Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β

IL-17-producing CD4+ T helper cells (TH17) have been extensively investigated in mouse models of autoimmunity. However, the requirements for differentiation and the properties of pathogen-induced human TH17 cells remain poorly defined. Using an approach that combines the in vitro priming of naive T cells with the ex vivo analysis of memory T cells, we describe here two types of human TH17 cells with distinct effector function and differentiation requirements. Candida albicans-specific TH17 cells produced IL-17 and IFN-γ, but no IL-10, whereas Staphylococcus aureus-specific TH17 cells produced IL-17 and could produce IL-10 upon restimulation. IL-6, IL-23 and IL-1β contributed to TH17 differentiation induced by both pathogens, but IL-1β was essential in C. albicans-induced TH17 differentiation to counteract the inhibitory activity of IL-12 and to prime IL-17/IFN-γ double-producing cells. In addition, IL-1β inhibited IL-10 production in differentiating and in memory TH17 cells, whereas blockade of IL-1β in vivo led to increased IL-10 production by memory TH17 cells. We also show that, after restimulation, TH17 cells transiently downregulated IL-17 production through a mechanism that involved IL-2-induced activation of STAT5 and decreased expression of ROR-γt. Taken together these findings demonstrate that by eliciting different cytokines C. albicans and S. aureus prime TH17 cells that produce either IFN-γ or IL-10, and identify IL-1β and IL-2 as pro- and anti-inflammatory regulators of TH17 cells both at priming and in the effector phase.     

The Drosophila melanogaster Genetic Reference Panel

A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics.     

Evaluating early warning and coincident indicators of business cycles using smooth trends

We present a composite coincident indicator designed to capture the state of the Spanish economy. Our approach, based on smooth trends, guarantees that the resulting indicators are reasonably smooth and issue stable signals, reducing the uncertainty. The coincident indicator has been checked by comparing it with the one recently proposed by the Spanish Economic Association index. Both indexes show similar behavior and ours captures very well the beginning and end of the official recessions and expansion periods. Our coincident indicator also tracks very well alternative mass media indicators typically used in the political science literature. We also update our composite leading indicator (Bujosa et al., Journal of Forecasting, 2013, 32(6), 481–499). It systematically predicts the peaks and troughs of the new Spanish Economic Association index and provides significant aid in forecasting annual gross domestic product growth rates. Using only real data available at the beginning of each forecast period, our indicator one-step-ahead forecast shows improvements over other individual alternatives and different forecast combinations.     

Circular polarimetry reveals helical magnetic fields in the young stellar object HH 135-136

Magnetic fields are believed to have a vital role in regulating and shaping the flow of material onto and away from protostars during their initial mass accretion phase. It is becoming increasingly accepted that bipolar outflows are generated and collimated as material is driven along magnetic field lines and centrifugally accelerated off a rotating accretion disk. However, the precise role of the magnetic field is poorly understood and evidence for its shape and structure has not been forthcoming. Here we report imaging circular polarimetry in the near-infrared and Monte Carlo modelling showing that the magnetic field along the bipolar outflow of the HH 135-136 young stellar object is helical. The field retains this shape for large distances along the outflow, so the field structure can also provide the necessary magnetic pressure for collimation of the outflow. This result lends further weight to the hypothesis--central to any theory of star formation--that the outflow is an important instrument for the removal of high-angular-momentum material from the accretion disk, thereby allowing the central protostar to increase its mass.     

Delayed ageing through damage protection by the Arf/p53 pathway

The tumour-suppressor pathway formed by the alternative reading frame protein of the Cdkn2a locus (Arf) and by p53 (also called Trp53) plays a central part in the detection and elimination of cellular damage, and this constitutes the basis of its potent cancer protection activity. Similar to cancer, ageing also results from the accumulation of damage and, therefore, we have reasoned that Arf/p53 could have anti-ageing activity by alleviating the load of age-associated damage. Here we show that genetically manipulated mice with increased, but otherwise normally regulated, levels of Arf and p53 present strong cancer resistance and have decreased levels of ageing-associated damage. These observations extend the protective role of Arf/p53 to ageing, revealing a previously unknown anti-ageing mechanism and providing a rationale for the co-evolution of cancer resistance and longevity.     

Range Extension and Channel Capacity Increase in Impulse-Radio Ultra-Wideband Communications

We theoretically analyze the channel capacity of a 5th-order Gaussian pulse-based ultra-wideband (UWB) system and experimentally demonstrate 2 Gbit/s UWB-over-fiber transmission systems incorporating wireless transmission. Both electrical and photonic UWB pulse generation methods are employed and its performance is compared. By utilizing optimum UWB pulse design and employing a digital signal processing (DSP) receiver, a bit-error-rate above the forward error correction (FEC) limit for 8 meters of wireless ...