Uncertainty in the mating strategy of honeybees causes bias and unreliability in the estimates of genetic parameters.

BACKGROUND: Breeding queens may be mated with drones that are produced by a single drone-producing queen (DPQ), or a group of sister-DPQs, but often only the dam of the DPQ(s) is reported in the pedigree. Furthermore, datasets may include colony phenotypes from DPQs that were open-mated at different locations, and thus to a heterogeneous drone population. METHODS: Simulation was used to investigate the impact of the mating strategy and its modelling on the estimates of genetic parameters and genetic trends when the DPQs are treated in different ways in the statistical evaluation model. We quantified the bias and standard error of the estimates when breeding queens were mated to one DPQ or a group of DPQs, assuming that this information was known or not. We also investigated four alternative strategies to accommodate the phenotypes of open-mated DPQs in the genetic evaluation: excluding their phenotypes, adding a dummy pseudo-sire in the pedigree, or adding a non-genetic (fixed or random) effect to the statistical evaluation model to account for the origin of the mates. RESULTS: The most precise estimates of genetic parameters and genetic trends were obtained when breeding queens were mated with drones of single DPQs that are correctly assigned in the pedigree. However, when they were mated with drones from one or a group of DPQs, and this information was not known, erroneous assumptions led to considerable bias in these estimates. Furthermore, genetic variances were considerably overestimated when phenotypes of colonies from open-mated DPQs were adjusted for their mates by adding a dummy pseudo-sire in the pedigree for each subpopulation of open-mating drones. On the contrary, correcting for the heterogeneous drone population by adding a non-genetic effect in the evaluation model produced unbiased estimates. CONCLUSIONS: Knowing only the dam of the DPQ(s) used in each mating may lead to erroneous assumptions on how DPQs were used and severely bias the estimates of genetic parameters and trends. Thus, we recommend keeping track of DPQs in the pedigree, and not only of the dams of DPQ(s). Records from DPQ colonies with queens open-mated to a heterogeneous drone population can be integrated by adding non-genetic effects to the statistical evaluation model.

Structure Constants of Short Operators in Planar N=4 Supersymmetric Yang-Mills Theory.

We present a conjecture for the three-point functions of single-trace operators in planar N=4 super-Yang-Mills theory at finite coupling, in the case where two operators are protected. Our proposal is based on the hexagon representation for structure constants of long operators, which we complete to incorporate operators of any length using data from the TBA-QSC formalism. We perform various tests of our conjecture, at weak and strong coupling, finding agreement with the gauge theory through 5 loops for the shortest three-point function and with string theory in the classical limit.

All-Orders Quadratic-Logarithmic Behavior for Amplitudes.

We classify origin limits of maximally helicity violating multigluon scattering amplitudes in planar N=4 super-Yang-Mills theory, where a large number of cross ratios approach zero, with the help of cluster algebras. By analyzing existing perturbative data and bootstrapping new data, we provide evidence that the amplitudes become the exponential of a quadratic polynomial in the large logarithms. With additional input from the thermodynamic Bethe ansatz at strong coupling, we conjecture exact expressions for amplitudes with up to eight gluons in all origin limits. Our expressions are governed by the tilted cusp anomalous dimension evaluated at various values of the tilt angle.

Reconstructing queen genotypes by pool sequencing colonies in eusocial insects: Statistical Methods and their application to honeybee.

