Biophysical Properties of Phenyl Succinic Acid Derivatised Hyaluronic Acid

Modification of hyaluronic acid (HA) with aryl succinic anhydrides results in new biomedical properties of HA as compared to non-modified HA, such as more efficient skin penetration, stronger binding to the skin, and the ability to blend with hydrophobic materials. In the present study, hyaluronic acid has been derivatised with the anhydride form of phenyl succinic acid (PheSA). The fluorescence of PheSA was efficiently quenched by the HA matrix. HA also acted as a singlet oxygen scavenger. Fluorescence lifetime(s) of PheSA in solution and when attached to the HA matrix has been monitored with ps resolved streak camera technology. Structural and fluorescence properties changes induced on HA-PheSA due to the presence of singlet oxygen were monitored using static light scattering (SLS), steady state fluorescence and ps time resolved fluorescence studies. SLS studies provided insight into the depolymerisation kinetics of PheSA derivatised HA matrix in the presence of singlet oxygen. Time resolved fluorescence studies grave insight into the dynamics of the reaction mechanisms induced on HA-PheSA by singlet oxygen. These studies provided insight into the medical relevance of PheSA derivatised HA: its capacity of scavenging singlet oxygen and of quenching PheSA fluorescence. These studies revealed that HA-PheSA is a strong quencher of electronic excited state PheSA and acts as a scavenger of singlet oxygen, thus medical applications of this derivatised form of HA may protect tissues and organs, such as skin, against reactive oxygen species damage.     

Mechanistic insights into dopaminergic and serotonergic neurotransmission – concerted interactions with helices 5 and 6 drive the functional outcome

Brain functions rely on neurotransmitters that mediate communication between billions of neurons. Disruption of this communication can result in a plethora of psychiatric and neurological disorders. In this work, we combine molecular dynamics simulations, live-cell biosensor and electrophysiological assays to investigate the action of the neurotransmitter dopamine at the dopaminergic D₂ receptor (D₂R). The study of dopamine and closely related chemical probes reveals how neurotransmitter binding translates into the activation of distinct subsets of D₂R effectors (i.e.: G_i2, G_oB, G_z and β-arrestin 2). Ligand interactions with key residues in TM5 (S5.42) and TM6 (H6.55) in the D₂R binding pocket yield a dopamine-like coupling signature, whereas exclusive TM5 interaction is typically linked to preferential G protein coupling (in particular G_oB) over β-arrestin. Further experiments for serotonin receptors indicate that the reported molecular mechanism is shared by other monoaminergic neurotransmitter receptors. Ultimately, our study highlights how sequence variation in position 6.55 is used by nature to fine-tune β-arrestin recruitment and in turn receptor signaling and internalization of neurotransmitter receptors.

Neurotransmitter contacts within the receptor binding site differentially contribute to the overall functional response: transmembrane helix (TM) 5 contacts promote G protein coupling whereas concerted TM5–TM6 contacts enhance β-arrestin recruitment.     

Dynamic light scattering from ternary polymer blends: critical behavior and bicontinuous microemulsions

We have used dynamic light scattering to study the dynamics of ternary polymer blends consisting of poly(dimethylsiloxane) (PDMS) and poly(ethylethylene) (PEE) homopolymers and a PDMS‐PEE diblock copolymer nearly symmetric in composition. The intensity autocorrelation functions for the binary blend are single‐exponential, and the associated correlation length ξ scales with reduced temperature ϵ in accordance with the Ising universality class (i.e., ξ ∼ ϵ^−ν, with ν = 0.63). An addition of copolymer depresses the critical temperature, but also increases the magnitude of ν. For compositions within the microemulsion channel, ξ exhibits a distinct maximum with decreasing temperature, near the Lifshitz line obtained from the static structure factor. For a particular composition, there is a “re‐entrant” microemulsion, as the system passes into and then out of the phase‐separated region upon cooling.     

