Zika virus (ZIKV) is a flavivirus that is responsible for an unprecedented current epidemic in Brazil and the Americas(1,2). ZIKV has been causally associated with fetal microcephaly, intrauterine growth restriction, and other birth defects in both humans(3-8) and mice(9-11). The rapid development of a safe and effective ZIKV vaccine is a global health priority(1,2), but very little is currently known about ZIKV immunology and mechanisms of immune protection. Here we show that a single immunization of a plasmid DNA vaccine or a purified inactivated virus vaccine provides complete protection in susceptible mice against challenge with a ZIKV outbreak strain from northeast Brazil. This ZIKV strain has recently been shown to cross the placenta and to induce fetal microcephaly and other congenital malformations in mice(11). We produced DNA vaccines expressing full-length ZIKV pre-membrane and envelope (prM-Env) as well as a series of deletion mutants. The full-length prM-Env DNA vaccine, but not the deletion mutants, afforded complete protection against ZIKV as measured by absence of detectable viremia following challenge, and protective efficacy correlated with Env-specific antibody titers. Adoptive transfer of purified IgG from vaccinated mice conferred passive protection, and CD4 and CD8 T lymphocyte depletion in vaccinated mice did not abrogate protective efficacy. These data demonstrate that protection against ZIKV challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection. Our findings suggest that the development of a ZIKV vaccine for humans will likely be readily achievable.
Two patients presented with loss of vision after viewing a smartphone screen in bed in the dark. The cause appeared to be differential bleaching of photopigment, with one eye becoming light-adapted while the other eye (blocked by a pillow) became dark-adapted.
The aim was to investigate associations between different measures of socioeconomic position (SEP) and incidence of brain tumours (glioma, meningioma and acoustic neuroma) in a nationwide population-based cohort.
Aedes aegypti mosquitoes are responsible for transmitting many medically important viruses such as those that cause Zika and dengue. The inoculation of viruses into mosquito bite sites is an important and common stage of all mosquito-borne virus infections. We show, using Semliki Forest virus and Bunyamwera virus, that these viruses use this inflammatory niche to aid their replication and dissemination in vivo. Mosquito bites were characterized by an edema that retained virus at the inoculation site and an inflammatory influx of neutrophils that coordinated a localized innate immune program that inadvertently facilitated virus infection by encouraging the entry and infection of virus-permissive myeloid cells. Neutrophil depletion and therapeutic blockade of inflammasome activity suppressed inflammation and abrogated the ability of the bite to promote infection. This study identifies facets of mosquito bite inflammation that are important determinants of the subsequent systemic course and clinical outcome of virus infection.
- Proceedings. Biological sciences / The Royal Society
- Published 8 days ago
Selecting the right habitat in a risky landscape is crucial for an individual’s survival and reproduction. In predator-prey systems, prey often can anticipate the habitat use of their main predator and may use protective associates (i.e. typically an apex predator) as shields against predation. Although never tested, such mechanisms should also evolve in systems in which sexual conflict affects offspring survival. Here, we assessed the relationship between offspring survival and habitat selection, as well as the use of protective associates, in a system in which sexually selected infanticide (SSI), rather than interspecific predation, affects offspring survival. We used the Scandinavian brown bear (Ursus arctos) population with SSI in a human-dominated landscape as our model system. Bears, especially adult males, generally avoid humans in our study system. We used resource selection functions to contrast habitat selection of GPS-collared mothers that were successful (i.e. surviving litters, n = 19) and unsuccessful (i.e. complete litter loss, n = 11) in keeping their young during the mating season (2005-2012). Habitat selection was indeed a predictor of litter survival. Successful mothers were more likely to use humans as protective associates, whereas unsuccessful mothers avoided humans. Our results suggest that principles of predator-prey and fear ecology theory (e.g. non-consumptive and cascading effects) can also be applied to the context of sexual conflict.
