Alternating Cationic-Hydrophobic Peptide/Peptoid Hybrids: Influence of Hydrophobicity on Antibacterial Activity and Cell Selectivity

The influence of hydrophobicity on antibacterial activity versus the effect on the viability of mammalian cells for peptide/peptoid hybrids was examined for oligomers based on the cationic Lys-like peptoid residue combined with each of 28 hydrophobic amino acids in an alternating sequence. Their relative hydrophobicity was correlated to activity against both Gram-negative and Gram-positive species, human red blood cells, and HepG2 cells. This identified hydrophobic side chains that confer potent antibacterial activity (e. g., MICs of 2–8 μg/mL against E. coli) and low toxicity toward mammalian cells (<10 % hemolysis at 400 μg/mL and IC₅₀>800 μg/mL for HepG2 viability). Most peptidomimetics retained activity against drug-resistant strains. These findings corroborate the hypothesis that for related peptidomimetics two hydrophobicity thresholds may be identified: i) it should exceed a certain level in order to confer antibacterial activity, and ii) there is an upper limit, beyond which cell selectivity is lost. It is envisioned that once identified for a given subclass of peptide-like antibacterials such thresholds can guide further optimisation.     

Structural transformation in Mn-substituted Sr2Bi2Ta2TiO12 Aurivillius phase synthesized by hydrothermal method: A comparative study and dielectric properties

In this study, a hydrothermal method was applied to synthesize the three-layer Aurivillius phase Sr₂Bi₂Ta₂TiO₁₂ (SBTTO) and Mn-substituted Sr_1·5Bi_2·5Ta₂Ti_0·5Mn_0·5O₁₂ (SBTTMO), with the use of NaOH as a mineralizer. The crystal structure, morphology, dielectric properties, and the correlation between the structural transformation and dielectric properties were investigated. The XRD data reveal that the SBTTO sample adopts a tetragonal crystal structure with the I4/mmm space group and is then transformed into an orthorhombic structure with the B2cb space group for SBTTMO. The morphology of both samples was observed by SEM, which showed anisotropic plate-like grains. With the Mn substitution, the ferroelectric transition temperature (T_c) significantly increases as the influence of the 6s² lone pair of Bi³⁺ increases, and this in turn further induces the relaxor-ferroelectric behavior. Consequently, the increase in T_c confirms the structural transformation from the paraelectric-tetragonal to the ferroelectric-orthorhombic phase.     

New,Non‐quinone Fluorogeldanamycin Derivatives Strongly Inhibit Hsp90

Streptomyces hygroscopicus is a natural producer of geldanamycin. Mutasynthetic supplementation of an AHBA‐blocked mutant with all possible monofluoro 3‐aminobenzoic acids provided new fluorogeldanamycins. These showed strong antiproliferative activity and inhibitory effects on human heat shock protein Hsp90. Binding to Hsp90 in the low nanomolar range was determined from molecular modelling, AFM analysis and by calorimetric studies.     

Chrysin,Apigenin and Acacetin Inhibit Tumor Necrosis Factor-Related Apoptosis—Inducing Ligand Receptor-1 (TRAIL-R1) on Activated RAW264.7 Macrophages

Expression level of Tumor Necrosis Factor—related apoptosis—inducing ligand (TRAIL) receptors is one of the most important factors of TRAIL-mediated apoptosis in cancer cells. We here report for the first time data concerning TRAIL-R1 and TRAIL-R2 receptor expression on RAW264.7 macrophages. Three substances belonging to flavones: chrysin, apigenin and acacetin which differ from their substituents at the 4'' position in the phenyl ring were used in assays because of the variety of biological activities (e.g., anticancer activity) of the polyphenol compounds. The expression of TRAIL-R1 and TRAIL-R2 death receptors on non-stimulated and LPS (lipopolysaccharide)-stimulated macrophages was determined using flow cytometry. We demonstrate that RAW264.7 macrophages exhibit TRAIL-R1 surface expression and that the tested compounds: chrysin, apigenin and acacetin can inhibit TRAIL-R1 death receptor expression level on macrophages.     

Psychological work characteristics,psychological workload and associated psychological and cognitive requirements of train drivers

This study aimed to assess the psychological work characteristics and psychological workload of train drivers and to define the psychological and cognitive requirements of their work. A systematic literature search was performed, and expert interviews were conducted. The following work demands were specific to train drivers: high emotional and mental demands, small amount of autonomy and skill discretion. No evidence of a high emotional workload, a high mental workload or short-term stress reactivity was found. In general, the drivers' fatigue complaints and recovery needs after work were comparable to that of other workers. However, severe sleepiness and high need for recovery did affect a substantial proportion of train drivers. The ability to stay aware, to anticipate, to remain attentive and to cope with fatigue are psychological and cognitive skills that are required to adequately and safely perform the train drivers' job. Including these requirements in periodic assessments of train drivers is recommended.     

What is moral about guilt? Acting “prosocially” at the disadvantage of others.

For centuries economists and psychologists have argued that the morality of moral emotions lies in the fact that they stimulate prosocial behavior and benefit others in a person's social environment. Many studies have shown that guilt, arguably the most exemplary moral emotion, indeed motivates prosocial behavior in dyadic social dilemma situations. When multiple persons are involved, however, the moral and prosocial nature of this emotion can be questioned. The present article shows how guilt can have beneficial effects for the victim of one's actions but also disadvantageous effects for other people in the social environment. A series of experiments, with various emotion inductions and dependent measures, all reveal that guilt motivates prosocial behavior toward the victim at the expense of others around—but not at the expense of oneself. These findings illustrate that a thorough understanding of the functioning of emotions is necessary to understand their moral nature. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Removal of neutrophil gelatinase‐associated lipocalin by extracorporeal therapies

Neutrophil gelatinase‐associated lipocalin (NGAL) protein is an early biomarker for acute kidney injury (AKI). It is unknown if extracorporeal therapies (EC) have an effect on circulating NGAL levels. This study was designed to describe the kinetics of NGAL molecule in different EC techniques and to evaluate NGAL clearance in different operational conditions. A mock hemofiltration (HF) and hemoperfusion (HP) setup was used. NGAL was added to the blood reservoir and then measured at 30‐minute intervals from arterial, venous, and ultrafiltrate (UF) lines. Removal kinetics and NGAL sieving coefficient were calculated. In our experiments, baseline NGAL concentration averaged 452 μg/L. There was a consistent downward trend throughout the experiment. NGAL concentration in the UF was between 80 and 90 μg/L, though it showed a slight increase in the second hour. The sieving coefficient of NGAL ranged from 0.2 to 0.4 during HF and it appeared to increase with time, suggesting an initial effect of membrane adsorption. HP proved clearly that there was adsorption of NGAL by the membrane and the point of saturation occured at approximately 60 minutes from the start of circulation. Our evaluation demonstrates that NGAL can be adsorbed and ultrafiltrated with polysulfone membranes. This should be taken into consideration when using NGAL as an AKI biomarker in patients undergoing EC circulation.