The Story of the Inquisition; what it was and what it did.

Mode of access: Internet.

Induction of apoptosis by mercury compounds depends on maturation and is not associated with microglial activation

The earliest sign of neurotoxicity observed after exposure of three-dimensional brain cell cultures to low concentrations of mercury compounds is a microglial reaction. We hypothesized that an induction of apoptosis by mercury compounds could be an activating signal of the microglial reaction. Aggregating brain cell cultures of fetal rat telencephalon were treated for 10 days with either mercury chloride or monomethylmercury chloride at noncytotoxic concentrations during two developmental periods: from day 5 to 15, corresponding to an immature stage, and from day 25 to 35 corresponding to a mature stage. Apoptosis was evaluated by the TUNEL technique. It was found that both mercury compounds caused a significant increase in the number of apoptotic cells, but exclusively in immature cultures exhibiting also spontaneous apoptosis. Double staining by the TUNEL technique combined with either neuronal or astroglial markers revealed that the proportion of cells undergoing apoptosis was highest for astrocytes. Furthermore neither an association nor a colocalization was found between apoptotic cells and microglial cells. In conclusion, it appears that the induction of apoptosis by mercury compounds in immature cells is only an acceleration of a spontaneously occurring process, and that it is not a directly related to the early microglial reaction.

A repository is NOT a digital archive

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Sodium bicarbonate supplementation improved MAOD but is not correlated with 200- and 400-m running performances: a double-blind, crossover, and placebo-controlled study

The aim of the study was to investigate the effects of acute supplementation of sodium bicarbonate (NaHCO3) on maximal accumulated oxygen deficit (MAOD) determined by a single supramaximal effort (MAODALT) in running and the correlation with 200- and 400-m running performances. Fifteen healthy men (age, 23 ± 4 years; maximal oxygen uptake, 50.6 ± 6.1 mL·kg(-1)·min(-1)) underwent a maximal incremental exercise test and 2 supramaximal efforts at 110% of the intensity associated with maximal oxygen uptake, which was carried out after ingesting either 0.3 g·kg(-1) body weight NaHCO3 or a placebo (dextrose) and completing 200- and 400-m performance tests. The study design was double-blind, crossover, and placebo-controlled. Significant differences were found between the NaHCO3 and placebo conditions for MAODALT (p = 0.01) and the qualitative inference for substantial changes showed a very likely positive effect (98%). The lactic anaerobic contribution in the NaHCO3 ingestion condition was significantly higher (p < 0.01) and showed a very likely positive effect (99% chance), similar to that verified for peak blood lactate concentration (p < 0.01). No difference was found for time until exhaustion (p = 0.19) or alactic anaerobic contribution (p = 0.81). No significant correlations were observed between MAODALT and 200- and 400-m running performance tests. Therefore, we can conclude that both MAODALT and the anaerobic lactic metabolism are modified after acute NaHCO3 ingestion, but it is not correlated with running performance.

Recruitment of SMRT/N-CoR-mSin3A-HDAC-repressing complexes is not a general mechanism for BTB/POZ transcriptional repressors: The case of HIC-1 and γFBP-B

Hypermethylated in cancer (HIC-1), a new candidate tumor suppressor gene located in 17p13.3, encodes a protein with five C2H2 zinc fingers and an N-terminal broad complex, tramtrack, and bric à brac/poxviruses and zinc-finger (BTB/POZ) domain found in actin binding proteins or transcriptional regulators involved in chromatin modeling. In the human B cell lymphoma (BCL-6) and promyelocityc leukemia (PLZF) oncoproteins, this domain mediates transcriptional repression through its ability to recruit a silencing mediator of retinoid and thyroid hormone receptor (SMRT)/nuclear receptor corepressor (N-CoR)-mSin3A-histone deacetylase (HDAC) complex, a mechanism shared with numerous transcription factors. HIC-1 appears unique because it contains a 13-aa insertion acquired late in evolution, because it is not found in its avian homologue, γF1-binding protein isoform B (γFBP-B), a transcriptional repressor of the γF-crystallin gene. This insertion, located in a conserved region involved in the dimerization and scaffolding of the BTB/POZ domain, mainly affects slightly the ability of the HIC-1 and γFBP-B BTB/POZ domains to homo- and heterodimerize in vivo, as shown by mammalian two-hybrid experiments. Both the HIC-1 and γFBP-B BTB/POZ domains behave as autonomous transcriptional repression domains. However, in striking contrast with BCL-6 and PLZF, both HIC-1 and γFBP-B similarly fail to interact with members of the HDAC complexes (SMRT/N-CoR, mSin3A or HDAC-1) in vivo and in vitro. In addition, a general and specific inhibitor of HDACs, trichostatin A, did not alleviate the HIC-1- and γFBP-B-mediated transcriptional repression, as previously shown for BCL-6. Taken together, our studies show that the recruitment onto target promoters of an HDAC complex is not a general property of transcriptional repressors containing a conserved BTB/POZ domain.

