BMP9-Induced survival effect in liver tumor cells requires p38MAPK activation

The study of bone morphogenetic proteins (BMPs) role in tumorigenic processes, and specifically in the liver, has gathered importance in the last few years. Previous studies have shown that BMP9 is overexpressed in about 40% of hepatocellular carcinoma (HCC) patients. In vitro data have also shown evidence that BMP9 has a protumorigenic action, not only by inducing epithelial to mesenchymal transition (EMT) and migration, but also by promoting proliferation and survival in liver cancer cells. However, the precise mechanisms driving these effects have not yet been established. In the present work, we deepened our studies into the intracellular mechanisms implicated in the BMP9 proliferative and pro-survival effect on liver tumor cells. In HepG2 cells, BMP9 induces both Smad and non-Smad signaling cascades, specifically PI3K/AKT and p38MAPK. However, only the p38MAPK pathway contributes to the BMP9 growth-promoting effect on these cells. Using genetic and pharmacological approaches, we demonstrate that p38MAPK activation, although dispensable for the BMP9 proliferative activity, is required for the BMP9 protective effect on serum withdrawal-induced apoptosis. These findings contribute to a better understanding of the signaling pathways involved in the BMP9 pro-tumorigenic role in liver tumor cells

Evidence-Based Teaching Strategies for Behavioral Neuroscience and Biological Psychology Classes

Courses in Behavioral Neuroscience and Biological Psychology were taught while implementing evidence based teaching practices and several additional innovations. Students engaged in think-pair-share activities, group projects, and novel innovations of assignments including incentivized exam re-earns and creating modern memes of neuroscience content. Students exhibited evidence of learning, enjoyment, and teaching effectiveness

What Are the Barriers and Motivators to Exercise in 50-65 Year-Old Adults?

Introduction. The benefit of exercise in adults has been well established. Research has demonstrated improved cardiovascular health, decreased bone fractures, and increased mental capacity. While the benefits of exercise has clearly been demonstrated, personal barriers to exercise are yet to be fully elucidated. Thus, in collaboration with the YMCA, this study aimed to clarify barriers to exercise in 50-65 year-old adults.https://scholarworks.uvm.edu/comphp_gallery/1085/thumbnail.jp

