IL-6 activated integrated BATF/IRF4 functions in lymphocytes are T-bet-independent and reversed by subcutaneous immunotherapy.

IL-6 plays a central role in supporting pathological TH2 and TH17 cell development and inhibiting the protective T regulatory cells in allergic asthma. TH17 cells have been demonstrated to regulate allergic asthma in general and T-bet-deficiency-induced asthma in particular. Here we found an inverse correlation between T-bet and Il-6 mRNA expression in asthmatic children. Moreover, experimental subcutaneous immunotherapy (SIT) in T-bet((-/-)) mice inhibited IL-6, IL-21R and lung TH17 cells in a setting of asthma. Finally, local delivery of an anti-IL-6R antibody in T-bet((-/-)) mice resulted in the resolution of this allergic trait. Noteworthy, BATF, crucial for the immunoglobulin-class-switch and TH2,TH17 development, was found down-regulated in the lungs of T-bet((-/-)) mice after SIT and after treatment with anti-IL-6R antibody, indicating a critical role of IL-6 in controlling BATF/IRF4 integrated functions in TH2, TH17 cells and B cells also in a T-bet independent fashion in allergic asthma

Prophylaxis of infectious complications with colony-stimulating factors in adult cancer patients undergoing chemotherapy—evidence-based guidelines from the Infectious Diseases Working Party AGIHO of the German Society for Haematology and Medical Oncology (DGHO)

We found convincing evidence from numerous randomised controlled trials that G-CSF, biosimilar G-CSF and pegfilgrastim reduce the risk to develop febrile neutropenia and infections. As a rule of thumb, it seems the relative benefit is highest for patients with an intermediate risk of infections. Compared to other guidelines, we rated the evidence for growth factors during AML induction chemotherapy and pegfilgrastim use in haematological malignancies lowe

Evolutionary stasis of the pseudoautosomal boundary in strepsirrhine primates

Sex chromosomes are typically comprised of a non-recombining region and a recombining pseudoautosomal region. Accurately quantifying the relative size of these regions is critical for sex-chromosome biology both from a functional and evolutionary perspective. The evolution of the pseudoautosomal boundary (PAB) is well documented in haplorrhines (apes and monkeys) but not in strepsirrhines (lemurs and lorises). Here, we studied the PAB of seven species representing the main strepsirrhine lineages by sequencing a male and a female genome in each species and using sex differences in coverage to identify the PAB. We found that during primate evolution, the PAB has remained unchanged in strepsirrhines whereas several recombination suppression events moved the PAB and shortened the pseudoautosomal region in haplorrhines. Strepsirrhines are well known to have much lower sexual dimorphism than haplorrhines. We suggest that mutations with antagonistic effects between males and females have driven recombination suppression and PAB evolution in haplorrhines

Identifying frequency decorrelated dust residuals in B-mode maps by exploiting the spectral capability of bolometric interferometry

Astrophysical polarized foregrounds represent the most critical challenge in Cosmic Microwave Background (CMB) B-mode experiments. Multi-frequency observations can be used to constrain astrophysical foregrounds to isolate the CMB contribution. However, recent observations indicate that foreground emission may be more complex than anticipated. We investigate how the increased spectral resolution provided by band splitting in Bolometric Interferometry (BI) through a technique called spectral imaging can help control the foreground contamination in the case of unaccounted Galactic dust frequency decorrelation along the line-of-sight. We focus on the next generation ground-based CMB experiment CMB-S4, and compare its anticipated sensitivities, frequency and sky coverage with a hypothetical version of the same experiment based on BI. We perform a Monte-Carlo analysis based on parametric component separation methods (FGBuster and Commander) and compute the likelihood on the recovered tensor-to-scalar ratio. The main result of this analysis is that spectral imaging allows us to detect systematic uncertainties on r from frequency decorrelation when this effect is not accounted for in component separation. Conversely, an imager would detect a biased value of r and would be unable to spot the presence of a systematic effect. We find a similar result in the reconstruction of the dust spectral index, where we show that with BI we can measure more precisely the dust spectral index also when frequency decorrelation is present. The in-band frequency resolution provided by BI allows us to identify dust LOS frequency decorrelation residuals where an imager of similar performance would fail. This opens the prospect to exploit this potential in the context of future CMB polarization experiments that will be challenged by complex foregrounds in their quest for B-modes detection.Comment: 13 Pages, 15 figures, 4 tables. Submitted to A&

