The role of Ken&Barbie in JAK/STAT signalling during development of Drosophila melanogaster

Cell-cell interactions during embryonic development are crucial in the co-ordination of growth, differentiation and maintenance of many different cell types. To achieve this co-ordination each cell must properly translate signals received from neighbouring cells, into spatially and temporally appropriate developmental responses. A surprisingly limited number of signal pathways are responsible for the differentiation of enormous variety of cell types. As a result, pathways are frequently 'reused' during development. Thus, in mammals the JAK/STAT pathway is required during early embryogenesis, mammary gland formation, hematopoiesis and, finally, plays a pivotal role in immune response. In the canonical way, the JAK/STAT pathway is represented by a transmembrane receptor associated with a Janus kinase (JAK), which upon stimulation by an extra-cellular ligand, phosphorylates itself, the receptor and, finally, the signal transducer and activator of transcription (STAT) molecules. Phosphorylated STATs dimerise and translocate to the nucleus where they activate transcription of target genes. The JAK/STAT pathway has been conserved throughout evolution, and all known components are present in the genome of Drosophila melanogaster. Besides hematopoietic and immunity functions, the pathway is also required during development for processes including embryonic segmentation, tracheal morphogenesis, posterior spiracle formation etc. This study describes Drosophila Ken&Barbie (Ken) as a selective regulator of JAK/STAT signalling. ken mutations identified in a screen for modulators of an eye overgrowth phenotype, caused by over-expression of the pathway ligand unpaired, also interact genetically with the pathway receptor domeless (dome) and the transcription factor stat92E. Over-expression of Ken can phenocopy developmental defects known to be caused by the loss of JAK/STAT signalling. These genetic interactions suggest that Ken may function as a negative regulator of the pathway. Ken has C-terminal Zn-finger domain, presumably for DNA binding, and N-terminal BTB/POZ domain, often found in transcriptional repressors. Using EGFP-fused construct expressed in vivo revealed nuclear accumulation of Ken. Therefore, it is proposed that Ken may act as a suppresser of STAT92E target genes. An in vitro assay, termed SELEX, determined that Ken specifically binds to a DNA sequence, with the essential for DNA recognition core overlapping that of STAT92E. This interesting observation suggests that not all STAT92E sites may also allow Ken binding. Strikingly, when effects of ectopic Ken on the expression of putative JAK/STAT pathway target genes were examined, only a subset of the genes tested, namely vvl, trh and kni, were down-regulated by Ken, whereas some others, such as eve and fj, appeared to be unresponsive. Further analysis of vvl, one of the genes susceptible to ectopic Ken, was undertaken. In the developing hindgut, expression of vvl is JAK/STAT pathway dependent, but remains repressed in the posterior spiracles, despite the stimulation of STAT92E by Upd in their primordia. Importantly, ken is also expressed in the developing posterior spiracles. Strikingly, up-regulation of vvl is observed in these tissues in ken mutant embryos. These imply that while ectopic Ken is sufficient to repress the expression of vvl in the hindgut, endogenous Ken is also necessary to prevent its activation in the posterior spiracles. It is therefore conceivable that ectopic vvl expression in the posterior spiracles of the ken mutants may be the result of de-repression of endogenous STAT92E activity. Another consequence of these observations is a fine balance that must exist between STAT92E and Ken activities. Apparently, endogenous level of Ken is sufficient to repress vvl, but not other, as yet unidentified, JAK/STAT pathway targets, whose presumable activation by STAT92E is required for posterior spiracle development as the embryos mutant for dome, the receptor of the pathway, show severe spiracle defects. These defects are also observed in the embryos mis-expressing Ken. Though it is possible that the posterior spiracle phenotype caused by higher levels of Ken results from a JAK/STAT pathway independent activity, it seems to be more likely that Ken acts in a dosage dependent manner, and extra Ken is able to further antagonise JAK/STAT pathway target genes. While STAT92E binding sites required for target gene expression have been poorly characterised, the existence of genome data allows the prediction of candidate STAT92E sites present in target genes promoters to be attempted. When a 6kb region containing the putative regulatory domains flanking the vvl locus are examined, only a single potential STAT92E binding site located 825bp upstream of the translational start can be detected. Strikingly, this site also includes a perfect Ken binding sequence. Such an in silico observation, though consistent with both Ken DNA binding assay in vitro and regulation of STAT92E target genes in vivo, however, requires further analysis. The JAK/STAT pathway is implicated in a variety of processes during embryonic and larval development as well as in imago. In each case, stimulation of the same transcription factor results in different developmental outcomes. While many potential mechanisms have been proposed and demonstrated to explain such pleiotropy, the present study indicates that Ken may represent another mechanism, with which signal transduction pathways are controlled. Ken selectively down-regulates a subset of potential target genes and so modifies the transcriptional profile generated by activated STAT92E - a mechanism, which may be partially responsible for differences in the morphogenetic processes elicited by JAK/STAT signalling during development.