Copeptin is not associated with menstrual cycle hormone.

Background: Copeptin (CP), a derivate from the antidiuretic hormone (ADH) precursor pre-pro-vasopressin, stochiometrically mirrors ADH secretion. CP is increasingly evaluated as a diagnostic and prognostic biomarker in different diseases. It is therefore important to recognize possible confounding factors when interpreting CP levels. In healthy regularly menstruating women, there is a small but measurable physiological variability of hormones involved in fluid regulation. ADH plasma levels have been found to be lowest at menstruation, increasing during the follicular phase with a peak at ovulation and a drop in the luteal phase. We investigated the variability of CP during the menstrual cycle (MC) and its correlation to MC hormones. Methods: In total, 15 healthy women with regular MC (from 26 to 33 days) were included in this study. Ovulation was confirmed by progesterone (prog) levels on day 21 of the MC before entering the study and during the study. Blood collection was performed on days 3, 5, 8-16, 18, 21, 24 and 27 of their MC. Serums were assayed for prog, estradiol (E2), LH, and CP. Mixed linear regression analysis for repeated measures was performed to study the changes of CP, prog, E2 and LH during the MC, and to test the correlation of CP with sex hormones during the MC. Results: Mean MC length in all subjects was 28.5±2.2 d. E2, prog, and LH exhibited characteristic changes during the MC (all P&lt; 0.05). All cycles were ovulatory (peak prog 54±15 nmol/l). CP levels did not change significantly throughout the MC, and were not associated with changes in prog, E2 or LH-levels (all P=ns). Conclusion: CP levels remain stable during the MC and are not influenced by changes in sex hormones. This implicates that it is not necessary to consider MC phases when using CP as a biomarker in premenopausal women.

The erythrocyte cytoskeleton protein 4.2 is not demonstrable in several mammalian species

Erythrocyte membrane proteins from 44 representative mammals were studied. Protein 4.2 was not detected in guinea pigs (Cavia porcellus) (N = 14), Southern Brazilian swamp large rats (Myocastor coypus) (N = 2), cutias (Dasyprocta sp) (N = 4), and horses (Equus caballus) (N = 13). These animals also presented high ankyrin concentrations except for the horse which did not exhibit a sharp band, although minor components located between proteins 2 and 3 could account for the ankyrin family. The rodents studied did present band 6, which was not detectable in other common rodents such as white rats (Rattus norvegicus) (N = 9) and mice (Mus musculus) (N = 12). Since the absence of protein 4.2 does not disrupt the cytoskeleton membrane, we suggest that it is not an essential protein. Its absence may be compensated physiologically by the higher ankyrin concentration observed.

Competitive fitness in coronaviruses is not correlated with size or number of double-membrane vesicles under reduced-temperature growth conditions

Positive-stranded viruses synthesize their RNA in membrane-bound organelles, but it is not clear how this benefits the virus or the host. For coronaviruses, these organelles take the form of double-membrane vesicles (DMVs) interconnected by a convoluted membrane network. We used electron microscopy to identify murine coronaviruses with mutations in nsp3 and nsp14 that replicated normally while producing only half the normal amount of DMVs. Viruses with mutations in nsp5 and nsp16 produced small DMVs but also replicated normally. Quantitative RT-PCR confirmed that the most strongly affected of these, the nsp3 mutant, produced more viral RNA than wild-type virus. Competitive growth assays were carried out in both continuous and primary cells to better understand the contribution of DMVs to viral fitness. Surprisingly, several viruses that produced fewer or smaller DMVs showed a higher relative fitness compared to wild-type virus, suggesting that larger and more numerous DMVs do not necessarily confer a competitive advantage in primary or continuous cell culture. For the first time, this directly demonstrates that replication and organelle formation may be, at least in part, studied separately during positive-stranded RNA virus infection.

