RESEARCH HIGHLIGHTS

inducing this expression program and in the amounts of miR-21* in pericardial heart maintaining these macrophages at this loca- fluid were increased, and intravenous admin- tion, which helped ameliorate inflammation. istration of a miR-21* antagomir reduced Functionally, activation of GATA6 by retinoic heart growth. acid in these macrophages regulated the Although the ‘passenger’ or ‘star’ strand production of IgA by peritoneal B-1 immune of miRNAs precursors is often degraded, the cells. finding that cardiac fibroblast–derived exo- Looking at other downstream effects of somes were enriched in star strands—includ- GATA6, Marcela Rosas and her colleagues ing miR-21*—points to the possibility that found that mice lacking Gata6 had altered star strands might be preferentially involved proliferation of tissue macrophages during in exosome-mediated communication.—MB homeostasis. In a mouse model of acute peritonitis, the absence of this factor inhib- ited recovery of macrophages and resulted in ■ NEURONAL DEVELOPMENT delayed resolution of inflammation. Although Environmental brain the authors did not pinpoint what induces GATA6 in peritoneal macrophages, ex vivo protection cultures confirmed that a local tissue signal The developing fetal brain is exposed to Science Source was needed.—CP many environmental factors, some of which flu-like illness ensues; however, subsequent increase the risk of developing a psychiat- infection with a different subtype can cause a ric or neurological disease later in life. Now, potentially lethal hemorrhagic fever. Despite ■ CARDIAC HYPERTROPHY Kazue Hashimoto-Torii and her colleagues the high incidence of DENV infection, there A miRNA star in the heart report that maternal exposure to some is no approved vaccine and only limited ani- environmental factors activates the stress- mal models to mimic the antibody-depen- MicroRNAs (miRNAs) packaged in microves- responsive transcription factor heat shock dent enhancement (ADE) of infection that icles or exosomes can help cells communi- factor 1 (HSF1) in fetal neurons in mice and is thought to be responsible for the lethal cate with one another. Claudia Bang and humans, which seems to protect the brain dengue fever. A new mouse model of ADE her colleagues now show that this type of from these insults (Neuron 82, 560–572, associated with maternal antibodies may cell-cell interaction occurs between cardiac 2014). help explain the increased susceptibility of fibroblasts and muscle cells in culture and The researchers showed that mater- some infants to severe dengue fever (PLoS may promote pathological heart growth in nal exposure to alcohol, methylmercury or Pathog. 10, e1004031, 2014). mice (J. Clin. Invest. 124, 2136–2146, chemically induced seizures could increase Jowin Kai Wei Ng and colleagues infected 2014). binding of HSF1 to one of its response female mice with a clinical isolate of DENV in the brains of fetal mice. This binding was serotype 1 (DENV1) and infected offspring also enhanced in human fetal brain slices from these mothers with a different serotype, exposed to alcohol. In the absence of HSF1 DENV2, to induce lethal disease. The off- Nature America, Inc. All rights reserved. America, Inc. © 201 4 Nature in fetal mice, normally benign amounts of spring of mothers that developed antibodies these environmental factors promoted abnor- against DENV1 showed more rapid onset of mal neuronal positioning, a reduction in the disease and death at 5 weeks of age com- npg thickness of the cortex, increased cell death pared to DENV2-infected offspring of naive of neural progenitor cells and a brain more mothers. The age at which offspring were prone to seizures. infected with the second DENV serotype In neural progenitor cells that were derived after birth also influenced the course of the from human induced pluripotent stem cells, disease. the authors found that the extent to which The findings suggest that although high these environmental factors could induce maternal antibody levels against DENV1 in HSF1 signaling was more variable in cells newborn mice can cross-neutralize DENV2

Thomas Deerinck, NCMIR / Science Source from patients with schizophrenia compared and slow disease progression, they wane After showing that cultured cardiac fibro- with controls. The findings suggest that vari- with aging of the offspring, and subneutral- blasts release miRNA-containing exosomes, able activation of a stress response system to izing concentrations may no longer block the authors found that one of these miR- environmental factors in developing neurons infection. Instead, these lower amounts of NAs, miR-21*, was transferred specifically could play a role in enhancing disease risk in antibodies can mediate uptake of antibody- into cultured cardiac muscle cells, causing these patients.—EC bound virus by monocytes, and facilitate an increase in their size. The authors then increased viral proliferation in these cells, identified the gene encoding SORBS2 as a leading to enhanced disease.—AF direct miR-21* target in the muscle cells. ■ DENGUE VIRUS SORBS2 and another , PDLIM5, are An enhanced model for good candidates for mediating the effect of miR-21* on cardiac muscle cell size, as defi- dengue virus Written by Michael Basson, Eva Chmielnicki, ciency of either protein led to increased cell Upon initial infection with any of the four Alison Farrell, Randy Levinson, Carolina Pola, size. In mice with pathological heart growth, serotypes of dengue virus (DENV), an acute Kendra Simpson & Hannah Stower

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