Task-dependent influence of genetic architecture and mating frequency on division of labour in social insect societies.

Division of labour is one of the most prominent features of social insects. The efficient allocation of individuals to different tasks requires dynamic adjustment in response to environmental perturbations. Theoretical models suggest that the colony-level flexibility in responding to external changes and internal perturbation may depend on the within-colony genetic diversity, which is affected by the number of breeding individuals. However, these models have not considered the genetic architecture underlying the propensity of workers to perform the various tasks. Here, we investigated how both within-colony genetic variability (stemming from variation in the number of matings by queens) and the number of genes influencing the stimulus (threshold) for a given task at which workers begin to perform that task jointly influence task allocation efficiency. We used a numerical agent-based model to investigate the situation where workers had to perform either a regulatory task or a foraging task. One hundred generations of artificial selection in populations consisting of 500 colonies revealed that an increased number of matings always improved colony performance, whatever the number of loci encoding the thresholds of the regulatory and foraging tasks. However, the beneficial effect of additional matings was particularly important when the genetic architecture of queens comprised one or a few genes for the foraging task's threshold. By contrast, a higher number of genes encoding the foraging task reduced colony performance with the detrimental effect being stronger when queens had mated with several males. Finally, the number of genes encoding the threshold for the regulatory task only had a minor effect on colony performance. Overall, our numerical experiments support the importance of mating frequency on efficiency of division of labour and also reveal complex interactions between the number of matings and genetic architecture.

Ontogeny of Sleeping in Color - Linking melanism to sleep architecture and rhythmicity variation in wild barn owl nestlings

