Inhibition of the alternative lengthening of telomeres pathway by subtelomeric sequences in Saccharomyces cerevisiae.

In the budding yeast Saccharomyces cerevisiae, telomerase is constitutively active and is essential for chromosome end protection and illimited proliferation of cell populations. However, upon inactivation of telomerase, alternative mechanims of telomere maintenance allow proliferation of only extremely rare survivors. S. cerevisiae type I and type II survivors differ by the nature of the donor sequences used for repair by homologous recombination of the uncapped terminal TG1-3 telomeric sequences. Type I amplifies the subtelomeric Y' sequences and is more efficient than type II, which amplifies the terminal TG1-3 repeats. However, type II survivors grow faster than type I survivors and can easily outgrow them in liquid cultures. The mechanistic interest of studying S. cerevisiae telomeric recombination is reinforced by the fact that type II recombination is the equivalent of the alternative lengthening of telomeres (ALT) pathway that is used by 5-15 % of cancer types as an alternative to telomerase reactivation. In budding yeast, only around half of the 32 telomeres harbor Y' subtelomeric elements. We report here that in strains harboring Y' elements on all telomeres, type II survivors are not observed, most likely due to an increase in the efficiency of type I recombination. However, in a temperature-sensitive cdc13-1 mutant grown at semi-permissive temperature, the increased amount of telomeric TG1-3 repeats could overcome type II inhibition by the subtelomeric Y' sequences. Strikingly, in the 100 % Y' strain the replicative senescence crisis normally provoked by inactivation of telomerase completely disappeared and the severity of the crisis was proportional to the percentage of chromosome-ends lacking Y' subtelomeric sequences. The present study highlights the fact that the nature of subtelomeric elements can influence the selection of the pathway of telomere maintenance by recombination, as well as the response of the cell to telomeric damage caused by telomerase inactivation.

Analysis of the impact of the absence of RAD51 strand exchange activity in Arabidopsis meiosis.

The ploidy of eukaryote gametes must be halved to avoid doubling of numbers of chromosomes with each generation and this is carried out by meiosis, a specialized cell division in which a single chromosomal replication phase is followed by two successive nuclear divisions. With some exceptions, programmed recombination ensures the proper pairing and distribution of homologous pairs of chromosomes in meiosis and recombination defects thus lead to sterility. Two highly related recombinases are required to catalyse the key strand-invasion step of meiotic recombination and it is the meiosis-specific DMC1 which is generally believed to catalyse the essential non-sister chromatid crossing-over, with RAD51 catalysing sister-chromatid and non-cross-over events. Recent work in yeast and plants has however shown that in the absence of RAD51 strand-exchange activity, DMC1 is able to repair all meiotic DNA breaks and surprisingly, that this does not appear to affect numbers of meiotic cross-overs. In this work we confirm and extend this conclusion. Given that more than 95% of meiotic homologous recombination in Arabidopsis does not result in inter-homologue crossovers, Arabidopsis is a particularly sensitive model for testing the relative importance of the two proteins-even minor effects on the non-crossover event population should produce detectable effects on crossing-over. Although the presence of RAD51 protein provides essential support for the action of DMC1, our results show no significant effect of the absence of RAD51 strand-exchange activity on meiotic crossing-over rates or patterns in different chromosomal regions or across the whole genome of Arabidopsis, strongly supporting the argument that DMC1 catalyses repair of all meiotic DNA breaks, not only non-sister cross-overs.

Telomere stability and development of ctc1 mutants are rescued by inhibition of EJ recombination pathways in a telomerase-dependent manner.

The telomeres of linear eukaryotic chromosomes are protected by caps consisting of evolutionarily conserved nucleoprotein complexes. Telomere dysfunction leads to recombination of chromosome ends and this can result in fusions which initiate chromosomal breakage-fusion-bridge cycles, causing genomic instability and potentially cell death or cancer. We hypothesize that in the absence of the recombination pathways implicated in these fusions, deprotected chromosome ends will instead be eroded by nucleases, also leading to the loss of genes and cell death. In this work, we set out to specifically test this hypothesis in the plant, Arabidopsis. Telomere protection in Arabidopsis implicates KU and CST and their absence leads to chromosome fusions, severe genomic instability and dramatic developmental defects. We have analysed the involvement of end-joining recombination pathways in telomere fusions and the consequences of this on genomic instability and growth. Strikingly, the absence of the multiple end-joining pathways eliminates chromosome fusion and restores normal growth and development to cst ku80 mutant plants. It is thus the chromosomal fusions, per se, which are the underlying cause of the severe developmental defects. This rescue is mediated by telomerase-dependent telomere extension, revealing a competition between telomerase and end-joining recombination proteins for access to deprotected telomeres.

