Analyzing Functional Interactions of Designed Peptides by NMR Spectroscopy

The development of small peptide-based therapeutics can be accelerated by the knowledge of relationships between the peptide structure and its functional interactions. Here, we report the analysis of two groups of synthetic peptides designed for two applications – broad bactericidal action and inhibition of protein-protein interactions in human cells. Novel amphiphilic peptides designed for antibacterial application incorporated arginine as cationic amino acids and non-natural amino acids that have aromatic side chains with similar hydrophobic properties as tryptophan. The interaction of lead cyclic peptides and their linear analogs with a phospholipid bilayer mimicking a bacterial membrane was studied using nuclear magnetic resonance (NMR) spectroscopy. These results provided insight into the mechanism of peptide bactericidal action and the role of the peptide structure in their activity. In the second example, we perform a structural characterization of a peptide designed to modulate the activation of the NF-kappaB signaling pathway. The peptide was designed to mimic the spatial structure of the HOIP-NZF1 domain interacting with the NEMO CC2-LZ domain to suppress the NF-kappaB activation. The structure elucidation of the designed peptide provided vital information about matching the required pharmacophore structure in the peptide

Absence of Pressure-Driven Supersolid Flow at Low Frequency

An important unresolved question in supersolid research is the degree to which the non-classical rotational inertia (NCRI) phenomenon observed in the torsional oscillator experiments of Kim and Chan, is evidence for a Bose-condensed supersolid state with superfluid-like properties. In an open annular geometry, Kim and Chan found that a fraction of the solid moment of inertia is decoupled from the motion of the oscillator; however, when the annulus is blocked by a partition, the decoupled supersolid fraction is locked to the oscillator being accelerated by an AC pressure gradient generated by the moving partition. These observations are in accord with superfluid hydrodynamics. We apply a low frequency AC pressure gradient in order to search for a superfluid-like response in a supersolid sample. Our results are consistent with zero supersolid flow in response to the imposed low frequency pressure gradient. A statistical analysis of our data sets a bound, at the 68% confidence level, of 9.6$\times 10^{-4}$ nm/s for the mass transport velocity carried by a possible supersolid flow. In terms of a simple model for the supersolid, an upper bound of 3.3$\times 10^{-6}$ is set for the supersolid fraction at 25 mK, at this same confidence level. These findings force the conclusion that the NCRI observed in the torsional oscillator experiments is not evidence for a frequency independent superfluid-like state. Supersolid behavior is a frequency-dependent phenomenon, clearly evident in the frequency range of the torsional oscillator experiments, but undetectably small at frequencies approaching zero.Comment: 6 pages, 5 figure

Analysis of Thin Film Parylene-Metal-Parylene Device Based on Mechanical Tensile Strength Measurement

International audienceThis paper presents an FEM analysis and experiment of parylene-metal-parylene flexible substrate for implantable medical devices. Tensile strength measurement of the parylene-metal-parylene has been carried out and corresponding FEM modeling and simulation has been done to understand its mechanical behaviour. Besides, frequently encountered metal delamination on parylene substrate has been studied based on cohesive zone model of interface between the two materials

Age-specific associations between serum cholesterol levels and suicidal behaviors in patients with depressive disorders: A naturalistic prospective observational cohort study

IntroductionThis study investigated the effects of total cholesterol levels on prevalent, and incident suicidal behaviors according to age group (<60 vs. ≥60 years) in depressed patients.MethodsConsecutive outpatients with depressive disorders who visited the Chonnam National University Hospital between March 2012 and April 2017 were recruited. Among 1,262 patients assessed at baseline, 1,094 agreed to blood sampling for measurement of serum total cholesterol levels. Among the patients, 884 completed the 12-week acute treatment phase and were followed up at least once during the 12-month continuation treatment phase. Suicidal behaviors assessed at baseline included baseline suicidal severity; behaviors assessed at the 1-year follow-up included increased suicidal severity and fatal/non-fatal suicide attempts. Associations of baseline total cholesterol levels with the above-mentioned suicidal behaviors were analyzed using logistic regression models after adjustment for relevant covariates.ResultsOf 1,094 depressed patients, 753 (68.8%) were women. The mean (SD) age of patients was 57.0 (14.9) years. Lower total cholesterol levels (87–161 mg/dl) were associated with increased suicidal severity (Linear Wald = 4.478, p < 0.05) and fatal/non-fatal suicide attempt (Linear Wald = 7.490, p < 0.01) in patients <60 years of age. U-shaped associations between total cholesterol levels and 1-year follow-up suicidal outcomes (increased suicidal severity, Quadratic Wald = 6.299, p < 0.05; fatal/non-fatal suicide attempt, Quadratic Wald = 5.697, p < 0.05) were observed in patients ≥60 years of age.ConclusionsThese findings suggest that differential consideration of serum total cholesterol levels according to age group may have clinical utility for predicting suicidality in patients with depressive disorders. However, because our research participants came from a single-hospital, the generalizability of our findings may be limited

