Cavity Lasing of Thioflavin T in the Condensed Phase for Discrimination between Surface Interaction and β-Sheet Groove Binding in Alzheimer-Linked Peptides.

This study investigates the lasing effects in a Fabry-Perot cavity to discern the binding interactions of thioflavin T (ThT) with various peptides associated with Alzheimer's disease, including Aβ(1-42), KLVFFA, and diphenylalanine (FF) in the condensed phase. Utilizing kinetic lasing measurements, the research explores ThT emission enhancements due to specific groove binding in β-sheet structures and highlights additional contributions from weak surface interactions and solvent-solute interactions. Lasing spectroscopy reveals a lack of transition of the FF system from its native state to an amyloid-like structure, challenging traditional ThT assay interpretations.

Thioflavin T─a Reporter of Microviscosity in Protein Aggregation Process: The Study Case of α-Synuclein.

Thioflavin T (ThT) informed microviscosity changes can be used to monitor protein aggregation. Steady-state, time-resolved and lasing spectroscopy were used to detect transient states in α-synuclein - a protein associated with Parkinson's disease. The major focus was on the nucleation phase, where conventional ThT fluorescence assay lacks appropriate sensitivity to detect early stage oligomers.

Two-photon excited lasing for detection of amyloids in brain tissue.

Two-photon excitation of emissive markers with near-infrared (NIR) light is of a particular interest for imaging in biology and medicine because NIR light is relatively weakly absorbed and scattered by tissues. At the same time the mechanism of two-photon absorption allows excitation of molecules located deep inside a scattering medium. In this work we demonstrate that the two-photon excitation combined with the effect of light amplification in the stimulated emission process provides a sensitive method for detecting amyloids of different forms.

Laser Emission of Thioflavin T Uncovers Protein Aggregation in Amyloid Nucleation Phase.

There is currently no definitive test for early detection of neurodegeneration which is linked with protein aggregation. Finding methods capable of detecting intermediate states of protein aggregates, named oligomers, is critical for the early stage diagnosis of over 30 neurodegenerative diseases including Alzheimer's or Parkinson's. Currently, fluorescence-based imaging using Thioflavin T (ThT) dye is the gold standard for detecting protein aggregation.

Two-photon excited lasing of Coumarin 307 for lysozyme amyloid fibrils detection.

Amyloid fibrils are a well-recognized hallmark of neurodegeneration. A common approach to detect amyloid fibrils is staining with organic molecules and monitoring optical properties using fluorescence spectroscopy. However, the structural diversity of amyloids necessitates new sensitive methods and probes that can be reliably used to characterize them.

Ultrafast Time-Resolved Studies on Fluorescein for Recognition Strands Architecture in Amyloid Fibrils.

Protein aggregation is associated with numerous devastating diseases such as Alzheimer's, Parkinson's, and prion diseases. Development of therapeutics would benefit from knowledge of the structural organization of protein molecules in these amyloid aggregates, particularly in their aqueous biological milieu. However, detailed structural studies to date have been mainly on the solid state and have required large quantities of purified aggregate.

Laser-Induced Population Inversion in Rhodamine 6G for Lysozyme Oligomer Detection.

Fluorescence spectroscopy is a common method for detecting amyloid fibrils in which organic fluorophores are used as markers that exhibit an increase in quantum yield upon binding. However, most of the dyes exhibit enhanced emission only when bound to mature fibrils, and significantly weaker signals are obtained in the presence of amyloid oligomers. In the concept of population inversion, a laser is used as an excitation source to keep the major fraction of molecules in the excited state to create the pathways for the occurrence of stimulated emission.

Interactions of binuclear ruthenium(II) complexes with oligonucleotides in hydrogel matrix: enantioselective threading intercalation into GC context.

A stretched poly(vinyl alcohol) (PVA) film provides a unique matrix that enables also short DNA oligonucleotide duplex to be oriented and studied by linear dichroism (LD). This matrix further allows controlling DNA secondary structure by proper hydration (A or B form), and such humid films could potentially also mimic the molecular crowding in cellular contexts. However, early attempts to study intercalators and groove binders for probing DNA in PVA failed due to competitive matrix binding.

Short oligonucleotides aligned in stretched humid matrix: secondary DNA structure in poly(vinyl alcohol) environment.

We report that short, synthetic, double- as well as single-stranded DNA can be aligned in stretched humid poly(vinyl alcohol) (PVA) matrix, and the secondary structure (nucleobase orientation) can be characterized with linear dichroism (LD) spectroscopy. Oligonucleotides of lengths varying between 10 (3.4 nm) and 60 bases (20.

Two-photon absorption of metal-organic DNA-probes.

We report remarkable multiphoton absorption properties of DNA intercalating ruthenium complexes: (1) [Ru(phen)(2)dppz](2+); (2) [(11,11'-bidppz)(phen)(4)Ru(2)](4+); (3) [11,11'-bipb(phen)(4)Ru(2)](4+). Two-photon spectra in the range from 460 to 1100 nm were measured using the Z-scan technique. In particular, complex 2 was found to exhibit very strong two- and three-photon absorption properties, which could be an effect of symmetric charge transfer from the ends towards the middle of the conjugated dimeric orbital system.

DNA in a polyvinyl alcohol matrix and interactions with three intercalating cyanine dyes.

We investigate how DNA interacts with drugs in humid polyvinyl alcohol (PVA) films by using a homologous set of cyanine dyes (YO(+), YO-PRO(2+), and YOYO(4+)) known to intercalate into DNA with increasing affinity with increasing charge. UV-vis spectroscopy shows that the PVA matrix destabilizes all three DNA-dye complexes compared to aqueous solution but to a lesser degree as the dye charge increases. The monovalent YO is fully dissociated from DNA within minutes, whereas the dissociation of the divalent YO-PRO takes about one hour and occurs by a two-step mechanism.

Effect of vitamin E and human placenta cysteine peptidase inhibitor on expression of cathepsins B and L in implanted hepatoma Morris 5123 tumor model in Wistar rats.

Aim: To examine the effectiveness of human placental inhibitors, by injecting vitamin E to rats with transplanted Morris-5123 hepatoma, on the expression of cathepsins B and L in tumor, liver, lung and blood sera after transplantation of Morris 5123 hepatoma.

Methods: Animals were divided into 10 groups receiving three different concentrations of vitamin E and inhibitors along or in combination and compared with negative control (healthy rats) and positive control (tumor rats). Effectiveness of treatment was evaluated with regard to survival time, tumor response and determination of the activities of proteolytic enzymes and their inhibitors using flurogenic substrates.