Role of BMP9 in chronic liver disease: "in vivo" and "in vitro" studies

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular II, leída el 31-03-2017El hígado realiza numerosas funciones complejas implicadas en el mantenimiento de la homeostasis del organismo. Un aspecto muy característico es su elevada capacidad de regeneración después del daño hepático, que se lleva a cabo por las células parenquimáticas. Sin embargo, si se ve comprometida la capacidad de regeneración de estas células, como en una lesión crónica o en presencia de sustancias que inhiben la proliferación de los de hepatocitos (Falkowski et al. 2003; Marshall et al. 2005), las células progenitoras hepáticas (HPC) son activada para apoyar o asumir el proceso regenerativo. Las HPCs (que son más conocidas en ratones como células ovales) constituyen una población de células bipotenciales del hígado adulto. Durante la patología hepática crónica, se activan, se expanden en el parénquima hepático y se diferencian a colangiocitos y/o hepatocitos para compensar la pérdida celular y ayudar a mantener la homeostasis de hígado, contribuyendo así a la regeneración del hígado en diferentes enfermedades hepáticas (Riehle et al. 2011). Sin embargo, algunas evidencias recientes apoyen el papel pro-fibrogénico de estas células (Kuramitsu et al. 2013); lo que junto al hecho de que estas células pueden ser objeto de una conversión maligna y transformarse en células iniciadoras de tumores (Lee et al. 2009) contribuye a alimentar la polémica sobre cual es el papel real que juegan durante el daño hepático. Ciertamente, una adecuada regulación de estas células en el contexto de la patología hepática crónica podría ser un determinante importante en la respuesta a la lesión hepática y su posterior desenlace. Todo esto anima a estudiar los mecanismos moleculares implicados en el potencial pro-regenerativo o pro-tumorigénico de las HPC, aún poco conocidos. El factor de crecimiento hepático (HGF) y su receptor tirosina quinasa, c-Met son esenciales para promover una eficaz respuesta regenerativa después del daño hepático agudo y crónico, actuando en los hepatocitos así como en las HPC (Borowiak et al. 2004; Huh et al. 2004; Ishikawa et al. 2012). Este papel pro-regenerativo es la consecuencia de sus actividades anti-inflamatorias, anti-fibróticas y anti-apoptóticas. Es interesante destacar que la ausencia de c-Met tiene profundos efectos en las células ovales, afectando múltiples procesos celulares necesarios para la regeneración, incluyendo la proliferación, supervivencia, diferenciación y migración (Ishikawa et al. 2012)...The liver performs many complex functions involved in maintaining the homeostasis of the organism. A very unique aspect is its high regenerative capacity after liver damage, which is carried out by parenchymal cells. However, if the regenerative capacity of these cells is compromised, such as in chronic injury states or in presence of substances inhibiting adult hepatocyte proliferation (Falkowski et al. 2003; Marshall et al. 2005), the hepatic progenitor cells (HPCs) are activated to support or take over the regenerative process. HPCs (better known as oval cells in rodents) constitute a bipotential cell population from adult liver. Under chronic liver disease (CLD), they become activated, expand into liver parenchyma and differentiate into cholangiocytes and/or hepatocytes to compensate for the cellular loss and to help maintain liver homeostasis; therefore contributing to sustain liver regeneration during several hepatic disorders (Riehle et al. 2011). However, recent evidence supports a pro-fibrogenic role for these cells (Kuramitsu et al. 2013); which together with the fact that they can also be target of malignant conversion and become tumor-initiating cells (Lee et al. 2009), adds to the confusion of which is their precise role during liver injury. Certainly, an appropriate regulation of these cells in the context of CLD could be a major determinant of the response to liver injury and its subsequent outcome. This encourages studying the molecular mechanisms involved in the pro-regenerative or pro-tumorigenic potential of the hepatic progenitor cells, still poorly understood. Hepatocyte growth factor (HGF) and its tyrosine kinase receptor, c-Met, has been demonstrated to be critical for a successful regenerative response after acute and chronic liver damage regulating both hepatocytes and progenitors population (Borowiak et al. 2004; Huh et al. 2004; Ishikawa et al. 2012). This pro-regenerative role is the consequence of its powerful anti-inflammatory, anti-fibrotic and anti-apoptotic activities. Interestingly, absence of c-Met has profound effects in oval cells, affecting multiple cellular processes required for regeneration, including proliferation, survival, differentiation and migration (Ishikawa et al. 2012)...Sección Deptal. de Bioquímica y Biología Molecular (Farmacia)Fac. de FarmaciaTRUEunpu

Particolare tenuità del fatto e sospensione del procedimento con messa alla prova dell’imputato nell’epoca panpenalistica: paradossi e limiti del sistema penale

Osservando l’attuale sistema politico-istituzionale, si scorge la tendenza a considerare la sanzione penale come l’escamotage più comodo per la soluzione dei principali problemi socio-culturali, i quali, a loro volta, non fanno altro che rafforzare il ruolo promozionale del diritto penale, innescando la sua deriva inflazionistica. Alla incapacità del legislatore di maneggiare i confini mobili della materia penale attraverso la concreta attuazione del principio di sussidiarietà ex ante, si è così cercato di porre rimedio adottando meccanismi di selezione punitiva, compendiati nella politica della «deflazione senza depenalizzazione». Configurata, pertanto, come il fil rouge che alimenta e attraversa le plurime componenti dell’apparato penale, il principio di sussidiarietà, nella sua nuova veste, si manifesta sotto forma di una serie di istituti giuridici che, seppur animati da caratteristiche tra loro estremamente eterogenee, conducono, almeno in astratto, alla medesima conclusione, ossia alla “non punibilità”, finale del tutto distante dalla promessa della tradizionale punizione del reato commesso ed accertato. Ed è proprio qui che si collocano la particolare tenuità del fatto e la sospensione del procedimento con messa alla prova che, pur avendo presupposti e conseguenze giuridiche tra loro differenti, sono accomunate dalla “disapplicazione finalizzata” della pena edittale in astratto prevista dalla legge e dalla contestuale applicazione di misure ugualmente cogenti ed afflittive.Observing the current political-institutional system, one can see the tendency to consider the penal sanction as the most convenient trick for solving the main socio-cultural problems, which, in turn, do nothing but strengthen the promotional role of the criminal law, triggering its inflationary drift. The inability of the legislator to manage the mobile boundaries of criminal matters through the concrete implementation of the principle of ex ante subsidiarity has thus sought to remedy this by adopting punitive selection mechanisms, summarized in the policy of "deflation without decriminalization". Configured, therefore, as the common thread that feeds and crosses the multiple components of the criminal apparatus, the principle of subsidiarity, in its new guise, manifests itself in the form of a series of legal institutions which, although animated by extremely heterogeneous characteristics , lead, at least in the abstract, to the same conclusion, that is to say "non-punishable", a final which is completely distant from the promise of the traditional punishment of the crime committed and ascertained. And it is precisely here that the particular tenuity of the fact and the suspension of the trial with trial are placed which, despite having different assumptions and legal consequences, are united by the "finalized nonapplication" of the abstract penalty imposed by law and by the contextual application of equally binding and afflictive measures