DNA methylation in Dictyostelium discoideum

DNA methyltransferases of type Dnmt2 are a highly conserved protein family with enigmatic function. The aim of this work was to characterize DnmA, the Dnmt2 methyltransferase in Dictyostelium discoideum, and further to investigate its implication in DNA methylation and transcriptional gene silencing. The genome of the social amoeba Dictyostelium encodes DnmA as the sole DNA methyltransferase. The enzyme bears all ten characteristic DNA methyltransferase motifs in its catalytic domain. The DnmA mRNA was found by RT-PCR to be expressed during vegetative growth and down regulated during development. Investigations using fluorescence microscopy showed that both DnmA-myc and DnmA-GFP fusions predominantly localised to the nucleus. The function of DnmA remained initially unclear, but later experiment revealed that the enzyme is an active DNA methyltransferase responsible for all DNA (cytosine) methylation in Dictyostelium. Neither in gel retardation assays, nor by the yeast two hybrid system, clues on the functionality of DnmA could be obtained. However, immunological detection of the methylation mark with an α - 5mC antibody gave initial evidence that the DNA of Dictyostelium was methylated. Furthermore, addition of 5-aza-cytidine as demethylating agent to the Dictyostelium medium and subsequent in vitro incubation of the DNA isolated from these cells with recombinant DnmA showed that the enzyme binds slightly better to this target DNA. In order to investigate further the function of the protein, a gene knock-out for dnmA was generated. The gene was successfully disrupted by homologous recombination, the knock-out strain, however, did not show any obvious phenotype under normal laboratory conditions. To identify specific target sequences for DNA methylation, a microarray analysis was carried out. Setting a threshold of at least 1.5 fold for differences in the strength of gene expression, several such genes in the knock-out strain were chosen for further investigation. Among the up-regulated genes were the ESTs representing the gag and the RT genes respectively of the retrotransposon skipper. In addition Northern blot analysis confirmed the up-regulation of skipper in the DnmA knock-out strain. Bisufite treatment and sequencing of specific DNA stretches from skipper revealed that DnmA is responsible for methylation of mostly asymmetric cytosines. Together with skipper, DIRS-1 retrotransposon was found later also to be methylated but was not present on the microarray. Furthermore, skipper transcription was also up-regulated in strains that had genes disrupted encoding components of the RNA interference pathway. In contrast, DIRS 1 expression was not affected by a loss of DnmA but was strongly increased in the strain that had the RNA directed RNA polymerase gene rrpC disrupted. Strains generated by propagating the usual wild type Ax2 and the DnmA knock-out cells over 16 rounds in development were analyzed for transposon activity. Northern blot analysis revealed activation for skipper expression, but not for DIRS-1. A large number of siRNAs were found to be correspondent to the DIRS-1 sequence, suggesting concerted regulation of DIRS-1 expression by RNAi and DNA methylation. In contrast, no siRNAs corresponding to the standard skipper element were found. The data show that DNA methylation plays a crucial role in epigenetic gene regulation in Dictyostelium and that different, partially overlapping mechanisms control transposon silencing for skipper and DIRS-1. To elucidate the mechanism of targeting the protein to particular genes in the Dictyostelium genome, some more genes which were up-regulated in the DnmA knock-out strain were analyzed by bisulfite sequencing. The chosen genes are involved in the multidrug response in other species, but their function in Dictyostelium is uncertain. Bisulfite data showed that two of these genes were methylated at asymmetrical C-residues in the wild type, but not in DnmA knock-out cells. This suggested that DNA methylation in Dictyostelium is involved not only in transposon regulation but also in transcriptional silencing of specific genes.

