The heterotetrameric architecture of the epithelial sodium channel (ENaC).

The epithelial sodium channel (ENaC) is a key element for the maintenance of sodium balance and the regulation of blood pressure. Three homologous ENaC subunits (alpha, beta and gamma) assemble to form a highly Na+-selective channel. However, the subunit stoichiometry of ENaC has not yet been solved. Quantitative analysis of cell surface expression of ENaC alpha, beta and gamma subunits shows that they assemble according to a fixed stoichiometry, with alpha ENaC as the most abundant subunit. Functional assays based on differential sensitivities to channel blockers elicited by mutations tagging each alpha, beta and gamma subunit are consistent with a four subunit stoichiometry composed of two alpha, one beta and one gamma. Expression of concatameric cDNA constructs made of different combinations of ENaC subunits confirmed the four subunit channel stoichiometry and showed that the arrangement of the subunits around the channel pore consists of two alpha subunits separated by beta and gamma subunits.

Comparative genomics of ParaHox clusters of teleost fishes: gene cluster breakup and the retention of gene sets following whole genome duplications.

BACKGROUND: The evolutionary lineage leading to the teleost fish underwent a whole genome duplication termed FSGD or 3R in addition to two prior genome duplications that took place earlier during vertebrate evolution (termed 1R and 2R). Resulting from the FSGD, additional copies of genes are present in fish, compared to tetrapods whose lineage did not experience the 3R genome duplication. Interestingly, we find that ParaHox genes do not differ in number in extant teleost fishes despite their additional genome duplication from the genomic situation in mammals, but they are distributed over twice as many paralogous regions in fish genomes. RESULTS: We determined the DNA sequence of the entire ParaHox C1 paralogon in the East African cichlid fish Astatotilapia burtoni, and compared it to orthologous regions in other vertebrate genomes as well as to the paralogous vertebrate ParaHox D paralogons. Evolutionary relationships among genes from these four chromosomal regions were studied with several phylogenetic algorithms. We provide evidence that the genes of the ParaHox C paralogous cluster are duplicated in teleosts, just as it had been shown previously for the D paralogon genes. Overall, however, synteny and cluster integrity seems to be less conserved in ParaHox gene clusters than in Hox gene clusters. Comparative analyses of non-coding sequences uncovered conserved, possibly co-regulatory elements, which are likely to contain promoter motives of the genes belonging to the ParaHox paralogons. CONCLUSION: There seems to be strong stabilizing selection for gene order as well as gene orientation in the ParaHox C paralogon, since with a few exceptions, only the lengths of the introns and intergenic regions differ between the distantly related species examined. The high degree of evolutionary conservation of this gene cluster's architecture in particular - but possibly clusters of genes more generally - might be linked to the presence of promoter, enhancer or inhibitor motifs that serve to regulate more than just one gene. Therefore, deletions, inversions or relocations of individual genes could destroy the regulation of the clustered genes in this region. The existence of such a regulation network might explain the evolutionary conservation of gene order and orientation over the course of hundreds of millions of years of vertebrate evolution. Another possible explanation for the highly conserved gene order might be the existence of a regulator not located immediately next to its corresponding gene but further away since a relocation or inversion would possibly interrupt this interaction. Different ParaHox clusters were found to have experienced differential gene loss in teleosts. Yet the complete set of these homeobox genes was maintained, albeit distributed over almost twice the number of chromosomes. Selection due to dosage effects and/or stoichiometric disturbance might act more strongly to maintain a modal number of homeobox genes (and possibly transcription factors more generally) per genome, yet permit the accumulation of other (non regulatory) genes associated with these homeobox gene clusters.

The molecular architecture of the TNF superfamily.

Ligands of the TNF (tumour necrosis factor) superfamily have pivotal roles in the organization and function of the immune system, and are implicated in the aetiology of several acquired and genetic diseases. TNF ligands share a common structural motif, the TNF homology domain (THD), which binds to cysteine-rich domains (CRDs) of TNF receptors. CRDs are composed of structural modules, whose variation in number and type confers heterogeneity upon the family. Protein folds reminiscent of the THD and CRD are also found in other protein families, raising the possibility that the mode of interaction between TNF and TNF receptors might be conserved in other contexts.

