Numerous endeavors have been undertaken to gain enhanced upconversion luminescence via surface plasmon resonance (SPR) generated by specially designed nanostructures of noble metals (e.g., Au, Ag). ...However, the SPR response of these metals is usually weak in the ultraviolet (UV) region because of their intrinsic electronic configurations; thus, only green and red upconversion emissions can undergo significant plasmonic enhancement yet without selectivity, while an efficient approach to selectively enhancing the blue upconversion luminescence has been lacking. Herein, by integrating the pronounced UV SPR of silica‐coated indium nanocrystals (InNCs) with blue‐emission upconversion nanoparticles (UCNPs) of NaYbF4:Tm, an up to tenfold selective luminescence enhancement at 450 nm is obtained upon 980 nm laser excitation. Precise manipulation of the silica shell thickness suggests an optimal working distance of 3 nm between InNCs and UCNPs. This study has, for the first time, realized selective blue upconversion luminescence enhancement by using an inexpensive, non‐noble metal material, which will not only enrich the fundamental investigations of SPR‐enhanced upconversion emission, but also widen the applications of blue light‐emitting nanomaterials, for example, in therapeutics.
Taking advantage of the ultraviolet surface plasmon resonance of indium nanocrystals (InNCs), an up to tenfold selective enhancement of blue upconversion luminescence of NaYbF4:Tm nanoparticles (UCNPs) at 450 nm is realized, by assembling InNCs outside the UCNPs separated by an optimized 3 nm silica shell.
Regulation of nuclear mRNA export is critical for proper eukaryotic gene expression. A key step in this process is the directional translocation of mRNA-ribonucleoprotein particles (mRNPs) through ...nuclear pore complexes (NPCs) that are embedded in the nuclear envelope. Our previous studies in Saccharomyces cerevisiae defined an in vivo role for inositol hexakisphosphate (InsP6) and NPC-associated Gle1 in mRNA export. Here, we show that Gle1 and InsP6 act together to stimulate the RNA-dependent ATPase activity of the essential DEAD-box protein Dbp5. Overexpression of DBP5 specifically suppressed mRNA export and growth defects of an ipk1 nup42 mutant defective in InsP6 production and Gle1 localization. In vitro kinetic analysis showed that InsP6 significantly increased Dbp5 ATPase activity in a Gle1-dependent manner and lowered the effective RNA concentration for half-maximal ATPase activity. Gle1 alone had minimal effects. Maximal InsP6 binding required both Dbp5 and Gle1. It has been suggested that Dbp5 requires unidentified cofactors. We now propose that Dbp5 activation at NPCs requires Gle1 and InsP6. This would facilitate spatial control of the remodelling of mRNP protein composition during directional transport and provide energy to power transport cycles.
Phosphorylation regulates transcription factor activity by influencing dimerization, cellular localization, activation potential, and/or DNA binding. Nevertheless, precisely how this post-translation ...modification mediates these processes is poorly understood. Here, we examined the role of phosphorylation on the DNA-binding properties of MafA and MafB, closely related transcriptional activators of the basic-leucine zipper (b-Zip) family associated with cell differentiation and oncogenesis. Many common phosphorylation sites were identified by mass spectrometry. However, dephosphorylation only precluded the detection of MafA dimers and consequently dramatically reduced DNA-binding ability. Analysis of MafA/B chimeras revealed that sensitivity to the phosphorylation status of MafA was imparted by sequences spanning the C-terminal dimerization region (amino acids (aa) 279–359), whereas the homologous MafB region (aa 257–323) conveyed phosphorylation-independent DNA binding. Mutational analysis showed that formation of MafA dimers capable of DNA binding required phosphorylation within the distinct N-terminal transactivation domain (aa 1–72) and not the C-terminal b-Zip region. These results demonstrate a novel relationship between the phosphoamino acid-rich transactivation and b-Zip domains in controlling MafA DNA-binding activity.
Three cases of avian influenza virus H10N8 were reported in Nanchang, China, as of April 2014. To identify the knowledge, attitudes, and practices (KAP) related to H10N8 among farmers' market ...workers, a cross-sectional survey was conducted in 63 farmers' markets in Nanchang. Using the resulting data, characteristics of poultry and non-poultry workers' knowledge, attitudes, and practice were described. Results suggest that interventions targeting high-risk workers should be developed and implemented by public health agencies to prevent the spread of H10N8. Additionally policies that encourage farmers' market workers to receive influenza vaccine should be developed, adopted, and enforced.
Defects in human DNA mismatch repair predispose to cancer, but many components of the pathway have not been identified. We report here the identification and characterization of a novel component ...required for mismatch repair in human cells. A 30-kDa protein was purified to homogeneity by virtue of its ability to complement a depleted HeLa extract in repair of mismatched heteroduplexes. The complementing activity was identified as HMGB1 (the high mobility group box 1 protein), a non-histone chromatin protein that facilitates protein-protein interactions and recognizes DNA damage. Evidence is also presented that HMGB1 physically interacts with MutSalpha and is required at a step prior to the excision of mispaired nucleotide in mismatch repair.