An Inquiry of Changes in Environmental Governance by Community-driven Process

Urban environmental depletion has been a critical problem among industrialized-transformed societies, especially at the local level where administrative authorities’ capacity lags behind changes. Derived from governance concept, the idea of civil society inclusion is highlighted. Focusing on an agglomerated case study, Bang Plee Community in Thailand, this research investigates on a non-state sector, 201-Community organization, as an agent for changes to improve urban environments on solid waste collection. Two roles are contested: as an agent for neighborhood internal change and as an intermediary toward governance changes in state-civil society interaction. By employing longitudinal analysis via a project intervention as research experiment, the outcomes of both roles are detected portrayed in three spheres: state, state-civil society interaction, and civil society sphere. It discovers in the research regarding agglomerated context that as an internal changes for environmental betterment, 201-Community organization operation brings on waste reduction at the minimal level. Community-based organization as an agent for changes – despite capacity input it still limited in efficiency and effectiveness – can mobilize fruitfully only at the individual and network level of civil society sectors, while fails managing at the organizational level. The positive outcomes result by economic waste incentive associated with a limited-bonded group rather than the rise of awareness at large. As an intermediary agent for shared governance, the community-based organization cannot bring on mutual dialogue with state as much as cannot change the state’s operation arena of solid waste management. The findings confine the shared governance concept that it does not applicable in agglomerated locality as an effective outcome, both in terms of being instrumental toward civil society inclusion and being provocative of internal change. Shared environmental governance as summarized in this research can last merely a community development action. It distances significantly from civil society inclusion and empowerment. However, the research proposes that community-based environmental management and shared governance toward civil society inclusion in urban environmental improvement are still an expectable option and reachable if their factors and conditions of key success and failure are intersected with a particular context. Further studies demand more precise on scale, scope, and theses factors of environmental management operation operated by civil society sectors.

Ontology merging with formal concept analysis

Ontologies have been established for knowledge sharing and are widely used as a means for conceptually structuring domains of interest. With the growing usage of ontologies, the problem of overlapping knowledge in a common domain becomes critical. In this short paper, we address two methods for merging ontologies based on Formal Concept Analysis: FCA-Merge and ONTEX. --- FCA-Merge is a method for merging ontologies following a bottom-up approach which offers a structural description of the merging process. The method is guided by application-specific instances of the given source ontologies. We apply techniques from natural language processing and formal concept analysis to derive a lattice of concepts as a structural result of FCA-Merge. The generated result is then explored and transformed into the merged ontology with human interaction. --- ONTEX is a method for systematically structuring the top-down level of ontologies. It is based on an interactive, top-down- knowledge acquisition process, which assures that the knowledge engineer considers all possible cases while avoiding redundant acquisition. The method is suited especially for creating/merging the top part(s) of the ontologies, where high accuracy is required, and for supporting the merging of two (or more) ontologies on that level.

