Investigating the interactions of the first 17 amino acid residues of Huntingtin with lipid vesicles using mass spectrometry and molecular dynamics

The first 17 amino acid residues of Huntingtin protein (Nt17 of htt) are thought to play an important role in the protein's function; Nt17 is one of two membrane binding domains in htt. In this study the binding ability of Nt17 peptide with vesicles comprised of two subclasses of phospholipids is studied using electrospray ionization ‐ mass spectrometry (ESI‐MS) and molecular dynamics (MD) simulations. Overall, the peptide is shown to have a greater propensity to interact with vesicles of phosphatidylcholine (PC) rather than phosphatidylethanolamine (PE) lipids. Mass spectra show an increase in lipid‐bound peptide adducts where the ordering of the number of such specie is 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine (DOPC) > 1‐palmitoyl‐2‐oleoyl‐glycero‐3‐phosphocholine (POPC) > 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3 phosphoethanolamine (POPE). MD simulations suggest that the compactness of the bilayer plays a role in governing peptide interactions. The peptide shows greater disruption of the DOPC bilayer order at the surface and interacts with the hydrophobic tails of lipid molecules via hydrophobic residues. Conversely, the POPE vesicle remains ordered and lipids display transient interactions with the peptide through the formation of hydrogen bonds with hydrophilic residues. The POPC system displays intermediate behavior with regard to the degree of peptide‐membrane interaction. Finally, the simulations suggest a helix stabilizing effect resulting from the interactions between hydrophobic residues and the lipid tails of the DOPC bilayer.     

A Short and Elegant Synthesis of (±)‐Streptopyrrolidine

A brief and efficient approach for the synthesis of (±)‐5‐benzyl‐4‐hydroxy‐2‐pyrrolidine ( 1 ) from phenylalanine racemate is described. The key step is the stereocontrolled reduction of the keto functionality of benzylated pyrrolidinone intermediate ( 6 ) via sodium borohydride in carboxylic acid medium furnishing both (R,R)‐ and (S,S)‐configured diastereomers. The natural (R,R) enantiomer ( 2 ), however, crystallized out from its racemic mixture. Structure of 2 was confirmed by NMR, IR, elemental analyzer, and single crystal X‐ray crystallographic techniques.     

The Effect of Water on the 2-Propanol Oxidation Activity of Co-Substituted LaFe1−xCoxO3 Perovskites

Perovskites are interesting oxidation catalysts due to their chemical flexibility enabling the tuning of several properties. In this work, we synthesized LaFe_1−xCo_xO₃ catalysts by co-precipitation and thermal decomposition, characterized them thoroughly and studied their 2-propanol oxidation activity under dry and wet conditions to bridge the knowledge gap between gas and liquid phase reactions. Transient tests showed a highly active, unstable low-temperature (LT) reaction channel in conversion profiles and a stable, less-active high-temperature (HT) channel. Cobalt incorporation had a positive effect on the activity. The effect of water was negative on the LT channel, whereas the HT channel activity was boosted for x>0.15. The boost may originate from a slower deactivation rate of the Co³⁺ sites under wet conditions and a higher amount of hydroxide species on the surface comparing wet to dry feeds. Water addition resulted in a slower deactivation for Co-rich catalysts and higher activity in the HT channel state.     

Lactucin,a Bitter Sesquiterpene from Cichorium intybus,Inhibits Cancer Cell Proliferation by Downregulating the MAPK and Central Carbon Metabolism Pathway

Lung cancer, especially adenocarcinoma, is the second most occurring and highest fatality-causing cancer worldwide. Many natural anticancer compounds, such as sesquiterpene lactones (SLs), show promising anticancer properties. Herein, we examined Lactucin, an SL from the plant Cichorium intybus, for its cytotoxicity, apoptotic-inducing, cell cycle inhibiting capacity, and associated protein expression. We also constructed a biotinylated Lactucin probe to isolate interacting proteins and identified them. We found that Lactucin stops the proliferation of A549 and H2347 lung adenocarcinoma cell lines while not affecting normal lung cell MRC5. It also significantly inhibits the cell cycle at G₀/G₁ stage and induces apoptosis. The western blot analysis shows that Lactucin downregulates the MAPK pathway, cyclin, and cyclin-dependent kinases, inhibiting DNA repair while upregulating p53, p21, Bax, PTEN, and downregulation of Bcl-2. An increased p53 in response to DNA damage upregulates p21, Bax, and PTEN. In an activity-based protein profiling (ABPP) analysis of A549 cell’s protein lysate using a biotinylated Lactucin probe, we found that Lactucin binds PGM, PKM, and LDHA PDH, four critical enzymes in central carbon metabolism in cancer cells, limiting cancer cells in its growth; thus, Lactucin inhibits cancer cell proliferation by downregulating the MAPK and the Central Carbon Metabolism pathway.     

