Urokinase plasminogen activator (uPA) is a crucial activator of the fibrinolytic system that modulates tissue remodeling, cancer progression, and inflammation. However, its role in membranous ...nephropathy (MN) remains unclear. To clarify this issue, an established BALB/c mouse model mimicking human MN induced by cationic bovine serum albumin (cBSA), with a T helper cell type 2–prone genetic background, was used. To induce MN, cBSA was injected into Plau knockout (Plau−/−) and wild-type (WT) mice. The blood and urine samples were collected to measure biochemical parameters, such as serum concentrations of immunoglobulin (Ig)G1 and IgG2a, using enzyme-linked immunoassay. The kidneys were histologically examined for the presence of glomerular polyanions, reactive oxygen species (ROS), and apoptosis, and transmission electron microscopy was used to examine subepithelial deposits. Lymphocyte subsets were determined using flow cytometry. Four weeks post–cBSA administration, Plau−/− mice exhibited a significantly higher urine protein-to-creatine ratio, hypoalbuminemia, and hypercholesterolemia than WT mice. Histologically, compared to WT mice, Plau−/− mice showed more severe glomerular basement thickening, mesangial expansion, IgG granular deposition, intensified podocyte effacement, irregular thickening of glomerular basement membrane and subepithelial deposits, and abolishment of the glycocalyx. Moreover, increased renal ROS levels and apoptosis were observed in Plau−/− mice with MN. B-lymphocyte subsets and the IgG1-to-IgG2a ratio were significantly higher in Plau−/− mice after MN induction. Thus, uPA deficiency induces a T helper cell type 2–dominant immune response, leading to increased subepithelial deposits, ROS levels, and apoptosis in the kidneys, subsequently exacerbating MN progression in mice. This study provides a novel insight into the role of uPA in MN progression.
We investigated the material properties of Cremonese soundboards using a wide range of spectroscopic, microscopic, and chemical techniques. We found similar types of spruce in Cremonese soundboards ...as in modern instruments, but Cremonese spruces exhibit unnatural elemental compositions and oxidation patterns that suggest artificial manipulation. Combining analytical data and historical information, we may deduce the minerals being added and their potential functions—borax and metal sulfates for fungal suppression, table salt for moisture control, alum for molecular crosslinking, and potash or quicklime for alkaline treatment. The overall purpose may have been wood preservation or acoustic tuning. Hemicellulose fragmentation and altered cellulose nanostructures are observed in heavily treated Stradivari specimens, which show diminished second‐harmonic generation signals. Guarneri's practice of crosslinking wood fibers via aluminum coordination may also affect mechanical and acoustic properties. Our data suggest that old masters undertook materials engineering experiments to produce soundboards with unique properties.
ICP‐MS is used to identify the unique mineral recipe used by Antonio Stradivari to treat his spruce wood, the material for the violin top plate. Chemical manipulation led to hemicellulose fragmentation and cellulose rearrangement. Incorporating engineered wood may contribute to the unique tonal qualities of these acclaimed instruments.
Violins made by Antonio Stradivari are renowned for having been the preferred instruments of many leading violinists for over two centuries. There have been long-standing questions about whether wood ...used by Stradivari possessed unique properties compared with modern tonewood for violin making. Analyses of maple samples removed from four Stradivari and a Guarneri instrument revealed highly distinct organic and inorganic compositions compared with modern maples. By solid-state 13C NMR spectroscopy, we observed that about one-third of hemicellulose had decomposed after three centuries, accompanied by signs of lignin oxidation. No apparent changes in cellulose were detected by NMR and synchrotron X-ray diffraction. By thermogravimetric analysis, historical maples exhibited reduced equilibrium moisture content. In differential scanning calorimetry measurements, only maples from Stradivari violins, but not his cellos, exhibited unusual thermooxidation patterns distinct from natural wood. Elemental analyses by inductively coupled plasma mass spectrometry suggested that Stradivari’s maples were treated with complex mineral preservatives containing Al, Ca, Cu, Na, K, and Zn. This type of chemical seasoning was an unusual practice, unknown to later generations of violin makers. In their current state, maples in Stradivari violins have very different chemical properties compared with their modern counterparts, likely due to the combined effects of aging, chemical treatments, and vibrations. These findings may inspire further chemical experimentation with tonewood processing for instrument making in the 21st century.
