Distribution of monocarboxylate transporters in the peripheral nervous system suggests putative roles in lactate shuttling and myelination.

Lactate, a product of glycolysis, has been shown to play a key role in the metabolic support of neurons/axons in the CNS by both astrocytes and oligodendrocytes through monocarboxylate transporters (MCTs). Despite such importance in the CNS, little is known about MCT expression and lactate function in the PNS. Here we show that mouse MCT1, MCT2, and MCT4 are expressed in the PNS. While DRG neurons express MCT1, myelinating Schwann cells (SCs) coexpress MCT1 and MCT4 in a domain-specific fashion, mainly in regions of noncompact myelin. Interestingly, SC-specific downregulation of MCT1 expression in rat neuron/SC cocultures led to increased myelination, while its downregulation in neurons resulted in a decreased amount of neurofilament. Finally, pure rat SCs grown in the presence of lactate exhibited an increase in the level of expression of the main myelin regulator gene Krox20/Egr2 and the myelin gene P0. These data indicate that lactate homeostasis participates in the regulation of the SC myelination program and reveal that similar to CNS, PNS axon-glial metabolic interactions are most likely mediated by MCTs.

Novel Roles of HCG/LH Signalling in the Mouse Mammary Gland and its Tumorigenesis.

Breast cancer is the most common cancer in women, and its development is intimately related to hormonal factors, but how hormones affect breast physiology and tumorigenesis is not sufficiently known. Pregnancy elicits long-term protection from breast cancer, but during the first ten years after pregnancy, breast cancer risk is increased. In previous studies, there has been conflicting data on the role of human chorionic gonadotropin (HCG) and the functionality of its receptor in extragonadal tissues. The aim of this study was to elucidate the role of chronically elevated HCG in mouse physiology. We have created a transgenic (TG) mouse model that overexpresses HCG. HCG is similar to lutenizing hormone (LH), but is secreted almost solely by the placenta during pregnancy. HCG and LH both bind to the LH receptor (LHR). In the current study, mammary gland tumors were observed in HCG TG mice. We elucidated the role of HCG in mammary gland signalling and the effects of LHR mediated signalling in mouse mammary gland gene expression. We also studied the effects of HCG in human breast epithelial cell cultures. Several endocrine disturbances were observed in HCGβ TG female mice, resulting in precocious puberty, infertility, obesity and pituitary and mammary gland tumors. The histology of the mammary gland tumors of HCGβ TG females resembled those observed in mouse models with activated Wnt/β-catenin signalling pathway. Wnts are involved in stem cell regulation and tumorigenesis, and are hormonally regulated in the mammary gland. We observed activated β-catenin signalling and elevated expression of Wnt5b and Wnt7b in TG tumors and mammary glands. Furthermore, we discovered that HCG directly regulates the expression of Wnt5b and Wnt7b in the mouse mammary gland. Pharmacological treatment with HCG also caused upregulation of several Wnt-pathway target genes in ovariectomized wild type (WT) mice in the presence of physiological concentrations of estradiol and progesterone. In addition, differential expression of several metabolic genes was observed, suggesting that HCG affects adipocyte function or glucose metabolism. When WT mice were transplanted with LHR deficient or wild type WT mammary epithelium, differential expression of several genes affecting the Wnt-signalling pathway was observed in microarray analysis. Diminished expression of several genes associated with LHR function in other tissues, such as the ovary, was observed in mammary glands deficient of epithelial LHR. In cultured human mammary epithelial cells HCG upregulated the expression of WNT5B, WNT7B similar to mouse, suggesting that the observations found are relevant in human physiology. These studies suggest that HCG/LHR signalling affects gene expression in non-gonadal tissues, and that Wnt-signalling is regulated by HCG/LH in human and mouse mammary glands.

Evolución de la enfermería y aparición de nuevos roles: Rol de la enfermera de Cuidados Paliativos

El papel de la enfermería se ha visto sometido a muchos cambios desde sus inicios hasta la actualidad. Cambios que han ayudado a que la profesión crezca y a que se fundamente en un cuerpo de conocimientos propios. Las enfermeras, inicialmente supeditadas al estamento médico, se encuentran actualmente con un nivel de formación que les permite desarrollar su rol autónomo. Las nuevas necesidades de cuidados, generadas por los cambios socio-demográficos, epidemiológicos y políticos, y la necesidad de dar respuesta a la demanda de la población, han generado una nueva perspectiva de los sistemas de salud. Los sistemas sanitarios tratan de adaptarse a las nuevas circunstancias generando modelos sanitarios eficaces y económicamente sostenibles, donde la enfermera tiene un papel primordial. Para poder dar la atención necesaria y profesional a todo este nuevo modelo asistencial se está procediendo cada vez más y de manera más activa, a la implantación de nuevos roles enfermeros (enfermera/o gestora/or de casos, enfermera de Enlace, etc.). Dentro de estos roles, destaca el de enfermera/o en Cuidados Paliativos (CP) por su gran complejidad e incluso desconocimiento, debido a que es un rol relativamente reciente. Dada la importancia para el colectivo enfermero de conocer y comprender los cambios que ha experimentado la enfermería, el presente trabajo pretende obtener una visión general de la evolución histórica de la enfermería y la aparición de nuevos roles, profundizando en el rol de CP. Para ello se realiza una revisión de la literatura. Palabras clave: Roles enfermería, cuidado, historia enfermería, evolución enfermería, cuidados paliativos, enfermería paliativa.