Responses to telomere erosion in plants.

In striking contrast to animals, plants are able to develop and reproduce in the presence of significant levels of genome damage. This is seen clearly in both the viability of plants carrying knockouts for key recombination and DNA repair genes, which are lethal in vertebrates, and in the impact of telomere dysfunction. Telomerase knockout mice show accelerated ageing and severe developmental phenotypes, with effects on both highly proliferative and on more quiescent tissues, while cell death in Arabidopsis tert mutants is mostly restricted to actively dividing meristematic cells. Through phenotypic and whole-transcriptome RNAseq studies, we present here an analysis of the response of Arabidopsis plants to the continued presence of telomere damage. Comparison of second-generation and seventh-generation tert mutant plants has permitted separation of the effects of the absence of the telomerase enzyme and the ensuing chromosome damage. In addition to identifying a large number of genes affected by telomere damage, many of which are of unknown function, the striking conclusion of this study is the clear difference observed at both cellular and transcriptome levels between the ways in which mammals and plants respond to chronic telomeric damage.

Awareness of the healthcare system and rights to healthcare in the Colombian population

Objectives: To analyze changes in users' awareness of the healthcare system and of their rights to healthcare in Colombia in the last 10 years, as well as the factors that influence users' awareness. Methods: We carried out a descriptive study to compare the results of two cross-sectional studies based on two surveys of users of the Colombian healthcare system. The first survey was performed in 2000 and the second in 2010. The municipalities of Tuluá (urban area) and Palmira (rural area) were surveyed. In both surveys, a stratified, multistage probability sample was selected. There were 1497 users in the first sample and 1405 in the second. Changes in awareness of the healthcare system and associated factors in each year were assessed through multivariate logistic regressions. Results: Users' awareness of the healthcare system was limited in 2000 and was significantly lower in 2010, except for that relating to health insurers and providers. In contrast, more than 90% of users in both surveys perceived themselves as having healthcare rights. The factors consistently associated with greater awareness were belonging to a high socioeconomic stratum and having higher education. Conclusions: The most underprivileged users were less likely to be aware of the healthcare system, hampering their ability to make informed decisions and to exercise their health rights. To correct this situation, health institutions and the government should act decisively to reduce social inequalities (AU)

Objetivos: Analizar cambios en el conocimiento y en los factores que influyen en este conocimiento de los usuarios del sistema de salud (SGSSS) y de sus derechos a la atención en salud en Colombia en los últimos 10 años. Métodos: Estudio descriptivo que compara resultados de dos estudios transversales basados en dos encuestas realizadas a usuarios del sistema de salud de Colombia, una en 2000 y otra en 2010. El área de estudio fueron los municipios de Tuluá (zona urbana) y Palmira (zona rural). En ambas encuestas se realizó un muestreo probabilístico estratificado multietápico, conformándose en la primera una muestra de 1497 usuarios y en la segunda de 1405. Se analizó el cambio en el conocimiento y los factores asociados en cada año mediante regresión logística multivariada. Resultados: El conocimiento del sistema de salud en 2000 era limitado y en 2010 disminuyó significativamente, excepto en relación con las aseguradoras y los proveedores. En contraste, los resultados muestran que más del 90% de los usuarios en ambas encuestas se perciben poseedores del derecho a la atención en salud. Pertenecer a estratos socioeconómicos altos y estudios superiores se asocia consistentemente a un mayor grado de conocimiento. Conclusiones: Los usuarios más desfavorecidos tienen menor posibilidad de conocer el SGSSS, lo cual es una barrera para tomar decisiones informadas y para hacer cumplir y ejercer sus derechos a la salud. Para revertir esta situación es necesaria una intervención decidida de las instituciones de salud, así como del gobierno en general, para reducir las inequidades sociales (AU)

Awareness of the healthcare system and rights to healthcare in the Colombian population.