Structural Tracking of a Bimolecular Reaction in Solution by Time‐Resolved X‐Ray Scattering

Molecular movies : Time‐resolved X‐ray scattering provides direct structural information on an electronically excited complex while it is formed in the bimolecular reaction between excited octahydrogen[tetrakis‐μ‐diphosphito‐1κP:2κP′‐diplatinate](4‐) (PtPOP*) and thallium ions. In the exciplex one thallium(I) and two platinum(II) ions are found to be collinear.

     

Revisiting the Perfluorinated Trityl Cation

Although ultimately not isolable for X-ray structural characterization, the free perfluorinated trityl cation was shown to be observable in neat triflic acid, which represents milder conditions than previous reports of this cation in “magic acid” or oleum. A triflate-bound species could be generated in organic solvents using stoichiometric amounts of triflic acid and was shown to be synthetically viable for hydride abstraction from Et₃SiH. It was demonstrated that the para-position on the -C₆F₅ rings is the primary point of attack for decomposition of the cation.     

Similarity structure of wave-collapse

Similarity transformations of the cubic Schrödinger equation (CSE) are investigated. The transformations are used to remove the explicit time variation in the CSE and reduce it to differential equations in the spatial variables only. Two different methods for similarity reduction are employed and the significance of similarity in the evolution of a collapsing wave packet is investigated. Numerical solutions in radial symmetry demonstrate that the similarity behaviour is local in space and time, and that some similarity solutions must be classified as improper solutions. The nature of the collapsing singularity is reexamined.     

ACTIVATION OF THE HUMAN IMMUNODEFICIENCY VIRUS PROMOTER BY UVA RADIATION IN COMBINATION WITH PSORALENS OR ANGELICINS

Abstract— The effects of mono- and bifunctional furocoumarins plus UVA radiation (PUVA and related treatments) on the human immunodeficiency virus-1 (HIV-1) promoter were studied using HeLa cells stably transfected with the chloramphenicol acetyl transferase gene under the control of the HIV-1 promoter. The experiments were performed with three psoralens (5-methoxypsoralen, 5-MOP; 8-methoxypsoralen, 8-MOP; and 4′-aminomethyl-4,8,5′-trimethyl-psoralen, AMT) and four angelicins (angelicin; 4,5′-diniethylangclicin, 4,5′-DMA; 6,4′-dimethylangelicin, 6,4′-DMA; and 4,6,4′-trimethylangelicin, TMA). The drugs alone and UVA radiation alone showed no erect on the HIV promoter. However, when the cells were incubated with the furocoumarins at 0.1–40 μg/mL and then irradiated. the HIV promoter was activated in distinct fluence ranges, i.e. (1) no promoter activity was discernible at low fluences (e.g. at 0.1 μg/mL of 8-MOP up to 100 kJ/m²), (2) as the fluence was increased, the promoter activity increased to reach a maximum (10–50-fold with respect to the unexposcd samples), and (3) as the fluence was further increased, the promoter activity decreased. Similar (although shifted on the fluence scale) pattcrns were observed with either > 340-nm UVA radiation or with UVA radiation contaminated with a small amount of UVB radiation (typical for PUVA lamps). The effective fluences were inversely related to the drug concentration. Experiments with 5-MOP and 8-MOP indicated reciprocity of the drug concentration and radiation hence. The HIV promoter response patterns were similar for monofunctional angelicins and bifunctional psoralens. This indicated that the furocoumarin-DNA crosslinks are not a prerequisite for the promoter activation and that the monoadducts suffice to elicit the HIV promoter response. The HIV promoter-activating effectiveness of diKcrent drugs correlated with their photosensitizing potential. Thus, among psoralens the effectiveness order was AMT >. 5-MOP >8-MOP, and among angelicins: TMA > 6,4′-DMA > 4,5′-DMA > angelicin. The ektiveness did not vary substantially for 5-MOP, 8-MOP, 4,5′-DMA, and 6,4′-DMA. The combined drug and UVA radiation doses were higher than those that elicit cellular responses or those that may be received by the human white blood cells during cxtracorporeal PUVA therapy (photopheresis).