Relationships between host plant architecture and gall abundance and survival

The plant architecture hypothesis predicts that variation in host plant architecture influences insect herbivore community structure, dynamics and performance. In this study we evaluated the effects of Macairea radula (Melastomataceae) architecture on the abundance of galls induced by a moth (Lepidoptera: Gelechiidae). Plant architecture and gall abundance were directly recorded on 58 arbitrarily chosen M. radula host plants in the rainy season of 2006 in an area of Cerrado vegetation, southeastern Brazil. Plant height, dry biomass, number of branches, number of shoots and leaf abundance were used as predicting variables of gall abundance and larval survival. Gall abundance correlated positively with host plant biomass and branch number. Otherwise, no correlation (p > 0.05) was found between gall abundance with shoot number or with the number of leaves/plant. From a total of 124 galls analyzed, 67.7% survived, 14.5% were attacked by parasitoids, while 17.7% died due to unknown causes. Larvae that survived or were parasitized were not influenced by architectural complexity of the host plant. Our results partially corroborate the plant architecture hypothesis, but since parasitism was not related to plant architecture it is argued that bottom-up effects may be more important than top-down effects in controlling the population dynamics of the galling lepidopteran. Because galling insects often decrease plant fitness, the potential of galling insects in selecting for less architectural complex plants is discussed.

The handaxe and the microscope: individual and social learning in a multidimensional model of adaptation

When individuals learn by trial-and-error, they perform randomly chosen actions and then reinforce those actions that led to a high payoff. However, individuals do not always have to physically perform an action in order to evaluate its consequences. Rather, they may be able to mentally simulate actions and their consequences without actually performing them. Such fictitious learners can select actions with high payoffs without making long chains of trial-and-error learning. Here, we analyze the evolution of an n-dimensional cultural trait (or artifact) by learning, in a payoff landscape with a single optimum. We derive the stochastic learning dynamics of the distance to the optimum in trait space when choice between alternative artifacts follows the standard logit choice rule. We show that for both trial-and-error and fictitious learners, the learning dynamics stabilize at an approximate distance of root n/(2 lambda(e)) away from the optimum, where lambda(e) is an effective learning performance parameter depending on the learning rule under scrutiny. Individual learners are thus unlikely to reach the optimum when traits are complex (n large), and so face a barrier to further improvement of the artifact. We show, however, that this barrier can be significantly reduced in a large population of learners performing payoff-biased social learning, in which case lambda(e) becomes proportional to population size. Overall, our results illustrate the effects of errors in learning, levels of cognition, and population size for the evolution of complex cultural traits. (C) 2013 Elsevier Inc. All rights reserved.

The Arcuated Lintel and the "Serlian Motif". Imperial Identity, Architectural and Symbolic Interactions in Ancient Rome

Essay on the origin, use and development of the arcuated lintel in ancient Rome and the configuration of the so– called ‘Serlian motif’. These architectural elements will be related to the architecture of prestige on its technical, functional, visual and symbolic sphere. Its depictions, in addition to buildings, can offer a rich repertory of images that speak about the relations between visual culture, religion and power. Furthermore, the analyzed motifs will become important elements of the Western cultural legacy for centuries. The analysis of these events will contribute to the comprehension of the role played by some resources of ancient Rome architecture of prestige and its success

Destruction of lymphoid organ architecture and hepatitis caused by CD4 T cells.

