The evolution of unicoloniality in ant societies : recognition, dispersal and population genetic structure

Introduction Societies of ants, bees, wasps and termites dominate many terrestrial ecosystems (Wilson 1971). Their evolutionary and ecological success is based upon the regulation of internal conflicts (e.g. Ratnieks et al. 2006), control of diseases (e.g. Schmid-Hempel 1998) and individual skills and collective intelligence in resource acquisition, nest building and defence (e.g. Camazine 2001). Individuals in social species can pass on their genes not only directly trough their own offspring, but also indirectly by favouring the reproduction of relatives. The inclusive fitness theory of Hamilton (1963; 1964) provides a powerful explanation for the evolution of reproductive altruism and cooperation in groups with related individuals. The same theory also led to the realization that insect societies are subject to internal conflicts over reproduction. Relatedness of less-than-one is not sufficient to eliminate all incentive for individual selfishness. This would indeed require a relatedness of one, as found among cells of an organism (Hardin 1968; Keller 1999). The challenge for evolutionary biology is to understand how groups can prevent or reduce the selfish exploitation of resources by group members, and how societies with low relatedness are maintained. In social insects the evolutionary shift from single- to multiple queens colonies modified the relatedness structure, the dispersal, and the mode of colony founding (e.g. (Crozier & Pamilo 1996). In ants, the most common, and presumably ancestral mode of reproduction is the emission of winged males and females, which found a new colony independently after mating and dispersal flights (Hölldobler & Wilson 1990). The alternative reproductive tactic for ant queens in multiple-queen colonies (polygyne) is to seek to be re-accepted in their natal colonies, where they may remain as additional reproductives or subsequently disperse on foot with part of the colony (budding) (Bourke & Franks 1995; Crozier & Pamilo 1996; Hölldobler & Wilson 1990). Such ant colonies can contain up to several hundred reproductive queens with an even more numerous workforce (Cherix 1980; Cherix 1983). As a consequence in polygynous ants the relatedness among nestmates is very low, and workers raise brood of queens to which they are only distantly related (Crozier & Pamilo 1996; Queller & Strassmann 1998). Therefore workers could increase their inclusive fitness by preferentially caring for their closest relatives and discriminate against less related or foreign individuals (Keller 1997; Queller & Strassmann 2002; Tarpy et al. 2004). However, the bulk of the evidence suggests that social insects do not behave nepotistically, probably because of the costs entailed by decreased colony efficiency or discrimination errors (Keller 1997). Recently, the consensus that nepotistic behaviour does not occur in insect colonies was challenged by a study in the ant Formica fusca (Hannonen & Sundström 2003b) showing that the reproductive share of queens more closely related to workers increases during brood development. However, this pattern can be explained either by nepotism with workers preferentially rearing the brood of more closely related queens or intrinsic differences in the viability of eggs laid by queens. In the first chapter, we designed an experiment to disentangle nepotism and differences in brood viability. We tested if workers prefer to rear their kin when given the choice between highly related and unrelated brood in the ant F. exsecta. We also looked for differences in egg viability among queens and simulated if such differences in egg viability may mistakenly lead to the conclusion that workers behave nepotistically. The acceptance of queens in polygnous ants raises the question whether the varying degree of relatedness affects their share in reproduction. In such colonies workers should favour nestmate queens over foreign queens. Numerous studies have investigated reproductive skew and partitioning of reproduction among queens (Bourke et al. 1997; Fournier et al. 2004; Fournier & Keller 2001; Hammond et al. 2006; Hannonen & Sundström 2003a; Heinze et al. 2001; Kümmerli & Keller 2007; Langer et al. 2004; Pamilo & Seppä 1994; Ross 1988; Ross 1993; Rüppell et al. 2002), yet almost no information is available on whether differences among queens in their relatedness to other colony members affects their share in reproduction. Such data are necessary to compare the relative reproductive success of dispersing and non-dispersing individuals. Moreover, information on whether there is a difference in reproductive success between resident and dispersing queens is also important for our understanding of the genetic structure of ant colonies and the dynamics of within group conflicts. In chapter two, we created single-queen colonies and then introduced a foreign queens originating from another colony kept under similar conditions in order to estimate the rate of queen acceptance into foreign established colonies, and to quantify the reproductive share of resident and introduced queens. An increasing number of studies have investigated the discrimination ability between ant workers (e.g. Holzer et al. 2006; Pedersen et al. 2006), but few have addressed the recognition and discrimination behaviour of workers towards reproductive individuals entering colonies (Bennett 1988; Brown et al. 2003; Evans 1996; Fortelius et al. 1993; Kikuchi et al. 2007; Rosengren & Pamilo 1986; Stuart et al. 1993; Sundström 1997; Vásquez & Silverman in press). These studies are important, because accepting new queens will generally have a large impact on colony kin structure and inclusive fitness of workers (Heinze & Keller 2000). In chapter three, we examined whether resident workers reject young foreign queens that enter into their nest. We introduced mated queens into their natal nest, a foreign-female producing nest, or a foreign male-producing nest and measured their survival. In addition, we also introduced young virgin and mated queens into their natal nest to examine whether the mating status of the queens influences their survival and acceptance by workers. On top of polgyny, some ant species have evolved an extraordinary social organization called 'unicoloniality' (Hölldobler & Wilson 1977; Pedersen et al. 2006). In unicolonial ants, intercolony borders are absent and workers and queens mix among the physically separated nests, such that nests form one large supercolony. Super-colonies can become very large, so that direct cooperative interactions are impossible between individuals of distant nests. Unicoloniality is an evolutionary paradox and a potential problem for kin selection theory because the mixing of queens and workers between nests leads to extremely low relatedness among nestmates (Bourke & Franks 1995; Crozier & Pamilo 1996; Keller 1995). A better understanding of the evolution and maintenance of unicoloniality requests detailed information on the discrimination behavior, dispersal, population structure, and the scale of competition. Cryptic genetic population structure may provide important information on the relevant scale to be considered when measuring relatedness and the role of kin selection. Theoretical studies have shown that relatedness should be measured at the level of the `economic neighborhood', which is the scale at which intraspecific competition generally takes place (Griffin & West 2002; Kelly 1994; Queller 1994; Taylor 1992). In chapter four, we conducted alarge-scale study to determine whether the unicolonial ant Formica paralugubris forms populations that are organised in discrete supercolonies or whether there is a continuous gradation in the level of aggression that may correlate with genetic isolation by distance and/or spatial distance between nests. In chapter five, we investigated the fine-scale population structure in three populations of F. paralugubris. We have developed mitochondria) markers, which together with the nuclear markers allowed us to detect cryptic genetic clusters of nests, to obtain more precise information on the genetic differentiation within populations, and to separate male and female gene flow. These new data provide important information on the scale to be considered when measuring relatedness in native unicolonial populations.

Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration.

BACKGROUND: Whether nucleoside reverse transcriptase inhibitors increase the risk of myocardial infarction in HIV-infected individuals is unclear. Our aim was to explore whether exposure to such drugs was associated with an excess risk of myocardial infarction in a large, prospective observational cohort of HIV-infected patients. METHODS: We used Poisson regression models to quantify the relation between cumulative, recent (currently or within the preceding 6 months), and past use of zidovudine, didanosine, stavudine, lamivudine, and abacavir and development of myocardial infarction in 33 347 patients enrolled in the D:A:D study. We adjusted for cardiovascular risk factors that are unlikely to be affected by antiretroviral therapy, cohort, calendar year, and use of other antiretrovirals. FINDINGS: Over 157,912 person-years, 517 patients had a myocardial infarction. We found no associations between the rate of myocardial infarction and cumulative or recent use of zidovudine, stavudine, or lamivudine. By contrast, recent-but not cumulative-use of abacavir or didanosine was associated with an increased rate of myocardial infarction (compared with those with no recent use of the drugs, relative rate 1.90, 95% CI 1.47-2.45 [p=0.0001] with abacavir and 1.49, 1.14-1.95 [p=0.003] with didanosine); rates were not significantly increased in those who stopped these drugs more than 6 months previously compared with those who had never received these drugs. After adjustment for predicted 10-year risk of coronary heart disease, recent use of both didanosine and abacavir remained associated with increased rates of myocardial infarction (1.49, 1.14-1.95 [p=0.004] with didanosine; 1.89, 1.47-2.45 [p=0.0001] with abacavir). INTERPRETATION: There exists an increased risk of myocardial infarction in patients exposed to abacavir and didanosine within the preceding 6 months. The excess risk does not seem to be explained by underlying established cardiovascular risk factors and was not present beyond 6 months after drug cessation.

W8 Touch and match

El proyecto Touch & match resolverá la necesidad de una joven empresa del sector de la salud, especializada en el cuidado de nuestros mayores, que pretende crear una plataforma para mejorar la agilidad mental a través de un sencillo juego que permita ir buscando cartas iguales destapándolas de dos en dos.

