Diversification of Specificity after Maturation of the Antibody Response to the HIV gp41 Epitope ELDKWA

During maturing antibody responses the increase in affinity for target antigens is achieved by genetic diversification of antibody genes followed by selection for improved binding. The effect this process has on the specificity of antibody for variants of the antigen is not well-defined, despite the potential role of antibody diversification in generating enhanced protection against pathogen escape mutants, or novel specificities after vaccination. To investigate this, a library of single amino-acid substitution epitope variants has been screened with serum obtained at different time-points after immunization of mice with the HIV gp41 peptide epitope ELDKWA. The serum IgG response is shown to mature and increase affinity for ELDKWA, and the titre and affinity of IgG against most epitope variants tested increases. Furthermore there is a bias towards high affinity serum IgG binding to variant epitopes with conservative substitutions, although underlying this trend there is also significant binding to many epitopes with non-conservative substitutions. Thus, maturation of the antibody response to a single epitope results in a broadening of the high-affinity response toward variant epitopes. This implies that many pathogen epitope escape variants that could manifest as single amino-acid substitutions would not emerge by escaping immune surveillance

Orbital density wave induced by electron-lattice coupling in orthorhombic iron pnictides

In this paper we explore the magnetic and orbital properties closely related to a tetragonal-orthorhombic structural phase transition in iron pnictides based on both two- and five-orbital Hubbard models. The electron-lattice coupling, which interplays with electronic interaction, is self-consistently treated. Our results reveal that the orbital polarization stabilizes the spin density wave (SDW) order in both tetragonal and orthorhombic phases. However, the ferro-orbital density wave (F-ODW) only occurs in the orthorhombic phase rather than in the tetragonal one. Magnetic moments of Fe are small in the intermediate Coulomb interaction region for the striped antiferromangnetic phase in the realistic five orbital model. The anisotropic Fermi surface in the SDW/ODW orthorhombic phase is well in agreement with the recent angle-resolved photoemission spectroscopy experiments. These results suggest a scenario that the magnetic phase transition is driven by the ODW order mainly arising from the electron-lattice coupling.Comment: 21 pages, 10 figure

Heat Shock Protein 70 Protects the Heart from Ischemia/Reperfusion Injury through Inhibition of p38 MAPK Signaling.

BackgroundHeat shock protein 70 (Hsp70) has been shown to exert cardioprotection. Intracellular calcium ([Ca2+]i) overload induced by p38 mitogen-activated protein kinase (p38 MAPK) activation contributes to cardiac ischemia/reperfusion (I/R) injury. However, whether Hsp70 interacts with p38 MAPK signaling is unclear. Therefore, this study investigated the regulation of p38 MAPK by Hsp70 in I/R-induced cardiac injury.MethodsNeonatal rat cardiomyocytes were subjected to oxygen-glucose deprivation for 6 h followed by 2 h reoxygenation (OGD/R), and rats underwent left anterior artery ligation for 30 min followed by 30 min of reperfusion. The p38 MAPK inhibitor (SB203580), Hsp70 inhibitor (Quercetin), and Hsp70 short hairpin RNA (shRNA) were used prior to OGD/R or I/R. Cell viability, lactate dehydrogenase (LDH) release, serum cardiac troponin I (cTnI), [Ca2+]i levels, cell apoptosis, myocardial infarct size, mRNA level of IL-1β and IL-6, and protein expression of Hsp70, phosphorylated p38 MAPK (p-p38 MAPK), sarcoplasmic/endoplasmic reticulum Ca2+-ATPase2 (SERCA2), phosphorylated signal transducer and activator of transcription3 (p-STAT3), and cleaved caspase3 were assessed.ResultsPretreatment with a p38 MAPK inhibitor, SB203580, significantly attenuated OGD/R-induced cell injury or I/R-induced myocardial injury, as evidenced by improved cell viability and lower LDH release, resulted in lower serum cTnI and myocardial infarct size, alleviation of [Ca2+]i overload and cell apoptosis, inhibition of IL-1β and IL-6, and modulation of protein expressions of p-p38 MAPK, SERCA2, p-STAT3, and cleaved-caspase3. Knockdown of Hsp70 by shRNA exacerbated OGD/R-induced cell injury, which was effectively abolished by SB203580. Moreover, inhibition of Hsp70 by quercetin enhanced I/R-induced myocardial injury, while SB203580 pretreatment reversed the harmful effects caused by quercetin.ConclusionsInhibition of Hsp70 aggravates [Ca2+]i overload, inflammation, and apoptosis through regulating p38 MAPK signaling during cardiac I/R injury, which may help provide novel insight into cardioprotective strategies