Immune responses have the important function of host defense and protection against pathogens. However, the immune response also causes inflammation and host tissue injury, termed immunopathology. For example, hepatitis B and C virus infection in humans cause immunopathological sequel with destruction of liver cells by the host's own immune response. Similarly, after infection with lymphocytic choriomeningitis virus (LCMV) in mice, the adaptive immune response causes liver cell damage, choriomeningitis and destruction of lymphoid organ architecture. The immunopathological sequel during LCMV infection has been attributed to cytotoxic CD8(+) T cells. However, we now show that during LCMV infection CD4(+) T cells selectively induced the destruction of splenic marginal zone and caused liver cell damage with elevated serum alanin-transferase (ALT) levels. The destruction of the splenic marginal zone by CD4(+) T cells included the reduction of marginal zone B cells, marginal zone macrophages and marginal zone metallophilic macrophages. Functionally, this resulted in an impaired production of neutralizing antibodies against LCMV. Furthermore, CD4(+) T cells reduced B cells with an IgM(high)IgD(low) phenotype (transitional stage 1 and 2, marginal zone B cells), whereas other B cell subtypes such as follicular type 1 and 2 and germinal center/memory B cells were not affected. Adoptive transfer of CD4(+) T cells lacking different important effector cytokines and cytolytic pathways such as IFNγ, TNFα, perforin and Fas-FasL interaction did reveal that these cytolytic pathways are redundant in the induction of immunopathological sequel in spleen. In conclusion, our results define an important role of CD4(+) T cells in the induction of immunopathology in liver and spleen. This includes the CD4(+) T cell mediated destruction of the splenic marginal zone with consecutively impaired protective neutralizing antibody responses.

Pleiotropy and the low cost of individual traits promote cooperation.

The evolution of cooperation is thought to be promoted by pleiotropy, whereby cooperative traits are coregulated with traits that are important for personal fitness. However, this hypothesis faces a key challenge: what happens if mutation targets a cooperative trait specifically rather than the pleiotropic regulator? Here, we explore this question with the bacterium Pseudomonas aeruginosa, which cooperatively digests complex proteins using elastase. We empirically measure and theoretically model the fate of two mutants-one missing the whole regulatory circuit behind elastase production and the other with only the elastase gene mutated-relative to the wild-type (WT). We first show that, when elastase is needed, neither of the mutants can grow if the WT is absent. And, consistent with previous findings, we show that regulatory gene mutants can grow faster than the WT when there are no pleiotropic costs. However, we find that mutants only lacking elastase production do not outcompete the WT, because the individual cooperative trait has a low cost. We argue that the intrinsic architecture of molecular networks makes pleiotropy an effective way to stabilize cooperative evolution. Although individual cooperative traits experience loss-of-function mutations, these mutations may result in weak benefits, and need not undermine the protection from pleiotropy.

Mitotic regulation by Polo-like kinase 1 and the Chromosomal Passenger Complex

During mitosis, the duplicated genome must be accurately divided between two daughter cells. Polo-like kinase 1 (Plk1) and Aurora B kinase, together with its binding partners Incenp, Survivin and Borealin (chromosomal passenger complex, CPC), have key roles in coordinating mitotic events. The accuracy of cell division is safeguarded by a signaling cascade termed the mitotic spindle checkpoint (SC), which ensures that chromosomes are not physically separated before correct bipolar attachments have been formed between kinetochores and spindle microtubules (MT). An inhibitory “wait anaphase” signal, which delays chromosome separation (anaphase onset), is created at individual kinetochores and broadcasted throughout the cell in response to lack of kinetochore-microtubule (kMT) attachment or proper interkinetochore tension. It is believed that the fast turnover of SC molecules at kinetochores contributes to the cell’s ability to produce this signal and enables rapid responses to changing cellular conditions. Kinetochores that lack MT attachment and tension express a certain phosphoepitope called the 3F3/2 phosphoepitope, which has been linked to SC signaling. In the experimental part, we investigated the regulation of the 3F3/2 phosphoepitope, analyzed whether CPC molecules turn over at centromeres, and dissected the mitotic roles of the CPC using a microinjection technique that allowed precise temporal control over its function. We found that the kinetochore 3F3/2 phosphoepitope is created by Plk1, and that CPC proteins exhibit constant exchange at centromeres. Moreover, we found that CPC function is necessary in the regulation of chromatid movements and spindle morphology in anaphase. In summary, we identified new functions of key mitotic regulators Plk1 and CPC, and provided insighs into the coordination of mitotic events.

