The secondary structure, amide hydrogen exchangeability, and intramembrane orientation of the hydrophobic peptide Ac-K2-(LA)12-K2-amide [(LA)12] were studied by a combination of circular dichroism (CD), Fourier transform infrared (FTIR), and proton nuclear magnetic resonance (1H NMR) spectroscopic techniques. All three techniques indicate that (LA)12 adopts predominantly helical conformations in various organic solvents, detergent micelles, and phospholipid bilayers. Also, attenuated total reflectance FTIR studies of oriented phospholipid bilayers demonstrate that (LA)12 is arranged with the long helical axis perpendicular to the bilayer plane. FTIR and 1H NMR studies of the exchangeability of the amide protons of (LA)12 indicate that in all media there are at least two populations of amide protons which exchange with the bulk solvent at markedly different rates. Moreover, the 1H NMR spectroscopic studies indicate that, in organic solvents and micellar dispersions, amide proton exchange rates decrease progressively from the N- or C-terminus of the peptide toward the central region. Our results are thus consistent with (LA)12 retaining a predominantly helical structure with so-called frayed ends in all media. The amide proton exchange studies also indicate that when (LA)12 is dispersed in lipid bilayers, the slowly exchanging population of amide protons is larger than that observed in organic solvents or in micellar dispersions and that most of that proton population is virtually unexchangeable. Such observations are consistent with the sequestration of the central regions of the peptide in the hydrophobic domains of the lipid bilayer. The CD and FTIR data indicate that although (LA)12 seems to retain conformations with a high alpha-helical content in all media examined, its conformation is sensitive to the composition of the surrounding medium, in contrast to the polyleucine-based analogues which have been studied previously. In particular, the FTIR spectroscopic data indicate that (LA)12 may exhibit an amide I absorption band between 1633 and 1639 cm-1 under some circumstances. The relative intensity of this band changes with the composition of the surrounding medium and its appearance has previously been correlated with the formation of 3(10)-helical structures [Miick et al. (1992) Nature 359, 653-655]. Thus (LA)12 may be interconverting between different helical conformations in response to changes in the physical properties of the medium in which the peptide is dispersed. Our results suggest that (LA)12 should serve as a good peptide model of hydrophobic, transmembrane helices which are conformationally sensitive to the properties of the lipid bilayer in which they reside.

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Background Orderly G2/M transition in the cell cycle is controlled by the cyclin-dependent kinase 1/cyclin B (CDK1/CCNB) complex. We aimed to comprehensively investigate the roles of CDK1, CCNB1, and CCNB2 via multi-omics analysis and their relationships with immune infiltration in hepatocellular carcinoma (HCC). Material/Methods The transcriptional data and the epigenetic and genetic alterations of CDK1 , CCNB1 , and CCNB2 , as well as their impacts on prognosis in HCC patients, were identified using multiple databases. The correlations between expression of these genes and immune infiltration in HCC were then explored using the TIMER database. Results Overall, mRNA expression of CDK1 , CCNB1 , and CCNB2 was up-regulated in various tumor tissues including HCC. Higher expression of these genes was associated with poorer prognosis in HCC patients. Lower promoter methylation of these genes might cause higher expression levels in tumor tissues of HCC. Genetic alterations and several methylated-CpG sites in these genes were significantly associated with survival. Notably, expression levels of CDK1 , CCNB1 , and CCNB2 were positively correlated with infiltrating levels of CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells in HCC. In addition, significant correlations between the expression of these genes and various immune markers in HCC, such as PD-1, PDL-1, and CTLA-4, were also observed. Conclusions CDK1 , CCNB1 , and CCNB2 are potential prognostic biomarkers and associated with immune cell infiltration in HCC. The genes may be utilized to predict the reaction of immunotherapy. Combining inhibitors of these genes with immunotherapy may improve the survival time of HCC patients.

For reaching a high-performance of electrode materials, it is generally believed that understanding the structure evolution and heterogeneous alignment effect is the key. Presently, a very simple and universal applicable...

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The thermotropic phase behavior of hydrated bilayers derived from binary mixtures of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG) was investigated by differential scanning calorimetry, Fourier-transform infrared spectroscopy and 31P-nuclear magnetic resonance spectroscopy. Binary mixtures of DMPC and DMPG that have not been annealed at low temperatures exhibit broad, weakly energetic pretransitions (approximately 11-15 degrees C) and highly cooperative, strongly energetic gel/liquid-crystalline phase transitions (approximately 23-25 degrees C). After low temperature incubation, these mixtures also exhibit a thermotropic transition form a lamellar-crystalline to a lamellar gel phase at temperatures below the onset of the gel/liquid-crystalline phase transition. The midpoint temperatures of the pretransitions and gel/liquid-crystalline phase transitions of these lipid mixtures are both maximal in mixtures containing approximately 30 mol% DMPG but the widths and enthalpies of the same thermotropic events exhibit no discernable composition dependence. In contrast, thermotropic transitions involving the Lc phase exhibit a very strong composition dependence, and the midpoint temperatures and transition enthalpies are both maximal with mixtures containing equimolar amounts of the two lipids. Our spectroscopic studies indicate that the Lc phases formed are structurally similar as regards their modes of hydrocarbon chain packing, interfacial hydration and hydrogen-bonding interactions, as well as the range and amplitudes of the reorientational motions of their phosphate headgroups. Our results indicate that although DMPC and DMPG are highly miscible, their mixtures do not exhibit ideal mixing. We attribute the non-ideality in their mixing behavior to the formation of preferential PC/PG contacts in the Lc phase due to the combined effects of steric crowding of the DMPC headgroups and charge repulsion between the negatively charged DMPG molecules.

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