Towards Robust Delivery of Antimicrobial Peptides to Combat Bacterial Resistance

Antimicrobial peptides (AMPs), otherwise known as host defence peptides (HDPs), are naturally occurring biomolecules expressed by a large array of species across the phylogenetic kingdoms. They have great potential to combat microbial infections by directly killing or inhibiting bacterial activity and/or by modulating the immune response of the host. Due to their multimodal properties, broad spectrum activity, and minimal resistance generation, these peptides have emerged as a promising response to the rapidly concerning problem of multidrug resistance (MDR). However, their therapeutic efficacy is limited by a number of factors, including rapid degradation, systemic toxicity, and low bioavailability. As such, many strategies have been developed to mitigate these limitations, such as peptide modification and delivery vehicle conjugation/encapsulation. Oftentimes, however, particularly in the case of the latter, this can hinder the activity of the parent AMP. Here, we review current delivery strategies used for AMP formulation, focusing on methodologies utilized for targeted infection site release of AMPs. This specificity unites the improved biocompatibility of the delivery vehicle with the unhindered activity of the free AMP, providing a promising means to effectively translate AMP therapy into clinical practice.

Comparative Analysis of Probabilistic Analysis and Deterministic Analysis by RESRAD Code

The decommissioning of nuclear facilities indicates that the site is finally released according to a limited or unlimited site reuse purpose. In this process, the assessment of exposure dose to decommissioning workers and nearby residents is essential. Based on MARSSIM, a widely used decommissioning guideline in the United States, derivation of the exposure dose and derived concentration guideline level (DCGL) is mandatory using the probabilistic analysis of the RESRAD code. Here, DCGL is the radionuclide-specific concentration that satisfies the site release criteria. By applying the priority 1 parameter, which has the greatest effect on the dose, the dose is derived through deterministic and probabilistic analyses. The results were compared and analyzed. The purpose of this study was to provide a basic database that can be applied to the development of parameter lists and distributions suitable for the characteristics of nuclear facilities in South Korea. In addition, the process of deriving the dose by applying the deterministic and probabilistic analyses of RESRAD was assessed.

A phosphoinositide-binding cluster in cavin1 acts as a molecular sensor for cavin1 degradation

Caveolae are abundant surface organelles implicated in a range of cellular processes. Two classes of proteins work together to generate caveolae: integral membrane proteins termed caveolins and cytoplasmic coat proteins called cavins. Caveolae respond to membrane stress by releasing cavins into the cytosol. A crucial aspect of this model is tight regulation of cytosolic pools of cavin under resting conditions. We now show that a recently identified region of cavin1 that can bind phosphoinositide (PI) lipids is also a major site of ubiquitylation. Ubiquitylation of lysines within this site leads to rapid proteasomal degradation. In cells that lack caveolins and caveolae, cavin1 is cytosolic and rapidly degraded as compared with cells in which cavin1 is associated with caveolae. Membrane stretching causes caveolar disassembly, release of cavin complexes into the cytosol, and increased proteasomal degradation of wild-type cavin1 but not mutant cavin1 lacking the major ubiquitylation site. Release of cavin1 from caveolae thus leads to exposure of key lysine residues in the PI-binding region, acting as a trigger for cavin1 ubiquitylation and down-regulation. This mutually exclusive PI-binding/ubiquitylation mechanism may help maintain low levels of cytosolic cavin1 in resting cells, a prerequisite for cavins acting as signaling modules following release from caveolae.

Dynamics of Cu, Mn, Ni, Sr and Zn release during decomposition of four types of litter in headwater riparian forests in northern Poland

The aim of the study was to compare the dynamics of Cu, Mn, Ni, Sr and Zn release during decomposition of leaves of Black alder (native material), Norway maple, Red oak and European beech (exogenous material) in the area of headwater riparian forests along the upper course of the Kamienna Creek (Northern Poland). Litter bag method was used in the experiment. Initial materials differed in terms of their chemical composition. Cu, Mn, Ni, Sr and Zn contents were low in general, and in fact, even a few times lower than limit values for decomposition rate. Different trends in the dynamics of the leaf metal content during decomposition were observed in particular tree species despite the fact, that every materials were exposed in the same site. Release dynamics was strongly affected by the content of metals in initial materials and in topsoil. Accumulation of Cu, Mn and Zn was observed during decomposition of poorest in the elements maple leaves, as well as Ni in alder leaves and Sr in the leaves of maple, alder and oak. In beech leaves we observed intensive leaching of Ni, whereas downward trends in the Cu concentration of beech leaves, as well as Mn and Zn in beech and oak leaves, were related to weight loss of the leaves. In some cases, the dynamics of metal release displayed a more complicated two- or three-stage character (release of Ni from maple and oak leaves; Cu from maple leaves; Sr from alder, maple and oak leaves; and Zn from alder and maple leaves).