AIP and MEN1 mutations and AIP immunohistochemistry in pituitary adenomas in a tertiary referral center.

Background: Pituitary adenomas have a high disease burden due to tumor growth/ invasion and disordered hormonal secretion. Germline mutations in genes such as MEN1 and AIP are associated with early onset of aggressive pituitary adenomas that can be resistant to medical therapy. Aims: We performed a retrospective screening study using published risk criteria to assess the frequency of AIP and MEN1 mutations in pituitary adenoma patients in a tertiary referral center. Methods: Pituitary adenoma patients with pediatric/adolescent onset, macroadenomas occurring ≤30 years of age, familial isolated pituitary adenoma (FIPA) kindreds and acromegaly or prolactinoma cases that were uncontrolled by medical therapy were studied genetically. We also assessed whether immunohistochemical staining for AIP (AIP-IHC) in somatotropinomas was associated with somatostatin analogs (SSA) response. Results: Fifty-five patients met the study criteria and underwent genetic screening for AIP/MEN1 mutations. No mutations were identified and large deletions/duplications were ruled out using MLPA. In a cohort of sporadic somatotropinomas, low AIP-IHC tumors were significantly larger (P = 0.002) and were more frequently sparsely granulated (P = 0.046) than high AIP-IHC tumors. No significant relationship between AIP-IHC and SSA responses was seen. Conclusions: Germline mutations in AIP/MEN1 in pituitary adenoma patients are rare and the use of general risk criteria did not identify cases in a large tertiary-referral setting. In acromegaly, low AIP-IHC was related to larger tumor size and more frequent sparsely granulated subtype but no relationship with SSA responsiveness was seen. The genetics of pituitary adenomas remains largely unexplained and AIP screening criteria could be significantly refined to focus on large, aggressive tumors in young patients

La ruta de señalización WNT en la determinación de progenitores pancreáticos

1 página. IX Jornadas Andaluzas Salud Investiga. Cádiz 20-22 octubre, 2010.Nuestro laboratorio trata de determinar los mecanismos moleculares implicados en la formación de los distintos tipos celulares pancreáticos adultos a partir de células progenitoras. Este conocimiento es fundamental para comprender las bases de enfermedades tan terribles como el cáncer pancreático. Además, es absolutamente necesario para el desarrollo de protocolos de formación in vitro de células beta productoras de insulina, una atractiva estrategia terapéutica para la diabetes. A este respecto, el papel de la ruta de señalización embrionaria Wnt parece ser importante ya que estudios previos han demostrado que la activación de esta ruta es necesaria para la formación de células pancreáticas a partir de células embrionarias. En nuestro proyecto nos hemos planteado determinar el efecto de la ruta Wnt sobre la formación de páncreas sobreactivando dicha ruta en progenitores pancreáticos en el ratón.Peer reviewe

On the Connectedness and Diameter of a Geometric Johnson Graph

Let $P$ be a set of $n$ points in general position in the plane. A subset $I$ of $P$ is called an \emph{island} if there exists a convex set $C$ such that $I = P \cap C$. In this paper we define the \emph{generalized island Johnson graph} of $P$ as the graph whose vertex consists of all islands of $P$ of cardinality $k$, two of which are adjacent if their intersection consists of exactly $l$ elements. We show that for large enough values of $n$, this graph is connected, and give upper and lower bounds on its diameter

Loss of pancreas upon activated Wnt signaling is concomitant with emergence of gastrointestinal identity

Organ formation is achieved through the complex interplay between signaling pathways and transcriptional cascades. The canonical Wnt signaling pathway plays multiple roles during embryonic development including patterning, proliferation and differentiation in distinct tissues. Previous studies have established the importance of this pathway at multiple stages of pancreas formation as well as in postnatal organ function and homeostasis. In mice, gain-of-function experiments have demonstrated that activation of the canonical Wnt pathway results in pancreatic hypoplasia, a phenomenon whose underlying mechanisms remains to be elucidated. Here, we show that ectopic activation of epithelial canonical Wnt signaling causes aberrant induction of gastric and intestinal markers both in the pancreatic epithelium and mesenchyme, leading to the development of gut-like features. Furthermore, we provide evidence that β -catenin-induced impairment of pancreas formation depends on Hedgehog signaling. Together, our data emphasize the developmental plasticity of pancreatic progenitors and further underscore the key role of precise regulation of signaling pathways to maintain appropriate organ boundaries

La frontera Colombia-Perú vista a través de la Operación de Apoyo al Desarrollo Binacional

Este artículo hace un estudio cualitativo, con enfoque analítico e inductivo, sobre las implicaciones, en materia de seguridad y desarrollo, de la implementación de la Operación de Apoyo al Desarrollo Binacional en la frontera colombo-peruana, durante el periodo 2007-2019. Para ello, se especificaron las acciones más representativas de la ejecución de la operación; se determinó la evolución de la calidad de vida, a partir de la conceptualización del desarrollo derivada de la operación, y, finalmente, se estableció el alcance y el cumplimento de las metas y objetivos propuestos por la Operación de Apoyo al Desarrollo Binacional Colombia-Perú. Este análisis permitió establecer, por un lado, la importancia de fortalecer operaciones como la de Apoyo al Desarrollo Binacional en esta zona de frontera y en otras de similares características, con el fin de impulsar el desarrollo territorial de la mano de los pobladores de la región, así como, por otro lado, la necesidad de vincular a más instituciones públicas, privadas y gobiernos extranjeros en la construcción de escenarios de cooperación internacional, en beneficio del desarrollo y la seguridad, en este caso particular, de la zona ribereña de los ríos Putumayo y Amazonas, territorios fronterizos entre Colombia y Perú