Morphology‐Dependent Electrochemical Properties of CuS Hierarchical Superstructures

Hierarchical superstructures formed by self‐assembled nanoparticles exhibit interesting electrochemical properties that can potentially be exploited in Li‐ion batteries (LIBs) as possible electrode materials. In this work, we tested two different morphologies of CuS superstructures for electrodes, namely, tubular dandelion‐like and ball‐like assemblies, both of which are composed of similar small covellite nanoparticles. These two CuS morphologies are characterized by their markedly different electrochemical performances, suggesting that their complex structures/morphologies influence the electrochemical properties. At 1.12 A g^?1, the cells made with CuS tubular structures delivered about 420 mAh g^?1, and at 0.56 A g^?1, the capacity was as high as about 500 mAh g^?1 with good capacity retention. Their ease of preparation and processing, together with good electrochemical performance, make CuS tubular dandelion‐like clusters attractive for developing low‐cost LIBs based on conversion reactions.     

Lipase immobilized on poly(VP-co-HEMA) hydrogel for esterification reaction

Lipase from Candida rugosa was immobilized by entrapment on poly(N-vinyl-2-pyrrolidone-co-2-hydroxyethyl methacrylate)(poly[VP-co-HEMA]) hydrogel, and divinylbenzene was the crosslinking agent. The immobilized enzymes were used in the esterification reaction of oleic acid and butanol in hexane. The activities of the immobilized enzymes and the leaching ability of the enzyme from the support with respect to the different compositions of the hydrogels were investigated. The thermal, solvent, and storage stability of the immobilized lipases was also determined. Increasing the percentage of composition of VP from 0 to 90, which corresponds to the increase in the hydrophilicity of the hydrogels, increased the activity of the immobilized enzyme. Lipase immobilized on VP(%):HEMA(%) 90∶10 exhibited the highest activity. Lipase immobilized on VP(%):HEMA(%) 50∶50 showed the highest thermal, solvent, storage, and operational stability compared to lipase immobilized on other compositions of hydrogels as well as the native lipase.     

In‐situ polymerization of aliphatic‐aromatic polyamide nanocomposites in the presence of Halloysite nanotubes

Nanocomposites consisting of semi‐aromatic polyamide (PA) and pristine or alkali activated halloysite nanotubes (HNT or mHNT, respectively) were synthesized by the in‐situ interfacial polymerization method. The condensation reactions were carried out between isophthaloyl dichloride in hexane and triethylenetetramine in water containing different amounts of HNT or mHNT. The interactions and crystallinity of the nanocomposites were studied by Fourier transform infrared (FTIR) spectroscopy and X‐ray diffraction (XRD) analysis, respectively. Development of hydrogen bonds between the functional groups of PA and hydroxyl groups of nanotubes was indicated by FTIR spectroscopy. According to the XRD analysis, the addition of HNT and mHNT nanotubes increased the crystallinity of the PA. This was ascribed to the role of nanotubes as nucleating agents in the PA matrix. Thermal resistance and char residue of PA, as revealed by thermogravimetric analysis, were enhanced by incorporating both HNT and mHNT and the latter was more effective in this regard. Furthermore, while the addition of pristine HNTs decreased the glass transition temperature (Tg) of the PA, the Tg could be increased by about 5°C, in the presence of 5 wt% of mHNTs. Finally, the facilely activated mHNT nanotubes were found to be highly efficient in improving the thermal and structural properties of semi‐aromatic PAs.     

Stability of Circular Orbits around a Tidal Charged Black Hole

We study the effects of the tidal charge on the equatorial circular motion of neutral test particles near a tidal charged black hole. This analysis investigates stable as well as unstable circular orbits in all possible configurations of nonextremal and extremal cases. It is found that a negative tidal charge will increase the energy and angular momentum of a neutral test particle moving around a black hole. We obtain a continuous region of stability for both extremal and nonextremal cases. We conclude that the region of stability as well as radius of last stable circular orbit shows increasing behavior for Q < 0.     

Fe3O4 nanoparticles as an efficient and reusable catalyst for the solvent-free synthesis of 9,9-dimethyl-9,10-dihydro-8H-benzo-[a]xanthen-11(12H)-ones

A simple and efficient method for the synthesis of 9,9‐dimethyl‐9,10‐dihydro‐8H‐benzo‐[α]xanthen‐11(12)‐one derivatives (DDBXs) was developed by the condensation reaction of various substituted aryl al...