Distinct roles of NMDA receptors at different stages of granule cell development in the adult brain.

NMDA receptor (NMDAR)-dependent forms of synaptic plasticity are thought to underlie the assembly of developing neuronal circuits and to play a crucial role in learning and memory. It remains unclear how NMDAR might contribute to the wiring of adult-born granule cells (GCs). Here we demonstrate that nascent GCs lacking NMDARs but rescued from apoptosis by overexpressing the pro-survival protein Bcl2 were deficient in spine formation. Insufficient spinogenesis might be a general cause of cell death restricted within the NMDAR-dependent critical time window for GC survival. NMDAR loss also led to enhanced mushroom spine formation and synaptic AMPAR activity throughout the development of newborn GCs. Moreover, similar elevated synapse maturation in the absence of NMDARs was observed in neonate-generated GCs and CA1 pyramidal neurons. Together, these data suggest that NMDAR operates as a molecular monitor for controlling the activity-dependent establishment and maturation rate of synaptic connections between newborn neurons and others.

Enzymes of yeast polyphosphate metabolism: structure, enzymology and biological roles.

Inorganic polyphosphate (polyP) is found in all living organisms. The known polyP functions in eukaryotes range from osmoregulation and virulence in parasitic protozoa to modulating blood coagulation, inflammation, bone mineralization and cellular signalling in mammals. However mechanisms of regulation and even the identity of involved proteins in many cases remain obscure. Most of the insights obtained so far stem from studies in the yeast Saccharomyces cerevisiae. Here, we provide a short overview of the properties and functions of known yeast polyP metabolism enzymes and discuss future directions for polyP research.

¿Qué significan los términos 'relaciones sexuales'? Definiciones y ejemplos proporcionados por jóvenes universitarios

Aims: The aim of this paper is to know what means for Spanish university students “sexual relations”, from a sexually transmitted infections prevention point of view. Method: Participants were seven hundred and fifty university students from 18 to 25 years (67.7% women; 65.5% between 18 and 21 years old) selected by multistage proportional sampling. They were asked to give a maximum of three free definitions or examples of “sexual relations”. They could use the language they feel more comfortable. An example of (vaginal sex) was provided and three blank spaces for answering were marked. Results: 23.5% of participants repeated the example provided (vaginal sex). The other answers were categorized in the following topics: euphemisms (42,3%), sex with penetration (40,3%), divagations (11,2%), sex without penetration (11,1%), anal sex (10,5%), oral sex (5,6%), masturbation (2,4%) and having an orgasm (1,5%). Conclusions: Young people’s meaning of “having sex” has become more diversified in the last years. These results must be useful in order to design future preventive campaigns

Roles of leadership in complex environments : Enhancing Knowledge Flows in Organisational Constellations through Practice-Based Innovation Processes

Global challenges, complexity and continuous uncertainty demand development of leadership approaches, employees and multi-organisation constellations. Current leadership theories do not sufficiently address the needs of complex business environments. First of all, before successful leadership models can be applied in practice, leadership needs to shift from the industrial age to the knowledge era. Many leadership models still view leadership solely through the perspective of linear process thinking. In addition, there is not enough knowledge or experience in applying these newer models in practice. Leadership theories continue to be based on the assumption that leaders possess or have access to all the relevant knowledge and capabilities to decide future directions without external advice. In many companies, however, the workforce consists of skilled professionals whose work and related interfaces are so challenging that the leaders cannot grasp all the linked viewpoints and cross-impacts alone. One of the main objectives of this study is to understand how to support participants in organisations and their stakeholders to, through practice-based innovation processes, confront various environments. Another aim is to find effective ways of recognising and reacting to diverse contexts, so companies and other stakeholders are better able to link to knowledge flows and shared value creation processes in advancing joint value to their customers. The main research question of this dissertation is, then, to seek understanding of how to enhance leadership in complex environments. The dissertation can, on the whole, be characterised as a qualitative multiple-case study. The research questions and objectives were investigated through six studies published in international scientific journals. The main methods applied were interviews, action research and a survey. The empirical focus was on Finnish companies, and the research questions were examined in various organisations at the top levels (leaders and managers) and bottom levels (employees) in the context of collaboration between organisations and cooperation between case companies and their client organisations. However, the emphasis of the analysis is the internal and external aspects of organisations, which are conducted in practice-based innovation processes. The results of this study suggest that the Cynefin framework, complexity leadership theory and transformational leadership represent theoretical models applicable to developing leadership through practice-based innovation. In and of themselves, they all support confronting contemporary challenges, but an implementable method for organisations may be constructed by assimilating them into practice-based innovation processes. Recognition of diverse environments, their various contexts and roles in the activities and collaboration of organisations and their interest groups is ever-more important to achieving better interaction in which a strategic or formal status may be bypassed. In innovation processes, it is not necessarily the leader who is in possession of the essential knowledge; thus, it is the role of leadership to offer methods and arenas where different actors may generate advances. Enabling and supporting continuous interaction and integrated knowledge flows is of crucial importance, to achieve emergence of innovations in the activities of organisations and various forms of collaboration. The main contribution of this dissertation relates to applying these new conceptual models in practice. Empirical evidence on the relevance of different leadership roles in practice-based innovation processes in Finnish companies is another valuable contribution. Finally, the dissertation sheds light on the significance of combining complexity science with leadership and innovation theories in research.

