Blimp-1-dependent and -independent natural antibody production by B-1 and B-1-derived plasma cells.

Natural antibodies contribute to tissue homeostasis and protect against infections. They are secreted constitutively without external antigenic stimulation. The differentiation state and regulatory pathways that enable continuous natural antibody production by B-1 cells, the main cellular source in mice, remain incompletely understood. Here we demonstrate that natural IgM-secreting B-1 cells in the spleen and bone marrow are heterogeneous, consisting of (a) terminally differentiated B-1-derived plasma cells expressing the transcriptional regulator of differentiation, Blimp-1, (b) Blimp-1+, and (c) Blimp-1neg phenotypic B-1 cells. Blimp-1neg IgM-secreting B-1 cells are not simply intermediates of cellular differentiation. Instead, they secrete similar amounts of IgM in wild-type and Blimp-1-deficient (PRDM-1ΔEx1A) mice. Blimp-1neg B-1 cells are also a major source of IgG3. Consequently, deletion of Blimp-1 changes neither serum IgG3 levels nor the amount of IgG3 secreted per cell. Thus, the pool of natural antibody-secreting B-1 cells is heterogeneous and contains a distinct subset of cells that do not use Blimp-1 for initiation or maximal antibody secretion

Institutional conditions for integrated mobility services (IMS): Towards a framework for analysis

The present text is a theoretical framework that has been developed with the aim to generate knowledge of and policy recommendations for the promotion of integrated mobility services (IMS), with specific regard to institutional dimensions. Integrated mobility services are services where the passenger’s transport needs are met by a service that not only integrates a range of mobility services, both public and private, but also provides one-stop access to all services through a common interface. These types of services are currently being developed in several cities globally, and the purpose of the project is to understand and explain how institutions can enable, but also impede, their realization. Institutions are defined as a relatively stable collection of rules and practices, embedded in structures that enable action. In the project a broad theoretical approach, developed by an interdisciplinary research team, will be applied. As such, the framework includes factors at the macro, meso and micro levels, thus including extensive societal trends as well as individual\u27s needs and behaviour. The macro level includes broader social and political factors, including both formal rules and more informal social norms and perceptions. The division between formal and informal variables recur on the meso and micro levels respectively. The meso level – which includes both public and private actors at regional and local levels – consists of both formal institutional factors such as taxation and regulations, and informal factors such as organizational culture and inherited networks between regional actors. Each actor enters the collaborative processes that signify IMS with their own ideals, interests and expectations, and it is in these processes of negotiation that the framework takes it point of departure. It is also in this context that business models will be developed, another central aspect of the realisation of IMS. Finally, the framework also includes the micro level, where an individual perspective is placed at centre stage. Individuals are affected by various formal incentives and push factors, as well as more informal aspects such as self-image and social status. Through the application of the framework in a number of case studies, empirical findings will help illuminate which institutional factors enable or constrain the development of IMS. The findings will provide the empirical and analytical foundation for suggestions on how formal and informal rules and practices can be modified to enable new IMS to contribute to sustainable mobility

Fitting and validating the genomic evaluation model to Polish Holstein-Friesian cattle

The aim of the study was to fit the genomic evaluation model to Polish Holstein-Friesian dairy cattle. A training data set for the estimation of additive effects of single nucleotide polymorphisms (SNPs) consisted of 1227 Polish Holstein-Friesian bulls. Genotypes were obtained by the use of Illumina BovineSNP50 Genotyping BeadChip. Altogether 29 traits were considered: milk-, fat- and protein- yields, somatic cell score, four female fertility traits, and 21 traits describing conformation. The prediction of direct genomic values was based on a mixed model containing deregressed national proofs as a dependent variable and random SNP effects as independent variables. The correlations between direct genomic values and conventional estimated breeding values estimated for the whole data set were overall very high and varied between 0.98 for production traits and 0.78 for non return rates for cows. For the validation data set of 232 bulls the corresponding correlations were 0.38 for milk-, 0.37 for protein-, and 0.32 for fat yields, while the correlations between genomic enhanced breeding values and conventional estimated breeding values for the four traits were: 0.43, 0.44, 0.31, and 0.35. This model was able to pass the interbull validation criteria for genomic selection, which indicates that it is realistic to implement genomic selection in Polish Holstein-Friesian cattle

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P < 0.001), age, bisphosphonate use, and rodding (P < 0.05).ConclusionFrom the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves

Comparison of analyses of the QTLMAS XII common dataset. I: Genomic selection

<p>Abstract</p> <p>A dataset was simulated and distributed to participants of the QTLMAS XII workshop who were invited to develop genomic selection models. Each contributing group was asked to describe the model development and validation as well as to submit genomic predictions for three generations of individuals, for which they only knew the genotypes. The organisers used these genomic predictions to perform the final validation by comparison to the true breeding values, which were known only to the organisers. Methods used by the 5 groups fell in 3 classes 1) fixed effects models 2) BLUP models, and 3) Bayesian MCMC based models. The Bayesian analyses gave the highest accuracies, followed by the BLUP models, while the fixed effects models generally had low accuracies and large error variance. The best BLUP models as well as the best Bayesian models gave unbiased predictions. The BLUP models are clearly sensitive to the assumed SNP variance, because they do not estimate SNP variance, but take the specified variance as the true variance. The current comparison suggests that Bayesian analyses on haplotypes or SNPs are the most promising approach for Genomic selection although the BLUP models may provide a computationally attractive alternative with little loss of efficiency. On the other hand fixed effect type models are unlikely to provide any gain over traditional pedigree indexes for selection.</p

Diversity, structure and sources of bacterial communities in earthworm cocoons.

