Designer DNA nanodevices have attracted extensive interest for detection of specific targets in living cells. However, it still remains a great challenge to construct DNA sensing devices that can be activated at desired time with a remotely applied stimulus. Here we report a rationally designed, synthetic DNA nanodevice that can detect ATP in living cells in an upconversion luminescence-activatable manner. The nanodevice consists of a UV light-activatable aptamer probe and lanthanide-doped upconversion nanoparticles which acts as the nanotransducers to operate the device in response to NIR light. We demonstrate that the nanodevice not only enables efficient cellular delivery of the aptamer probe into live cells, but also allows the temporal control over its fluorescent sensing activity for ATP by NIR light irradiation in vitro and in vivo. Ultimately, with the availability of diverse aptamers selected in vitro, the DNA nanodevice platform will allow NIR-triggered sensing of various targets as well as modulation of biological functions in living systems.
Developing simple and general approaches for the synthesis of nanometer-sized DNAm aterials with specific morphologies and functionalities is important for various applications.H erein, an ovel approachf or the synthesis of anew set of DNA-based nanoarchitectures through coordination-driven self-assembly of Fe II ions and DNAm olecules is reported. By fine-tuning the assembly,F e-DNAn anospheres of precise sizes and controlled compositions can be produced. The hybrid nanoparticles can be tailored for delivery of functional DNAt oc ells in vitro and in vivo with enhanced biological function. This highlights the potential of metal ion coordination as at ool for directing the assembly of DNA architectures,w hichc onceptualizes an ew pathway to expand the repertoire of DNA-based nanomaterials.This methodology will advance both the fields of DNAn anobiotechnology and metal-ligand coordination chemistry.The past decade has witnessed worldwide interest in the construction of DNA-based nanomaterials due to their numerous applications ranging from biomedicine to biotechnology. [1][2][3][4][5] Because DNAi su nable to penetrate cell membranes,integration of DNAwith functional nanocarriers (e.g. cationic polymeric and liposomal systems) to promote the delivery is of interest. [2] Recently,D NA-nanotechnologyenabled nanomaterials (e.g., DNAo rigami and spherical nucleic acids), which enable delicate structure tailoring and good biocompatibility, [3][4][5] have shown great potential to transport therapeutic nucleic acids or molecular cargos into cells for various applications. [1] However,t he current approaches are often limited by sophisticated materials synthesis and formulation processes.S trategies aiming at reducing complexity in the synthesis process and increasing scalability and functionality remain ac entral theme in the field of DNA-based nanomaterials.Coordination-driven self-assembly has proven to be one of the most attractive strategies in supramolecular chemistry for the bottom-up construction of functional molecular architectures and materials. [6] Examples of such ensembles range from coordination polymers (CPs), [7] metal-organic frameworks (MOFs), [8] to supramolecular polymer gels. [9] The integration of organic and inorganic components into these materials at the molecular level could increase their structural complexity and endow them with advanced functionalities and broader applications. [6][7][8][9] In particular, nanoscale CPs are rapidly emerging as one of the most active research fields among the chemistry and materials communities,a sd emonstrated by versatile applications for catalysis,o ptical and magnetic materials,a nd nanomedicine. [7] To date,m ost of such systems are built from small organic molecules and metal ions. [7a-f] Most recently,s mall biomolecules (e.g,t annic acid and dipeptides) have been explored for the assembly of functional CP nanoparticles (NPs) for potential bioimaging and drug delivery applications. [7g-i] Despite successful attempts,t oo ur knowledge,c ontrolled syn...
Extracellular ATP is an emerging target for cancer treatment because it is a key messenger for shaping the tumor microenvironment (TME) and regulating tumor progression. However, it remains a great challenge to design biochemical probes for targeted imaging of extracellular ATP in the TME. A TME‐driven DNA nanomachine (Apt‐LIP) that permits spatially controlled imaging of ATP in the extracellular milieu of tumors with ultrahigh signal‐to‐background ratio is reported. It operates in response to the mild acidity in the TME with the pH (low) insertion peptide (pHLIP) module, thus allowing the specific anchoring of the structure‐switching signaling aptamer unit to the membrane of tumor cells for “off–on” fluorescence imaging of the extracellular ATP. Apt‐LIP allows for acidity driven visualization of different extracellular concentrations of exogenous ATP, as well as the monitoring of endogenous ATP release from cells. Furthermore, it is demonstrated that Apt‐LIP represents a promising platform for the specific imaging of the extracellular ATP in both primary and metastatic tumors. Ultimately, since diverse aptamers are obtained through in vitro selection, this design strategy can be further applied for precise detection of various extracellular targets in the TME.
