxorubicin leads to future research for a potentialnovel role for Gli as an adjuvant in breast cancer treatment.Fil: Nuñez, Mariel Alejandra. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Medina, Vanina Araceli. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cricco, Graciela Patricia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Croci, Máximo. Instituto de Inmuno Oncología "Dr. Ernesto J. V. Crescenti"; ArgentinaFil: Cocca, Claudia Marcela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rivera, Elena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Bergoc, Rosa Maria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Instituto Universidad de la Fundación "Héctor Barceló"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martin, Gabriela Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia. Departamento del Magdalena

En el presente documento se comparte el último trabajo del diplomado de Profundización en Acompañamiento Psicosocial en Escenario de Violencia. Esta actividad deja en evidencia claramente la situación que ha vivido el país (Colombia) a lo largo de los años con el conflicto armado que iniciaron los grupos al margen de la ley, principalmente las FARC, grupo que le ha causado mucho daño al país. A lo largo de este trabajo se puede observar testimonios o algunos casos que algunas víctimas les ha tocado padecer en carne propia en diferentes lugares del país y en distintos años. En los mismos relatos se puede entrever las consecuencias que estos episodios traumáticos ha dejado en sus vidas y en las de su familia, también como esto les logro cambiar la vida completamente, ya que en algunas ocasiones llegaban a perder un trabajo y en otras recibir amenazas de muerte. En este caso en particular se explorará abiertamente el relato de Camilo, un chico afro sobreviviente de la guerra, la cual le causo muchos inconvenientes que lo han afectado en todos los aspectos de su vida.This document shares the latest work of the Diploma in Deepening in Psychosocial Accompaniment in the Scene of Violence. This activity clearly shows the situation that the country (Colombia) has experienced over the years with the armed conflict that was started by groups outside the law, mainly the FARC, a group that has caused much damage to the country. Throughout this work you can see testimonies or some cases that some victims have suffered in their own flesh in different parts of the country and in different years. In the same stories, it is possible to glimpse the consequences that these traumatic episodes have left in their lives and in those of their family, also how this managed to change their lives completely, since on some occasions they lost a job and on others received threats. of death. In this particular case, the story of Camilo, an Afro boy survivor of the war, which caused him many inconveniences that have affected him in all aspects of his life, will be openly explored

Dopamine D-4 receptor counteracts morphine-induced changes in µ opioid receptor signaling in the striosomes of the rat caudate putamen

The mu opioid receptor (MOR) is critical in mediating morphine analgesia. However, prolonged exposure to morphine induces adaptive changes in this receptor leading to the development of tolerance and addiction. In the present work we have studied whether the continuous administration of morphine induces changes in MOR protein levels, its pharmacological profile, and MOR-mediated G-protein activation in the striosomal compartment of the rat CPu, by using immunohistochemistry and receptor and DAMGO-stimulated [S-35]GTP gamma S autoradiography. MOR immunoreactivity, agonist binding density and its coupling to G proteins are up-regulated in the striosomes by continuous morphine treatment in the absence of changes in enkephalin and dynorphin mRNA levels. In addition, co-treatment of morphine with the dopamine D-4 receptor (D4R) agonist PD168,077 fully counteracts these adaptive changes in MOR, in spite of the fact that continuous PD168,077 treatment increases the [H-3]DAMGO B-max values to the same degree as seen after continuous morphine treatment. Thus, in spite of the fact that both receptors can be coupled to G(i/0) protein, the present results give support for the existence of antagonistic functional D4R-MOR receptor-receptor interactions in the adaptive changes occurring in MOR of striosomes on continuous administration of morphine

Factores psicosociales - estrés, en el trabajadores del hotel Siar en la ciudad Bogotá.

Evaluar los factores de riesgos psicosociales que inciden en el estrés laboral del personal del hotel Siar ubicado en Bogotá, por medio de la herramienta de evaluación y prevención de los riesgos psicosociales CoPsoQ-istas21.El trabajo de investigación se llevó a cabo en el Hotel Siar ubicado en la ciudad de Bogotá D.C. Presentando como objetivo principal, la evaluación del riesgo psicosocial, permitiendo conocer el estrés laboral que maneja el personal de servicio al cliente. Se utiliza el modelo de Cuestionario Psicosocial de Copenhague CoPsoQ Istas21 el cual fue aplicado a 15 trabajadores. Este cuestionario permite la identificación y medición de factores que afectan la calidad de vida del trabajador, tales como; exigencias psicológicas, doble presencia, control sobre el trabajo, apoyo social y calidad de liderazgo, compensaciones por el trabajo, donde la confiabilidad es máxima, se practica de manera voluntaria y confidencial. Una vez aplicado el instrumento se hace un análisis e interpretación de datos, luego se procede al diseño del material didáctico que incluye una cartilla de buenas prácticas, y actividades lúdicas las cuales serán el entregable al Hotel, todo esto encaminado a la prevención y control de los factores de riesgo psicosocial y estrés laboral.The research work was carried out at the Siar Hotel located in Bogota D.C. presenting as its main objective, the evaluation of psychosocial risk, allowing to know the work stress that the customer service personnel handle. The Copenhagen Psychosocial Questionnaire model CoPsoQ Istas21 was used, which was applied to 15 workers. This questionnaire allows the identification and measurement of factors that affect the quality of the worker, such as; psychological demands, double presence, control over work, social support and leadership quality, compensation for work, where reliability is maximum, is practiced voluntarily and confidentially. Once the instrument is applied, an analysis and interpretation of data is made, then the didactic material is designed, which includes a booklet of good practices, and recreational activities which will be deliverable to the Hotel, all aimed at the prevention and control of psychosocial risk factors and work stress