Rukous on perintöä suvusta sukuun : Ikääntyneet ja uskonto vuosituhannen vaihteen Suomessa

"Prayer, a heritage from generation to generation" The elderly and religion in Finland at the turn of the 21st century The strong demographic changes in Europe mean that research on the elderly is highly needed, and also from the viewpoint of their resources and opportunities. Further, it is important to determine, how the elderly could find a meaningful place as members of the chain of generations in our rapidly changing society. The aim of this study was to find out how the elderly build and perceive their place in the society through religious texts. The study was based on religious texts written by elderly people in the study groups of the Finnish pensioners organization Pension Union (Eläkeliitto). These 943 short prayers, poems, and aphorisms were collected during the Tree of Life (Elämänpuu) project in 1998-1999 and were then analysed applying qualitative content analysis and grounded theory methodology. The social construction of aging and the view of communication as a collective signifying process were used as the mainstays of the research perspective. The themes brought forward by the elderly writers were grouped around three key themes: the self, the world and religion. In this examination religion with its forms of expression appeared to be deeply rooted to each of these themes and thus seems a vital part of the elderly writers' culture. In connection with the theme of the self, the religious forms of expression provided a means of building a coherent and culturally accepted self-image which is further supported by positive views of personal history and current life situation. In relation to the world theme, the elderly writers stressed the importance of close social relationships and at the same time expressed anxiety with regard to the changing world. Concerning the theme of religion, the religious forms of expression were first and foremost used in building and creating a sense of personal safety and a belief in the future. The study suggests that skill in the use of religious language enable the elderly to cope with equivocal life events and cognitive dissonance. At the social level the religious forms of expression seemed to connect the writers to the Finnish linguistic culture and identity, as well as to the collective memory, where religion plays a central part. By using religious language the elderly both exploit and maintain these considerable social resources. The key result of the study is that the elderly were found to have a significant and separate role in the continuity and well-being of society. Bound to the religious tradition, the elderly seem to carry significant information as regards the identity of the Finnish people, information which is essentially passed on to future generations. By sustaining traditions and thus the collective identity, they perform a uniquely productive task and their life experience could be seen as a particular type of capital in the society. This result also raises a grave question: Will the elderly of the future be able to undertake this task that so profoundly requires religious literacy?

GPRA and the asthma locus on chromosome 7p14-p15

The basis of this work was the identification of a genomic region on chromosome 7p14-p15 that strongly associated with asthma and high serum total immunoglobulin E in a Finnish founder population from Kainuu. Using a hierarchical genotyping approach the linkage region was narrowed down until an evolutionary collectively inherited 133-kb haplotype block was discovered. The results were confirmed in two independent data sets: Asthma families from Quebec and allergy families from North-Karelia. In all the three cohorts studied, single nucleotide polymorphisms tagging seven common gene variants (haplotypes) were identified. Over half of the asthma patients carried three evolutionary closely related susceptibility haplotypes as opposed to approximately one third of the healthy controls. The risk effects of the gene variants varied from 1.4 to 2.5. In the disease-associated region, there was one protein-coding gene named GPRA (G Protein-coupled Receptor for Asthma susceptibility also known as NPSR1) which displayed extensive alternative splicing. Only the two isoforms with distinct intracellular tail sequences, GPRA-A and -B, encoded a full-length G protein-coupled receptor with seven transmembrane regions. Using various techniques, we showed that GPRA is expressed in multiple mucosal surfaces including epithelial cells throughout the respiratory tract. GPRA-A has additional expression in respiratory smooth muscle cells. However, in bronchial biopsies with unknown haplotypes, GPRA-B was upregulated in airways of all patient samples in contrast to the lack of expression in controls. Further support for GPRA as a common mediator of inflammation was obtained from a mouse model of ovalbumin-induced inflammation, where metacholine-induced airway hyperresponsiveness correlated with elevated GPRA mRNA levels in the lung and increased GPRA immunostaining in pulmonary macrophages. A novel GPRA agonist, Neuropeptide S (NPS), stimulated phagocytosis of Esterichia coli bacteria in a mouse macrophage cell line indicating a role for GPRA in the removal of inhaled allergens. The suggested GPRA functions prompted us to study, whether GPRA haplotypes associate with respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in infants sharing clinical symptoms with asthma. According to the results, near-term RDS and asthma may also share the same susceptibility and protective GPRA haplotypes. As in asthma, GPRA-B isoform expression was induced in bronchial smooth muscle cells in RDS and BPD suggesting a role for GPRA in bronchial hyperresponsiveness. In conclusion, the results of the present study suggest that the dysregulation of the GPRA/NPS pathway may not only be limited to the individuals carrying the risk variants of the gene but is also involved in the regulation of immune functions of asthma.

Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects

Segmentation defects of the vertebrae (SDV) are caused by aberrant somite formation during embryogenesis and result in irregular formation of the vertebrae and ribs. The Notch signal transduction pathway plays a critical role in somite formation and patterning in model vertebrates. In humans, mutations in several genes involved in the Notch pathway are associated with SDV, with both autosomal recessive (MESP2, DLL3, LFNG, HES7) and autosomal dominant (TBX6) inheritance. However, many individuals with SDV do not carry mutations in these genes. Using whole-exome capture and massive parallel sequencing, we identified compound heterozygous mutations in RIPPLY2 in two brothers with multiple regional SDV, with appropriate familial segregation. One novel mutation (c.A238T:p.Arg80*) introduces a premature stop codon. In transiently transfected C2C12 mouse myoblasts, the RIPPLY2 mutant protein demonstrated impaired transcriptional repression activity compared with wild-type RIPPLY2 despite similar levels of expression. The other mutation (c.240-4T>G), with minor allele frequency <0.002, lies in the highly conserved splice site consensus sequence 5' to the terminal exon. Ripply2 has a well-established role in somitogenesis and vertebral column formation, interacting at both gene and protein levels with SDV-associated Mesp2 and Tbx6. We conclude that compound heterozygous mutations in RIPPLY2 are associated with SDV, a new gene for this condition. © The Author 2014.

Receptor guanylyl cyclase C (GC-C): regulation and signal transduction

Receptor guanylyl cyclase C (GC-C) is the target for the gastrointestinal hormones, guanylin, and uroguanylin as well as the bacterial heat-stable enterotoxins. The major site of expression of GC-C is in the gastrointestinal tract, although this receptor and its ligands play a role in ion secretion in other tissues as well. GC-C shares the domain organization seen in other members of the family of receptor guanylyl cyclases, though subtle differences highlight some of the unique features of GC-C. Gene knock outs in mice for GC-C or its ligands do not lead to embryonic lethality, but modulate responses of these mice to stable toxin peptides, dietary intake of salts, and development and differentiation of intestinal cells. It is clear that there is much to learn in future about the role of this evolutionarily conserved receptor, and its properties in intestinal and extra-intestinal tissues.