Rheological behaviour of submicron mullite-carbon nanofiber suspensions for Atmospheric Plasma Spraying coatings

Mullite is widely used as a structural material for applications like thermal and environmental barriers coatings. For some of these applications, thermal spray is a suitable technique due to its fast production time and versatility. This makes mullite a very interesting coating material for thermal spray industry. In the present work, the viability to produce coatings by thermal spray using mullite-CNFs agglomerated powders is analyzed. The stability of aqueous mullite and mullite-CNFs suspensions was studied in terms of zeta potential and rheological behaviour of concentrated slurries. Slurries were optimized in terms of dispersant concentration and solid content. The optimized suspensions were used for the granules preparation by spray drying technology. The obtained granules were characterized through the determination of particle size distribution and shape factor by field emission scanning electron microscopy and laser scattering. These granules were used to form the coatings by Atmospheric Plasma Spraying which were characterized by evaluating the composition, structure, shape, and thickness

Effect of Epas1 and Pcx inactivation in pancreatic β-cell formation and function.

According to the consensus model for GSIS (Glucose-Stimulated Insulin Secretion), glucose is rapidly metabolized and coupled to insulin secretion involving a substantial number of cofactors and metabolites intermediates such as ATP, NADPH and citrate, among many others (1). In particular, pyruvate carboxylase (PC) is a fundamental enzyme in redox cycling between NADH and NADPH and also participates in an intricate process known as “pyruvate cycling” which allows the anaplerotic entry of pyruvate in the krebs cycle (2).Pancreatic β-cells express abnormally high levels of pyruvate carboxylase (PC) and insignificant levels of phosphoenolpyruvate carboxylase, the enzyme necessary for gluconeogenesis. This implies that PC must play a different role in β-cells, such as insulin secretion, which is required for the "metabolic switch" from glycolytic to aerobic metabolism during β-cell maturation. It is also known that pyruvate carboxylase activity is elevated in mature β-cells but diminished under diabetic conditions. Recent studies have revealed that the Hypoxia Inducible factor (HIF) pathway plays an important role of in β-cell function (cita algun articulo nuestro). Both overexpression and inactivation of HIF-1α in β cells cause defects in insulin secretion. However, the role of HIF-2α in β-cell formation and function has been largely ignored despite been reported to be activated during diabetic conditions.In this project, we hypothesize that HIF-2α and pyruvate carboxylase activity during late pancreatic HIF-2α formation is critical for the metabolic switch that ocurrs in β-cell during early postnatal development and thus for proper β-cell function.In this study, we will analyze the expression of Epas1 (the gene encoding HIF-2α and Pcx) at different prenatal and postnatal stages by mRNA TaqMan essay. Using Cre/lox technology in mice, we will inactivate Epas1 and Pcx specifically in β-cells. Immunofluorescence and immunohistochemical assays will be carried out to determine specific markers of cell identity, vascularization, proliferation, and polarity in pancreatic tissue of Epas1- and Pcx-deficient mice. Finally, we will also evaluate the in vivo behavior of pancreatic β-cells in transgenic mice through glucose and insulin tolerance assays (GTT and ITT). This will help us understand the relationship between HIF-2 and PC activity and β-cell development and function, as well as whether HIF-2 and PC activity play a role in β-cell failure during diabetes

Flow disposicional en salvamento deportivo : una aproximación desde la teoría de la autodeterminación

This study analyzed the relationships between perceived motivational climates, psychological mediators, selfdetermined motivation and dispositional flow in lifesaving sport. The study variables also examined differences according to gender, age and daily practice time. A total of 283 athletes with a mean age of 17.27 years (SD = 3.36) who completed the Perceived Motivational Climate in Sport Questionnaire-2 (PMCSQ-2), the Motivational Mediators in Sport Scale (EMMD), the Sport Motivational Scale (SMS) and the Dispositional Flow Scale (DFS) participated in the study. The results revealed that perceived task and ego-involving motivational climates, perceived competence and autonomy, and selfdetermined motivation positively predicted dispositional flow with 50% of the variance explained. Men reported higher scores in autonomy, competence and dispositional flow than women did. Older athletes displayed a higher level of perceived autonomy than younger ones. The results are discussed in connection with the motivational factors important to improving dispositional flow

Stacked GaAs(Sb)(N)-capped InAs/GaAs quantum dots for enhanced solar cell efficiency

Different approaches have arisen aiming to exceed the Shockley-Queisser efficiency limit of solar cells. Particularly, stacking QD layers allows exploiting their unique properties, not only for intermediate-band solar cells or multiple exciton generation, but also for tandem cells in which the tunability of QD properties through the capping layer (CL) could be very useful

Carbon dioxide activation assisted by a bis(chlorodimethylsilyl)cyclopentadienyl titanium compound

A great deal of interest has focused on the role of metal ions\ud as the active centers in the fixation of CO2 and its transformation. Activation of CO2 by hydroxo and oxo metal complexes to afford metal hydrogencarbonato and carbonato\ud species, respectively, is related to the function of the carbonic\ud anhydrase metalloenzyme, which catalyzes the physiologically\ud important hydration of CO2 to hydrogencarbonate