31 research outputs found
Combining computational modelling, NMR spectroscopy and assembly-line synthesis for studying molecular conformations
Full chirality transfer in the synthesis of hindered tertiary boronic esters under in situ lithiation–borylation conditions
Using non-cryogenic lithiation–borylation, sterically hindered tertiary neopentyl glycol boronic esters can be prepared from secondary benzylic carbamates with full chirality transfer.</p
Recommended from our members
FGF-induced Pea3 transcription factors program the genetic landscape for cell fate determination
FGF signaling is a potent inducer of lacrimal gland development in the eye, capable of transforming the corneal epithelium into glandular tissues. Here, we show that genetic ablation of the Pea3 family of transcription factors not only disrupted the ductal elongation and branching of the lacrimal gland, but also biased the lacrimal gland epithelium toward an epidermal cell fate. Analysis of high-throughput gene expression and chromatin immunoprecipitation data revealed that the Pea3 genes directly control both the positive and negative feedback loops of FGF signaling. Importantly, Pea3 genes are also required to suppress aberrant Notch signaling which, if gone unchecked, can compromise lacrimal gland development by preventing the expression of both Sox and Six family genes. These results demonstrate that Pea3 genes are key FGF early response transcriptional factors, programing the genetic landscape for cell fate determination
PALMD regulates aortic valve calcification via altered glycolysis and NF-κB-mediated inflammation
Recent genome-wide association and transcriptome-wide association studies have identified an association between the PALMD locus, encoding palmdelphin, a protein involved in myoblast differentiation, and calcific aortic valve disease (CAVD). Nevertheless, the function and underlying mechanisms of PALMD in CAVD remain unclear. We herein investigated whether and how PALMD affects the pathogenesis of CAVD using clinical samples from CAVD patients and a human valve interstitial cell (hVIC) in vitro calcification model. We showed that PALMD was upregulated in calcified regions of human aortic valves and calcified hVICs. Furthermore, silencing of PALMD reduced hVIC in vitro calcification, osteogenic differentiation, and apoptosis, whereas overexpression of PALMD had the opposite effect. RNA-Seq of PALMD-depleted hVICs revealed that silencing of PALMD reduced glycolysis and nuclear factor-κB (NF-κB)–mediated inflammation in hVICs and attenuated tumor necrosis factor α–induced monocyte adhesion to hVICs. Having established the role of PALMD in hVIC glycolysis, we examined whether glycolysis itself could regulate hVIC osteogenic differentiation and inflammation. Intriguingly, the inhibition of PFKFB3-mediated glycolysis significantly attenuated osteogenic differentiation and inflammation of hVICs. However, silencing of PFKFB3 inhibited PALMD-induced hVIC inflammation, but not osteogenic differentiation. Finally, we showed that the overexpression of PALMD enhanced hVIC osteogenic differentiation and inflammation, as opposed to glycolysis, through the activation of NF-κB. The present study demonstrates that the genome-wide association– and transcriptome-wide association–identified CAVD risk gene PALMD may promote CAVD development through regulation of glycolysis and NF-κB–mediated inflammation. We propose that targeting PALMD-mediated glycolysis may represent a novel therapeutic strategy for treating CAVD
Liposomal Curcumin Targeting Endometrial Cancer Through the NF-κB Pathway
Background/Aims: Emerging evidence suggests that curcumin possesses chemopreventive properties against various cancers. However, its poor bioavailability limits its clinical application. In this study, we aimed to utilize encapsulation in liposomes (Lipo) as a strategy for the clinical administration of curcumin for endometrial carcinoma (EC). Methods: Curcumin was encapsulated in a liposomal delivery system to prepare a formulation of liposomal curcumin (LC). EC cell lines Ishikawa and HEC-1 were treated with the compound and cell proliferation was measured using MTT assay. Hoechst 33258 staining assay and flow cytometry were used to detect apoptosis of the cells. Wound healing and cell invasion assays were employed to monitor cell motility. Underlying target signaling, such as NF-κB, caspases, and MMPs, were further studied via qRT-PCR and western blot. Thereafter, a zebrafish model was used to assess the toxicity of LC. Finally, a zebrafish transplantation tumor model of EC was grown and treated with LC. Tumors were monitored and harvested to study the expression of NF-κB. Results: The formation of LC was successfully developed with excellent purity and physical properties. In vitro, LC resulted in dose-dependent inhibition of proliferation, induction of apoptosis, and suppression of Ishikawa and HEC-1 cell motility. LC treatment also suppressed the activation and/or expression of NF-κB, caspase-3, and MMP-9. No demonstrable toxicity was found in the zebrafish model and tumors were suppressed after treatment with LC. PCR analysis also showed down-regulated expression of NF-κB. Conclusions: LC was successfully prepared and played biological roles against EC probably through negative regulation of the NF-κB pathway in vitro and in vivo, which demonstrates its potential therapeutic effects in EC
Baulamycin NMR FIDs
This data contains raw NMR (nuclear magnetic resonance) spectroscopy FIDs used to support the structure elucidation of Baulamycin A and B. Data are in raw NMR (FID) formats and require the use of NMR processing software in order to open e.g. MestreNova (from MestreLabs SL), TopSpin (from Bruker), Delta (from JEOL) or SpecManager (from ACDLabs)
Theory study of H
There are three main crystal forms of TiO2 in nature: rutile, anatase and brookite. In this paper, the GGA-PBE method of density functional theory was used to study the H2O molecules adsorbed (110) surface of these three kinds of titanium dioxide. H2O molecules tend to polymerize into dimmers due to the increase of H-O bond length on the surface of rutile than anatase. The lowest adsorption energies of H2O molecules adsorbed on these three structures are −5.479, −0.085 and 4.278 eV, respectively. H2O molecule is most likely to be adsorbed on the (110) surface of anatase. As for H2O molecules adsorbed in the (110) surface of these structures, rutile exhibits the smallest changes of both host TiO2 and H2O molecules
New synthesis design of reliable robust tracking controllers using LMI
Dimirovski, Georgi M. (Dogus Author) -- Conference full title: 2006 9th IEEE International Workshop on Advanced Motion Control : Istanbul, Turkey, 27-29 March 2006The synthesis and design problem for reliable tracking controller against actuator faults is studied in this paper. A more practical and general model of actuator faults for linear uncertain systems is presented. Sufficient conditions for the existence of a reliable tracking controller are derived. Then the design of a state feedback reliable controller design is accomplished by means of LMI based methodology. Comparison analysis is carried out of control system employing reliable tracking controller and the system without, which demonstrated the necessity of reliable tracking control concept. The example also illustrates the effectiveness of the proposed synthesis