Porlyl oligopeptidase in development

Prolyl oligopeptidase (POP, prolyl endopeptidase, EC 3.4.21.26) is a serine-type peptidase (family S9 of clan SC) hydrolyzing peptides shorter than 30 amino acids. POP has been found in various mammalian and bacterial sources and it is widely distributed throughout different organisms. In human and rat, POP enzyme activity has been detected in most tissues, with the highest activity found mostly in the brain. POP has gained scientific interest as being involved in the hydrolyzis of many bioactive peptides connected with learning and memory functions, and also with neurodegenerative disorders. In drug or lesion induced amnesia models and in aged rodents, POP inhibitors have been able to revert memory loss. POP may have a fuction in IP3 signaling and it may be a possible target of mood stabilizing substances. POP may also have a role in protein trafficking, sorting and secretion. The role of POP during ontogeny has not yet been resolved. POP enzyme activity and expression have shown fluctuation during development. Specially high enzyme activities have been measured in the brain during early development. Reduced neuronal proliferation and differentation in presence of POP inhibitor have been reported. Nuclear POP has been observed in proliferating peripheral tissues and in cell cultures at the early stage of development. Also, POP coding mRNA is abundantly expressed during brain ontogeny and the highest levels of expression are associated with proliferative germinal matrices. This observation indicates a special role for POP in the regulation of neurogenesis during development. For the experimental part, the study was undertaken to investigate the expression and distribution of POP protein and enzymatic activity of POP in developing rat brain (from embryonic day 14 to post natal day 7) using immunohistochemistry, POP enzyme activity measurements and western blot-analysis. The aim was also to find in vivo confirmation of the nuclear colocalization of POP during early brain ontogeny. For immunohistochemistry, cryosections from the brains of the fetuses/rats were made and stained using specific antibody for POP and fluorescent markers for POP and nuclei. The enzyme activity assay was based on the fluorescence of 7- amino-4-methylcoumarin (AMC) generated from the fluorogenic substrate succinyl-glycyl-prolyl-7-amino-4-methylcoumarin (Suc-Gly-Pro-AMC) by POP. The amounts of POP protein and the specifity of POP antibody in rat embryos was confirmed by western blot analysis. We observed that enzymatic activity of POP is highest at embryonic day 18 while the protein amounts reach their peak at birth. POP was widely present throughout the developmental stages from embryonic day 14 to parturition day, although the POP-immunoreactivity varied abundantly. At embryonic days 14 and 18 notably amounts of POP was distributed at proliferative germinal zones. Furthermore, POP was located in the nucleus early in the development but is transferred to cytosol before birth. At P0 and P7 the POP-immunoreactivity was also widely observed, but the amount of POP was notably reduced at P7. POP was present in cytosol and in intercellular space, but no nuclear POP was observed. These findings support the idea of POP being involved in specific brain functions, such as neuronal proliferation and differentation. Our results in vivo confirm the previous cell culture results supporting the role of POP in neurogenesis. Moreover, an inconsistency of POP protein amounts and enzymatic activity late in the development suggests a strong regulation of POP activity and a possible non-hydrolytic role at that stage.

Distinct and Contrasting Transcription Initiation Patterns at Mycobacterium tuberculosis Promoters

Although sequencing of Mycobacterium tuberculosis genome lead to better understanding of transcription units and gene functions, interactions occurring during transcription initiation between RNA polymerase and promoters is yet to be elucidated. Different stages of transcription initiation include promoter specific binding of RNAP, isomerization, abortive initiation and promoter clearance. We have now analyzed these events with four promoters of M. tuberculosis viz. P-gyrB1, P-gyrR, P-rrnPCL1 and P-metU. The promoters differed from each other in their rates of open complex formation, decay, promoter clearance and abortive transcription. The equilibrium binding and kinetic studies of various steps revealed distinct rate limiting events for each of the promoter, which also differed markedly in their characteristics from the respective promoters of Mycobacterium smegmatis. Surprisingly, the transcription at gyr promoter was enhanced in the presence of initiating nucleotides and decreased in the presence of alarmone, pppGpp, a pattern typically seen with rRNA promoters studied so far. The gyr promoter of M. smegmatis, on the other hand, was not subjected to pppGpp mediated regulation. The marked differences in the transcription initiation pathway seen with rrn and gyr promoters of M. smegmatis and M. tuberculosis suggest that such species specific differences in the regulation of expression of the crucial housekeeping genes could be one of the key determinants contributing to the differences in growth rate and lifestyle of the two organisms. Moreover, the distinct rate limiting steps during transcription initiation of each one of the promoters studied point at variations in their intracellular regulation.