Eusocial insects are crucial to many ecosystems, and particularly the honeybee (Apis mellifera). One approach to facilitate their study in molecular genetics, is to consider whole-colony genotyping by combining DNA of multiple individuals in a single pool sequencing experiment. Cheap and fast, this technique comes with the drawback of producing data requiring dedicated methods to be fully exploited. Despite this limitation, pool sequencing data have been shown to be informative and cost-effective when working on random mating populations. Here, we present new statistical methods for exploiting pool sequencing of eusocial colonies in order to reconstruct the genotypes of the queen of such colony. This leverages the possibility to monitor genetic diversity, perform genomic-based studies or implement selective breeding. Using simulations and honeybee real data, we show that the new methods allow for a fast and accurate estimation of the queen's genetic ancestry, with correlations of about 0.9 to that obtained from individual genotyping. Also, it allows for an accurate reconstruction of the queen genotypes, with about 2% genotyping error. We further validate these inferences using experimental data on colonies with both pool sequencing and individual genotyping of drones. In brief, in this study we present statistical models to accurately estimate the genetic ancestry and reconstruct the genotypes of the queen from pool sequencing data from workers of an eusocial colony. Such information allows to exploit pool sequencing for traditional population genetics analyses, association studies and for selective breeding. While validated in Apis mellifera, these methods are applicable to other eusocial hymenopterans.

Complex population structure and haplotype patterns in the Western European honey bee from sequencing a large panel of haploid drones.

Honey bee subspecies originate from specific geographical areas in Africa, Europe and the Middle East, and beekeepers interested in specific phenotypes have imported genetic material to regions outside of the bees' original range for use either in pure lines or controlled crosses. Moreover, imported drones are present in the environment and mate naturally with queens from the local subspecies. The resulting admixture complicates population genetics analyses, and population stratification can be a major problem for association studies. To better understand Western European honey bee populations, we produced a whole genome sequence and single nucleotide polymorphism (SNP) genotype data set from 870 haploid drones and demonstrate its utility for the identification of nine genetic backgrounds and various degrees of admixture in a subset of 629 samples. Five backgrounds identified correspond to subspecies, two to isolated populations on islands and two to managed populations. We also highlight several large haplotype blocks, some of which coincide with the position of centromeres. The largest is 3.6 Mb long and represents 21% of chromosome 11, with two major haplotypes corresponding to the two dominant genetic backgrounds identified. This large naturally phased data set is available as a single vcf file that can now serve as a reference for subsequent populations genomics studies in the honey bee, such as (i) selecting individuals of verified homogeneous genetic backgrounds as references, (ii) imputing genotypes from a lower-density data set generated by an SNP-chip or by low-pass sequencing, or (iii) selecting SNPs compatible with the requirements of genotyping chips.

A simulation study of a honeybee breeding scheme accounting for polyandry, direct and maternal effects on colony performance.

BACKGROUND: Efficient breeding programs are difficult to implement in honeybees due to their biological specificities (polyandry and haplo-diploidy) and complexity of the traits of interest, with performances being measured at the colony scale and resulting from the joint effects of tens of thousands of workers (called direct effects) and of the queen (called maternal effects). We implemented a Monte Carlo simulation program of a breeding plan designed specifically for Apis mellifera's populations to assess the impact of polyandry versus monoandry on colony performance, inbreeding level and genetic gain depending on the individual selection strategy considered, i.e. complete mass selection or within-family (maternal lines) selection. We simulated several scenarios with different parameter setups by varying initial genetic variances and correlations between direct and maternal effects, the selection strategy and the polyandry level. Selection was performed on colony phenotypes. RESULTS: All scenarios showed strong increases in direct breeding values of queens after 20 years of selection. Monoandry led to significantly higher direct than maternal genetic gains, especially when a negative correlation between direct and maternal effects was simulated. However, the relative increase in these genetic gains depended also on their initial genetic variability and on the selection strategy. When polyandry was simulated, the results were very similar with either 8 or 16 drones mated to each queen. Across scenarios, polyandrous mating resulted in equivalent or higher gains in performance than monoandrous mating, but with considerably lower inbreeding rates. Mass selection conferred a ~ 20% increase in performance compared to within-family selection, but was also accompanied by a strong increase in inbreeding levels (25 to 50% higher). CONCLUSIONS: Our study is the first to compare the long-term effects of polyandrous versus monoandrous mating in honeybee breeding. The latter is an emergent strategy to improve specific traits, such as resistance to varroa, which can be difficult or expensive to phenotype. However, if used during several generations in a closed population, monoandrous mating increases the inbreeding level of queens much more than polyandrous mating, which is a strong limitation of this strategy.