Separation and economic recovery of strontium from Nanyishan oil-field water, China

The mass ratio of Ca to Sr is greater than 10 in Nanyishan oil-field water, which causes significant problems during the economic extraction and recovery of selected trace elements in the oil-field water. The oilfield water was isothermally evaporated and various salts such as Li, K, Mg, Ca, Na, Sr, Rb, Cs, Br, and I were obtained from the solution. The Sr content of each phase was determined by ICP-AES, the Sr distribution rule in this process was obtained, and the best separation stage for Sr was identified, to optimize the separation of Sr from Nanyishan oil-field water

Synthesis of Enantiomers of Chiral Ester Derivatives Containing an Amide Group and their Chiral Recognition by ¹H NMR Spectroscopy

Enantiomers of Chiral Ester Derivatives Containing an Amide Group and Possessing One or Two Stereogenic Centers Were Prepared from L- and D-Α-Amino Acids, and Glycine with (S)- and (R)-Mandelic Acid for Probing their Chiral Recognition as a New Class of Chiral Guests by 1H NMR Spectroscopy, Since Chiral Ester Derivatives Have Been Rarely Used as Chiral Substrates for Chiral Recognition by 1H NMR Technology. the Results Indicated that These Chiral Ester Derivatives Have Been Successfully Differentiated in the Presence of Tetraaza Macrocyclic Chiral Solvating Agents (TAMCSAs) 1 A–1 C. in Order to Better Understand their Chiral Discriminating Behavior, Job Plots, Association Constants (Ka), and Theoretical Calculations of (S,S)-G1 and (R,R)-G1, as a Representative Example, Were Performed, respectively. in Order to Evaluate their Practical Application, the 1H NMR Spectra of G1 and G9 with Various Optical Purities Were Measured (Up to 98 % Ee). in This Work, a Practical Strategy Has Been Effectively Established for Chiral Recognition of Chiral Ester Derivatives Containing an Amide Group and Possessing One or Two Chiral Centers in the Presence of Tetraaza Macrocyclic Chiral Solvating Agents 1 A–1 C by Means of 1H NMR Spectroscopy

Electronic correlations and energy gap in the bilayer nickelate La3_{3}Ni2_{2}O7_{7}

The discovery of superconductivity with a critical temperature of 80~K in La$_{3}$Ni$_{2}$O$_{7}$ under pressure has received enormous attention. La$_{3}$Ni$_{2}$O$_{7}$ is not superconducting under ambient pressure but exhibits a density-wave-like transition at $T^{\ast} \simeq 115$~K. Understanding the electronic correlations, charge dynamics and dominant orbitals are important steps towards the mechanism of superconductivity and other instabilities. Here, our optical study shows that La$_{3}$Ni$_{2}$O$_{7}$ features strong electronic correlations which significantly reduce the electron's kinetic energy and place it in the proximity of the Mott phase. The low-frequency optical conductivity reveals two Drude components arising from multiple bands dominated by the Ni-$d_{x^2 - y^2}$ and Ni-$d_{3z^2 - r^2}$ orbitals at the Fermi level. Above $T^{\ast}$, the scattering rates for both Drude components vary linearly with temperature, indicating non-Fermi-liquid behavior which may be associated with spin-fluctuation scattering. Below $T^{\ast}$, a gap opens in the Ni-$d_{3z^2 - r^2}$ orbital, suggesting the importance of the Ni-$d_{3z^2 - r^2}$ orbital in the density-wave-like instability. Our experimental results provide key insights into the mechanism of the density-wave-like order and superconductivity in La$_{3}$Ni$_{2}$O$_{7}$.Comment: 26 pages, 4 figures, Comments are welcome and appreciate