15-OR: Multi-phase postmortem CT angiography of pulmonary embolism: technique-related artefacts or real findings?

Multi-phase postmortem CT angiography (MPMCTA) is recognized as a valuable tool to explore the vascular system, with higher sensitivity than conventional autopsy. However, a limitation is the impossibility to diagnose pulmonary embolism (PE) due to post-mortem blood clots situated in pulmonary arteries. The purpose of this study was to explore an eventual possibility to distinguish between real PE and artefacts mimicking PE. Our study included 416 medico-legal cases. All of them underwent MPMCTA, conventional autopsy and histological examination. We selected cases presenting arterial luminal filling defects in the pulmonary arteries. Their radiological interpretation was confronted to the one of autopsy and histological examination. We also investigated an eventual correlation between artefacts in pulmonary arteries and those in other parts of the vascular system. In 123 cases, filling defects of pulmonary arteries were described during MPMCTA. In 57 cases, this was interpreted as artefact and in 4 cases as suspected PE. In 62 cases only a differential diagnosis was made. Autopsy and histology could clearly identify the artefacts as such. Only one case of real PE was radiologically misinterpreted as artefact. In 6 of the 62 cases with no interpretation a PE was diagnosed. In 3 out of 4 suspected cases, PE was confirmed. We found out that filling defects in pulmonary arteries are nearly always associated to other vascular artefacts. Therefore, we suggest following some rules for radiological interpretation in order to allow a reliable diagnosis of pulmonary embolism after MPMCTA.

Optimizing the supply chain strategy of a multi-unit Finnish nursery company

Abstract

Prediction of cross-recognition of peptide-HLA A2 by Melan-A-specific cytotoxic T lymphocytes using three-dimensional quantitative structure-activity relationships.

The cross-recognition of peptides by cytotoxic T lymphocytes is a key element in immunology and in particular in peptide based immunotherapy. Here we develop three-dimensional (3D) quantitative structure-activity relationships (QSARs) to predict cross-recognition by Melan-A-specific cytotoxic T lymphocytes of peptides bound to HLA A*0201 (hereafter referred to as HLA A2). First, we predict the structure of a set of self- and pathogen-derived peptides bound to HLA A2 using a previously developed ab initio structure prediction approach [Fagerberg et al., J. Mol. Biol., 521-46 (2006)]. Second, shape and electrostatic energy calculations are performed on a 3D grid to produce similarity matrices which are combined with a genetic neural network method [So et al., J. Med. Chem., 4347-59 (1997)] to generate 3D-QSAR models. The models are extensively validated using several different approaches. During the model generation, the leave-one-out cross-validated correlation coefficient (q (2)) is used as the fitness criterion and all obtained models are evaluated based on their q (2) values. Moreover, the best model obtained for a partitioned data set is evaluated by its correlation coefficient (r = 0.92 for the external test set). The physical relevance of all models is tested using a functional dependence analysis and the robustness of the models obtained for the entire data set is confirmed using y-randomization. Finally, the validated models are tested for their utility in the setting of rational peptide design: their ability to discriminate between peptides that only contain side chain substitutions in a single secondary anchor position is evaluated. In addition, the predicted cross-recognition of the mono-substituted peptides is confirmed experimentally in chromium-release assays. These results underline the utility of 3D-QSARs in peptide mimetic design and suggest that the properties of the unbound epitope are sufficient to capture most of the information to determine the cross-recognition.

Cytolytic T lymphocyte recognition of the murine cytomegalovirus nonstructural immediate-early protein pp89 expressed by recombinant vaccinia virus.

The murine immediate-early (IE) protein pp89 is a nonstructural virus-encoded phosphoprotein residing in the nucleus of infected cells, where it acts as transcriptional activator. Frequency analysis has shown that in BALB/c mice the majority of virus-specific CTL recognize IE antigens. The present study was performed to assess whether pp89 causes membrane antigen expression detected by IE-specific CTL. Site-directed mutagenesis has been used to delete the introns from gene ieI, encoding pp89, for subsequent integration of the continuous coding sequence into the vaccinia virus genome. After infection with the vaccinia recombinant, the authentic pp89 was expressed in cells that became susceptible to lysis by an IE-specific CTL clone. Priming of mice with the vaccinia recombinant sensitized polyclonal CTL that recognized MCMV-infected cells and transfected cells expressing pp89. Thus, a herpesviral IE polypeptide with essential function in viral transcriptional regulation can also serve as a dominant antigen for the specific CTL response of the host.