BACKGROUND: Milbemectin and abamectin are frequently used to control the spider 35 mite Tetranychus urticae. The development of abamectin resistance in this major pest 36 has become an increasing problem worldwide, potentially compromising the use of 37 milbemectin. In this study, a large collection of European field populations was 38 screened for milbemectin and abamectin resistance, allowing to thoroughly evaluate 39 any potential cross-resistance risk, and both target-site and metabolic resistance 40 mechanisms were investigated.41 RESULTS: High to very high levels of abamectin resistance were found in one third of 42 all populations, while milbemectin resistance levels were low for most populations. The 43 occurrence of well-known target-site resistance mutations in glutamate-gated chloride 44 channels (G314D in GluCl1 and G326E in GluCl3) was documented in the most 45 resistant populations. However, a new mutation, I321T in GluCl3, was also uncovered 46 in three resistant populations. A differential gene-expression analysis revealed the 47 overexpression of detoxification genes, more specifically cytochrome P450 48 monooxygenase (P450) and UDP-glycosyltransferase (UGT) genes. Subsequently, 49 multiple UGTs were functionally expressed, and their capability to glycosylate 50 abamectin and milbemectin, was tested and confirmed. 51 CONCLUSIONS: We found a clear correlation between abamectin and milbemectin 52 resistance in European populations of T. urticae, but as milbemectin resistance levels 53 were low, the observed cross-resistance is probably not of operational importance. The 54 presence of target-site resistance mutations in GluCl genes was confirmed in most but 55 not all resistant populations. Gene-expression analysis andr functional characterization 56 of P450s and UGTs suggests that also metabolic abamectin resistance mechanisms 57 are common in European T. urticae populations.
Odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) of aphids are thought to be responsible for the initial molecular interactions during olfaction that mediate detection of chemical signals. Analysis of the diversity of proteins involved comprises critical basic research work that will facilitate the development of sustainable pest control strategies. To help us better understand differences in the olfactory system between winged and wingless grain aphids, we constructed an antennal transcriptome from winged and wingless Sitobion avenae (Fabricius), one of the most serious pests of cereal fields worldwide. Among the 133,331 unigenes in the antennal assembly, 13 OBP and 5 CSP putative transcripts were identified with 6 OBP and 3 CSP sequences representing new S. avenae annotations. We used qPCR to examine the expression profile of these genes sets across S. avenae development and in various tissues. We found 7 SaveOBPs and 1 SaveCSP were specifically or significantly elevated in antennae compared with other tissues, and that some transcripts (SaveOBP8, SaveCSP2 and SaveCSP5) were abundantly expressed in the legs of winged or wingless aphids. The expression levels of the SaveOBPs and SaveCSPs varied depending on the developmental stage. Possible physiological functions of these genes are discussed. Further molecular and functional studies of these olfactory related genes will explore their potential as novel targets for controlling S. avenae.