Relationships between crown architecture and available irradiance in two cerrado species with different leaf phenologies

Structural differences between cerrado species with different leaf phenologies are linked to crown architecture, leaf production, and biomass allocation to shoots and leaves. The present study characterized crown structures and the patterns of biomass allocation to leaves and shoots in two woody cerrado species with contrasting leaf phenologies and quantified the irradiance reaching their leaves to determine the best period during the day for photosynthetic activity. The shoots and leaves of five individuals of both Annona coriacea (deciduous) and Hymenaea stigonocarpa (evergreen) were collected along a 50 m transect in a cerrado fragment within the urban perimeter of Catalão - GO, to determine their patterns of biomass allocation in their crowns. The evergreen H. stigonocarpa had significantly higher mean values of shoot inclination (SI), petiole length (PL), leaf area (LA), leaf display index (LDI), and individual leaf area per shoot (ILA), while the deciduous species A. coriacea had significantly higher leaf numbers (LN). The more complex crown of H. stigonocarpa had shoots in more erect positions (orthotropic), with intense self-shading within shoots; A. coriacea, on the other hand, had slanting (plagiotropic) shoots in the crown, allowing similar irradiance levels to all leaf surfaces. The production of plagiotropic shoots by the deciduous species (A. coriacea) is a strategy that enables its use of incident sunlight early in the morning and preventing excessive water loss or excessive irradiance. Hymenaea stigonocarpa (an evergreen), by contrast, had orthotropic shoots and uses intense self-shading as a strategy to avoid excessive irradiance, especially at midday. Differences in crown architectures between evergreen and deciduous species of cerrado sensu stricto can therefore be viewed as adaptations to the environmental light regime.

Relationship between the quality of life and the severity of obstructive sleep apnea syndrome

The effects of sleep disorders on the quality of life (QOL) have been documented in the literature. Excessive sleepiness and altered circadian rhythms may negatively affect ability to learn, employment, and interpersonal relations, and directly degrade QOL. The objective of the present study was to evaluate the impact of obstructive sleep apnea syndrome of varying severity on QOL. The study was conducted on 1892 patients aged 18 years or older referred by a physician to the Sleep Institute, São Paulo, with complaints related to apnea (snoring, excessive daytime sleepiness, hyperarousal, and fatigue). They were submitted to overnight polysomnography for the diagnosis of sleep disorders from August 2005 through April 2006. The patients completed the Epworth Sleepiness Scale and QOL SF-36 sleep questionnaires. They were classified as non-physically active and physically active and not-sleepy and sleepy and the results of polysomnography were analyzed on the basis of the apnea hypopnea index (AHI). The apneic subjects showed a reduction in QOL which was proportional to severity. There was a significant decrease in all domains (physical functioning, role physical problems, bodily pain, general health perceptions, vitality, social functioning, emotional problems, general mental health) for apneics with AHI >30, who generally were sleepy and did not participate in physical activities (P < 0.05). The present study provides evidence that the impact of sleep disorders on QOL in apneics is not limited to excessive daytime sleepiness and that physical activity can contribute to reducing the symptoms. Thus, exercise should be considered as an adjunct interventional strategy in the management of obstructive sleep apnea syndrome.

Changes in canola plant architecture and seed physiological quality in response to different sowing densities

The aim of this study was to evaluate changes in canola yield components and seed physiological quality in response to different sowing densities. The study was made in a greenhouse at the REIPESOL Company Technological Center, Madrid - Spain, with the commercial "Toccata" hybrid variety. The initial sowing density was 360,000 plants/ha and the plant population was later thinned down to include treatments of 250 and 180 thousand plants/ha. Harvested seeds were sent to the Seed Technology Center Laboratory (CATES) at the Madrid Polytechnic University (UPM) to evaluate changes in plant architecture and yield components, as well as the seed physiological quality of different plant parts. Results demonstrated that canola plants showed changes in morphology and yield components in response to different sowing densities. The population of 250,000 plants/ha showed the best seed yield demonstrating that maximum yield is directly related to a correct sowing density. The number of pods/plant was the most important component for increased seed yield/plant and seed yield/area. The spatial distribution of canola seeds in the plant and canola sowing density did not affect seed physiological quality.

