99 research outputs found
Automated solution-phase synthesis of β-mannans
In order to provide a strategy which could produce the biologically important beta-mannans in a highly efficient and economical way, this dissertation illustrates the development of the automated solution-phase synthesis of different beta-mannans including the fungal beta-1,2-mannans by using both oxidation-reduction and beta-directing mannuronate strategies, and also reveals a new strategy for beta-mannan synthesis by reduction of mannuronate esters to alcohols. The following chapter shows the power of this automated solution-phase method to create beta-1,4-mannuronate and beta-1,4-mannan oligomers up to hexasaccharides. The subsequent chapter demonstrates the application of this new beta-mannan synthesis strategy for the synthesis of the insect N-glycan terminal trimannosides for fluorous microarray and isothermal titration calorimetry (ITC) studies to investigate the binding affinity of the pea enation mosaic virus (PEMV) in the aphid digestion system for clues to the virus transmission pathway of the virus in these notorious pests. Finally, the automated solution-phase synthesis of beta-1,6-mannan and beta-1,3-mannan oligomers presents the scope of the automated solution-phase synthesis of beta-mannans and its potential for synthesizing other oligosaccharides containing this challenging linkage
Cell volume restriction by mercury chloride reduces M1-like inflammatory response of bone marrow-derived macrophages
Dysregulation of macrophages in the pro-inflammatory (M1) and anti-inflammatory (M2) sub-phenotypes is a crucial element in several inflammation-related diseases and injuries. We investigated the role of aquaporin (AQP) in macrophage polarization using AQP pan-inhibitor mercury chloride (HgCl2). Lipopolysaccharides (LPSs) induced the expression of AQP-1 and AQP-9 which increased the cell size of bone marrow-derived macrophages. The inhibition of AQPs by HgCl2 abolished cell size changes and significantly suppressed M1 polarization. HgCl2 significantly reduced the activation of the nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways and inhibited the production of IL-1β. HgCl2 attenuated LPS-induced activation of mitochondria and reactive oxygen species production and autophagy was promoted by HgCl2. The increase in the light chain three II/light chain three I ratio and the reduction in PTEN-induced kinase one expression suggests the recycling of damaged mitochondria and the restoration of mitochondrial activity by HgCl2. In summary, the present study demonstrates a possible mechanism of the AQP inhibitor HgCl2 in macrophage M1 polarization through the restriction of cell volume change, suppression of the p38 MAPK/NFκB pathway, and promotion of autophagy
Potential of Core-Collapse Supernova Neutrino Detection at JUNO
JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve
Detection of the Diffuse Supernova Neutrino Background with JUNO
As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO
Automated solution-phase synthesis of β-mannans
In order to provide a strategy which could produce the biologically important beta-mannans in a highly efficient and economical way, this dissertation illustrates the development of the automated solution-phase synthesis of different beta-mannans including the fungal beta-1,2-mannans by using both oxidation-reduction and beta-directing mannuronate strategies, and also reveals a new strategy for beta-mannan synthesis by reduction of mannuronate esters to alcohols. The following chapter shows the power of this automated solution-phase method to create beta-1,4-mannuronate and beta-1,4-mannan oligomers up to hexasaccharides. The subsequent chapter demonstrates the application of this new beta-mannan synthesis strategy for the synthesis of the insect N-glycan terminal trimannosides for fluorous microarray and isothermal titration calorimetry (ITC) studies to investigate the binding affinity of the pea enation mosaic virus (PEMV) in the aphid digestion system for clues to the virus transmission pathway of the virus in these notorious pests. Finally, the automated solution-phase synthesis of beta-1,6-mannan and beta-1,3-mannan oligomers presents the scope of the automated solution-phase synthesis of beta-mannans and its potential for synthesizing other oligosaccharides containing this challenging linkage.</p
Automated Solution-Phase Synthesis of β‑1,4-Mannuronate and β‑1,4-Mannan
The
first automated solution-phase synthesis of β-1,4-mannuronate
and β-1,4-mannan oligomers has been accomplished by using a
β-directing C-5 carboxylate strategy. By utilizing fluorous-tag
assisting purification after repeated reaction cycles, β-1,4-mannuronate
was synthesized up to a hexasaccharide with limited loading of a glycosyl
donor (up to 3.5 equiv) for each glycosylation cycle due to the homogeneous
solution-phase reaction condition. After a global reduction of the
uronates, the β-1,4-mannan hexasaccharide was obtained, thereby
demonstrating a new approach to β-mannan synthesis
Automated Solution-Phase Synthesis of Insect Glycans to Probe the Binding Affinity of Pea Enation Mosaic Virus
Pea
enation mosaic virus (PEMV)î—¸a plant RNA virus transmitted
exclusively by aphidsî—¸causes disease in multiple food crops.
However, the aphid-virus interactions required for disease transmission
are poorly understood. For virus transmission, PEMV binds to a heavily
glycosylated receptor aminopeptidase N in the pea aphid gut and is
transcytosed across the gut epithelium into the aphid body cavity
prior to release in saliva as the aphid feeds. To investigate the
role of glycans in PEMV–aphid interactions and explore the
possibility of viral control through blocking a glycan interaction,
we synthesized insect <i>N</i>-glycan terminal trimannosides
by automated solution-phase synthesis. The route features a mannose
building block with C-5 ester enforcing a β-linkage, which also
provides a site for subsequent chain extension. The resulting insect <i>N</i>-glycan terminal trimannosides with fluorous tags were
used in a fluorous microarray to analyze binding with fluorescein
isothiocyanate-labeled PEMV; however, no specific binding between
the insect glycan and PEMV was detected. To confirm these microarray
results, we removed the fluorous tag from the trimannosides for isothermal
titration calorimetry studies with unlabeled PEMV. The ITC studies
confirmed the microarray results and suggested that this particular
glycan–PEMV interaction is not involved in virus uptake and
transport through the aphid
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