Master Plan for Renewable Energy based Electricity Generation in The Gambia

The principal objective of this paper is to develop a methodology for the formulation of a master plan for renewable energy based electricity generation in The Gambia, Africa. Such a master plan aims to develop and promote renewable sources of energy as an alternative to conventional forms of energy for generating electricity in the country. A tailor-made methodology for the preparation of a 20-year renewable energy master plan focussed on electricity generation is proposed in order to be followed and verified throughout the present dissertation, as it is applied for The Gambia. The main input data for the proposed master plan are (i) energy demand analysis and forecast over 20 years and (ii) resource assessment for different renewable energy alternatives including their related power supply options. The energy demand forecast is based on a mix between Top-Down and Bottom-Up methodologies. The results are important data for future requirements of (primary) energy sources. The electricity forecast is separated in projections at sent-out level and at end-user level. On the supply side, Solar, Wind and Biomass, as sources of energy, are investigated in terms of technical potential and economic benefits for The Gambia. Other criteria i.e. environmental and social are not considered in the evaluation. Diverse supply options are proposed and technically designed based on the assessed renewable energy potential. This process includes the evaluation of the different available conversion technologies and finalizes with the dimensioning of power supply solutions, taking into consideration technologies which are applicable and appropriate under the special conditions of The Gambia. The balance of these two input data (demand and supply) gives a quantitative indication of the substitution potential of renewable energy generation alternatives in primarily fossil-fuel-based electricity generation systems, as well as fuel savings due to the deployment of renewable resources. Afterwards, the identified renewable energy supply options are ranked according to the outcomes of an economic analysis. Based on this ranking, and other considerations, a 20-year investment plan, broken down into five-year investment periods, is prepared and consists of individual renewable energy projects for electricity generation. These projects included basically on-grid renewable energy applications. Finally, a priority project from the master plan portfolio is selected for further deeper analysis. Since solar PV is the most relevant proposed technology, a PV power plant integrated to the fossil-fuel powered main electrical system in The Gambia is considered as priority project. This project is analysed by economic competitiveness under the current conditions in addition to sensitivity analysis with regard to oil and new-technology market conditions in the future.

Capturing Emergent Semantics from Social Annotation Systems

The ongoing growth of the World Wide Web, catalyzed by the increasing possibility of ubiquitous access via a variety of devices, continues to strengthen its role as our prevalent information and commmunication medium. However, although tools like search engines facilitate retrieval, the task of finally making sense of Web content is still often left to human interpretation. The vision of supporting both humans and machines in such knowledge-based activities led to the development of different systems which allow to structure Web resources by metadata annotations. Interestingly, two major approaches which gained a considerable amount of attention are addressing the problem from nearly opposite directions: On the one hand, the idea of the Semantic Web suggests to formalize the knowledge within a particular domain by means of the "top-down" approach of defining ontologies. On the other hand, Social Annotation Systems as part of the so-called Web 2.0 movement implement a "bottom-up" style of categorization using arbitrary keywords. Experience as well as research in the characteristics of both systems has shown that their strengths and weaknesses seem to be inverse: While Social Annotation suffers from problems like, e. g., ambiguity or lack or precision, ontologies were especially designed to eliminate those. On the contrary, the latter suffer from a knowledge acquisition bottleneck, which is successfully overcome by the large user populations of Social Annotation Systems. Instead of being regarded as competing paradigms, the obvious potential synergies from a combination of both motivated approaches to "bridge the gap" between them. These were fostered by the evidence of emergent semantics, i. e., the self-organized evolution of implicit conceptual structures, within Social Annotation data. While several techniques to exploit the emergent patterns were proposed, a systematic analysis - especially regarding paradigms from the field of ontology learning - is still largely missing. This also includes a deeper understanding of the circumstances which affect the evolution processes. This work aims to address this gap by providing an in-depth study of methods and influencing factors to capture emergent semantics from Social Annotation Systems. We focus hereby on the acquisition of lexical semantics from the underlying networks of keywords, users and resources. Structured along different ontology learning tasks, we use a methodology of semantic grounding to characterize and evaluate the semantic relations captured by different methods. In all cases, our studies are based on datasets from several Social Annotation Systems. Specifically, we first analyze semantic relatedness among keywords, and identify measures which detect different notions of relatedness. These constitute the input of concept learning algorithms, which focus then on the discovery of synonymous and ambiguous keywords. Hereby, we assess the usefulness of various clustering techniques. As a prerequisite to induce hierarchical relationships, our next step is to study measures which quantify the level of generality of a particular keyword. We find that comparatively simple measures can approximate the generality information encoded in reference taxonomies. These insights are used to inform the final task, namely the creation of concept hierarchies. For this purpose, generality-based algorithms exhibit advantages compared to clustering approaches. In order to complement the identification of suitable methods to capture semantic structures, we analyze as a next step several factors which influence their emergence. Empirical evidence is provided that the amount of available data plays a crucial role for determining keyword meanings. From a different perspective, we examine pragmatic aspects by considering different annotation patterns among users. Based on a broad distinction between "categorizers" and "describers", we find that the latter produce more accurate results. This suggests a causal link between pragmatic and semantic aspects of keyword annotation. As a special kind of usage pattern, we then have a look at system abuse and spam. While observing a mixed picture, we suggest that an individual decision should be taken instead of disregarding spammers as a matter of principle. Finally, we discuss a set of applications which operationalize the results of our studies for enhancing both Social Annotation and semantic systems. These comprise on the one hand tools which foster the emergence of semantics, and on the one hand applications which exploit the socially induced relations to improve, e. g., searching, browsing, or user profiling facilities. In summary, the contributions of this work highlight viable methods and crucial aspects for designing enhanced knowledge-based services of a Social Semantic Web.