A constructivist grounded theory of firefighter perceptions of stress, coping and the relationship to health

This qualitative research was a constructivist grounded theory designed to develop an understanding of how firefighters perceive and cope with stressful situations and the impact this has on their perceptions of health. This study was framed in a social ecological perspective with the community of firefighting providing the environment within which to explore stress and coping. Of particular concern here are the stressors associated with firefighting. Prior research with firefighters has often been epidemiological and statistical in nature, focusing on measures of cardiovascular disease, cancer, and depression (Baker & Williams, 2001 ; Brown et al., 2002; Murphy et al.,1999; Regehr et al., 2002; Regehr et al., 2003). Qualitative research examining the perception of stress among firefighters that includes personal stories allows firefighters the opportunity to describe what it is like to be met with physically and mentally challenging situations on a daily basis. Twelve in-depth, semi-structured, face-to-face interviews with a brief questionnaire were conducted with firefighters from a Southern Ontario Fire Department. Four main themes emerged describing the persona of the firefighter, the stressors of firefighters, coping strategies of firefighters, and firefighters' perceptions of health. Stressors include requirements of the job, traumatic calls, tensions with co-workers, the struggle between the family at home and the family at work, political stressors with the City, and the inner struggle. Avoidance coping, approach coping, and gaining perspective emerged as the three coping styles of firefighters. Health was defined as including physical, mental, social and spiritual aspects. A model of the findings is provided that depicts the cyclical nature of the stress-coping-health relationship among firefighters.

Understanding deep architectures and the effect of unsupervised pre-training

Cette thèse porte sur une classe d'algorithmes d'apprentissage appelés architectures profondes. Il existe des résultats qui indiquent que les représentations peu profondes et locales ne sont pas suffisantes pour la modélisation des fonctions comportant plusieurs facteurs de variation. Nous sommes particulièrement intéressés par ce genre de données car nous espérons qu'un agent intelligent sera en mesure d'apprendre à les modéliser automatiquement; l'hypothèse est que les architectures profondes sont mieux adaptées pour les modéliser. Les travaux de Hinton (2006) furent une véritable percée, car l'idée d'utiliser un algorithme d'apprentissage non-supervisé, les machines de Boltzmann restreintes, pour l'initialisation des poids d'un réseau de neurones supervisé a été cruciale pour entraîner l'architecture profonde la plus populaire, soit les réseaux de neurones artificiels avec des poids totalement connectés. Cette idée a été reprise et reproduite avec succès dans plusieurs contextes et avec une variété de modèles. Dans le cadre de cette thèse, nous considérons les architectures profondes comme des biais inductifs. Ces biais sont représentés non seulement par les modèles eux-mêmes, mais aussi par les méthodes d'entraînement qui sont souvent utilisés en conjonction avec ceux-ci. Nous désirons définir les raisons pour lesquelles cette classe de fonctions généralise bien, les situations auxquelles ces fonctions pourront être appliquées, ainsi que les descriptions qualitatives de telles fonctions. L'objectif de cette thèse est d'obtenir une meilleure compréhension du succès des architectures profondes. Dans le premier article, nous testons la concordance entre nos intuitions---que les réseaux profonds sont nécessaires pour mieux apprendre avec des données comportant plusieurs facteurs de variation---et les résultats empiriques. Le second article est une étude approfondie de la question: pourquoi l'apprentissage non-supervisé aide à mieux généraliser dans un réseau profond? Nous explorons et évaluons plusieurs hypothèses tentant d'élucider le fonctionnement de ces modèles. Finalement, le troisième article cherche à définir de façon qualitative les fonctions modélisées par un réseau profond. Ces visualisations facilitent l'interprétation des représentations et invariances modélisées par une architecture profonde.