by
Gabriel L. Hamer;
Tavis K. Anderson;
Danielle J. Donovan;
Jeffrey D. Brawn;
Bethany L. Krebs;
Allison M. Gardner;
Marilyn O. Ruiz;
William M. Brown;
Uriel Kitron;
Christina M. Newman;
Tony L. Goldberg;
Edward D. Walker
Dispersal is a critical life history behavior for mosquitoes and is important for the spread of mosquito-borne disease. We implemented the first stable isotope mark-capture study to measure mosquito dispersal, focusing on Culex pipiens in southwest suburban Chicago, Illinois, a hotspot of West Nile virus (WNV) transmission. We enriched nine catch basins in 2010 and 2011 with 15 N-potassium nitrate and detected dispersal of enriched adult females emerging from these catch basins using CDC light and gravid traps to distances as far as 3 km. We detected 12 isotopically enriched pools of mosquitoes out of 2,442 tested during the two years and calculated a mean dispersal distance of 1.15 km and maximum flight range of 2.48 km. According to a logistic distribution function, 90% of the female Culex mosquitoes stayed within 3 km of their larval habitat, which corresponds with the distance-limited genetic variation of WNV observed in this study region. This study provides new insights on the dispersal of the most important vector of WNV in the eastern United States and demonstrates the utility of stable isotope enrichment for studying the biology of mosquitoes in other disease systems.
Gain control of primary afferent neurotransmission at their intraspinal terminals occurs by several mechanisms including primary afferent depolarization (PAD). PAD produces presynaptic inhibition via a reduction in transmitter release. While it is known that descending monoaminergic pathways complexly regulate sensory processing, the extent these actions include modulation of afferent-evoked PAD remains uncertain. We investigated the effects of serotonin (5HT), dopamine (DA) and noradrenaline (NA) on afferent transmission and PAD. Responses were evoked by stimulation of myelinated hindlimb cutaneous and muscle afferents in the isolated neonatal mouse spinal cord. Monosynaptic responses were examined in the deep dorsal horn either as population excitatory synaptic responses (recorded as extracellular field potentials; EFPs) or intracellular excitatory postsynaptic currents (EPSCs). The magnitude of PAD generated intraspinally was estimated from electrotonically back-propagating dorsal root potentials (DRPs) recorded on lumbar dorsal roots. 5HT depressed the DRP by 76%. Monosynaptic actions were similarly depressed by 5HT (EFPs 54%; EPSCs 75%) but with a slower time course. This suggests that depression of monosynaptic EFPs and DRPs occurs by independent mechanisms. DA and NA had similar depressant actions on DRPs but weaker effects on EFPs. IC50 values for DRP depression were 0.6, 0.8 and 1.0 mM for 5HT, DA and NA, respectively. Depression of DRPs by monoamines was nearly-identical in both muscle and cutaneous afferentevoked responses, supporting a global modulation of the multimodal afferents stimulated. 5HT, DA and NA produced no change in the compound antidromic potentials evoked by intraspinal microstimulation indicating that depression of the DRP is unrelated to direct changes in the excitability of intraspinal afferent fibers, but due to metabotropic receptor activation. In summary, both myelinated afferent-evoked DRPs and monosynaptic transmission in the dorsal horn are broadly reduced by descending monoamine transmitters. These actions likely integrate with modulatory actions elsewhere to reconfigure spinal circuits during motor behaviors.
Epigenetics allows for the inheritance of information in cellular lineages during differentiation, independent of changes to the underlying genetic sequence. This raises the question of whether epigenetic mechanisms also function in post-mitotic neurons. During the long life of the neuron, fluctuations in gene expression allow the cell to pass through stages of differentiation, modulate synaptic activity in response to environmental cues, and fortify the cell through age-related neuroprotective pathways. Emerging evidence suggests that epigenetic mechanisms such as DNA methylation and histone modification permit these dynamic changes in gene expression throughout the life of a neuron. Accordingly, recent studies have revealed the vital importance of epigenetic players in the central nervous system and during neurodegeneration. Here, we provide a review of several of these recent findings, highlighting novel functions for epigenetics in the fields of Rett syndrome, Fragile X syndrome, and Alzheimer's disease research. Together, these discoveries underscore the vital importance of epigenetics in human neurological disorders.