To Treat or Not to Treat Bees? Handy VarLoad: A Predictive Model for Varroa destructor Load.

The parasitic Varroa destructor is considered a major pathogenic threat to honey bees and to beekeeping. Without regular treatment against this mite, honey bee colonies can collapse within a 2-3-year period in temperate climates. Beyond this dramatic scenario, Varroa induces reductions in colony performance, which can have significant economic impacts for beekeepers. Unfortunately, until now, it has not been possible to predict the summer Varroa population size from its initial load in early spring. Here, we present models that use the Varroa load observed in the spring to predict the Varroa load one or three months later by using easily and quickly measurable data: phoretic Varroa load and capped brood cell numbers. Built on 1030 commercial colonies located in three regions in the south of France and sampled over a three-year period, these predictive models are tools designed to help professional beekeepers' decision making regarding treatments against Varroa. Using these models, beekeepers will either be able to evaluate the risks and benefits of treating against Varroa or to anticipate the reduction in colony performance due to the mite during the beekeeping season.

Chemical detection triggers honey bee defense against a destructive parasitic threat.

Invasive species events related to globalization are increasing, resulting in parasitic outbreaks. Understanding of host defense mechanisms is needed to predict and mitigate against the consequences of parasite invasion. Using the honey bee Apis mellifera and the mite Varroa destructor, as a host-parasite model, we provide a comprehensive study of a mechanism of parasite detection that triggers a behavioral defense associated with social immunity. Six Varroa-parasitization-specific (VPS) compounds are identified that (1) trigger Varroa-sensitive hygiene (VSH, bees' key defense against Varroa sp.), (2) enable the selective recognition of a parasitized brood and (3) induce responses that mimic intrinsic VSH activity in bee colonies. We also show that individuals engaged in VSH exhibit a unique ability to discriminate VPS compounds from healthy brood signals. These findings enhance our understanding of a critical mechanism of host defense against parasites, and have the potential to apply the integration of pest management in the beekeeping sector.

Evaluation of Suppressed Mite Reproduction (SMR) Reveals Potential for Varroa Resistance in European Honey Bees (Apis mellifera L.).

In the fight against the Varroa destructor mite, selective breeding of honey bee (Apis mellifera L.) populations that are resistant to the parasitic mite stands as a sustainable solution. Selection initiatives indicate that using the suppressed mite reproduction (SMR) trait as a selection criterion is a suitable tool to breed such resistant bee populations. We conducted a large European experiment to evaluate the SMR trait in different populations of honey bees spread over 13 different countries, and representing different honey bee genotypes with their local mite parasites. The first goal was to standardize and validate the SMR evaluation method, and then to compare the SMR trait between the different populations. Simulation results indicate that it is necessary to examine at least 35 single-infested cells to reliably estimate the SMR score of any given colony. Several colonies from our dataset display high SMR scores indicating that this trait is present within the European honey bee populations. The trait is highly variable between colonies and some countries, but no major differences could be identified between countries for a given genotype, or between genotypes in different countries. This study shows the potential to increase selective breeding efforts of V. destructor resistant populations.

Thermodynamic Bethe Ansatz for Biscalar Conformal Field Theories in Any Dimension.

We present the TBA equations for the exact spectrum of multi-magnon local operators in the D-dimensional bi-scalar fishnet CFT. The mixing matrix of such operators is given in terms of fishnet planar graphs of multiwheel and multispiral type. These graphs probe the two key building blocks of the TBA approach, the magnon dispersion relation and scattering matrix, which we obtain by diagonalizing suitable graph-building operators. We also obtain the dual version of the TBA equations, which relates, in the continuum limit, D-dimensional graphs to two-dimensional sigma models in AdS_{D+1}.

Descriptive Analysis of the Varroa Non-Reproduction Trait in Honey Bee Colonies and Association with Other Traits Related to Varroa Resistance.