A multi-level multi-scale approach to study essential genes in Mycobacterium tuberculosis

Background: The set of indispensable genes that are required by an organism to grow and sustain life are termed as essential genes. There is a strong interest in identification of the set of essential genes, particularly in pathogens, not only for a better understanding of the pathogen biology, but also for identifying drug targets and the minimal gene set for the organism. Essentiality is inherently a systems property and requires consideration of the system as a whole for their identification. The available experimental approaches capture some aspects but each method comes with its own limitations. Moreover, they do not explain the basis for essentiality in most cases. A powerful prediction method to recognize this gene pool including rationalization of the known essential genes in a given organism would be very useful. Here we describe a multi-level multi-scale approach to identify the essential gene pool in a deadly pathogen, Mycobacterium tuberculosis. Results: The multi-level workflow analyses the bacterial cell by studying (a) genome-wide gene expression profiles to identify the set of genes which show consistent and significant levels of expression in multiple samples of the same condition, (b) indispensability for growth by using gene expression integrated flux balance analysis of a genome-scale metabolic model, (c) importance for maintaining the integrity and flow in a protein-protein interaction network and (d) evolutionary conservation in a set of genomes of the same ecological niche. In the gene pool identified, the functional basis for essentiality has been addressed by studying residue level conservation and the sub-structure at the ligand binding pockets, from which essential amino acid residues in that pocket have also been identified. 283 genes were identified as essential genes with high-confidence. An agreement of about 73.5% is observed with that obtained from the experimental transposon mutagenesis technique. A large proportion of the identified genes belong to the class of intermediary metabolism and respiration. Conclusions: The multi-scale, multi-level approach described can be generally applied to other pathogens as well. The essential gene pool identified form a basis for designing experiments to probe their finer functional roles and also serve as a ready shortlist for identifying drug targets.

Sonic hedgehog-responsive lipoxygenases and cyclooxygenase-2 modulate Dectin-1-induced inflammatory cytokines

Immune responses during fungal infections are predominately mediated by 5/15-lipoxygenases (LO)-or cyclooxygenase (COX)-2-catalysed bioactive eicosanoid metabolites like leukotrienes, lipoxins and prostaglandins. Although few host mediators of fungi-triggered eicosanoid production have been established, the molecular mechanism of expression and regulation of 5-LO, 15-LO and COX-2 are not well-defined. Here, we demonstrate that, macrophages infected with representative fungi Candida albicans, Aspergillus flavus or Aspergillus fumigatus or those treated with Curdlan, a selective agonist of pattern recognition receptor for fungi Dectin-1, displays increased expression of 5-LO, 15-LO and COX-2. Interestingly, Dectin-1-responsive Syk pathway activates mTOR-sonic hedgehog (SHH) signaling cascade to stimulate the expression of these lipid metabolizing enzymes. Loss-of-function analysis of the identified intermediaries indicates that while Syk-mTOR-SHH pathway-induced 5-LO and 15-LO suppressed the Dectin-l-responsive pro-inflammatory signature cytokines like TNE-alpha, IL-1 beta and IL-12, Syk-mTOR-SHH-induced COX-2 positively regulated these cytokines. Dectin-1-stimulated IL-6, however, is dependent on 5-LO, 15-LO and COX-2 activity. Together, the current study establishes Dectin-1-arbitrated host mediators that direct the differential regulation of immune responses during fungal infections and thus are potential candidates of therapeutic intervention. (C) 2015 Elsevier Ltd. All rights reserved.

La libertad de expresión en el sistema interamericano de protección de los derechos humanos y su incidencia en el derecho interno de los estados parte

Como dice el título de la presente disertación, abordaré la situación de la libertad de expresión en el sistema interamericano de protección de los derechos humanos y su incidencia en el derecho interno de los Estados parte. Voy a dividir esta presentación en tres partes: 1) Una breve descripción del sistema interamericano dentro del marco del Derecho Internacional de los Derechos Humanos, como núcleo del nuevo paradigma del Estado Constitucional de Derecho; 2) Una descripción de la situación de la libertad de expresión en el mencionado marco; 3) Por último, terminaré con algunas reflexiones personales. Como se puede apreciar, la primera y segunda parte son más descriptivas del cuadro de situación y la última más reflexiva de la misma desde el punto de vista filosófico.