Travelling in time with networks: revealing present day hybridization versus ancestral polymorphism between two species of brown algae, Fucus vesiculosus and F. spiralis

Background: Hybridization or divergence between sympatric sister species provides a natural laboratory to study speciation processes. The shared polymorphism in sister species may either be ancestral or derive from hybridization, and the accuracy of analytic methods used thus far to derive convincing evidence for the occurrence of present day hybridization is largely debated. Results: Here we propose the application of network analysis to test for the occurrence of present day hybridization between the two species of brown algae Fucus spiralis and F. vesiculosus. Individual-centered networks were analyzed on the basis of microsatellite genotypes from North Africa to the Pacific American coast, through the North Atlantic. Two genetic distances integrating different time steps were used, the Rozenfeld (RD; based on alleles divergence) and the Shared Allele (SAD; based on alleles identity) distances. A diagnostic level of genotype divergence and clustering of individuals from each species was obtained through RD while screening for exchanges through putative hybridization was facilitated using SAD. Intermediate individuals linking both clusters on the RD network were those sampled at the limits of the sympatric zone in Northwest Iberia. Conclusion: These results suggesting rare hybridization were confirmed by simulation of hybrids and F2 with directed backcrosses. Comparison with the Bayesian method STRUCTURE confirmed the usefulness of both approaches and emphasized the reliability of network analysis to unravel and study hybridization

Fully Bayesian tests of neutrality using genealogical summary statistics

<p>Abstract</p> <p>Background</p> <p>Many data summary statistics have been developed to detect departures from neutral expectations of evolutionary models. However questions about the neutrality of the evolution of genetic loci within natural populations remain difficult to assess. One critical cause of this difficulty is that most methods for testing neutrality make simplifying assumptions simultaneously about the mutational model and the population size model. Consequentially, rejecting the null hypothesis of neutrality under these methods could result from violations of either or both assumptions, making interpretation troublesome.</p> <p>Results</p> <p>Here we harness posterior predictive simulation to exploit summary statistics of both the data and model parameters to test the goodness-of-fit of standard models of evolution. We apply the method to test the selective neutrality of molecular evolution in non-recombining gene genealogies and we demonstrate the utility of our method on four real data sets, identifying significant departures of neutrality in human influenza A virus, even after controlling for variation in population size.</p> <p>Conclusion</p> <p>Importantly, by employing a full model-based Bayesian analysis, our method separates the effects of demography from the effects of selection. The method also allows multiple summary statistics to be used in concert, thus potentially increasing sensitivity. Furthermore, our method remains useful in situations where analytical expectations and variances of summary statistics are not available. This aspect has great potential for the analysis of temporally spaced data, an expanding area previously ignored for limited availability of theory and methods.</p

QUBIC instrument for CMB polarization measurements

Measurements of cosmic microwave background (CMB) polarization may reveal the presence of a background of gravitational waves produced during cosmic inflation, providing thus a test of inflationary models. The Q&U Bolometric Interferometer for Cosmology (QUBIC) is an experiment designed to measure the CMB polarization. It is based on the novel concept of bolometric interferometry, which combines the sensitivity of bolometric detectors with the properties of beam synthesis and control of calibration offered by interferometers. To modulate and extract the input polarized signal of the CMB, QUBIC exploits Stokes polarimetry based on a rotating half-wave plate (HWP). In this work, we illustrate the design of the QUBIC instrument, focusing on the polarization modulation system, and we present preliminary results of beam calibrations and the performance of the HWP rotator at 300 K