TUTA ABSOLUTA (MEYRICK, 1917) (LEPIDOPTERA GELECHIIDAE) ADULT FEEDING ON TOMATO LEAVES. NOTES ON THE BEHAVIOUR AND THE MORPHOLOGY OF THE PARTS RELATED.

Introduction: The Tomato Leaf Miner, Tuta absoluta (Meyrick) (Lepidoptera Gelechiidae), is actually a most dangerous pest of solanaceous crops. Aims: While demonstrating the Tomato Leaf Miner adults, both male and female, ability to feed on tomato leaves we report an unexpected behaviour for this microlepidoptera. This paper details also morphological adaptation of the proboscis involved in feeding and evidences of the action on the leaves. Materials and Methods: Observation were given by digital camera-equipped stereoscope and Cryo-SEM. Results: We discuss the mean of adult feeding in respect to moth mating and egg laying. A possible use of adult feeding in Tomato Leaf Miner IPM is also discussed. Discussion and conclusions: The adult Tomato Leaf Miner is capable to feed by wounding tomato leaf by its proboscis

Impact of Semantic Relatedness on Associative Memory: An ERP Study

Encoding and retrieval processes in memory for pairs of pictures are thought to be influenced by inter-item similarity and by features of individual items. Using Event-Related Potentials (ERP), we aimed to identify how these processes impact on both the early mid-frontal FN400 and the Late Positive Component (LPC) potentials during associative retrieval of pictures. Twenty young adults undertook a sham task, using an incidental encoding of semantically related and unrelated pairs of drawings. At test, we conducted a recognition task in which participants were asked to identify target identical pairs of pictures, which could be semantically related or unrelated, among new and rearranged pairs. We observed semantic (related and unrelated pairs) and condition effects (old, rearranged and new pairs) on the early mid-frontal potential. First, a lower amplitude was shown for identical and rearranged semantically related pairs, which might reflect a retrieval process driven by semantic cues. Second, among semantically unrelated pairs, we found a larger negativity for identical pairs, compared to rearranged and new ones, suggesting additional retrieval processing that focuses on associative information. We also observed an LPC old/new effect with a mid-parietal and a right occipito-parietal topography for semantically related and unrelated old pairs, demonstrating a recollection phenomenon irrespective of the degree of association. These findings suggest that associative recognition using visual stimuli begins at early stages of retrieval, and differs according to the degree of semantic relatedness among items. However, either strategy may ultimately lead to recollection processes

Unusual Feeding in Adult Gelechiidae Moth Tuta Absoluta (Meyrick, 1917)

Introduction: The tomato leaf miner Tuta absoluta (Meyrick, 1917) is a key pest for solanaceous crops, mostly tomato and potato, in many areas of the World. Aims: In this study we present evidences that T. absoluta adults, both males and females, feed on tomato leaves by proboscis. Materials and Methods: Observation were given by a digital camera-equipped stereoscope and confirmed by a Cryo-SEM. Results: We describe and illustrate the adult feeding behaviour and the consequent wounds and scars on the leaves. Discussion and conclusions: A discussion about the role of this unusual behaviour in tomato leafminer biology is given