Tuning cell motility : roles of nestin and vimentin in cancer cell invasion and motility

The cytoskeleton is a key feature of both prokaryotic and eukaryotic cells. Itis comprised of three protein families, one of which is the intermediate filaments (IFs). Of these, the IFs are the largest and most diverse. The IFs are expressed throughout life, and are involved in the regulation of cell differentiation, homeostasis, ageing and pathogenesis. The IFs not only provide structural integrity to the cell, they are also involved in a range of cellular functions from organelle trafficking and cell migration to signalling transduction. The IFs are highly dynamic proteins, able to respond and adapt their network rapidly in response to intra- and extra- cellular cues. Consequently they interact with a whole host of cellular signalling proteins, regulating function, and activity, and cellular localisation. While the function of some of the better-known IFs such as the keratins is well studied, the understanding of the function of two IFs, nestin and vimentin, is poor. Nestin is well known as a marker of differentiation and is expressed in some cancers. In cancer, nestin is primarily described as is a promoter of cell motility, however, how it fulfils this role remains undefined. Vimentin too is expressed in cancer, and is known to promote cell motility and is used as a marker for epithelial to mesenchymal transition (EMT). It is only in the last decade that studies have addressed the role that vimentin plays in cell motility and EMT. This work provides novel insight into how the IFs, nestin and vimentin regulate cell motility and invasion. In particular we show that nestin regulates the cellular localisation and organisation of two key facilitators of cell migration, focal adhesion kinase and integrins. We identify nestin as a regulator of extracellular matrix degradation and integrin-mediated cell invasion. Two further studies address the specific regulation of vimentin by phosphorylation. A detailed characterisation study identified key phosphorylation sites on vimentin, which are critical for proper organisation of the vimentin network. Furthermore, we show that the bioactive sphingolipids are vimentin network regulators. Specifically, the sphingolipids induced RhoA kinasedependent (ROCK) phosphorylation at vimentin S71, which lead to filament reorganisation and inhibition of cell migration. Together these studies shed new light into the regulation of nestin and vimentin during cell motility.

Individual learner, peer group and teacher roles in fostering autonomous language-learning behaviour

Julkaisumaa: Bulgaria

La "cultura de la vida": desplazamientos estratégicos del activismo católico conservador frente a los derechos sexuales y reproductivos

El artículo considera las principales dimensiones del activismo católico conservador sobre la sexualidad a partir del análisis de la Encíclica Evangelium Vitae (1995). El análisis se focaliza en tres dimensiones: la oposición entre cultura de la vida y cultura de la muerte como el enmarque político; los desplazamientos del activismo católico conservador para intervenir en los principales debates públicos; las principales estrategias propuestas para evitar la sanción o la vigencia de los derechos sexuales y reproductivos. A través de estos ejes, se contribuye a la comprensión de las rearticulaciones en las formas de intervención de la Iglesia Católica como una parte constitutiva de la política sexual contemporánea.

Nuevas configuraciones religiosas/seculares: las ONG “pro-vida” en las disputas por las políticas sexuales en Argentina

Resumen En América Latina, desde hace algunos años, una serie de actores religiosos vienen articulando estrategias para oponerse a los derechos sexuales y reproductivos. Si bien la jerarquía de la Iglesia Católica y algunas iglesias evangélicas continúan siendo centrales en la oposición a estos derechos, en las últimas décadas distintos sectores de la sociedad civil han comenzado también a activarse políticamente en pos de resistir el avance de la agenda de los derechos sexuales y reproductivos. Desde aquí, diversas ONG “pro-vida” vienen adquiriendo cada vez mayor relevancia en el contexto argentino. El presente artículo busca describir e identificar la emergencia y el desarrollo de estas ONG en Argentina, así como las transformaciones en sus identidades públicas y sus acciones. Se destaca cómo han mutado sus identidades religiosa, desplazando estos elementos a un segundo plano. Así, se da cuenta de las complejidades que adquieren las fronteras entre lo religioso y secular en su accionar político.