Background The impurity effect of hyperon on atomic nuclei has received a renewed interest in nuclear physics since the first experimental observation of appreciable reduction of E2 transition strength in low-lying states of hypernucleus 7 Λ Li. Many more data on low-lying states of Λ hypernuclei will be measured soon for sd-shell nuclei, providing good opportunities to study the Λ impurity effect on nuclear low-energy excitations.Purpose We carry out a quantitative analysis of Λ hyperon impurity effect on the low-lying states of sd-shell nuclei at the beyond-mean-field level based on a relativistic point-coupling energy density functional (EDF), considering that the Λ hyperon is injected into the lowest positive-parity (Λs) and negative-parity (Λp) states.Method We adopt a triaxially deformed relativistic mean-field (RMF) approach for hypernuclei and calculate the Λ binding energies of hypernuclei as well as the potential energy surfaces (PESs) in (β, γ) deformation plane. We also calculate the PESs for the Λ hypernuclei with good quantum numbers using a microscopic particle rotor model (PRM) with the same relativistic EDF. The triaxially deformed RMF approach is further applied in order to determine the parameters of a five-dimensional collective Hamiltonian (5DCH) for the collective excitations of triaxially deformed core nuclei. Taking 25,27Λ Mg and 31 Λ Si as examples, we analyse the impurity effects of Λs and Λp on the low-lying states of the core nuclei. Results We show that Λs increases the excitation energy of the 2 + 1 state and decreases the E2 transition strength from this state to the ground state by 12% − 17%. On the other hand, Λp tends to develop pronounced energy minima with larger deformation, although it modifies the collective parameters in such a way that the collectivity of the core nucleus can be either increased or decreased.Conclusions The quadrupole deformation significantly affects the Λ binding energies of deformed hypernuclei. A beyondmean-field approach with the dynamical correlations due to restoration of broken symmetries and shape fluctuation is essential in order to study the Λ impurity effect in a quantitative way.
BACKGROUND In spider mites, mutations in the mitochondrial cytochrome b Qo pocket have been reported to confer resistance to the Qo inhibitors bifenazate and acequinocyl. In this study, we surveyed populations of the two‐spotted spider mite Tetranychus urticae for mutations in cytochrome b, linked newly discovered mutations with resistance and assessed potential pleiotropic fitness costs. RESULTS We identified two novel mutations in the Qo site: G132A (equivalent to G143A in fungi resistant to strobilurins) and G126S + A133T (previously reported to cause bifenazate and acequinocyl resistance in Panonychus citri). Two T. urticae strains carrying G132A were highly resistant to bifenazate but not acequinocyl, whereas a strain with G126S + A133T displayed high levels of acequinocyl resistance, but only moderate levels of bifenazate resistance. Bifenazate and acequinocyl resistance were inherited maternally, providing strong evidence for the involvement of these mutations in the resistance phenotype. Near isogenic lines carrying G132A revealed several fitness penalties in T. urticae; a lower net reproductive rate (R0), intrinsic rate of increase (rm) and finite rate of increase (LM); a higher doubling time (DT); and a more male‐biased sex ratio. CONCLUSIONS Several lines of evidence were provided to support the causal role of newly discovered cytochrome b mutations in bifenazate and acequinocyl resistance. Because of the fitness costs associated with the G132A mutation, resistant T. urticae populations might be less competitive in a bifenazate‐free environment, offering opportunities for resistance management. © 2019 Society of Chemical Industry
BACKGROUND The cys‐loop ligand‐gated ion channels, including the glutamate‐gated chloride channel (GluCl) and GABA‐gated chloride channel (Rdl) are important targets for drugs and pesticides. The macrocyclic lactone abamectin primarily targets GluCl and is commonly used to control the spider mite Tetranychus urticae, an economically important crop pest. However, abamectin resistance has been reported for multiple T. urticae populations worldwide, and in several cases was associated with the mutations G314D in GluCl1 and G326E in GluCl3. Recently, an additional I321T mutation in GluCl3 was identified in several abamectin resistant T. urticae field populations. Here, we aim to functionally validate this mutation and determine its phenotypic strength. RESULTS The GluCl3 I321T mutation was introgressed into a T. urticae susceptible background by marker‐assisted backcrossing, revealing contrasting results in phenotypic strength, ranging from almost none to 50‐fold. Next, we used CRISPR‐Cas9 to introduce I321T, G314D and G326E in the orthologous Drosophila GluCl. Genome modified flies expressing GluCl I321T were threefold less susceptible to abamectin, while CRISPRed GluCl G314D and G326E flies were lethal. Last, functional analysis in Xenopus oocytes revealed that the I321T mutation might reduce GluCl3 sensitivity to abamectin, but also suggested that all three T. urticae Rdls are affected by abamectin. CONCLUSION Three different techniques were used to characterize the role of I321T in GluCl3 in abamectin resistance and, combining all results, our analysis suggests that the I321T mutation has a complex role in abamectin resistance. Given the reported subtle effect, additional synergistic factors in resistance warrant more investigation. © 2020 Society of Chemical Industry
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