Improved timed-mating, non-invasive method using fewer unproven female rats with pregnancy validation via early body mass increases

For studies requiring accurate conception-timing, reliable, efficient methods of detecting oestrus reduce time and costs, whilst improving welfare. Standard methods use vaginal cytology to stage cycle, and breeders are paired–up using approximately five proven females with proven males to achieve at least one conception on a specific day. We describe an alternative, fast, consistent, non-invasive method of timed-mating using detection of lordosis behaviour in Wistar and Lister-Hooded rats that used unproven females with high success rates. Rats under reverse-lighting had body masses recorded pre-mating, day (d) 3-4, d8, d10 and d18 of pregnancy. Using only the presence of the oestrus dance to time-mate females for 24-hrs, 89% Wistar and 88% Lister-Hooded rats successfully conceived. We did not observe behavioural oestrus in Sprague-Dawleys without males present. Significant body mass increases following mating distinguished pregnant from non-pregnant rats, as early as d4 of pregnancy (10% ± 1.0 increase cf 3% ± 1.2). The pattern of increases throughout gestation was similar for all pregnant rats until late pregnancy, when there were smaller increases for primi- and multiparous rats (32% ± 2.5; 25% ± 2.4), whereas nulliparous rats had highest gains (38% ± 1.5). This method demonstrated a distinct refinement of the previous timed-mating common practice used, as disturbance of females was minimised. Only the number required of nulli-, primi- or multiparous rats were mated, and body mass increases validated pregnancy status. This new breeding-management method is now established practice for two strains of rat and resulted in a reduction in animal use

Second trimester inflammatory and metabolic markers in women delivering preterm with and without preeclampsia.

ObjectiveInflammatory and metabolic pathways are implicated in preterm birth and preeclampsia. However, studies rarely compare second trimester inflammatory and metabolic markers between women who deliver preterm with and without preeclampsia.Study designA sample of 129 women (43 with preeclampsia) with preterm delivery was obtained from an existing population-based birth cohort. Banked second trimester serum samples were assayed for 267 inflammatory and metabolic markers. Backwards-stepwise logistic regression models were used to calculate odds ratios.ResultsHigher 5-α-pregnan-3β,20α-diol disulfate, and lower 1-linoleoylglycerophosphoethanolamine and octadecanedioate, predicted increased odds of preeclampsia.ConclusionsAmong women with preterm births, those who developed preeclampsia differed with respect metabolic markers. These findings point to potential etiologic underpinnings for preeclampsia as a precursor to preterm birth

Entomological Surveillance of Behavioural Resilience and Resistance in Residual Malaria Vector Populations.

The most potent malaria vectors rely heavily upon human blood so they are vulnerable to attack with insecticide-treated nets (ITNs) and indoor residual spraying (IRS) within houses. Mosquito taxa that can avoid feeding or resting indoors, or by obtaining blood from animals, mediate a growing proportion of the dwindling transmission that persists as ITNs and IRS are scaled up. Increasing frequency of behavioural evasion traits within persisting residual vector systems usually reflect the successful suppression of the most potent and vulnerable vector taxa by IRS or ITNs, rather than their failure. Many of the commonly observed changes in mosquito behavioural patterns following intervention scale-up may well be explained by modified taxonomic composition and expression of phenotypically plastic behavioural preferences, rather than altered innate preferences of individuals or populations. Detailed review of the contemporary evidence base does not yet provide any clear-cut example of true behavioural resistance and is, therefore, consistent with the hypothesis presented. Caution should be exercised before over-interpreting most existing reports of increased frequency of behavioural traits which enable mosquitoes to evade fatal contact with insecticides: this may simply be the result of suppressing the most behaviourally vulnerable of the vector taxa that constituted the original transmission system. Mosquito taxa which have always exhibited such evasive traits may be more accurately described as behaviourally resilient, rather than resistant. Ongoing national or regional entomological monitoring surveys of physiological susceptibility to insecticides should be supplemented with biologically and epidemiologically meaningfully estimates of malaria vector population dynamics and the behavioural phenotypes that determine intervention impact, in order to design, select, evaluate and optimize the implementation of vector control measures

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution

Genomic hotspots for adaptation: the population genetics of Müllerian mimicry in Heliconius erato