Heritage Science In their Research Article on page 19144, Hwan‐Ching Tai et al. use ICP‐MS to identify the unique mineral recipe used by Antonio Stradivari to treat his spruce wood, the material for ...the violin top plate.
The vaccinia viral protein A27 in mature viruses specifically interacts with heparan sulfate for cell surface attachment. In addition, A27 associates with the viral membrane protein A17 to anchor to ...the viral membrane; however, the specific interaction between A27 and A17 remains largely unclear. To uncover the active binding sites and the underlying binding mechanism, we expressed and purified the N-terminal (18–50 residues) and C-terminal (162–203 residues) fragments of A17, which are denoted A17-N and A17-C. Through surface plasmon resonance, the binding affinity of A27/A17-N (KA = 3.40 × 108m−1) was determined to be approximately 3 orders of magnitude stronger than that of A27/A17-C (KA = 3.40 × 105m−1), indicating that A27 prefers to interact with A17-N rather than A17-C. Despite the disordered nature of A17-N, the A27-A17 interaction is mediated by a specific and cooperative binding mechanism that includes two active binding sites, namely 32SFMPK36 (denoted as F1 binding) and 20LDKDLFTEEQ29 (F2). Further analysis showed that F1 has stronger binding affinity and is more resistant to acidic conditions than is F2. Furthermore, A27 mutant proteins that retained partial activity to interact with the F1 and F2 sites of the A17 protein were packaged into mature virus particles at a reduced level, demonstrating that the F1/F2 interaction plays a critical role in vivo. Using these results in combination with site-directed mutagenesis data, we established a computer model to explain the specific A27-A17 binding mechanism.
Background: Vaccinia viral protein A27 associates with viral membrane protein A17 for anchoring to the viral membrane.
Results: A27 specifically interacts with two binding regions within the N-terminal domain of A17.
Conclusion: The A27-A17 interaction is mediated through a specific and cooperative binding mechanism.
Significance: As demonstrated, the F1 and F2 bindings are critical for A27 anchoring to the viral membrane and virion assembly.
Heritage Science Im Forschungsartikel auf S. 19293 nutzen Hwan‐Ching Tai et al. ICP‐MS, um die einzigartige Mineralienrezeptur zu identifizieren, die Antonio Stradivari zur Behandlung seines ...Fichtenholzes, des Materials für die Geigendecke, verwendete.
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► Solid-state NMR provides a sensitive tool for analyzing steroid hormone conformation. ► 17β-Estradiol reveals
singlet patterns in the
13C NMR spectra. ► 17α-Estradiol reveals
...multiplet patterns in the
13C NMR spectra. ► 17α- and 17β-estradiol are flexible to adopt different conformations in the lipid environment.
Solid-state {
1H}
13C cross-polarization/magic angle spinning (CP/MAS) NMR spectroscopy has been applied to 17β-estradiol (E2) and 17α-estradiol (E2α), to analyze the steroidal ring conformations of the two isomers in the absence and presence of lipids at the atomic level. In the absence of lipid, the high-resolution
13C NMR signals of E2 in a powdered form show only
singlet patterns, suggesting a single ring conformation. In contrast, the
13C signals of E2α reveal
multiplet patterns with splittings of 20–300
Hz, implying multiple ring conformations. In the presence of a mimic of the lipid environment, made by mixing 1,2-dimyristoyl-
sn-glycero-3-phosphocholine (DMPC) and 1,2-diheptanoyl-
sn-glycero-3-phosphocholine (DHPC) in a molar ratio 3:1, E2 and E2α revealed
multiplet patterns different from those seen in the absence of lipids, indicating that the two isomers adopt multiple conformations in the lipid environment. In this work, on the basis of chemical shift isotropy and anisotropy analysis, we demonstrated that E2 and E2α prefer to adopt multiple steroidal ring conformations in the presence of a lipid environment, distinct from that observed in solution phase and powdered form.
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► Solid-state NMR provides a sensitive tool for analyzing steroid hormone conformation. ► DHEA and spironolactone reveal
multiplet pattern in
13C NMR spectra. ► DHEA and ...spironolactone undergo a conformational change in lipids. ► DHEA and spironolactone are flexible and can adopt slightly different conformations.