Peripheral processes that mediate beneficial effects of exercise on the brain remain sparsely explored. Here, we show that a muscle secretory factor, cathepsin B (CTSB) protein, is important for the cognitive and neurogenic benefits of running. Proteomic analysis revealed elevated levels of CTSB in conditioned medium derived from skeletal muscle cell cultures treated with AMP-kinase agonist AICAR. Consistently, running increased CTSB levels in mouse gastrocnemius muscle and plasma. Furthermore, recombinant CTSB application enhanced expression of brain-derived neurotrophic factor (BDNF) and doublecortin (DCX) in adult hippocampal progenitor cells through a mechanism dependent on the multifunctional protein P11. In vivo, in CTSB knockout (KO) mice, running did not enhance adult hippocampal neurogenesis and spatial memory function. Interestingly, in Rhesus monkeys and humans, treadmill exercise elevated CTSB in plasma. In humans, changes in CTSB levels correlated with fitness and hippocampus-dependent memory function. Our findings suggest CTSB as a mediator of effects of exercise on cognition.
Autonomous vehicles (AVs) should reduce traffic accidents, but they will sometimes have to choose between two evils, such as running over pedestrians or sacrificing themselves and their passenger to save the pedestrians. Defining the algorithms that will help AVs make these moral decisions is a formidable challenge. We found that participants in six Amazon Mechanical Turk studies approved of utilitarian AVs (that is, AVs that sacrifice their passengers for the greater good) and would like others to buy them, but they would themselves prefer to ride in AVs that protect their passengers at all costs. The study participants disapprove of enforcing utilitarian regulations for AVs and would be less willing to buy such an AV. Accordingly, regulating for utilitarian algorithms may paradoxically increase casualties by postponing the adoption of a safer technology.
Theories of the formation and early evolution of planetary systems postulate that planets are born in circumstellar disks, and undergo radial migration during and after dissipation of the dust and gas disk from which they formed. The precise ages of meteorites indicate that planetesimals-the building blocks of planets-are produced within the first million years of a star’s life. Fully formed planets are frequently detected on short orbital periods around mature stars. Some theories suggest that the in situ formation of planets close to their host stars is unlikely and that the existence of such planets is therefore evidence of large-scale migration. Other theories posit that planet assembly at small orbital separations may be common. Here we report a newly born, transiting planet orbiting its star with a period of 5.4 days. The planet is 50 per cent larger than Neptune, and its mass is less than 3.6 times that of Jupiter (at 99.7 per cent confidence), with a true mass likely to be similar to that of Neptune. The star is 5-10 million years old and has a tenuous dust disk extending outward from about twice the Earth-Sun separation, in addition to the fully formed planet located at less than one-twentieth of the Earth-Sun separation.
Performance-enhancing substances (PESs) are used commonly by children and adolescents in attempts to improve athletic performance. More recent data reveal that these same substances often are used for appearance-related reasons as well. PESs include both legal over-the-counter dietary supplements and illicit pharmacologic agents. This report reviews the current epidemiology of PES use in the pediatric population, as well as information on those PESs in most common use. Concerns regarding use of legal PESs include high rates of product contamination, correlation with future use of anabolic androgenic steroids, and adverse effects on the focus and experience of youth sports participation. The physical maturation and endogenous hormone production that occur in adolescence are associated with large improvements in strength and athletic performance. For most young athletes, PES use does not produce significant gains over those seen with the onset of puberty and adherence to an appropriate nutrition and training program.
Our knowledge of Cretaceous plumage is limited by the fossil record itself: compression fossils surrounding skeletons lack the finest morphological details and seldom preserve visible traces of colour, while discoveries in amber have been disassociated from their source animals. Here we report the osteology, plumage and pterylosis of two exceptionally preserved theropod wings from Burmese amber, with vestiges of soft tissues. The extremely small size and osteological development of the wings, combined with their digit proportions, strongly suggests that the remains represent precocial hatchlings of enantiornithine birds. These specimens demonstrate that the plumage types associated with modern birds were present within single individuals of Enantiornithes by the Cenomanian (99 million years ago), providing insights into plumage arrangement and microstructure alongside immature skeletal remains. This finding brings new detail to our understanding of infrequently preserved juveniles, including the first concrete examples of follicles, feather tracts and apteria in Cretaceous avialans.