The Developmental Transcriptome of the Mosquito Aedes aegypti, an Invasive Species and Major Arbovirus Vector

Mosquitoes are vectors of a number of important human and animal diseases. The development of novel vector control strategies requires a thorough understanding of mosquito biology. To facilitate this, we used RNA-seq to identify novel genes and provide the first high-resolution view of the transcriptome throughout development and in response to blood feeding in a mosquito vector of human disease, Aedes aegypti, the primary vector for Dengue and yellow fever. We characterized mRNA expression at 34 distinct time points throughout Aedes development, including adult somatic and germline tissues, by using polyA+ RNA-seq. We identify a total of 14,238 novel new transcribed regions corresponding to 12,597 new loci, as well as many novel transcript isoforms of previously annotated genes. Altogether these results increase the annotated fraction of the transcribed genome into long polyA+ RNAs by more than twofold. We also identified a number of patterns of shared gene expression, as well as genes and/or exons expressed sex-specifically or sex-differentially. Expression profiles of small RNAs in ovaries, early embryos, testes, and adult male and female somatic tissues also were determined, resulting in the identification of 38 new Aedes-specific miRNAs, and ~291,000 small RNA new transcribed regions, many of which are likely to be endogenous small-interfering RNAs and Piwi-interacting RNAs. Genes of potential interest for transgene-based vector control strategies also are highlighted. Our data have been incorporated into a user-friendly genome browser located at www.Aedes.caltech.edu, with relevant links to Vectorbase (www.vectorbase.org

Conversion of Danger Signals into Cytokine Signals by Hematopoietic Stem and Progenitor Cells for Regulation of Stress-Induced Hematopoiesis

During an infection, the body increases the output of mature immune cells to fight off the pathogen. Despite convincing evidence that hematopoietic stem and progenitor cells (HSPCs) can sense pathogens directly, how this contributes to hematopoietic cell output remains unknown. Here we have combined mouse models with a single cell proteomics platform to show that in response to toll-like receptor stimulation, short-term HSCs and multipotent progenitor cells produce copious amount of diverse cytokines through the NF-κB signaling. Interestingly, the cytokine production ability of HSPCs trumps mature immune cells in both magnitude and breadth. Among cytokines produced by HSPCs, IL-6 is a particularly important regulator of myeloid differentiation and HSPC proliferation in a paracrine manner and in mediating rapid myeloid cell recovery during neutropenia. This study has uncovered a novel property of HSPCs that enables them to convert danger signals into versatile cytokine signals for regulation of stress hematopoiesis

C. elegans maximum velocity correlates with healthspan and is maintained in worms with an insulin receptor mutation

Ageing is marked by physical decline. Caenorhabditis elegans is a valuable model for identifying genetic regulatory mechanisms of ageing and longevity. Here we report a simple method to assess C. elegans' maximum physical ability based on the worms' maximum movement velocity. We show maximum velocity declines with age, correlates well with longevity, accurately reports movement ability and, if measured in mid-adulthood, is predictive of maximal lifespan. Contrary to recent findings, we observe that maximum velocity of worm with mutations in daf-2(e1370) insulin/IGF-1 signalling scales with lifespan. Because of increased odorant receptor expression, daf-2(e1370) mutants prefer food over exploration, causing previous on-food motility assays to underestimate movement ability and, thus, worm health. Finally, a disease-burden analysis of published data reveals that the daf-2(e1370) mutation improves quality of life, and therefore combines lifespan extension with various signs of an increased healthspan

The cell biology of aging

One of the original hypotheses of organismal longevity posits that aging is the natural result of entropy on the cells, tissues, and organs of the animal—a slow, inexorable slide into nonfunctionality caused by stochastic degradation of its parts. We now have evidence that aging is instead at least in part genetically regulated. Many mutations have been discovered to extend lifespan in organisms of all complexities, from yeast to mammals. The study of metazoan model organisms, such as Caenorhabditis elegans, has been instrumental in understanding the role of genetics in the cell biology of aging. Longevity mutants across the spectrum of model organisms demonstrate that rates of aging are regulated through genetic control of cellular processes. The regulation and subsequent breakdown of cellular processes represent a programmatic decision by the cell to either continue or abandon maintenance procedures with age. Our understanding of cell biological processes involved in regulating aging have been particularly informed by longevity mutants and treatments, such as reduced insulin/IGF-1 signaling and dietary restriction, which are critical in determining the distinction between causes of and responses to aging and have revealed a set of downstream targets that participate in a range of cell biological activities. Here we briefly review some of these important cellular processes