Fishes rely on both chemical and tactile senses to orient themselves to avoid predators, and to detect and taste food. This is likely achieved by highly coordinated reception of signals by mechano- and chemosensory receptors in fish. A small co-receptor from zebrafish, receptor activity modifying protein (RAMP)-like triterpene glycoside receptor (RL-TGR), was previously found to be involved in recognition of triterpene glycosides, a family of naturally occurring compounds that act as chemical defenses in various prey species. However, its localization, function, and how it impacts sensory organ development in vivo is not known. Here we show that RL-TGR is expressed in zebrafish in both i) apical microvilli of the chemosensory cells of taste buds including the epithelium of lips and olfactory epithelium, and ii) mechanosensory cells of neuromasts belonging to the lateral line system. Loss-of-function analyses of RL-TGR resulted in significantly decreased number of neuromasts in the posterior lateral line system and decreased body length, suggesting that RL-TGR is involved in deposition and migration of the neuromasts. Collectively, these results provide the first in vivo genetic evidence of sensory cell-specific expression of this unusual co-receptor and reveal its additional role in the lateral line development in zebrafish.
Background
Historically, mosquito control programs successfully helped contain malaria and yellow fever, but recent efforts have been unable to halt the spread of dengue, chikungunya, or Zika, all transmitted by Aedes mosquitoes. Using a dengue transmission model and results from indoor residual spraying (IRS) field experiments, we investigated how IRS-like campaign scenarios could effectively control dengue in an endemic setting.
Methods and findings
In our model, we found that high levels of household coverage (75% treated once per year), applied proactively before the typical dengue season could reduce symptomatic infections by 89.7% (median of 1000 simulations; interquartile range [IQR]:[83.0%, 94.8%]) in year one and 78.2% (IQR: [71.2%, 88.0%]) cumulatively over the first five years of an annual program. Lower coverage had correspondingly lower effectiveness, as did reactive campaigns. Though less effective than preventative campaigns, reactive and even post-epidemic interventions retain some effectiveness; these campaigns disrupt inter-seasonal transmission, highlighting an off-season control opportunity. Regardless, none of the campaign scenarios maintain their initial effectiveness beyond two seasons, instead stabilizing at much lower levels of benefit: in year 20, median effectiveness was only 27.3% (IQR: [-21.3%, 56.6%]). Furthermore, simply ceasing an initially successful program exposes a population with lowered herd immunity to the same historical threat, and we observed outbreaks more than four-fold larger than pre-intervention outbreaks. These results do not take into account evolving insecticide resistance, thus long-term effectiveness may be lower if new, efficacious insecticides are not developed.
Conclusions
Using a detailed agent-based dengue transmission model for Yucatán State, Mexico, we predict that high coverage indoor residual spraying (IRS) interventions can largely eliminate transmission for a few years, when applied a few months before the typical seasonal epidemic peak. However, vector control succeeds by preventing infections, which precludes natural immunization. Thus, as a population benefits from mosquito control, it gradually loses naturally acquired herd immunity, and the control effectiveness declines; this occurs across all of our modeled scenarios, and is consistent with other empirical work. Long term control that maintains early effectiveness would require some combination of increasing investment, complementary interventions such as vaccination, and control programs across a broad region to diminish risk of importation.
The hermaphrodite germline of Caenorhabditis elegans initially engages in spermatogenesis and then switches to oogenesis during late stages of larval development. TRA-1, a member of the Ci/Gli family of transcriptional repressors, plays an essential role in this switch by repressing genes that promote spermatogenesis. WDR5 proteins are conserved components of histone methyltransferase complexes normally associated with gene activation. However, two C. elegans WDR5 homologs, wdr-5.1 and wdr-5.2 are redundantly required for normal TRA-1 dependent repression, and this function is independent of their roles in histone methylation. Animals lacking wdr-5.1/wdr-5.2 function fail to switch to oogenesis at 25°C, resulting in a masculinization of germline (Mog) phenotype. The Mog phenotype is caused by ectopic expression of fog-3, a direct target of TRA-1 repression. WDR-5.1 associates with the fog-3 promoter and is required for TRA-1 to bind to fog-3 promoter. Other direct targets of TRA-1 are similarly derepressed in the double mutant. These results show that WDR5 plays a novel and important role in stabilizing transcriptional repression during C. elegans sex determination, and provide evidence that this important protein may operate independently of its established role in histone methyltransferase complexes.
