FOXP3 interacts with hnRNPF to modulate pre-mRNA alternative splicing

FOXP3 promotes the development and function of regulatory T cells mainly through regulating the transcription of target genes. RNA alternative splicing has been implicated in a wide range of physiological and pathophysiological processes. We report here that FOXP3 associates with heterogeneous nuclear ribonucleoprotein (hnRNP) F through the exon 2-encoded region of FOXP3 and the second quasi-RNA recognition motif (qRRM) of hnRNPF. FOXP3 represses the ability of hnRNPF to bind to its target pre-mRNA and thus modulates RNA alternative splicing. Furthermore, overexpression of mouse hnRNPF in in vitro-differentiated regulatory T cells (Tregs) reduced their suppressive function. Thus, our studies identify a novel mechanism by which FOXP3 regulates mRNA alternative splicing to modulate the function of regulatory T cells

A New Itch to Scratch for TSLP

Atopic dermatitis (AD) is characterized by allergic inflammation and itch. Thymic stromal lymphopoietin (TSLP) is a pro-allergic cytokine implicated in AD. A paper in Cell transforms the understanding of TSLP’s functional repertoire in general and in AD in particular showing that TSLP can directly stimulate sensory neurons and provoke itch

Chance, long tails, and inference: a non-Gaussian, Bayesian theory of vocal learning in songbirds

Traditional theories of sensorimotor learning posit that animals use sensory error signals to find the optimal motor command in the face of Gaussian sensory and motor noise. However, most such theories cannot explain common behavioral observations, for example that smaller sensory errors are more readily corrected than larger errors and that large abrupt (but not gradually introduced) errors lead to weak learning. Here we propose a new theory of sensorimotor learning that explains these observations. The theory posits that the animal learns an entire probability distribution of motor commands rather than trying to arrive at a single optimal command, and that learning arises via Bayesian inference when new sensory information becomes available. We test this theory using data from a songbird, the Bengalese finch, that is adapting the pitch (fundamental frequency) of its song following perturbations of auditory feedback using miniature headphones. We observe the distribution of the sung pitches to have long, non-Gaussian tails, which, within our theory, explains the observed dynamics of learning. Further, the theory makes surprising predictions about the dynamics of the shape of the pitch distribution, which we confirm experimentally

IL-9 by INFERence

Despite discovery of the cytokine over 20 years ago, the relevant biological sources of IL-9 have remained a mystery. In this issue of Immunity, Licona-Limón et al. (2013) use a newly generated reporter mouse to demonstrate a role for IL-9-secreting T cells in helminthic parasite immunity

‘Relax and Repair’ to restrain aging

The maintenance of genomic integrity requires the precise identification and repair of DNA damage. Since DNA is packaged and condensed into higher order chromatin, the events associated with DNA damage recognition and repair are orchestrated within the layers of chromatin. Very similar to transcription, during DNA repair, chromatin remodelling events and histone modifications act in concert to ‘open’ and relax chromatin structure so that repair proteins can gain access to DNA damage sites. One such histone mark critical for maintaining chromatin structure is acetylated lysine 16 of histone H4 (AcH4K16), a modification that can disrupt higher order chromatin organization and convert it into a more ‘relaxed’ configuration. We have recently shown that impaired H4K16 acetylation delays the accumulation of repair proteins to double strand break (DSB) sites which results in defective genome maintenance and accelerated aging in a laminopathy-based premature aging mouse model. These results support the idea that epigenetic factors may directly contribute to genomic instability and aging by regulating the efficiency of DSB repair. In this article, the interplay between epigenetic misregulation, defective DNA repair and aging is discussed

Characteristics of multiple‐year nitrous oxide emissions from conventional vegetable fields in southeastern China

The annual and interannual characteristics of nitrous oxide (N2O) emissions from conventional vegetable fields are poorly understood. We carried out 4 year measurements of N2O fluxes from a conventional vegetable cultivation area in the Yangtze River delta. Under fertilized conditions subject to farming practices, approximately 86% of the annual total N2O release occurred following fertilization events. The direct emission factors (EFd) of the 12 individual vegetable seasons investigated ranged from 0.06 to 14.20%, with a mean of 3.09% and a coefficient of variation (CV) of 142%. The annual EFd varied from 0.59 to 4.98%, with a mean of 2.88% and an interannual CV of 74%. The mean value is much larger than the latest default value (1.00%) of the Intergovernmental Panel on Climate Change. Occasional application of lagoon‐stored manure slurry coupled with other nitrogen fertilizers, or basal nitrogen addition immediately followed by heavy rainfall, accounted for a substantial portion of the large EFds observed in warm seasons. The large CVs suggest that the emission factors obtained from short‐term observations that poorly represent seasonality and/or interannual variability will inevitably yield large uncertainties in inventory estimation. The results of this study indicate that conventional vegetable fields associated with intensive nitrogen addition, as well as occasional applications of manure slurry, may substantially account for regional N2O emissions. However, this conclusion needs to be further confirmed through studies at multiple field sites. Moreover, further experimental studies are needed to test the mitigation options suggested by this study for N2O emissions from open vegetable fields