OBJECTIVES: To analyze changes in users' awareness of the healthcare system and of their rights to healthcare in Colombia in the last 10 years, as well as the factors that influence users' awareness. METHODS: We carried out a descriptive study to compare the results of two cross-sectional studies based on two surveys of users of the Colombian healthcare system. The first survey was performed in 2000 and the second in 2010. The municipalities of Tuluá (urban area) and Palmira (rural area) were surveyed. In both surveys, a stratified, multistage probability sample was selected. There were 1497 users in the first sample and 1405 in the second. Changes in awareness of the healthcare system and associated factors in each year were assessed through multivariate logistic regressions. RESULTS: Users' awareness of the healthcare system was limited in 2000 and was significantly lower in 2010, except for that relating to health insurers and providers. In contrast, more than 90% of users in both surveys perceived themselves as having healthcare rights. The factors consistently associated with greater awareness were belonging to a high socioeconomic stratum and having higher education. CONCLUSIONS: The most underprivileged users were less likely to be aware of the healthcare system, hampering their ability to make informed decisions and to exercise their health rights. To correct this situation, health institutions and the government should act decisively to reduce social inequalities.

Differing requirements for RAD51 and DMC1 in meiotic pairing of centromeres and chromosome arms in Arabidopsis thaliana.

During meiosis homologous chromosomes pair, recombine, and synapse, thus ensuring accurate chromosome segregation and the halving of ploidy necessary for gametogenesis. The processes permitting a chromosome to pair only with its homologue are not fully understood, but successful pairing of homologous chromosomes is tightly linked to recombination. In Arabidopsis thaliana, meiotic prophase of rad51, xrcc3, and rad51C mutants appears normal up to the zygotene/pachytene stage, after which the genome fragments, leading to sterility. To better understand the relationship between recombination and chromosome pairing, we have analysed meiotic chromosome pairing in these and in dmc1 mutant lines. Our data show a differing requirement for these proteins in pairing of centromeric regions and chromosome arms. No homologous pairing of mid-arm or distal regions was observed in rad51, xrcc3, and rad51C mutants. However, homologous centromeres do pair in these mutants and we show that this does depend upon recombination, principally on DMC1. This centromere pairing extends well beyond the heterochromatic centromere region and, surprisingly, does not require XRCC3 and RAD51C. In addition to clarifying and bringing the roles of centromeres in meiotic synapsis to the fore, this analysis thus separates the roles in meiotic synapsis of DMC1 and RAD51 and the meiotic RAD51 paralogs, XRCC3 and RAD51C, with respect to different chromosome domains.

Changes in awareness and utilization of social participation mechanisms of the Colombian health care system in the last 10 years.

This article seeks to analyze changes in awareness and utilization of social participation mechanisms of the Colombian health care system in the last 10 years by comparing two cross-sectional studies based on surveys among health care users in 2000 and 2010. The results show that while in 2000, the level of awareness and utilization of the mechanisms were low, in 2010 researchers identified a significant tendency toward further diminishing of awareness and utilization. In both surveys, the best-known and most-used participation mechanisms were the market mechanisms. Also in both surveys, individuals from the rural zone were aware of and used the mechanisms. In the first survey, men were more aware of the mechanisms and used them more frequently, but it was women in the second survey who presented higher rates of awareness and use; these differences, however, were not statistically significant. The results herein indicate that effective social participation in the General Social Security System in Health is far from being achieved. The policy has failed to materialize, as evidenced by the lack of balance in the participation of one of the main actors of the General Social Security System in Health: the users.

Arabidopsis ATM and ATR kinases prevent propagation of genome damage caused by telomere dysfunction.

The ends of linear eukaryotic chromosomes are hidden in nucleoprotein structures called telomeres, and loss of the telomere structure causes inappropriate repair, leading to severe karyotypic and genomic instability. Although it has been shown that DNA damaging agents activate a DNA damage response (DDR), little is known about the signaling of dysfunctional plant telomeres. We show that absence of telomerase in Arabidopsis thaliana elicits an ATAXIA-TELANGIECTASIA MUTATED (ATM) and ATM AND RAD3-RELATED (ATR)-dependent DDR at telomeres, principally through ATM. By contrast, telomere dysfunction induces an ATR-dependent response in telomeric Conserved telomere maintenance component1 (Ctc1)-Suppressor of cdc thirteen (Stn1)-Telomeric pathways in association with Stn1 (CST)-complex mutants. These results uncover a new role for the CST complex in repressing the ATR-dependent DDR pathway in plant cells and show that plant cells use two different DNA damage surveillance pathways to signal telomere dysfunction. The absence of either ATM or ATR in ctc1 and stn1 mutants significantly enhances developmental and genome instability while reducing stem cell death. These data thus give a clear illustration of the action of ATM/ATR-dependent programmed cell death in maintaining genomic integrity through elimination of genetically unstable cells.