The function of sleep remains unknown. To gain insight into the function of sleep in natural conditions, I assessed variation in sleep architecture and its link with fitness-related phenotypic traits. I considered melanin-based coloration because its underlying genetic basis is very well known giving an opportunity to examine whether some genes pleiotropically regulate both coloration and sleep. The melanocortin system is known to generate covariation between melanin-based coloration and other phenotypes like behaviour, physiology and life history traits. I investigated whether this system of genes could participate in the co-expression of coloration and sleep. I carried out a study with nestling barn owls (Tyto alba) in order to tackle the potential link between variation in color traits and the ontogeny of sleep under natural conditions. For this I established a suitable method for recording the brain activity (electroencephalogram) of owls in nature. Birds are especially interesting, because they convergently evolved sleep states similar to those exhibited by mammals. As in mammals, I found that in owlets time spent in rapid eye movement (REM) sleep declines with age, a relationship thought to eflect developmental changes in the brain. Thus this developmental trajectory appears to reflect a fundamental feature of sleep. Additionally, I discovered an association between a gene involved in melanism expressed in the feather follicles (proprotein convertase subtilisin/kexin type 2, PCSK2) and the age-related changes in sleep in the brain. Nestlings with higher expression levels of PCSK2 showed a more precocial pattern of sleep development and a higher degree of melanin-based coloration compared to nestlings with lower PCSK2 expression. Also sleep architecture and the development of rhythmicity in brain and physical activity was related to plumage traits of the nestlings and their biological parents. This pattern during ontogeny might reflect differences in life l history strategies, antipredator behaviour and developmental pace. Therefore, differently colored individuals may differentially deal with trade-offs between the costs and benefits of sleep which in turn lead to differences in brain organization and ultimately fitness. These results should stimulate evolutionary biologists to consider sleep as a major life history trait. Résumé La fonction du sommeil reste inconnue. Afin d'acquérir une meilleur compréhension de la fonction du sommeil dans les conditions naturelles, j'ai analysé la variation dans l'architecture du sommeil et son lien avec d'autres traits phénotypiques liés au succès reproducteur (fitness). J'ai choisi et examiné la coloration mélanique, car ses bases génétiques sont bien connues et il est ainsi possible d'étudier si certains gènes, de façon pléiotropique régulent à la fois la coloration et le sommeil. J'ai exploré si ce système génétique était impliqué dans la co-expression de la coloration et du sommeil. J'ai effectué mon étude sur des poussins de chouette effraie (Tyto alba) en condition naturelle, pour rechercher ce lien potentiel entre la variation de la coloration et l'ontogenèse du sommeil. Dans ce but, j'ai établi une méthodologie permettant d'enregistrer l'activité cérébrale (électroencéphalogramme) des chouettes dans la nature. Les oiseaux sont particulièrement intéressants car ils ont développé, par évolution convergente, des phases de sommeil similaires à celles des mammifères. De manière semblable à ce qui a été montré chez les mammifères, j'ai découvert que le temps passé dans le sommeil paradoxal diminue avec l'âge des poussins. On pense que ceci est dû aux changements développementaux au niveau du cerveau. Cette trajectoire développementale semble refléter une caractéristique fondamentale du sommeil. J'ai également découvert une association entre l'un des gènes impliqué dans le mélanisme, exprimé dans les follicules plumeux (proprotein convertase subtilisin/kexin type 2, PCSK2), et les changements dans la structure du sommeil avec l'âge. Les poussins ayant un niveau d'expression génétique élevé de la PCSK2 présentent une structure du sommeil plus précoce et un taux de coloration dû à la mélanine plus élevé que des poussins avec un niveau d'expression moindre de la PCSK2. L'architecture du sommeil et le développement de la rythmicité dans le cerveau ainsi que l'activité physique sont également liés à la coloration des plumes des poussins et pourraient ainsi refléter des différences de stratégies d'histoire de vie, de comportements anti-prédateur et de vitesses développementales. Ainsi, des individus de coloration différente sembleraient traiter différemment les coûts et les bénéfices du sommeil, ce qui aurait des conséquences sur l'organisation cérébrale et pour finir, sur le succès reproducteur. Ces résultats devraient encourager les biologistes évolutionnistes à considérer le sommeil comme un important trait d'histoire de vie. Zusammenfassung Die Funktion von Schlaf ist noch unbekannt. Um mehr Einsicht in diese unter natürlichen Bedingungen zu bekommen, habe ich die Variation in der Schlafarchitektur und die Verknüpfung mit phänotypischen Merkmalen, die mit der Fitness zusammenhängen, studiert. Ich habe mir melanin-basierte Färbung angesehen, da die zugrunde liegende genetische Basis bekannt ist und somit die Möglichkeit gegeben ist, zu untersuchen, ob einige Gene beides regulieren, Färbung und Schlaf. Das melanocortin System generiert eine Kovariation zwischen melanin-basierter Färbung und anderen phänotypischer Merkmale wie Verhalten, Physiologie und Überlebensstrategien. Ich habe untersucht, ob dieses Gensystem an einer gleichzeitigen Steuerung von Färbung und Schlaf beteiligt ist. Dazu habe ich Schleiereulen (Tyto alba) studiert um einen möglichen Zusammenhang zwischen der Variation in der Pigmentierung und der Entwicklung des Schlafs unter natürlichen Bedingungen zu entdecken. Für diese Studie entwickelte ich eine Methode um die Gehirnaktivität (Elektroenzephalogramm) bei Eulen in der Natur aufzunehmen. Vögel sind besonders interessant, da sie die gleichen Schlafstadien aufweisen wie Säugetiere und diese unabhängig konvergent entwickelt haben. Genauso wie bei Säugetieren nahm die Dauer des sogenannten ,,rapid eye movement" (REM) - Schlafes mit zunehmendem Alter ab. Es wird angenommen, dass dieser Zusammenhang die Entwicklung des Gehirns widerspiegelt. Daher scheint dieses Entwicklungsmuster ein fundamentaler Aspekt von Schlaf zu sein. Zusätzlich entdeckte ich einen Zusammenhang zwischen der Aktivität eines Gens in den Federfollikeln (proprotein convertase subtilisin/kexin type 2, PCSK2), das für die Ausprägung schwarzer Punkte auf den Federn der Eulen verantwortlich ist, und den altersabhängigen Änderungen im Schlafmuster im Gehirn. Küken mit höherer Aktivität von PCSK2 zeigten eine frühreifere Schlafentwicklung und eine dunklere Färbung als Küken mit niedriger PCSK2 Aktivität. Die Architekture des Schlafes und die Entwicklung der Rhythmik im Gehirn und die der physischen Aktivität ist mit der Färbung des Gefieders von den Küken und ihren Eltern verknüpft. Dieses Muster während der Entwicklung kann Unterschiede in Überlebensstrategien, Feindabwehrverhalten und in der Entwicklungsgeschwindigkeit reflektieren. Unterschiedlich gefärbte Individuen könnten unterschiedliche Strategien haben um zwischen den Kosten und Nutzen von Schlaf zu entscheiden, was zu Unterschieden in der Gehirnstruktur führen kann und letztendlich zur Fitness. Diese Ergebnisse sollten Evolutionsbiologen stimulieren Schlaf als einen wichtigen Bestandteil des Lebens zu behandeln.