Competitive fitness in coronaviruses is not correlated with size or number of double-membrane vesicles under reduced-temperature growth conditions.

Positive-stranded viruses synthesize their RNA in membrane-bound organelles, but it is not clear how this benefits the virus or the host. For coronaviruses, these organelles take the form of double-membrane vesicles (DMVs) interconnected by a convoluted membrane network. We used electron microscopy to identify murine coronaviruses with mutations in nsp3 and nsp14 that replicated normally while producing only half the normal amount of DMVs under low-temperature growth conditions. Viruses with mutations in nsp5 and nsp16 produced small DMVs but also replicated normally. Quantitative reverse transcriptase PCR (RT-PCR) confirmed that the most strongly affected of these, the nsp3 mutant, produced more viral RNA than wild-type virus. Competitive growth assays were carried out in both continuous and primary cells to better understand the contribution of DMVs to viral fitness. Surprisingly, several viruses that produced fewer or smaller DMVs showed a higher fitness than wild-type virus at the reduced temperature, suggesting that larger and more numerous DMVs do not necessarily confer a competitive advantage in primary or continuous cell culture. For the first time, this directly demonstrates that replication and organelle formation may be, at least in part, studied separately during infection with positive-stranded RNA virus. IMPORTANCE The viruses that cause severe acute respiratory syndrome (SARS), poliomyelitis, and hepatitis C all replicate in double-membrane vesicles (DMVs). The big question about DMVs is why they exist in the first place. In this study, we looked at thousands of infected cells and identified two coronavirus mutants that made half as many organelles as normal and two others that made typical numbers but smaller organelles. Despite differences in DMV size and number, all four mutants replicated as efficiently as wild-type virus. To better understand the relative importance of replicative organelles, we carried out competitive fitness experiments. None of these viruses was found to be significantly less fit than wild-type, and two were actually fitter in tests in two kinds of cells. This suggests that viruses have evolved to have tremendous plasticity in the ability to form membrane-associated replication complexes and that large and numerous DMVs are not exclusively associated with efficient coronavirus replication.

Structure-function analyses of {\it PAX6\/} and the molecular bases of aniridia

PAX6 is a transcription activator that regulates eye development in animals ranging from Drosophila to human. The C-terminal region of PAX6 is proline/serine/threonine-rich (PST) and functions as a potent transactivation domain when attached to a heterologous DNA-binding domain of the yeast transcription factor, GAL4. The PST region comprises 152 amino acids encoded by four exons. The transactivation function of the PST region has not been defined and characterized in detail by in vitro mutagenesis. I dissected the PST domain in two independent systems, a heterologous system using a GAL4 DNA-binding site and the native system of PAX6. In both systems, the results show consistently that all four constituent exons of the PST domain are responsible for the transactivation function. The four exon fragments act cooperatively to stimulate transcription, although none of them can function individually as an independent transactivation domain. Combinations of two or more exon fragments can reconstitute substantial transactivation activity when fused to the DNA-binding domain of GAL4, but they surprisingly do not produce much activity in the context of native PAX6 even though the mutant PAX6 proteins are stable and their DNA-binding function remains unaffected. I conclude that the PAX6 protein contains an unusually large transactivation domain that is evolutionarily conserved to a high degree, and that its full transactivation activity relies on the cooperative action of the four exon fragments.^ Most PAX6 mutations detected in patients with aniridia result in truncations of the protein. Some of the truncation mutations occur in the PST region of PAX6, resulting in mutant proteins that retain their DNA-binding ability but have no significant transactivation activity. It is not clear whether such mutants are true loss-of-function or dominant-negative mutants. I show that these mutants are dominant-negative if they are coexpressed with wild-type PAX6 in cultured cells and that the dominant-negative effects result from enhanced DNA-binding ability of these mutants due to removal of the PST domain. These mutants are able to repress the wild-type PAX6 activity not only at target genes with paired domain binding sites but also at target genes with homeodomain binding sites.^ Mutations in the human PAX6 gene produce various phenotypes, including aniridia, Peters' anomaly, autosomal dominant keratitis, and familial foveal dysplasia. The various phenotypes may arise from different mutations in the same gene. To test this theory, I performed a functional analysis of two missense mutations in the paired domain: the R26G mutation reported in a case of Peters' anomaly, and the I87R mutation identified in a patient with aniridia. While both the R26 and the I87 positions are conserved in the paired boxes of all known PAX genes, X-ray crystallography has shown that only R26 makes contact with DNA. I found that the R26G mutant failed to bind a subset of paired domain binding sites but, surprisingly, bound other sites and successfully transactivated promoters containing those sites. In contrast, the I87R mutant had lost the ability to bind DNA at all tested sites and failed to transactivate promoters. My data support the haploinsufficiency hypothesis of aniridia, and the hypothesis that R26G is a hypomorphic allele. ^