In the current context of worldwide honey bee colony losses, among which the varroa mite plays a major role, the hope to improve honey bee health lies in part in the breeding of varroa resistant colonies. To do so, methods used to evaluate varroa resistance need better understanding. Repeatability and correlations between traits such as mite non-reproduction (MNR), varroa sensitive hygiene (VSH), and hygienic behavior are poorly known, due to practical limitations and to their underlying complexity. We investigate (i) the variability, (ii) the repeatability of the MNR score, and (iii) its correlation with other resistance traits. To reduce the inherent variability of MNR scores, we propose to apply an empirical Bayes correction. In the short-term (ten days), MNR had a modest repeatability of 0.4, whereas in the long-term (a month), it had a low repeatability of 0.2, similar to other resistance traits. Within our dataset, there was no correlation between MNR and VSH. Although MNR is amongst the most popular varroa resistance estimates in field studies, its underlying complex mechanism is not fully understood. Its lack of correlation with better described resistance traits and low repeatability suggest that MNR needs to be interpreted cautiously, especially when used for selection.

Origin of the Six-Gluon Amplitude in Planar N=4 Supersymmetric Yang-Mills Theory.

We study the maximally-helicity-violating six-gluon scattering amplitude in planar N=4 super-Yang-Mills theory at finite coupling when all three cross ratios are small. It exhibits a double logarithmic scaling in the cross ratios, controlled by a handful of "anomalous dimensions" that are functions of the coupling constant alone. Inspired by known seven-loop results at weak coupling and the integrability-based pentagon operator product expansion, we present conjectures for the all-order resummation of these anomalous dimensions. At strong coupling, our predictions agree perfectly with the string theory analysis. Intriguingly, the simplest of these anomalous dimensions coincides with one describing the lightlike limit of the octagon, namely, the four-point function of large-charge Bogomol'nyi-Prasad-Sommerfield (BPS) operators.

Autosomal and Mitochondrial Adaptation Following Admixture: A Case Study on the Honeybees of Reunion Island.

The honeybee population of the tropical Reunion Island is a genetic admixture of the Apis mellifera unicolor subspecies, originally described in Madagascar, and of European subspecies, mainly A. m. carnica and A. m. ligustica, regularly imported to the island since the late 19th century. We took advantage of this population to study genetic admixing of the tropical-adapted indigenous and temperate-adapted European genetic backgrounds. Whole genome sequencing of 30 workers and 6 males from Reunion, compared with samples from Europe, Madagascar, Mauritius, Rodrigues, and the Seychelles, revealed the Reunion honeybee population to be composed on an average of 53.2 ± 5.9% A. m. unicolor nuclear genomic background, the rest being mainly composed of A. m. carnica and to a lesser extent A. m. ligustica. In striking contrast to this, only 1 out of the 36 honeybees from Reunion had a mitochondrial genome of European origin, suggesting selection has favored the A. m. unicolor mitotype, which is possibly better adapted to the island's bioclimate. Local ancestry was determined along the chromosomes for all Reunion samples, and a test for preferential selection for the A. m. unicolor or European background revealed 15 regions significantly associated with the A. m. unicolor lineage and 9 regions with the European lineage. Our results provide insights into the long-term consequences of introducing exotic specimen on the nuclear and mitochondrial genomes of locally adapted populations.

Gluing Ladder Feynman Diagrams into Fishnets.

We use integrability at weak coupling to compute fishnet diagrams for four-point correlation functions in planar ϕ^{4} theory. The results are always multilinear combinations of ladder integrals, which are in turn built out of classical polylogarithms. The Steinmann relations provide a powerful constraint on such linear combinations, leading to a natural conjecture for any fishnet diagram as the determinant of a matrix of ladder integrals.

Whole-genome resequencing of honeybee drones to detect genomic selection in a population managed for royal jelly.