Social network architecture and the maintenance of deleterious cultural traits.

How have changes in communications technology affected the way that misinformation spreads through a population and persists? To what extent do differences in the architecture of social networks affect the spread of misinformation, relative to the rates and rules by which individuals transmit or eliminate different pieces of information (cultural traits)? Here, we use analytical models and individual-based simulations to study how a 'cultural load' of misinformation can be maintained in a population under a balance between social transmission and selective elimination of cultural traits with low intrinsic value. While considerable research has explored how network architecture affects percolation processes, we find that the relative rates at which individuals transmit or eliminate traits can have much more profound impacts on the cultural load than differences in network architecture. In particular, the cultural load is insensitive to correlations between an individual's network degree and rate of elimination when these quantities vary among individuals. Taken together, these results suggest that changes in communications technology may have influenced cultural evolution more strongly through changes in the amount of information flow, rather than the details of who is connected to whom.

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.

A survey of transposable element classification systems--a call for a fundamental update to meet the challenge of their diversity and complexity.

The increase of publicly available sequencing data has allowed for rapid progress in our understanding of genome composition. As new information becomes available we should constantly be updating and reanalyzing existing and newly acquired data. In this report we focus on transposable elements (TEs) which make up a significant portion of nearly all sequenced genomes. Our ability to accurately identify and classify these sequences is critical to understanding their impact on host genomes. At the same time, as we demonstrate in this report, problems with existing classification schemes have led to significant misunderstandings of the evolution of both TE sequences and their host genomes. In a pioneering publication Finnegan (1989) proposed classifying all TE sequences into two classes based on transposition mechanisms and structural features: the retrotransposons (class I) and the DNA transposons (class II). We have retraced how ideas regarding TE classification and annotation in both prokaryotic and eukaryotic scientific communities have changed over time. This has led us to observe that: (1) a number of TEs have convergent structural features and/or transposition mechanisms that have led to misleading conclusions regarding their classification, (2) the evolution of TEs is similar to that of viruses by having several unrelated origins, (3) there might be at least 8 classes and 12 orders of TEs including 10 novel orders. In an effort to address these classification issues we propose: (1) the outline of a universal TE classification, (2) a set of methods and classification rules that could be used by all scientific communities involved in the study of TEs, and (3) a 5-year schedule for the establishment of an International Committee for Taxonomy of Transposable Elements (ICTTE).

The fine-scale architecture of structural variants in 17 mouse genomes.