Animals start interactions with the bacteria that will constitute their microbiomes at embryonic stage. After mating, earthworms produce cocoons externally which will be colonized with bacteria from their parents and the environment. Due to the key role bacterial symbionts play on earthworm fitness, it is important to study bacterial colonization during cocoon formation. Here we describe the cocoon microbiome of the earthworms Eisenia andrei and E. fetida, which included 275 and 176 bacterial species, respectively. They were dominated by three vertically-transmitted symbionts, Microbacteriaceae, Verminephrobacter and Ca. Nephrothrix, which accounted for 88% and 66% of the sequences respectively. Verminephrobacter and Ca. Nephrothrix showed a high rate of sequence variation, suggesting that they could be biparentally acquired during mating. The other bacterial species inhabiting the cocoons came from the bedding, where they accounted for a small fraction of the diversity (27% and 7% of bacterial species for E. andrei and E. fetida bedding). Hence, earthworm cocoon microbiome includes a large fraction of the vertically-transmitted symbionts and a minor fraction, but more diverse, horizontally and non-randomly acquired from the environment. These data suggest that horizontally-transmitted bacteria to cocoons may play an important role in the adaptation of earthworms to new environments or diets

Impacts of both reference population size and inclusion of a residual polygenic effect on the accuracy of genomic prediction

<p>Abstract</p> <p>Background</p> <p>The purpose of this work was to study the impact of both the size of genomic reference populations and the inclusion of a residual polygenic effect on dairy cattle genetic evaluations enhanced with genomic information.</p> <p>Methods</p> <p>Direct genomic values were estimated for German Holstein cattle with a genomic BLUP model including a residual polygenic effect. A total of 17,429 genotyped Holstein bulls were evaluated using the phenotypes of 44 traits. The Interbull genomic validation test was implemented to investigate how the inclusion of a residual polygenic effect impacted genomic estimated breeding values.</p> <p>Results</p> <p>As the number of reference bulls increased, both the variance of the estimates of single nucleotide polymorphism effects and the reliability of the direct genomic values of selection candidates increased. Fitting a residual polygenic effect in the model resulted in less biased genome-enhanced breeding values and decreased the correlation between direct genomic values and estimated breeding values of sires in the reference population.</p> <p>Conclusions</p> <p>Genetic evaluation of dairy cattle enhanced with genomic information is highly effective in increasing reliability, as well as using large genomic reference populations. We found that fitting a residual polygenic effect reduced the bias in genome-enhanced breeding values, decreased the correlation between direct genomic values and sire's estimated breeding values and made genome-enhanced breeding values more consistent in mean and variance as is the case for pedigree-based estimated breeding values.</p

The importance of identity-by-state information for the accuracy of genomic selection

<p>Abstract</p> <p>Background</p> <p>It is commonly assumed that prediction of genome-wide breeding values in genomic selection is achieved by capitalizing on linkage disequilibrium between markers and QTL but also on genetic relationships. Here, we investigated the reliability of predicting genome-wide breeding values based on population-wide linkage disequilibrium information, based on identity-by-descent relationships within the known pedigree, and to what extent linkage disequilibrium information improves predictions based on identity-by-descent genomic relationship information.</p> <p>Methods</p> <p>The study was performed on milk, fat, and protein yield, using genotype data on 35 706 SNP and deregressed proofs of 1086 Italian Brown Swiss bulls. Genome-wide breeding values were predicted using a genomic identity-by-state relationship matrix and a genomic identity-by-descent relationship matrix (averaged over all marker loci). The identity-by-descent matrix was calculated by linkage analysis using one to five generations of pedigree data.</p> <p>Results</p> <p>We showed that genome-wide breeding values prediction based only on identity-by-descent genomic relationships within the known pedigree was as or more reliable than that based on identity-by-state, which implicitly also accounts for genomic relationships that occurred before the known pedigree. Furthermore, combining the two matrices did not improve the prediction compared to using identity-by-descent alone. Including different numbers of generations in the pedigree showed that most of the information in genome-wide breeding values prediction comes from animals with known common ancestors less than four generations back in the pedigree.</p> <p>Conclusions</p> <p>Our results show that, in pedigreed breeding populations, the accuracy of genome-wide breeding values obtained by identity-by-descent relationships was not improved by identity-by-state information. Although, in principle, genomic selection based on identity-by-state does not require pedigree data, it does use the available pedigree structure. Our findings may explain why the prediction equations derived for one breed may not predict accurate genome-wide breeding values when applied to other breeds, since family structures differ among breeds.</p

Periodic eclipses of the young star PDS 110 discovered with WASP and KELT photometry

We report the discovery of eclipses by circumstellar disc material associated with the young star PDS 110 in the Ori OB1a association using the SuperWASP and Kilodegree Extremely Little Telescope surveys. PDS 110 (HD 290380, IRAS 05209-0107) is a rare Fe/Ge-type star, an similar to 10 Myr-old accreting intermediate-mass star showing strong infrared excess (L-IR/L-bol similar or equal to 0.25). Two extremely similar eclipses with a depth of 30 per cent and duration similar to 25 d were observed in 2008 November and 2011 January. We interpret the eclipses as caused by the same structure with an orbital period of 808 +/- 2 d. Shearing over a single orbit rules out diffuse dust clumps as the cause, favouring the hypothesis of a companion at similar to 2 au. The characteristics of the eclipses are consistent with transits by an unseen low-mass (1.8-70M(Jup)) planet or brown dwarf with a circumsecondary disc of diameter similar to 0.3 au. The next eclipse event is predicted to take place in 2017 September and could be monitored by amateur and professional observatories across the world