Kinetic analysis of DNA double-strand break repair pathways in Arabidopsis.

Double-strand breaks in genomic DNA (DSB) are potentially lethal lesions which separate parts of chromosome arms from their centromeres. Repair of DSB by recombination can generate mutations and further chromosomal rearrangements, making the regulation of recombination and the choice of recombination pathways of the highest importance. Although knowledge of recombination mechanisms has considerably advanced, the complex interrelationships and regulation of pathways are far from being fully understood. We analyse the different pathways of DSB repair acting in G2/M phase nuclei of irradiated plants, through quantitation of the kinetics of appearance and loss of γ-H2AX foci in Arabidopsis mutants. These analyses show the roles for the four major recombination pathways in post-S-phase DSB repair and that non-homologous recombination pathways constitute the major response. The data suggest a hierarchical organisation of DSB repair in these cells: C-NHEJ acts prior to B-NHEJ which can also inhibit MMEJ. Surprisingly the quadruple ku80 xrcc1 xrcc2 xpf mutant can repair DSB, although with severely altered kinetics. This repair leads to massive genetic instability with more than 50% of mitoses showing anaphase bridges following irradiation. This study thus clarifies the relationships between the different pathways of DSB repair in the living plant and points to the existence of novel DSB repair processes.

Recombination proteins and telomere stability in plants.

Repair of DNA damage is essential for the maintenance of the integrity and transmission of the genome in development and reproduction. Telomeres are nucleoprotein structures which protect the ends of (linear) eukaryotic chromosomes. Telomere dysfunction results in loss of this protection and the telomeres being recognised as DNA damage by the cellular DNA Damage Repair and Response (DDR) machinery, leading to senescence or cell death. Telomeric homeostasis is thus tightly controlled and many specific and non-specific proteins are involved in its regulation. Among these, DNA damage and Repair proteins contribute both to the recognition of telomere dysfunction and more surprisingly, are directly implicated in telomere homeostasis itself. Plants offer a great opportunity to study these mechanisms due to the fact that many key DNA repair and recombination proteins are non-essential in plants, in contrast to vertebrates. In the following text, after a brief summary of the current state of knowledge on telomere-specific proteins in plants, we review the DDR processes and the related proteins implicated in plant telomere stability. We focus specifically on telomere signalling and on recombination events induced by unprotected telomeres, at the origin of genome rearrangements and instability when telomere function is affected.

Distinct roles of the ATR kinase and the Mre11-Rad50-Nbs1 complex in the maintenance of chromosomal stability in Arabidopsis.

Signaling of chromosomal DNA breaks is of primary importance for initiation of repair and, thus, for global genomic stability. Although the Mre11-Rad50-Nbs1 (MRN) complex is the first sensor of double-strand breaks, its role in double-strand break (DSB) signaling is not fully understood. We report the absence of γ-ray-induced, ATM/ATR-dependent histone H2AX phosphorylation in Arabidopsis thaliana rad50 and mre11 mutants, confirming that the MRN complex is required for H2AX phosphorylation by the ATM and ATR kinases in response to irradiation-induced DSB in Arabidopsis. rad50 and mre11 mutants spontaneously activate a DNA damage response, as shown by the presence of γ-H2AX foci and activation of cell cycle arrest in nonirradiated plants. This response is ATR dependent as shown both by the absence of these spontaneous foci and by the wild-type mitotic indices of double rad50 atr and mre11 atr plants. EdU S-phase labeling and fluorescence in situ hybridization analysis using specific subtelomeric probes point to a replicative S-phase origin of this chromosome damage in the double mutants and not to telomere destabilization. Thus, the data presented here show the exclusive involvement of ATR in DNA damage signaling in MRN mutants and provide evidence for a role for ATR in the avoidance of S-phase DNA damage.

ERCC1/XPF protects short telomeres from homologous recombination in Arabidopsis thaliana.

