High-resolution crystal structure of the non-specific lipid-transfer protein from maize seedlings

AbstractBackground: The movement of lipids between membranes is aided by lipid-transfer proteins (LTPs). Some LTPs exhibit broad specificity, transferring many classes of lipids, and are termed non-specific LTPs (ns-LTPs). Despite their apparently similar mode of action, no sequence homology exists between mammalian and plant ns-LTPs and no three-dimensional structure has been reported for any plant ns-LTP.Results We have determined the crystal structure of ns-LTP from maize seedlings by multiple isomorphous replacement and refined the structure to 1.9 å resolution. The protein comprises a single compact domain with four α-helices and a long C-terminal region. The eight conserved cysteines form four disulfide bridges (assigned as Cys4–Cys52, Cys14–Cys29, Cys30–Cys75, and Cys50–Cys89) resolving the ambiguity that remained from the chemical determination of pairings in the homologous protein from castor bean. Two of the bonds, Cys4–Cys52 and Cys50–Cys89, differ from what would have been predicted from sequence alignment with soybean hydrophobic protein. The complex between maize ns-LTP and hexadecanoate (palmitate) has also been crystallized and its structure refined to 1.8 å resolution.Conclusion The fold of maize ns-LTP places it in a new category of all-α-type structure, first described for soybean hydrophobic protein. In the absence of a bound ligand, the protein has a tunnel-like hydrophobic cavity, which is large enough to accommodate a long fatty acyl chain. In the structure of the complex with palmitate, most of the acyl chain is buried inside this hydrophobic cavity

Structure and spectral features of H+(H2O)(7): Eigen versus Zundel forms

The two dimensional (2D) to three dimensional (3D) transition for the protonated water cluster has been controversial, in particular, for H+(H2O)(7). For H+(H2O)(7) the 3D structure is predicted to be lower in energy than the 2D structure at most levels of theory without zero-point energy (ZPE) correction. On the other hand, with ZPE correction it is predicted to be either 2D or 3D depending on the calculational levels. Although the ZPE correction favors the 3D structure at the level of coupled cluster theory with singles, doubles, and perturbative triples excitations [CCSD(T)] using the aug-cc-pVDZ basis set, the result based on the anharmonic zero-point vibrational energy correction favors the 2D structure. Therefore, the authors investigated the energies based on the complete basis set limit scheme (which we devised in an unbiased way) at the resolution of the identity approximation Moller-Plesset second order perturbation theory and CCSD(T) levels, and found that the 2D structure has the lowest energy for H+(H2O)(7) [though nearly isoenergetic to the 3D structure for D+(D2O)(7)]. This structure has the Zundel-type configuration, but it shows the quantum probabilistic distribution including some of the Eigen-type configuration. The vibrational spectra of MP2/aug-cc-pVDZ calculations and Car-Parrinello molecular dynamics simulations, taking into account the thermal and dynamic effects, show that the 2D Zundel-type form is in good agreement with experiments. (c) 2006 American Institute of Physics.open353

Association between harmful alcohol use and periodontal status according to gender and smoking

BACKGROUND: the aim of this study is to assess the association of harmful alcohol use based on the alcohol use disorders identification test (AUDIT) score with periodontal status according to gender and smoking in a representative sample of Korean adults. METHODS: This study analyzed 5,291 participants older than 19 years whose data of harmful alcohol use and periodontal status were available. Harmful alcohol use was defined by the WHO guidelines for the administration of AUDIT. The periodontal status was assessed by the Community Periodontal Index (CPI). Multivariate logistic regression analysis was performed with adjustment for socio-demographic variables, oral and general health behavior, oral health status and systemic conditions. All analyses considered a complex sampling design, and multivariate analysis was also performed in the subgroups. RESULTS: Multivariate logistic regression analysis revealed a marginal association between harmful alcohol use and higher CPI in the total sample. The adjusted odds ratio (OR) of harmful alcohol use was 1.16 (0.97 to 1.38) for higher CPI. Higher CPI was significantly associated with harmful alcohol use in men (OR: 1.28; 95% CI: 1.03-1.60) and non-smokers (OR: 1.29; 95% CI: 1.06-1.57). CONCLUSION: Periodontal status is significantly associated with harmful alcohol use in men and non-smokers in a representative sample of Korean adults

