Near-infrared (NIR) dye-sensitized upconversion nanoparticles (UCNPs) can broaden the absorption range and boost upconversion efficiency of UCNPs. Here, we achieved significantly enhanced upconversion luminescence in dye-sensitized core/active shell UCNPs via the doping of ytterbium ions (Yb3+) in the UCNP shell, which bridged the energy transfer from the dye to the UCNP core. As a result, we synergized the two most practical upconversion booster effectors (dye-sensitizing and core/shell enhancement) to amplify upconversion efficiency. We demonstrated two biomedical applications using these UCNPs. By using dye-sensitized core/active shell UCNP embedded poly(methyl methacrylate) polymer implantable systems, we successfully shifted the optogenetic neuron excitation window to a biocompatible and deep tissue penetrable 800 nm wavelength. Furthermore, UCNPs were water-solubilized with Pluronic F127 with high upconversion efficiency and can be imaged in a mouse model.

Pain signaling in vertebrates is modulated by neuropeptides like Substance P (SP). To determine whether such modulation is conserved and potentially uncover novel interactions between nociceptive signaling pathways we examined SP/Tachykinin signaling in a Drosophila model of tissue damage-induced nociceptive hypersensitivity. Tissue-specific knockdowns and genetic mutant analyses revealed that both Tachykinin and Tachykinin-like receptor (DTKR99D) are required for damage-induced thermal nociceptive sensitization. Electrophysiological recording showed that DTKR99D is required in nociceptive sensory neurons for temperature-dependent increases in firing frequency upon tissue damage. DTKR overexpression caused both behavioral and electrophysiological thermal nociceptive hypersensitivity. Hedgehog, another key regulator of nociceptive sensitization, was produced by nociceptive sensory neurons following tissue damage. Surprisingly, genetic epistasis analysis revealed that DTKR function was upstream of Hedgehog-dependent sensitization in nociceptive sensory neurons. Our results highlight a conserved role for Tachykinin signaling in regulating nociception and the power of Drosophila for genetic dissection of nociception.DOI: http://dx.doi.org/10.7554/eLife.10735.001

The transient receptor potential A1 (TRPA1) channel is an evolutionarily conserved detector of temperature and irritant chemicals. Here, we show that two specific isoforms of TRPA1 in Drosophila are H 2 O 2 sensitive and that they can detect strong UV light via sensing light-induced production of H 2 O 2 . We found that ectopic expression of these H 2 O 2 -sensitive Drosophila TRPA1 (dTRPA1) isoforms conferred UV sensitivity to light-insensitive HEK293 cells and Drosophila neurons, whereas expressing the H 2 O 2 -insensitive isoform did not. Curiously, when expressed in one specific group of motor neurons in adult flies, the H 2 O 2 -sensitive dTRPA1 isoforms were as competent as the blue light-gated channelrhodopsin-2 in triggering motor output in response to light. We found that the corpus cardiacum (CC) cells, a group of neuroendocrine cells that produce the adipokinetic hormone (AKH) in the larval ring gland endogenously express these H 2 O 2 -sensitive dTRPA1 isoforms and that they are UV sensitive. Sensitivity of CC cells required dTRPA1 and H 2 O 2 production but not conventional phototransduction molecules. Our results suggest that specific isoforms of dTRPA1 can sense UV light via photochemical production of H 2 O 2 . We speculate that UV sensitivity conferred by these isoforms in CC cells may allow young larvae to activate stress response-a function of CC cells-when they encounter strong UV, an aversive stimulus for young larvae.UV sensing | dTRPA1 isoforms | reactive oxygen species | Drosophila | optogenetics

SUMMARY Topographic projection of afferent terminals into two-dimensional maps in the central nervous system (CNS) is a general strategy used by the nervous system to encode the locations of sensory stimuli. In vertebrates, it is known that while guidance cues are critical for establishing a coarse topographic map, neural activity directs fine-scale topography between adjacent afferent terminals [1–4]. However, the molecular mechanism underlying activity-dependent regulation of fine-scale topography is poorly understood. Molecular analysis of the spatial relationship between adjacent afferent terminals requires reliable localization of the presynaptic terminals of single neurons as well as genetic manipulations with single-cell resolution in vivo. Although both requirements can potentially be met in Drosophila melanogaster [5, 6], no activity-dependent topographic system has been identified in flies [7]. Here we report a topographic system that is shaped by neuronal activity in Drosophila. With this system, we found that topographic separation of the presynaptic terminals of adjacent nociceptive neurons requires different levels of Trim9, an evolutionarily conserved signaling molecule [8–11]. Neural activity regulates Trim9 protein levels to direct fine-scale topography of sensory afferents. This study offers both a novel mechanism by which neural activity directs fine-scale topography of axon terminals and a new system to study this process at single-neuron resolution.

Background Whole genome duplication is a useful genetic tool because it allows immediate and complete genetic homozygosity in gynogenetic offspring. A whole genome duplication method in zebrafish, Heat Shock, involves a heat pulse in the period 13 – 15 minutes post-fertilization (mpf) to inhibit cytokinesis of the first mitotic cycle. However, Heat Shock produces a relatively low yield of gynogenotes. Results A heat pulse at a later time point during the first cell cycle (22 mpf, HS2) results in a high (>80%) frequency of embryos exhibiting a precise one-cell division stall during the second cell cycle, inducing whole genome duplication. Coupled with haploid production, HS2 generates viable gynogenetic diploids with yields up to 4 times higher than those achieved through standard Heat Shock. The cell cycle delay also causes blastomere cleavage pattern variations, supporting a role for cytokinesis in spindle orientation during the following cell cycle. Conclusions Our studies provide a new tool for whole genome duplication, induced gynogenesis and cleavage pattern alteration in zebrafish, based on a time period prior to the initiation of cell division that is sensitive to temperature-mediated interference with centrosome duplication. Targeting of this period may also facilitate genetic and developmental manipulations in other organisms.