Recognition of major histoincompatibilities after transplantation with marrow from HLA closely matched donors.

BACKGROUND: To determine the extent to which major histoincompatibilities are recognized after bone marrow transplantation, we characterized the specificity of the cytotoxic T lymphocytes isolated during graft-versus-host disease. We studied three patients transplanted with marrow from donors who were histoincompatible for different types of HLA antigens. METHODS: Patient 1 was mismatched for one "ABDR-antigen" (HLA-A2 versus A3). Two patients were mismatched for antigens that would usually not be taken into account by standard selection procedures: patient 2 was mismatched for an "HLA-A subtype" (A*0213 versus A*0201), whereas patient 3 was mismatched for HLA-C (HLA-C*0501 versus HLA-C*0701). All three HLA class I mismatches were detected by a pretransplant cytotoxic precursor test. RESULTS: Analysis of the specificity of the cytotoxic T lymphocyte clones isolated after transplantation showed that the incompatibilities detected by the pretransplant cytotoxic precursor assay were the targets recognized during graft-versus-host disease. CONCLUSIONS: Independent of whether the incompatibility consisted of a "full" mismatch, a "subtype" mismatch, or an HLA-C mismatch, all clones recognized the incompatible HLA molecule. In addition, some of these clones had undergone antigen selection and were clearly of higher specificity than the ones established before transplantation, indicating that they had been participating directly in the antihost immune response.

Multi-Purpose ESS/ITS Data Collection Sites, SPR72-00-0003-042, 2014

This document presents the results of a state-of-practice survey of transportation agencies that are installing intelligent transportation sensors (ITS) and other devices along with their environmental sensing stations (ESS) also referred to as roadway weather information system (RWIS) assets.

A Multi-SNP Locus-Association Method Reveals a Substantial Fraction of the Missing Heritability.

There are many known examples of multiple semi-independent associations at individual loci; such associations might arise either because of true allelic heterogeneity or because of imperfect tagging of an unobserved causal variant. This phenomenon is of great importance in monogenic traits but has not yet been systematically investigated and quantified in complex-trait genome-wide association studies (GWASs). Here, we describe a multi-SNP association method that estimates the effect of loci harboring multiple association signals by using GWAS summary statistics. Applying the method to a large anthropometric GWAS meta-analysis (from the Genetic Investigation of Anthropometric Traits consortium study), we show that for height, body mass index (BMI), and waist-to-hip ratio (WHR), 3%, 2%, and 1%, respectively, of additional phenotypic variance can be explained on top of the previously reported 10% (height), 1.5% (BMI), and 1% (WHR). The method also permitted a substantial increase (by up to 50%) in the number of loci that replicate in a discovery-validation design. Specifically, we identified 74 loci at which the multi-SNP, a linear combination of SNPs, explains significantly more variance than does the best individual SNP. A detailed analysis of multi-SNPs shows that most of the additional variability explained is derived from SNPs that are not in linkage disequilibrium with the lead SNP, suggesting a major contribution of allelic heterogeneity to the missing heritability.

Low TCR avidity and lack of tumor cell recognition in CD8(+) T cells primed with the CEA-analogue CAP1-6D peptide.

The use of "altered peptide ligands" (APL), epitopes designed for exerting increased immunogenicity as compared with native determinants, represents nowadays one of the most utilized strategies for overcoming immune tolerance to self-antigens and boosting anti-tumor T cell-mediated immune responses. However, the actual ability of APL-primed T cells to cross-recognize natural epitopes expressed by tumor cells remains a crucial concern. In the present study, we show that CAP1-6D, a superagonist analogue of a carcinoembriyonic antigen (CEA)-derived HLA-A*0201-restricted epitope widely used in clinical setting, reproducibly promotes the generation of low-affinity CD8(+) T cells lacking the ability to recognized CEA-expressing colorectal carcinoma (CRC) cells. Short-term T cell cultures, obtained by priming peripheral blood mononuclear cells from HLA-A*0201(+) healthy donors or CRC patients with CAP1-6D, were indeed found to heterogeneously cross-react with saturating concentrations of the native peptide CAP1, but to fail constantly lysing or recognizing through IFN- gamma release CEA(+)CRC cells. Characterization of anti-CAP1-6D T cell avidity, gained through peptide titration, CD8-dependency assay, and staining with mutated tetramers (D227K/T228A), revealed that anti-CAP1-6D T cells exerted a differential interaction with the two CEA epitopes, i.e., displaying high affinity/CD8-independency toward the APL and low affinity/CD8-dependency toward the native CAP1 peptide. Our data demonstrate that the efficient detection of self-antigen expressed by tumors could be a feature of high avidity CD8-independent T cells, and underline the need for extensive analysis of tumor cross-recognition prior to any clinical usage of APL as anti-cancer vaccines.

