Chronobiotics KL001 and KS15 Extend Lifespan and Modify Circadian Rhythms of Drosophila melanogaster

Chronobiotics are a group of drugs, which are utilized to modify circadian rhythms targeting clock-associated molecular mechanisms. The circadian clock is known as a controller of numerous processes in connection with aging. Hypothesis: KL001 and KS15 targeting CRY, affect lifespan, locomotor activity and circadian rhythm of Drosophila melanogaster. We observed a slight (2%, p < 0.001) geroprotective effect on median lifespan (5 µM solution of KL001 in 0.1% DMSO) and a 14% increase in maximum lifespan in the same group. KS15 10 µM solution extended males’ median lifespan by 8% (p < 0.05). The statistically significant positive effects of KL001 and KS15 on lifespan were not observed in female flies. KL001 5 µM solution improved locomotor activity in young male imagoes (p < 0.05), elevated morning activity peak in aged imagoes and modified robustness of their circadian rhythms, leaving the period intact. KS15 10 µM solution decreased the locomotor activity in constant darkness and minimized the number of rhythmic flies. KL001 5 µM solution improved by 9% the mean starvation resistance in male flies (p < 0.01), while median resistance was elevated by 50% (p < 0.0001). This phenomenon may suggest the presence of the mechanism associated with improvement of fat body glucose depos’ utilization in starvation conditions which is activated by dCRY binding KL001

Long-lived exciton coherence in mixed-halide perovskite crystals

Compositional engineering of the optical properties of hybrid organic-inorganic lead halide perovskites is one of the cornerstones for the realization of efficient solar cells and tailored light-emitting devices. We study the effect of compositional disorder on coherent exciton dynamics in a mixed FA$_{0.9}$Cs$_{0.1}$PbI$_{2.8}$Br$_{0.2}$ perovskite crystal using photon echo spectroscopy. We reveal that the homogeneous linewidth of excitons can be as narrow as 16$\mu$eV at a temperature of 1.5K. The corresponding exciton coherence time of $T_2=83$ps is exceptionally long being attributed to the localization of excitons due to variation of composition at the scale of ten to hundreds of nanometers. From spectral and temperature dependences of the two- and three-pulse photon echo decay we conclude that for low-energy excitons, pure decoherence associated with elastic scattering on phonons is comparable with the exciton lifetime, while for excitons with higher energies, inelastic scattering to lower energy states via phonon emission dominates

Long-Lived Exciton Coherence in Mixed-Halide Perovskite Crystals

Compositional engineering of the optical properties of hybrid organic–inorganic lead halide perovskites is crucial for the realization of efficient solar cells and light-emitting devices. We study the effect of band gap fluctuations on coherent exciton dynamics in a mixed FA₀.₉Cs₀.₁PbI₂.₈Br₀.₂ perovskite crystal by using photon echo spectroscopy. We reveal a narrow homogeneous exciton line width of 16 μeV at a temperature of 1.5 K. The corresponding exciton coherence time T₂ = 83 ps is exceptionally long due to the localization of excitons at the scale of tens to hundreds of nanometers. From spectral and temperature dependences of the two- and three-pulse photon echo decay, we conclude that for low-energy excitons pure decoherence associated with elastic scattering on phonons is comparable with the exciton lifetime, while for excitons with higher energies, inelastic scattering to lower energy states via phonon emission dominates.ISSN:1530-6984ISSN:1530-699

Tissue-Specific Knockdown of Genes of the Argonaute Family Modulates Lifespan and Radioresistance in Drosophila melanogaster

Small RNAs are essential to coordinate many cellular processes, including the regulation of gene expression patterns, the prevention of genomic instability, and the suppression of the mutagenic transposon activity. These processes determine the aging, longevity, and sensitivity of cells and an organism to stress factors (particularly, ionizing radiation). The biogenesis and activity of small RNAs are provided by proteins of the Argonaute family. These proteins participate in the processing of small RNA precursors and the formation of an RNA-induced silencing complex. However, the role of Argonaute proteins in regulating lifespan and radioresistance remains poorly explored. We studied the effect of knockdown of Argonaute genes (AGO1, AGO2, AGO3, piwi) in various tissues on the Drosophila melanogaster lifespan and survival after the γ-irradiation at a dose of 700 Gy. In most cases, these parameters are reduced or did not change significantly in flies with tissue-specific RNA interference. Surprisingly, piwi knockdown in both the fat body and the nervous system causes a lifespan increase. But changes in radioresistance depend on the tissue in which the gene was knocked out. In addition, analysis of changes in retrotransposon levels and expression of stress response genes allow us to determine associated molecular mechanisms

Tissue-Specific Knockdown of Genes of the <i>Argonaute</i> Family Modulates Lifespan and Radioresistance in <i>Drosophila melanogaster</i>

Small RNAs are essential to coordinate many cellular processes, including the regulation of gene expression patterns, the prevention of genomic instability, and the suppression of the mutagenic transposon activity. These processes determine the aging, longevity, and sensitivity of cells and an organism to stress factors (particularly, ionizing radiation). The biogenesis and activity of small RNAs are provided by proteins of the Argonaute family. These proteins participate in the processing of small RNA precursors and the formation of an RNA-induced silencing complex. However, the role of Argonaute proteins in regulating lifespan and radioresistance remains poorly explored. We studied the effect of knockdown of Argonaute genes (AGO1, AGO2, AGO3, piwi) in various tissues on the Drosophila melanogaster lifespan and survival after the γ-irradiation at a dose of 700 Gy. In most cases, these parameters are reduced or did not change significantly in flies with tissue-specific RNA interference. Surprisingly, piwi knockdown in both the fat body and the nervous system causes a lifespan increase. But changes in radioresistance depend on the tissue in which the gene was knocked out. In addition, analysis of changes in retrotransposon levels and expression of stress response genes allow us to determine associated molecular mechanisms

Prospects for multimodal visualisation of biological tissues using fluorescence imaging

We investigate skin optical clearing in laboratory animals ex vivo and in vivo by means of low-molecular-weight paramagnetic contrast agents used in magnetic resonance imaging (MRI) and a radiopaque agent used in computed tomography (CT) to increase the sounding depth and image contrast in the methods of fluorescence laser imaging and optical coherence tomography (OCT). The diffusion coefficients of the MRI agents Gadovist®, Magnevist®, and Dotarem®, which are widely used in medicine, and the Visipaque® CT agent in ex vivo mouse skin, are determined from the collimated transmission spectra. MRI agents Gadovist® and Magnevist® provide the greatest optical clearing (optical transmission) of the skin, which allowed: 1) an almost 19-fold increase in transmission at 540 nm and a 7 – 8-fold increase in transmission in the NIR region from 750 to 900 nm; 2) a noticeable improvement in OCT images of skin architecture; and 3) a 5-fold increase in the ratio of fluorescence intensity to background using TagRFP-red fluorescent marker protein expressed in a tumour, after application to the skin of animals in vivo for 15 min. The obtained results are important for multimodal imaging of tumours, namely, when combining laser fluorescence and OCT methods with MRI and CT, since the contrast agents under study can simultaneously enhance the contrast of several imaging methods