Infection with the novel H10N8 virus in humans has raised concerns about its pandemic potential worldwide. We report the results of a cross-sectional study of avian influenza viruses (AIVs) in live ...poultry markets (LPMs) in Nanchang, China, after the first human case of H10N8 virus infection was reported in the city. A total of 201 specimens tested positive for AIVs among 618 samples collected from 24 LPMs in Nanchang from December 2013 to January 2014. We found that the LPMs were heavily contaminated by AIVs, with H9, H10, and H5 being the predominant subtypes and more than half of the LPMs providing samples that were positive for the H10 subtype. Moreover, the coexistence of different subtypes was common in LPMs. Of the 201 positive samples, 20.9% (42/201) had mixed infections with AIVs of different HA subtypes. Of the 42 mixed infections, 50% (21/42) showed the coexistence of the H9 and H10 subtypes, with or without H5, and were from chicken samples. This indicated that the H10N8 virus probably originated from segment reassortment of the H9 and H10 subtypes.
The level of the MafA transcription factor is regulated by a variety of effectors of β cell function, including glucose, fatty acids, and insulin. Here, we show that phosphorylation at Ser65 of ...mammalian MafA influences both protein stability and transactivation potential. Replacement of Ser65 with Glu to mimic phosphorylation produced a protein that was as unstable as the wild type, whereas Asp or Ala mutation blocked degradation. Analysis of MafA chimeric and deletion constructs suggests that protein phosphorylation at Ser65 alone represents the initial degradation signal, with ubiquitinylation occurring within the C terminus (amino acids 234–359). Although only wild type MafA and S65E were polyubiquitinylated, both S65D and S65E potently stimulated transactivation compared with S65A. Phosphorylation at Ser14 also enhanced activation, although it had no impact on protein turnover. The mobility of MafA S65A was profoundly affected upon SDS-PAGE, with the S65E and S65D mutants influenced less due to their ability to serve as substrates for glycogen synthase kinase 3, which acts at neighboring N-terminal residues after Ser65 phosphorylation. Our observations not only illustrate the sensitivity of the cellular transcriptional and degradation machinery to phosphomimetic mutants at Ser65, but also demonstrate the singular importance of phosphorylation at this amino acid in regulating MafA activity.
Ethyl carbamate (EC) is a potential carcinogen widely found in various fermented foods and beverages, including Huangjiu (Chinese rice wine). Urea is the main precursor of ethyl carbamate in Huangjiu ...and the ethyl carbamate concentration increases gradually during storage. In this work, the changes of urea and EC content were investigated during the storage of Huangjiu under different conditions. The results indicated that urea hydrolysis is the dominant mechanism in urea consumption during storage. Then the kinetic models of urea consumption and EC formation were established based on the Arrhenius equation and Eyring equation, respectively. The prediction results of urea and EC concentrations based on these two models were consistent with experimental data, while the model based on the Eyring equation gave a better performance. The corresponding urea control indicators for Huangjiu with different alcohol concentrations under different storage conditions and specific EC benchmark limits can be calculated based on the model. The urea concentration of Huangjiu should be less than 2 mg/L to have a low risk for EC to exceed the standard of 100 μg/L after storage. Low-temperature storage can slow down and reduce the production of EC. These results are helpful to solve critical problems such as content prediction of urea and EC, condition control for storage and limit standards for EC in Huangjiu.
•A kinetic model for EC formation from urea during Huangjiu storage was established.•Hydrolysis is the dominant mechanism in urea depletion during Huangjiu storage.•Urea and EC contents in stored Huangjiu can be accurately predicted by the models.•Urea control limits and storage conditions can be proposed based on the models.
Replication protein A (RPA) is involved in multiple stages of DNA mismatch repair (MMR); however, the modulation of its functions between different stages is unknown. We show here that ...phosphorylation likely modulates RPA functions during MMR. Unphosphorylated RPA initially binds to nicked heteroduplex DNA to facilitate assembly of the MMR initiation complex. The unphosphorylated protein preferentially stimulates mismatch-provoked excision, possibly by cooperatively binding to the resultant single-stranded DNA gap. The DNA-bound RPA begins to be phosphorylated after extensive excision, resulting in severalfold reduction in the DNA binding affinity of RPA. Thus, during the phase of repair DNA synthesis, the phosphorylated RPA readily disassociates from DNA, making the DNA template available for DNA polymerase δ-catalyzed resynthesis. These observations support a model of how phosphorylation alters the DNA binding affinity of RPA to fulfill its differential requirement at the various stages of MMR.
Type 2 diabetes (T2DM) commonly arises from islet β cell failure and insulin resistance. Here, we examined the sensitivity of key islet-enriched transcription factors to oxidative stress, a condition ...associated with β cell dysfunction in both type 1 diabetes (T1DM) and T2DM. Hydrogen peroxide treatment of β cell lines induced cytoplasmic translocation of MAFA and NKX6.1. In parallel, the ability of nuclear PDX1 to bind endogenous target gene promoters was also dramatically reduced, whereas the activity of other key β cell transcriptional regulators was unaffected. MAFA levels were reduced, followed by a reduction in NKX6.1 upon development of hyperglycemia in db/db mice, a T2DM model. Transgenic expression of the glutathione peroxidase-1 antioxidant enzyme (GPX1) in db/db islet β cells restored nuclear MAFA, nuclear NKX6.1, and β cell function in vivo. Notably, the selective decrease in MAFA, NKX6.1, and PDX1 expression was found in human T2DM islets. MAFB, a MAFA-related transcription factor expressed in human β cells, was also severely compromised. We propose that MAFA, MAFB, NKX6.1, and PDX1 activity provides a gauge of islet β cell function, with loss of MAFA (and/or MAFB) representing an early indicator of β cell inactivity and the subsequent deficit of more impactful NKX6.1 (and/or PDX1) resulting in overt dysfunction associated with T2DM.
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