Characterization of Lipid Droplets and Functional Analysis of Lipid Droplet-Associated Proteins in Dictyostelium discoideum

Lipid droplets (LDs) are the universal storage form of fat as a reservoir of metabolic energy in animals, plants, bacteria and single celled eukaryotes. Dictyostelium LD formation was investigated in response to the addition of different nutrients to the growth medium. LDs were induced by adding exogenous cholesterol, palmitic acid (PA) as well as growth in bacterial suspension, while glucose addition fails to form LDs. Among these nutrients, PA addition is most effective to stimulate LD formation, and depletion of PA from the medium caused LD degradation. The neutral lipids incorporated into the LD-core are composed of triacylglycerol (TAG), steryl esters, and an unknown neutral lipid (UKL) species when the cells were loaded simultaneously with cholesterol and PA. In order to avoid the contamination with other cellular organelles, the LD-purification method was modified. The isolated LD fraction was analysed by mass spectrometry and 100 proteins were identified. Nineteen of these appear to be directly involved in lipid metabolism or function in regulating LD morphology. Together with a previous study, a total of 13 proteins from the LD-proteome were confirmed to localize to LDs after the induction with PA. Among the identified LD-proteins, the localization of Ldp (lipid droplet membrane protein), GPAT3 (glycerol-3-phosphate acyltransferase 3) and AGPAT3 (1-acylglycerol-3-phosphate-acyltransferase 3) were further verified by GFP-tagging at the N-termini or C-termini of the respective proteins. Fluorescence microscopy demonstrated that PA-treatment stimulated the translocation of the three proteins from the ER to LDs. In order to clarify DGAT (diacylglycerol acyltransferase) function in Dictyostelium, the localization of DGAT1, that is not present in LD-proteome, was also investigated. GFP-tagged DGAT1 localized to the ER both, in the presence and absence of PA, which is different from the previously observed localization of GFP-tagged DGAT2, which almost exclusively binds to LDs. The investigation of the cellular neutral lipid level helps to elucidate the mechanism responsible for LD-formation in Dictyostelium cells. Ldp and two short-chain dehydrogenases, ADH (alcohol dehydrogenase) and Ali (ADH-like protein), are not involved in neutral lipid biosynthesis. GPAT, AGPAT and DGAT are three transferases responsible for the three acylation steps of de novo TAG synthesis. Knock-out (KO) of AGPAT3 and DGAT2 did not affect storage-fat formation significantly, whereas cells lacking GPAT3 or DGAT1 decreased TAG and LD accumulation dramatically. Furthermore, DGAT1 is responsible for the accumulation of the unknown lipid UKL. Overexpression of DGAT2 can rescue the reduced TAG content of the DGAT1-KO mutant, but fails to restore UKL content in these cells, indicating that of DGAT1 and DGAT2 have overlapping functions in TAG synthesis, but the role in UKL formation is unique to DGAT1. Both GPAT3 and DGAT1 affect phagocytic activity. Mutation of GPAT3 increases it but a DGAT1-KO decreases phagocytosis. The double knockout of DGAT1 and 2 also impairs the ability to grow on a bacterial lawn, which again can be rescued by overexpression of DGAT2. These and other results are incorporated into a new model, which proposes that up-regulation of phagocytosis serves to replenish precursor molecules of membrane lipid synthesis, whereas phagocytosis is down-regulated when excess fatty acids are used for storage-fat formation.  