Habla ahora o calla (forzosamente) para siempre : las convenciones en contra de toda forma de discriminación e intolerancia y su amenaza a la libertad de expresión en los Estados Americanos

En junio de 2013, la Organización de Estados Americanos (en adelante, la “OEA”) adoptó las Convenciones Interamericanas en Contra del Racismo, la Discriminación Racial y Todas las Formas Relacionadas de Intolerancia (en adelante, “CCDI”). Entre otras cosas, estos nuevos instrumentos –que al tiempo de escribir estas líneas no han sido ratificados por ningún Estado de la región– tendrán el efecto de ampliar enormemente la extensión de las llamadas categorías prohibidas de discriminación más allá de lo que hoy existe en los tratados vigentes que tocan la materia, además de crear un amplio rango de nuevas obligaciones y deberes para los Estados partes en el sentido de promover la igualdad y eliminar la discriminación y la intolerancia. Aún cuando existen múltiples aspectos de esta convención que son susceptibles de ser criticados desde una perspectiva jurídica y de política pública, este ensayo lidia exclusivamente con la cuestión de la novel definición legal de la “intolerancia” como un acto o expresión prohibida, y con los deberes que asumirán los Estados en relación con la misma...

A política polissêmica: fazeres, dizeres e silêncio nos programas Fale com o Deputado e Fale com a Ouvidoria da Câmara dos Deputados

Estudo sobre os programas Fale com o Deputado e Fale com a Ouvidoria da Câmara dos Deputados, a fim de se captarem representações, crenças e valores sobre a política. O trabalho assume a perspectiva de uma antropologia da política, desnaturalizando conceitos como democracia, participação e representação política, para captar as concepções dos sujeitos envolvidos no diálogo proposto pela Câmara dos Deputados, por intermédio desses canais de correio eletrônico. Assim, a tese não estuda os programas Fale com o Deputado e Fale com a Ouvidoria, mas nos programas. As mensagens enviadas, juntamente com os documentos produzidos pela Casa Legislativa acerca dos programas, bem como notícias e entrevistas com parlamentares e assessores sobre eles, são suportes de expressão de significados associados ao mundo da política, muitas vezes, concebidos como excludentes. Assim, eles são veículos de expressão, mas também de ação, que expõem combinações, normalmente contrapostas, por uma espécie de ficção construída em torno da noção de modernidade: indivíduo e pessoa, diretos e favores, particular e universal. Os documentos abordados revelam conciliações e embates discursivos que acenam para distintas maneiras de os atores fazerem a política, as quais acabam por revelar entendimentos sobre como se dá a gestão interna à Casa desses programas e questionamentos a respeito dos limites e possibilidades da Internet no fazer político.

El tipo cómico del δύσκολος en la Declamación XXVII de Libanio

[ES] La declamación XXVII de Libanio muestra el enfrentamiento entre un padre y su joven hijo, con la particularidad de que aquél es un viejo malhumorado, un δύσκολος, que presenta los rasgos que generalmente caracterizan a este tipo en la comedia. Es un individuo de mal genio, que odia el contacto con cualquier ser humano, el cariño y, sobre todo, la risa. Como el δύσκολος cómico demuestra su irritabilidad recurriendo a la violencia física, con el empleo de piedras, palos y todos los componentes de su "arsenal", y a la violencia verbal, que se manifiesta en frecuentes maldiciones e insultos. La relación con el tipo de la comedia queda de relieve también en la forma de expresar la irritabilidad, por medio de frases muy breves y del asíndeton, reflejo de lo que Webster denomina staccato style.