This is the final version of the article. Available from the publisher via the DOI in this record.Wing pattern evolution in Heliconius butterflies provides some of the most striking examples of adaptation by natural selection. The genes controlling pattern variation are classic examples of Mendelian loci of large effect, where allelic variation causes large and discrete phenotypic changes and is responsible for both convergent and highly divergent wing pattern evolution across the genus. We characterize nucleotide variation, genotype-by-phenotype associations, linkage disequilibrium (LD), and candidate gene expression patterns across two unlinked genomic intervals that control yellow and red wing pattern variation among mimetic forms of Heliconius erato. Despite very strong natural selection on color pattern, we see neither a strong reduction in genetic diversity nor evidence for extended LD across either patterning interval. This observation highlights the extent that recombination can erase the signature of selection in natural populations and is consistent with the hypothesis that either the adaptive radiation or the alleles controlling it are quite old. However, across both patterning intervals we identified SNPs clustered in several coding regions that were strongly associated with color pattern phenotype. Interestingly, coding regions with associated SNPs were widely separated, suggesting that color pattern alleles may be composed of multiple functional sites, conforming to previous descriptions of these loci as "supergenes." Examination of gene expression levels of genes flanking these regions in both H. erato and its co-mimic, H. melpomene, implicate a gene with high sequence similarity to a kinesin as playing a key role in modulating pattern and provides convincing evidence for parallel changes in gene regulation across co-mimetic lineages. The complex genetic architecture at these color pattern loci stands in marked contrast to the single casual mutations often identified in genetic studies of adaptation, but may be more indicative of the type of genetic changes responsible for much of the adaptive variation found in natural populations.Funding: Funding for this study was provided by National Science Foundation grants to WOM (DEB-0715096 and IBN-0344705) and BAC (DEB-0513424). Funding for work on H. melpomene came from a BBSRC grant to CDJ and RHf-C (011845). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Search for Heavy Neutral and Charged Leptons in e+ e- Annihilation at LEP

A search for exotic unstable neutral and charged heavy leptons as well as for stable charged heavy leptons is performed with the L3 detector at LEP. Sequential, vector and mirror natures of heavy leptons are considered. No evidence for their existence is found and lower limits on their masses are set

Search for an invisibly decaying Higgs boson in e^+e^- collisions at \sqrt{s} = 183 - 189 GeV

A search for a Higgs boson decaying into invisible particles is performed using the data collected at LEP by the L3 experiment at centre-of-mass energies of 183 GeV and 189 GeV. The integrated luminosities are respectively 55.3 pb^-1 and 176.4 pb^-1. The observed candidates are consistent with the expectations from Standard Model processes. In the hypothesis that the production cross section of this Higgs boson equals the Standard Model one and the branching ratio into invisible particles is 100%, a lower mass limit of 89.2 GeV is set at 95% confidence level

Search for Extra Dimensions in Boson and Fermion Pair Production in e+e- Interactions at LEP

Extra spatial dimensions are proposed by recent theories that postulate the scale of gravity to be of the same order as the electroweak scale. A sizeable interaction between gravitons and Standard Model particles is then predicted. Effects of these new interactions in boson and fermion pair production are searched for in the data sample collected at centre-of-mass energies above the Z pole by the L3 detector at LEP. In addition, the direct production of a graviton associated with a Z boson is investigated. No statistically significant hints for the existence of these effects are found and lower limits in excess of 1 TeV are derived on the scale of this new theory of gravity

Search for a Higgs Boson Decaying to Weak Boson Pairs at LEP

A Higgs particle produced in association with a Z boson and decaying into weak boson pairs is searched for in 336.4 1/pb of data collected by the L3 experiment at LEP at centre-of-mass energies from 200 to 209 GeV. Limits on the branching fraction of the Higgs boson decay into two weak bosons as a function of the Higgs mass are derived. These results are combined with the L3 search for a Higgs boson decaying to photon pairs. A Higgs produced with a Standard Model e+e- --> Zh cross section and decaying only into electroweak boson pairs is excluded at 95% CL for a mass below 107 GeV

Measurement of the Lifetime of the Tau Lepton

The tau lepton lifetime is measured with the L3 detector at LEP using the complete data taken at centre-of-mass energies around the Z pole resulting in tau_tau = 293.2 +/- 2.0 (stat) +/- 1.5 (syst) fs. The comparison of this result with the muon lifetime supports lepton universality of the weak charged current at the level of six per mille. Assuming lepton universality, the value of the strong coupling constant, alpha_s is found to be alpha_s(m_tau^2) = 0.319 +/- 0.015(exp.) +/- 0.014 (theory)