Many repair and recombination proteins play essential roles in telomere function and chromosome stability, notwithstanding the role of telomeres in "hiding" chromosome ends from DNA repair and recombination. Among these are XPF and ERCC1, which form a structure-specific endonuclease known for its essential role in nucleotide excision repair and is the subject of considerable interest in studies of recombination. In contrast to observations in mammalian cells, we observe no enhancement of chromosomal instability in Arabidopsis plants mutated for either XPF (AtRAD1) or ERCC1 (AtERCC1) orthologs, which develop normally and show wild-type telomere length. However, in the absence of telomerase, mutation of either of these two genes induces a significantly earlier onset of chromosomal instability. This early appearance of telomere instability is not due to a general acceleration of telomeric repeat loss, but is associated with the presence of dicentric chromosome bridges and cytologically visible extrachromosomal DNA fragments in mitotic anaphase. Such extrachromosomal fragments are not observed in later-generation single-telomerase mutant plants presenting similar frequencies of anaphase bridges. Extensive FISH analyses show that these DNAs are broken chromosomes and correspond to two specific chromosome arms. Analysis of the Arabidopsis genome sequence identified two extensive blocks of degenerate telomeric repeats, which lie at the bases of these two arms. Our data thus indicate a protective role of ERCC1/XPF against 3' G-strand overhang invasion of interstitial telomeric repeats. The fact that the Atercc1 (and Atrad1) mutants dramatically potentiate levels of chromosome instability in Attert mutants, and the absence of such events in the presence of telomerase, have important implications for models of the roles of recombination at telomeres and is a striking illustration of the impact of genome structure on the outcomes of equivalent recombination processes in different organisms.

[Users' and community leaders' perceptions of their capacity to influence the quality of health care: case studies of Colombia and Brazil]. / Percepciones de usuarios y líderes comunitarios sobre su capacidad para influenciar en la calidad de los servicios de salud: un estudio de casos de Colombia y Brasil.

Health system reforms in Colombia and Brazil introduced policies that promote social participation in health care quality control. The objective of this paper was to analyze users' and leaders' perceptions of their capacity to achieve changes in the countries' health services. An exploratory and descriptive qualitative study was performed with individual interviews and focus groups of users and leaders in Colombia and Brazil. Most informants perceived themselves as having the capacity to induce changes to improve the quality of health services. They attributed this capacity primarily to internal factors related to their participatory behavior, plus only one external factor, the availability of institutional participatory spaces. The lack of capacity to influence change was only related to passive attitudes and fear of retaliation in Colombia. The existence of a population with high self-perceived capacity to achieve change appears as a potential factor to be strengthened, while institutional democratic space needs to improve in order to enhance the effectiveness of social participation in health policies.

Percepciones de usuarios y líderes comunitarios sobre su capacidad para influenciar en la calidad de los servicios de salud: un estudio de casos de Colombia y Brasil / Users' and community leaders' perceptions of their capacity to influence the quality of health care: case studies of Colombia and Brazil

Los sistemas de salud en Colombia y Brasil incluyen políticas que promueven la participación de la población en el control de la calidad de los servicios de salud. El objetivo del artículo es analizar la percepción de usuarios y líderes de ambos países sobre su capacidad para lograr cambios en los servicios de salud. Se realizó un estudio cualitativo, exploratorio y descriptivo mediante grupos focales y entrevistas individuales a usuarios y líderes en Colombia y Brasil. La gran mayoría de usuarios y líderes se perciben con capacidad de inducir cambios que mejoren la calidad de los servicios de salud. Capacidad que atribuyen fundamentalmente a factores internos, relacionados con su comportamiento participativo y únicamente a un factor externo, la existencia de espacios de participación en las instituciones. La ausencia de capacidad se relacionaba con actitudes conformistas y temor a las represalias - sólo en Colombia. La existencia de una población con alta capacidad de logro percibida se revela como potencial a fortalecer, al tiempo que se mejora la apertura democrática de las instituciones, para aumentar la efectividad de las políticas de participación en salud.

Health system reforms in Colombia and Brazil introduced policies that promote social participation in health care quality control. The objective of this paper was to analyze users' and leaders' perceptions of their capacity to achieve changes in the countries' health services. An exploratory and descriptive qualitative study was performed with individual interviews and focus groups of users and leaders in Colombia and Brazil. Most informants perceived themselves as having the capacity to induce changes to improve the quality of health services. They attributed this capacity primarily to internal factors related to their participatory behavior, plus only one external factor, the availability of institutional participatory spaces. The lack of capacity to influence change was only related to passive attitudes and fear of retaliation in Colombia. The existence of a population with high self-perceived capacity to achieve change appears as a potential factor to be strengthened, while institutional democratic space needs to improve in order to enhance the effectiveness of social participation in health policies.

