Antimicrobial HPA3NT3 peptide analogs: Placement of aromatic rings and positive charges are key determinants for cell selectivity and mechanism of action

AbstractIn an earlier study, we determined that HP(2‐20) (residues 2‐20 of parental HP derived from the N-terminus of the Helicobacter pylori ribosomal protein L1) and its analog, HPA3NT3, had potent antimicrobial effects. However, HPA3NT3 also showed undesirable cytotoxicity against HaCaT cells. In the present study, we designed peptide analogs including HPA3NT3-F1A (‐F1A), HPA3NT3-F8A (‐F8A), HPA3NT3-F1AF8A (‐F1AF8A), HPA3NT3-A1 (‐A1) and HPA3NT3-A2 (‐A2) in an effort to investigate the effects of amino acid substitutions in reducing their hydrophobicity or increasing their cationicity, and any resulting effects on their selectivity in their interactions with human cells and pathogens, as well as their mechanism of antimicrobial action. With the exception of HPA3NT3-A1, all of these peptides showed potent antimicrobial activity. Moreover, substitution of Ala for Phe at positions 1 and/or 8 of the HPA3NT3 peptides (‐F1A, -F8A and -F1AF8A) dramatically reduced their cytotoxicity. Thus the cytotoxicity of HPA3NT3 appears to be related to its Phe residues (positions 1 and 8), which strongly interact with sphingomyelin in the mammalian cell membrane. HPA3NT3 exerted its bactericidal effects through membrane permeabilization mediated by pore formation. In contrast, fluorescent dye leakage and nucleic acid gel retardation assays showed that ‐A2 acted by penetrating into the cytoplasm, where it bound to nucleic acids and inhibited protein synthesis. Notably, Staphylococcus aureus did not develop resistance to -A2 as it did with rifampin. These results suggest that the -A2 peptide could potentially serve as an effective antibiotic agent against multidrug-resistant bacterial strains

Simulation of Flood Propagation Due to Levee Break Using the Cartesian Cut Cell Method

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv

To the Edge of M87 and Beyond: Spectroscopy of Intracluster Globular Clusters and Ultra Compact Dwarfs in the Virgo Cluster

We present the results from a wide-field spectroscopic survey of globular clusters (GCs) in the Virgo Cluster. We obtain spectra for 201 GCs and 55 ultracompact dwarfs (UCDs) using the Hectospec on the Multiple Mirror Telescope, and derive their radial velocities. We identify 46 genuine intracluster GCs (IGCs), not associated with any Virgo galaxies, using the 3D GMM test on the spatial and radial velocity distribution.They are located at the projected distance 200 kpc $\lesssim$ R $\lesssim$ 500 kpc from the center of M87. The radial velocity distribution of these IGCs shows two peaks, one at $v_{\rm r}$ = 1023 km s$^{-1}$ associated with the Virgo main body, and another at $v_{\rm r}$ = 36 km s$^{-1}$ associated with the infalling structure. The velocity dispersion of the IGCs in the Virgo main body is $\sigma_{\rm{GC}} \sim$ 314 km s$^{-1}$, which is smoothly connected to the velocity dispersion profile of M87 GCs, but much lower than that of dwarf galaxies in the same survey field, $\sigma_{\rm{dwarf}} \sim$ 608 km s$^{-1}$. The UCDs are more centrally concentrated on massive galaxies, M87, M86, and M84. The radial velocity dispersion of the UCD system is much smaller than that of dwarf galaxies. Our results confirm the large-scale distribution of Virgo IGCs indicated by previous photometric surveys. The color distribution of the confirmed IGCs shows a bimodality similar to that of M87 GCs. This indicates that most IGCs are stripped off from dwarf galaxies and some from massive galaxies in the Virgo.Comment: 19 pages, 20 figures, 8 tables, accepted for publication in Ap

A plausible mode of action of pseudin-2, an antimicrobial peptide from Pseudis paradoxa