Aqueous Synthesis of CdTe Quantum Dot Using Dithiol-Functionalized Ionic Liquid

We report on an aqueous synthesis of cadmium telluride (CdTe) nanocrystals by using dithiol-functionalized ionic liquids (dTFILs). The dTFILs were designed to have dithiol and vinylimidazolium functional groups and used as a ligand molecule of CdTe quantum dot (QD) to utilize the bidendate chelate interaction afforded by the dithiol groups of dTFILs. The photoluminescence quantum yield of dTFIL-capped CdTe QDs reached up to ~40%, and their luminescent property was maintained for 8 weeks, suggesting an improved stability in water phase. This approach will provide a new synthetic route to the water soluble QDs

Endovascular Treatment of Symptomatic Basilar Artery Stenosis

Purpose While symptomatic basilar artery (BA) stenosis is associated with a higher risk of recurrent stroke or death, there is no consensus on the management of these patients who are refractory to antiplatelet therapy. This study retrospectively assesses the outcomes of endovascular treatment (EVT) for symptomatic BA stenosis. Materials and Methods We conducted a retrospective review of patients with symptomatic BA stenosis who underwent EVT, including angioplasty or stenting, from 2006 to 2018. A total of 15 patients, who experienced transient ischemic attacks or strokes despite dual antiplatelet therapy, were included. EVT was performed under local anesthesia after pretreatment with antiplatelet medications. Angiographic follow-up was performed at 12 and 24 months post-EVT. Clinical outcomes were evaluated using the modified Rankin Scale (mRS). Results EVT was successfully completed in all patients. Peri/post-procedural complications occurred in 33% of cases, including in-stent thrombosis, intracranial hemorrhage, and pontine infarction. At long-term follow-up (mean 98.5±80.5 months), 73.3% of patients achieved a favorable functional outcome (mRS≤2) without disability or mortality. Patients with unfavorable outcomes had previous infarcts, with 2 experiencing new pontine infarctions after stenting. Conclusion This study suggests that EVT, including angioplasty and stenting, may offer promise as a treatment option for symptomatic BA stenosis refractory to medical therapy. However, the procedure carries a notable risk of complications, especially in patients with severe stenosis and previous infarcts. Careful patient selection, based on clinical and radiological criteria, is crucial

An Electrophilic Deguelin Analogue Inhibits STAT3 Signaling in H-Ras-Transformed Human Mammary Epithelial Cells: The Cysteine 259 Residue as a Potential Target

Signal transducer and activator of transcription 3 (STAT3) is a point of convergence for numerous oncogenic signals that are often constitutively activated in many cancerous or transformed cells and some stromal cells in the tumor microenvironment. Persistent STAT3 activation in malignant cells stimulates proliferation, survival, angiogenesis, invasion, and tumor-promoting inflammation. STAT3 undergoes activation through phosphorylation on tyrosine 705, which facilitates its dimerization. Dimeric STAT3 translocates to the nucleus, where it regulates the transcription of genes involved in cell proliferation, survival, etc. In the present study, a synthetic deguelin analogue SH48, discovered by virtual screening, inhibited the phosphorylation, nuclear translocation, and transcriptional activity of STAT3 in H-ras transformed human mammary epithelial MCF-10A cells (MCF10A-ras). We speculated that SH48 bearing an alpha,beta-unsaturated carbonyl group could interact with a thiol residue of STAT3, thereby inactivating this transcription factor. Non-electrophilic analogues of SH48 failed to inhibit STAT3 activation, lending support to the above supposition. By utilizing a biotinylated SH48, we were able to demonstrate the complex formation between SH48 and STAT3. SH48 treatment to MCF10A-ras cells induced autophagy, which was verified by staining with a fluorescent acidotropic probe, LysoTracker Red, as well as upregulating the expression of LC3II and p62. In conclusion, the electrophilic analogue of deguelin interacts with STAT3 and inhibits its activation in MCF10A-ras cells, which may account for its induction of autophagic death.