Finding Spaces for Urban Food Production – Matching Spatial and Stakeholder Analysis with Urban Agriculture Approaches in the Urban Renewal Area of Dortmund-Hörde, Germany

Using the case of an economically declined neighbourhood in the post-industrial German Ruhr Area (sometimes characterized as Germany’s “Rust Belt”), we analyse, describe and conclude how urban agriculture can be used as a catalyst to stimulate and support urban renewal and regeneration, especially from a socio-cultural perspective. Using the methodological framework of participatory action research, and linking bottom-up and top-down planning approaches, a project path was developed to include the population affected and foster individual responsibility for their district, as well as to strengthen inhabitants and stakeholder groups in a permanent collective stewardship for the individual forms of urban agriculture developed and implemented. On a more abstract level, the research carried out can be characterized as a form of action research with an intended transgression of the boundaries between research, planning, design, and implementation. We conclude that by synchronously combining those four domains with intense feedback loops, synergies for the academic knowledge on the potential performance of urban agriculture in terms of sustainable development, as well as the benefits for the case-study area and the interests of individual urban gardeners can be achieved.

Categorization in IT and PFC: Model and Experiments

In a recent experiment, Freedman et al. recorded from inferotemporal (IT) and prefrontal cortices (PFC) of monkeys performing a "cat/dog" categorization task (Freedman 2001 and Freedman, Riesenhuber, Poggio, Miller 2001). In this paper we analyze the tuning properties of view-tuned units in our HMAX model of object recognition in cortex (Riesenhuber 1999) using the same paradigm and stimuli as in the experiment. We then compare the simulation results to the monkey inferotemporal neuron population data. We find that view-tuned model IT units that were trained without any explicit category information can show category-related tuning as observed in the experiment. This suggests that the tuning properties of experimental IT neurons might primarily be shaped by bottom-up stimulus-space statistics, with little influence of top-down task-specific information. The population of experimental PFC neurons, on the other hand, shows tuning properties that cannot be explained just by stimulus tuning. These analyses are compatible with a model of object recognition in cortex (Riesenhuber 2000) in which a population of shape-tuned neurons provides a general basis for neurons tuned to different recognition tasks.

Análisis de la Política de Educación Media Articulada con la Educación Superior en Bogotá : 2005-2008

La Política (public policy) de Educación Media Articulada con la Educación Superior en Bogotá , implementada durante las alcaldías de Luis Eduardo Garzón y Samuel Moreno, apunta a disminuir la falta de oportunidades en el acceso a la educación superior de los bachilleres bogotanos, a través de la transformación de los colegios a nivel pedagógico, administrativo, físico y organizacional para que los estudiantes de décimo y once cursen créditos de educación superior en los colegios a la par que terminan su educación media. No obstante los objetivos loables de la política, varias críticas y efectos negativos acompañaron su implementación. Este es el tema de la monografía, que pretende analizar el desarrollo de la política a la luz de los enfoques teóricos de políticas públicas (Top-down y bottom-up entre otros) en su formulación, implementación y evaluación.

Detecció o desenvolupament del talent? Factors que motiven una nova orientació del procés de detecció de talents.

Resumen tomado del autor

¿Renovación, crisis o más de lo mismo? La revocatoria de mandato en los gobiernos locales latinoamericanos

In the public agenda in Latin America recall has gained of importance since the controversies generated by the votes in Venezuela (2004) and Bolivia (2008) in order to recall Presidents Hugo Chavez and Evo Morales, respectively (both attempts failed). However, it is on the local level where this institution got activated  most frequently and where it could be responsible for major political changes. In  this article, we analyze the introduction, use and consequences of the recall on  the local level in Bolivia, Colombia, Ecuador, Peru and Venezuela. We briefly  discuss recall in the light of the current debate on representative democracy and its adoption as a mechanism of direct democracy (MDD) from ‘bottom-up’, initiated  by the citizens. Furthermore, we describe the context under which MDDs have proliferated in various places of the world. More specifically, we then continue  to explore where and in which context in Latin America recall was promoted  as an element of participatory democracy. Finally, we com  up with tentative conclusions about the potential and risks involved with this particular mechanism of direct democracy.

