Antibacterial Coatings Derived from Novel Chemically Responsive Vesicles

In order for a drug, or any material used for the purpose of eliciting a change in an organisms’ physical or chemical state, to be effective it must reach the intended target intact and for a sustained rate over time. Drug delivery systems encapsulate a drug to protect it from degradation, prevent side reactions, increase solubility, improve accumulation rates at target sites, and release drugs at a controlled rate. Controlled and sustained release of drugs is achieved by degradation of the carrier triggered by breaking dynamic chemical bonds caused by changes in the chemical environment such as pH or redox conditions. Slow, first order kinetic release of drugs increase therapeutic efficacy while also reducing side effects and other cytotoxicity issues. Up and coming drug delivery systems include hydrogels and nanocarriers such as vesicles. Hydrogel drug delivery systems are unique three-dimensional networks of crosslinked hydrophilic polymers that contain anywhere from 50-90 wt% of water. Drugs can be loaded via encapsulation during the gelation process or may be covalently bound to the polymer backbone before gelation. Amphiphilic molecules or polymers that self-assemble in aqueous solutions to form supramolecular nanostructures, such as vesicles, can encapsulate hydrophilic drugs in the aqueous interior or hydrophobic drugs in the lipophilic bilayer membrane. This study seeks to embed vesicles into a hydrogel to create a hybrid drug delivery system which may be applied as a coating to medical devices to prevent bacterial adhesion and growth, injected directly to a target site, or as an additive for wound dressings. This hybrid system mitigates burst release from the hydrogel, as well as stabilizes the vesicles to afford a longer shelf life. Vesicles are prepared from a novel supramolecular amphiphile composed of thio-alkyl modified��-cyclodextrin as a macrocyclic host, and an adamantyl-dithiopropionic acid modified poly(ethylene glycol) as a linear guest. This host-guest system forms inclusion complexes that self-assemble to bilayered vesicles, which may encapsulate a payload, in aqueous solutions. These vesicles serve as three-dimensional multivalent junctions to form a hydrogel, which may encapsulate a second payload, through a dynamic disulfide exchange crosslinking reaction. This novel drug delivery system will be capable of dual and selective release of two different encapsulated payloads. A pH sensitive acid labile bond embedded in the crosslinker will cleave under acidic conditions to release the payload enclosed in the hydrogel matrix, while a disulfide bond embedded in the supramolecular amphiphile of the free vesicle can be cleaved in the presence of naturally occurring antioxidant glutathione, GSH, to release the second payload. It has been discovered that vesicles efficaciously form, can encapsulate a payload, and are stable for several weeks, up to a month. Vesicle stability is examined in the presence of both intracellular and extracellular concentrations of GSH, and it is found that vesicles are more stable in extracellular concentrations of GSH. Crosslinking of vesicles is attempted at several molecular weights of linear thiol terminated poly(ethylene glycol) crosslinker, concentrations ratios of crosslinker: vesicle, pHs, and temperatures. It can be concluded that the crosslinking density with the linear crosslinker is not high enough to form a hydrogel. Future studies will include 4-arm crosslinkers which are predicted to increase the number of crosslinking points and hence the crosslinking density

Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo

Meeting Abstracts: Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo Clearwater Beach, FL, USA. 9-11 June 201

Expression and localization of neuronal nitric oxide synthase in the brain and sensory tissues of the African cichlid fish Astatotilapia burtoni

Nitric oxide (NO) produced by the enzyme neuronal nitric oxide synthase serves as an important neurotransmitter in the central nervous system that is involved in reproductive regulation, learning, sensory processing, and other forms of neural plasticity. Here, we map the distribution of nnos-expressing cells in the brain and retina of the cichlid fish Astatotilapia burtoni using in situ hybridization. In the brain, nnos-expressing cells are found from the olfactory bulbs to the hindbrain, including within specific nuclei involved in decision-making, sensory processing, neuroendocrine regulation, and the expression of social behaviors. In the retina, nnos-expressing cells are found in the inner nuclear layer, presumably in amacrine cells. We also used quantitative PCR to test for differences in nnos expression within the eye and olfactory bulbs of males and females of different reproductive states and social statuses. In the eye, males express more nnos than females, and socially dominant males express more nnos than subordinate males, but expression did not differ among female reproductive states. In the olfactory bulbs, dominant males had greater nnos expression than subordinate males. These results suggest a status-specific function for NO signaling in the visual and olfactory systems that may be important for sensory perception related to mating or territorial interactions to maintain the social hierarchy. The widespread distribution of nnos-expressing cells throughout the cichlid brain is similar to that in other teleosts, with some conserved localization patterns across vertebrates, suggesting diverse functions for this important neurotransmitter system

Endocrine and neuroendocrine regulation of social status in cichlid fishes

Position in a dominance hierarchy profoundly impacts group members\u27 survival, health, and reproductive success. Thus, understanding the mechanisms that regulate or are associated with an individuals\u27 social position is important. Across taxa, various endocrine and neuroendocrine signaling systems are implicated in the control of social rank. Cichlid fishes, with their often-limited resources of food, shelter, and mates that leads to competition, have provided important insights on the proximate and ultimate mechanisms related to establishment and maintenance of dominance hierarchies. Here we review the existing information on the relationships between endocrine (e.g., circulating hormones, gonadal and other tissue measures) and neuroendocrine (e.g., central neuropeptides, biogenic amines, steroids) systems and dominant and subordinate social rank in male cichlids. Much of the current literature is focused on only a few representative cichlids, particularly the African Astatotilapia burtoni, and several other African and Neotropical species. Many hormonal regulators show distinct differences at multiple biological levels between dominant and subordinate males, but generalizations are complicated by variations in experimental paradigms, methodological approaches, and in the reproductive and parental care strategies of the study species. Future studies that capitalize on the diversity of hierarchical structures among cichlids should provide insights towards better understanding the endocrine and neuroendocrine mechanisms contributing to social rank. Further, examination of this topic in cichlids will help reveal the selective pressures driving the evolution of endocrine-related phenotypic traits that may facilitate an individual\u27s ability to acquire and maintain a specific social rank to improve survival and reproductive success

Genomic reconstruction of the SARS-CoV-2 epidemic in England

AbstractThe evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.</jats:p