The chromatin interaction assays 5C and HiC have advanced our understanding of genomic spatial organization, but analysis approaches for these data are limited by usability and flexibility. The HiFive tool suite provides efficient data handling and a variety of normalization approaches for easy, fast analysis and method comparison. Integration of MPI-based parallelization allows scalability and rapid processing time. In addition to single-command analysis of an entire experiment from mapped reads to interaction values, HiFive has been integrated into the open-source, web-based platform Galaxy to connect users with computational resources and a graphical interface. HiFive is open-source software available from http://taylorlab.org/software/hifive/.
Studies of 3D chromatin organization have suggested that chromosomes are hierarchically organized into large compartments composed of smaller domains called topologically associating domains (TADs). Recent evidence suggests that compartments are smaller than previously thought and that the transcriptional or chromatin state is responsible for interactions leading to the formation of small compartmental domains in all organisms. In vertebrates, CTCF forms loop domains, probably via an extrusion process involving cohesin. CTCF loops cooperate with compartmental domains to establish the 3D organization of the genome. The continuous extrusion of the chromatin fibre by cohesin may also be responsible for the establishment of enhancer–promoter interactions and stochastic aspects of the transcription process. These observations suggest that the 3D organization of the genome is an emergent property of chromatin and its components, and thus may not be only a determinant but also a consequence of its function.
by
Sasha R. Azar;
Christopher M. Roundy;
Shannan L. Rossi;
Jing H. Huang;
Grace Leal;
Ruimei Yun;
Ildefonso Fernandez-Salas;
Christopher J. Vitek;
Igor A. D. Paploski;
Pamela M. Stark;
Jeremy Vela;
Mustapha Debboun;
Martin Reyna;
Uriel Kitron;
Guilherme S. Ribeiro;
Kathryn A. Hanley;
Nikos Vasilakis;
Scott C. Weaver
To evaluate the potential role of Aedes albopictus (Skuse) as a vector of Zika virus (ZIKV), colonized mosquitoes of low generation number (≤ F5) from Brazil, Houston, and the Rio Grande Valley of Texas engorged on viremic mice infected with ZIKV strains originating from Senegal, Cambodia, Mexico, Brazil, or Puerto Rico. Vector competence was established by monitoring infection, dissemination, and transmission potential after 3, 7, and 14 days of extrinsic incubation. Positive saliva samples were assayed for infectious titer. Although all three mosquito populations were susceptible to all ZIKV strains, rates of infection, dissemination, and transmission differed among mosquito and virus strains. Aedes albopictus from Salvador, Brazil, were the least efficient vectors, demonstrating susceptibility to infection to two American strains of ZIKV but failing to shed virus in saliva. Mosquitoes from the Rio Grande Valley were the most efficient vectors and were capable of shedding all three tested ZIKV strains into saliva after 14 days of extrinsic incubation. In particular, ZIKV strain Dakar 41525 (Senegal 1954) was significantly more efficient at dissemination and saliva deposition than the others tested in Rio Grande mosquitoes. Overall, our data indicate that, while Ae. albopictus is capable of transmitting ZIKV, its competence is potentially dependent on geographic origin of both the mosquito population and the viral strain.
Pluripotent stem cells transition between distinct naive and primed states that are controlled by overlapping sets of master regulatory transcription factors. In this issue of Cell Stem Cell, Buecker et al. (2014) and Factor et al. (2014) demonstrate that alternate enhancer usage, regulated by state-specific binding partners of master regulators, defines these pluripotent state transitions.