The analysis of the basketball coach speech during the moments of game and pause in relation to the performance in competition

In the area of the professional competition, the coach is a fundamental part in the management of a team and more concretely in the game planning. During the competition, the management of the times of pause and times out as well as the conduct of the coach during the same ones is an aspect to analyze in the sports performance. It is for this that it becomes necessary to know some of the behaviors that turn out to be more frequent by the coach and that are more related to a positive performance of his players. For it there has been realized a study of 7 cases of expert coaches in those that his verbal behavior has observed during 4 games. It has focused on the content of the information only to verbal level, on his meaning. The information that have been obtained in the study shows a major quantity of information elaborated during the pauses of the games and a major tactical content with regard to the moments of game. On the other hand, a relation exists between a major number of questions and a minor number of psychological instructions when the score is adverse, whereas in case of victory, a direct relation does not exist with any category. The rest of categories of the speech do not meet influenced directly for the result, for what it is not possible to consider a direct and immediate relation between the coach verbal behavior during the pauses and the result of the game, except in punctual moments.

Twelve lectures in illustration and defence of Christian Unitarianism: : delivered in the Meeting-House of the First Presbyterian Congregation, Belfast. /

What it is, and what it is not -- The faith of the Old Testament -- The faith of our Lord Jesus Christ -- The faith of the Apostles. Part I -- The faith of the Apostles. Part II -- The faith of the primitive church -- A rational faith -- A devotional faith -- A benevolent faith -- A holy faith -- A consolatory faith -- A progressive faith.

Ciudad y espacio público, perspectivas complementarias y nuevos desafíos

La ciudad y los procesos que ésta desencadena en su entorno territorial han variado, de acuerdo con el momento histórico y contexto geográfico donde ocurrió, está ocurriendo o sucederá, por lo tanto, lo primero y lo segundo, son tan cambiantes, como lo son los elementos constitutivos de ese espacio ocupado, apropiado y gobernado.Son pocos los asuntos sobre los cuales coinciden las distintas comunidades académicas y disciplinas que se encargan del estudio de los procesos urbanos, como urbanistas, arquitectos, geógrafos, sociólogos, politólogos, ingenieros o planificadores; por ejemplo, con relación a la definición de lo urbano o lo qué podemos entender por ciudad; tal vez hay mayor acuerdo por lo que no es, como se constata con los espacios dedicados, exclusiva o principalmente a las actividades productivas agropecuarias. De la misma manera, sobre lo que se considera como espacio público, ya que algunos le dan un énfasis estructural y físico, como uno de los elementos rígidos que constituyen el espacio ocupado, mientras que otros, además de lo físico, rescatan de él referentes históricos, culturales y simbólicos.En la actualidad viene ganando audiencia la postura que combina lo físico y material de la ciudad y el espacio público, con lo inmaterial y simbólico de los mismos, lo que le confiere un nuevo sentido. De este tipo de convergencias, surge el escenario que contribuye a construir el ciudadano que requiere y demanda la ciudad.De acuerdo con lo anterior, el análisis que aquí se presenta se aborda a partir de tres aspectos relevantes: en primer lugar, se reiteran algunos de los caminos andados, para esbozar algunas de las nuevas perspectivas sobre la ciudad y el espacio público, tal como se sugiere en el título del artículo; en segundo lugar, relacionar aspectos históricos, conceptuales y aplicados sobre la ciudad y de esta con el espacio público, con base en el caso de Bogotá y finalmente plantear algunos de los desafíos que surgen de esta interacción, a partir de algunas reflexiones que buscan vincular esta temática con las ciencias sociales y en particular con la ciencia política.-----The city and the processes triggered by the city in its territorial environment have changed, according to the historical moment and the geographical context in which it happened, is happening, or will happen; therefore, the former and the latter are as changing as the elements of that occupied, appropriated, and governed space.There are very few subjects on which there is an agreement among the different academic communities and disciplines that study urban processes, such as town planners, architects, geographers, sociologists, political scientists, engineers, or planners. For example, regarding the definition of the urban matters or what we may understand as a city, a greater agreement may be found on what it is not, as shown with spaces exclusively or mainly dedicated to the productive agricultural/livestock activities. Likewise, regarding what is deemed as public space, because some people stress the structural and physical aspect as one of the rigid elements that comprise the occupied space, while others rescue, in addition to the physical, the historical, cultural, and symbolic references.The position that considers the physical and material city and public space combined with their immaterial and symbolic aspects has been gaining terrain lately, providing them with a whole new sense. From these convergences arises the scenario that contributes to the building of the citizenship required and demanded by the city.According to the foregoing, the analysis presented here is addressed from three relevant aspects: First, reiterating some of the already treated topics to outline some new perspectives on the city and the public space, as suggested in the title of this article; second, relating historical, conceptual, and applied aspects of the city and such aspects of the city related to the public space, based on the case of Bogotá; and finally, formulating some challenges arising form this interaction, based on certain thoughts that seek to link this topic with the Social Sciences and, in particular, with the Political Sciences.

