Many plants emit significant amounts of isoprene, which is hypothesized to help leaves tolerate short episodes of high temperature. Isoprene emission is found in all major groups of land plants including mosses, ferns, gymnosperms, and angiosperms; however, within these groups isoprene emission is variable. The patchy distribution of isoprene emission implies an evolutionary pattern characterized by many origins or many losses. To better understand the evolution of isoprene emission, we examine the phylogenetic relationships among isoprene synthase and monoterpene synthase genes in the angiosperms. In this study we identify nine new isoprene synthases within the rosid angiosperms. We also document the capacity of a myrcene synthase in Humulus Isoprene emission occurs from the leaves of many but not all plant species. It is produced enzymatically in the chloroplast from dimethylallyl diphosphate (DMADP; Silver and
BackgroundFetal alcohol exposure is a leading cause of preventable birth defects, yet drinking during pregnancy remains prevalent worldwide. Studies suggest that activation of the neuroimmune system plays a role in the effects of alcohol exposure during the rodent equivalent to the third trimester of human pregnancy (i.e., first week of neonatal life), particularly by contributing to neuronal loss. Here, we performed a comprehensive study investigating differences in the neuroimmune response in the cerebellum and hippocampus, which are important targets of third trimester-equivalent alcohol exposure.MethodsTo model heavy, binge-like alcohol exposure during this period, we exposed rats to alcohol vapor inhalation during postnatal days (P)3–5 (blood alcohol concentration = 0.5 g/dL). The cerebellar vermis and hippocampus of rat pups were analyzed for signs of glial cell activation and neuronal loss by immunohistochemistry at different developmental stages. Cytokine production was measured by reverse transcriptase polymerase chain reaction during peak blood alcohol concentration and withdrawal periods. Additionally, adolescent offspring were assessed for alterations in gait and spatial memory.ResultsWe found that this paradigm causes Purkinje cell degeneration in the cerebellar vermis at P6 and P45; however, no signs of neuronal loss were found in the hippocampus. Significant increases in pro-inflammatory cytokines were observed in both brain regions during alcohol withdrawal periods. Although astrocyte activation occurred in both the hippocampus and cerebellar vermis, microglial activation was observed primarily in the latter.ConclusionsThese findings suggest that heavy, binge-like third trimester-equivalent alcohol exposure has time- and brain region-dependent effects on cytokine levels, morphological activation of microglia and astrocytes, and neuronal survival.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-015-0382-9) contains supplementary material, which is available to authorized users.
Although public health campaigns advise pregnant women to abstain from ethanol, drinking during pregnancy is pervasive. Here, we highlight recent studies that have clearly demonstrated long-lasting neurobehavioral deficits in offspring of laboratory animals exposed to moderate levels of ethanol during development. Alterations in learning, memory, motor coordination, social behavior, and stress responses were identified in these animals. Increased vulnerability to substance abuse was also demonstrated. These behavioral alterations have been associated with impairments in neurotransmitter systems, neuromodulators, and/or synaptic plasticity in several brain regions. With this review, we hope to contribute to a better appreciation of the potential effects of developmental exposure to moderate ethanol levels, leading to better interventions aimed at relieving fetal alcohol spectrum disorders.
Pulmonary exposure to multiwalled carbon nanotubes (MWCNTs) causes indirect systemic inflammation through unknown pathways. MWCNTs translocate only minimally from the lungs into the systemic circulation, suggesting that extrapulmonary toxicity may be caused indirectly by lung-derived factors entering the circulation. To assess a role for MWCNT-induced circulating factors in driving neuroinflammatory outcomes, mice were acutely exposed to MWCNTs (10 or 40 μg/mouse) via oropharyngeal aspiration. At 4 h after MWCNT exposure, broad disruption of the blood-brain barrier (BBB) was observed across the capillary bed with the small molecule fluorescein, concomitant with reactive astrocytosis. However, pronounced BBB permeation was noted, with frank albumin leakage around larger vessels (>10 μm), overlain by a dose-dependent astroglial scar-like formation and recruitment of phagocytic microglia. As affirmed by elevated inflammatory marker transcription, MWCNT-induced BBB disruption and neuroinflammation were abrogated by pretreatment with the rho kinase inhibitor fasudil. Serum from MWCNT-exposed mice induced expression of adhesion molecules in primary murine cerebrovascular endothelial cells and, in a wound-healing in vitro assay, impaired cell motility and cytokinesis. Serum thrombospondin-1 level was significantly increased after MWCNT exposure, and mice lacking the endogenous receptor CD36 were protected from the neuroinflammatory and BBB permeability effects of MWCNTs. In conclusion, acute pulmonary exposure to MWCNTs causes neuroinflammatory responses that are dependent on the disruption of BBB integrity.nanoparticle | blood-brain barrier | microglia | thrombospondin-1 | multiwalled carbon nanotube
2-Methyl-3-buten-2-ol (MBO) is a five-carbon alcohol produced and emitted in large quantities by many species of pine native to western North America. MBO is structurally and biosynthetically related to isoprene and can have an important impact on regional atmospheric chemistry. The gene for MBO synthase was identified from Pinus sabiniana, and the protein encoded was functionally characterized. MBO synthase is a bifunctional enzyme that produces both MBO and isoprene in a ratio of ϳ90:1. Divalent cations are required for activity, whereas monovalent cations are not. MBO production is enhanced by K ؉ , whereas isoprene production is inhibited by K ؉ such that, at physiologically relevant [K ؉ ], little or no isoprene emission should be detected from MBO-emitting trees. The K m of MBO synthase for dimethylallyl diphosphate (20 mM) is comparable with that observed for angiosperm isoprene synthases and 3 orders of magnitude higher than that observed for monoterpene and sesquiterpene synthases. Phylogenetic analysis showed that MBO synthase falls into the TPS-d1 group (gymnosperm monoterpene synthases) and is most closely related to linalool synthase from Picea abies. Structural modeling showed that up to three phenylalanine residues restrict the size of the active site and may be responsible for making this a hemiterpene synthase rather than a monoterpene synthase. One of these residues is homologous to a Phe residue found in the active site of isoprene synthases. The remaining two Phe residues do not have homologs in isoprene synthases but occupy the same space as a second Phe residue that closes off the isoprene synthase active site.Hemiterpenes are the smallest members of the isoprenoid family. Two are important in biosphere-atmosphere interactions, isoprene (2-methyl-1,3-butadiene) and an isomer of methylbutenol (2-methyl-3-buten-2-ol (MBO)). 2 Isoprene is given off by trees such as oak and poplar, and averaged over the globe, the amount of isoprene that enters the atmosphere each year is approximately equal to the input of all other hydrocarbons combined (1). MBO is similar to isoprene and is given off by many species of pine trees in western North America (2-4). Isoprene and MBO are made from dimethylallyl diphosphate (DMADP) (5-7).Isoprene emission occurs from a wide range of taxa, including members of the moss, fern, gymnosperm, and angiosperm families (4,8). Two families of isoprene synthase sequences are known from angiosperms (several from Populus species (9 -12) and one from kudzu (9)). Both groups of isoprene synthases closely resemble angiosperm monoterpene synthases in sequence and structure (9, 13). MBO emission has been found only in a subset of the pines (gymnosperms) in North America (2, 4).The plant terpene synthase (TPS) gene family consists of several different subfamilies (14, 15). In angiosperms, monoterpene synthases group together in the TPS-b subfamily and typically have a functional C-terminal ␣-domain and a vestigial N-terminal -domain (13, 15). Isoprene synthases from angiosperms (flo...
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