Solid-state
1H/
13C cross-polarization/magic angle spinning (CP/MAS) NMR spectroscopy has been applied to two steroid compounds: dehydroepiandrosterone (DHEA) and spironolactone (SPI), to analyze their conformations at the atomic level. In the absence of lipid, the high-resolution
13C CP/MAS NMR signals of DHEA and SPI in a powder form reveal multiple patterns, with splittings of 30–160
Hz, indicating the existence of multiple conformations. In the mimic lipid environment formed by mixing 1,2-dimyristoyl-
sn-glycero-3-phosphocholine (DMPC) and 1,2-diheptanoyl-
sn-glycero-3-phosphocholine (DHPC) in a molar ratio 3:1, the resulting DHEA and SPI spectra revealed mostly
singlet patterns, suggesting that these steroids undergo a conformational change leading to a specific conformation in the lipid environment. Evidence from chemical shift isotropy and anisotropy analysis indicates that DHEA might adopt conformations subtly different from that seen in solution and in the powder form. In conclusion, we demonstrate by solid-state NMR that the structures of DHEA and SPI may adopt slightly different conformations in different chemical environments.
碩士
國立嘉義大學
應用化學系研究所
99
Vaccinia virus (VACV) is the prototype of the Orthopoxvirus genus of the Poxviridae family, which infects various cell lines and animals. The viral genome is 190 kb in size that ...encodes more than 200 proteins. Among them, A27 and H3 bind to heparan sulfate, whereas D8 binds to chondroitin sulfate specifically facilitate virus attachment to cell surface. Heparin or heparan sulfate (HS) binding protein A27 is an extracellular domain viral protein that associates with membrane protein A17 to be able to expose to outer-membrane. A27 tends to self-assemble forming oligomers and A17 membrane protein precipitates that obstacle the studies of A27/A17 interaction. Till now, the A27/A17 binding sites and its binding mechanism remain largely unclear.
A17 (203 aa) consists of transmembrane domains (61-161) and extracellular domains at N- and C-terminal region (1-60 and 162-203), respectively. A27 (110 aa) consists of a random coil (1-32), containing HS binding domain, a coil-coiled (43-84) and a Leu
博士
國立臺灣大學
化學研究所
106
Stradivari violins were renowned for their extraordinary tone over three centuries. There are many hypotheses to explain the unique tone, one of which is that the wood used by ...Stradivari is different from modern tonewood. In this study, we used a combination of five analytical methods including nuclear magnetic resonance (NMR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and inductively coupled plasma-mass spectrometry (ICP-MS) to analyze maple specimens removed from four Stradivari and Guarneri instrument. By NMR, we observed around one-third of the hemicellulose undergoing decomposition and slight lignin oxidation in Stradivari instruments. In Stradivari’s maple, the crystalline cellulose remained stable to provide structural support, without obvious alteration in crystalline domain sizes measured by synchrotron XRD. By TGA measurement, Stradivari maple showed lower equilibrium moisture content due to the reduction of hemicellulose. Surprisingly, in DSC measurement, there were unique exothermic profiles observed only in Stradivari violins, but not in his cellos and natural maples. We speculated that the distinctive pattern may be due to long-term high-frequency vibration in violins. In addition, to confirm whether Stradivari’s maples were subjected to chemical treatment, the elemental content of maple specimens were measured by ICP-MS. The unnatural elemental abundance in Stradivari’s maples compared to natural maples demonstrated complex mineral treatments containing B, Al, Ca, Cu, Na, K, and Zn. Among these, the boron and aluminum in the violins were confirmed to crosslink with the wood fiber molecules. For aluminum, there were three types of coordination sites in violins (4-,5- and 6-coordination), but only one type in the cellos and modern maples (6-coordination). It seemed that the wood used by Stradivari was subjected to the combination of chemical treatments, natural aging, and long-term vibrations, and hence exhibited distinctive chemical properties compared with modern tonewood. Therefore, modern violinmakers may experiment with various chemical and physical treatments of tonewood based on our findings and try to reproduce the extraordinary sound of the Stradivarius.
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