Um certo olhar sobre a velhice : a narrativa memorialista de Pedro Nava

Este trabalho tem como objetivo investigar as transformações do envelhecimento que se dão pelas narrativas produzidas pelas lembranças. Busca destacar a especificidade do papel da memória no processo de envelhecimento e a sua força de transformação e resistência. A pertinência do tema está ligada a marcada expressão que o contingente de pessoas idosas adquiriu nos anos recentes ao ganhar visibilidade cada vez maior, impondo-se como um grupo com demandas e características próprias. No estudo, articulam-se os conceitos de sujeito, de memória e de narratividade. Na primeira parte, desenvolve-se a noção de sujeito, desde um eu central, fundamento de uma unidade de expressão, até a fragmentação desse eu, que se torna múltitiplo e expressão crítica do homem moderno. Na segunda parte, o estudo da memória, acompanhamos a passagem de uma memória definida como permanente e reprodutora para uma descrição de memória como uma habilidade criativa, capaz de retrospectivamente produzir novas narrativas. Na terceira parte, estudamos o conceito de narratividade, explorando diversos aspectos para além do campo literário. Finalmente, com a rede conceitual sujeito - memória - narrativa estabelecida, reconhecemos na obra de Pedro Nava o surgimento de múltiplos narradores, que, frente a velhice, em vez de se defender e negar a vida, aceitam o desafio de um confronto e se afirmam, forjados em suas diferenças.

Deleuze e a literatura: o devir pelas linhas da escrita

Este trabalho tem como desafio falar da Literatura como experimentação de vida, sob a ótica filosofia. A prática de uma abordagem filosófica tendo como horizonte o universo da escrita tende a enriquecer as duas práticas. E sobretudo, a vida, quando não é separada do pensamento. O desafio é mostrar que a vida está presente em todas as manifestações do que é vivo. Sem distinção quanto a sujeito, objeto ou representação. Experimentar é dar as mãos a vida e seus infinitos modos de ser. Não obstante, o trabalho busca mostrar que a arte é essencialmente experimentalista. E que múltiplos caminhos podem levar a ela. Para a enorme tafera temos a companhia de Gilles Deleuze, grande filósofo francês, e seu, não menos importante parceiro, Félix Guattari. Em específico, trata-se de um trabalho que investiga os trajetos da Linguagem como instrumento de expressão em todos os caminhos e conexões possíveis. Deleuze encontrou na Literatura um destino para a criação, uma inspiração para a vida. Ele vislumbrou o escrever como experiência de Devir, como prática essencial, abertura da estrada para o desejo e para a fala coletiva. Para Deleuze, a linguagem é algo vivo, que sofre desvios, que enriquece na medida que se conecta com o seu fora. A linguagem é algo que cresce e se retrai de acordo com os agenciamentos que a envolvem. Falaremos do sopro que emerge das as entrelinhas do texto, o ilimitado da rachadura, a força dos signos. Em suma, falemos da força da escrita e da escritura de novos destinos.

Liberdade de Expressão e os Mecanismos de Promoção do Pluralismo nos Meios de Comunicação Social

O objetivo deste trabalho é demonstrar que intervenção regulatória para promoção do pluralismo nos meios de comunicação social é condizente com a ordem democrática instituída pela Constituição Brasileira de 1988, e tem papel fundamental na garantia do pleno exercício do direito à liberdade de expressão. Demonstraremos que a proposta está em harmonia com as concepções contemporâneas sobre o regime democrático, que emergiram na segunda metade do século XX. Serão explorados os preceitos constitucionais que incidem sobre a discussão, quais sejam, o pluralismo político, a liberdade de expressão e o dever de proporcionalidade, que vincula a atividade dos poderes públicos. Delinearemos os contornos do conceito de regulação, expondo a discussão sobre sua aplicabilidade ao setor de comunicação social, e os tipos de políticas públicas comuns nesse sentido, o que inclui a promoção de pluralismo. Listaremos os mecanismos de promoção de pluralismo interno e externo verificados no direito comparado. À luz dos entendimentos consignados no texto e das discussões em voga sobre a regulação do mercado de comunicação, iremos propor parâmetros de interpretação para futuras políticas públicas de promoção do pluralismo no mercado de comunicação social brasileiro.