Actitudes y opiniones de actores implicados en la política participativa del control de la calidad de los servicios de salud en Colombia / Attitudes and opinions of actors involved in the participatory policy of quality control of health services in Colombia

La participación es uno de los ejes de la reforma al sector salud y su implantación depende de muchos factores como las actitudes de quienes están involucrados. El objetivo de este trabajo es analizar las actitudes y opiniones sobre la participación en salud de usuarios, personal de salud y formuladores de políticas en Colombia. Se realizó una investigación exploratoria y descriptiva, combinando métodos cualitativos a través de 25 grupos focales, con 210 usuarios y 40 líderes, y 36 entrevistas individuales semi-estructuradas a personal de salud, con una encuesta a 1.497 usuarios. Se encontró que casi todos los actores tienen una actitud positiva frente a la participación, la cual era más favorable entre usuarios mujeres, personas con estudios básicos, de niveles socioeconómicos bajos, jubilados y desempleados. Se observaron en el personal de salud actitudes ambivalentes determinadas por factores culturales, de favorabilidad hacia la participación, pero desfavorables hacia elementos situacionales que la determinan. Esto indicaría que se requiere por parte de los actores, en especial de los profesionales, un cambio en la manera de percibir y comprender la realidad social, para promover una participación efectiva en el control social del sistema de salud.

Participation is the core of reform to the health sector; its implementation depends on many factors as the attitudes of individuals involved. The author’s objective was to analyze attitudes and opinions on participation of Colombian users, health care personnel and policy makers. An exploratory and descriptive research was carried out, in 25 focal groups of 210 users, 40 leaders, and 36 individual semi-structured interviews to health care personnel, combiningqualitative and quantitative methods with a survey to 1497 users. It was found that most of the actors have a positive attitude towards participation, which was more favorable among women, people with basic studies and low socioeconomic level, retirees and the unemployed. It was also found that health care personnel had ambivalent attitudes favorable opinions towards participation, but unfavorable ones about the situational elements that determine it. These findings indicate that a change in the manner of perceiving and understanding social reality is required from actors especially from professionals to promote effective participation in the health care system social control.

Two roles for Rad50 in telomere maintenance.

We describe two roles for the Rad50 protein in telomere maintenance and the protection of chromosome ends. Using fluorescence in situ hybridisation (FISH) and fibre-FISH analyses, we show that absence of AtRad50 protein leads to rapid shortening of a subpopulation of chromosome ends and subsequently chromosome-end fusions lacking telomeric repeats. In the absence of telomerase, mutation of atrad50 has a synergistic effect on the number of chromosome end fusions. Surprisingly, this 'deprotection' of the shortened telomeres does not result in increased exonucleolytic degradation, but in a higher proportion of anaphase bridges containing telomeric repeats in atrad50/tert plants, compared to tert mutant plants. Absence of AtRad50 thus facilitates the action of recombination on these shortened telomeres. We propose that this protective role of Rad50 protein on shortened telomeres results from its action in constraining recombination to sister chromatids and thus avoiding end-to-end interactions.

Participación social en salud: conceptos de usuarios, líderes comunitarios, gestores y formuladores de políticas en Colombia. Una mirada cualitativa / Social participation in health: user community leaders, managers and policy makes in Colombia. A qualitative view

Fundamento: Las reformas del sector salud llevadas a cabo enColombia durante la década de los noventa incluyen políticas quepromocionan la participación social en el sistema de salud, consideradaesencial para el buen funcionamiento. El objetivo de este artículoes analizar el sentido y significado de la participación en saludpara los diferentes actores sociales involucrados en la implantaciónde la política en Colombia.Métodos: Se realizó un estudio cualitativo, descriptivo, de tipoexploratorio, a través de grupos focales (GF) y entrevistas individualessemi-estructuradas (E) a diferentes actores sociales: 210 usuarios(GF), 40 líderes comunitarios (GF), 3 formuladores de políticas (E)y 36 entre el personal de salud (E). Se hizo un análisis narrativo decontenido. El área de estudio la constituyeron los municipios Tuluá yPalmira en Colombia.Resultados: El concepto de participación presentó diferentessentidos según el actor analizado: usuarios y líderes articulaban elconcepto alrededor de aportar ideas, estar en espacios sociales, la solidaridady con frecuencia, la utilización de los servicios de salud. Elpersonal de salud otorgaba sentido de participación social a las actividadesde las instituciones con la comunidad, así como al uso de losservicios y la vinculación al sistema de salud. Los formuladores depolíticas lo dotaban de un sentido de evaluación y control de los serviciosde salud por parte de la comunidad, para mejorar su calidad.Conclusiones: Los distintos conceptos de participación muestrandiferencias entre el sentido de la política y lo que entienden y asumenlos diversos agentes sociales en su interacción con los servicios desalud. Estos diferentes conceptos han de ser tenidos en cuenta paraconseguir la vinculación entre la sociedad y los servicios de salud