Intraoperative adverse events during laparoscopic colorectal resection-better laparoscopic treatment but unchanged incidence. Lessons learnt from a Swiss multi-institutional analysis of 3,928 patients.

PURPOSE: Intraoperative adverse events significantly influence morbidity and mortality of laparoscopic colorectal resections. Over an 11-year period, the changes of occurrence of such intraoperative adverse events were assessed in this study. METHODS: Analysis of 3,928 patients undergoing elective laparoscopic colorectal resection based on the prospective database of the Swiss Association of Laparoscopic and Thoracoscopic Surgery was performed. RESULTS: Overall, 377 intraoperative adverse events occurred in 329 patients (overall incidence of 8.4 %). Of 377 events, 163 (43 %) were surgical complications and 214 (57 %) were nonsurgical adverse events. Surgical complications were iatrogenic injury to solid organs (n = 63; incidence of 1.6 %), bleeding (n = 62; 1.6 %), lesion by puncture (n = 25; 0.6 %), and intraoperative anastomotic leakage (n = 13; 0.3 %). Of note, 11 % of intraoperative organ/puncture lesions requiring re-intervention were missed intraoperatively. Nonsurgical adverse events were problems with equipment (n = 127; 3.2 %), anesthetic problems (n = 30; 0.8 %), and various (n = 57; 1.5 %). Over time, the rate of intraoperative adverse events decreased, but not significantly. Bleeding complications significantly decreased (p = 0.015), and equipment problems increased (p = 0.036). However, the rate of adverse events requiring conversion significantly decreased with time (p < 0.001). Patients with an intraoperative adverse event had a significantly higher rate of postoperative local and general morbidity (41.2 and 32.9 % vs. 18.0 and 17.2 %, p < 0.001 and p < 0.001, respectively). CONCLUSIONS: Intraoperative surgical complications and adverse events in laparoscopic colorectal resections did not change significantly over time and are associated with an increased postoperative morbidity.

The QUASAR reproducibility study, Part II: Results from a multi-center Arterial Spin Labeling test-retest study.

Arterial Spin Labeling (ASL) is a method to measure perfusion using magnetically labeled blood water as an endogenous tracer. Being fully non-invasive, this technique is attractive for longitudinal studies of cerebral blood flow in healthy and diseased individuals, or as a surrogate marker of metabolism. So far, ASL has been restricted mostly to specialist centers due to a generally low SNR of the method and potential issues with user-dependent analysis needed to obtain quantitative measurement of cerebral blood flow (CBF). Here, we evaluated a particular implementation of ASL (called Quantitative STAR labeling of Arterial Regions or QUASAR), a method providing user independent quantification of CBF in a large test-retest study across sites from around the world, dubbed "The QUASAR reproducibility study". Altogether, 28 sites located in Asia, Europe and North America participated and a total of 284 healthy volunteers were scanned. Minimal operator dependence was assured by using an automatic planning tool and its accuracy and potential usefulness in multi-center trials was evaluated as well. Accurate repositioning between sessions was achieved with the automatic planning tool showing mean displacements of 1.87+/-0.95 mm and rotations of 1.56+/-0.66 degrees . Mean gray matter CBF was 47.4+/-7.5 [ml/100 g/min] with a between-subject standard variation SD(b)=5.5 [ml/100 g/min] and a within-subject standard deviation SD(w)=4.7 [ml/100 g/min]. The corresponding repeatability was 13.0 [ml/100 g/min] and was found to be within the range of previous studies.

Maximum likelihood Linear Programming Data Fusion for Speaker Recognition

Biometric system performance can be improved by means of data fusion. Several kinds of information can be fused in order to obtain a more accurate classification (identification or verification) of an input sample. In this paper we present a method for computing the weights in a weighted sum fusion for score combinations, by means of a likelihood model. The maximum likelihood estimation is set as a linear programming problem. The scores are derived from a GMM classifier working on a different feature extractor. Our experimental results assesed the robustness of the system in front a changes on time (different sessions) and robustness in front a change of microphone. The improvements obtained were significantly better (error bars of two standard deviations) than a uniform weighted sum or a uniform weighted product or the best single classifier. The proposed method scales computationaly with the number of scores to be fussioned as the simplex method for linear programming.