Four main evolutionary lineages of A. mellifera have been described including eastern Europe (C) and western and northern Europe (M). Many apiculturists prefer bees from the C lineage due to their docility and high productivity. In France, the routine importation of bees from the C lineage has resulted in the widespread admixture of bees from the M lineage. The haplodiploid nature of the honeybee Apis mellifera, and its small genome size, permits affordable and extensive genomics studies. As a pilot study of a larger project to characterise French honeybee populations, we sequenced 60 drones sampled from two commercial populations managed for the production of honey and royal jelly. Results indicate a C lineage origin, whilst mitochondrial analysis suggests two drones originated from the O lineage. Analysis of heterozygous SNPs identified potential copy number variants near to genes encoding odorant binding proteins and several cytochrome P450 genes. Signatures of selection were detected using the hapFLK haplotype-based method, revealing several regions under putative selection for royal jelly production. The framework developed during this study will be applied to a broader sampling regime, allowing the genetic diversity of French honeybees to be characterised in detail.

Influence of grand-mother diet on offspring performances through the male line in Muscovy duck.

BACKGROUND: In mammals, multigenerational environmental effects have been documented by either epidemiological studies in human or animal experiments in rodents. Whether such phenomena also occur in birds for more than one generation is still an open question. The objective of this study was to investigate if a methionine deficiency experienced by a mother (G0) could affect her grand-offspring phenotypes (G2 hybrid mule ducks and G2 purebred Muscovy ducks), through their Muscovy sons (G1). Muscovy drakes are used for the production of mule ducks, which are sterile offspring of female common duck (Anas platyrhynchos) and Muscovy drakes (Cairina moschata). In France, mule ducks are bred mainly for the production of "foie gras", which stems from hepatic steatosis under two weeks of force-feeding (FF). Two groups of female Muscovy ducks received either a methionine deficient diet or a control diet. Their sons were mated to Muscovy or to common duck females to produce Muscovy or Mule ducks, respectively. Several traits were measured in the G2 progenies, concerning growth, feed efficiency during FF, body composition after FF, and quality of foie gras and magret. RESULTS: In the G2 mule duck progeny, grand-maternal methionine deficiency (GMMD) decreased 4, 8, and 12 week body weights but increased weight gain and feed efficiency during FF, and abdominal fat weight. The plasmatic glucose and triglyceride contents at the end of FF were higher in the methionine deficient group. In the G2 purebred Muscovy progeny, GMMD tended to decrease 4 week body weight in both sexes, and decreased weight gain between the ages of 4 and 12 weeks, 12 week body weight, and body weight at the end of FF in male offspring only. GMMD tended to increase liver weight and increased the carcass proportion of liver in both sexes. CONCLUSION: Altogether, these results show that the mother's diet is able to affect traits linked to growth and to lipid metabolism in the offspring of her sons, in Muscovy ducks. Whether this transmission through the father of information induced in the grand-mother by the environment is epigenetic remains to be demonstrated.

Collinear limit of scattering amplitudes at strong coupling.

In this Letter, we consider the collinear limit of gluon scattering amplitudes in planar N=4 super-Yang-Mills theory at strong coupling. We argue that in this limit scattering amplitudes map into correlators of twist fields in the two dimensional nonlinear O(6) sigma model, similar to those appearing in recent studies of entanglement entropy. We provide evidence for this assertion by combining the intuition springing from the string world-sheet picture and the predictions coming from the operator product expansion series. One of the main implications of these considerations is that scattering amplitudes receive equally important contributions at strong coupling from both the minimal string area and its fluctuations in the sphere.

Spacetime and flux tube S-matrices at finite coupling for N=4 supersymmetric Yang-Mills theory.

We propose a nonperturbative formulation of planar scattering amplitudes in N=4 supersymmetric Yang-Mills theory, or, equivalently, polygonal Wilson loops. The construction is based on the operator product expansion approach and introduces a new decomposition of the Wilson loop in terms of fundamental building blocks named pentagon transitions. These transitions satisfy a simple relation to the worldsheet S matrix on top of the so-called Gubser-Klebanov-Polyakov vacuum which allows us to bootstrap them at any value of the coupling. In this Letter we present a subsector of the full solution which we call the gluonic part. We match our results with both weak and strong coupling data available in the literature.

Identification of QTL with effects on intramuscular fat content and fatty acid composition in a Duroc x Large White cross.

