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Highlights d Ablation of Gclc in Tregs causes autoimmunity and increases anti-tumor responses d Gclc-derived GSH is needed for the suppressive function of Tregs in vitro and in vivo d GSH in Tregs regulates serine concentrations and metabolism. which impact mTOR and FoxP3 d Serine-and glycine-deficient diet rescues mutant mice from lethal inflammation

BackgroundIn Europe, Ixodes ricinus ticks are the most important vectors of diseases threatening humans, livestock, wildlife and companion animals. Nevertheless, genomic sequence information is missing and functional annotation of transcripts and proteins is limited. This lack of information is restricting studies of the vector and its interactions with pathogens and hosts. Here we present and integrate the first analysis of the I. ricinus genome with the transcriptome and proteome of the unfed I. ricinus midgut.MethodsWhole genome sequencing was performed on I. ricinus ticks and the sequences were de novo assembled. In parallel, I. ricinus ticks were dissected and the midgut transcriptome sequenced. Both datasets were integrated by transcript discovery analysis to identify putative genes and genome contigs were screened for homology. An alignment-based and a motif-search-based approach were combined for the annotation of the midgut transcriptome. Additionally, midgut proteins were identified and annotated by mass spectrometry with public databases and the in-house built transcriptome database as references and results were cross-validated.ResultsThe de novo assembly of 1 billion DNA sequences to a reference genome of 393 Mb length provides an unprecedented insight into the I. ricinus genome. A homology search revealed sequences in the assembled genome contigs homologous to 89 % of the I. scapularis genome scaffolds indicating coverage of most genome regions. We identified moreover 6,415 putative genes. More than 10,000 transcripts from naïve midgut were annotated with respect of predicted function and/or cellular localization. By combining an alignment-based with a motif-search-based annotation approach, we doubled the number of annotations throughout all functional categories. In addition, 574 gel spots were significantly identified by mass spectrometry (p < 0.05) and 285 distinct proteins expressed in the naïve midgut were annotated functionally and/or for cellular localization. Our systems approach reveals a midgut metabolism of the unfed tick that is prepared to sense and process an anticipated blood meal.ConclusionsThis multiple-omics study vastly extends the publicly available DNA and RNA databases for I. ricinus, paving the way for further in-depth analysis of the most important European disease vector and its interactions with pathogens and hosts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1981-7) contains supplementary material, which is available to authorized users.

Despite its wide spread and high prevalence in sub-Saharan Africa, hepatitis B virus genotype E (HBV/E) has a surprisingly low genetic diversity, indicating an only recent emergence of this genotype in the general African population. Here, we performed extensive phylogeographic analyses, including Bayesian MCMC modeling. Our results indicate a mutation rate of 1.9×10−4 substitutions per site and year (s/s/y) and confirm a recent emergence of HBV/E, most likely within the last 130 years, and only after the transatlantic slave-trade had come to an end. Our analyses suggest that HBV/E originated from the area of Nigeria, before rapidly spreading throughout sub-Saharan Africa. Interestingly, viral strains found in Haiti seem to be the result of multiple introductions only in the second half of the 20th century, corroborating an absence of a significant number of HBV/E strains in West Africa several centuries ago. Our results confirm that the hyperendemicity of HBV(E) in today's Africa is a recent phenomenon and likely the result of dramatic changes in the routes of viral transmission in a relatively recent past.