BACKGROUND: Accurate catalogs of structural variants (SVs) in mammalian genomes are necessary to elucidate the potential mechanisms that drive SV formation and to assess their functional impact. Next generation sequencing methods for SV detection are an advance on array-based methods, but are almost exclusively limited to four basic types: deletions, insertions, inversions and copy number gains. RESULTS: By visual inspection of 100 Mbp of genome to which next generation sequence data from 17 inbred mouse strains had been aligned, we identify and interpret 21 paired-end mapping patterns, which we validate by PCR. These paired-end mapping patterns reveal a greater diversity and complexity in SVs than previously recognized. In addition, Sanger-based sequence analysis of 4,176 breakpoints at 261 SV sites reveal additional complexity at approximately a quarter of structural variants analyzed. We find micro-deletions and micro-insertions at SV breakpoints, ranging from 1 to 107 bp, and SNPs that extend breakpoint micro-homology and may catalyze SV formation. CONCLUSIONS: An integrative approach using experimental analyses to train computational SV calling is essential for the accurate resolution of the architecture of SVs. We find considerable complexity in SV formation; about a quarter of SVs in the mouse are composed of a complex mixture of deletion, insertion, inversion and copy number gain. Computational methods can be adapted to identify most paired-end mapping patterns.

The shared allelic architecture of adiponectin levels and coronary artery disease.

OBJECTIVE: A large body of epidemiologic data strongly suggests an association between excess adiposity and coronary artery disease (CAD). Low adiponectin levels, a hormone secreted only from adipocytes, have been associated with an increased risk of CAD in observational studies. However, these associations cannot clarify whether this relationship is causal or due to a shared set of causal factors or even confounding. Genome-wide association studies have identified common variants that influence adiponectin levels, providing valuable tools to examine the genetic relationship between adiponectin and CAD. METHODS: Using 145 genome wide significant SNPs for adiponectin from the ADIPOGen consortium (n = 49,891), we tested whether adiponectin-decreasing alleles influenced risk of CAD in the CARDIoGRAM consortium (n = 85,274). RESULTS: In single-SNP analysis, 5 variants among 145 SNPs were associated with increased risk of CAD after correcting for multiple testing (P < 4.4 × 10(-4)). Using a multi-SNP genotypic risk score to test whether adiponectin levels and CAD have a shared genetic etiology, we found that adiponectin-decreasing alleles increased risk of CAD (P = 5.4 × 10(-7)). CONCLUSION: These findings demonstrate that adiponectin levels and CAD have a shared allelic architecture and provide rationale to undertake a Mendelian randomization studies to understand if this relationship is causal.

Glomus intraradices induces changes in root system architecture of rice independently of common symbiosis signaling

? Arbuscular mycorrhizal fungi colonize the roots of most monocotyledons and dicotyledons despite their different root architecture and cell patterning. Among the cereal hosts of arbuscular mycorrhizal fungi, Oryza sativa (rice) possesses a peculiar root system composed of three different types of roots: crown roots; large lateral roots; and fine lateral roots. Characteristic is the constitutive formation of aerenchyma in crown roots and large lateral roots and the absence of cortex from fine lateral roots. Here, we assessed the distribution of colonization by Glomus intraradices within this root system and determined its effect on root system architecture. ? Large lateral roots are preferentially colonized, and fine lateral roots are immune to arbuscular mycorrhizal colonization. Fungal preference for large lateral roots also occurred in sym mutants that block colonization of the root beyond rhizodermal penetration. ? Initiation of large lateral roots is significantly induced by G. intraradices colonization and does not require a functional common symbiosis signaling pathway from which some components are known to be needed for symbiosis-mediated lateral root induction in Medicago truncatula. ? Our results suggest variation of symbiotic properties among the different rice root-types and induction of the preferred tissue by arbuscular mycorrhizal fungi. Furthermore, signaling for arbuscular mycorrhizal-elicited alterations of the root system differs between rice and M. truncatula.

Regulation of membrane trafficking and organ separation by the NEVERSHED ARF-GAP protein.