Modifying effect of the serum level of brain-derived neurotrophic factor (BDNF) on the association between BDNF methylation and long-term cardiovascular outcomes in patients with acute coronary syndrome

IntroductionThis study investigated the potential modifying effects of the serum brain-derived neurotrophic factor (sBDNF) level on the association between BDNF methylation status and long-term cardiovascular outcomes in acute coronary syndrome (ACS) patients.MethodsFrom 2006 to 2012, hospitalized ACS patients were consecutively recruited. The sBDNF level and BDNF methylation status were assessed at baseline in 969 patients who were followed up for major adverse cardiac events (MACEs) over 5–12 years, until 2017 or death. Cox proportional hazards models were utilized to compare the time to first composite or individual MACEs between individuals with lower and those with higher average BDNF methylation levels in the low and high sBDNF groups, respectively. The modifying effects of the sBDNF and average BDNF methylation levels on first composite and individual MACEs were analyzed using Cox proportional hazards models after adjusting for potential covariates.ResultsIn the low sBDNF group, a higher average BDNF methylation level was linked to an increase in composite MACEs independent of confounding variables, but not in the high sBDNF group [HR (95 percent CI) = 1.04 (0.76–1.44)]. The interaction effect between the sBDNF and average BDNF methylation levels on composite MACEs was significant after adjusting for covariates (P = 0.008).ConclusionCombining the BDNF methylation status and sBDNF levels may help identify ACS patients who are likely to have unfavorable clinical outcomes

Time-Resolved in Situ Visualization of the Structural Response of Zeolites During Catalysis

Zeolites are three-dimensional aluminosilicates having unique properties from the size and connectivity of their sub-nanometer pores, the Si/Al ratio of the anionic framework, and the charge-balancing cations. The inhomogeneous distribution of the cations affects their catalytic performances because it influences the intra-crystalline diffusion rates of the reactants and products. However, the structural deformation regarding inhomogeneous active regions during the catalysis is not yet observed by conventional analytical tools. Here we employ in situ X-ray free electron laser-based time-resolved coherent X-ray diffraction imaging to investigate the internal deformations originating from the inhomogeneous Cu ion distributions in Cu-exchanged ZSM-5 zeolite crystals during the deoxygenation of nitrogen oxides with propene. We show that the interactions between the reactants and the active sites lead to an unusual strain distribution, confirmed by density functional theory simulations. These observations provide insights into the role of structural inhomogeneity in zeolites during catalysis and will assist the future design of zeolites for their applications

Modifying Effect of the Interleukin-18 Level on the Association between BDNF Methylation and Long-Term Cardiovascular Outcomes in Patients with Acute Coronary Syndrome

This study investigated the potential modifying effects of the level of the serum interleukin-18 (IL-18) on the association between BDNF methylation status and long-term cardiovascular outcomes in patients with acute coronary syndrome (ACS). Hospitalized ACS patients were recruited sequentially from 2006 to 2012. At baseline, the IL-18 level and BDNF methylation status were evaluated in 969 patients who were followed for major adverse cardiac events (MACEs) for 5–12 years, until 2017 or death. The time to first composite or individual MACE was compared between individuals with lower and higher average BDNF methylation levels (in the low- and high-IL-18 groups, respectively) using a Cox proportional hazards model. After adjusting for potential covariates, the modifying effects of IL-18 and average BDNF methylation levels on the initial composite and individual MACEs were examined. In the high-IL-18 group, but not in the low-IL-18 group, a higher average BDNF methylation level was associated with increases in composite MACEs (HR (95% CI) = 2.15 (1.42–3.26)), all-cause mortality (HR (95% CI) = 1.89 (1.11–3.22)), myocardial infarction (HR (95% CI) = 1.98 (1.07–3.67)), and percutaneous coronary intervention (HR (95% CI) = 1.81 (1.01–3.23)), independent of confounding variables. The interaction effect between the IL-18 and average BDNF methylation levels on composite MACEs (p = 0.019) and myocardial infarction (p = 0.027) was significant after adjusting for covariates. Analysis of BDNF methylation status and IL-18 levels may help identify ACS patients who are most likely to have adverse clinical outcomes