Convergencia de vías de señalización en un modelo de apoptosis

La sepsis es un evento inflamatorio generalizado del organismo inducido por un daño causado generalmente por un agente infeccioso. El patógeno más frecuentemente asociado con esta entidad es el Staphylococcus aureus, responsable de la inducción de apoptosis en células endoteliales debida a la producción de ceramida. Se ha descrito el efecto protector de la proteína C activada (PCA) en sepsis y su relación con la disminución de la apoptosis de las células endoteliales. En este trabajo se analizó la activación de las quinasas AKT, ASK1, SAPK/JNK y p38 en un modelo de apoptosis endotelial usando las técnicas de Western Blotting y ELISA. Las células endoteliales (EA.hy926), se trataron con C2-ceramida (130μM) en presencia de inhibidores químicos de cada una de estas quinasas y PCA. La supervivencia de las células en presencia de inhibidores químicos y PCA fue evaluada por medio de ensayos de activación de las caspasas 3, 7 y 9, que verificaban la muerte celular por apoptosis. Los resultados evidencian que la ceramida reduce la activación de AKT y aumenta la activación de las quinasas ASK, SAPK/JNK y p38, en tanto que PCA ejerce el efecto contrario. Adicionalmente se encontró que la tiorredoxina incrementa la activación/fosforilación de AKT, mientras que la quinasa p38 induce la defosforilación de AKT.

El costo de la atención ambulatoria del lupus eritematoso sistémico en Colombia. Contrastes y comparaciones con otras poblaciones.

Introducción: el lupus eritematoso sistémico (LES) es considerado una enfermedad de alto costo. La expresión clínica de la enfermedad depende de la ubicación geografía y la etnicidad. El objetivo de este estudio fue el calcular los costos ambulatorios relacionado al LES en una cohorte colombiana, identificar los predictores de costos y comparar nuestro resultados con otras poblaciones. Métodos: Se realizó una aproximación de tipo prevalencia en 100 pacientes LES en quienes se evaluaron los costos directos médicos, directos no médicos, indirectos e intangibles. Todos los costos médicos fueron evaluados usando una metodología abajo hacia arriba. Los costos directos fueron valorados desde una perspectiva social usando una metodología de micro-costeo. Los costos indirectos se evaluaron mediante una aproximación de capital humano, y los costos intangibles calculados a partir de los años de vida ajustados por calidad (AVAC). Se analizaron los datos por medio de un análisis multivariado. Para comparaciones con otras poblaciones todos los costos fueron expresados como la razón entre los costos y producto interno bruto nacional per cápita. Resultados: La media de costos totales fue 13.031±9.215 USD (ajustados por el factor de conversión de paridad del poder adquisitivo), lo cual representa el 1,66 del PIB per capita de Colombia. Los costos directos son el 64% de los costos totales. Los costos médicos representan el 80% de los costos directos,. Los costos indirectos fueron el 10% y los costos intangibles el 25% de los costos totales. Los medicamentos representaron el 45% de los costos directos. Mayores costos se relacionaron con el estrato socioeconómico, seguro médico privado, AVAC, alopecia, micofenolato mofetilo, y terapia anticoagulante. Los costos directos ajustados de los pacientes con LES en Colombia fueron mayores que en Norte América y en Europa. Conclusiones: el LES impone una carga económica importante para la sociedad. Los costos relacionados con la atención médica y AVAC fueron los principales contribuyentes al alto costo de la enfermedad. Estos resultados pueden ser referencia para determinar políticas en salud pública así como comparar el gasto en salud de forma internacional.

La competencia auditiva en el aula ELE en la era de ALAO : una propuesta de investigación experimental.

Resumen basado en el de la publicación