Cell separation, or abscission, is a highly specialized process in plants that facilitates remodeling of their architecture and reproductive success. Because few genes are known to be essential for organ abscission, we conducted a screen for mutations that alter floral organ shedding in Arabidopsis. Nine recessive mutations that block shedding were found to disrupt the function of an ADP-ribosylation factor-GTPase-activating protein (ARF-GAP) we have named NEVERSHED (NEV). As predicted by its homology to the yeast Age2 ARF-GAP and transcriptional profile, NEV influences other aspects of plant development, including fruit growth. Co-localization experiments carried out with NEV-specific antiserum and a set of plant endomembrane markers revealed that NEV localizes to the trans-Golgi network and endosomes in Arabidopsis root epidermal cells. Interestingly, transmission electron micrographs of abscission zone regions from wild-type and nev flowers reveal defects in the structure of the Golgi apparatus and extensive accumulation of vesicles adjacent to the cell walls. Our results suggest that NEV ARF-GAP activity at the trans-Golgi network and distinct endosomal compartments is required for the proper trafficking of cargo molecules required for cell separation.

Inventory and description of disease management programs in Switzerland

Background: Disease management, a system of coordinated health care interventions for populations with chronic diseases in which patient self-care is a key aspect, has been shown to be effective for several conditions. Little is known on the supply of disease management programs in Switzerland. Objectives: To systematically search, record and evaluate data on existing disease management programs in Switzerland. Methods: Programs met our operational definition of disease management if their interventions targeted a chronic disease, included a multidisciplinary team and lasted at least 6 months. To find existing programs, we searched Swiss official websites, Swiss web-pages using Google, medical electronic database (Medline), and checked references from selected documents. We also contacted personally known individuals, those identified as possibly working in the field, individuals working in major Swiss health insurance companies and people recommended by previously contacted persons (snow ball strategy). We developed an extraction grid and collected information pertaining to the following 8 domains: patient population, intervention recipient, intervention content, delivery personnel, method of communication, intensity and complexity, environment and clinical outcomes (measures?). Results: We identified 8 programs fulfilling our operational definition of disease management. Programs targeted patients with diabetes, hypertension, heart failure, obesity, alcohol dependence, psychiatric disorders or breast cancer, and were mainly directed towards patients. The interventions were multifaceted and included education in almost all cases. Half of the programs included regularly scheduled follow-up, by phone in 3 instances. Healthcare professionals involved were physicians, nurses, case managers, social workers, psychologists and dietitians. None fulfilled the 6 criteria established by the Disease Management Association of America. Conclusions: Our study shows that disease management programs, in a country with universal health insurance coverage and little incentive to develop new healthcare strategies, are scarce, although we may have missed existing programs. Nonetheless, those already implemented are very interesting and rather comprehensive. Appropriate evaluation of these programs should be performed in order to build upon them and try to design a generic disease management framework suited to the Swiss healthcare system.

Inventory and perspectives of chronic disease management programs in Switzerland: an exploratory survey.

OBJECTIVE: To describe chronic disease management programs active in Switzerland in 2007, using an exploratory survey. METHODS: We searched the internet (Swiss official websites and Swiss web-pages, using Google), a medical electronic database (Medline), reference lists of pertinent articles, and contacted key informants. Programs met our operational definition of chronic disease management if their interventions targeted a chronic disease, included a multidisciplinary team (>/=2 healthcare professionals), lasted at least six months, and had already been implemented and were active in December 2007. We developed an extraction grid and collected data pertaining to eight domains (patient population, intervention recipient, intervention content, delivery personnel, method of communication, intensity and complexity, environment, clinical outcomes). RESULTS: We identified seven programs fulfilling our operational definition of chronic disease management. Programs targeted patients with diabetes, hypertension, heart failure, obesity, psychosis and breast cancer. Interventions were multifaceted; all included education and half considered planned follow-ups. The recipients of the interventions were patients, and healthcare professionals involved were physicians, nurses, social workers, psychologists and case managers of various backgrounds. CONCLUSIONS: In Switzerland, a country with universal healthcare insurance coverage and little incentive to develop new healthcare strategies, chronic disease management programs are scarce. For future developments, appropriate evaluations of existing programs, involvement of all healthcare stakeholders, strong leadership and political will are, at least, desirable.