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BackgroundKiwi, comprising five species from the genus Apteryx, are endangered, ground-dwelling bird species endemic to New Zealand. They are the smallest and only nocturnal representatives of the ratites. The timing of kiwi adaptation to a nocturnal niche and the genomic innovations, which shaped sensory systems and morphology to allow this adaptation, are not yet fully understood.ResultsWe sequenced and assembled the brown kiwi genome to 150-fold coverage and annotated the genome using kiwi transcript data and non-redundant protein information from multiple bird species. We identified evolutionary sequence changes that underlie adaptation to nocturnality and estimated the onset time of these adaptations. Several opsin genes involved in color vision are inactivated in the kiwi. We date this inactivation to the Oligocene epoch, likely after the arrival of the ancestor of modern kiwi in New Zealand. Genome comparisons between kiwi and representatives of ratites, Galloanserae, and Neoaves, including nocturnal and song birds, show diversification of kiwi’s odorant receptors repertoire, which may reflect an increased reliance on olfaction rather than sight during foraging. Further, there is an enrichment of genes influencing mitochondrial function and energy expenditure among genes that are rapidly evolving specifically on the kiwi branch, which may also be linked to its nocturnal lifestyle.ConclusionsThe genomic changes in kiwi vision and olfaction are consistent with changes that are hypothesized to occur during adaptation to nocturnal lifestyle in mammals. The kiwi genome provides a valuable genomic resource for future genome-wide comparative analyses to other extinct and extant diurnal ratites.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0711-4) contains supplementary material, which is available to authorized users.

Background:The relevance of the widely expressed GPCR P2Y 14 is only partially understood. Results: Analysis of P2Y 14 -KO mice revealed decreased gastrointestinal emptying, reduced glucose tolerance, and insulin release. Conclusion: P2Y 14 function is required for proper intestine emptying and adequate glucose response. Significance: P2Y 14 plays a role in smooth muscle function and maintaining energy homeostasis by influencing insulin release.

ARGONAUTE-2 and associated miRNAs form the RNA-induced silencing complex (RISC), which targets mRNAs for translational silencing and degradation as part of the RNA interference pathway. Despite the essential nature of this process for cellular function, there is little information on the role of RISC components in human development and organ function. We identify 13 heterozygous mutations in AGO2 in 21 patients affected by disturbances in neurological development. Each of the identified single amino acid mutations result in impaired shRNA-mediated silencing. We observe either impaired RISC formation or increased binding of AGO2 to mRNA targets as mutation specific functional consequences. The latter is supported by decreased phosphorylation of a C-terminal serine cluster involved in mRNA target release, increased formation of dendritic P-bodies in neurons and global transcriptome alterations in patient-derived primary fibroblasts. Our data emphasize the importance of gene expression regulation through the dynamic AGO2-RNA association for human neuronal development.

GPR34 is a Gi/o protein-coupled receptor (GPCR) of the nucleotide receptor P2Y12 -like group. This receptor is highly expressed in microglia, however, the functional relevance of GPR34 in these glial cells is unknown. Previous results suggested an impaired immune response in GPR34-deficient mice infected with Cryptococcus neoformans. Here we show that GPR34 deficiency results in morphological changes in retinal and cortical microglia. RNA sequencing analysis of microglia revealed a number of differentially expressed transcripts involved in cell motility and phagocytosis. We found no differences in microglial motility after entorhinal cortex lesion and in response to laser lesion. However, GPR34-deficient microglia showed reduced phagocytosis activity in both retina and acutely isolated cortical slices. Our study identifies GPR34 as an important signaling component controlling microglial function, morphology and phagocytosis.

In this population of CL patients displaying variable degrees of complexity and severity, almost two-thirds of patients could be initially managed without systemic therapy. Of these, 60 were cured before day 60. The WHO-recommended stepwise approach favoring initial local therapy therefore resulted in at least 44% of all patients being cured without exposure to the risk of systemic adverse events. Efforts are needed to further simplify local therapy of CL and to improve the management of patients with complex lesions and/or preexisting comorbidities.

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