Background: Health sector reforms taking place in Colombiaduring the Nineties included policies to promote social participationin the health system, which is considered essential to its functioning.The aim of this article is to analyse the meaning and the significanceof participation in health for the different social actorsinvolved in implementing policies in Colombia.Methods: A qualitative, descriptive, exploratory study wascarried out using focal groups (FG) and semi-structured individualinterviews (I) of the different social actors: 210 users (FG), 40 communityleaders (FG), 3 policy makers (E) and 36 healthcare professionals(E). A carried out analysis was content up of the contents.The study area corresponded to the municipalities of Tulua and Palmirain Colombia.Results: The concept of participation was interpreted differentlydepending on the actor studied: for users and leaders the conceptreferred to contributing ideas, presence in social spaces, solidarityand frequently, and use of the health services. Healthcare professionalsconsidered the activities carried out by institutions togetherwith the community as social participation, the use of services andaffiliation to the health system. Policy markers considered participationto concern evaluation and control of the health services by thecommunity, to improve its quality.Conclusions: The different concepts of participation reveal differencesbetween the content of the policy and how it is understoodand interpreted by the different social actors in their interaction withthe health services. These different perspectives must be taken intoaccount to develop a link between society and the health services

[Social participation in health: user community leaders, managers and policy makers in Colombia. A qualitative view]. / Participación social en salud: conceptos de usuarios, líderes comunitarios, gestores y formuladores de políticas en Colombia. Una mirada cualitativa.

BACKGROUND: Health sector reforms taking place in Colombia during the Nineties included policies to promote social participation in the health system, which is considered essential to its functioning. The aim of this article is to analyse the meaning and the significance of participation in health for the different social actors involved in implementing policies in Colombia. METHODS: A qualitative, descriptive, exploratory study was carried out using focal groups (FG) and semi-structured individual interviews (I) of the different social actors: 210 users (FG), 40 community leaders (FG), 3 policy makers (E) and 36 healthcare professionals (E). A carried out analysis was content up of the contents. The study area corresponded to the municipalities of Tulua and Palmira in Colombia. RESULTS: The concept of participation was interpreted differently depending on the actor studied: for users and leaders the concept referred to contributing ideas, presence in social spaces, solidarity and frequently, and use of the health services. Healthcare professionals considered the activities carried out by institutions together with the community as social participation, the use of services and affiliation to the health system. Policy markers considered participation to concern evaluation and control of the health services by the community, to improve its quality. CONCLUSIONS: The different concepts of participation reveal dif ferences between the content of the policy and how it is understood and interpreted by the different social actors in their interaction with the health services. These different perspectives must be taken into account to develop a link between society and the health services.

Telomerase dependence of telomere lengthening in Ku80 mutant Arabidopsis.

We have identified a ku80 mutant of Arabidopsis and show that telomerase is needed to generate the longer telomeres observed in this mutant. Telomeres are specialized nucleoprotein structures at the ends of chromosomes that permit cells to distinguish chromosome ends from double-strand breaks, thus preventing chromosome fusion events. Ku80 deficiency results in the lengthening of telomeres, a phenotype also seen in an Arabidopsis ku70 mutant. Furthermore, homogeneous populations of ku80 mutant cells show a steady increase in the length of telomere tracts, which reach an equilibrium length and then stabilize. In contrast to that in mammals, Ku80 deficiency in Arabidopsis cells does not cause end-to-end fusion of chromosomes. This telomere lengthening is dependent on the presence of telomerase, although it is not attributable to a significant increase in telomerase activity per se. These results demonstrate the essential role of the Ku80 protein as a negative regulator of telomerase function in plant cells.