AbstractThe search for new antibiotic agents is continuous, reflecting the continuous emergence of antibiotic-resistant pathogens. Among the new agents are the antimicrobial peptides (AMPs), which have the potential to become a leading alternative to conventional antibiotics. Studies for the mechanisms of action of the naturally occurring parent peptides can provide the structural and functional information needed for the development of effective new antibiotic agents. We therefore characterized pseudin-2, an AMP isolated from the skin of the South American paradoxical frog Pseudis paradoxa. We found that pseudin-2 organized to an aggregated state in aqueous solution, but that it dissociated into monomers upon binding to lipopolysaccharide (LPS), even though it did not neutralize LPS in Gram-negative bacteria. In addition, pseudin-2 assumed an α-helical structure in the presence of biological membranes and formed pores in both bacterial and fungal membranes, through which it entered the cytoplasm and tightly bound to RNA. Thus, the potent antimicrobial activity of pseudin-2 likely results from both the formation of pores capable of collapsing the membrane potential and releasing intracellular materials and its inhibition of macromolecule synthesis through its binding to RNA

Feasibility of using red cell distribution width for prediction of postoperative mortality in severe burn patients: an association with acute kidney injury after surgery

Background Severe burns cause pathophysiological processes that result in mortality. A laboratory biomarker, red cell distribution width (RDW), is known as a predictor of mortality in critically-ill patients. We examined the association between RDW and postoperative mortality in severe burn patients. Methods We retrospectively analyzed medical data of 731 severely burned patients who underwent surgery under general anesthesia. We evaluated whether preoperative RDW value can predict 3-month mortality after burn surgery using receiver operating characteristic (ROC) curve analysis, logistic regression, and Cox proportional-hazards regression analysis. Mortality was also analyzed according to preoperative RDW values and incidence of postoperative acute kidney injury (AKI). Results The 3-month mortality rate after burn surgery was 27.1% (198/731). The area under the ROC curve of preoperative RDW to predict mortality after burn surgery was 0.701 (95% confidence interval [CI], 0.667–0.734; P 12.9 was 1.238 (95% CI, 1.138–1.347; P 12.9. Preoperative RDW was considered an independent risk factor for mortality (odds ratio, 1.679; 95% CI, 1.378–2.046; P 12.9 and postoperative AKI may further increase mortality after burn surgery

Carotid Intimal-Medial Thickness Is Not Increased in Women with Previous Gestational Diabetes Mellitus

BackgroundGestational diabetes mellitus (GDM) is known to increase the risk of cardiovascular diseases. Measuring the carotid artery intimal-medial thickness (CIMT) is a non-invasive technique used to evaluate early atherosclerosis and to predict future cardiovascular diseases. We examined the association between CIMT and cardiovascular risk factors in young Korean women with previous GDM.MethodsOne hundred one women with previous GDM and 19 women who had normal pregnancies (NP) were recruited between 1999 and 2002. At one year postpartum, CIMT was measured using high-resolution B-mode ultrasonography, and oral glucose tolerance tests were performed. Fasting glucose, glycated hemoglobin A1c (HbA1c), insulin levels and lipid profiles were also measured. CIMTs in the GDM and NP groups were compared, and the associations between CIMT and cardiovascular risk factors were analyzed in the GDM group.ResultsCIMT results of the GDM group were not significantly different from those of the NP group (GDM, 0.435±0.054 mm; NP, 0.460±0.046 mm; P=0.069). In the GDM group, a higher HbA1c was associated with an increase in CIMT after age adjustment (P=0.011). CIMT results in the group with HbA1c >6.0% were higher than those of the normal HbA1c (HbA1c ≤6.0%) (P=0.010). Nine of the patients who are type 2 diabetes mellitus converters within one year postpartum but showed no significant difference in CIMT results compared to NP group.ConclusionHigher HbA1c is associated with an increase in CIMT in women with previous GDM. However, CIMT at one year postpartum was not increased in these women compared to that in NP women