BACKGROUND: Improving pork quality can be done by increasing intramuscular fat (IMF) content. This trait is influenced by quantitative trait loci (QTL) sought out in different pig populations. Considering the high IMF content observed in the Duroc pig, it was appealing to determine whether favourable alleles at a major gene or QTL could be found. The detection was performed in an experimental F2 Duroc x Large White population first by segregation analysis, then by QTL mapping using additional molecular information. RESULTS: Segregation analysis provided evidence for a major gene, with a recessive Duroc allele increasing IMF by 1.8% in Duroc homozygous pigs. However, results depended on whether data were normalised or not. After Box-Cox transformation, likelihood ratio was indeed 12 times lower and no longer significant. The QTL detection results were partly consistent with the segregation analysis. Three QTL significant at the chromosome wide level were evidenced. Two QTL, located on chromosomes 13 and 15, showed a high IMF Duroc recessive allele with an overall effect slightly lower than that expected from segregation analysis (+0.4 g/100 g muscle). The third QTL was located on chromosome 1, with a dominant Large White allele inducing high IMF content (+0.5 g/100 g muscle). Additional QTL were detected for muscular fatty acid composition. CONCLUSION: The study presented results from two complementary approaches, a segregation analysis and a QTL detection, to seek out genes involved in the higher IMF content observed in the Duroc population. Discrepancies between both methods might be partially explained by the existence of at least two QTL with similar characteristics located on two different chromosomes for which different boars were heterozygous. The favourable and dominant allele detected in the Large White population was unexpected. Obviously, in both populations, the favourable alleles inducing high IMF content were not fixed and improving IMF by fixing favourable alleles using markers can then be applied both in Duroc and LW populations. With QTL affecting fatty acid composition, combining an increase of IMF content enhancing monounsaturated fatty acid percentage would be of great interest.

Cambios estructurales en la hipertensión arterial: regresión con la terapia; seguimiento a 12 años / Treatment induced regression of structural and functional changes associated with hypertension

Se estudian los cambios órgano-funcionales presentes en hipertensos primarios al ingreso a un Programa de tratamiento y su cambio a través del tiempo en 401 pacientes seguidos desde 1974 por 12 años y que tenían exámenes anuales completos. 216 eran H. y 185, M., edad x : 57+8,8 años (rango 34-71). Seguimiento x : 7,6 años. El avance lesional se definió según criterio OMS, el compromiso retinal según Wagener-Keith-Berger, el cardíaco por Rx (vol. cardíaco) y ECG (criterio HVI según Sokolw), el renal por creatininemia 1,4 mg%, N ureico y protinuria de 24 hrs. Los esquemas terapéuticos más utilizados fueron diuréticos, b-bloqueadores y vasodilatadores, solos o en diversas combinaciones. Los cambios órgano-funcionales se correlacionaron con la cuantía de la reducción de la PA, fijando como límite de normotensión una PA diastólica de pié 99 mmHG como promedio a través de todo el seguimiento. Al ingreso, 192 pac. (48%) estaban en etapa I OMS, 145 (36,6%) en etapa II y 64 (16%) en III. Del total, un 65% de los pac. redujo la PAD 99 mmHg., un 26% lo hizo a niveles entre 100 y 110 y un 9% mantuvo cifras sobre 110 mmHg. Hubo un 14% de abandonos. La HVI al ECG desapareció en un 29%, disminuyó en un 7% y empeoró en un 11%. El FO alterado mejoró en un 22%, se normalizó en un 14% y empeoró en un 1%. Si estaba normal se deterioró en un 9% de los casos. La función renal alterada se normalizó en el 38%, mejoró en el 2% y progresó en el 25% de los casos. Los pac. normotensados mantuvieron el ECG, la radiología y el FO normal con mayor frecuencia estadística que los no normotensados. Se concluye que en un seguimiento a largo plazo, los hipertensos tratados pueden revertir sus cambios parenquimatosos entre 14 y un 38% según el órgano "blanco" considerado