Utilidad de la relación estratégica comunitaria y el marketing en empresas el sector salud

La necesidad de involucrar el concepto de comunidad y sus estrategias con el sector salud, generan el problema de investigación de determinar ¿Cuál es la utilidad de la relación estratégica comunitaria y el marketing en empresas del sector salud? El sector salud ha apartado las actividades relacionales con sus clientes, el cual es caracterizado por la atracción, desarrollo y mantenimiento de relaciones con los clientes. El objetivo de la investigación es determinar cuál es la utilidad de la relación estratégica comunitaria y el marketing en empresas del sector salud y los objetivos específicos son: describir el uso de comunidad e Identificar la utilidad de aplicar las estrategias comunitarias en el sector. La metodología es la investigación y análisis de caso, estudiando una organización relevante dentro del sector salud, anexando fuentes de información secundarias como que aporten a los resultados. El análisis arroja una brecha entre la teoría y la utilización de comunidad, donde la organización la define como sus clientes y empleados. Posteriormente cabe determinar si son aplicadas las estrategias comunitarias por la compañía, donde se encontró que algunas lo son. Al encontrar el uso de estrategias cabe estudiar si generan utilidad a los resultados demostrando que conservar y mejorar relaciones con los clientes es de beneficio para la compañía, sin dejar de atraer nuevos clientes para ampliar las posibilidades de ser una compañía rentable y perdurable. Finalmente se establece un eje estratégico que genere un impacto positivo a la empresa - comunidad para crear relaciones más efectivas y rentables.

Tipos de lógica utilizadas en la toma de decisiones estratégicas de marketing

Para el administrador el proceso de la toma de decisiones es uno de sus mayores retos y responsabilidades, ya que en su desarrollo se debe definir el camino más acertado en un sin número de alternativas, teniendo en cuenta los obstáculos sociales, políticos y económicos del entorno empresarial. Para llegar a la decisión adecuada no hay que perder de vista los objetivos y metas propuestas, además de tener presente el proceso lógico, detectando, analizando y demostrando el porqué de esa elección. Consecuentemente el análisis que propone esta investigación aportara conocimientos sobre los tipos de lógica utilizados en la toma de decisiones estratégicas al administrador para satisfacer las demandas asociadas con el mercadeo para que de esta manera se pueda generar y ampliar eficientemente las competencia idóneas del administrador en la inserción internacional de un mercado laboral cada vez mayor (Valero, 2011). A lo largo de la investigación se pretende desarrollar un estudio teórico para explicar la relación entre la lógica y la toma de decisiones estratégicas de marketing y como estos conceptos se combinan para llegar a un resultado final. Esto se llevara a cabo por medio de un análisis de planes de marketing, iniciando por conceptos básicos como marketing, lógica, decisiones estratégicas, dirección de marketing seguido de los principios lógicos y contradicciones que se pueden llegar a generar entre la fundamentación teórica